THE NEWBORN BRAIN SURFACE

THE NEWBORN BRAIN SURFACE - keywords
1 / 219 NAVIGATOR Paul Govaert, 2026 The newborn brain surface 18 19,30,127 surface development in cranial ultrasound; the challenge of correlating an anomaly or lesion with its anatomical location; the maturation of the brain surface in the neonatal period Karlen et al; Gloor 21 Neubauer 22 de Abreu 23 Triarhou 37 Medina 39,40 Puelles 92 Gonzalez, Allmann 140 Bajic 178 Purves Navigator 2 / 219 NAVIGATOR Introduction transient structures references scanning protocol nomenclature brain function Sulcus cinguli maturation variation sulci rostrales lobulus paracentralis Comparative brain development neocortex expansion globularity conserved sulci pseudosylvian, lateral, parallel, central, lunatus, frontal, insula Sulcus temporalis superior auditory cortex (sub)pallium morphogens organisers parcelling neocortical connections Other temporal sulci hearing gyrus fusiformis Sulcus collateralis and hippocampus structure of hippocampus midline and hippocampus connections and limbic functions Sulci frontales precentralis prefrontal orbitofrontal Sulci parietales intraparietalis postcentralis subparietalis Sulci occipitales calcarinus calcar avis Other surface structures ventral forebrain corpora mammillaria olfactory structures septum midline Ultrasound scores neonatal: Murphy, Stein, Koning fetal: Chen, Pistorius, Hahner asymmetry Brain segmentation Gyrification Ontogenesis of human primary sulci The interhemispheric fissure grey matter hypothesis, OSVZ anchors critical period annectant gyri prematurity effect Retzius 1896 Chi et al. 1977 Nishikuni and Ribas 2013 schemes ultrasound recognition development anomalies The transverse fissure The lateral fissure The insula of Reil Sulcus centralis deep and superficial segments opercularisation gyri breves and longi development and size von Economo neurons function < parcels role in pain shape, division and variation r1 and r2 Functional ultrasound Abnormal ultrasound cases Abbreviations References Cerebellum NAVIGATOR Abbreviations most abbreviations are in the image legends CP cortical plate CUS cranial ultrasound CST corticospinal tract EC entorhinal cortex EEG electro-encephalography GA gestational age HC hippocampal cortex ICV internal cerebral vein IPC intermediate precursor cell IPL inferior parietal lobule ISVZ inner subventricular zone OR optic radiation PT pars triangularis LGE lateral ganglionic eminence MGE medial ganglionic eminence MRI magnetic resonance imaging MZ marginal zone OSVZ outer subventricular zone PET positron emission tomography PMA postmenstrual age SAT spontaneous activity transient sc sulcus centralis SP subplate SPL superior parietal lobule sr sulcus rhinalis SVZ subventricular zone 3 / 219 4 / 219 NAVIGATOR Introduction and nomenclature The brain surface is one of several compartments to be studied with ultrasound; serial imaging starts at the viable age of around 23-24 w PMA until term equivalent age in preterm infants. Many lesions occur in fragile “transient tissues”, others are vessel-related or change the development of white matter tracts. transient structures with developmental fragility • • • • • • • white matter midline coronal section at the foramen of Monro, 34 w PMA matrix cortex germinal matrix (neurons, oligodendrocytes), outer subventricular zone subplate, claustrum, pulvinar external granular layer of the cerebellum corpus callosum premyelinating white matter veins, vessel walls arachnoid trabeculae and spaces deep grey matter ventricle cavities hindbrain 5 / 219 NAVIGATOR Why study the newborn brain surface ? Although apparently counter-intuitive to the body of “knowledge” about sulci, gyri, lobes and regional cortical activity, the question remains appropriate. On the one hand there is the certainty that consciousness (even if we ever define what it is) is poor or absent without cortex and thalamus, on the other it is still not possible for many brain functions to delineate the parts of the brain (and cortex) involved in it. Memory may be organised (encoded and registered) by entorhinal cortex and hippocampus, but memory engrams are all over the brain (surface). Sensory perception of the body may occur in the postcentral gyrus, but lesions there can be followed by extra-ordinary plasticity and recovery of function. … Cranial ultrasound uses a window in lifetime where direct access to structure is available because of the presence of fontanels. Many small preterm infants have rather large fontanels. Ultrasound vendors - rarely focusing on neonatal brain work - did provide probes with a round scanhead, so that major portions of the cranial content can be observed. Ultrasound, with no real documented side effects when used wisely as we do in clinical practice, can be performed bedside, with very limited disturbance to the infant, without pain. Above all it can be done serially at acceptable cost. There is no other tool that is practical to study the brain surface of one infant for weeks on end, every week, without harm. Neither gross anatomy, nor histology and histochemistry, nor animal experiments, nor PET scan, nor fMRI have been able to describe how specific actions really operate. Images based on neurovascular coupling, like the bold signal in fMRI, are at best crude surrogates of function. The same goes for EEG and derivatives. This is because of the daunting complexity of the circuits in our brain. Every neuron is in fact a microcomputer and billions of them all work together with nuance (modulation). Although one knows that some neurons in the fusiform gyrus are specialised in face recognition, this does not mean that they are “the tool” for face recognition. They are merely part of a complex circuitry with parallel and hierarchical pathways, with feed forward and backward communications, in itself integrated with networks for other functions, e.g. linking the perceived face to the sound it makes. In this publication we focus on the normal and abnormal developmental anatomy of the brain surface in the neonatal period. This is for two reasons: to understand normal development (sulcation, gyrification) and to try and understand the impact of lesions or congenital anomalies. In future attempts at neonatal neuroprotection, to prove that an intervention is beneficial will most likely also depend on description of changes at the brain surface. On the other hand, as neonatologists, we all know that devastating brain damage as with asphyxia, leukomalacia, extensive focal infarction and other entities, is followed by profound weakening of the cognitive and motor repertoire. We also realised that subtle lesions, even just being born prematurely, changes the brain. This means that some structures, cells, tracts, are essential from early on in life and are best not damaged after a certain postmenstrual age. You cannot grow a new corticospinal tract or a long association tract in preterm infants at viable age, that process has occurred in utero. Subplate, with functions and fragilities, is a transient structure, no longer operating after about 34 w PMA. The neocortex is only formed once. Although neuronal precursors persist in hippocampus, repair after birth by neurogenesis in the central nervous system, is at best very limited. • Cobb Matthew (2020). The idea of the brain. Profile books ltd. CUS of the newborn brain surface • • • normal sulcation, variation, influence of lesions early asymmetry annectant gyri maturation scores • • • • • • • arhinencephaly from abnormal insula to syndrome lobar dysplasia, stenogyria lesion in relation to tracts (OR, CST, cingulum) abnormal midline, interhemispheric fissure abnormal cerebellar shape and foliation differentiate between venous and arterial lesions 6 / 219 NAVIGATOR Book references. References are appropriately added throughout. As this publication aims to deliver basic neuro-anatomy for neonatologists, important sources are listed here. Readers should be critical about this knowledge. As with any “fact”, several views on function, expressed here as a reflection of contemporary insight, are most likely wrong. When neonatologists start to look at maturation of sulci with MR and ultrasound, new ideas bout the mechanisms and timing of sulcation may come up. Especially the early annectant gyri, forerunners of function, are of interest. The impact of deep lesions on the brain surface also requires further research. Lessons learnt from anatomy and comparative development should prove useful in the hands of researchers who focus on neuroprotection, be it after injury to the (near) term brain or challenges of the preterm brain. Although understanding plasticity after injury will mainly depend on experimental work, biochemistry and genetics, bedside implementation of protective strategies should be supervised by clinicians who try to understand “simple” brain anatomy and function. Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The fissure of Rolando. pp 161-192. Extensive reference to older literature. Basis of 3D brain drawings. Smith CG, van der Kooy DJ (1985) Basic Neuroanatomy. 3rd Edn. Toronto: Collamore Press. images adapted by courtesy Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. Gloor P (1997) The temporal lobe and limbic system. Oxford University press. Testut L, Latarjet A (1948) Traité d’anatomie Humaine, Vol. 2. Paris: Doin. Ribas G (2010) The cerebral sulci and gyri. Neurosurg Focus 28(2): 1-24. Paturet G (1964) Traité d’Anatomie Humaine. Tome IV. Système Nerveux. Paris: Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. Digital version by Martin Hirsch named ‘Interbrain’. REFERENCE LIST Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates. ten Donkelaar HJ, Tsourio-Mazoyer N, Mai JK (2019) Toward a common terminology for the gyri and sulci of the human cerebral cortex. Frontiers in Neuroanatomy 12: artil 93. NAVIGATOR Book references: Cunningham 1892. Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The fissure of Rolando. pp 161-192. Extensive reference to older literature. Basis of 3D brain drawings in this tutorial. Thanks to bedside in vivo study with ultrasound, the study of the brain surface is as challenging and fresh as it was in 1892. 7 / 219 8 / 219 NAVIGATOR The scanning protocol. the immature brain at 24 w in a viable preterm infant In many European neonatal units cranial ultrasound (CUS) is performed in a serial scheme, by neonatologists; they focus on disorders they know in the newborn brain, their typical presentation and evolution, the mechanisms behind them and the importance for a neurodevelopmental prognosis. The use of standard planes is nothing but a logical anatomical approach, there is no proof of its validity, neither in clinical use nor in research: it is a method for saving images for retrospective interpretation (serial comparison, medicolegal issues) and for prospective studies that require standardisation. Additional (non-standard) sections and movies focusing on lesions, are as important as standard sections. GMH There are 5 “standard” coronal planes and 5 parasagittal planes per hemisphere; with the sagittal plane this adds up to 15 standard sections through the anterior fontanelle, covering most aspects of the four cortical lobes. F P ICV T O convexity left mesial left fossa Sylvii superior inferior Dudink J, Steggerda S, Horsch S; eurUS.brain group. State-of-the-art neonatal cerebral ultrasound: technique and reporting. Pediatr Res. 2020 Mar;87(Suppl 1):3-12. 9 / 219 NAVIGATOR Anterior fontanel sections. 10 5 1 9 4 3 2 coronal planes 8 (para)sagittal planes 7 6 1 2 3 4 5 anterior to the foramen of Monro at olfactory level near the foramen of Monro through ventrolateral thalamus through ventricle atrium and glomus choroideum posterior to the lateral ventricles midsagittal 6 through the caudothalamic groove 7 through thalamus and basal ganglia 8 through insula 9 through fronto-parietal cortex 10 repeat 7-10 for the other side 11-14 most ultrasound sections are with a micro-convex probe (around 8 MHz); details and images in very preterm infants are with a linear probe (around 18 MHz) 10 / 219 NAVIGATOR Nomenclature (1). The primary sulci on a (standardised) convexity surface. c sulcus precentralis medialis calc sulcus calcarinus cing sulcus cinguli f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis (Wernicke) gs gyrus subcallosus LL limbic lobe pa sulcus parolfatorius anterior pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior pnm preoccipital nocth of Meynert po sulcus parieto-occipitalis poc sulcus postcentralis pp sulcus parolfactorius posterior PT pars triangularis r sulcus centralis (Rolando) ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis rsm ramus supramarginalis sulci cinguli sa sulcus subcentralis anterior sang sulcus angularis sB sulcus parietalis transversus (Brissaud) scoll sulcus collateralis sd sulcus diagonalis (Eberstaller) sip sulcus intraparietalis sipj sulcus intermedius primus Jensen sise sulcus intermedius secundus Eberstaller sl sulcus lunatus sli sulcus lingualis soa sulcus occipitalis anterior soi sulcus occipitalis inferior sot sulcus occipito-temporalis sp sulcus subcentralis posterior spa sulcus paracentralis sr sulcus rhinalis sri sulcus rostralis inferior srs sulcus rostralis superior ssp sulcus subparietalis st sulcus occipitalis transversus (Ecker) sts sulcus temporalis superior sti sulcus temporalis inferior 1 2 3 4 5 6 7 8 gyrus parahippocampalis T5 gyrus fusiformis T4 gyrus lingualis O5 lobulus paracentralis precuneus PC cuneus O6 gyrus supramarginalis gyrus angularis F1 P1 sB P2 sipj F2 sise F3 sa O1 sp T1 O2 E T2 O3 T3 F1, F2, F3, superior, middle, and inferior frontal gyri O1, O2, O3, superior, middle, and inferior occipital gyri P1, P2, superior and inferior parietal lobules T1, T2, T3, superior, middle, and inferior temporal gyri E descending occipital gyrus of Ecker EC entorhinal cortex I isthmus gyri cingul PC po pa O6 I gs pp T5 EC T4 sli O5 pnm Although there is a consensus paper on nomenclature (ten Donkelaar et al. 2019), there remains the need to interchangeably use english and latin terms for many structures. Although debatable and confusing, for some anatomical specifications the original author’s name is still in use. Petrides M (2014) Neuroanatomy of language regions of the human brain. Elsevier Academic Press. Smith CG, van der Kooy DJ (1985) Basic Neuroanatomy. 3rd Edn. Toronto: Collamore Press. ten Donkelaar HJ, Tsourio-Mazoyer N, Mai JK (2019) Toward a common terminology for the gyri and sulci of the human cerebral cortex. Frontiers in Neuroanatomy 12: artil 93. NAVIGATOR 11 / 219 Nomenclature (2). Sulci that demarcate Brodmann areae. Although many sulci do not follow cytoarchitectonic patterns, to therefore conclude that the shape and location of sulci is of little relevance, is wrong for many reasons: - plenty of sulci do correspond to a border between functional entities sc 4 - the central groove does separate the motor brain from the other parts 1 7 - the sulci and lobules of the left inferior frontal gyrus do differ from the 2 right because they are special in language operations 7 - development of sulci does correlate with a regression of the olfactory dominance and a progression of the visual dominance in the mammalian neocortex - the complexity of the insula in phylogenetics does relate to the more poc pci 44 40 sip 19 39 6 elaborate “awareness” in the human (and some other) species 22 - the lateral fissure is not a sulcus, neither are the transverse and interhemispheric fissure sts 21 - cortex between sulcus cinguli and corpus callosum is the output area of the limbic system - the pericentral area, with connections to the brainstem and spinal cord, is vulnerable to injury in newborns, in itself and due to subjacent white matter lesions - gyrus temporalis superior is crucial in language processsing pci sulcus precentralis inferior poc sulcus postcentralis sc sulcus centralis sip sulcus intraparietalis sts sulcus temporalis superior - annectant gyri cross sulci at specific sites, not in disarray - … Brodmann, K. (1909). Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Transl. by L.J. Garey in English (1999) Brodmann’s Localisation in the Cerebral Cortex. Leipzig, Barth, London: Imperial College Press. NAVIGATOR 12 / 219 Nomenclature 3: general view of the brain surface. The cerebrum can be seen as a collection of four lobes (Gratiolet), in itself forming an outer neocortical circle around the middle ring of the cingulum, amygdala and insula, in themselves concentrated around the hippocampus and hypothalamus. The parieto-occipital sulcus forms as a consequence of the appearance of the posterior most portion of the corpus callosum, which results in the invagination of the medial surface and the consequent creation of that sulcus. Sulci have been divided into 4 types: limiting, axial, opercular, and complete: The first sulci to emerge are the sulcus hippocampi between archi- and paleocortex (the latter covering gyrus parahippocampalis), and the sulcus rhinalis between paleocortex (hippocampal and piriform) and neocortex. Two pericentral gyri stand vertically between the transversely oriented frontal, parietal and temporal gyri. Gyri should not just be seen as structures between sulci, because many sulci, in their hidden deeper parts, harbor annectant (transverse or opposing) gyri that form bridges between the gyri. Some surface furrows are just the top of such annectant gyri. To identify sulci, and consequently gyri, the characterisation of a given sulcus does not necessarily imply that it is composed of a single continuous space (Ribas 2010). A sulcus can consist of several parts, long or short, isolated or connected to other sulci. human - limiting sulci separate functionally different areas (e.g. the central sulcus, which separates the motor and sensory area); - axial sulci develop along the axis of a functionally homogeneous area, as in the case of the posterior portion of the calcarine fissure, which is actually a fold situated in the center of the striate visual cortex; - opercular sulci are situated between cortical areas that are structurally and functionally different, but the separations exist only along their edges and not in their fundi (e.g. the lunate sulcus, which, when present, is oriented vertically, separating the striate from peristriate areas of the surface and including the submerged parastriate area within its walls); - complete sulci are those whose fundi produce rises in the walls of the lateral ventricles (e.g. the collateral sulcus creates the collateral eminence on the floor of the inferior horn, and the calcarine fissure causes the calcar avis in the medial wall of the posterior horn). chimpanzee Gratiolet 1854 Gratiolet LP: Memoire Sur Les Plis Cerébraux de L’homme et des Primates. Paris: Bertrand, 1854 Ribas G (2010) The cerebral sulci and gyri. Neurosurg Focus 28(2): 1-24. primary sulci in grey, typical gyri in red NAVIGATOR Nomenclature 4: brain operations. 13 / 219 NAVIGATOR Comparative brain development Overview of development of the mammalian cortex. Ancestral mammals possessed a highly developed olfactory bulb and ancient cortex, with a compact neocortex dorsal to it, containing a range of areas shared with extant mammals. To build on existing structures is the evolutionary way of vertebrates, not to add outright innovations. In mammals, the cerebral cortex includes the 6-layered neocortex and the 3layered hippocampal allocortex and olfactory paleocortex. Cortex size in mammals increases principally by surface expansion and not by increasing cortical thickness, which increases by only about two-fold. The primary visual area (V1) receives typical retino-geniculate input, whereas the middle temporal visual area (MT) receives input from a separate, parallel visual pathway that relays through the optic tectum and then the thalamic lateral posterior nucleus and pulvinar (retino-tectopulvinar connection). All mammals additionally share a primary auditory area (A1), a primary somatosensory area (S1) and an adjacent second somatosensory area (S2). Cerebral organisation in the opossum, a living marsupial, is representative of that in ancestral mammals. Its small, smooth neocortex is demarcated from the relatively large olfactory cortex by a deep sulcus rhinalis. The size of sensory areas does not scale linearly with the overall surface: mammals with a highly expanded neocortex, such as humans, have a larger proportion of non-primary-sensory and higher order association cortex. The relatively tiny human olfactory and hippocampal cortices are displaced into the temporal lobe by the expansion of the highly folded neocortex. An extensive neocortex-associated white matter mass with myelinated axons sits below the neocortical grey matter. When different species possess similar characteristics because they inherited them from a common ancestor, the characteristics are said to be homologous. This does not mean they are identical in structure or function. Characteristics that have evolved independently are referred to as analogous. Briscoe SD, Ragsdale CW (2019) Evolution of the Chordate Telencephalon. Curr Biol. 29(13):R647-R662. Medina L, Abellán A, Desfilis E (2022) Evolving Views on the Pallium. Brain Behav Evol 96(4-6):181-199. 14 / 219 NAVIGATOR 15 / 219 Comparative neurodevelopment (neuro-paleontology) is related to historical insight into brain anatomy and function. Egypt, 3000 BC: marrow of the skull (Smith papyrus copy 1600 BC) Greece 500 BC: the senses are incapable of action if the brain is disturbed (Alcmaeon —> Hippocrates and Plato) Alexandria ~ 300 BC: brain and ventricles (Herophilus, Erasistratus)(intestines in the skull)(soul is in calamus scriptorius)(veins only carry blood) Turkey, Rome: Galen of Pergamon 129-199 AD: function of the brain is in the pneuma, an undefined flow of air through the ventricles, form subordinate to function —> —> Padua, Brussels, 1514-1564 AD: Andreas Vesalius (“de humani corporis fabrica”): functions are in the substance (the matter), not the ventricles; convolutions are not human specific London, 1621-1675 AD: Thomas Willis (“Cerebri anatome”); movement and memory come from brain substance; circle of Willis, Willis’ chords in veins France, Descartes 1662 (“De Homine”): realistic drawings of the brain surface; function is in the pineal gland Leiden, de la Mettrie 1748 (“L’homme machine”): the brain is thinking matter England, Joseph Priestley 1732-1804: the matter of the brain is sensitive to certain vibrations that form the basis of thought France, Leuret 1797-1851) and his pupil Gratiolet (1818-1865): comparative neurodeveloment in detail, development of gyri in primates and in the human fetus (“Mémoire sur les plis cérébraux de l’homme et des primates”, 1854) Germany, Franz Joseph Gall 1758-1828: tracts shape gyri (phrenology correct only for location of language and speech) sulcus centralis: Rolando 1809 Byzantium, 300-400 AD: different functions in brain chambers (Poseidonius) Paris 1748-1794, Felix Vicq d’Azyr: convolutions of human are asymmetrical and more complex than of monkey Cobb Matthew (2020). The idea of the brain. Profile books ltd. Marshall LH, Magoun HW 1998: Discoveries in the human brain. Humana Press, Totowa, New Jersey. fissura lateralis: Bartholin 1641, Sylvius 1663 NAVIGATOR Evolution of the animal brain. life plants other 1000 million years ago fungi choanozoans (buddding yeast, choanoflagellates) metazoans (animals) eumetazoans central nervous system -> 16 / 219 poriferans/ctenophores (sponges, jellyfish) bilaterians deuterostome cnidarians strong gyrencephalic clades neocortex and corpus callosum Gyrification developed independently in several clades: monotremes (A), marsupials (B) and placental mammals. protostome echinoderms (sea urchin) chordates 700 million years ago invertebrates vertebrates jawless vertebrates jawed vertebrates 252 to 66 million years ago dinosaurs bony fish birds myelination -> tetrapods embryo in fluid, with a skin -> amniotes 100-300 million years ago behaviour is driven mainly by pheromones via vomeronasal organ to amygdala to hypothalamus; amphibians limited polysensory integration in hippocampus; maps in mesencephalon, not in isocortex mammals “Mammals are characterized as much by their modified neocortex as they are by their mammary glands” (Kaas and Preuss 2008). neocortex (pallium) expanding vertically (to 6 layers) and horizontally (by gyrification); this cortex is modular and flexible; initially olfactory-, later audition- and vision driven; many topographic maps develop typically with thalamic input reptiles 3-layered dorsal cortex, dorsal ventricular ridge in stead of isocortex and striatum Kaas JH, Preuss TM (2008) Human brain evolution. CH 44 in Fundamental Neuroscience: Squire L, Bloom FE, Spitzer NC, du Lac S, Ghosh A, Berg D: eds; pp1019-1037. Elsevier Science. NAVIGATOR An extinct early mammal. The oppossum, a currently living primitive mammal. Phenacodus is an extinct (ungulate) mammal from the Paleocene, 55 million years ago; a cranial endocast reveals the limited size of the neocortex and the large piriform and olfactory lobes; sulcus rhinalis is between them (sr). in these animals there is already some shift from vomeronasal system to olfactory processing via amygdala and hippocampus. V1 and V2 visual areas are a subdivision for lower and upper visual field (calcarine groove is in between them in most mammals). (stereo)Vision is important for hunting and eye-hand coordination. S1,2 and PV: sensory fields are surrounded by somatosensory belts SC and SR. There is no specific motor field. olfactory lobes sr isocortex sr piriform lobe colliculi cerebellum Gloor P (1997) The temporal lobe and limbic system. Oxford University press. O'Rahilly R, Müller F (2010) Developmental stages in human embryos: revised and new measurements. Cells Tissues Organs 192(2):73-84. 17 / 219 NAVIGATOR 18 / 219 Evolution of the mammalian neocortex. Some headlines in mammalian brain development: 1 the brain increases in absolute size; 5 there is no relative increase in size of primary motor or primary visual areas; 2 there is not necessarily expansion of existent, but mainly addition of new cortical functional areas (e.g. in parietal association cortex); 6 changes also occur at a cellular level (e.g. spindle cells (VENs in anterior cingulate cortex)(increased GABAergic contingent); 3 telencephalic asymmetry advances; 7 changes also occur in innervation patterns and neurotransmittors. 4 there is an increase in relative size of prefrontal cortex (Brodmann 10 and 44/45 mainly); All mammals studied possess a primary visual area (V1; dark blue), a primary somatosensory area (S1, dark red), and a primary auditory area (A1, dark green). These primary areas have a specific architectonic appearance and pattern of connectivity. In addition, most possess other cortical fields devoted to processing information from a single sensory system. Combined, these larger subdivisions of the neocortex are termed sensory domains. Only multimodal cortex sends information to hippocampus via the entorhinal cortex. Amygdala are informed by unimodal and multimodal cortices. Different species have different relative sizes of cortical areas and sensory domains, and this variability is thought to parallel the behavioral diversity between various mammals. visual domain in brown somatosensory domain in light and dark green auditory domain in light and dark red Karlen SJ, Hunt DL, Krubitzer L (2010) Ch 18. Cross-Modal Plasticity in the Mammalian Neocortex. pp 357-374. in Oxford Handbook of Developmental Behavioral Neuroscience. Blumberg MS, Freeman JH, Robinson SR (eds). NAVIGATOR 19 / 219 Bassic design of the vertebrate pallia. Dorsal pallium, medial palliumto become hippocampus, amygdala and septum are demonstrated here for several vertebrates. Development of the midline and expansion of the visual cortex occurs at the expense of the olfactory cortex, changing the brain surface extensively. In the amphibian the amygdala are still primarily connected to the vomeronasal organ (pheromone detection), later in comparative development the amygdala shift to entorhinal-hippocampal input (olfactory functions integrated in complex functional appreciation and memory). This is an example of Herrick’s (1948) suggestion that the brain developed complex networks to evolve from foragers into skilled predators: reflex-based action was replaced by a “pregnant phase” between stimulus and response, during which impending (re-)action is weighed by “affect” and memory. The anterior commissure is initially subpallial, later it also acquires pallial fibers. In primates only it is primarily a neocortical connection. SH AC anterior commissure Am amygdaloid nuclear complex HC hippocampal commissure Hy hypothalamus LT lamina terminalis S septum T thalamus TO tractus opticus Gloor P (1997) The temporal lobe and limbic system. Oxford University press. NAVIGATOR 20 / 219 Circular elongation of the limbic system in mammals. The basis of the subpallium between septum and amygdala (both from subpallial origin) remains an unaltered anchor, while the pallium expands mainly in a dorsal and posterior direction. This explains the semicircular shape of structures like the caudate nucleus and the stria terminalis around the internal capsule. It also explains the increased distance between septum and ventral (postcommissural) hippocampus. Brainstem, amygdala, hypothalamus and septum remain close to each other connected in the medial forebrain bundle (containing a.o. the ventral amygdalofugla pathway). acallosal mammal (opossum) callosal mammal (primate) amphibia, reptile StT S MP DP MP LP DP AM LP DP with internal capsule MP StT Am amygdala DP dorsal pallium LP lateral pallium MP medial pallium O olfactory bulb S septum StT stria terminalis (dorsal efferent of amygdala) VAF ventral amygdalofugal pathway H hippocampus Neocortex O olfactory system S septum St striatum S H N St shark rat Gloor P (1997) The temporal lobe and limbic system. Oxford University press. LP MP During evolution the neocortex expanded into human size by x 100 or more, the amygdala and septum by x 4; the only regressing structure is the olfactory system. O VAF human NAVIGATOR 21 / 219 Skull globularity in hominids. Globularity (rounder shape) is characteristic of increase in brain volume in the human species. Globular shape mainly comes from development of parietal lobes and cerebellar hemispheres. This evolution runs parallel with progress in behaviour: worked bone, ornaments, pigments … neandertal larger volume, less globular H erectus larger volume, more globular H sapiens brain volume in cm3 brain volume in hominids gradually increases compared to monkeys million years ago adapted from Neubauer S, Hublin JJ, Gunz P (2018) The evolution of modern human brain shape. Sci Adv 4(1):eaao5961. NAVIGATOR 22 / 219 Primary sulci in primates. Phylogenetically, the first sulcus to appear was the hippocampal, which delimits the archicortex, and the second was the rhinal, which separates the paleo- from the neocortex; these two sulci are also present in almost lissencephalic primates such as Galago and Callithrix and persist in more complex brains such as apes and humans. Highly conserved in primate brains are the lateral, cingulate, calcarine, hippocampal and rhinal sulcus and the longitudinal fissure. 6 7 5 Differences in relation to new parts in primate brains in comparison with other mammals: 1) enhanced complexity of the occipital cortex and visual pathways, for stereoscopic vision 2) enhanced tactile sensibility in hand/feet or pads 3) diminution of olfactory capabilities. 1 2 4 7 5 3 8 1 4 2 8 brachyteles arachnoides (wooly spider monkey) 9 3 1 sulcus centralis 2 fissura lateralis 3 sulcus temporalis superior 4 sulcus frontalis inferior 5 sulcus precentralis inferior 6 sulcus precentralis superior 7 sulcus postcentralis 8 sulcus lunatus 9 sulcus occipitalis inferior 10 sulcus cinguli 11 sulcus corporis callosi 12 sulcus parieto-occipitlais 13 sulcus calcarinus 14 sulcus rostralis 15 sulcus rhinalis 10 12 11 13 14 15 de Abreu T, Tavares MCH, Bretas R, Rodrigues RC, Pissinati A, Aversi-Ferreira TA (2021) Comparative anatomy of the encephalon of new world primates with emphasis for the Sapajus sp. PLoS One 16(9):e0256309. NAVIGATOR 23 / 219 Many mammals are gyrencephalic due to enhanced neurogenesis. The evolution from lissencephaly to gyrencephaly (gyrification) provided mammals and marsupials more cortex within the confines of their skull. Cetaceans (dolphins, whales) are the most gyrencephalic mammals, regardless of brain mass, which may be explained by their post-terrestrial return to a marine environment. The fact that there is a similar pattern in gyration across members within a species, but a different pattern between species, indicates that gyrification is a genetically-programmed process. The DNA-associated protein Trnp1 regulates cortical expansion. Another gene, ARHGAP11B, which is unique to humans, promotes basal progenitor cell generation in the subventricular zone. Highly gyrated complex brains have von Economo neurons in the anterior insula agranular area and in the cingulate cortex. The evolution with a two-step pattern of neurogenesis (asymmetrical and symmetrical) played an important role in the amplification of cell numbers underlying the radial and tangential cortical expansion. human whale The GPR56 gene encodes a heterotrimeric G-binding protein-coupled receptor expressed in cortical progenitor cells and required for normal cortical development, with functions in cell adhesion and guidance. In defining cortical areas, connectivity (not only genetics) is key. elephant giraffe porpoise fur seal Triarhou LC (2017) The Comparative Neurology of Neocortical Gyration and the Quest for Functional Specialization. Front Syst Neurosci 18;11:96. llama NAVIGATOR 24 / 219 Complex gyration is not primate-specific. insula adult elephant, mesial brain surface Gratiolet P (1854) Mémoire sur les plis cérébraux de l’homme et des primates. A. Bertrand, Paris. adult elephant, convexity brain surface NAVIGATOR 25 / 219 The adult primate brain surface resembles the human newborn brain surface. adult orang adult chimpansee Gratiolet P (1854) Mémoire sur les plis cérébraux de l’homme et des primates. Bertrand, Paris. human brain images at term from Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. human neonate at term (Retzius 1896) NAVIGATOR Relative regression of olfactory (piriform) cortex from amphibians to mammals. adapted from Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. 26 / 219 NAVIGATOR 27 / 219 Relative regression of olfactory function, competition between visual and association cortex in higher mammals. Sulcus lunatus. Visual neocortex (primary, area 17) has to make way for higher modality visual and association cortex in higher mammals. Although the primary visual cortex seems to become smaller, human multimodal neocortex involved in visual processing spans about half of the surface. Hominoid visual brain structure volumes vary more than previously appreciated. Humans have relatively reduced primary visual cortex and lateral geniculate nucleus volumes as compared to allometric predictions from other hominoids (de Sousa et al. 2010). The position of the lunate sulcus in fossil endocasts has served as a potential marker of cognitive development in extinct hominid species. While the lunate sulcus is reliably present in great apes and forms the anterolateral boundary of the primary visual cortex, in humans its presentation is variable, and even if present, it does not correspond to a functional region. Using high-resolution MRI, the presence/ absence and course of the lunate sulcus was studied in 110 adults (Allen et al. 2006): in the vast majority, lunate sulci identified on the surface of the occipital lobe actually composed of smaller sulcal segments that converge into an apparently continuous composite lunate sulcus. Only 3 examples in 220 hemispheres (1.4%) of continuous lunate sulci resembled ape lunate sulci in form (albeit in a more posterior position). Composite lunate sulci were found in 32.7% of left and 26.4% of right hemispheres. Human and ape lunate sulci are therefore not homologous. neopallium sulcus centralis olfactory bulb sulcus rhinalis piriform lobe olfactory bulb monkey temporal lobe sulcus centralis frontal lobe olfactory bulb Allen JS, Bruss J, Damasio H. Looking for the lunate sulcus: a magnetic resonance imaging study in modern humans. Anat Rec A Discov Mol Cell Evol Biol. 2006 Aug;288(8):867-76. de Sousa AA, Sherwood CC, Mohlberg H, Amunts K, Schleicher A, MacLeod CE, Hof PR, Frahm H, Zilles K. Hominoid visual brain structure volumes and the position of the lunate sulcus. J Hum Evol. 2010 Apr;58(4):281-92. Gloor P (1997) The temporal lobe and limbic system. Oxford University press. NAVIGATOR Sulcation in cynomolgus monkey, compared to humans. Based on cerebral growth (brain weight, cerebral volume, and fronto-occipital length of the cerebral hemisphere) and the developmental pattern of gyrification in cynomolgus monkeys, the gyrification process can be divided into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; emerging corticocortical long associative fibers Stage 2. Demarcation of primary = neocortical gyri; expansion of cerebrum Stage 3. Emergence of secondary and tertiary sulci Stage 4. Growth of sulcal length and depth; cortical maturation. Cynomolgus monkey Human ---------------------------------------------------------------------------------------------------------------PRIMARY SULCI ED 70 Lateral fissure (lf) GW 14 Lateral fissure ED 80 Parietooccipital sulcus (pos) GW 16 Parietooccipital sulcus Olfactory sulcus (olf) Olfactory sulcus Calcarine sulcus (cal) GW 18 Calcarine sulcus Cingulate sulcus Superior temporal sulcus (sts) ED 90 Central sulcus (cs) GW 20 Central sulcus GW 23 Superior temporal sulcus Collateral sulcus ED 100 Cingulate sulcus (cgs) Intraparietal sulcus (ips) GW 26 Intraparietal sulcus ED 120 Ant. middle temporal sulcus (amt) Inferior temporal sulcus Occipitotemporal sulcus (ots) GW 30 Occipitotemporal sulcus Collateral sulcus (cos) CEREBRAL GYRI ED 80 ED 100 ED 110 ED 120 Superior temporal gyrus Parahippocampal gyrus Precentral gyrus Supramarginal gyrus Angular gyrus Cingulate gyrus Cuneus Postcentral gyrus Superior frontal gyrus Superior parietal lobule Middle temporal gyrus Middle frontal gyrus Inferior temporal gyrus Inferior occipital gyrus Lingual gyrus Fusiform gyrus 28 / 219 mean gyrification index brain weight gain in grams per day secondary and tertiary sulcation primary sulcation primary sulci, stage 2 150 embryonic days embryonic days human PMA weeks 14 24 stage 1 stage 2 duration of gestation = 140-150 d) 70 limbic demarcation 100 neocortical demarcation GW 23 Superior temporal gyrus Parahippocampal gyrus GW 24 Precentral gyrus stage 3 GW 25 Postcentral gyrus Superior frontal gyrus GW 26 Superior parietal lobule Middle temporal gyrus GW 27 Middle frontal gyrus Inferior occipital gyrus Lingual gyrus Fusiform gyrus Cuneus GW 28 Supramarginal gyrus Angular gyrus GW 30 Inferior temporal gyrus 32 120 stage 4 term term Sawada K, Fukunishi K, Kashima M, Saito S, Sakata-Haga H, Aoki I, Fukui Y (2012) Fetal Gyrification in Cynomolgus Monkeys: A Concept of Developmental Stages of Gyrification. The anatomical record 295: 1065-1074. NAVIGATOR 29 / 219 Sulci in apes. As for phylogenetic proximity chimpanzees, bonobos, gorillas, and orangutans are models for the study of human evolution. Some gyri and sulci are common for all primates, whereas others exist in non-human primates but not in modern humans. “It would be a paradox to concur that natural selection produced human gyri for specific functional outcomes, while in other species the presence of numerous gyri just serves to fill the cranial cavity” (Triarhou 2017). Galago Callithrix Saimiri Sapajus Alouatta Ateles Brachyteles Macaca Papio Pan Homo Lontgitudinalis X X X X X X X X X X X Centralis - - X X X X X X X X X Precentralis - - - X X X X X X X X Postcentralis - - - X X X X X X X X Frontalis inferior - - - X X X X X X X X Lateralis X X X X X X X X X X X Temporalis superior - X X X X X X X X X X Temporalis inferior - - - X X X X X X X X Lunatus - - X X X X X X X X rare Occipitalis inferior - - - X X X X X X X X Cinguli X - X X X X X X X X X Not found X X X Not found Not found X X Not found Not found X Rostralis - - - X X X X X X X X Subparietalis - - X X - - - X X X X Parieto-occipitalis - - X X X X X X X X X Calcarinus X X X X X X X X X X X Calcarinus ramus - - X X X X X X X X Occipitotemporalis - - - X X X - X X X X Hippocampi X X X X X X X X X X X Collateralis - - X X X X X X X X X Rhinalis X X X X X X X X X X X Sulcus Corporis callosi ateles de Abreu T, Tavares MCH, Bretas R, Rodrigues RC, Pissinati A, Aversi-Ferreira TA (2021) Comparative anatomy of the encephalon of new world primates with emphasis for the Sapajus sp. PLoS One 16(9):e0256309. Triarhou LC (2017) The Comparative Neurology of Neocortical Gyration and the Quest for Functional Specialization. Front Syst Neurosci 18;11:96. NAVIGATOR Callosal development, expansion of olfactory and visual cortices: shift of the entorhinal cortex. Following complex rotations and shifts of structures by reduction of olfactory cortex, expansion of visual and language cortex, development of the corpus callosum … profound changes occur at the surface of the vertebrate brain. In this image the entorhinal cortex is shown in red, the olfactory tract in yellow, the olfactory bulb in green and the prepiriform/periamygdaloid cortex in light green. The rhinal sulcus (red) shifts from the convexity to the mesial temporal area. Entorhinal cortex shifts from the posterior pole to a position near amygdala and hippocampus. Entorhinal cortex is limited to the retrocommissural (also called ventral) hippocampus. C cingulate cortex CC corpus callosum DH dorsal hippocampus E entorhinal cortex OB olfactory bulb P prepiriform/periamygaldoid mesocortex PS pre- and parasubiculum R retrosplenial cortex RS sulcus rhinalis TO tractus olfactorius VH ventral hippocampus adapted from Gloor P (1997) The temporal lobe and limbic system. Oxford University press. 30 / 219 NAVIGATOR 31 / 219 The insula of Reil in the cat. Some precursors of human sulci. Kappers 1967: a series of parallel gyri develop in mammals around the pseudosylvian fissure. Sulci in cat (a mammal) resemble those in non-primate prosimians. Around the pseudosylvian fissure develop gyrus arcuatus primus and gyrus arcuatus secundus (the former limited by the ectosylvian, the latter by the suprasylvian sulci). cat As the lateral fissure develops by opercularisation, only the posterior part of the gyrus arcuatus secundus remains superficial to become the gyrus temporalis superior with the Heschl gyri in it; the pseudosylvian sulcus is not homologue to the lateral fissure, it becomes the sulcus precentralis insulae. gyru s ∆ reu n 8 iens 7 human fetus 28 w PMA The rhinal sulcus disappears from the lateral convexity. The central sulcus has a precursor in primates. Primary auditory cortex develops at the superior transition between ecto- and parasylvian gyri (∆). The insula develops from the gyrus arcuatus primus and the anterior part of the ectosylvian gyrus. This anterior part connects to the orbitofrontal area via the gyrus reuniens in lower mammals like cats and ogs. - the sulcus centralis insulae is homologue to the pseudoSylvian sulcus - the Sylvian fossa develops around the pseudo-Sylvian sulcus => homologue to the sulcus supra-Sylvius anterior is the ramus ascendens of the lateral fissure - the sulcus temporalis superior is homologue to the sulcus supra-Sylvius posterior - the gyrus reuniens is the anterior insula with a lateral orbital connection; the anterior gyrus brevis is different in comparative development from the middle and posterior gyrus brevis. 1 3 9 ins 8 anteula rior 1 2 3 4 5 6 7 8 9 7 ∆ sulcus supra-Sylvius anterior sulcus supra-Sylvius posterior sulcus ecto-Sylvius anterior sulcus ecto-Sylvius posterior gyrus arcuatus primus gyrus arcuatus secundus pseudo-sylvian sulcus (primitive sylvian sulcus) presylvia sulcus transversus gyri reunientis Anthony R, de Santa Maria AS (1912) Le territoire central du neopallium chez les primates. Le circulaire superieur de reil et la suprasylvia chez les lemuriens, les singes et l’homme. Revue Anthropologique pp 275-290. de Abreu T, Tavares MCH, Bretas R, Rodrigues RC, Pissinati A, Aversi-Ferreira TA (2021) Comparative anatomy of the encephalon of new world primates with emphasis for the Sapajus sp. PLoS One 16(9):e0256309. Triarhou LC (2017) The Comparative Neurology of Neocortical Gyration and the Quest for Functional Specialization. Front Syst Neurosci 18;11:96. Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. NAVIGATOR 32 / 219 Comparative development of the insula of Reil. The insular lobe and its cortex, claustrum and underlying striatum are outgrown by frontal and temporal lobes. These lobes cover the insula (opercularisation) and the fissure remaining at the meeting of these operculae is the lateral fissure. This fissure extends below these opercula in a complex manner, along the limen insulae to the lateral margin of the substantia perforata anterior. Sylvian fossa 6 1 6 3 5 5 6 2 4 1 2 3 4 5 6 Sylvian fossa sulcus supra-Sylvius anterior sulcus supra-Sylvius posterior sulcus ecto-Sylvius anterior sulcus ecto-Sylvius posterior gyrus arcuatus primus gyrus arcuatus secundus Kappers 1967: the cat brain convexity: the precursor to the Sylvian fossa around the pseudo-Sylvian sulcus; homologue to the sulcus supra-Sylvius anterior is the ramus ascendens of the lateral fissure; homologue to the sulcus supra-Sylvius posterior is the sulcus temporalis superior Anthony and de Santa Maria 1912 the insular depression (fossa Sylvii) between the frontal and temporal operculum at 18w and 28w PMA (postmortem human fetus); the sulcus circularis insulae is the border between the fossa and the operculae; it appears prior to emergence of insular sulci adult human: the primary pseudo-Sylvian sulcus is homologue either the sulcus centralis insulae or the groove between the two gyri longi insulae Anthony R, de Santa Maria AS (1912) Le territoire central du neopallium chez les primates. Le circulaire superieur de reil et la suprasylvia chez les lemuriens, les singes et l’homme. Revue Anthropologique pp 275-290. Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. Mallela AN, Deng H, Brisbin AK, Bush A, Goldschmidt E (2020) Sylvian fissure development is linked to differential genetic expression in the prefolded brain. Scientific Reports, Nature Research, 10; 14489. NAVIGATOR Comparative development of the sulcus centralis. Homologous to the sulcus centralis of primates are the sulcus ansatus and sulcus coronalis of lower mammals like the bear (Kappers et al. 1967). The existence of a divided sulcus centralis in man (around 1/300 adult brains according to Heschl 1877) may be independent of this dual homologous origin. adapted from Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. 33 / 219 NAVIGATOR 34 / 219 Comparative development of the sulcus temporalis superior and sulcus lunatus. The parallel sulcus, in humans named superior temporal sulcus, ascends behind the lateral fissure. The angular sulcus (branch 2) joins the superior parallel sulcus close to the origin of the sulcus annectans. The upper segment of the anterior occipital sulcus (branch 3) ends as the sulcus prelunatus. Fragmentary medial temporal sulci join the inferior segment of the same sulcus. 1 standardised human newborn brain 2 poc sl 3 sc pci Shellshear 1927: adult human: the parallel sulcus (sulcus temporalis superior) A sulcus resembling sulcus lunatus of apes is uncommon in humans. In hominid apes sulcus lunates lies on the convexity, posterior to the intraparietal and superior temporal sulci, at the rostral end of the primary visual cortex. Relative shrinkage of the primary visual cortex corresponds to “disappearance” of this characteristic “simian” groove. ic ra rh sip po fl sd f3 spia poc 1 sang 2 sts st 3 soa sl sti soi PG Kappers 1967: lemur convexity AR arcuatus C centralis Lat lateralis (~sulcus intraparietalis) LP lateralis posterior OI occipitalis inferior OT occipitalis transversus OS occipitalis superior S pseudosylvian sulcus (~sulcus insularis posterior) SL sulcus lunatus TS sulcus temporalis superior (parallel sulcus) Kappers 1967: spider monkey convexity f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis pci sulcus precentralis inferior po sulcus parieto-occipitalis poc sulcus postcentralis ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis sang sulcus angularis sc sulcus centralis sd sulcus diagonalis sip sulcus intraparietalis sl sulcus lunatus soa sulcus occipitalis anterior (prelunatus) soi sulcus occipitalis inferior (lateralis) sot sulcus occipito-temporalis spia sulcus parietalis inferior anterior st sulcus occipitalis transversus sti sulcus temporalis inferior sts sulcus temporalis superior Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. Shellshear JL (1927) The evolution of the parallel sulcus. J Anat 61: 276-278. NAVIGATOR 35 / 219 Comparative development of the frontal sulci. Based on homology between primates, the nomenclature of the frontal sulci has been updated: • sulcus arcuatus and sulcus principalis are not singular, but composite; • precentral dimple is forerunner of sulcus precentralis superior prcs; • inferior frontal dimple is forerunner of inferior frontal sulcus; • arcuate spur is part of prcis; • below genu part of arcuate sulcus is homologue to prci inferior; • fi and inferior frontal dimple separate area 45 below from area 9/46 above; • fi always ends in a fork in human and chimpanzee; • sulcus principalis homologue to pmfsi, pmfsa and imfsh. fs 1 2 3 4 5 pcs fm sulcus arcuatus sulcus principalis precentral dimple inferior frontal dimple arcuate spur fi 3 pci 5 fma 2 4 chimpanzee 1 macaque pcs~24-27 w f1 ~ 24-27 w sc ~20-23 w poc ~24-27 w fm ~24-27 w fi -> f3 sulcus frontalis inferior fm -> f2 sulcus frontalis medialis fma sulcus frontomarginalis fs -> f1 sulcus frontalis superior (anterior, posterior) imfs sulcus intermedio-frontalis (horizontal, vertical) pmfs sulcus postero-medialis (anterior, intermediate, posterior) pci sulcus precentralis inferior (superior, posterior, inferior) pcs sulcus precentralis superior imfsv pmfsa imfsh pmfsp pmfsi sip ~ 24-27 w pci ~24-27 w fma f3 ~ 28-31 w sts ~ 20-23 w sulcus circularis insulae ~ 16-19 w sti ~ 24-27 w human PG Amiez C, Sallet J, Giacometti C, Verstraete C, Gandaux C, Morel-Latour V, Meguerditchian A, Hadj-Bouziane F, Ben Hamed S, Hopkins WD, Procyk E, Wilson CRE, Petrides M. A revised perspective on the evolution of the lateral frontal cortex in primates. Sci Adv. 2023 May 19;9(20):eadf9445. NAVIGATOR 36 / 219 Brain segmentation and regional development The final shape of the brain (surface) is influenced by processes like regional differentiation, telencephalisation, development of the commissures, cell proliferation, tract development, gyrification, networking (dendrites and functional synapses) and myelination. hem 2 T 1 3 4 D 5 T telencephalon D diencephalon M mesencephalon P pons MO medulla oblongata C cerebellum T M subpallium P C D M MO P C MO rostrocaudal and dorsoventral gradients induce regional differentiation: the prosomeric model has hypothalamus at its rostral end 1 2 3 4 5 medial pallium dorsal pallium (neocortex) dorsolateral pallium lateral pallium ventral pallium two telencephalic hemispheres develop out of one prosencephalon: pallium and subpallium form per hemisphere commissures influence brain shape and displace hippocampus T T M olfactory tract and bulb D D striatum T insula operculum operculum expansion of thalamus and striatum is parallel with neocortex growth surface increases by sulcation (A to D) and gyration; opercularisation of the insula shapes the alteral fissure ; the neocortex bends into a C shape with the limbic lobe at it’s entry; early functional networks NAVIGATOR 37 / 219 Subdivisions of pallium, progressive telencephalisation. coronal section 1 medial pallium -> hippocampus (Lhx2) 2 dorsal pallium -> 6-layered neocortex (no Lhx9); 3 dorsolateral pallium -> claustrum, insular agranular and dysgranular cortex, perirhinal and lateral entorhinal cortex (continuous with orbitofrontal cortex)(Lhx9, cadherin 8, cerebellin 2) 4 lateral pallium -> dorsal endopiriform nucleus and piriform cortex (olfactory cortex) 5 ventral pallium (anterior, intermediate) -> ventral endopiriform nucleus and piriform cortex, pallial amygdala (Nr2f2/COUP-TF2) 6 ventrocaudal pallium -> posterior part of pallial amygdala * telencephalon/opto-hypothalamic division x lateral olfactory tract zli zona limitans intrathalamica PALLIUM amygdala are of pallial and subpallial origin SUBPALLIUM hem 2 1 3 MP medial pallium DP dorsal pallium LP lateral pallium 4 5 STA striato-amygdaloid grey S septum MGE, LGE, CGE x subpallium rostral view anterolateral view left rostral view 2 2 4 1 2 3,4 zli 4 5 3 S 1 3 5 thalamus 6 5,6 1 6 hypothalamus subpallium * adapted from Medina et al. 2022 Briscoe SD, Ragsdale CW (2019) Evolution of the Chordate Telencephalon. Curr Biol. 29(13):R647-R662. Medina L, Abellán A, Desfilis E (2022) Evolving Views on the Pallium. Brain Behav Evol 96(4-6):181-199. Montiel JF, Aboitiz F (2015) Pallial patterning and the origin of the isocortex. Front Neurosci 9:377. NAVIGATOR 38 / 219 Morphogens and organising centers of the early pallium: protomap and patterning centers. • • • Pax6: progenitor cells for neocortex (radial glia and Cajal-Retzius cells) are produced under dorsalising influence of hem (with BMP and Wnt) —> mainly dorsal and medial pallium, later formation of corpus callosum; the neurons for upper cortical layers mainly develop under influence of Pax6, after formation of deep layers under influence of the hem antihem mainly influences formation of ventral pallium, limited in mammals by expansion of the hem anterior forebrain FGF (fibroblast growth factor) influences diencephalon, subpallium (pituitary and olfactory) and commissures. Cortical areas develop from a periventricular neuroepithelial protomap (Rakic and coworkers). The phenotype of cortical neurons and their species-specific laminar and areal identity is set at the time of their last cell division. Gradients of expressed molecules change with time and are specific per cortical layer in addition to the defining location in the protomap. This protomap is shaped, modified by input that at postnatal stages can be modulated by experience. An early sign of cortical regionalization is the emergence of molecular gradients. The onset of diversification of neural stem cells in the proliferative VZ coincides with the appearance of cortical patterning centers, which exert their influence in a rostro-caudal and medio-lateral extent. Gradients of progenitors are based on the expression of different molecules. A set of markers organises the primitive neocortex. Together they shape the ultimate neocortical landscape that is highly partitioned. Bmp telencephalic vesicle PALLIUM Wnt hem RA Pax6 rostralising EMX2 antihem LGE FGF SUBPALLIUM MGE Sp8 anterior forebrain centre SHH Emx2 caudalising EGF mesencephalon preoptic commissural area eye RA = retinoic acid LGE and MGE = ganglonic eminences SHH = sonic hedge hog A completer list is available at: http:// rakiclab.med.yale.edu/pages/molecules.php. Abbreviations: Id2, Inhibitor of DNA binding 2; Lhx2, LIM homeobox 2; Lmo3, LIM domain only 3; ROR-b, retinoid-related orphan receptor b. Briscoe SD, Ragsdale CW (2019) Evolution of the Chordate Telencephalon. Curr Biol. 29(13):R647-R662. Medina L, Abellán A, Desfilis E (2022) Evolving Views on the Pallium. Brain Behav Evol 96(4-6):181-199. Montiel JF, Aboitiz F (2015) Pallial patterning and the origin of the isocortex. Front Neurosci 9:377. Rakic P, Ayoub AE, Breunig JJ, Dominguez MH (2009) Decision by division: making cortical maps. Trends in Neurosciences Vol.32 No.5 adapted from Medina et al. 2022 NAVIGATOR 39 / 219 Neuromeres are based on morphology and molecular expression. The telencephalon is a specialisation of the alar area of the hypothalamus above the anterior neural ridge (ANR). The rostral brain extends from mesencephalon via diencephalon to hypothalamus, where it ends at the telencephalon impar between septal nuclei and optic chiasm. human 8 wks PMA 1 PALLIUM neocortex striatum pallidum preoptic area septal roofplate (part of ANR) anterior commissure zli zona limitans intrathalamica (sulcus limitans diversion to diencephalic roof) 8 eye 9 hypothalamus peduncular hp2 (PHy) 10 hypothalamus terminal hp1 (THy) 11 subthalamus 12 mammillary body 13 substantia nigra, VTA 14 midbrain 15 rhombomeres 16 isthmus 17 cerebellum 18 cephalic flexure 19 cervical flexure 20 pituitary gland 21 roofplate orange, floorplate red 22 pineal gland (no neural crest anterior to it) 22 1 2 3 4 5 6 7 21 14 P2 P1 sulcus limitans 7 2 16 13 18 P3 3 15 11 12 9 9 sulcus limitans 5 10 SUBPALLIUM 6 4 19 10 8 telencephalon impar 17 20 acroterminal domain (Six3 expression)(FGFs) adapted from Puelles L, Harrison M, Paxinos G, Charles Watson C (2013) A developmental ontology for the mammalian brain based on the prosomeric model. Trends in Neurosciences, October 2013, Vol. 36, No. 10 NAVIGATOR 40 / 219 Primary and secondary organisers, for pallium and subpallium. The brain is induced by the notochord and the prechordal plate. Primary organisers induce neuroepithelium, neural crest and placodes. Secondary organisers subdivide forebrain, diencephalon and midbrain. Organisers are characterised by diffusible molecules that interact with the genomic plan (differential genomic sensitivity to molecules pallium (EMX2, Tbr1) at antagonistic molecular boundaries). Secondary organisers are characterised by limited neurogenesis. 1 The end result is a map with different histogenetic areas; variation in secondary organisers in part explains phylogenetic divergence. rostral end of the forebrain = acroterminal region (Six3 positive) roof plate alar = anterior commissure basal = preoptic area, optic chiasm ZLI in red r p or o l f t la e ba sa l ala optic 5 other cranial nerves midbrain 2 diencephalon olfactory 7 4 subpallium (Mash 1, Dlx 2) 1 hem (medial) 2 antihem (lateral) 3 ANR (anterior neural ridge)(participates in neural tube closure) 4 ZLI (zona limitans intrathalamica) 5 roofplate 6 floor plate 7 IO (isthmic organiser) 8-11 additional suspected organisers 8 subpallial organiser (induced by prechordal plate) 9 acroterminal organiser (alar) 10 acroterminal organiser (basal) 11 VHO organiser (Wnt8, between tuber and co. mammillaria) (1-7 under influence of notochord) (8-11 under influence of the prechordal plate) 7 6 3 PHy FGF8 PHy hypothalamus preplate influence striatum subpallial organiser: preoptic area producing (SHH+) cells for pallium and subpallium in the telencephalic sector of PHy; it borders on the medial ganglionic eminence LGE MGE SHH 11 8 9 10 adapted from Puelles L, Harrison M, Paxinos G, Charles Watson C (2013) A developmental ontology for the mammalian brain based on the prosomeric model. Trends in Neurosciences, October 2013, Vol. 36, No. 10 NAVIGATOR 41 / 219 Pallial and subpallial gradients in mammals. control of proliferation Pax6 Wnt3a, upregulation at cortical hem - renewal of radial glial cells dp mp cortical hem Wnt, Emx, Ngn2 sp subpallium Tbr2 progenitors leading to Tbr1 projection neurons control of neocortical differentiation + SFRPs (secreted Frizzled Related Proteins) from anti-hem lp mp medial pallium dp dorsal pallium lp lateral pallium vp ventral pallium + + Pax6 antihem vp PSB Dlx1/2,Gsh2, Mash1 sp pallial-subpallial boundary PSB: source of insular neurons Mash1 - subpallial neuron cascade control of proliferation + differentiation of basal ganglia Dlx1/2 + GAD 65/67 adapted from Montiel JF, Aboitiz F (2015) Pallial patterning and the origin of the isocortex. Front Neurosci 9:377. differentiation of GABAergic neurons NAVIGATOR 42 / 219 Neocortical histology and circuitry. motor (agranular) neocortex agranular motor neocortex at term II III piriform mesocortex visual (granular) neocortex IV IV intracortical V Betz cells in layer V V VI subplate granular parietal association neocortex in 7 months fetus neuromodulators to commissural to thalamus subcortical and structures claustrum 1 from cortical layer 4 to layer 1 ascending dendrites converge with increased packing density 2 3 from other from neocortex thalamus local circuit neuron a local circuit interneuron, makes axonal synaptic contact with apical dendrites of a layer 5 pyramidal cell IV 4 V 5 hippocampal allocortex 6 pyramidal cell after Shepherd, Gordon M. The Synaptic Organization of the Brain, 5th edn (New York, 2004). VI subplate NAVIGATOR 43 / 219 Neocortical afferents. Neocortex is the motor for the expansion of the primate brain, together with cerebellum. The cortex is about 2 mm thick and per mm3 contains around 50.000 neurons. Some areas stand out by cytoarchitecture, others by degree dopamine - from ventral tegmental area - synapses on spiny and smooth neurons - to all layers, except layer IV - especially strong to prefrontal cortex, where it excites pyramidal neurons cholinergic - from basal nuclei of Meynert and nucleus of the diagonal band of Broca - reach all cortical layers, most dense in layer I - some bias for GABAergic neurons as target amygdalo-cortical - reciprocal - limbic efferent via orbitofrontal and anterior cingulate cortex claustro-cortical - reciprocal - segregation of functions, no evidence of integration of different modalities serotonin from raphe nuclei - variable laminar specificity - transient surges during maturation of layer IV of myelination. Language production and reception best explain human cortical expansion. NOR from locus coeruleus - rougly topographic - strong to primary motor and somatosensory cortex - axons ramify mostly in layer VI - involved in arousal, changes the EEG cortico-cortical - is major input of any neocortical area - major targets are pyramidal neurons - only restricted subsets of neurons form lang distance connections - superfical layer to middle (feed forward to layer IV), deep layer to superficial and middle (feedback) - constraint on volume is the reason for formation of multiple different cortical areas thalamo-cortical - dense to middle layers (mainly IV) - highly ordered, topographic, very specific clustering leading to functional segregation (e.g. ocular dominance columns) - magnification for specific functions e.g. fovea, hand, whiskers - arbors may extend to 5 mm wide, at least 1000 separate relays may affect one point in the cortex Douglas R, Markram H, Martin K. Neocortex. CH 12, pp 499-558. In Shepherd, Gordon M. (ed.), The Synaptic Organization of the Brain, 5th edn (New York, 2004). NAVIGATOR 44 / 219 Gyrification The process that leads to the formation of gyri is called gyrification (folding). The sequential anatomical shaping of specific sulci and gyri are called sulcation and gyration. the gyrification index across life Development of primary sulci occurs between 22 w and 34 w PMA; the index of gyrification increases after term birth to peak around one to two years of age. Uninjured preterm infants have a lower average gyrification index than normal term controls, preterm infants with brain injury score even lower. This effect has been demonstrated with early (neonatal) and late (childhood) MR studies. 4 years Zilles et al. 2013 surface in mm2 (MRI method) MRI at childhood age: - cohort: 17 low-risk preterms (mean GA : 32 weeks) and 16 term children matched for age at scan, gender, handedness and socio-cultural status - preterms at low neurodevelopmental risk: surface and maximum depth measures of four sulci, scanned around 9 years of age - sulci measured: olfactory sulcus, parieto-occipital sulcus, superior temporal sulcus and orbitofrontal sulcus reduced superior temporal sulcus surface in preterms on neonatal MRI: Zubiaurre-Elorza et al. 2009 Zilles K, Palomero-Gallagher N, Amunts K (2013) Development of cortical folding during evolution and ontogeny. Trends in Neurosciences, Vol. 36, No. 5. Zubiaurre-Elorza L, Soria-Pastor S, Junque C, Vendrell P, Padilla N, Rametti G, Bargallo N, Botet F (2009) Magnetic resonance imaging study of cerebral sulci in low-risk preterm children. Int J Devl Neuroscience 7; 559-565. NAVIGATOR 45 / 219 The mechanisms behind formation of gyri. Explanations for folding focus either on forces external or intrinsic to the brain. The latter emphasize axonal tension, differential proliferation and tangential expansion of developing structures that are bonded to one another. Various explanations are not mutually exclusive (Striedter et al. 2015). The first folds, that usually develop into the final deepest pit basin parts of sulci, are termed sulcal pits in fetal MRI (Im and Grant 2017). A sulcal pit can be identified with MRI in a sulcal basin by using structural information of small connecting gyri (focal elevations of the sulcal bottom, also called annectant gyri, submerged or not). The first major folds show smaller spatial variance as they deepen and have a stronger spatial covariance with functional areas under closer genetic control than later developing sulci, reflecting the the stability of the human-specific protomap. The role of the outer subventricular zone in gyral development (Lewitus et al. 2013, Zilles et al. 2013, Striedter et al. 2015), explains how deep brain lesions may alter primary gyration. Primary gyration is driven by genetic mechanisms that control proliferation of cells in the outer subventricular zone. Basal radial glia progenitors form transit-amplifying progenitors in the OSVZ. A discrepant conical expansion of cells in this zone occurs under future gyral crowns. The number of cells produced and their spreading lead to gyral folding. The stage of likely interference with primary gyration is in the fetal (20-23 w) and early preterm (24-32 w) phases of development when cholinergic, thalamocortical and callosal afferents connect to outer subplate targets before connecting to targets in the deep cortical plate (Kostovic and JovanovMilosevic 2006). This is a period of massive cell production in ventricular and subventricular zones, during which the subplate is thick by abundant extracellular matrix and early synapse formation. This is also when surfacenegative large EEG transients emerge from the subplate. It is a period of vigorous structural plasticity, preceding cortico-cortical connectivity around 33-35 w PMA, which itself precedes reorganization following disappearance of transient structures. It was demonstrated by applying frontal cortical resections in primates during gestation that not only local but also distant changes (in the remote occipital areas on both sides, even with unilateral lesions) occur in the formation of primary sulci: new and deep sulci appear, consequent not to abnormal prolongation of neurogenesis but to rerouting (“plasticity”) of thalamocortical fibers coming from the mediodorsal thalamic nucleus (Goldman-Rakic PS 1980). Beyond 32 w post-primary sulcation continues until around 1 year of age after term birth and is also driven by external, in addition to intrinsic factors. Sulcal length increases in this stage. Tension in subcortical white matter then becomes important, whereas such tension is not relevant to primary gyration. Primary gyration co-occurs with early development of long associative tracts but is not related to myelination. tertiary primary sulcus secondary Altman J, Bayer SA (2015) Development of the human neocortex: a review and interpretation of the histological record. A Free eBook from the Laboratory of Developmental Neurobiology, Inc. www.neurondevelopment.org © 2015, The Laboratory of Developmental Neurobiology, Inc. Ocala, FL 34481, USA Goldman-Rakic PS (1980) Morphological consequences of prenatal injury to the primate brain. Progress in Brain Research 53: 3-19. Kostovic I, Jovanov-Milosevic N (2006) The development of cerebral connections during the first 20-45 weeks' gestation. Seminars in Fetal and Neonatal Medicine 11: 415-422. Lewitus E, Kelavaand I, Huttner WB (2013) Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development . Frontiers in human neuroscience. Volume7|Article424 |1-10. Sawada K, Fukunishi K, Kashima M, Saito S, Sakata-Haga H, Aoki I, Fukui Y (2012) Fetal Gyrification in Cynomolgus Monkeys: A Concept of Developmental Stages of Gyrification. The anatomical record 295: 1065-1074. Striedter GF, Srinivasan S, Monuki ES (2015) Cortical folding: when, where, how, and why? Annu Rev Neurosci. 38:291-307. White T, Su S, Schmidt M, Kao C-Y, Sapiro G (2010) The development of gyrification in childhood and adolescence. Brain Cogn 72(1): 36-55. Zilles K, Palomero-Gallagher N, Amunts K (2013) Development of cortical folding during evolution and ontogeny. Trends in Neurosciences, Vol. 36, No. 5. NAVIGATOR 46 / 219 Anchors. Early fibers from thalamic relay nuclei and pulvinar throw an anchor at the expanding neocortex. These are hypothesized to serve as “guide wires” that resist expansion while neurons migrating and fibers growing towards the neocortex elevate the expanding cortex at the unanchored sites. In the region where thalamic fibers arrive early, the cortical surface becomes “anchored”. That region becomes the depth of the future sulcus. At the presumed anchored sites the white matter tends to remain narrow. As later arriving differential tangential expansion external constraints differential proliferation r zon icula r t n e subv axonal tension binding areas e ventricular zone early thalamocortical anchors fibers and neurons reach the adjacent areas, the pressure exerted causes the cortical surface to bulge at unanchored sites. A putative example of such anchor is the interoceptive thalamocortical tract that “fixates” the margin of the insular fossa, to facilitate opercularisation (Evrard 2019). One teleological explanation is that interoceptive information is kept close to thalamus because of its homeostatic function. bonding around an elastic core buckling of a shell with radial attachments thalamic projections to cortical neurons in the depth of early sulci, are “anchors” that keep sulci closer to thalamus the insula is early generated (and anchored) cortex with a very limited amount of white matter later thalamic projections connect to unanchored neurons in what becomes the gyral core other early anchors are at sulcus centralis, parieto-occipitalis and calcarinus after Altman and Bayer 2015 Altman J, Bayer SA (2015) Development of the human neocortex: a review and interpretation of the histological record. A Free eBook from the Laboratory of Developmental Neurobiology, Inc. www.neurondevelopment.org © 2015, The Laboratory of Developmental Neurobiology, Inc. Ocala, FL 34481, USA. Evrard HC (2019) The Organization of the Primate Insular Cortex. Front Neuroanat 13:43. NAVIGATOR 47 / 219 The grey matter hypothesis of primary sulcation: OSVZ and subplate. The subventricular zone of the fetal hemisphere is subdivided into an inner (ISVZ) and outer (OSVZ) part. The OSVZ contains lineages of neural stem and progenitor cells that expand it considerably between gestational weeks 11 and 16 in humans, immediately before the onset of cortical folding. The OSVZ modifies the trajectory of immature neurons by a cell type, the unipolar intermediate radial glia cell (IPC), which is a self-amplifying progenitor cell that generates a radially oriented scaffold in addition to the scaffold formed by the classical apical and bipolar radial glia cells. The proliferation of IPCs is a driving force behind the early tangential expansion of the fetal cortex and folding. The subplate zone SP also plays a part in gyrification. It is characterized by a slow and long-lasting developmental period. SP has its largest dimension subjacent to late maturing and folding association cortices. It contains transient corticocortical and callosal connections before they enter the cortical plate. Protracted development of the SP explains the regional heterochronicity of cortical folding and the numerous, mainly smaller-sized gyri in the multimodal association regions, as well as the early interaction between cell proliferation and migration and the influence of fiber tension on folding. Subpial Granular layer Marginal Zone density of progenitors is increased and the angle of migration of their fibers is more oblique at sites of developing gyri, compared to sulci Cortical Plate SubPlate Radial Glial Fiber Ventricular zone radial glia Intermediate Zone Intermediate progenitor cell outer Radial glia from SVZ Gabaergic Neuron Glutatamatergic Neuron outer Subplate Neuron Subventricular Zone Cajal-Retzius cell inner Thalamic Neuron Subpial Granular cell Oligodendroglia Astroglia Ventricular Zone parallel fibers diverging fibers sulcus gyrus PG Borrell V, Reillo I (2012) Emerging Roles of Neural Stem Cells in Cerebral Cortex Development and Evolution. Develop Neurobiol 72: 955– 971. Lewitus E, Kelavaand I, Huttner WB (2013) Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development . Frontiers in human neuroscience. Volume7|Article 424 |1-10. NAVIGATOR 48 / 219 Migrating cell intercalation. In species with gyrencephalic brains, the radial fiber scaffold may display two conformations: parallel or divergent (Borrell and Reillo 2012). If radial fibers are parallel, the massive number of neurons generated by cortical progenitors will migrate in parallel trajectories and accumulate on thick layers, without tangential dispersion. If radial fibers are divergent, migrating neurons follow divergent trajectories. This results in the tangential divergent radial fibers: migrating neurons use the available RG fibers, including those from basal RG cells, to follow divergent trajectories, resulting in tangential dispersion of neurons (intercalation) -> higher degree of folding (gyrencephalic brains) dispersion of radially migrating neurons, increasing the degree of cortical folding. Compared to a sulcus, early on anchored to thalamus, a gyrus forms due to intercalation of a large contingent of migrating neurons above the subplate. Sulci are therefore very different from fissures in their mechanism of development. future gyrus future sulcus parallel radial fibers: the massive number of neurons generated by cortical progenitors migrate in parallel trajectories and accumulate on thick layers, without tangential dispersion; this is the only mechanism in lissencephalic brains the density of progenitors in the proliferative compartment is increased and the angle of migration of their fibers more oblique at sites of developing gyri compared to sulci proliferation and spreading of OSVZ offspring determines primary gyration between 20 and 31 w GA Borrell V, Reillo I (2012) Emerging Roles of Neural Stem Cells in Cerebral Cortex Development and Evolution. Develop Neurobiol 72: 955– 971. Engelhardt A, Inder TE, Alexopoulos D, Dierker DL, Hill J, Van Essen D, Neil JJ (2015) Regional Impairments of Cortical Folding in Premature Infants. Ann Neurol 77; 154-162. NAVIGATOR 49 / 219 Critical period of primary folding. In rhesus monkey, the convolutional pattern is initiated around the end of the second trimester of gestation. The first grooves are the sylvian and rolandic around E100. During the last third of gestation, other primary and most secondary sulci become recognizable so that at the end of this period the adult pattern is established. The period of primary folding coincides with the time interval over which there is an influx of thalamic and corticocortical afferents into the cortex. According to studies of the visual system, thalamocortical innervation of the occipital lobe occurs between E91 and E124. Other thalamic connections invade their cortical targets over the same period of time. Corticocortical and callosal fibers innervate the cortex somewhat later roughly between E124 and E150 (Goldman-Rakic 1980). Conspicuous anomalies in the sulcal pattern can be experimentally induced in monkeys only when operated before the end of this period: a disruption of a small part of the cortex produces widespread changes It wasIfdemonstrated applying frontal of the entire surface of both hemispheres. prefrontalbyneurons are cortical resections in primates during gestation that not only removed before their axons have reached their ipsilateral cortical local but also distant changes (in the remote occipital targets, these target neurons - with abnormal numbers andwith arrangement areas on both sides, even unilateral lesions) occur in the formation of primary sulci: new and deep of ingrowing fibers - degenerate in greater proportions in fetal than in sulci appear, consequent not to abnormal prolongation more mature animals. Finally, this effect is transferred callosal of neurogenesis but tovia rerouting of thalamocortical fibers coming from the mediodorsal thalamic nucleus. neurons to corresponding loci in the opposite hemisphere which also This remote change in primary sulci only occurs when becomes rearranged resulting in local mirror-symmetric changes inrhesus monkeys, fetuses are lesioned before E124 for because later mediodorsal thalamic nuclei homotopic cortical zones. transsynaptically whither when their cortical target is This sequence of events explains location, timetable bilaterality of lesioned after thatand moment. abnormal convolutions. Thus, abnormal sulci: Goldman-Rakic PS (1980) Morphological consequences - tend to be located in target areas of the prefrontal cortico-cortical of prenatal injury to the primate brain. Progress in Brainin Research 3-19. efferent system and are notably absent areas 53: such as the sensorimotor cortex; - develop just before these connections are fully formed. According to this model, protection from transneuronal degenerative processes occurs with the collateralization of afferent and efferent systems. Thalamic neuronal survival than leads to abnormal wiring. Extrpolating from these date, the critical period for humans is near the end of the seventh month of pregnancy (PMA 30 w). rh monkey pregnancy 166 d human ~ 280 d abnormal sulci in red unoperated prenatal surgery at E106 Unoperated. Prenatal surgery E106. postnatal surgery at P50 Postnatal surgery P50. - frontal cortical resections in primates during gestation not only produce local but also distant changes (in remote occipital areas on both sides, even with unilateral lesions): new deep sulci appear, consequent not to abnormal prolongation of neurogenesis but to rerouting of thalamocortical fibers coming from the mediodorsal thalamic nucleus - this remote change only occurs when rhesus monkey fetuses are lesioned before E124, because mediodorsal thalamic nuclei transsynaptically wither when their cortical target is destroyed later Goldman-Rakic PS (1980) Morphological consequences of prenatal injury to the primate brain. Progress in Brain Research 53: 3-19. References ibidem. NAVIGATOR 50 / 219 Annectant gyri. Annectant gyri (submerged transverse gyri) develop near sulcal pits as early as their corresponding sulci are formed. They most likely reflect early pre-functional connections. divided sulcus centralis “pli fronto-pariétal moyen” a frontal annectant gyrus an annectant gyrus breaches the surface c sc f1 pcs pcs f1 sc f2 sc f3 pci fl f3 pci fl Sernoff 1877: term newborn planum polare pli fronto-pariétal inférieur c sulcus precentralis medialis f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis pci sulcus precentralis inferior pcs sulcus precentralis superior sc sulcus centralis pcs planum temporale sc sc f1 Brückenwindungen (adult, Retzius 1896) Gratiolet P (1854) Mémoire sur les plis cérébraux de l’homme et des primates. A. Bertrand, Paris. Mangin JF, Le Guen Y, Labra N, Grigis A, Frouin V, Guevara M, Fischer C, Rivière D, Hopkins WD, Régis J, Sun ZY (2019) "Plis de passage" Deserve a Role in Models of the Cortical Folding Process. Brain Topogr 32(6):1035-1048. Regis J, Mangin J, Ochiai T, Frouin V, Riviere D, Cachia A, Tamura M, Samson Y (2005) “Sulcal root” generic model: a hypothesis to overcome the variability of the human cortex folding patterns. Neurol Med Chir 45:1–17. Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. NAVIGATOR 51 / 219 Some annectant gyri are accessible to serial detection with cranial ultrasound. frontolimbic annectant gyrus "plis de passage fronto-pariétales" (Paul Broca) m middle i inferior s superior (mesial) s f1 pcs gyrus cunei m poc sc po pci fm f3 PT rh ra i fl sts sc sup sti 26w, Retzius 1896 sc inf pli FP moyen NAVIGATOR 52 / 219 The effects of extreme prematurity on gyrification. To reconfirm by CUS research done with MRI, that documents the effect of extreme prematurity on the brain surface at term equivalent age, may not seem relevant. On the other hand, simple deductions with CUS may guide postneonatal follow-up and treatment without recurrence to complicated techniques. 37w PMA first week general effects Lefèvre et al. 2016 preterms have increased intensity and sharpness of gyrification (higher gyrification index) shallower sulci at term, lower gyrification index Dubois et al. 2008 - advanced sulcation by IUGR for similar surface area - delayed sulcation in twins Zubiaurre-Elorza et al. 2009 reduced sulcus surface in low risk preterm infants for orbitofrontal, olfactory, superior temporal sulcus and parieto-occipital sulcus 24w GA PMA 37 weeks focal effects Dubois et al. 2010 - deeper STS on the right side and larger posterior region of the sylvian fissure on the left side, close to planum temporale - larger anterior region of the sylvian fissure on the left side, close to Broca's region Kersbergen et al. 2016 - the central sulcus, lateral fissure and insula are present at early MRI (around 30w PMA) in all preterm infants; the other sulci (post-central sulcus, superior temporal sulcus, superior and inferior frontal sulcus) are only seen in part of the infants - relative growth from 30w PMA to term is largest in the superior frontal sulcus - rightward shift of timing of development at both examinations except for the LF, which showed a leftward asymmetry at both time points - lower birth weight z-score, multiple pregnancy and prolonged mechanical ventilation have negative effects on cortical folding Engelhardt et al. 2015 reduced cortical surface area and gyrification index in term equivalent ex preterms without significant injury Im and Grant 2017 sulcal pits in the sulcal basins are identified on the white matter surface using watershed segmentation applied to a sulcal depth map derived from segmentation of T2 MR images; relations between sulcal pits can be used to study variation in anatomy and anomalies like callosal agenesis, by reconstruction of the sulcal graph from them Clouchoux et al. 2012 - reduced cortical plate area in preterms - similar left and right gyrification indices Lee et al. 2021 at term equivalent age increased axial diffusivity values (adjusted AD) in the left gyrus cinguli are correlated with language scores at 2 years (Bayley III) Clouchoux C, Kudelski D, Gholipour A, Warfield SK, Viseur S, Bouyssi-Kobar M, Mari JL, Evans AC, du Plessis AJ, Limperopoulos C (2012) Quantitative in vivo MRI measurement of cortical development in the fetus. Brain Struct Funct 217(1):127-39. Dubois J, Benders M, Borradori-Tolsa C, Cachia A, Lazeyras F, Ha-Vinh Leuchter R, Sizonenko SV, Warfield SK, Mangin JF, Hüppi PS (2008) Primary cortical folding in the human newborn: an early marker of later functional development. Brain 131(Pt 8):2028-41. Dubois J, Benders M, Lazeyras F, Borradori-Tolsa C, Leuchter RH, Mangin JF, Hüppi PS (2010) Structural asymmetries of perisylvian regions in the preterm newborn. NeuroImage 52; 32–42. Engelhardt A, Inder TE, Alexopoulos D, Dierker DL, Hill J, Van Essen D, Neil JJ (2015) Regional Impairments of Cortical Folding in Premature Infants. Ann Neurol 77; 154-162. Im K, Grant PE (2017) Sulcal pits and patterns in developing human brains. Neuroimage 1-10. Kersbergen KJ, Leroy F, Išgum I, Groenendaal F, de Vries LS, Claessens NH, van Haastert IC, Moeskops P, Fischer C, Lee HJ, Kwon H, Kim JI, Lee JY, Lee JY, Bang S, Lee J-M (2021) The cingulum in vry preterm infants relates to language and social-emotional impairment at 2 years of term-equivalent age. NeuroImage Clinical 29; 102528. Lefèvre J, Germanaud D, Dubois J, Rousseau F, de Macedo Santos I, Angleys H, Mangin JF, Hüppi PS, Girard N, De Guio F (2016) Are Developmental Trajectories of Cortical Folding Comparable Between Cross-sectional Datasets of Fetuses and Preterm Newborns? Cereb Cortex 26(7):3023-35. Mangin JF, Viergever MA, Dubois J, Benders MJ (2016) Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants. Neuroimage 142:301-310. Zubiaurre-Elorza L, Soria-Pastor S, Junque C, Vendrell P, Padilla N, Rametti G, Bargallo N, Botet F (2009) Magnetic resonance imaging study of cerebral sulci in low-risk preterm children. Int J Devl Neuroscience 7; 559-565. NAVIGATOR 53 / 219 Ontogenesis of human primary sulci: sulcation and gyration Gyri, sulci and fissures. Cortical folding (gyrification) is characteristic of mammalian brains, intenser with increasing brain size (Zilles et al. 2013). In human fetuses, a rapid increase in brain size is associated with increase of surface relative to volume. The cerebral cortex changes from lissencephalic (smooth) to gyrencephalic (Orasanu et al. 2016). A larger surface area has been associated with better cognitive performance, and inversely many neurodevelopmental disorders are associated with abnormal cortical folding. Sulci and gyri are distinguished by using anatomical atlases and nomenclature is based - as long as feasible - on Latin official terms (Eberstaller 1890, Cunningham 1892, Retzius 1896, Testut and Latarjet 1948, Paturet 1964, Smith and van der Kooij 1985, Feess-Higgins and Laroche 1987, Nieuwenhuys et al. 1988, Naidich et al. 1994, O’Rahilly and Müller 1994, Tamraz and Comhair 2006, Destrieux et al. 2010, Nishikuni and Ribas 2013, Altman and Bayer 2015, ten Donkelaar et al. 2019). From this complex body of knowledge we summarize features most authors have agreed upon. Assuming that there is an association between early sulcal patterns and later functional development (Mangin et al. 2010), that folding can be affected by pre- and perinatal factors (Haukvik et al. 2012) and that preterm infants show aberrant cortical folding (Kersbergen et al. 2016), assessment of abnormal folding can be an imaging biomarker of the effects of prematurity on the brain (Hedderich et al. 2019). This means that perinatal interventions alter macrodevelopment of the cerebral surface (Jha et al. 2019).It is necessary to compare folding observed in utero with folding that takes place in extrauterine life as the environment after preterm birth itself may have an impact on folding (Lefevre et al. 2016). The name fissures (“scissures”) is best retained for the grooves that are the result of gross expansion of the hemispheres: interhemispheric, transverse and lateral. The sulci, resulting from variable local cell proliferation and migration, are handled per lobe (temporal, frontal, parietal, occipital), but first sulcus centralis, lateral fissure, insula and sulcus cinguli are described as they mark the general subdivision into lobes. Although gyrification is in fact the active process, for anatomical studies sulcation has been in focus, both at postmortem (Chi et al. 1977, Nishikuni and Ribas 2013), with in vivo antenatal magnetic resonance imaging (MRI)(van der Knaap et al. 1996) and antenatal ultrasound (Monteagudo and Timor-Tritsch 1997). All studies converge on a stable temporal sequence. Three successive folding “waves” follow one another (Chi et al. 1977), with the sequential appearance of early primary folds from 16 weeks of post-menstrual age (w PMA), secondary folds from 32w PMA and tertiary folds after 38w PMA. Cranial ultrasound (CUS) offers to observe the rapidly changing preterm brain sequentially, in a safe and cost-effective manner. The sonographic study of sulci is a challenge however, due to the difficulty of obtaining reproducible two-dimensional planes between observers. 3D CUS permits navigating in the three orthogonal planes (Abdul-Khaliq et al. 2000, Benavente-Fernandez et al. 2021). In addition it enables to obtain an optimized 2D view and to focus on a region of interest (ROI) in coronal, sagittal and axial planes. 2D images of specific sulci can be compared with 3D analyses. Reproducible routine use of quantification in vivo of the evolution of specific sulci and gyri is lacking, but - given that there is remarkable inter-subject variability of folding - the description of representative neonatal patterns can still be useful (Naidich 1994, Gonçalves and Hwang 2021). Also in term infants focal brain lesions differ in prognosis as they differentially affect cerebral lobes and gyri, necessitating correct anatomical description of injury to the cerebral surface. NAVIGATOR 54 / 219 The term brain by Retzius. c pcs f1 c sulcus precentralis medialis calc sulcus calcarinus cing sulcus cinguli f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis (Wernicke) h ramus horizontalis of pci lun sulcus lunatus olf sulcus and tractus olfactorius paracing sulcus paracinguli pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior po sulcus parieto-occipitalis poc sulcus postcentralis PT pars triangularis ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis rsm ramus supramarginalis sulci cinguli sang sulcus angularis sc sulcus centralis (Rolando) scoll sulcus collateralis sd sulcus diagonalis (Eberstaller) sip sulcus intraparietalis soa sulcus occipitalis anterior soi sulcus occipitalis inferior sol sulcus orbitalis lateralis som sulcus orbitalis medialis sotr sulcus orbitalis transversus sot sulcus occipito-temporalis spa sulcus paracentralis sr sulcus rhinalis sri sulcus rostralis inferior srs sulcus rostralis superior ssa sulcus subcentralis anterior ssp sulcus subcentralis posterior sspa sulcus subparietalis st sulcus occipitalis transversus (Ecker) sts sulcus temporalis superior sti sulcus temporalis inferior sc sip poc f2 gyrus supramarginalis pci sip gyrus angularis fm f3 ra sd st fl PT soa sts lun sti soi spa c sc cing paracing cing rsm fm po sspa f1 srs f2 sri scoll calc gyrus lingua lis brain images at term from Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. pcs pcs sc sc rsm poc sip NAVIGATOR 55 / 219 The term brain by Retzius, inferior surface. 2 fm 2 olf 1 som sol sotr som 4 medial anterior posterior lateral orbital gyri rh ra 3 PP sr sr H scoll 1 2 3 4 4 sol 1 3 fm sulcus frontomarginalis (Wernicke) olf sulcus and tractus olfactorius ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis scoll sulcus collateralis sol sulcus orbitalis lateralis som sulcus orbitalis medialis sotr sulcus orbitalis transversus sot sulcus occipito-temporalis sr sulcus rhinalis sotr olf H PT sot sot PP planum polare PT planum temporale H Heschl gyri (transverse gyri) brain images at term from Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. NAVIGATOR Sulcation chronology. 56 / 219 lateral dorsal basal A pictorial summary of the development of sulci at postmortem, mainly based on Chi et al. 1977: (some of the) right sulci develop before left sulci by 1 to 2 weeks the primary sulci develop before 28 w Ga - the tertiary sulci (second branches) develop after 31 w GA - there is an advanced development in IUGR fetuses - development is slower in twins - development is slower on the side of unilateral ventriculomegaly (fetal CUS). - 20-23w sulci present at viable preterm age Time lag in appearance of sulci between anatomy and fetal MRI (Hahner et al. 2017): mean time lag ± sd (w) normal brain mild ventriculomegaly range (w) 1.9 ± 2.2 4.4 ± 3.2 p value 0-8 < 0.1 In isolated fetal ventriculomegaly the time lage between postmortem and fetal MRI detection of sulci seems to be doubled from around 2 to 4 weeks. 24-27w 28-31w ± 23w PMA ± 36w PMA Retzius 1896 Afif A, Bouvier R, Buenerd A, Trouillas J, Mertens P (2007) Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct 212: 335-346. Afif A, Trouillas J, Mertens P (2014) Development of the sensorimotor cortex in the human fetus: a morphological description. Surg Radiol Anat 37: 153-160. Chi JG, Dooling EC, Gilles FH (1977) Gyral development of the human brain. Annals of Neurology 1: 86-93. Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The fissure of Rolando. pp 161-192. Extensive reference to older literature. Hahner N, Puerto B, Perez-Cruz M, Policiano C, Monterde E, Crispi F, Gratacos E, Eixarch E (2017) Altered cortical development in fetuses with isolated nonsevere ventriculomegaly assessed by neurosonography. Prenatal Diagnosis 38: 365-375. Retzius G (1896) Das Menschenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. 32-35w 36-44w NAVIGATOR Brain surface development after Retzius. fifth fetal month 18 to 23 w PMA present: olfactory, parieto-occipital, calcarine sulcus (anterior part first): grow from centre to brain margin early indication of sulcus collateralis, centralis (rarely two different origins) prominent sulcus centralis, temporalis superior, olfactorius, posterior intraparietalis sixth fetal month 24-28w present sulcus precentralis (inferior before superior), postcentralis, cinguli (interrupted, no supramarginal ramus yet) emerging sulcus temporalis inferior, frontomarginalis, frontalis inferior, orbitofrontal sulci, sulcus rostralis seventh fetal month sulcus centralis approaching convexity; complete: sulcus cinguli with ramus supramarginalis, sulcus intraparietalis 29-33 w emerging: sulcus subparietalis, paracentralis, occipitalis anterior (from sulcus temporalis superior), frontalis superior brain images in the sixth fetal month from Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. 57 / 219 NAVIGATOR 58 / 219 The brain surface at early viable preterm age. fifth fetal month 18 to 23 w PMA pcs present: olfactory, parieto-occipital, calcarine sulcus (anterior part first): grow from centre to brain margin sc early indication of sulcus collateralis, centralis (rarely two different origins) poc sip pci PT ra fl prominent sulcus centralis, temporalis superior, olfactorius, posterior intraparietalis sixth fetal month 24-28w sang sts present sulcus precentralis (inferior before superior), postcentralis, cinguli (interrupted, no supramarginal ramus yet) sti emerging sulcus temporalis inferior, frontomarginalis, frontalis inferior, orbitofrontal sulci, sulcus rostralis rsm seventh fetal month sulcus centralis approaching convexity; complete: sulcus cinguli with ramus supramarginalis, sulcus intraparietalis 29-33 w emerging: sulcus subparietalis, paracentralis, occipitalis anterior (from sulcus temporalis superior), frontalis superior cing srs po calc scoll sot PG sr calc sulcus calcarinus cing sulcus cinguli fl ramus posterior fissurae lateralis pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior po sulcus parieto-occipitalis poc sulcus postcentralis PT pars triangularis ra ramus ascendens fissurae lateralis rsm ramus supramarginalis sulci cinguli sang sulcus angularis sc sulcus centralis (Rolando) scoll sulcus collateralis sip sulcus intraparietalis sot sulcus occipito-temporalis sr sulcus rhinalis srs sulcus rostralis superior sts sulcus temporalis superior sti sulcus temporalis inferior NAVIGATOR 59 / 219 Sulcation timetable. sulcus present in 25-50 % present in 75-100 % comments interhemispheric fissure 8w 10w lateral fissure 14w su olfactorius 16w from posterior to anterior, prominent by 24w su parieto-occipitalis 16w fist linear, later tortuous su calcarinus 16w 18w after 18w cuneus and gyrus lingualis distinctly separated su cinguli 18w 24w from anterior to posterior, ramus supramarginalis and paracentralis after 30w su temporalis superior 24w 26w Heschl gyri after 30w develops rostral to caudal 14w 21w 28w su temporalis inferior 30w su occipitotemporalis 27w 30w su frontalis superior 24w 25w su frontalis inferior 28w su centralis 18-20w su precentralis 24w su postcentralis 25w su collateralis 23w su intraparietalis 26w su orbitales 28w insular sulci 28w pars triangularis visible by 28w 23w right one week before left right before left 40w 28w PG three to four sulci visible by 34w Chi JG, Dooling EC, Gilles FH (1977) Gyral development of the human brain. Annals of Neurology 1: 86-93. NAVIGATOR 60 / 219 Sulcation versus fetal body weight. Nishikuni et al. 2013: development of sulci in relation to fetal body weight. Two hundred fourteen brain hemispheres from 107 human brain specimens were examined to evaluate the timing of sulcal formation. These brains were obtained from cadavers ranging in age from 12 weeks of gestation to 8 months of postnatal life. All primary sulci are formed during fetal life. The appearance of each sulcus follows a characteristic time pattern, a reliable guide to gestational age and normal fetal development. The order of appearance of the sulci, and the number and percentages of specimens found were as follows: longitudinal cerebral fissure at 12 weeks (10/10, 100%); callosal sulcus at 12 weeks (10/10, 100%); hippocampal sulcus at 15 weeks (7/10, 70%); lateral sulcus at 17 weeks (20/22, 90.9%); circular insular sulcus at 17 weeks (18/22, 81.8%); olfactory sulcus at 17 weeks (18/22, 81.8%); calcarine sulcus at 17 weeks (14/22, 63.6%); parietooccipital sulcus at 17 weeks (11/22, 50%); cingulate sulcus at 19 weeks (16/20, 80%); central sulcus at 21 weeks (22/38, 57.9%); orbital sulcus at 22 weeks (9/16, 56.2%); lunate sulcus at 24 ± 2 weeks (12/16, 75%); collateral sulcus at 24 ± 2 weeks (8/16, 50%); superior frontal sulcus at 25 ± 2 weeks (5/6, 83.3%); rhinal sulcus at 25 ± 2 weeks (3/6, 50%); precentral sulcus at 26 ± 3 weeks (2/4, 50%); postcentral sulcus at 26 ± 3 weeks (2/4, 50%); superior temporal sulcus at 26 ± 3 weeks (2/4, 50%); central insular sulcus at 29 ± 2 weeks (4/4, 100%); intraparietal sulcus at 29 ± 2 weeks (2/4, 50%); paraolfactory sulcus at 29 ± 2 weeks (2/4, 50%); inferior frontal sulcus at 30 ± 3 weeks (2/4, 50%); transverse occipital sulcus at 30 ± 3 weeks (2/4, 50%); occipitotemporal sulcus at 30 ± 3 weeks (2/4, 50%); marginal branch of the cingulate sulcus at 30 ± 3 weeks (2/4, 50%); paracentral sulcus at 30 ± 3 weeks (2/4, 50%); subparietal sulcus at 30 ± 3 weeks (2/4, 50%); inferior temporal sulcus at 31 ± 3 weeks (3/6, 50%); transverse temporal sulcus at 33 ± 3 weeks (6/8, 75%); and secondary sulcus at 38 ± 3 weeks (2/4, 50%). Nishikuni K, Carvalhal Ribas G (2013) Study of fetal and postnatal morphological development of the brain sulci. J Neurosurg Pediatrics 11: 1-11. Fetal Body Weight Group (g) Postmenstrual Age (wks) 20-100 12 lateral sulcus 101-200 17 circular insular sulcus 101-200 17 central insular sulcus 801-900 29 ± 2 central sulcus 301-400 21 precentral sulcus 601-700 26 ± 3 superior frontal sulcus 501-600 25 ± 2 inferior frontal sulcus 901-100 30 ± 3 postcentral sulcus 601-700 26 ±3 intraparietal sulcus 801-900 29 ± 2 transverse occipital sulcus 901-1000 30 ± 3 lunate sulcus 401-500 24 ± 2 superior temporal sulcus 601-700 26 ± 3 inferior temporal sulcus 1001-1250 31 ± 3 transverse temporal sulcus 1251-1500 33 ± 3 olfactory sulcus 101-200 17 orbital sulcus 401-500 22 hippocampal sulcus 20-100 15 rhinal sulcus 501-600 25 ± 2 collateral sulcus 401-500 24 ± 2 occipitotemporal sulcus 901-1000 30 ± 3 callosal sulcus 20-100 12 cingulate sulcus 201-300 19 marginal branch of cingulate sulcus 901-1000 30 ± 3 paracentral sulcus 901-1000 30 ± 3 paraolfactory sulcus 801-900 29 ± 2 subparietal sulcus 901-1000 30 ± 3 calcarine sulcus 101-200 17 parietoccipital sulcus 101-200 17 2251-2500 38 ± 3 longitudinal cerebral fissure superolateral cerebral surface inferior cerebral surface medial cerebral surface secondary sulci NAVIGATOR 61 / 219 A “standardised” 3D brain presenting primary gyri in their typical shape and location. gyrus frontalis superior gyrus rectus gyrus postcentralis gyrus precentralis gyrus frontalis medius gyrus supramarginalis gyri orbitales uncus gyrus angularis pars triangularis gyrus temporalis superior gyrus fusiformis gyrus temporalis inferior gyrus temporalis medius gyrus frontalis superior lobulus paracentralis gyrus cinguli leg arm hand precuneus face tongue MCA cuneus gyrus lingualis gyrus parah gyrus fusiformis uncus ippoc a mpa lis PG NAVIGATOR 62 / 219 Primary sulci at the convexity around term. f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis (Wernicke) h ramus horizontalis of pci he Heschl gyri j Jensen anterior inferior partietal sulcus lun sulcus lunatus olf sulcus and tractus olfactorius pci sulcus precentralis inferior pcs sulcus precentralis superior po sulcus parieto-occipitalis poc sulcus postcentralis PT pars triangularis ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis sang sulcus angularis sc sulcus centralis (Rolando) sd sulcus diagonalis (Eberstaller) sip sulcus intraparietalis soa sulcus occipitalis anterior soi sulcus occipitalis inferior spt sulcus parietalis transversus (Brissaud) ssa sulcus subcentralis anterior ssp sulcus subcentralis posterior st sulcus occipitalis transversus (Ecker) sts sulcus temporalis superior sti sulcus temporalis inferior sc f1 poc pcs spt f2 j h f3 pci sd sang fm ssp ssa ra rh po sip fl PT he he st soa olf sts lun soi sti PG The primary sulci of a transparent cerebral cortex, demonstrating location of sulci on the convexity in relation to deep structures. NAVIGATOR 63 / 219 Primary sulci at the mesial side of the hemisphere around term. spa paracing calc sulcus calcarinus cing sulcus cinguli olf sulcus and tractus olfactorius paracing sulcus paracinguli po sulcus parieto-occipitalis rsm ramus supramarginalis sulci cinguli sc sulcus centralis (Rolando) scc sulcus corprosi callosi scoll sulcus collateralis sh sulcus hippocampi sol sulcus olfactorius sot sulcus occipito-temporalis spa sulcus paracentralis spt sulcus parietalis transversus (Brissaud) sr sulcus rhinalis srs sulcus rostralis superior sspa sulcus subparietalis rsm spt sspa cing po srs calc sh sol scoll sr sot PG The primary sulci of a transparent cerebral cortex, demonstrating location of sulci on the mesial side in relation to deep structures. NAVIGATOR 64 / 219 Brodmann areae and cortical parcelling. unimodal association areas on Brodmann map somatosensory: 1,2,3 to 5,7 motor: 4 to 6,8,44 visual: 17 to 18,19,20,21,37 auditory: 41,42 to 22 multimodal association areas on Brodmann map prefrontal cortex parietotemporal association cortex medial temporal association cortex NAVIGATOR 65 / 219 Thalamo-cortical map. 41,42 3 8 1 2 Brodmann areae —> 6 17 1 2 3 4 5 6 7 lateral geniculate to striate area (Brodmann 17) medial geniculate to Heschl gyri (41-42) ventral anterior and lateral to (pre)motor cortex (4,6,8= frontal eye field) ventral posterior to postcentral gyrus (1,2,3) pulvinar to parietal association cortex anterior to cingulate cortex medial to prefrontal cortex 5 1 3 4 2 6 7 NAVIGATOR Cranial ultrasound areas of interest for sulci. overview 66 / 219 NAVIGATOR 67 / 219 The interhemispheric fissure The interhemispheric fissure (“longitudinal cerebral fissure” between telencephalic hemispheres) develops at 7 to 8 w PMA. interhemispheric fissure Fissures as a term can be used to refer to those grooves at the brain surface that develop by discrepant growth between neighbouring areas: the lateral fissure by growing opercula above the insula, the interhemispheric fissure by expansion of telencephalic hemispheres meeting in the midline, the transverse fissure by covering of the diencephalon by the growing temporal lobe. 2 4 1 the interhemispheric fissure before callosal development 1 2 3 4 diencephalon tela choroidea striatum substantia perforata anterior 3 1 transverse fissure Retzius 1896, end month 3 NAVIGATOR 68 / 219 The interhemispheric fissure can be absent, blurred by fusion of the hemispheres or irregular due to interdigitation with contralateral mesial gyri. absence interdigitation alobar holoprosencephaly fusion normal frontal IHF at term megalencephaly and cardiomyopathy (NONO mutation) courtesy Neelam Gupta, Southampton cobblestone lissencephaly (Walker-Warburg s., dystroglycanopahy) ∆∆ distortion of the frontal interhemispheric fissure: Aicardi syndrome, syntelencephaly, schizencephaly with septal agenesis, chromosomal anomalies NAVIGATOR 69 / 219 The transverse fissure The transverse fissure (“fente cérébrale” de Bichat) develops between temporal lobe and diencephalon after around 10 w PMA. It contains nerves and vessels in relation to the hippocampus and its major efferent tract, the fornix. Its posterior part ends in an unpaired cistern, inferior to the fornix and superior to the thalami, contributing to the roof of the 3rd ventricle. The internal cerebral veins and posterior choroidal arteries traverse this superior part of the cistern, often called cavum veli interpositi. Because choroid plexus leaves it into the ventricle cavities, this fissure has also been referred to as the choroidal fissure. PG 10w PMA term NAVIGATOR 70 / 219 9 3 2 5 1 4 13 8 6 14 10 7 15 12 11 parasagittal thalamus sulcus collateralis 1 2 3 4 5 6 7 8 corpus callosum cavum septi pellucidi sulcus cinguli lateral fissure frontal operculum temporal operculum temporal core ventrolateral thalamus 9 sulcus frontalis superior 10 transverse fissure (Bichat) 11 vermis 12 cerebellar hemisphere 13 sulcus centralis insulae 14 interpeduncular cistern 15 facies superior cerebelli (foliation) NAVIGATOR 71 / 219 The lateral fissure The insula, claustrum and underlying striatum are outgrown by the frontal and temporal lobes. These lobes cover the insula (opercularisation) and the fissure remaining at the meeting of these operculae is the lateral fissure (“scissure de Sylvius”, fissura lateralis). First described by Bartholin in 1641 and in more detail by Sylvius (Francois de le Boe) in 1652, the lateral fissure is a major landmark on the convexity. partes orbitalis (“tête”), triangularis (“cap”) and opercularis frontalis (“pied”). The anterior horizontal ramus separates the pars orbitalis (orbitofrontal cortex) from triangularis; the anterior ascending ramus separates pars triangularis from opercularis. The pars triangularis is usually situated above the anterior gyrus brevis insulae. Ramus ascendens is positioned above the tip of the temporal lobe. In some brains the ramus ascendens and horizontalis are replaced by one anterior oblique fissure. The partes triangularis and opercularis frontalis form Broca’s speech area. Pars orbitalis is bordered inferiorly by the lateral orbital sulcus. There is important inderindividual variation in the gyrus frontalis inferior, to the extent that the pars triangularis may even be unrecognizable. It extends from the lateral border of the substantia perforata anterior and passes over the limen insulae in a posterior concave path. By definition lateral fissure ramifications cut an opercular margin, develop during primary gyration and arise in front of the sulcus precentralis inferior. The posterior branch of the superficial lateral fissure (between parietal and temporal operculum) usually bifurcates at its end (in about 70% of the cases), forming a long ascending and a short descending part. The latter is also called the posterior transverse temporal sulcus, more frequently found on the right (70% of cases). The ascending branch ascends from the region of the pterion to its termination in the inferior parietal lobule, where gyrus supramarginalis wraps around its end. This gyrus is located above the posterior insular gyri. The lateral fissure guides the MCA and its branches to the cerebral surface and frontal lobe. The posterior part of the lateral fissure tends to be longer and more often straigher (without ascension) on the left. The deep portion of the lateral fissure is divided into sphenoidal and operculoinsular compartments. The sphenoidal compartment (“la vallée Sylvienne) lies behind the sphenoidal ridge, starting at the anterior clinoid process. Its medial border is the lateral olfactory stria, its lateral border the limen insulae. The operculo-insular compartment is formed by two narrow clefts: the opercular cleft is situated between the opposing lips of the frontoparietal operculum above and the temporal operculum below; the insular cleft is situated between the insula and the medial surface of the opercula. The insular cleft has two limbs: the superior limb between the insula and the medial surface of the frontoparietal operculum, the inferior limb between the insula and the medial surface of the temporal operculum. The superficial portion of the lateral fissure is composed of an anterior horizontal, anterior ascending and posterior branch. The anterior branches are almost constant, of similar length but with a divergent course, delimiting a triangular space between them whose apex faces the lateral fissure (PT pars triangularis). These rami start in the fissure separately (forming a U or V together) or with a common trunk (one third of cases). They divide the inferior frontal gyrus, from rostral to caudal, into the Opercularisation is early along the posterior (horizontal) branch of the lateral fissure and the temporal operculum slightly overlaps the centro-parietal operculum as the horizontal part of the lateral fissure is covered. The anterior insula remains exposed until late in fetal life and even early after term birth. The anterior rami become more prominent when maturation approaches 30 w PMA. The vertical ramus ascendens is usually deep and slightly anteriorly oriented. The anterior horizontal ramus sits around the baso-lateral margin of the convexity, most often visible on the lateral convexity and always lateral to the external orbital sulcus. Eberstaller 1890, Cunningham 1892, Retzius 1896, Testut and Latarjet 1948, Paturet 1964, Nieuwenhuys et al. 1988, Tanriover et al. 2004, Govaert et al. 2004, Tamraz and Comair 2006, O’Rahilly and Müller 2006 and 2008, Afif et al. 2007 (detailed measurements of the fetal insula), Ribas 2010, Ribas et al. 2017, ten Donkelaar et al. 2018, Evrard 2019 NAVIGATOR 72 / 219 the insular depression (fossa Sylvii) between the frontal, parietal and temporal operculum at 18 w PMA (postmortem) opercularisation starts from around 24 w PMA sylvian fossa external capsule in relation to the lateral fissure • • • uf: uncinate fascicle (temporal pole to orbitofrontal cortex ifof: inferior frontooccipital fascicle (occipital, parietal and temporal to superior and middle frontal cortex claustrocortical fibers ra rp rh ifof opercularisation from caudal to rostral uf rp ra ± 36 w PMA rh 29 w PMA NAVIGATOR 73 / 219 Fetal evolution of lateral fissure branches. a rostral caudal FP F h sylvian fossa T O opercula F frontal FP frontoparietal O orbital P parietal T temporal ramus ascendens a horizontalis h in month four in month five sylvian fossa in month six in month seven 7 month fetus (28 w PMA): insula without arteries pars triangularis P in month eight and nine ra rp rh insula Retzius 1896 NAVIGATOR 74 / 219 Ultrasound description of the lateral fissure. The lateral fissure can be studied from the anterior fontanel, in several coronal planes. One can distinguish 3 parasagittal planes through the insula: (a) the fissural plane: through the sulcus circularis inferior which is overlaid by the posterior part of the lateral fissure, (b) the insular plane: through the insular cortex, and (c) the opercular plane: through the opercula and the lateral fissure between them. As a dense ondulating line, the lateral fissure continues under the insula from front to back as a border with the temporal lobe. In parasagittal sections this fissure seems to cross/ blend with the infero-posterior circular sulcus of the insula, but the lateral fissure alone extends posterior to the insula. The lack of opercularisation during early periods confers a figure 8-shape to the brain surface in coronal planes. At 24-26 w PMA the posterior insula starts to be covered by the opercula, and this progresses anteriorly. Around 30 weeks PMA, the insula is almost completely covered and the lateral fissure and sulcus circularis together acquire the shape of a recumbent letter Y that separates frontal from temporal lobes. In posterior coronal sections the transition point from insula to gyrus supramarginalis can be placed where the sulcus circularis insulae ends and the lateral fissure is the only local sulcus continuing caudally. Around 34 w PMA visibility of anterior branches of the lateral fissure is increasing. Clinical relevance Lateral fissure anatomy and aberrations from normal are important in disorders of neuronal proliferation and migration. Temporal lobe lesions may displace the lateral fissure leading to asymmetry in coronal planes. lateral fissure internal part lateral olfactory stria ——> © limen optic radiation lateral fissure The optic radiations (dark arrows) point from the lateral geniculate above the temporal lobe to the calcarine cortex; they present in preterm infants as hyperechoic areas between lateral fissure and upper third of the atrium. NAVIGATOR 75 / 219 Typical CUS insular anatomy. at limen at posterior angle f1 f2 rp cing sulcus centralis lf sts ramus ascendens sulcus precentralis inferior sulci subcentrales GA 33w now PMA 35w parasagittal plane through the insula of Reil: coronal sections through rostral and caudal insula cing sulcus cinguli lf lateral fissure rp ramus posterior of the lateral fissure sts sulcus temporalis superior NAVIGATOR 76 / 219 A 3D ultrasound approach of the lateral fissure. operculum frontale scs opercular insular fissural 26w PMA lf sts sci lf lateral fissure sci sulcus circularis inferior scs sulcus circularis superior sts sulcus temporalis superior operculum temporale 32w PMA fissural insular opercular courtesy Nuria Blesa Carreras, Barcelona 35w PMA NAVIGATOR 77 / 219 The insula of Reil The insula of Reil is the smallest lobe, nested in the lateral fissure. It is triangular with an anteroinferior dome (apex) just above and outside of the limen. The insula is covered by frontoparietal and temporal opercula. Limen insulae (“pli falciforme de Broca”) is a slightly raised, arched ridge located at the junction of the sphenoidal and operculo-insular compartments of the lateral fissure (lateral to the lateral olfactory stria), bulging by the underlying fasciculus uncinatus. A shallow recess devoid of perforator arteries, referred to as the “limen recess,” exists between the medial border of the limen insulae and the point of entrance of the most lateral perforator artery, which originates either from the MCA M1 segment prior to bifurcation, or from its posterior or anterior trunk. The central artery of the insula is identical to the central cerebral artery. 3 11 The insula is surrounded by the circular (limiting) sulcus of the insula (sulcus circularis insulae of Reil, “rigoles insulaires”). This sulcus has three parts: anterior, superior, and inferior. The anterior limiting sulcus rises upward and slightly forward, deep to the pars orbitalis of the frontal operculum. The superior limiting sulcus is oriented horizontally. It extends beneath the frontoparietal operculum from the anterior superior edge of the insula to the posterior end of the inferior limiting sulcus. Beneath the temporal operculum at the lower edge of the insula lies the inferior limiting sulcus, which can in fact be subdivided into a posterior (slightly more ascending) and inferior part. The longest limiting sulcus is the superior; the shortest, the anterior. The posterior part of the lateral fissure parallels and covers the insula near the sulcus limitans inferior/posterior, but it extends more caudal than the insula and above it. The pars triangularis of the frontal operculum nearly always covers the anterior gyrus brevis insulae. The inferior limiting sulcus is located medial and cranial to the superior temporal sulcus. 12 8 4 The insula contains several vertical gyri, usually three short gyri breves (anterior, middle and posterior), and one or two gyri longi (anterior and posterior), separated by the sulcus centralis insulae, which courses almost parallel to the sulcus centralis of the hemisphere (it extends around the opercular lip in about 1/5 brains and thus both sulci centrales may rarely be connected). The gyri breves converge to the pole of the insula (where all gyri converge between the limen and the apex), and are linked - medial to the insular limen - to the orbital part of the inferior frontal gyrus by the transverse insular gyrus. This transverse gyrus runs into the lateral olfactory gyrus (of Retzius 1896). An inconstant vertical gyrus accessorius may exist (about 1/2) above the transverse insular gyrus, between anterior gyrus brevis and anterior limiting sulcus; it is usually small but can be 3 2 5 1 4 1 limen insulae 2 sulcus circularis anterior 3 sulcus circularis superior 4 sulcus circularis postero-inferior 5 MCA bifurcation 6 gyri breves 7 gyri longi 8 sulcus circularis insulae 9 gyrus accessorius 10 gyrus transversus 11 striatum 12 thalamus NAVIGATOR prominent and appear at the level of the gyrus brevis anterior both in hight and length. Of the gyri breves, the middle one is usually smallest, surrounded anteriorly by the sulcus insularis anterior, and posteriorly by the sulcus precentralis insulae (most often a triangular depression more than a sulcus, but in fetal life it may be relatively prominent compared to the sulcus centralis insulae). The gyri breves often bifurcate at their superior, broad end. The highest point of the insula, the apex, is usually on the inferior part of the middle gyrus brevis, slightly posterior to the pole of the insula. The sulcus postcentralis insulae starts from the superior limiting sulcus (not far in front of its posterior angle), ends at some distance from the insular pole and divides the posterior insula in two gyri longi. These communicate with the polar/limbic temporal area (“pli temporoinsulaire”), whereas the anterior insula communicates upward with the corresponding parts of the frontoparietal operculum (e.g. gyrus brevis posterior insulae with gyrus precentralis cerebri, gyrus longus anterior insulae with gyrus postcentralis cerebri, gyrus longus posterior insulae with supramarginal gyrus). The macro-anatomy of the insula appears between 24 and 34 w PMA, at a variable pace (Afif et al. 2007). In the region of the future frontal and temporal lobe an elliptic depression is the first sign of insular development at the end of the embryonic period, referred to as sylvian fossa. In the weeks before viability, between 20 and 24 w PMA, the triangular shape of the insular fossa is clearly established. At 24-26 w PMA the posterior insula starts to be covered by the opercula, and it progresses anteriorly. Around 30 w PMA, the insula is mostly covered except for the anterior part. R L right insular sulcation advanced versus left (32w PMA) 78 / 219 3 13 8 6 7 5 9 15 4 10 16 11 2b 14 2a Retzius 1896, adult 1 sulcus circularis anterior 2 a,b sulcus circularis inferior (horizontal and posterior parts) 3 sulcus circularis superior 4 sulcus centralis insulae 5 gyrus accessorius 6 anterior insular point 7 gyrus brevis anterior 8 gyrus brevis medius 9 gyrus brevis posterior 10 gyrus longus anterior 11 gyrus longus posterior 12 limen insulae 13 posterior insular point 14 gyrus transversus 15 insular dome (apex) 16 gyrus temporalis transversus Heschl Testut L, Latarjet A (1948) Traité d’anatomie Humaine, Vol. 2. Paris: Doin. Türe U, Yaşargil DC, Al-Mefty O, Yaşargil MG. Topographic anatomy of the insular region. J Neurosurg. 1999 Apr;90(4):720-33. 7 9 15 12 4 10 11 16 NAVIGATOR 79 / 219 (peri-)Insular gyri. sc Acc gyrus accessorius insulae ALG anterior long gyrus ASG anterior short gyrus fl fissura lateralis gH gyrus of Heschl MSG middle short gyrus P insular pole pci sulcus precentralis inferior PLG posterior long gyrus PT pars terminalis ra ramus ascendens sc sulcus centralis T gyrus transversus insulae pci fl ra ALG MSG ASG PSG PLG gH PT Acc P rh T limen PG NAVIGATOR 80 / 219 Transition from insula to orbitofrontal cortex. olfactory stimuli activate monkey orbitofrontal cortex in area 12 (Walker 1940) inferior view in detail mesial lateral 8 1 10 14 13 12 2 9 3 11 multimodal function of “flavor”: experiences related to food 6 olfactory allocortex 4 1 2 3 4 olfactory tract in sulcus olfactorius olfactory trigone lateral olfactory stria olfactory sensory area in temporal pole: piriform or rhinal cortex (ends at entorhinal cortex)(former prepiriform plus periamygdaloid cortex); extends to limen insulae 5 amygdaloid nuclei (cortical nucleus) in gyrus semilunatus 6 anterior perforated substance (over ventral forebrain area) 7 sulcus rhinalis 8 gyrus rectus 9 diagonal band (Broca) between septum and hippocampus (also called paraterminal gyrus) 10 sulcus parolfactorius anterior 11 limen insulae 12 gyrus transversus insulae ( ~= gyrus olfactorius lateralis of Retzius) 13 gyrus parolfactorius (subcallosus) 14 insular pole direct indirect 5 7 MD thalamus anterior agranular insular area dysgranular posterolateral orbital isocortex (right only in human) gustatory Retzius 1896; adult Mesulam MM, Mufson EJ. Insula of the old world monkey. I. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. J Comp Neurol. 1982 Nov 20;212(1):1-22. Nieuwenhuys R (2012) The insular cortex: a review. Ch 7, pp 123-163. In Hofman MA, Falk D (eds) Progress in brain research, vol 195. Elsevier. NAVIGATOR 81 / 219 Coronal ultrasound sections with insular profiles. parafrontal germinolysis ——> at gyrus transversus at limen with MCA at precentral gyri at central sulcus near posterior insular point NAVIGATOR limen at the site of MCA bifurcation 82 / 219 SPS Five stages can be discerned of insular gyral and sulcal development. central sulci 13-17 w PMA 18-19 w PMA insular sulci stage 1: appearance of the posterior inferior part of the sulcus circularis insulae around 15 w PMA; MCA and M2 branches visible stage 1: appearance of the inferior part of the central cerebral sulcus as a faint depression stage 2: insular area more conspicuous by elevation of surrounding tissue; postero-inferior but also superior peri-insular sulci are shallow but visible; the superior part of the anterior silcus circularis becomes visible; opercularisation has not yet started; anterior and posterior insular regions are separated by a fine groove that will become the central sulcus of the insula; the inferior part of the central cerebral sulcus becomes identifiable; both central sulci are better identified on the right; anastomosis between the MCA and ACA on the peri-Rolandic convexity 20-22 w PMA stage 2: development of the pericentral lateral regions and beginning of opercularization stage 3: progressive development of the temporal and parietal before the frontal opercula, earlier on the right; the inferior part of the anterior sulcus circularis is identifiable; the lower extremity of the central cerebral sulcus is localized 1–2 mm anterior to the superior extremity of the central insular sulcus; it is possible to identify the early precentral sulci (insular and cerebral) by the 20th w GA, and postcentral sulci (insular and cerebral) by the 22nd w; diameter of MCA and its branches M2 and M3 have increased; the central cerebral artery continues from the central insular artery (most often a collateral of the anterior division of the MCA) 24-26 w PMA stage 3: development of parietal and temporal cortices and covering of the postcentral insular region stage 4: covering of the posterior insula, with only partial covering of the anterior tip and the anterior sulcus circularis; the upper end of the sulcus centralis insulae separates the superior sulcus circularis into two anterior thirds and one posterior third; the post-central insular sulcus can be seen stage 4: maturation of the central cerebral regions stage 5: closure of the lateral fissure by coverage of the insula by the opercula (except orbitofrontal parts, especially on the left); the shape of the insula takes the definitive trapezoid form; the central insular sulcus is deeper than the surrounding later sulci 27-28 w PMA APS SPS PIPS CIS A APS PIPS I Anterior short gyrus II middle short gyrus III precentral gyrus IV postcentral gyrus V posterior long gyrus VI insular pole APS anterior periinsular sulcus SPS superior periinsular sulcus PIPS posteroinferior periinsular sulcus 1 Anterior insular sulcus 2 precentral sulcus 3 central insular sulcus (CIS) 4 postcentral sulcus parasagittal power doppler B limen at the site of MCA bifurcation Afif A, Bouvier R, Buenerd A, Trouillas J, Mertens P (2007) Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct 212: 335-346. NAVIGATOR Ultrasonographic description of the insula of Reil. 83 / 219 planes after 35 w PMA. Also visible are the superior temporal sulcus and anterior branch of the circular groove. The long insular gyri (two) can sometimes be seen apart from each other. In many infants an accessory insular gyrus can be seen in front of the gyri breves. A sulcus (posterior to the transverse insular gyrus) prolongs the anterior circular sulcus in the direction of the midline in near term infants. At 24-26 w PMA the posterior insula starts to be covered by the opercula, and this progresses anteriorly. Around 30 w PMA, the insula is almost completely covered and the lateral fissure and sulcus circularis together acquire the shape of a recumbent letter Y that separates frontal from temporal lobes. In posterior coronal sections the transition point from insula to gyrus supramarginalis can be placed where the sulcus circularis insulae ends and the lateral fissure is the only local sulcus to continue caudally. Some structures in the insular area (opercular opening and insular cortex height in the coronal plane) permit reproducible measurement of maturation when a standard plane is used (Stein et al. 2023). Sonographic opercularisation begins around the 24th w PMA and progresses cranially. On coronal section through glomus choroideum at atrial level, the insular space forms a shallow groove at 24 w PMA, becomes a slit (partially opercularised insula) at 28 w PMA, that grows longer and develops branches at first linear, later curved - after 32 w PMA. At 28 w PMA the ascending anterior part of the circular groove and the lateral fissure at the bottom of the insula are seen in parasagittal section. Clinical relevance Lateral fissure anatomy and aberrations from normal are important in congenital anomalies. Flattening of the insula and poor development of sulci can be seen in polymicrogyria and chromosomal anomalies. Given the ease of recognition of the limen, the anterior and posterior insular corner, it is surprising that there are no studies yet of size of the insula measured by sequential CUS in preterm infants. The impact of very preterm birth on its development may prove to be relevant. Damage to insular cortex is observed with MCA stroke, asphyxia and intraoperative encephalopathy. Decompression injury can also include the insula. Secondary gyri become visible in the insular dome between 30 and 34 w PMA (Huang 1991). In a parasagittal view 2 to 3 sulci between the short insular gyri become visible. The sulcus centralis insulae gradually deepens in coronal parasagittal ultrasound section through the insula of Reil 6 1 2 3 4 5 6 sulcus circularis anterior sulcus circularis superior sulcus circularis postero-inferior sulcus centralis insulae limen insulae sulcus centralis cerebri 2 1 4 5 3 2 1 4 5 Eberstaller 1890, Cunningham 1892, Retzius 1896, Testut and Latarjet 1948, Paturet 1964, Nieuwenhuys et al. 1988, Huang 1991, Türe et al. 1999; Tanriover et al. 2004, Tamraz and Comair 2006, O’Rahilly and Müller 2006 and 2008, Afif et al. 2007 (detailed measurements of the fetal insula), Ribas 2010, Ribas et al. 2017, ten Donkelaar et al. 2018, Evrard 2019, Stein et al. 2023 NAVIGATOR Ultrasound sections with insular profiles at different stages of maturation. 84 / 219 coronal parasagittal 25w opercular insular fissural 32w 28w 34w 40w Govaert P, Swarte R, De Vos A, Lequin M (2004) Sonographic appearance of the (ab)normal insula of Reil. Dev Med Child Neurol 46: 610-616. term NAVIGATOR Connections of insular cortex to neocortex. parasagittal ultrasound sections to illustrate the frontal connection of the anterior insula and the temporal connection of the posterior insula transverse insular gyrus ———> 85 / 219 NAVIGATOR 86 / 219 The transverse gyrus of the insula (1). term tri 21 anterior insula <—— gyrus orbitalis anterior transverse insular gyrus ——> gyrus rectus ——> gyrus orbitalis medialis ——> <—— gyrus orbitalis lateralis gyrus orbitalis inferior ——> tractus olfactorius ——> <—— anterior insula transverse insular gyrus ——> lateral olfactory gyrus ——> P <—— insular pole temporal pole <—— transverse insular gyrus Naidich TP, Kang E, Fatterpekar GM, Delman BN, Gultekin SH, Wolfe D, Ortiz O, Yousry I, Weismann M, Yousry TA. The insula: anatomic study and MR imaging display at 1.5 T. AJNR Am J Neuroradiol. 2004 Feb;25(2):222-32. NAVIGATOR 87 / 219 The transverse gyrus of the insula (2). Acc accessory insular gyrus c connection to orbitofrontal cortex in lateral olfactory gyrus P insular pole T transverse insular gyrus = lateral olfactory gyrus Acc Acc c P T c T P c c T P Retzius 36w PMA Retzius adult NAVIGATOR 88 / 219 Gyrus accessorius and MCA branching. ra sc fl PT gyri breves Acc rh T gyri longi Heschl gyrus Acc fl P Acc gyrus accessorius l limen fl fissura lateralis P pole PT pars triangularis ra ramus ascendens rh ramus horizontalis sc sulcus centralis sts sulcus temporalis superior T gyrus transversus l coronal power doppler: MCA segments in relation to the insula sts sulcus frontalis superior sulcus centralis M3 insula M2 fissura lateralis M4 erior ralis sup o p m e t sulcus M1 NAVIGATOR 89 / 219 Functional anatomy of the insula. The insula is an interface in the interoceptive shaping of cognitive processes, including somatic and emotional awareness (Evrard 2019). A concentric olfactory-directed model in macaque primates proposes that interoceptive afferents, representing the status of body organs, are first received in the granular dorsal part of the insula or “primary interoceptive cortex,” then processed through a series of dysgranular poly-modal “insular stripes,” and finally integrated in anterior agranular areas that serve as sensory platform for visceral and somatic functions and as an output stage for autonomic regulation. prefrontal cortex 4 anterior insular cortex 5 posterior insular cortex 6 7 ventral tegmental area SNr hypothalamus thalamus VPM parabrachial nucleus 3 nucleus tractus solitarii 2 neocortex insular cortex amygdala thalamus hypothalamus parabrachial nucleus nucleus tractus solitarii somatosensory cortex anterior cingulate cortex amygdala 1 One of the agranular areas hosts specialized von Economo and fork neurons, which could provide evolutionary advantage for the insula in autonomic and emotional binding inherent to subjective awareness. This agranular area anterior to the limen, is caudal to the anterior circular sulcus of the insula. 1 2 3 4 5 6 7 orbitofrontal cortex reticular formation 2 dorsal root ganglion cells cranial nerve ganglion nodosum/jugulare peripheral organs Chen WG, Schloesser D, Arensdorf AM, Simmons JM, Cui C, Valentino R, Gnadt JW, Nielsen L, Hillaire-Clarke CS, Spruance V, Horowitz TS, Vallejo YF, Langevin HM (2021) The Emerging Science of Interoception: Sensing, Integrating, Interpreting, and Regulating Signals within the Self. Trends Neurosci 44(1):3-16. Evrard HC. The Organization of the Primate Insular Cortex. Front Neuroanat. 2019 May 8;13:43. NAVIGATOR 90 / 219 The insula of Reil: functional areas in a primate, extrapolated to humans (Nieuwenhuys 2012). also visceromotor control: e.g. seizures and cardiac arrrest, stroke and prolonged QT interval; effect mainly for right insular strokes taste and other non-taste oral stimuli nucleus of the solitary tract posterior to anterior concept parabrachial nucleus SENSORY PROCESSING, GRANULAR CORTEX neocortex VPMpc med VPMpc lat sharing VENeurons with anterior cingulate cortex VMPo gustatory I cognitive control: self-awareness, limb ownership, self recognition, individual and social emotions viscerosensory nociceptive and thermoceptive right hemisphere dominance gustatory II orbital network together with caudal orbitofrontal cortex: analysis and integration of food-related information motor insular area somatosensory, auditory, association right hemisphere dominance vestibular VPS, VPI anterior agranular zone limbic autonomic reactions to emotions via hypothalamus right hemisphere dominant olfactory cortex amygdala hippocampus POLYMODAL ASSOCIATION AND RESPONSE, DYSGRANULAR AND AGRANULAR CORTEX Nieuwenhuys R (2012) The insular cortex: a review. Ch 7, pp 123-163. In Hofman MA, Falk D (eds) Progress in brain research, vol 195. Elsevier. cingulate cortex NAVIGATOR 91 / 219 The insula of Reil: functional areas in a primate, with indication of von Economo neurons. The anterior agranular zone of the insula integrates interoceptive and exteroceptive information. The stream of integration is from superior back to inferior front and assembes vestibular, nociceptive, thermoreceptive, viscerosensory, gustatory, olfactory, somatosensory and limbic information. The insula thus has this multi-modal role in a strategic location. Insular cortex is connected with the frontal, temporal, parietal and occipital lobes, hence its contribution in functions including visceral and somatosensory processing, olfaction, hearing, language, motivation, craving, addiction and emotions (such as pain, empathy and disgust). This implicate numerous related subcortical structures. Based on these premises, using MR algorithms, one has explored the subcortical connectivity of the insula with the thalamus, amygdala, hippocampus, putamen, globus pallidus, caudate nucleus and nucleus accumbens (Ghaziri et al. 2018). Fiber connections can be depicted with HARDI (high angular resolution diffusion imaging) and particle fiber tractography (streamlining based on anatomical prior knowledge): insular cortex is highly connected to all substructures studied. von Economo (VEN) and fork neurons in anterior insular cortex - large somata, in layer Vb of anterior cingulate cortex ACC and frontal insular area FI - less than 5 % of pyramidal neurons in layer V - glutamatergic excitatory neurotransmission - rôle in monoamine modulatory function (no synthesis of but vesicular transport of GABA)(also serotonin and dopamine receptors) - projection to ipsilateral anterior cingulate cortex - not restricted to large-brained or socially complex species - function as global workspace consciousness ?; link between awareness and arousal; preparing targets for imminent pyramidal input; rôle in autonomic regulation of cognitive processes - most develop after term birth in humans after Evrard HC (2019) The Organization of the Primate Insular Cortex. Front Neuroanat 13:43. granular dysgranular agranular NAVIGATOR Development of the insula from the pallial-subpallial boundary (PSB) with a special radial glial fiber tract. 92 / 219 Von Economo neurons (VENs) ventricle the subventricular zone of the PSB gives rise to a distinct radial glia fiber fascicle (RGF), which courses lateral to the putamen in the external capsule, crossing the internal capsule RGF has several components PF descending from the prefrontal PSB to the anterior insula FP descending from the fronto-parietal PSB toward the intermediate insula T ascending from the temporal PSB and merging with components FP and PT striatum the RGF guides migrating principal neurons toward the future agranular, dysgranular, and granular insular areas, which show an adult-like definition at 32 GW These are an evolved cell type, active during fast intuitive assessment of complex situations. The VENs relay from frontoinsular and anterior cingulate cortex to frontal and temporal cortex where intuition is mixed with slower, deliberative judgment. The VENs emerge mainly after birth and increase in number until age 4 yrs. González-Arnay E, González-Gómez M, Meyer G (2017) A Radial Glia Fascicle Leads Principal Neurons from the Pallial-Subpallial Boundary into the Developing Human Insula. Front Neuroanat 11:111. Allman JM, Watson KK, Tetreault NA, Hakeem AY (2005) Intuition and autism: a possible role for Von Economo neurons. Trends Cogn Sci 9(8):367-73. Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Park S, Goubert V, Hof PR (2010) The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 214(5-6):495-517. NAVIGATOR 93 / 219 The insula and pain processing. anterior cingulate cortex (ACC) and insula endogenous opioid targets amygdala the anterolateral pain system: 2 parallel pathways (discriminative and emotional) visceral pain via a dorsal column pathway (near midline) visceral discriminative parabrachial nucleus VPL/VPM VPL median, intralaminar lemniscal crossing spinal crossing descending pain modulator emotional-affective spinal crossing periaqueductal grey ACC to spinothalamic tract (brainstem and thalamus) peripheral and central sensitisation at posterior horn level insula downward modulation Aß fibers (large myelinated): mechanoreceptor layer striatum RTN A∂ and C fibers (small myelinated and unmyelinated): mechanoreceptor and pain layer RF superior colliculus periaqueductal grey marginal layer amygdala substantia gelatinosa nucleus proprius projection neurons from layers I and V to ventral horn (flexor reflex) first pain: intensity “prick” A∂ fibers intrinsic neuromodulation (gate control) wide dynamic range projection neurons second pain: “burning”, prurireceptors (itch), innocuous temperature sensation, non-discriminative touch C fibers allocortex parabrachial nucleus other TRP channels, Piezo 2, ASIC3 (heart ischaemia) transient receptor potential TRP channels in dorsal root ganglion cells, like TRPV1 for heat heat and other Jones EG (2007) The Thalamus. Cambridge University Press. Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. Sherman SM, Guillery RW (2001) Exploring the thalamus. Academic Press. polymodal, including pain and chemicals A∂ fibers C fibers NAVIGATOR 94 / 219 Sulcus centralis Sulcus centralis is the middle of the ascending sulci halfway between the frontal and occipital pole of the cerebrum. It separates the frontal from the parietal lobe. Characteristics of the adult sulcus centralis were summarised by Rolando 1831, Eberstaller 1890, Cunningham 1892 and Retzius 1896. It is in general rostroconvex but sinuous and slightly oblique from inferior/anterior to superior/ posterior. It can be divided in three parts. The superior part is a rostroconvex arch, followed by a sharp posterior convex middle part, itself followed by a faint rostroconvex third arch in the direction of the lateral genu superior fissure. In between the arches two genua are present. The cortex under the genu superior, facing the sulcus frontalis superior anteriorly, represents the middle portion of the precentral gyrus innervating the forearm. genu inferior In about 3 adults in 5 sulcus centralis cuts the upper hemisphere border (with an acute angle to the frontal pole of around 70°) and ends on the mesial surface with a posterior hook (“le crochet ou la encoche rolandique”), which never joins the ramus supramarginalis sulci cinguli. The sulcus lies within the lobulus paracentralis, itself bordered rostrally by the paracentral sulcus (a branch arising from sulcus cinguli) and caudally by the ramus supramarginalis sulci cinguli. In 1/5 of the remaining brains each, the sulcus centralis just reaches the convexity top without posterior bend, or falls short of the convexity margin with a posterior hook. If sulcus centralis reaches the convexity border, this occurs around term. In the large majority the lower end of the sulcus centralis is separated from the lateral fissure by an inferior frontoparietal annectant gyrus (the subcentral gyrus = pli fronto-pariétal inférieur, also called the rolandic operculum, see below). Both anterior and posterior this subcentral gyrus is bordered by the sulcus subcentralis anterior or posterior respectively, each short upward branches of the lateral fissure. In a minority (around 1/5) the sulcus centralis is connected to the lateral fissure by an inferior transverse sulcus (Eberstaller). Anastomoses with the sub-, pre- and postcentral sulci are frequent, occurring in about 50% of cases and easily observed with CUS after 34 w PMA. Variations of sulcal (and gyral) anatomy were pcs sip f2 sc h poc pci f3 fm sd fl sang ra rh PT st sts sti 36w, Retzius 1896 f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis (Wernicke) h ramus horizontalis of pci pci sulcus precentralis inferior pcs sulcus precentralis superior poc sulcus postcentralis PT pars triangularis ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis sang sulcus angularis sc sulcus centralis (Rolando)(highlighted) sd sulcus diagonalis st sulcus occipitalis transversus (Ecker) sts sulcus temporalis superior sti sulcus temporalis inferior term, Retzius 1896 NAVIGATOR studied at postmortem in the 19th century. The significance of detecting such variation in newborn brains is not investigated. In the depth of the sulcus centralis, rostrocaudal annectant gyri (Cunningham 1892) between pre- and postcentral gyri are always present (“pli frontopariétales” by Broca). Two in particular are important: a “pli frontoparietal moyen” at the hand knob and a “pli frontoparietal inférieur” at the lower end of the sulcus centralis The “pli fronto-pariétal moyen” is visible in nearly all ultrasound scans after 30 w PMA as an interruption of the central groove basin in outward parasagittal sections. If the central groove is divided (interrupted) it is at this site, likely due to relative elevation of this annectant gyrus, with a prevalence around 1/300 brains (figures by Sernoff 1887 in Cunningham 1892 and by Kappers 1967, De Bisschop et al. 2020). The exceptional nature of this phenomenon of interruption of the sulcus centralis is in contrast with the almost constant existence of an interrupted sulcus precentralis. 95 / 219 Cunningham 1892: early seventh month; early sulcus centralis may develop in two parts, interrupted at the pli fronto-parietal moyen pcs poc r1 ann annectant gyrus co central operculum pcs precentral superior sulcus pci precentral inferior sulcus poc postcentral sulcus r1 lower sulcus centralis r2 upper sulcus centralis co The first appearance of the central groove at postmortem is in the 19th or 20th w PMA, the sulcus is rarely visible at or before 17 w PMA (Chi et al. 1977, Afif et al. 2014). It is usually a distinct gutter by 23 w PMA. The right sulcus appears in general one week earlier than the left. For comparison the precentral sulcus usually appears around 24 w PMA and the postcentral sulcus at 25 w PMA. The sulcus centralis develops independently from the central insular sulcus: early on, the inferior extremity of the sulcus centralis is located anterior to that of the superior extremity of the sulcus centralis insulae. Development of the sulcus centralis is inherent to development of the sensorimotor cortex (Afif et al. 2014): stage 1: appearance at 18–19 w PMA of the inferior part of the central cerebral sulcus; stage 2: development of the pericentral lateral regions and beginning of opercularization at 20–22 w PMA; stage 3: development of parietal and temporal cortices and covering of the postcentral insular region at 24–26 w PMA; finally stage 4: maturation of the central cerebral regions at 27–28 w PMA. The lower portion of the sulcus centralis develops first as a linear depression, separated in some fetuses or preterm infants from the superior part of the groove initially appearing as a sulcal pit (depression). Very soon after formation the lower part of the groove merges with the upper part transforming in the mean time into a single groove. It may be possible to observe this transient separation at 25 w PMA. Such bipartite development is also seen in primates but not in lower apes. In late pregnancy the postcentral gyrus is often slightly elevated above the precentral gyrus and the sulcus centralis moves slightly caudal (away from the coronal suture) due to relative faster growth of the frontal lobe. r2 Retzius 1896: seventh month fetus with divided sulcus centralis at transition between r1 and r2 (“pli fronto-pariétal moyen” up to the surface on one side) r2 pcs poc ann r1 pci Sernoff 1877: term newborn NAVIGATOR Clinical relevance. The sulcus centralis and its surroundings can be implicated in global forebrain ischaemia, middle cerebral (MCA) and anterior cerebral artery (ACA) stroke, superior sagittal sinus thrombosis and bacterial meningitis/encephalitis. Integrity of the corticospinal tract in ultrasound is studied by locating sulcus centralis and gyri pre- and postcentrales, following the trajectory from there into the posterior limb of the internal capsule. In ELBW infants the impact of medullary venous infarction on development of the overlying sulcus centralis and motor function, requires further investigation. 96 / 219 Retzius 1896: variations of the sulcus centralis; In red a large anterior ramification of the central groove is contacting the sulcus frontalis medius Afif A, Trouillas J, Mertens P (2014) Development of the sensorimotor cortex in the human fetus: a morphological description. Surg Radiol Anat 37: 153-160. Chi JG, Dooling EC, Gilles FH (1977) Gyral development of the human brain. Annals of Neurology 1: 86-93. Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The praecentral and other sulci in the external surface of the frontal lobe. pp 244-302. De Vareilles E, Sun Z, Benders M, Fischer C, Leroy F, de Vries L, Groenendaal F, Rivière D, Dubois J, Mangin J-F () A longitudinal study of the evolution of the central sulcus’ shape in preterm infants using manifold learning. Eberstaller O (1890) Das Stirnhirn. Urban & Schwarzenberg, Wien und Leipzig. Ecker 1869: https://digi.ub.uni-heidelberg.de/diglit/ecker1869/0007 Hopkins WD, Meguerditchian A, Coulon O, Bogart S, Mangin JF, Sherwood CC, Grabowski MW, Bennett AJ, Pierre PJ, Fears S, Woods R, Hof PR, Vauclair J. Evolution of the central sulcus morphology in primates. Brain Behav Evol. 2014;84(1):19-30. Kappers A, Huber C, Crosby E (1967) The Comparative Anatomy of the Nervous System of Vertebrates, including Man. Hafner publishing company, New York. Naidich TP, Grant JL, Altman N, Zimmerman RA, Birchansky SB. Braffman B, Daniel JL (1994) The developing cerebral surface. Neuroimaging Clinics of North America 2: 201-24 Paturet G (1964) Traité d’anatomie humaine. Tome IV: Système nerveux. Masson & co, Paris. Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Sockholm: PA Norstedt 1-167. Ribas G (2010) The cerebral sulci and gyri. Neurosurg Focus 28(2): 1-24 Schweizer R, Helms G, Frahm J (2014) Revisiting a historic human brain with magnetic resonance imaging the first description of a divided sulcus centralis. Frontiers in Neuroanatomy 8: art 35: 1-8. Tamraz JC, Comair YG (2006) Brain cortical mantle and white matter core. Ch 3, pp 51-116. In Atlas of regional anatomy of the brain using MRI. Springer Verlag. ten Donkelaar HJ, Tzourio-Mazoyer N and Mai JK (2018) Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex. Front. Neuroanat. 12:93. Wagner, R (1860). “Über die typischen Verschiedenheiten der Windungen der Hemisphären und über die Lehre vom Hirngewicht, mit besondrer Rücksicht auf die Hirnbildung intelligenter Männer”, in Vorstudien zu Einer Wissenschaftlichen Morphologie und Physiologie des Menschlichen Gehirns als Seeleorgan. Göttingen, verlag der Dieterischschen Bucchandlung NAVIGATOR 97 / 219 The motor hand knob. During imaging it is often practical to try and locate the hand motor area: - structures involved in motor hand function are located in a 2 characteristic ‘precentral knob’ which is a landmark for identifying the precentral gyrus (3); it faces and forms the ‘middle segment’ of the central sulcus - the knob is a protrusion of the precentral gyrus into the central sulcus (c), posterior to the intersection of the superior frontal sulcus (a) with the superior precentral sulcus (b)(separating superior and middle frontal gyri 1 and 2) a 1 b c 3 3 c 4 2 3 4 - in the sagittal plane the knob has the shape of a posteriorly directed hook facing the postcentral gyrus (4). sections showing the precentral knob, which can look like an inverted omega or a horizontal epsilon when cut axially omega Crichton P, Crichton J [corrected to Crichton P]. Penfield's homunculus. J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):525. epsilon NAVIGATOR 98 / 219 Appearance of the sulcus centralis on postnatal MRI in preterm infants. 27 w, twin 29 w 32 w 30 w sulcus precentralis sulcus centralis sulcus centralis sulcus postcentralis term equivalent MRI in ELBW infant sulcus cinguli sulcus centralis sulcus centralis e l fissur latera insula sulcus parietooccipitalis NAVIGATOR 99 / 219 Midline and sulcus centralis at 25w GA, on day 1. genu ——> <—— splenium pcs sc poc limen NAVIGATOR 100 / 219 Appearance of the sulcus centralis in parasagittal CUS sections. The sulcus centralis can be recognized in several coronal ultrasound planes as a relatively straight line pointing from the surface to the ventricle. In postatrial sections sulcus centralis can approach the midline near term, but ends just rostral to the ramus supramarginalis sulci cinguli. In parasagittal sections sulcus centralis is recognized - beyond 30w PMA - as the tortuous groove flanked rostrally by the (almost always) double sulcus precentralis (inferior and superior) and caudally by the sulcus postcentralis. There is a delay of 2 to 4 weeks between postmortem appearance (see above) and convincing recognition with postnatal CUS. In scans before 28w PMA the sulcus may still be a gutter with separated lips and not a single line. high section pcs sc sc sulcus centralis @ 27w PMA sulcus centralis @ 30w PMA sc sulcus centralis @ 36w PMA low section pcs sc pci sc sc poc poc sulcus centralis @ 37w PMA poc sulcus postcentralis pci sulcus precentralis inferior sulcus centralis @ 36w PMA NAVIGATOR 101 / 219 Different aspects of normal sulcus centralis variation. a normal right central groove high section low section sc rs sc sup poc pli FP moyen sc inf sc sulcus centralis in the depth of the sulcus centralis there is a normal annectant gyrus apparently interrupting the sulcus; only of this annectant gyrus reaches the surface, the sulcus centralis is referred to as being divided the ascending ramus supramarginalis sulci cinguli (rs) cuts the hemisphere convexity in between the ascending parts of the postcentral and central sulci R asymmetry of the sulcus centralis: large anterior branch on the left GA 27w1d plus 32d L early in the development of sulcus centralis, asymmetry can be detected with ease; in this infant the right sulcsu developed tortuosity slower than the left NAVIGATOR Preterm of GA 30w, second week of life: early tortuosity in the sulcus centralis, prominent near the future hand knob. 102 / 219 NAVIGATOR 103 / 219 Early detection of the interruption (division) of the left sulcus centralis in two different ELBW infants. 24w PMA 24w GA, 33w PMA L R left GMH sc sc 28w PMA L R sc sc sc sc sc = sulcus centralis (central groove) NAVIGATOR 104 / 219 Evolution of the sulcus centralis above porencephaly due to terminal vein infarction in an ELBW preterm infant (GA 24w). R d12 L sc sc at term different tortuosity of the sulci centrales: less fluent and smaller ondulations on the affected side R L NAVIGATOR 105 / 219 Sulcus cinguli from Also called the callosomarginal or supracallosal sulcus, sulcus cinguli begins below the callosal rostrum before it sweeps around the genu running more or less parallel to the callosal trunk. Phylogenetically, in primates, unlike in antecedent mammals, sulcus cinguli disconnects from sulcus calcarinus. In the anterior part it separates the superior frontal gyrus above the cingulate gyrus below and behind. In front of the precallosal part, two inconstant vertical sulci run parallel to sulcus cinguli. The sulcus rostralis superior of Eberstaller (1884, emerging just before 30 w PMA)(“sillon susorbital de Broca”) courses front to back around the rostrum of the corpus callosum, originating near the “carrefour olfactif“ of Broca, and ends closely behind the frontal pole. It is independent and roughly parallel to the anterior sulcus cinguli, frequently accompanied by a shallower sulcus rostralis inferior. In about a third the superior rostral sulcus is connected to sulcus cinguli. Below the genu corporis callosi and below the initial point of sulcus cinguli, a short arched and vertical sulcus, called sulcus parolfactorius anterior, separates the mesial frontal lobe from the subcallosal (parolfactory) area (with septal nuclei and precommissural hippocampus) in front of the lamina terminalis. giraffe lemur po calc man early ramus supramarginalis Caudally sulcus cinguli ends with a constant ascending ramus supramarginalis in the parietal lobe, separating precuneus from the paracentral lobule. This - often festooned - ramus has a characteristic relationship to the central sulcus, ending about 1 cm (in adults) posterior to it. Short upward secondary branches of sulcus cinguli create the appearance in the mature stage of a cockscomb (“crête de coq”). A posterior connection between the ramus supramarginalis and sulcus subparietalis (developing after 26 w PMA) occurs in about one brains in three. 24w A constant branch, sulcus paracentralis (“sillon préovalaire de Broca”), ascends in front of the mesial end of the sulcus centralis: this branch and the ramus supramarginalis itself delineate the lobulus paracentralis. Several interruptions of sulcus cinguli are frequent along its course. Submerged annectant gyri (from 2 to 8 in the adult brain, “plis de passage fronto-limbiques”) lead to invaginations of the superior frontal gyrus or paracentral lobule into the gyrus cinguli. An unbranched sulcus cinguli is not most common (around one brain in three). These folding patterns have been confirmed with MRI based on sulcal pit calc: su. calcarinus po: su. parieto-occipitalis inguli sulcus c 29w mesial postmortem view at 29w GA term NAVIGATOR (deepest point) analysis (Meng et al. 2016). Gyrus cinguli narrows at the isthmus behind the splenium, to continue in gyrus parahippocampalis above the anterior part of sulcus calcarinus. The sulcus cinguli is duplicated in about one third of hemispheres, mainly in its anterior segment, the “double” groove being referred to as sulcus paracinguli, situated either above or below sulcus cinguli itself. Doubling of the anterior sulcus cinguli occurs more on the left: over half on the left and around one third on the right. The sulcus cinguli starts to be visible at postmortem in some fetuses just before 20 w PMA, in some preterms first indications of it appear only around 24 w PMA. Between 24 and 28 w PMA the interrupted cingulate lines coalesce and by 29w usually form one line (if uninterrupted later on)(Slagle et al. 1989). Around 28 w PMA cingulate sulci can be about 2 mm deep in the coronal plane, around 32 weeks about 4-5 mm deep, around term 8-9 mm on average. Some initial branching starts around 32 w PMA. Ultrasonographic description of sulcus cinguli. In a near sagittal plane sulcus cinguli can most often be depicted in its entire length. It becomes an uninterupted line around 29 w PMA. Sulcus paracinguli is easy to detect, either under or above sulcus cinguli around the genu corporis callosi. Ramus supramarginalis and sulcus paracentralis (borders of the lobulus paracentralis) can often be observed after 32 w PMA. In coronal sections, both sulci cinguli are readily seen above the corpus callosum; they are of increasing but variable depth with maturation and start to be seen around 24 w PMA. They are most often not at the same level in relation to the interhemispheric fissure. 106 / 219 sc sulcus cinguli spc sulcus paracinguli (either under or above sulcus cinguli) rsm ramus supramarginalis sulci cinguli f l ramus lobularis (paracentralis) f ramus frontalis c ramus cinguli p ramus posterior sc ssp sulcus subparietalis scc sulcus corporis callosi c spo sulcus parieto-occipitalis calc sulcus calcarinus sulcus paracinguli (spc) spc interruption by fronto-limbic annectant gyri typical anatomy: asymmetry is normal l c scc rsm c p ssp spo calc NAVIGATOR 107 / 219 Clinical relevance. The sulcus and gyrus cinguli can be implicated in global forebrain ischaemia, ACA stroke, and bacterial meningitis/encephalitis. Abnormalities of the midline clearly alter cingulate anatomy. A maturational delay but not an alteration in shape (compared to the normal detailed description from a discontinuous sulcus around 26 w PMA, to continuity by 30 w PMA and branching in the following 4 weeks) was suggested by postnatal CUS study of the developing cingular groove, following unilateral medullary venous infarction in preterm infants with PMA below 32 w PMA (Slagle et al. 1989). The striking variation with either existence or not of sulcus paracinguli and fronto-limbic annectant gyri can be easily described in the newborn but this has so far not been done in a clinical context. As it delimits the limbic system from prefrontal cortex, further study of abnormal development of sulcus cinguli could prove useful in understanding higher brain function. sulcus rostralis (superior and inferior) in the direction of the frontal pole lobulus and sulcus paracentralis ramus supramarginalis of sulcus cinguli sulcus parietooccipitalis postatrial parietal homogenous hyperechoic area occipital lobe Eberstaller 1890, Cunningham 1892, Retzius 1896, Testut and Latarjet 1948, Paturet 1964, Chi et al 1977, Ebeling et al. 1989, Slagle et al. 1989, Paus et al. 1996, Tamraz and Comair 2006, Ribas 2010, Spasojevic et al. 2010, Meng et al. 2016, ten Donkelaar et al. 2018 NAVIGATOR 108 / 219 3D CUS scoring of sulcus cinguli maturation. coronal sulcus cinguli description absent barely visible indentation score parasagittal sulcus cinguli description absent or barely visible 0 incomplete doubling 1 2 2 incipient branching I-shape 0 1 complete + ramus supramarginalis clear indentation score definite branching 3 multiple tortuous or long branches 4 typical images at term courtesy Nuria Carreras Blesa, Barcelona, to be validated by ongoing research 3 4 5 NAVIGATOR 109 / 219 Sulcus and lobulus paracentralis. term sulcus paracentralis 30w GA, 35w PMA rsm rsm r poc term 27w GA, 35w PMA pre pre sulcus paracentralis rsm sc posterior section with precentral (pre), central (sc) and postcentral sulci (rsm ramus supramarginalis sulci cinguli) GA 33w, PMA 34w rsm = ramus supramarginalis sulci cinguli lateral convexity mesial convexity rsm NAVIGATOR 110 / 219 The cingulum: connections and function in the limbic systems. Within the limbic system, cingulate cortex has functions that differ between the anterior part, which is mainly involved in decision making, and the posterior part, involved in self awareness. sensorimotor decisions subsystem value of a stimulus encoded (reward or punishment) OFC (orbitofrontal cortex) amygdala striatum cognitive spatial map subsystem emotional subsystem anterior insula midbrain grey MCC PCC ACC ACC (anterior cingulate cortex) emotion: value in contact with action and its result: goal directed motor behaviour by motivation MCC (midcingulate cortex) encoding of the relation between an action and outcome value, initiation of decision of action what ? pathway HC and EC sensory core motor core cerebellar loop sensory belt motor belt striatal loop sensory association cortex frontal association cortex limbic systems sensory and association neocortex PCC (posterior cingulate cortex) spatial and memory context for an action episodic memory: what happened where ? where in space ? pathway (and when ?) Catani M, Dell'acqua F, Thiebaut de Schotten M. A revised limbic system model for memory, emotion and behaviour. Neurosci Biobehav Rev. 2013 Sep;37(8):1724-37. Mastrogiuseppe M, Bertelsen N, Bedeschi MF, Lee SA. The spatiotemporal organization of episodic memory and its disruption in a neurodevelopmental disorder. Sci Rep. 2019 Dec 5;9(1):18447. Rolls ET (2019) The cingulate cortex and limbic systems for action, emotion and memory. Chapter 2 in Handbook of Clinical Neurology: Cingulate cortex vol 166, BA Vogt Editor. pp 23-37. Vogt BA (2019) Cingulate cortex in three limbic subsystems. Chapter 3 in Handbook of Clinical Neurology: Cingulate cortex vol 166, BA Vogt Editor. pp 39-51. NAVIGATOR 111 / 219 The limbic systems as part of the motor behaviour network. pain conflict between responses lateral orbitofrontal cortex (unpleasant, aversive stimuli) MCC PCC es of va lu le as ca medial orbitofrontal cortex (rewards, pleasant stimuli) 23 (-) 32 hippocampus to PCC: autobiographical memory, self-reflection, state between tasks, strategic decision making PMA/SMA 24 29-30 ACC (+) subgenual ACC 25 Am 28 ventromedial prefrontal cortex autonomic response 35-36 hypothalamus numbers = Brodmann areae 28 = entorhinal cortex limbic plus paralimbic are mesocortex 24,25 and 32: anterior cingulate cortex brainstem autonomic nuclei 1 hippocampal formation (inner ring) 2 limbic (parahippocampal) cortex 3 paralimbic (proneocortical) cortex NAVIGATOR 112 / 219 Complex cingulate porencephaly mimicking schizencephaly in a preterm infant following subdural and parenchymal haemorrhage. <— subdural haematoma subdural haematoma d7 PMA 25w parenchymal damage parenchymal damage no flow in the right transverse to sigmoid sinus transition hyperechoic thrombus in the left transverse to sigmoid sinus transition d14 PMA 26w d49 PMA 31w complete recovery of flow without heparinisation NAVIGATOR 113 / 219 Sulcus temporalis superior Lobus temporalis is shaped at the convexity by the superior, middle and inferior temporal gyri, numbered T1, T2, and T3, separated by sulcus temporalis superior and inferior, numbered t1 and t2. The temporopolar cortex is a heterogeneous transition area between lateral neocortex and mediodorsal paleocortex (olfactory plus hippocampal). On the upper surface of gyrus temporalis superior, the planum polare, the transverse gyri (gyrus temporalis transversus anterior and posterior of Heschl) and the planum temporale can be distinguished, separated by specific sulci. A late appearing and small transverse sulcus may cut the temporal pole in front of the anterior end of the sulcus temporalis superior; a vertical temporopolar gyrus lies lateral to it in front of the horizontal large temporal gyri and sulci of the convexity. Sulcus temporalis superior (t1) is a constant, phylogenetically old sulcus (the “parallel” sulcus, in course similar to the lateral fissure). It is deep and extends, from near the inferior insula, parallel to the opercular surface of the superior temporal gyrus to its end in a bifurcation at the angular gyrus. The rostral end of the sulcus temporalis superior never extends into the temporal tip. This explains the apparent spreading of the superior temporal gyrus over the temporal pole in contact with the rostral end of the gyrus temporalis medius. Its caudal end, the ramus ascendens of the sulcus temporalis superior, rises above the posterior end of the lateral fissure. The anterior parietal sulcus of Jensen descends behind the upward branch of the sulcus temporalis superior, thus separating the gyrus supramarginalis in front of it from the gyrus angularis (“pli courbe”) behind it. The angular sulcus is the main branch produced by the expansion of the cortex forming area 39 (the angular gyrus, a fold of cortex around the angular sulcus, usually in the shape of a U with its concave face looking to anterior and inferior). The angular gyrus often splits into two limbs as it runs over into the occipital lobe. 3 6 4 2 1 8 * pt 41 42 pp sts T1 T2 * Broca’s area T3 areae Brodmann (1909) 1,2,3 sensory 4 motor 6 premotor and supplementary motor 8 frontal eye field 17 visual 41,42 auditory 21,22,44,45 language 6 Ø olfactory area ECF extreme capsule fasciculus FA fasciculus arcuatus FLS fasiculus longitudinalis superior pp planum polare pt planum temporale scoll sulcus collateralis sr sulcus rhinalis sts sulcus temporalis superior 4 31 2 scoll 17 Ø sr Brodmann, K. (1909). Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Transl. by L.J. Garey in English (1999) Brodmann’s Localisation in the Cerebral Cortex. Leipzig, Barth, London: Imperial College Press. Zilles K (2018) Brodmann: a pioneer of human brain mapping-his impact on concepts of cortical organization. Brain: a journal of neurology, 141(11). NAVIGATOR Below the angular sulcus a third branch, the anterior occipital sulcus can be recognised as a boundary to the pre-occipital area in front of a (rare in humans) sulcus lunatus. Sulcus temporalis superior may be divided near the transverse gyri of Heschl into an anterior and posterior part. Its most consistent interruption (around 1 adult brain in 3) is at the level of the sulcus centralis where a large annectant gyrus reaches the surface and 114 / 219 connects the transverse gyri of Heschl over the superior temporal gyrus with the middle temporal gyrus. At this level there is an inconstant sulcus acousticus ascending from sulcus temporalis superior towards the lateral fissure, indicating the anterior extent of the Heschl gyri. Brodmann area 21 is situated approximately in the middle temporal gyrus; it blends gradually with neighbouring areas. A simplified view on some Brodmann cytoarchitectonic areas visible in the CUS window. Based on variations in the thickness, cell density and other histological features of the six neocortical laminae, the human brain can be divided into some 50 cytoarchitectonic areas, typically those recognized by the neuroanatomist Korbinian Brodmann around 1909. sc sts sts anterior lateral view: Heschl gyri in relation to the insula, 1 to 3 gyri, usually larger on the left (Braus 1932)(sc sulcus centralis (Rolando), sts sulcus temporalis superior) Bartha-Doering L, Kollndorfer K, Schwartz E, Fischmeister FPS, Langs G, Weber M, Lackner-Schmelz S, Kienast P, Stümpflen M, Taymourtash A, Mandl S, Alexopoulos J, Prayer D, Seidl R, Kasprian G. Fetal temporal sulcus depth asymmetry has prognostic value for language development. Commun Biol. 2023 Jan 27;6(1):109. Becker Y, Phelipon R, Sein J, Renaud L, Meguerditchian A (2021) Planum temporale grey matter volume asymmetries in newborn monkeys (Papio anubis). Brain Structure and Function, may 2021. Braus, Hermann. Anatomie des Menschen: ein Lehrbuch für Studierende und Ärzte (Band 3): Centrales Nervensystem Berlin, Heidelberg, 1932 Brodmann K (1909) Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Transl. by L.J. Garey in English (1999) Leipzig, Barth, London: Imperial College Press. Chau AMT, Stewart F, Gragnaniello C (2014). Sulcal and gyral anatomy of the basal occipital-temporal lobe. Surgical Radiological Anatomy, 36, 959-965. Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The praecentral and other sulci in the external surface of the frontal lobe. pp 244-302. Eberstaller O (1890) Das Stirnhirn. Urban & Schwarzenberg, Wien und Leipzig. Heschl RL (1878) Über die vordere quere Schläfenwindung des menschlichen Grosshirns. Braumuller, Vienna. Paturet G (1964) Traité d’anatomie humaine. Tome IV: Système nerveux. Masson & co, Paris. Kasprian G, Langs G, Brugger PC, Bittner M, Weber M, Arantes M, Prayer D (2011) The prenatal origin of hemispheric asymmetry: an in utero neuroimaging study. Cerebral cortex 21: 1076-1083. Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Sockholm: PA Norstedt 1-167. Shellshear JL (1927) The evolution of the parallel sulcus. J Anat 61: 276-278. Tamraz JC, Comair YG (2006) Brain cortical mantle and white matter core. Ch 3, pp 51-116. In Atlas of regional anatomy of the brain using MRI. Springer Verlag. ten Donkelaar HJ, Tzourio-Mazoyer N and Mai JK (2018) Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex. Front. Neuroanat. 12:93. NAVIGATOR 115 / 219 Processing of sound in the central nervous system (1). frontal eye field 1 2 3 4 5 6 cochlear nuclei superior olivary nuclei (medial and lateral) lateral lemniscus (with its nuclei) inferior collicle medial geniculate primary auditory cortex (Heschl gyrus, area 41, auditory core) 7 auditory belt and parabelt (superior temporal gyrus and sulcus) spatial nonspatial auditory processing is bilateral (callosal connections from area 41, 42 and 22) with a final left level of hearing in 94 % of the right handers 6 5 7 medial geniculate: preferred responce to specific spectral combinations and to specific time intervals: principal nucleus is the ventral one (parvocellular) with connections to area 41; medial and dorsal magnocellular nuclei send information to belt and parabelt modulating feedback colliculus inferior: mainly in central nucleus, laminar by frequence specificity; representation of auditory space and tuning of sound by frequency, and location of sound by precedence effect; pericentral nuclei send info to colliculus superior; dorsomedial nuclei send info to the other side 4 lateral lemniscus nuclei (especially dorsal nucleus) codes signal onset and duration of sound (large in animals with echolocation); information on balance between ears sent to colliculus inferior colliculus superior: spatial map of sound congruent with visual map: reflex movement of head and eyes the cochlea separates ear input into several parallel pathways: VCN (ventral cochlear nucleus)(efferents via ventral acoustic stria) - bushy cells (AMPA) receive ± 10 axons, transmit to superior olives: sound structure, pitch - stellate cells (NMDA) receive 10 axons, transmit to several nuclei: spectrum of sound energy by tonic firing - octopus cells (AMPA) detect coinicidence firing in ± 60 axons: sound patterns (periodic like in vowels or music, broadband onset like in consonants); transmit to contralateral nucleus of the lateral lemniscus via stria acoustica intermedia interaural intensity difference (ILD) detected by lateral superior olive LSO (coincident arrival due to asymmetry in cell and axon size) and medial nucleus of the trapezoid body neurons; reduced in humans 3 interaural time difference (phase, ITD) detected by medial superior olive MSO neurons < 4 KHz = coincidence detectors; specialised in low frequency, very large in humans to pre-olivary and lateral olivary nuclei 1 inhibition via glycine (one side to the other), via glycine and GABA dorsal to ventral, via cap nucleus ipsilateral pre-olivary cells: descending control nucleus of the trapezoid body: vestigial in humans phase-locked transmission (up to 3 KHz) in auditory nerves: input to brain favours speciesspecific natural sounds; each axon has place code and frequency code (specific tuning curve) DCN (dorsal cochlear nucleus): fusiform cells interpret spectral cues (cochlear axons via deep layer) compared to predictable cues (molecular layer axons from granule cells) for sound localisation; efferents via dorsal acoustic stria 2 3 17 4 tonotopy: high frequency near base, low frequencies near helicotrema (where basilar membrane is widest and less stiff): continuous array of frequencies NAVIGATOR 116 / 219 Processing of sound in the central nervous system (2). The ABR (auditory brainstem response to sound). Core, belt and parabelt. Normal trace in the term newborn. The waves indicate the trajectory of the acoustic stimulus. Wave I: auditory nerve near the cochlea. Wave II: intracranial portion of the nerve and cochlear nucleus at the medulla oblongata. Wave III: superior olive complex at the lower pons. Wave IV: nucleus of the lateral lemniscus at the upper pons. Wave V: inferior colliculus Brodmann area 41: core area 42: belt 41 22 37 42 21 20 Peripheral disorder (auditory nerve, spiral ganglion, middle ear or external auditory meatus) • Absent I wave with normal III-V relative latency • Complete lack of responses Central disorder • Normal wave I but prolonged I-V latency • No waves after wave I • Normal wave I and prolonged I-III or III-V relative latency auditory cortex core (lemniscal): processing pitch and species-specific vocalisations (area 41); regular patches, cortex columns = “rain shower”; sequence medial (high pitch) to lateral - 2D tonotopic map (low freq. rostral) - map of aural interaction - clustering re bandwidth and biological - significance loudness adaptive (early disruption possible) Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates. Sherman SM, Guillery RW (2001) Exploring the thalamus. Academic Press. auditory cortex belt: processing syllables and cues like time, context and attention (area 42) association cortex area 22: the superior temporal area forms a homogeneous structural region (the parabelt) - it encroaches on the posterior two-thirds of the superior temporal gyrus; anteriorly it extends in front of the level of the sulcus centralis where it climbs onto the medial surface of the superior temporal gyrus; posteriorly it attains the level of the vertical branch of the lateral fissure and gradually blends with the supramarginal area (Brodmann area 40) - even higher processing of sound occurs here, anterior: voice selective, posterior: face/speech selective NAVIGATOR 117 / 219 Further neocortical processing of sound, language. core: area 41: primary auditory cortex in anterior transverse gyrus of Heschl; afferents from ventral area of medial geniculate nucleus; point to point tonotopic map with alternating stripes of EE (excitation both ears) and EI (inhibition ipsilateral ear); specialised for vocalisation (perception of pitch) posterior temporal to prefrontal stream: spatial integration of sound sulcus temporalis superior anterior temporal to prefrontal stream: non-spatial (higher function) integration of sound PT Wernicke area core PP belt belt: area 42: auditory association cortex in posterior transverse gyrus of Heschl; afferents from rest of medial geniculate nucleus; less precise tonotopic map temporopolar Against a rudimentary Brodmann map, the major connections for language function are demonstrated. Injury to the cortex in connected areas and/or to underlying tracts may impair language (development). FA fasciculus arcuatus FLS fasciculus longitudinalis superior ECF external capsule fibers parabelt: area 22: processing hierarchy from posterior to anterior; perception of speech syllables; activation dependent on context (speech); what and where auditory streams parabelt m oly p l ra o p superior tem ual ral vis tempo on cortex ati associ cortex temporopolar cortex: paralimbic belt: perception of complex visual stimuli leading to consolidated (remote) object recognition like autobiographic events and faces; lesions lead to retrograde amnesia x te or c al od at convexity PP: planum polare PT: planum temporale uncus temporopolar cortex mesial temporal visual association cortex Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates. NAVIGATOR 118 / 219 Ultrasonographic description of temporal sulci. Sulcus temporalis superior is visible under the insula as one moves to the surface of the temporal lobe in parasagittal sections. The angular gyrus around its caudal end can often be visualised partially. In coronal sections it is the deep sulcus under the lateral fissure at atrial level. In fetal MR studies it is more common to find a deeper right than left superior temporal sulcus (Bartha-Doering et al. 2023), which contrasts with the left preference for language development. has not been done. This is due to the difficulty of delineation of the anterior and posterior borders of these gyri. Gyrus and sulcus temporalis superior are analyzed in MR studies that focus on language development of preterm infants (Monson et al. 2018). At term equivalent age, diffusion parameters for auditory cortex are different between preterm infants and term control infants. Preterm birth has most impact on the insula, superior temporal sulcus and ventral portions of the pre- and postcentral sulci in both hemispheres (Engelhardt et al. 2015). Clinical relevance. Although variation in size and form of gyrus parahippocampalis and of the temporal and fusiform gyri may have important functional relevance to memory, hearing, speech and facial recognition, detailed description with CUS The location of a temporal lobar parenchymal or subarachnoid haematoma should be defined in relation to the temporal sulci and gyri for better understanding of their impact on outcome (Hoogstraate et al. 2008). within BVR thrombosis aneurysm rupture @ circle of Willis deficient haemostasis SMCV or vein of Labbé thrombosis direct vein laceration temporal matrix haemorrhage with venous infarction bleeding around primitive tentorial sinus NAVIGATOR 119 / 219 CUS appearance of the sulcus temporalis superior. 35w PMA, coronal anterior to posterior Sulcus temporalis superior is usually seen at postmortem around 24 w PMA, clearly present by 26 w PMA. Earliest visible are its middle and posterior parts. The anterior part and the ascending branch develop after 30 w PMA, as does the sulcus temporalis inferior which appears around 28 tot 30 w PMA. There are early left-right asymmetries in sulcus temporalis superior: already at 26 w PMA the right sulcus temporalis superior tends to be more prominent and deeper than the left; on the other hand the left lateral fissure tends to be longer. The left planum temporale tends to be larger than the right from early on. This complex of asymmetries - there is a also higher frequency of a left sulcus diagonalis - is probably communication-related (language in humans). sulcus rhinalis coronal sulcus collateralis parasagittal sc insula insula gyrus temporalis superior sections at 38w PMA (GA 24w5d) 34w PMA, arrow = sulcus temporalis superior 35w PMA, arrows = sulcus temporalis superior fissura lateralis NAVIGATOR 120 / 219 Twin GA 35w 6d, now PMA 37w sulcus temporalis superior sulcus temporalis inferior GA 38w, PMA 39w sulcus temporalis superior sulcus temporalis inferior NAVIGATOR 121 / 219 Sulcus temporalis superior and its relations. axial temporal Sulcus occipitotemporalis is well observed in mastoid view: the sulcus collateralis points in the direction of the bottom of the temporal part of the lateral ventricle. The gyrus fusiformis lies superficial to the sulcus collateralis often with an undeep sulcus on top, and the sulcus occipitotemporalis is proximal to this gyrus. cornu Ammonis parasagittal gyrus fusiformis gyrus parahippocampalis gyrus supramarginalis insula Heschl gyri vermis 38w PMA, arrow = sulcus collateralis 38w PMA, arrow = sulcus temporalis superior parasagittal parasagittal 35w PMA, arrow = sulcus temporalis inferior uncus 35w PMA, arrow = sulcus rhinalis gyrus angularis NAVIGATOR 122 / 219 A rostral temporal tract mimicking a sulcus. term, RDS STS preterm near term STS hyperchoic line in the core of the temporal white matter near the temporal pole, compatible with fasculus longitudinalis inferior ELBW now 34w PMA STS SGA preterm now 34wPMA NAVIGATOR 123 / 219 Other temporal sulci One or two transverse temporal gyri (Heschl 1878) cross the dorsal aspect of the superior temporal gyrus, in the depth of the lateral fissure, just lateral and posterior to the inferior sulcus circularis insulae. They are oriented from anterior and out to posterior and in, towards the posterior superior angle of the insula. Brodmann areae 41 and 42, for primary cortical auditory perception, are the surface of these gyri. More frequently doubled on the right side (Pfeifer 1936), they gyri are separated, at least partly, by an intermediate transverse temporal sulcus. They are posteriorly separated from the planum temporale, by the transverse supratemporal sulcus (Holl 1908) originating from the lateral fissure. The anterior extent of the of these gyri is demarcated by the sulcus acousticus (also called sulcus temporalis anterior transversus). In front of the sulcus acousticus is the planum polare. The triangular planum temporale borders medially on the posterior superior angle of the insula. parasagittal Heschl gyri insula gyrus supramarginalis gyrus angularis sulcus temporalis superior -> 38w PMA planum polare lateral medial Heschl gyrus planum temporale sulcus circularis insulae posterior superior angle superior view of right temporal operculum: area 41 = Heschl’s transverse gyrus Heschl RL (1878) Über die vordere quere Schläfenwindung des menschlichen Grosshirns. Braumuller, Vienna. Holl M (1908) Die Insel des Menschen und Affenhirns in ihren Beziehung zum Schlafenlappen. Sitz Berl Akad Wissensch Wien Math Naturw Kl 117(3):365–410. lateral fissure ior super s i l a r o temp gyrus NAVIGATOR Sulcus temporalis inferior. This sulcus borders the middle temporal gyrus below. It runs horizontal in its anterior part, is often interrupted into small transverse grooves between annectant gyri to end in an ascending branch. The middle temporal gyrus is wider and more curved than the straighter superior temporal gyrus. Inferolateral to the anterior occipital sulcus (inferior branch of the superior temporal sulcus) this gyrus runs into the occipital lobe. The inferior temporal gyrus lateral to it is bordered by the occipitotemporal sulcus that separates it from the gyrus fusiformis: it is often discontinuous, mainly posteriorly, extending like the fusiform gyrus close to the preoccipital notch. At this level, it is continuous with the inferior occipital gyrus. Sulcus temporalis inferior is usually present at postmortem by 30 w PMA. Sulcus occipito-temporalis. The occipito-temporal sulcus courses lateral to the collateral sulcus, near the inferolateral margin of the hemisphere, usually ending close to the preoccipital notch in front of the gyrus lingualis (itself bordered caudally by the sulcus calcarinus). Anteriorly it moves towards the collateral sulcus. It has frequent interruptions, and is continuous in less than half. It constitutes the outer boundary of the gyrus fusiformis, which does not reach the temporal pole. Width of gyrus fusiformis increases from rostral to caudal before it becomes smaller again to merge with the inferior occipital lobe. It is so called because it is spindle-like (“fuseau”) in configuration with a larger midpart compared to its extremes. Typically it can be recognized by the presence of a midfusiform groove. On coronal sections this superficial midfusiform sulcus creates an omega-like appearance of the gyrus fusiformis. Sulcus occipito-temporalis is usually present at postmortem inspection by 28 w PMA. The gyrus fusiformis is an area of visual processing, a.o. facial recognition. 124 / 219 section slightly inward from the sulcus temporalis superior sulcus temporalis inferior 31w PMA, arrows = sulcus temporalis superior and inferior sulcus collateralis—— ———————> gyrus fusiformis gyrus <—————lingulais sulcus calcarinus NAVIGATOR 125 / 219 3D visualisation of temporal sulci. parasagittal scans (35w PMA) numbers are Brodmann areae rasts fl ra 41 22 gts sts gsm 40 39 fl fissura lateralis ft fissura transversa (Bichat) gang gyrus angularis gfus gyrus fusiformis gph gyrus parahippocampalis gsm gyrus supramarginalis gts/m/i gyrus temporalis superior/ medius/inferior gang sts sulcus temporalis superior ra ramus ascendens of sts sc sulcus centralis scoll sulcus collateralis sot sulcus occipito-temporalis coronal scans (35w PMA) 21 parasagittal scans (35w PMA) gts sts ft gph gtm gti gfus scoll ft scoll uncus sot gph 40 gang 21 sulcus temporalis superior axial planes from 3D recording gfus gti scoll sot gph 32 w PMA 35 w PMA courtesy Nuria Carreras Blesa, Barcelona NAVIGATOR 126 / 219 Sulcus collateralis and hippocampus The sulcus collateralis is an elongated S-shaped groove, often uninterrupted and very constant. At the caudal end it may fuse with sulcus calcarinus or pass below it for a short distance, not more posterior than splenium. The sulcus collateralis separates the parahippocampal and lingual gyri above (ento- and perirhinal cortex) from the fusiform gyrus below (neocortex). It elevates the inferior wall of the atrium and the temporal horn of the lateral ventricle, as observed in coronal sections. At postmortem the sulcus collateralis is usually present by 24 w PMA. 11 8 4 14 13 15 9 EX ORT C NAL RHI O T EN 6 lateral view 6 stria terminalis (caudal amygdalofugal pathway) gyrus dentatus gyri Andrea Retzii limbus Giacomini (~2) fornix (hippocampal efferent pathway) sulcus rhinalis … sulcus collateralis gyrus ambiens (mesocortex) gyrus semilunaris (over cortical amygdaloid nuclei) gyrus parahippocampalis adapted from Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. 2 16 12 7 1 2 3 4 5 6 7 8 9 3 1 17 Gyrus parahippocampalis is bordered above by the sulcus hippocampi. It splits under the splenium into a part above above (towards the isthmus cinguli) and below the rostral part of the sulcus calcarinus (into the gyrus lingualis). The area in front of the sulcus calcarinus and above the gyrus fusiformis has the appearance of a tongue with an incisure in the middle: the gyrus lingualis. Under the uncus, in front of sulcus collateralis, the sulcus rhinalis (a phylogenetically early sulcus separating transitional cortex from expanding neocortex) lies rostral and somewhat inferior to sulcus collateralis in a similar horizontal course against the mesial part of the temporal lobe. Above sulcus rhinalis the uncus is bordered below by the uncal sulcus. An inconstant sulcus at the tentorial edge (sulcus intrarhinalis) lies between sulcus rhinalis and uncus. Sulcus collateralis is visible in the parasagittal plane through uncus and gangliothalamic egg, as a relatively straight line that diverges caudally from the transverse fissure to border the gyrus lingualis anteriorly. It presents just below the level of the floor of the temporal horn that is seen more laterally. In coronal sections between uncus and the atrium sulcus collateralis extends from the mesial temporal surface in the direction of the sharp echoic line that is the floor of the temporal horn. Sulcus rhinalis is inferior and anterior to it. 5 10 10 11 12 13 14 15 16 17 gyrus paraterminalis gyrus subcallosus cornu ammonis (gyri digitati externi) fimbria hippocampi gyrus uncinatus (CA1) uncal apex (gyrus intralimbicus)(CA3) subiculum endorhinal sulcus NAVIGATOR 127 / 219 1 2 3 4 5 6 sulcus rhinalis sulcus collateralis gyrus lingualis gyrus fusiformis sulcus calcarinus temporal pole 6 1 2 3 5 courtesy Silvia Planas, Barcelona (term human newborn brain inferior surface) 4 NAVIGATOR 128 / 219 The effect of midline development on hippocampus. Some headlines on midline development: - non-mammals: pallial commissure - protomammals: anterior commissure (almost olfactory only) and hippocampal commissure - callosal mammals: anterior commissure (olfactory and isocortical), hippocampal commissure, callosal commissure formed in the hippocampal formation (isocortex only) - primates: anterior commissure (olfactory but mainly isocortical), hippocampal commissure, callosal commissure expanded in the massa commissuralis; pre-, supra- and postcallosal hippocampus (H1, H2, H3). acallosal mammal H HC M T AC LT AC anterior commissure AM amygdala CC callosal commissure, corpus callosum F fornix H hippocampus (1 precommissural, 2 supracommissural, 3 retrocommissural) Hy hypothalamus HC hippocampal commissure LT lamina terminalis Monro (foramen interventriculare) PO preoptic area S septum T thalamus F H PO AM corpus callosum splits the hippocampal commissure in a dorsal and a ventral part in orange: mesocortex in grey: isocortex in blue: choroidal fissure callosal mammal H2 CC HC M AC T H1 PO LT Gloor P (1997) The temporal lobe and limbic system. Oxford University press. F H AM H3 NAVIGATOR Corpus callosum changes the hippocampal system. 1 2 3 4 5 6 precommissural hippocampus postcommissural hippocampus supracommissural hippocampus entorhinal cortex amygdala psalterium 129 / 219 NAVIGATOR 130 / 219 CH crown-heel length CR crown-rump Infolding of ammon’s horn on the dentate gyrus. - 13 to 14 weeks gestation: open hippocampal sulcus - 15 to 16 weeks: the dentate gyrus and cornu ammonis are infolding; CA1, CA2, and CA3 fields of the cornu ammonis are arranged linearly - 18 to 20 weeks: dentate gyrus and cornu ammonis have folded into the temporal lobe; hippocampus and subiculum approximate each other across a narrow hippocampal sulcus 4 3 4 A Ammon’s horn (CA 1-4) F fimbria M molecular stratum of dentate gyrus T temporal horn G germinal matrix S subiculum P entorhinal cortex small arrowheads: dentate gyrus Basma J, Guley N, Michael Ii L, et al. (2020) The Evolutionary Development of the Brain As It Pertains to Neurosurgery. Cureus 12(1): e6748. Humphrey T (1967) The development of the human hippocampal fissure. J Anat 101(Pt 4):655-76. Kier EL, Kim JH, Fulbright RK, Bronen RA (1997) Embryology of the Human Fetal Hippocampus: MR Imaging, Anatomy, and Histology. AJNR Am J Neuroradiol 18:525–532. Lemire RJ, Loeser JD, Leech RW, Alvord EC (1975) Normal and Abnormal Development of the Human Nervous System. Hagerstown, Md: Harper & Row; 260–265. length in mm 2 1 3 2 1 days months PMA NAVIGATOR 131 / 219 Structure and connections of hippocampus. SMA/PMA + reward system from medial orbitofrontal cortex to subgenual ACC - non-reward (punishers) system from lateral orbitofrontal cortex to supracallosal ACC MCC 10 PCC 24 supracallosal (-) 1 ACC 26 22 12 27 subgenual (+) 21 20 19 15 14 OFC 18 11 5 where pathway: spatial 18 23 6 16 9 1 28 8 29 15 17 25 7 2 3 uncus 6 5 what pathway: content 4 1 6 4 16 2 temporal horn EC adapted < Smith and van der Kooy 1985 3 5 coronal section parasagittal section 5 30 6 13 31 1 2 3 4 5 6 fimbria and fornix dentate gyrus subiculum alveus sulcus rhinalis … collateralis gyrus parahippocampalis (EC ento- and perirhinal cortex) 7 amygdala 8 septal nuclei (gyrus paraterminalis) 9 fasciculus uncinatus 10 cingulum (anterior, middle and posterior) 11 12 13 14 15 16 17 18 19 20 21 olfactory sensory cortex (piriform cortex) anterior nucleus of thalamus gyrus fusiformis caudate tail tractus opticus cornu Ammonis stria terminalis (taenia) taenia fimbriae gyri A Retzii (dentes subiculi) subcallosal gyrus sulcus parolfactorius anterior 22 23 24 25 26 27 28 29 30 31 sulcus calcarinus corpus mammillare corpus callosum retro/subsplenial cortex cavum septi pellucidi epiphysis foramen of Monro anterior commissure eminentia collateralis gyrus fusiformis NAVIGATOR 132 / 219 Structure and function of hippocampus. Hippocampus macro-structure: - the pes hippocampi forms the hippocampal digitations (digitationes hippocampi); - these leave impressions in the ventricle floor (the paw) and form external digitations in the uncal notch the pes forms the head or anterior segment (caput or pars anterior) and it bends towards the midline at the junction with the body or middle segment (corpus or pars media) the tail or posterior segment (cauda or pars posterior) also approaches the midline the gyri of Anders Retzius or subsplenial gyri (dentes subiculi or gyri subspleniales) described by Gustav Retzius 1896, are a series of small bumps marking the caudal limit of the CA1 field. The parahippocampal gyrus meets the retrosplenial region caudally. Two obliquely oriented small gyri are located above and deep to the gyri of Andreas Retzius. The medial one is the fasciola cinerea, the visible caudal end of the dentate gyrus. The lateral one, corresponding to the caudal end of the CA3 field, is the gyrus fasciolaris.Caudally the gyrus dentatus extends into the fasciola cinerea as it becomes the induseum griseum covering the corpus callosum. Gyrus dentatus extends rostrally into the bundle (limbus) of Giacomini that crosses the uncus and separates the apex of the uncus (CA3, former gyrus intralimbicus) from the gyrus uncinatus (CA1). Entorhinal cortex covers the area between sulcus rhinalis-collateralis and the gyrus uncinatus. In adults cell islands in layer 2 of the entorhinal cortex creat a verrucous (lattice-like) change of the surface of the rostral gyrus parahippocampalis. This verrucous surface differs considerably between individuals. Between temporal neocortex and entorhinal cortex is the transentorhinal region in the depth of the sulcus rhinalis, a portal of entry for information to the hippocampus. The efferent hippocampal system is mainly from subiculum via fimbria and fornix. The fimbria form behind the sulcus hippocampi and uncal apex, to run caudally and become the crura fornicis at the splenium. The uncal recessus, the mesial extension of the temporal horn into the uncus, becomes a slit at the junction between amygdala and pes hippocampus; this recessus is often be seen in neonatal sonograms (the “uncal ventricle”). The limbic loop is fed by extensive sensory association cortical areas that project to the lateral prefrontal cortex for planning and organisation of motor behaviour. The excursion of neocortical information along the limbic loop adds emotion to behaviour, and all of this is strongly related to memory. Hippocampus participates in declarative (explicit, conscious) memory formation and registration: a cognitive map of acquired kowledge is organised (not stored) by hippocampus. The main information feeder is the entorhinal cortex, itself informed by association, limbic, insular and prefrontal cortex. The entry into the hippocampus (to dentate gyrus projection neurons) is via the perforant path. The main efferent of the limbic loop is the gyrus cinguli informed via fornix and mammillary bodies plus anterior thalamus, but storage of memeory is organised in association cortices and ventral striatum as well as amygdala. The interaction between amygdala and hippocampal formation is complex. Direct (reciprocal) connections are between amygdalar nuclei and subiculum plus ammon's horn, indirect connections via entorhinal cortex are to dentate gyrus. Basolateral nuclei in amygdala modulate consolidation of memories with emotional experience. Fear conditioning and extinction are mediated by specific neurons in the basolateral nucleus. The amygdalohippocampal complex generates several, synchronous EEG oscillations of different nature: (1) slow oscillations (1 Hz) during slow wave sleep (memory consolidation ?) and in anesthaesia; (2) theta rythms (4-8 Hz) related to fear processing; (3) fast gamma oscillations (40-100 Hz) during appetitive learning when information from neocortex is transferred to the hippocampus. These oscillations are formed by glutamatergic pyramidal neurons but with a feedforward long range GABAergic modulation prior to it. Selective absence of the amygdalar contribution (as in Urbach-Wiethe disease) eliminates declarative memory of emotional material only, sparing memorisation of neutral material. This amygdalohippocampal network is involved in memory dysfunction of Alzheimer disease and temporal lobe epilepsy. Braak H, Braak E, Yilmazer D, Bohl J (1996) Functional anatomy of human hippocampal formation and related structures. J Child Neurol 11; 265-275. Gloor P (1997) The temporal lobe and limbic system. Oxford University press. Insausti R, Amaral DG (2004) Hippocampal formation. in Paxinos G, Mai JK (Eds.), The Human Nervous System, second ed. Elsevier, Amsterdam, pp. 871-914. McDonald AJ, Mott DD (2017) Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory. J Neurosci Res 95: 797-820. O’Rahilly R, Müller F (2006) The Embryonic Human Brain. An Atlas of Developmental Stages, third ed. Wiley-Liss, Hoboken, NJ. Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. Testut L, Latarjet A (1948) Traité d’anatomie Humaine, Vol. 2. Paris: Doin. NAVIGATOR 133 / 219 Entorhinal cortex. SEPTUM X TE S OR PU C M L CA PA PO M P I A H OC IPP H RA PA AMYGDALA PARAHIP POCAMP AL CORTEX midline thalamus raphe septum claustrum VTA hypothalamus nu. Meynert EN A HIN TOR L locus coeruleus other subcortical nuclei TEX COR perforant path from superficial layers caudal pathway amygdala ventrolateral pathway via nu. accumbens EX CORT L A N I H PERIR sulcus hippocampi ◊ parahippocampus and pre- parasubiculum entorhinal cortex sulcus rhinalis ◊ perirhinal cortex hippocampus (dentate gyrus with limbus Giacomini and fasciola cinerea, CA1-4, subiculum with dentes subiculi (gyri AR)) multimodal association cortex related to pulvinar, temporopolar cortex multimodal association cortex in sulcus temporalis superior somatosensory verbal memory (left hemisphere) spatial perception linked to memory second order association cortex visual first order visual extrastriate cortex auditory definition of objects olfactory allocortex third order association isocortex somatosensory visual gustatory from anterior insula cingulate and orbitofrontal cortex auditory NAVIGATOR Memories are consolidated under the influence of the amygdala. The hippocampal complex is crucial in memory, but anterograde amnesia may also be the result of dysfunction in systems connected to the hippocampus (mediodorsal thalamus, mammillary bodies, basal nucleus of Meynert). Explicit memories are stored all over the brain after a training period (of months); once stored, destruction of hippocampus can no longer cause retrograde amnesia. 134 / 219 ENGRAM location - Lashley 1926: the entire neocortex stores memory - synaptic changes are related to memory engrams - first pass is through medial temporal lobe where an engram is stored for some things - most engrams are stored in other neocortex (e.g. facial recognition in gyrus fusiformis) - some memory deficits follow damage to thalamus (DM nuclei) and to mammillary bodies - current model: multiple traces together are subparts of a memory (both in HC/EC and neocortex) - frontal lobes are active during attempts to retrieve a memory, hippocampus becomes active once it is retrieved (conscious awareness of the result) thalamus neocortex T S dentate gyrus hippocampal formation allocortex M A H entorhinal cortex nucleus accumbens extensive reciprocal connections between association neocortex and hippocampal region (A amygdala, H hippocampus, M mammillary bodies, S septum, T thalamus) direct mesocortex indirect amygdalar nuclei - cortical - basolateral - central - extended amgygdala the medial temporal lobe memory and emotion system - fear conditioning and extinction - amygdalar modulation/consolidation of hippocampal mnemonic functions NAVIGATOR 135 / 219 The uncal ventricle. axial section through dentate gyrus uncal ventricle mesencephalon axial section through uncus amygdala 1 sulcus collateralis hippocampal fissure uncal ventricle hippocampus 2 uncal ventricle 3 1 uncal ventricle (recessus) 2 hippocampal fissure 3 sulcus collateralis pons uncal ventricle Altman and Bayer 2015: 29w PMA Altman and Bayer 2015: myelin staining at 4 months after term Altman J, Bayer SA (2015) Development of the human neocortex: a review and interpretation of the histological record. A Free eBook from the Laboratory of Developmental Neurobiology, Inc. www.neurondevelopment.org © 2015, The Laboratory of Developmental Neurobiology, Inc. Ocala, FL 34481, USA NAVIGATOR 136 / 219 Sulci near the uncus. 4 3 5 3 6 1 A H 6 1 Bichat's fissure su collateralis -> gyrus lingualis 1 2 3 4 5 6 sulcus rhinalis fissura transversa amygdala A to hippocampus H contact endorhinal sulcus sulcus uncalis (uncal notch) ? ventricle related 4 A H 6 1 Bichat's fissure su collateralis 3 5 2 6 NAVIGATOR 137 / 219 Sulcus collateralis versus ventricle walls. 1 3 4 2 2 1 2 3 4 uncus with amygdala sulcus rhinalis or collateralis gyrus ambiens sulcus uncalis amygdala to hippocampus meeting <- sulcus collateralis amygdala mesencephalon pes transverse fissure hippocampus nuchal view, courtesy T Mühlbacher, Zürich sulcus uncalis ventricle roof ventricle roof sulcus collateralis or ventricle floor NAVIGATOR 138 / 219 Amygdala meet pes hippocampus. Am pes H sulcus uncalis —> <— transverse fissure <— ventricle floor <— sulcus collateralis NAVIGATOR 139 / 219 Entorhinal cortex in a CUS coronal section. <— transverse fissure Am pes H <— sulcus uncalis <— sulcus rhinalis entorhinal cortex NAVIGATOR 140 / 219 Mesial temporal lobe anatomy disturbed by lobar haematoma. day 15 day 8 T2 term, grunting and apnoea immediately after delivery, left temporal focal epileptic EEG sulcus collateralis T2 injury to gyrus parahippocampalis sulcus temporalis superior T1 compressed gyrus temporalis superior patent left transverse sinus NAVIGATOR An ultrasound study of hippocampal maturation. 141 / 219 Neonatal disorders affecting hippocampus. • • • • • • • • • • • normal flat elliptoid gyrus parahippocampalis asphyxia/ischaemia; intraoperative encephalopathy hypoglycaemia kernicterus ECMO arterial stroke sinovenous thrombosis of the basal vein of Rosenthal lobar temporal haematoma seizure induced neuronal death dexamethasone metabolic disorders chronic stress incompletely inverted hippocampus with pyramidal shape Bajic D, Ewald U, Raininko R (2010) Hippocampal development at gestation weeks 23 to 36. An ultrasound study of preterm neonates. Neuroradiology 52; 489-494. NAVIGATOR 142 / 219 Sulci frontales Frontal gyri are numbered from 1 to 3, starting in F1 above the sulcus frontalis superior, through F2 between sulcus frontalis superior and inferior, F3 between the lateral fissure and the sulcus frontalis inferior. F2 is connected along the rostral pole with the orbitofrontal cortex (between sulcus olfactorius and sulcus orbitalis externus). F3 is connected to the orbitofrontal cortex lateral to the sulcus orbitalis externus and to the olfactory cortex behind the cruciform sulcus of Hervé (sulcus orbitalis transversus). Size of gyrus frontalis superior and medius is inversely related. The sulcus precentralis is nearly always interrupted, either in an inferior and superior part, or in three parts, hence “sulci precentrales” in plural. There is (mirrored around sulcus centralis) similarity between the frontal (sulcus precentralis inferior with sulcus frontalis inferior) and the parietal complex (sulcus postcentralis inferior with sulcus intraparietalis). The (horizontal) sulcus frontalis superior (f1) is connected to the vertical sulcus precentralis superior in a similar way as the sulcus frontalis inferior (f3) connects to the vertical sulcus precentralis inferior. Broca’s expressive speech area is located underneath the sulcus frontalis inferior and in front of sulcus precentralis inferior, including the pars triangularis between ramus ascendens and ramus orbitalis of the lateral fissure. There is no significant volume asymmetry of the pars triangularis. There is volume asymmetry of the pars opercularis, significantly related to the asymmetrical presence of sulcus diagonalis which is more common on the left and expands the Broca area when present. Sulcus precentralis inferior and frontalis inferior appear around 24 w PMA at postmortem, not much later followed by sulcus precentralis and frontalis superior; some variation is present but these four sulci should be visible at postmortem before 28w PMA (often visible on ultrasound around that stage). Although they become branched later on, they are simple lines at first. Before these lines are formed there are initial sulcal pits between primitive annectant connections. Sulcus precentralis inferior is homologue to the vertical portion of the arcuate (presylvian) sulcus in gyrated mammals. It is composed of a vertical and horizontal part, rarely separated by an annectant gyrus up to the surface. The vertical part of the sulcus precentralis inferior runs parallel to the sulcus centralis, in front of the lower third of the gyrus precentralis inferior. Sulcus symmetry of frontal and parietal sulci around the central sulci sc f2 h sip fm pci poc sot precentralis inferior usually does not reach the lateral fissure, but it can be connected to it via a sulcus diagonalis (rostral to it) or a sulcus subcentralis anterior (caudal to it), in about one in five instances each. Typically therefore, the sulcus precentralis inferior is the vertical groove between ramus ascendens of the lateral fissure and the sulcus centralis. Variants (less than 25 %) depend on the presence of a sulcus diagonalis and/or on the absence of the ramus ascendens. The sulcus precentralis inferior can be bifid at the lateral fissure. The horizontal part of the sulcus precentralis inferior sits on top of the vertical part, together looking like an oblique T. The posterior end of this horizontal part ascends in the precentral gyrus behind the lower end of the sulcus precentralis superior. If disconnected, this posterior branch can be named sulcus precentralis medius. The anterior branch of the horizontal part is often long and ascends forward in the middle frontal gyrus until about the posterior end of the sulcus frontalis medius. This anterior branch is often connected (at continuous (atypical) versus discontinuous (typical) precentral sulci pcs pcm sc pci NAVIGATOR least superficially) from above to the sulcus frontalis inferior that runs below it over the pars triangularis. The vertical part of the sulcus precentralis inferior appears around 24 w PMA, but around 34 w PMA both parts are still separated, which suggests that connections develop later because ultimately in most brains there is a connection between sulcus frontalis inferior and sulcus precentralis inferior (either with vertical or horizontal part). 143 / 219 A cruciform connection can also exist at this junction, with a short branch from it into the gyrus precentralis. Around its upper part the superior frontal gyrus connects to the lobulus paracentralis at the convexity upper margin. Sulcus precentralis medius is inconstant, starting posterior to the sulcus precentralis inferior and ending in front of the lower end of the sulcus precentralis superior. It may appear as a separated posterior part of the horizontal branch of the sulcus precentralis inferior, although in other variants it is connected to the sulcus precentralis superior. In some (about 1/10) sulcus precentralis medius connects sulci precentralis inferior and superior with each other, so that a complete sulcus precentralis appears as one line parallel to the sulcus centralis. This complete constellation however, occurs more often in the sulcus postcentralis (in about 7/10). Sulcus precentralis medius can also reach the lateral fissure. Sulcus precentralis superior is often one uninterrupted groove that runs parallel to sulcus centralis in front of the upper half of the gyrus precentralis. It ends below the convexity margin in a short transverse sulcus, the sulcus precentralis marginalis. Its lower part ends between the anterior and posterior parts of the horizontal branch of the sulcus precentralis inferior. Usually the sulcus frontalis superior is connected to the centre of sulcus precentralis superior. A surfacing annectant gyrus may on occasion exist at this connection. sprem f1 pcs f1 sc f2 PT fm f3 sr h sc pci pci pcs f2 h f2 f3 f1 F1 pcs F2 fl ra f3 fm F3 ra sd pci PT rh fl frontal sulci around 30w PMA (sulcus frontalis medius in red) f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis (Wernicke) h ramus horizontalis of pci frontal sulci and annectant gyri around 33w PMA (early eigth month) pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior PT pars triangularis ra ramus ascendens fissurae lat. rh ramus horizontalis fissurae lat. frontal sulci around 6 months after term birth sc sulcus centralis (Rolando) sd sulcus diagonalis sprem sulcus precentralis mesialis sr sulcus radiatus Eberstaller 1890, Cunningham 1892, Retzius 1896, Paturet 1964, Ebeling et al. 1989, Tamraz and Comair 2006, Keller et al. 2007, Ribas 2010, ten Donkelaar 2018 sc NAVIGATOR Sulcus subcentralis anterior ascends from the lateral fissure obliquely up and forward, underlining the gyrus subcentralis. A large sulcus subcentralis anterior may mimick a sulcus precentralis inferior. Sulcus diagonalis (Eberstaller) arises near the lateral fissure behind its ramus ascendens. It lies in front of the sulcus precentralis inferior and ascends while shifting posteriorly. A long sulcus diagonalis may mimick a sulcus precentralis inferior. Such sulcus diagonalis is present in less than half of the brains and is more often seen on the left where it increases the cortical volume of the pars opercularis of F3. Its morphology is not uniform, as it occasionally merges with the anterior ascending ramus of the Sylvian fissure or extends from the inferior precentral sulcus or inferior frontal sulcus. Four connections of the diagonal sulcus are possible: (a) with the ascending horizontal ramus of the lateral fissure; (b) with the inferior precentral sulcus; (c) with the inferior frontal sulcus; (d) no connection with surrounding sulci. In (near) term infants sulcus diagonalis can sometimes be observed with CUS. Sulcus frontalis superior (f1) This sulcus runs rostrally from the middle of the sulcus precentralis superior and ascends slightly toward the convexity margin. A series of several small parallel sulci may separate the mesial from the lateral part of the gyrus frontalis superior. These align with the sulcus precentralis marginalis above f1. The sulcus frontalis superior is continuous in about half but interrupted in two or more short sulci. There is less often a connection to the sulcus frontomarginalis than is the case for the sulcus frontalis medius. The pial artery in this sulcus is a branch of the ACA. Sulcus frontalis medius (f2) This sulcus is more variable than the sulcus frontalis inferior and superior. It divides gyrus frontalis medius in two parts. Its posterior end forms a bifurcation about halfway in the frontal lobe (starting at the level of the anterior end of the horizontal part of the sulcus precentralis inferior). Its anterior end is also a bifurcation, the lower end of which is the vertical and descending part of the sulcus frontomarginalis. The sulcus frontalis medius is rarely continuous and on the other hand may be interrupted in up to five pieces. It can be visible at 26 w, usually rather at 30 w PMA. Sulcus frontalis inferior (f3) The posterior end of this groove usually sits below the horizontal part of the sulcus precentralis inferior. It follows an anterior course immediately over the ramus ascendens of the lateral fissure and ends in a bifurcation: the lower end of this bifurcation descends into the pars triangularis (as sulcus triangularis or 144 / 219 “incisura capitis”), the upper end aims for the border between convexity and orbital surface. In front of this bifurcation, the sulcus radiatus (also called pretriangular sulcus) is a vertical sulcus, with an upward extension that may connect to the sulcus frontalis medius or inferior. It is visible from around 30 w PMA, present in about 1/2. Even more rostral descends the lateral part of the frontomarginal sulcus, which may emerge before the sulcus frontalis inferior. The sulcus frontalis inferior is continuous in about half, in the remainder it is subdivided into two parts, anterior and posterior. There are several types of connections between the posterior inferior frontal sulcus and the ventral (or horizontal) segment of the inferior precentral sulcus: (1) a true connection; (2) a superficial connection on the surface, with a submerged bridge of cortex interrupting it; (3) no connection. Typically two pits are the first indication of the appearance of this sulcus, around 26 w PMA. This sulcus may, in adults, contact the lateral orbital sulcus when it extends far anteriorly. Sulcus frontomarginalis (Wernicke) The anterior (transverse) part of this sulcus (also called sulcus frontopolaris) cuts the anterior cerebral pole in two, thus separating the lower orbital part from the upper prefrontal part. The sulcus frontomarginalis runs down on the convexity as a vertical lateral part, described above as a sulcus in front of the sulcus radiatus and ramus horizontalis of the lateral fissure. This complex of sulci is most often connected to the sulcus frontalis medius. The gyrus below it is the transverse frontopolar gyrus. Sulcus frontalis medialis An interrupted sulcus, parallel to the sulcus frontalis superior may be present at the convexity margin. This sulcus separates gyrus frontalis superior on the lateral convexity from the medial frontal gyrus on the mesial convexity, above the sulcus cinguli. NAVIGATOR 145 / 219 Typical relation between insula, frontal sulci and lateral fissure. F P f1 pcs sc f2 sip f3 pci ra ra ramus ascendens f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior sc sulcus centralis (Rolando) sip sulcus intraparietalis sts sulcus temporalis superior fl sts O T NAVIGATOR 146 / 219 Broca speech area: “circonvolution de Broca”. 1 6 typical anatomy 1 gyrus frontalis medius 2 gyrus frontalis inferior 3 ramus horizontalis fissurae lateralis 4 ramus ascendens fissurae lateralis 5 sulcus precentralis inferior 6 sulcus centralis 7 sulcus frontalis inferior 7 2 7 5 4 3 1 2 4 5 GA 34 w, PMA 35 w: pars triangularis three adult Broca areas, differences in shape of the gyrus frontalis inferior Paturet 1964 NAVIGATOR Variation of sulcus precentralis inferior. 147 / 219 Leftward volume asymmetry of the pars opercularis. four connections of the diagonal sulcus a) connection with the ascending horizontal ramus of the Sylvian fissure b) connection with the inferior precentral sulcus c) connection with the inferior frontal sulcus d) no connection with surrounding sulci f3 sulcus frontalis inferior pci sulcus pecentralis inferior ra ramus ascendens fissurae lateralis rh ramus horizontalis fissurae lateralis sd sulcus diagonalis analysis, in 50 healthy subjects using MRI, of the sulcal asymmetry and volume of the otor speech region performed in combination with an analysis of the morphology and volume asymmetry of the planum temporale: - significant inter-hemispheric difference in the presence of (1) the diagonal sulcus within the pars opercularis, and (2) horizontal termination of the posterior sylvian fissure (relative to upward oblique termination), both with an increased leftward incidence - significant leftward volume asymmetry of the pars opercularis, significantly related to the asymmetrical presence of the diagonal sulcus - significant leftward volume asymmetry of the planum temporale, associated with the shape of the posterior sylvian fissure as a unilateral right or left upward oblique termination was associated with leftward or rightward volume asymmetry respectively Ebeling U, Steinmetz H, Huang Y, Kahn T (1989) Topography and identification of the inferior precentral sulcus in MR imaging. Am J Neuroradiol 10: 937-942. Keller SS, Highley JR, Garcia-Finana M, Sluming V, Rezaie R, Roberts N (2007) Sulcal variability, stereological measurement and asymmetry of Broca’s area on MR images. J. Anat 211, pp534–555. NAVIGATOR 148 / 219 CUS views on the developing precentral sulci. f1 pcs sc f1 f2 pcs pci h pcs f3 poc PT typical parasagittal ultrasound configuration at 28 w PMA ra pci sd pcm sulcus precentralis medius pcs sulcus precentralis superior PT pars triangularis ra ramus ascendens fissurae lat. sc sulcus centralis (Rolando) sd sulcus diagonalis L f1 f1 f1 f2 f3 sc pci PT sc ra pci ra sc pci ra GA 26 w, PMA 34 w asymmetry in frontal sulci sc parasagittal ultrasound at term typical parasagittal ultrasound configuration at 36 w PMA f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis h ramus horizontalis of pci pci sulcus precentralis inferior R pci sc ra GA 36 w, PMA 37 w NAVIGATOR 149 / 219 Parcelling of the frontal lobe. SEF M1 SMA pre-SMA DLPFC FEF B Broca speech area (BA 44,45) CMA cingulate motor area DLPFC dorsolateral prefrontal cortex: executive functions, inactive during REM sleep (BA 46, BA 9) FPC B B F1 primary motor area VLPFC FEF frontal eye field FPC frontopolar cortex MPFC medial prefrontal cortex: emotional aspects of motor behaviour, connections to limbic system OPFC orbital prefrontal cortex: rewarding emotional aspects of motor behaviour (BA 47, BA 11-14) SEF supplementary eye field pre-SMA SMA supplementary motor area (BA6) SMA CMA VLPC ventrolateral prefrontal cortex (BA 47, BA 12) MPFC FPC OPFC Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. M1 NAVIGATOR 150 / 219 Functions of prefrontal and cingulate cortex. dorsolateral prefrontal cortex - action switchboard - short term memory ventrolateral prefrontal cortex - override function (inhibition) - self control dorsal and anterior cingulate cortex - monitoring the result of decisions, detect need to change - active during conflict situations orbitofrontal and ventromedial prefrontal cortex - attribution of values to options - reward prediction error RPE using dopamine from brainstem - wanting Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates. insula - evaluation of “milieu interieur”: body awareness (somatic marker system) - emotional awareness - short term memory posterior cingulate cortex - awareness of self (part in default mode network DMN) - state between tasks - strategic decision making: autobiography and relations in the future NAVIGATOR 151 / 219 Early human frontal lobe development. Circuitry Activity Embryonic 6–7 PCW Nonsynaptic preplate network Oscillating, spontaneous activity Early fetal 8–14 PCW Two synaptic strata, in SP and MZ; cholinergic (basal forebrain) and monoaminergic (tegmentum) afferents; regional differences Transient spontaneous activity modulated by monoamines Endogenous (not sensory dependent) Midfetal and late fetal 15–23 PCW Transient lamination in marginal zone, prominent SP with synaptogenesis (60 % glutamatergic, 40 % GABAergic), no layer IV yet in CP; output to striatum, pons and spinal cord; highly developed subventricular zone producing neurons and glial cells Transient spontaneous activity, modulated by extrinsic thalamic afferents and axons from basal forebrain and amygdala Endogenous + brain stem and cholinergic basal forebrain (not sensory dependent) Early preterm 24–32 PCW The peak of SP, afferents in CP from thalamus (nonsensory MD nucleus for frontal lobe), MZ has sublayers and a subpial granular layer, initial lamination in the cortical plate; predominantly glial cell production in SVZ Transient circuitry (subplate, intrinsic) and permanent (cortical plate) thalamocortical afferents coexist; output to striatum (Muratoff bundle) into developing striatal cell islands; increasing projection and commissural fibers Endogenous; SATs emerge from around 24w, transform around 30w and disappear near term; first general movements Late preterm 33–35 PCW Primary gyration achieved, secondary gyration active; CP layers differ from mature pattern; synaptogenesis in CP, pyramidal differentiation, cytoarchitectonic belts; decreasing SP size parallel to development of white matter in corona radiata; glial cell production but still migrating late-arriving neurons Second wave of dendritic differentiation in the cortical plate; coexistence of increasingly permanent and transient circuitry; exuberant callosal fiber formation and developing long associative fascicles, external capsule and cingulate fasciculus Sensory-sensitive asynchrony (EEG) but in general more continuous EEG; switched cortical dipole (now predominantly superficial generation of electrical activity); writhing general movements Neonatal 1–2 months Tertiary gyration; long afferents within the target; layer V pyramids differentiation; ubiquitous granular layer IV; wide transition layer VI to disappearing subplate Permanent circuitry with transient elements; extensive dendtritic formation in CP and SP, rapidly increasing number of synapses Sensory-sensitive synchrony (rapidly changing electrical activity), few remaining SATs; experience expectant but still low attention span Early infancy 2–6 months Reorganization of corticocortical pathways; rapid synaptogenesis and spinogenesis (dendritic differentiation of pyramidal neurons); retraction of exuberant pathways, e.g. in corpus callosum (starts before birth) Permanent circuitry with resolving transient elements; explosive synaptic density Sensory-driven, layer V centered Late infancy 7–12 months Long connectivity established; layer III pyramids “dormant” until 16 months of life (association neurons); areal differentiation; granular-dysgranular differentiation; initial differentiation of inhibitory neurons; no longer SP Initial “cognitive” circuitry with early environmentally driven executive functions due to cortico-cortical activity Sensory-driven; columnar processing Early childhood 12–24 months Maturity of layer III pyramids and local circuits; maximal synaptogenesis Cognitive Environmentally driven; extrinsic-intrinsic through local circuitry Rakic P, Arellano JI, Breunig J (2009) Development of the primate cerebral cortex. In Gazzaniga (ed) The cognitive neurosciences, MIT press. NAVIGATOR 152 / 219 Sulci orbito-frontales. Relatively constant sulci subdivide the orbitofrontal surface. Gyrus rectus is bordered by the straight sulcus olfactorius (= sulcus orbitalis medialis), which ends at the rostral end of the anterior perforated substance with two branches, of which the lateral one connects to the lateral fissure. It courses roughly parallel to the interhemispheric fissure. The olfactory gyrus is separated by the sulcus rostralis inferior from the rest of the frontal lobe on the mesial convexity, and is a part of the longitudinal arciform region corresponding to the orbital portion of the superior frontal convolution. 4 7 3 2 8 1 5 9 6 11 1 gyrus rectus 2 gyrys orbitalis medialis 3 gyrus orbitalis lateralis 4 gyrus orbitalis anterior 5 gyrus orbitalis posterior 6 sulcus olfactorius (orbitalis medialis) 7 sulcus orbitalis transversus (Hervé) 8 sulcus orbitalis lateralis 9 gyrus frontalis inferior 10 frontal pole 11 transverse insular gyrus * convergence of the frontal gyri (Hervé) superior frontal gyrus PP A complicated cruciform groove (shaped H, X or K) (cruciform sulcus of Hervé, sulcus orbitalis transversus) subdivides the core of the orbitofrontal cortex into anterior, medial, lateral and posterior orbital gyri. The transverse part of this cruciform sulcus is convex to the frontal pole. The posterior orbital gyrus, connected to the insula via the transverse insular gyrus and often has a crescent shape and a smooth surface (“désert olfactif de Broca”). An inconstant lateral olfactory sulcus (sulcus orbito-frontalis) borders these orbital gyri near the convexity, it limits the orbitofrontal lobe where it meets the inferior frontal gyrus. middle frontal gyrus 10 GA 14 w inferior frontal gyrus GA 24 w Retzius 1896, inferior brain surface H 4 H 2 3 1 9 PT 7 8 6 5 PP planum polare PT planum temporale H Heschl gyri (transverse gyri) gph * gf gf gyrus fusiformis gl gyrus lingualis gph gyrus parahippocampalis gl NAVIGATOR Orbitofrontal and prefrontal cortex. 153 / 219 dorsolateral PFC superior frontal gyrus area 9, 46 area 10 inferior frontal gyrus orbitofrontal cortex OFC ventrolateral PFC area 10, 11, 13, 14 area12,45 area 47 term 1 sulcus olfactorius (orbitalis medialis) 2 sulcus orbitalis transversus (Hervé) more to frontal pole just before genu coronal sections at genu to in 2 2 1 1 sula NAVIGATOR 154 / 219 CUS views on the developing frontal sulci at the convexity. Due to the location of the anterior fontanel, frontal sulci are accessible to inspection with CUS. As one tilts the section from sagittal to parasagittal it suffices to rotate gently for inspection of either the very frontopolar area or the fronto-parietal transition. GA 28w PMA 36w pcs su. frontalis superior fm su. frontalis medius f1 sulcus frontalis superior f2 sulcus frontalis medius f3 sulcus frontalis inferior fl ramus posterior fissurae lateralis fm sulcus frontomarginalis h ramus horizontalis of pci pci sulcus precentralis inferior pcm sulcus precentralis medius pcs sulcus precentralis superior ra ramus ascendens fissurae lat. sc sulcus centralis (Rolando) sc f3 pci ra * <— su. frontomarginalis —> * su diagonalis ? f1 section close to insula f2 pcs sc f3 f3 ra ra limen fl pci sc NAVIGATOR 155 / 219 CUS views on some early frontal sulci at the convexity. GA 28w PMA 34w sulcus diagonalis R L sulcus precentralis inferior sulcus precentralis inferior sulcus diagonalis ? or f3 sc sc NAVIGATOR 156 / 219 Sulcus diagonalis. GA 35w 6d, PMA 37 w; sulcus diagonalis on the left R L pci ra pci ra GA 33w, PMA 35 w; sulcus diagonalis on the right arrow= sulcus diagonalis pci = sulcus precentralis inferior pcs = sulcus precentralis superior ra = ramus ascendens of the lateral fissure sc = sulcus centralis NAVIGATOR 157 / 219 Clinical relevance The frontal lobe can be implicated in ACA and MCA stroke, superior sagittal sinus thrombosis and bacterial meningitis/encephalitis. Contusion affects the superior frontal gyrus in a specific way (Delanghe et al. 2015). Inspection of abnormal frontal lobe sulcation is an easy guide to some rare congenital anomalies like lobar dysplasia or tuberous sclerosis. For focal injury it would be logical to relate outcome to damage either to orbitofrontal, mesial and lateral (on the convexity) frontal changes. GA 32w PMA 36w R f1 f2 pcs The striking variation but also the relatively constant basic sulcal pattern make the frontal lobe an obvious area of interest for research into the relation between anatomy and functional outcome, especially for the prefrontal cortex. f3 PT ra sc pci poc L f1 no effect of cystic periventricular leukomalacia (onset often after 28 w PMA) on primary sulci in frontal lobe pcs f3 R L PT Delanghe G, Squier W, Sonnaert M, Dudink J, Lequin M, Govaert P (2018) Neonatal subcortical bruising. Clin Case Rep 6(2):407-415. ra pci sc poc NAVIGATOR 158 / 219 Cortical watershed zone between f1 and f2. GA 38 w 1d, PMA 39 w, septic shock by enterococcus sepsis and omphalitis f2 f2 sulcus frontalis medius f3 sulcus frontalis inferior ra = ramus ascendens of the lateral fissure sc sulcus centralis arrows = hyperechoic change in watershed areas between ACA and MCA f3 sc ra NAVIGATOR 159 / 219 Sulci parietales The parietal lobe, above the lateral fissure and behind the sulcus centralis, extends to an arbitrary line connecting the parietooccipital sulcus at the convexity to the preoccipital notch. It extends to the medial aspect of the hemisphere as precuneus. Its largest portion is on the convexity where it contains gyrus postcentralis, lobulus parietalis superior and inferior (numbered P1 and P2, respectively) separated by the sulcus intraparietalis. Caudally, the parietal lobe is connected with the occipital lobe by the parieto-occipital “arc of Gratiolet” behind the sulcus intraparietalis, and with a gyral connection between gyrus angularis and gyrus occipitalis superior, behind sulcus occipitalis anterior. The inferior parietal lobule (IPL) is situated between the lateral fissure, the horizontal segment of the intraparietal sulcus, and the postcentral segment of the intraparietal sulcus. It consists of gyrus supramarginalis and gyrus angularis. Gyrus supramarginalis surrounds the posterior ascending end of the lateral fissure. Gyrus angularis lies around the caudal (often bifurcated) end of the superior temporal gyrus. The first intermediate sulcus (of Jensen) may divide the inferior parietal lobule into the supramarginal and angular gyri. The second intermediate sulcus (of Eberstaller) is posterior to the Jensen sulcus, and divides gyrus angularis in two parts. Located dorsal to the inferior parietal lobule, the superior parietal lobule (SPL) is limited inferiorly by the intraparietal sulcus, anteriorly by the superior postcentral sulcus, and posteriorly by the lateral extremity of the parieto-occipital sulcus. Gyrus postcentralis is bordered by the sulcus postcentralis. Its lower end may be traversed by a posterior subcentral sulcus from the lateral fissure, forming a small indentation in the parietal operculum. Sulcus postcentralis is a complex of segments separated by annectant, mostly submerged, gyri: in the majority the postcentral sulcus is separated into up to five fragments, but in some it remains continuous (around 1/8). Up to four submerged gyri can separate these postcentral fetal sulcal units. Cunningham (1892) drew attention to the near constant occurrence of a deep gyrus (the anterior deep annectant gyrus of Eberstaller) separating the initial segment of the sulcus intraparietalis and the sulcus postcentralis inferior. Sulcus postcentralis is visible in sonograms by 31 w PMA (Huang 1991). In a minority sulcus intraparietalis (SIP) is continuous, most often it is interrupted by surfacing annectant gyri. It almost touches the lateral ventricle. It is described in three parts: the anterior horizontal, the posterior descending (often separated by a submerged annectant gyrus) and a terminal occipital segment. The sulcus of Jensen (sulcus parietalis inferior anterior, present in at least one brain in two) descends between the horizonal and descending segments; rarely it merges with the sulcus temporalis superior, usually it cuts into the supramarginal gyrus between the first and second branch of the superior temporal sulcus. The sulcus of Jensen thus separates the anterior intraparietal cortex (involved in high-level sensorimotor control) from the cortex around the posterior part of the sulcus intraparietalis (involved in visuospatial attention processing)(Zlatkina and Petrides 2014). The horizontal segment has variable relations with the postcentral sulcus. Most often sulcus intraparietalis is continuous with both inferior and superior postcentral sulci (40%). The occipital segment of sulcus intraparietalis may even reach the occipital pole, end is therefore also referred to as paroccipital or superior occipital sulcus. This segment has a T-shaped end in about 70%, by some called the transverse occipital sulcus. The anterior half of the SIP overlies the atrium. Four consecutive white matter layers are identified between SIP and the atrium: (1) the arcuate fibers, (2) the arcuate fasciculus F, (3) the corona radiata and (4) tapetum. The SIP-postcentral sulcus meeting point, is close to the underlying arcuate segment of the superior longitudinal fasciculus SLF. SIP runs parallel to the interhemispheric fissure in about half, in the others it gradually approaches the fissure from anterior to posterior. SIP runs above the atrium, the optic radiation is always lateral to it. The SIP runs between two “plis pariétooccipitales de Gratiolet”, major connections in humans, whereas in lower primates the sulcus parieto-occipitalis courses over the convexity in the way it runs on the mesial part of the hemisphere (‘la fente simienne”). Clinical relevance The parietal lobe, an important passageway for exteroreceptive information, is only partially accessible to CUS. It can be implicated in ACA and MCA stroke, superior sagittal sinus thrombosis and bacterial meningitis/ encephalitis. Lobar parietal haematoma is the least common of the lobar haematomas. Knowledge of its boundaries is useful to avoid misnaming of “posterior” lesions (like leukomalacia variants) as being occipital in location. Eberstaller 1890, Cunningham 1892, Brissaud 1893, Retzius 1896, Paturet 1964, Chi et al. 1977, Ebeling et al. 1989, Huang 1991, Paus et al. 1996, Tamraz and Comair 2006, Keller et al. 2007, Spasojevic et al. 2010, Zlatkina and Petrides 2010, Ribas 2010, Koutsarnakis et al. 2017, ten Donkelaar 2018, Diedzic et al. 2021 NAVIGATOR 160 / 219 Functional anatomy of the sulcus intraparietalis. sip SPL sip sulcus postcentralis and sulcus intraparietalis develop between 26 and 28 w PMA and are visible in sonograms after 30 w PMA sB sc sc gsm ang poc inf fl po sipj sip poc inf sip sot sipj fl typical sulcus intraparietalis in the newborn according to Cunningham 1892 f1 sulcus frontalis superior fl ramus posterior fissurae lateralis pci sulcus precentralis inferior pcs sulcus precentralis superior po sulcus parieto-occipitalis (16-19 w PMA) poc sulcus postcentralis (24-27 w PMA) rsm ramus supramarginalis sulci cinguli sc sulcus centralis (Rolando)(20-23 w PMA) sB sulcus of Brissaud sip sulcus intraparietalis (24-27 w PMA) sipj sulcus intermedius primus (Jensen) sise sulcus intermedius secundus (Eberstaller) sot sulcus occipitalis transversus SPL superior parietal lobule pci pcs poc sB po radiatio optica (crossing the lateral wall of the atrium and overlying the roof of the occipital horn) sulcus intraparietalis: interrupted in about 1/3; there is always at least 1 annectant gyrus traversing the sulcus; cortex of the SIP involved in saccadic eye movements, memory retrieval, multimodal processing (e.g. in visual guided grasping), symbolic number skills (mathematics) sc sipj rsm sip brain image @ 35w from Retzius 1896 fasciculus arcuatus (from Wernicke’s area to inferior frontal gyrus) f1 sJ sulcus of Jensen (sulcus intraparietalis intermedius anterior aipJ); present in at least 1/2 sB sulcus of Brissaud (sulcus parietalis transversus); present in at least 1/2, most often posterior to J NAVIGATOR 161 / 219 The rostral part of the sulcus intraparietalis in CUS. constant annectant gyrus (pli de passage, submerged or visible) sps poc sup SPL sip po sB sipj gyrus supramarginalis sc sise sip-posterior poc inf gyrus angularis sot fl ramus posterior fissurae lateralis po sulcus parieto-occipitalis (16-19w) poc sulcus postcentralis (24-27w) sang sulcus angularis sc sulcus centralis (Rolando)(20-23w, over convexity 30w) sB sulcus of Brissaud sip sulcus intraparietalis (24-27w) sipj anterior intermediate parietal sulcus of Jensen sise posterior intermediate parietal sulcus of Eberstaller sot sulcus occipitalis transversus SPL superior parietal lobule sps superior parietal sulcus sts sulcus temporalis superior (20-23w) sang fl sts parietal convexity detail spoc spoc sipj near term sulcus intraparietalis Cunningham DJ (1892) Contribution to the surface anatomy of the cerebral hemispheres. The praecentral and other sulci in the external surface of the frontal lobe. pp 244-302. Koutsarnakis C, Liakos F, Kalyvas AV, Liouta E, Emelifeonwu J, Kalamatianos T, Sakas DE, Johnson E, Stranjalis G. Approaching the Atrium Through the Intraparietal Sulcus: Mapping the Sulcal Morphology and Correlating the Surgical Corridor to Underlying Fiber Tracts. Oper Neurosurg (Hagerstown). 2017 Aug 1;13(4):503-516. Zlatkina V, Petrides M (2014) Morphological patterns of the intraparietal sulcus and the anterior intermediate parietal sulcus of Jensen in the human brain. Proc Biol Sci. 281(1797). NAVIGATOR 162 / 219 Sulcus parieto-occipitalis. Sulcus parieto-occipitalis (“sillon perpendiculaire”) is constant, deep and characteristic of the primate brain. Situated principally on the posterior mesial aspect of the hemisphere, it extends as a straight line down and rostral from the dorsal margin of the hemisphere to the splenium where it joins the stem of the calcarine fissure, from which it is frequently separated by the gyrus cunei, which connects the apex of the cuneus to the isthmus gyri cinguli. It can have a number of additional submerged connections between cuneus and precuneus. It continues as a deep external incisure on the lateral aspect of the hemisphere only for a short distance to end in the parieto-occipital annectant gyrus. At the dorsal margin it may have a branch, the sulcus limitans precunei, connected to the sulcus intraparietalis in 1/4. Sulcus parieto-occipitalis develops in synchrony but separate from the calcarine sulcus. Sulcus calcarinus and parieto-occipitalis are the first (and therefore deep) primary sulci to appear around 16 w PMA, indicative of early maturation of visual pathways between lateral geniculate and occipital cortex. A mirrored imaginary line of the mesial sulcus parieto-occipitalis on the convexity, in the direction of the occipital incisure, separates the parietal from the occipital lobe. Sulcus parieto-occipitalis is especially well known to fetal ultrasound specialists (Pistorius et al. 2010): sulcus calcarinus and sulcus parieto-occipitalis are both visible in fetal sonograms at 20 w PMA. gi limbic cortex po splenium cuneus gc cla calc (stem) gyrus lingualis scoll cla 5 1 8 3 4 8 hippocampus amygdala gyrus parahippocampalis cingulum septal nuclei precuneus 10 2 1 2 3 4 5 4 9 7 fe mesial view after Cunningham 1892) convexity view 6 calc sulcus calcarinus cla cuneo-lingual annectant gyri fe fissura extrema (Seitz) gc deep gyrus cunei gi deep gyrus intercuneatus lun sulcus lunatus lv lateral ventricle po sulcus parieto-occipitalis scoll sulcus collateralis soa sulcus occipitalis anterior st sulcus occipitalis transversus (Ecker) sts sulcus temporalis superior 1 sulcus angularis 2 gyrus angularis (pli courbe) 3 sulcus temporalis superior 4 sulcus temporalis inferior 5 fissura lateralis 6 gyrus supramarginalis 7 sulcus intraparietalis 8 plis pariéto-occipitales de Gratiolet 9 sulcus parietalis anterior inferior (Jensen) 10 sulcus parieto-occipitalis 5 2 1 3 cuneus gyrus lingualis Eberstaller 1890, Cunningham 1892, Brissaud 1893, Retzius 1896, Paturet 1964, Ebeling et al. 1989, Chi et al. 1977, Paus et al. 1996, Tamraz and Comair 2006, Keller et al. 2007, Spasojevic et al. 2010, Zlatkina and Petrides 2010, Pistorius et al. 2010, Ribas 2010, Koutsarnakis et al. 2017, ten Donkelaar 2018, Diedzic et al. 2021 NAVIGATOR 163 / 219 Ultrasonographic description of sulcus intraparietalis. parasagittal section via anterior fontanel at 36 w PMA R posterior coronal section via anterior fontanel at 36w PMA R L f1 behind the sulcus centralis, in far posterior (almost tangential) coronal sections, sulcus postcentralis superior and sulcus intraparietalis can be seen after 32 w PMA in most infants pcs sc f2 poc sc in parasagittal sections the onset of the sulcus intraparietalis from the sulcus postcentralis is readily seen, with the gyrus supramarginalis under it; more posterior inspection is impossible from the anterior fontanel ssp lobulus parietalis superior poc sip po sip gyrus supramarginalis parasagittal section at 36w PMA f1 sulcus frontalis superior f2 sulcus frontalis medius pcs sulcus precentralis superior poc sulcus postcentralis sc sulcus centralis (Rolando) sip sulcus intraparietalis ssp sulcus subparietalis R GA 32 w, PMA 35 w: asymmetry of origin of the sulcus intraparietalis sc sip sc L NAVIGATOR 164 / 219 Ultrasonographic description of sulci centrales and sulcus intraparietalis at PMA 35w and 36w (GA 32w). PMA 35w pcs pcs sc sc sc rsm pci poc pci poc ssp sip sip pcs PMA 36w sc rsm poc ssp sip NAVIGATOR 165 / 219 Typical appearance of sulcus parieto-occipitalis (po) and calcarinus (calc). coronal 35w PMA po po calc calc in coronal sections the coupled sulci create the appearance of spectacles po gyru s cu n lv ei calcar avis calcar avis is the protrusion of cerebral cortex into the lateral ventricle (lv) from the midline; it is also the location of a constant submerged gyrus (gyrus cunei) between cuneus and isthmus cinguli NAVIGATOR 166 / 219 Sulcus postcentralis. The sulcus postcentralis is rather a complex of segments separated by gyri, most submerged deep within it, although a proportion may be observed from the surface. In the majority of the hemispheres (73.75%), the postcentral sulcus is separated into two or three segments or, less frequently, into four or five segments (12.5%), or it remains continuous (13.75%). The postcentral and intraparietal sulci may appear to join on the surface of the brain but they are in fact always separated by an annectant gyrus. fl ramus posterior fissurae lateralis pci sulcus precentralis inferior pcs sulcus precentralis superior poc sulcus postcentralis (24-27 w PMA) sc sulcus centralis (Rolando)(20-23 w PMA) sip sulcus intraparietalis (24-27 w PMA) tpoc transverse postcentral sulcus pcs sc poc pci sip fl tpoc sts In 32.5% of the hemispheres, a dorsoventrally oriented sulcus, the transverse postcentral sulcus, is located anterior to the postcentral sulcus on the lower part of the postcentral gyrus. typical anatomy poc poc sip fl fl tpoc relation of postcentral sulcus (poc) to lateral (lf) and interhemispheric fissure; transverse postcentral sulcus = tpoc patterns formed by the postcentral sulcal complex (poc) and the horizontal segment of the intraparietal sulcus (sip) on the surface of the brain Zlatkina V, Petrides M (2010) Morphological Patterns of the Postcentral Sulcus in the Human Brain. The Journal of Comparative Neurology | Research in Systems Neuroscience 518:3701–3724. NAVIGATOR 167 / 219 Sulcus parietalis transversus. The sulcus parietalis transversus (of Brissaud 1893), thus subdividing the superior parietal lobule (SPL) into anterior and posterior portions, can extend from the mesial side to the superolateral aspect of the cerebrum. It is present in about 1/2, starting most often posterior to the sulcus of Jensen and reaching the mesial part of the brain in some infants, between ramus supramarginalis sulci cinguli and sulcus parieto-occipitalis. sB spoc sB sip sB sB: sulcus parietalis transversus sB Brissaud E (1893) Anatomie du cerveau de l’homme. Masson, Paris. rsmsc NAVIGATOR 168 / 219 Sulcus subparietalis. Between ramus supramarginalis sulci cinguli and sulcus parieto-occipitalis the mesial parietal lobe (lobus quadrangularis or precuneus) is dominated by a variable sulcus subparietalis, separating gyrus cinguli from the parietal lobe. It takes the form of an H with limbs perpendicular to gyrus cinguli in more than half, or of a Y with one limb pointing toward the centre. One to three branches point from it to corpus callosum, a similar number may point up to the convexity. Parieto-limbic annectant gyri are common. A connection to the caudal part of sulcus cinguli is present in about 1/3 brains. The transverse parietal sulcus of Brissaud can extend from the convexity to the mesial aspect and cut into precuneus. Inferior to the subparietal sulcus, gyrus cinguli tapers sharply at the splenium forming the isthmus cinguli connecting to the gyrus parahippocampalis. preterm term pcs sc poc ssp pcs sulcus precentralis superior poc sulcus postcentralis sc sulcus centralis (Rolando) sip sulcus intraparietalis ssp sulcus subparietalis sip ssp NAVIGATOR Sulci occipitales The occipital lobe is bounded superiorly by the sulcus parieto-occipitalis, which terminates as a notch on the hemisphere’s border due to the presence of two longitudinal parieto-occipital gyral connections on the convexity. The first connection parallels this border and links the superior parietal gyrus to the superior occipital gyrus, situated posterior to the occipital segment of the sulcus intraparietalis. The second parietooccipital connection is located rostral to the sulcus intraparietalis, connecting the angular gyrus to the middle occipital gyrus. The middle occipital gyrus constitutes the largest portion of the lobe on the convexity and can be subdivided into superior and inferior regions by a middle occipital sulcus (sulcus prelunatus). The posterior end of the sulcus prelunatus may connect to a highly variable sulcus lunatus. The middle occipital gyrus is bordered superiorly by the sulcus occipitalis transversus and inferiorly by the sulcus occipitalis inferior, which extends to the occipital pole. The anterior end of the inferior occipital gyrus is to the level of the preoccipital incisure (notch), an inconstant indentation of the infero-lateral border of the hemisphere. The inferior occipital gyrus runs anteriorly into the middle or inferior temporal gyrus. When one uses the numerical approach, the first occipital gyrus O1 is above the sulcus occipitalis superior, the second O2 is between sulcus occipitalis superior and inferior (containing sulcus lunatus and prelunatus), the third O3 is between sulcus occipitalis inferior and the convexity border. On the mesial side the fourth occipital gyrus O4 is the posterior part of gyrus fusiformis, the fifth occipital gyrus O5 is the lobus lingualis and finally the sixt occipital gyrus O6 is cuneus, between sulcus calcarinus and sulcus parieto-occipitalis. The shallow sulci of the inferior temporal-occipital region show many ramifications with divergent descriptions (Duvernoy et al. 1991). Gyrus lingualis forms the inferior part of the occipital lobe on the mesial side; it is bordered by sulcus calcarinus but connected to cuneus by one or two cuneo-lingual annectant gyri. An inconstant sulcus lingualis subdivides the gyrus lingualis into superior and inferior parts, both connected anteriorly to the gyrus parahippocampalis. Triangular in shape, the cuneus is the only well delimited occipital gyrus. It is continuous with the lateral surface. 169 / 219 Sulcus calcarinus. The sulcus calcarinus originates behind and slightly below the splenium, descending to the occipital pole. At the occipital pole, it bifurcates into a vertical retrocalcarine sulcus (fissura extrema of Seitz), inferior to which lies the gyrus descendens of Ecker (1869). The latter may occasionally be situated on the lateral aspect of the hemisphere. The calcarine sulcus extends anteriorly, terminating above the posterior extent of the collateral sulcus, where the isthmus of the gyrus cinguli extends into the gyrus parahippocampalis. The cuneus is connected to the posterior aspect of the adjacent gyrus cinguli by a deeply situated gyrus cunei (cuneolimbic annectant gyrus, Ecker 1869). The fusiform lobe, located in front of the sulcus calcarinus, above the sulcus occipito-temporalis, is the gyrus lingualis. The sulcus calcarinus develops as two segments, separated at the site of contact with the sulcus parieto-occipitalis. The rostral segment, the anterior calcarine sulcus (the calcarine “stem”), participates in the formation of calcar avis. The caudal segment, the posterior calcarine sulcus described above, develops later than the anterior part. Both parieto-occipital and calcarine sulci become visible around 16 weeks post-menstrual age (PMA). By 24 weeks PMA, the cuneus and subjacent gyrus lingualis are distinctly demarcated. It is uncommon for the sulcus calcarinus to be absent after 22 weeks PMA. The parieto-occipital sulcus develops separately from the calcarine stem, and even when they align at the surface (rarely), a gyrus cunei is always present. The course and form of the posterior calcarine sulcus exhibit variability, typically situated anteriorly to the medial segment of the transverse sinus. Within the posterior calcarine segment, one or two submerged gyri, namely the anterior and posterior cuneolingual folds of Déjérine, may be present. These early sulcal pits, from which the calcarine sulcus develops, are located between these annectant gyri. Consequently, during fetal development, the middle calcarine sulcus is usually discernible and separated from the vertical posterior portion by cuneolingual annectant gyri. However, in approximately 1/20 of brains, one of these gyri becomes superficial and permanently interrupts the calcarine sulcus. The upper and lower lips of the posterior calcarine sulcus, as well as the lower lip of the anterior calcarine sulcus, correspond to the striate cortex (area 17), which is the primary visual cortex. Additionally, a smaller limiting (parallel) calcarine sulcus may be present both above and below the sulcus calcarinus. Ecker 1869, Eberstaller 1890, Cunningham 1892, Retzius 1896, Testut and Latarjet 1948, Paturet 1964, Chi et al. 1977, Duvernoy et al. 1991, Paus et al. 1996, Tamraz and Comair 2006, ten Donkelaar 2018 NAVIGATOR 170 / 219 Calcar avis. The calcar avis (“ergot de Morand”, “ergot d’oiseau”) is a piece of cortex and subcortical white matter under the incurved calcarine fissure at its merger with the sulcus parieto-occipitalis. The calcarine fissure is formed around the 16th w PMA. Between the 32nd and the 40th week it stretches, thus shifting a piece of cortex and white matter into the occipital horn. The calcar avis will be more or less prominent dependent upon the depth of the gyri. An echogram through the posterior fontanel clearly shows this structure. Distinction should be made with haemorrhage in the occipital horn, in that case showing as dense reflections from the lower margin of the occipital horn rather than its lateral and superior wall. The use of Doppler imaging to illustrate the absence of vessels in a clot can be helpful to make this distinction, especially if viewed from the posterior fontanel. parasagittal postmortem at 30 weeks calcar avis in formation at 24 weeks (Retzius 1896) po sulcus parieto-occipitalis calc sulcus calcarinus coronal po calc DiPietro MA, Brody BA, Teele RL (1985) The calcar avis: demonstration with cranial US. Radiology 156: 363–364. Retzius G (1896) Das Menshenhirn: Studien in der Makroskopischen Morphologie. Stockholm: PA Norstedt 1-167. NAVIGATOR 171 / 219 Typical sulcus parieto-occipitalis and calcarinus. posterior fontanel sagittal, preterm spa cing splenium lobulus paracentralis gyrus cinguli rsm srs calc sulcus calcarinus po sulcus parieto-occipitalis rsm ramus supramarginalis sulci cinguli v4 fourth ventricle sri ssp anel splenium po cuneus precuneus uncus po sr scoll calc gyrus fusiformis gyrus lingualis vermis cuneus calc v4 calc sulcus calcarinus cing sulcus cinguli po sulcus parieto-occipitalis poc sulcus postcentralis rsm ramus supramarginalis scoll sulcus collateralis spa sulcus paracentralis sr sulcus rhinalis sri sulcus rostralis inferior srs sulcus rostralis superior ssp sulcus subparietalis atrium rsm posterior fontanel sagittal, term po calc po po calc vermis 35w PMA, coronal 35w PMA, axial temporal fontanel calc NAVIGATOR 172 / 219 Calcar avis in CUS. calcar avis appears as a soft hyperechoic swelling in the mesial wall of the occipital horn of the lateral ventricle; it contains cortex around the anterior sulcus calcarinus the incumbent calcarine sulcus (arrow) is readily seen in the image of an infant with colpocephaly due to callosal and septal agenesis (parasagittal from posterior fontanel) parasagittal T1 MR section with calcar in front of the occpital horn tip parasagittal posterior. fontanel section with calcar in front of the occpital horn tip NAVIGATOR 173 / 219 Preterm GA 31w, PMA 33w: calcar avis. lv lv NAVIGATOR Preterm GA 32w, PMA 35w: posterior fontanel sections. calc sulcus calcarinus po sulcus parieto-occipitalis 174 / 219 NAVIGATOR Ultrasonographic description of occipital sulci Sulcus calcarinus can often be seen from the anterior fontanel in its superior part. Calcar avis is the well known impression by sulcus calcarinus into the occipital horn, at its connection to sulcus parieto-occipitalis. Direct inspection of the sulcus calcarinus is possible from the posterior fontanel. 175 / 219 bilateral hyperechoic change at calcar avis, due to occipital subdural haematoma (*) Clinical relevance The occipital lobe is difficult to assess with CUS. It can be implicated in PCA stroke, hypoglycaemia and superior sagittal sinus thrombosis. Subdural haematoma in the occipital area can be studied via the posterior fontanel, as can superior sagittal sinus thrombosis. SSS * * calc calc coronal at posterior fontanel NAVIGATOR 176 / 219 Other surface areas Ventral forebrain The term “ventral forebrain” replaces “substantia innominata”. It refers to an area containing the septal nuclei, the ventral striatum and pallidum with antero-inferior fusion called nucleus accumbens septi, the (cholinergic) basal nucleus of Meynert and its anteriorly connected nucleus of the diagonal band, plus the extended amygdala. This part of the forebrain is accessible to inspection with CUS, situated between the septal area and the insular limen, below the anterior commissure. Because of the presence of arterial perforators its surface is called area perforata anterior. Inferior striate veins descend to this area to contribute to the formation of the basal vein of Rosenthal. corpus callosum b 4 2 a 5 2 1 3 14 13 15 6 10 11 7 8 11 9 1 16 12 5 7 corpus callosum 2 corpus callosum matrix 9 1 10 2 12 16 16 2 14 5 4 17 13 thalamus 15 15 11 11 11 ACA MCA 4 chiasma opticum 7 anterior commissure at 26 w PMA ventral forebrain at term Smith and van der Kooy 1985, Höhmann et al. 1991, Gloor 1997, Haines 2004 1 nucleus lentiformis 2 caudate head 3 caudate tail 4 motor projection fibers (a head, b foot) 5 anterior limb of the internal capsule 6 olfactory trigone 7 amygdaloid nucleus 8 geniculocalcarine fibers (optic radiation) 9 insula 10 claustrum 11 ventral forebrain - nu. basalis ‘Meynert’; connects to nu. of the diagonal band - ventral striatum with nu. accumbens septi - septal nuclei - extended amygdala 12 diagonal band (nucleus) 13 pallidum 14 fornix and septal nuclei 15 anterior commissure 16 nu. accumbens septi 17 gyrus paraterminalis NAVIGATOR PMA 22w + 6d, triplet, hockey stick GE L6-24 courtesy dr Schwarz, Essen 177 / 219 NAVIGATOR 178 / 219 Corpora mammillaria The main bundle of the fornix traverses the hypothalamus, where most of its fibers terminate in the mammillary bodies. Other mammillary afferents come from the lateral septal nucleus, the medial preoptic nucleus and other hypothalamic nuclei. A direct frontomammillary pathway, originating mainly from the orbital areas 10, 11 and 47, has been described. The efferent fibers out of the mammillary body form a compact bundle, the fasciculus mammillaris princeps. This bundle passes dorsally for a short distance and then splits into the larger mammillothalamic and the smaller mammillotegmental tract. The mammillothalamic tract, which passes to the anterior thalamic nuclei, is part of the limbic system: it distributes its fibers to all three components of the anterior thalamic nucleus, where, in turn, massive projections originate to the cingulate gyrus. The mammillotegmental tract curves caudally into the tegmentum of the midbrain and terminates in the dorsal tegmental nucleus of Gudden and in the nucleus reticularis tegmenti pontis of Bechterew. A mammillotegmental reciprocal connection ascends along the ventral surface of the midbrain to the mammillary body, where most of its fibers terminate. Some of them join the medial forebrain bundle and spread to the lateral preoptico-hypothalamic zone and septum. By way of this tract, the mammillary bodies (and ultimately the hippocampus) influence activity of the reticular formation. The mammillary bodies play a role in the construction of memories. Hypothalamic loops (from the corpora mammillaria and the adjacent area) supplement direct hippocampus-neocortex connections with iterative reprocessing, paced by theta rhythmicity (McNaughton and Vann 2022). Recirculation in these loops progressively enhances desired connections necessary for complex learning and memory. The mammillary bodies are consistently damaged in Korsakoff ’s syndrome, which includes selective anterograde and retrograde amnesia, confabulations and severe learning disabilities. It is a sequel of Wernicke’s encephalopathy, an alcohol-induced disease caused by thiamine deficiency. Injury to the mammillary bodies (detected with high resolution diffusion tensor imaging) is common in perinatal hypoxia-ischaemia (Lequin et al. 2022), which may have an impact on declarative memory later on. Nieuwenhuys et al. 1988, Peterson et al. 2021, McNaughton and Vann 2022, Lequin et al. 2022 hypothalamic loops (from the corpora mammillaria) supplement direct hippocampal-cortical connections with iterative reprocessing these reiterations are paced by theta rhythmicity these hypothalamic nodes and loops provide motivation for engram enhancement during memory consolidation 7 9 3 ø 4 2 1 5 6 example of a long mammillary to thalamus to cortex to entorhinal area loop 1 2 3 4 5 6 7 9 corpora mammillaria + supramammillary area hypothalamus thalamus (anterior nuclei) hippocampus, entorhinal area, retrosplenial cortex reticular formation vestibular nuclei prefrontal and cingulate cortex parieto-occipital cortex NAVIGATOR 1 2 3 4 5 6 179 / 219 corpora mammillaria + supramammillary area hypothalamus hippocampus, entorhinal area, retrosplenial cortex processus intermammillaris diagonal band of Broca tuber cinereum optic tract 5 6 2 Retzius 1896 fetus 34 cm CRL ø 4 mesencephalon via entorhinal area 1 co mammillaria direct 3 example of a short mammillary-hippocampal loop pedunculus term birth asphyxia, diffusion weighted MRI on day 4, after total body cooling: high signal in diffusion restricted mammillary bodies co mammillaria axial section at 25w PMA axial section at 25w PMA Lequin MH, Steggerda SJ, Severino M, Tortora D, Parodi A, Ramenghi LA, Groenendaal F, Meys KME, Benders MJNL, de Vries LS, Vann SD. Mammillary body injury in neonatal encephalopathy: a multicentre, retrospective study. Pediatr Res. 2022 Jul;92(1):174-179. NAVIGATOR 180 / 219 Olfactory structures and function early fourth month The olfactory tract develops in late first trimester. The olfactory recessus, an extension of the lateral ventricle into the olfactory bulb, obliterates in late second trimester, but occasionally hydrocephalus (e.g. with preterm IVH) may reopen this recessus. The nasal olfactory epithelium develops in early third trimester, with specific receptor proteins present around 28 w PMA. The olfactory chemical sensor system is active in preterm infants around 28 w PMA: pure aromatic testing under the nostrils during quit sleep or drowsiness can elicit a reflex of swallowing or a withdrawal response e.g. to peppermint oil. 1 2 3 4 5 6 1 2 Odorants stimulate protrusions of these cells and open coupled G protein receptors which send axon potentials to the olfactory bulb. From the nasal mucosa, unmyelinated axons cross the lamina cribrosa as cranial nerve nr 1 to make synapses with the glomeruli at the base of the olfactory bulb. Glomeruli are odorant-specific. Dendrites of mitral neurons in these glomeruli pick up signals from the nasal epithelium. These signals converge on bulb mitral neurons. The main output from the olfactory bulb is to the anterior olfactory nucleus in the olfactory bulb and tract (similar to thalamic relay for other sensory systems), to the piriform cortex, to the amygdala, to entorhinal cortex, to the contralateral olfactory bulb via the anterior commissure, to septal nuclei and hypothalamus. The bulb neurons are present from around 18 w PMA, but mature marker expression occurs around term (NeuN, and LFB for myelin after term birth). 6 3 5 4 Gray’s anatomy 7 In coronal sonograms and coronal T2 MRI, the olfactory sulci can be depicted from around 25 w PMA, and should be visible at 30 w PMA. Their depth increases so that around 35 w PMA it is 5 mm, approaching 1 cm in some term infants. Asymmetry in growth is possible. The olfactory tract is hidden in nearby dura and bone reflections. MRI can show the olfactory tract itself. 2 9 3 8 5 Specific mutations can exclude odors from activity (specific anosmias). Total anosmia exists with arhinia (absent nose base) and with arhinencephaly (wich can be unilateral). Syndromes with arhinencephaly: CHARGE association (CHD7, 22q11.2), Kallman - de Morsier syndrome, septo-optic dysplasia, Waardenburg s., aneuploidies (48xxx+21) and holoprosencephalies. Dysplastic enlargement of the olfactory bulb is seen in hemimegalencephaly and orbitofrontal cortical dysplasia. medial olfactory lobe lateral olfactory lobe gyrus ambiens gyrus semilunaris gyrus diagonalis optic chiasm 6 4 6 Retzius 1896 @ adult Gloor P (1997) The temporal lobe and limbic system. Oxford University press. Sarnat HB, Flores-Sarnat L, Wei XC (2017) Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine-Tasting. J Child Neurol 32(6):566-578. Sarnat HB, Flores-Sarnat L (2017) Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses. J Child Neurol 32(6):579-593. https://commons.wikimedia.org/wiki/File:Gray655.png 1 olfactory tract 2 olfactory trigone (region of anterior olfactory nucleus) 3 lateral olfactory stria 4 amygdaloid nuclei ‘cortical, medial) under gyrus semilunaris (with peri-amygdaloid allocortex) 5 anterior perforated substance (underneath it is the ventral forebrain area)(homologue to tuberculum olfactorium of lower mammals) 6 uncus 7 gyrus rectus 8 diagonal band (Broca) into gyrus paraterminalis 9 transverse insular gyrus NAVIGATOR The olfactory epithelium and olfactory function. olfactory sensory neuron in nasal mucosa OSN cranial nerve 1 convergence olfactory bulb locus coeruleus and raphe nuclei anterior olfactory nucleus divergence amygdala (cortical nuclei) entorhinal cortex MD thalamus gyrus rectus hippocampus/ subiculum contralateral olfactory bulb via anterior commissure (myelination after term) piriform cortex septal nuclei hypothalamus orbitofrontal neocortex amygdala/ limbic system adapted from Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates. 181 / 219 NAVIGATOR The olfactory glomeruli. 182 / 219 from olfactory epithelium in nose Golgi C 1875 1 axons from nasal olfactory epithelium: unmyelinated, calretinin-reactive; specialized glial ensheathing cells guide formation of axons throughout life; myelination occurs after term birth 2 glomeruli: precise synaptic ratios between olfactory axons and mitral cell dendrites for amplification; periglomerular cells co-express GABA and dopamine 3 external plexiform layer: tufted neurons, otherwise cell-sparse; dendrodendritic synapses 4 mitral neuronal cell layer: forms at 9 wks PMA; axons extend into olfactory tract 5 internal plexiform layer: neurites; cell- and synapse sparse 6 granular neurons in core of olfactory bulb; form laminae alternating with sheets of dendrodendritic synapses; main reservoir of resident progenitor cells; no axons; granular layer extends into the olfactory tract where it forms the anterior olfactory nucleus which has a rôle similar to thalamic relay for other sensory modalities (mainly inhibitory) to olfactory bulb and tract Shepherd GM, Greer CA, Mazzarello P, Sassoè-Pognetto M. The first images of nerve cells: Golgi on the olfactory bulb 1875. Brain Res Rev. 2011 Jan 7;66(1-2):92-105. NAVIGATOR 183 / 219 The piriform cortex. 1 2 sagittal detail 10 3 4 13 septum 11 7 5 14 12 12 15 6 hypothalamus Retzius 1896; adult 8 9 19 17 16 1 olfactory bulb 2 olfactory tract 3 olfactory tubercle or trigone with vestigial anteior olfactory nucleus in front) 4 lateral olfactory stria 5 olfactory sensory area in temporal pole: piriform or rhinal cortex (ends at entorhinal cortex)(spans from insula to amygdala) 6 amygdaloid nuclei (cortical nucleus) 7 anterior perforated substance (substantia innominata underneath = ventral forebrain area) (some of it has prepiriform cortex) 8 uncus 9 sulcus collateralis 10 gyrus rectus 11 sulcus rhinalis 12 diagonal band (Broca) along gyrus paraterminalis (septal. nuclei to amygdala) 13 sulcus cinguli 14 sulcus rostralis inferior 15 sulcus parolfactorius anterior 16 sulcus parolfactorius posterior 17 gyrus parolfactorius (“carrefour olfactif” de Broca) (gyrus subcallosus) 18 anterior olfactory nucleus 19 stria terminalis NAVIGATOR 184 / 219 The olfactory area and surrounding anatomy. inferior view in detail mesial lateral 8 1 2 3 4 olfactory tract olfactory trigone lateral olfactory stria olfactory sensory area in temporal pole: piriform or rhinal cortex (ends at entorhinal cortex)(former prepiriform plus peri-amygdaloid cortex) 5 amygdaloid nuclei (cortical nucleus) in gyrus semilunatus 6 anterior perforated substance (= ventral forebrain area) 7 sulcus rhinalis 8 gyrus rectus 9 diagonal band (Broca) between septum and hippocampus/amygdala (also called paraterminal gyrus at the mesial end) 10 sulcus parolfactorius anterior 11 limen insulae 12 gyrus transversus insulae ( ~= gyrus olfactorius lateralis of Retzius) 13 gyrus parolfactorius (subcallosus) 14 insular pole 1 10 12 13 2 9 ten Donkelaar HJ (2011) Clinical neuroanatomy. Brain circuitry and its disorders. Springer. 6 3 11 4 Retzius 1896; adult The diagonal band (TNA Latin: Stria diagonalis; eponym: diagonal band of Broca) is a band of fibers extending into the amygdaloid body from the paraterminal gyrus on the medial side of the frontal lobe ventrally and along the lateral margin of the optic tract, marking the caudal boundary of the anterior perforated substance or olfactory tubercle; it is also known as the olfactory radiation of Zuckerkandl. The diagonal band can be further subdivided into horizontal and vertical limbs, containing neurons, collectively called the nucleus of the diagonal band (TNA Latin: Nucleus striae diagonalis). 14 5 7 NAVIGATOR 185 / 219 The piriform cortex in evolution. rat human fetus 5-6 months 1 2 7 1 5 OT 10 9 8 6 Retzius 1896 @ 22w PMA 14 2 13 3 5 4 11 10 12 4 12 11 14 Retzius 1896 @ 40w PMA P 1 olfactory tract 2 olfactory trigone (region of anterior olfactory nucleus)(surrounds olfactory tubercle OT) 3 lateral olfactory stria 4 amygdaloid nuclei ‘cortical, medial) under gyrus semilunaris (with peri-amygdaloid allocortex) 5 anterior perforated substance (substantia innominata underneath = ventral forebrain area) (homologue to tuberculum olfactorium of lower mammals) 6 uncus Nieuwenhuys R, Voogd J, van Huijzen C (2008) The human central nervous system. Fourth revised edition. Springer-Verlag. 7 gyrus rectus 8 diagonal band (Broca) into gyrus paraterminalis 9 medial olfactory stria to gyrus parolfactorius (subcallosus) 10 (pre)pririform (olfactory) allocortex 11 entorhinal cortex 12 sulcus rhinalis 13 insular pole ℗, agranular insular cortex 14 posterior dysgranular orbital cortex NAVIGATOR 186 / 219 The orbitofrontal olfactory area. olfactory epithelium olfactory bulb lateral olfactory tract olfactory allocortex olfactory stimuli activate monkey orbitofrontal cortex in area 12 of Walker (1940) MD thalamus endopiriform nucleus indirect ventral agranular insular area olfactory allocortex direct multimodal function of “flavor” posterolateral orbital isocortex (right only in human) gustatory Gloor P (1997) The temporal lobe and limbic system. Oxford University press. dysgranular posterior orbital neocortex ventral agranular area of the insula MD thalamus NAVIGATOR 187 / 219 Arhinencepahly. sulcus olfactorius at 25w1d PMA arhinencephaly: Charge association (CDH7 mutation) holoprosencephaly Frijns syndrome SLO syndrome Aicardi syndrome Joubert syndrome Kallman-Demorsier syndrome (GnRH defic. and anosmia) chromosomal anomalies median lipoma fronto-naso-ethmoidal encephalocele craniotelencephalic dysplasia giant diencephalic hamartoma sulcus olfactorius at 34w PMA unilateral arhinencephaly NAVIGATOR 188 / 219 Septum a cavum septi pellucidi b septal nuclei (septum verum) c commissura anterior d lamina terminalis e gyrus subcallosus (Zûckerkandl) with precommissural hippocampus f sulcus parolfactorius anterior a c b a e b c e d d f Retzius ~ term Retzius ~ 26w PMA 1 17 20 19 2 18 3 4 5 21 7 9 22 23 6 s 8 t 7 14 13 10 11 12 26 15 16 24 25 27 1 cingulate gyrus 2 indusium griseum 3 body of the caudate nucleus 4 pontes grisei 5 septum pellucidum 6 septal nuclei 7 putamen 8 claustrum 9 insula 10 nucleus of the diagonal band (s septal part, t tuberal part) 11 accumbens nucleus: St -> Hb -> A -> H -> C <— posterior commissure morphological age d13 morphological age d15.5 H—> optic chiasm ——> morphological age d14 anterior commissure corpus callosum fornix and fornical commissure habenular commissure optic chiasm posterior commissure stria terminalis <— stria terminalis morphological age d16 <— C morphological age d14.5 habenular commissure —> fornix columns —> morphological age d17 morphological age d15 1 5 mm adapted after Wahlsten D (1981) Prenatal schedule of appearance of mouse brain commissures. Dev Brain Res 1:461–473. <— A NAVIGATOR 194 / 219 An invention of some mammals: the corpus callosum. Archicortex and paleocortex are displaced by the developing corpus callosum; hippocampus curls at the same time: - the dentate gyrus curls medially at the tip of the hippocampal formation - the cornu ammonis moves laterally, forming an "S" shape on coronal sections - dentate gyrus loses its connection with the hippocampus proper and curls as an final position of the hippocampus independent C structure around it - the limbic rotation moves the hippocampus from the roof to the floor of the ventricle; development of corpus callosum in the glial sling displaces the hippocampus caudally and later into the temporal lobe. callosal mammal proto-mammal acallosal mammal E PS H ST CC CA HC LFB DG LFB T ST MFB RS ST H hippocampus HC hippocampal commissure CC corpus callosum MFB medial forebrain bundle RS sulcus rhinalis ST striatum T thalamus LFB lateral forebrain bundle (internal capsule) T CA RS MFB DG H PS SR adapted from Gloor P (1997) The temporal lobe and limbic system. Oxford University press. S CA tex cor allo isocortex mesocortex E entorhinal cortex PS presubiculum S subiculum CA cornu ammonis DG dentate gyrus SR sulcus rhinalis/collateralis DG NAVIGATOR 195 / 219 Steps in commissure formation. interhemispheric integration of sensory cortices, becomes more performant than anterior and hippocampal commissures of nonplacental mammals pioneering fibers use the axons of the hippocampal commissure across the midline specialised glia secrete axon guidance cues, both of which may lead to callosal agenesis if impaired or absent corpus callosum (rostrum, trunk and splenium) is complete around the 15th week; splenium is fully grown by 20 weeks; both commissural anchors are present until 14 w PMA 1 CG 6 CG cingulate gyrus GW glial wedge (repellent) IGG induseum griseum glia (repellent) MZG midline zipper glia (attractant) SS subcallosal sling PMA 11w 5 attracting axons 4 2 IGG repelling axons 3 SS GW 1. to send a cingulate pioneer axon ventrally toward the intermediate zone, repelling from the marginal zone 2. turning toward the midline (choose internal capsule or corpus callosum) 3. cross at the corticoseptal boundary (funnelling) 4. dorsal turn at corticoseptal boundary of other side, repelled from midline 5. locate neocortical target 6. locate correct layer and innervate MZG midline fusion, above median telencephalic sulcus Slits (Slit 1,2,3 and Robo receptors: repelling axons at the midline), Comm (inhibiting repulsion by Robo), Netrins (to floor plate after crossing), Ephrins, NF1A and B Wnt family (attraction to rostral), heparan sulphate proteoglycans coronal sections at forebrain rostral FGF and DRAXIN in the formation of midline glial structures caudal 3 3 2 1 NAVIGATOR 196 / 219 Complete callosal agenesis with Probst bundle. in the absence of a permissive glial substrate, the interhemispheric fissure deepens; axons divert at an area where collaterals are formed in normal commissurating axons pioneer axon turns posterior above and medial to the lateral ventricle in a U-turn and form the bundle described by Probst pioneer axon turns posterior above and medial to the lateral ventricle in a U-turn and form the bundle described by Probst (ectopic or rerouted ?) to contralateral ( heterotopic) cortex via hippocampal commissure causes - structural 12 % (midline lipoma, interhemispheric cyst or tumour …) - genetic 83 % (failure secreted cues and/or midline glia, e.g. indusium griseum glia and zipper glia) - other: gamma irradiation, ZIKA virus … to ipsilateral septal area to ipsilateral cortex sigmoid bundle: frontal to contralateral parieto-occipital via aberrant tract Probst bundle - above and medial to the lateral ventricle - coiled (tortuous) - broader rostral than caudal - rostrocaudal direction in the mature stage (initially bidrectional) - partly ventromedial to fornix, partly exuberant connections to septum - functional both in ipsilateral and contralateral hemisphere v v P cingulum P Probst bundle v ventricle Lynton Z, Suárez R, Fenlon LR. Brain plasticity following corpus callosum agenesis or loss: a review of the Probst bundles. Front Neuroanat. 2023 Nov 6;17:1296779. doi: 10.3389/ fnana.2023.1296779. PMID: 38020213; PMCID: PMC10657877. Raybaud C. The corpus callosum, the other great forebrain commissures and the septum pellucidum: anatomy, development and malformation. Neuroradiology 2010; 52:447-477. P NAVIGATOR Regional subdivsion of callosal fibers. adapted from Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. oxford University press. 197 / 219 NAVIGATOR 198 / 219 The human midline at PMA 10-20w. CC CV 1 anterior commissure (AC) 2 fornix and hippocampal commissure (primordium hippocampi)(HC) 3 corpus callosum (CC) 4 septal area (ventral lamina reuniens) 5 optic chiasm (OC) 6 lamina terminalis 7 future cavum septi pellucidi (initially open to the arachnoid space due to the fact that the rostrum is not formed)(CSP) 8 cavum Vergae (CV) 9 olfactory to septum connection (gyrus paraterminalis into diagondal band of Broca) 10 striae longitudinales HC F CSP Hb AC PC PC HC AC OC PMA 10w OC PMA 15w Retzius fetus 17 cm, about 14w post conception, PMA 16w Retzius fetus 28 cm, about PMA 20w 3 7 2 3 4 6 sulci are postmortem artefacts 8 1 7 10 2 5 2 9 4 1 6 NAVIGATOR 199 / 219 The cavum veli interpositi in relation to the internal cerebral vein and tectum. cavum velum interpositum (space between folded plicae choroideae) extends posteriorly into the pineal region beneath the splenium of the corpus callosum; the course of the internal cerebral veins is away from the splenium the fornices are downwardly displaced with the presence of the cavum septi pellucidi (SP) and the cavum vergae (CV), resulting in a concave upper border of the cavum velum interpositum ICV F CSP O O CV CSP < ———— —CVI O F fornix O pineal gland Chen CY, Chen FH, Lee CC, Lee KW, Hsiao HS. Sonographic characteristics of the cavum velum interpositum. AJNR Am J Neuroradiol. 1998 Oct;19(9):1631-5. Rakic P, Yakovlev PI (1968) Development of the Corpus Callosum and Cavum Septi in Man. J Comparative Neurology 1968 NAVIGATOR 200 / 219 Fornix between cavum Vergae and cavum veli interpositi. 1 2 3 4 5 6 7 8 9 lateral ventricle third ventricle fornix cavum septi pellucidi “sixth ventricle”/cavum Vergae cavum veli interpositi internal cerebral vein medial posterior choroidal artery plexus corpus callosum fornix is above cavum veli interpositi fornix is below cavum Vergae posterior the cavum Vergae is bounded anteriorly by the columnae fornicis, superiorly by the body and splenium of the corpus callosum, inferiorly by splenium the psalterium and hippocampal commissure; it extends laterally under the floor of the lateral ventricles 1 9 4 3 cavum Vergae aqueductus ventriculi septi 5 6 7 8 deep grey matter 2 fornix caudate cavum septi pellucidi 1 3 9 4 8 2 anterior 2 Dandy WE (1931) Congenital cerebral cysts of the cavum septi pellucidi (fifth ventricle) and cavum Vergae (sixth ventricle). Verga Diagnosis and 1851 treatment. Arch Neurol Psychiatry 25: 44-66. NAVIGATOR 201 / 219 Midsagittal structures in CUS. 9 15 1 10 16 13 14 2 3 4 11 12 7 8 5 1 2 3 4 5 6 7 8 genu splenium v3 sulcus parieto-occipitalis v4 vermis basis pontis tegmentum pontis 6 9 sulcus cinguli 10 sulcus rostralis superior 11 quadrigeminal cistern 12 interpeduncular cistern 13 tela choroidea 14 sulcus hypothalamicus 15 ramus supramarginalis sulci cinguli 16 sulcus subparietalis NAVIGATOR 202 / 219 Corpus callosum in sagittal sections of CUS. cingulum tela callosal septa in CUS at 30w + 5w PMA normal normal corpus callosum hypoplasia/atrophy hypoplasia or atrophy hypogenesis hypogenesis focal destruction or focal hypoplasia midsagittal section at term focal destruction or hypoplasia Leuret F, Gratiolet P (1839) Anatomie comparée du système nerveux, considérée dans ses rapports avec l’intelligence, vol 1 and 2. Baillière, Paris. Atlas. Masson, Paris NAVIGATOR 203 / 219 Midsagittal plane: cavities, fornix and internal cerebral vein. midsagittal section @ 25w PMA midsagittal section @ 27w PMA CSP CSP fornix CSP fornix ICV CV AI AI CV CVI CVI v3 tectum base of pons midline cavities: CSP cavum septi pellucidi CV cavum Vergae CVI cavum veli interpositi AI adhesio interthalamica ICV internal cerebral vein 1 5 4 mesial surface at 29w GA 2 3 1 2 3 4 5 sulcus sulcus sulcus sulcus fornix cinguli parieto-occipitalis calcarinus (posterior) rostralis superior near term template tegmentum of pons v4 tonsil NAVIGATOR 204 / 219 Coronal plane: cavities and fornix. low resolution, through the foramen of Monro CC C F anterior to the foramen of Monro CC C F S AC high resolution, just anterior to the foramen of Monro CC AC anterior commissure C cavum septi pellucidi CC corpus callosum F fornix S septum C F S courtesy Silvia Planas, Barcelona NAVIGATOR 205 / 219 Growth of cavum septi pellucidi and cavum Vergae. cavum septi pellucidi CSP width in mm cavum Vergae CV CSP width in mm PMA in weeks PMA in weeks after Jarvis and Griffiths 2020 based on fetal MRI Jarvis D, Griffiths PD: Normal appearances and dimensions of the foetal cavum septi pellucidi and vergae on in utero MR imaging. Neuroradiology (2020) 62:617–627 NAVIGATOR Midline cavities. 206 / 219 NAVIGATOR 207 / 219 Ultrasound maturation scores of the cerebral surface 2D neonatal CUS pattern scoring of cerebral sulcus maturation in three planes Murphy et al. 1989 Pistorius et al. 2010 2D and 3D fetal CUS maturation pattern score of several sulci in several planes Hahner et al. 2017 2D fetal CUS maturation pattern score of sulcus parietooccipitalis and the lateral fissure in two axial planes 2D neonatal CUS maturation pattern score of sulcus cinguli and the insular surface Stein et al. 2023 Koning et al. 2017 2D fetal CUS maturation pattern score of several sulci in axial planes Chen et al. 2017 insular height in cm (coronal) Chaithanya A, Sakalecha AK, Srinivasa BCR. Role of Ultrasonography in the Evaluation of Normal Developmental Pattern of Fetal Cerebral Sulci Between 18 and 32 Weeks of Gestational Age. Cureus. 2022 Feb 24;14(2):e22581. Chen X, Li SL, Luo GY, Norwitz ER, Ouyang SY, Wen HX, Yuan Y, Tian XX, He JM. Ultrasonographic Characteristics of Cortical Sulcus Development in the Human Fetus between 18 and 41 Weeks of Gestation. Chin Med J (Engl). 2017 Apr 20;130(8):920-928. Hahner N, Puerto B, Perez-Cruz M, Policiano C, Monterde E, Crispi F, Gratacos E, Eixarch E (2017) Altered cortical development in fetuses with isolated non-severe ventriculomegaly assessed by neurosonography. Prenatal Diagnosis 38: 365-375. Koning IV, van Graafeiland AW, Groenenberg IAL, Husen SC, Go ATJI, Dudink J, Willemsen SP, Cornette JMJ, Steegers-Theunissen RPM (2017) Prenatal influence of congenital heart defects on trajectories of cortical folding of the fetal brain using three-dimensional ultrasound. Prenat Diagn 37(10):1008-1016. Murphy NP, Rennie J, Cooke RWI (1989) Cranial ultrasound assessment of gestational age in low birthweight infants. Archives of Disease in Childhood 64: 569–572. Pistorius LR, Stoutenbeek P, Groenendaal F, de Vries L, Manten G, Mulder E, Visser G (2010) Grade and symmetry of normal fetal cortical development: a longitudinal two- and threedimensional ultrasound study. Ultrasound Obstet Gynecol 36(6):700-8. Stein A, Sody E, Bruns N, Felderhoff-Müser U. Development of an Ultrasound Scoring System to Describe Brain Maturation in Preterm Infants. AJNR Am J Neuroradiol. 2023 Jul;44(7):846-852. Tarui T, Madan N, Graham G, Kitano R, Akiyama S, Takeoka E, Reid S, Yun HJ, Craig A, Samura O, Grant E, Im K. Comprehensive quantitative analyses of fetal magnetic resonance imaging in isolated cerebral ventriculomegaly. Neuroimage Clin. 2023;37:103357. NAVIGATOR Asymmetry of the brain, dominances (= complementary specialisation). - - - lateralisation more outspoken in males => advantage for visuospatial tasks, disadvantage for language amygdala are informed by both hemispheres among left handed persons: more artists, mathematicians, twins callosotomy => no longer dreaming, some memory loss (posterior hippocampal commissure cut), many disconnection effects in praxis and language -> corpus callosum harmonises function for almost any activity or function eye and ear side preference not related to handedness foot preference best related to cerebral dominance topic right brain dominance for functions affective aspects of speech left brain analytic, functional affective aspects of speech, word priming visuospatial tasks (forms, shape, distance) music, writing hearing words negative feelings positive feelings mental image based on metrics mental image based on description IFS inferior frontal sulcus SFS superior frontal sulcus PCS postcentral sulcus STS superior temporal sulcus INS insula LF lateral fissure CS central sulcus attention to both sides of the visual space speech dominance in speech 5% right-handed (90 %) speech 95 % speech dominance in 5-10 % left-handed (10 %) 70% most not left are bilaterally organised apraxia, some facial agnosia perinatal left competition between hemisphere lesion language and visuospatial abilities persisting structural usually two Heschl gyri asymmetry (auditory primary cortex); claustrum about 10 % larger MR confirmation of a 19th centry finding: sulci are far from perfectly symmetrical, especially language dominance on the left shifts structures such that primary sulci develop asymmetrically. comments routine facial recognition structural asymmetry in right before left: almost developing preterms all sulci Regional asymmetry in sequential neonatal MRI. speech, language, mental activity around meaning, verbal-literal holistic typical lesions spatial agnosia, facial agnosia, amusia, neglect 208 / 219 pathological left handedness left before right: sulcus calcarinus and parietooccipitalis larger planum temporale; longer and less ascending lateral fissure; larger pars triangularis and more diagonal sulci Springer SP, Deutsch G (1989) Left brain, right brain. Fifth edition. WH Freeman and Co, New York. Kersbergen KJ, Leroy F, Išgum I, Groenendaal F, de Vries LS, Claessens NH, van Haastert IC, Moeskops P, Fischer C, Mangin JF, Viergever MA, Dubois J, Benders MJ (2016) Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants. Neuroimage. 142:301-310. NAVIGATOR 209 / 219 Surface targets for functional ultrasound It is expected that, most likely by measuring neurovascular coupling in specific areas of the brain surface, bedside analysis of brain function will be possible with ultrasound (functional ultrasound or fUSi). This will depend on robust high resolution doppler analysis, but also on a simple paradigm for stimulation of the function to be recorded. Given easy access to the anterior and mastoid fontanels, the following cortical areas are candidates for fUSi: the pericentral area near the hand knob, the primary auditory cortex and its belt, the olfactory cortex, the cerebellum, striatum. Studies will need to find out whether preterm prefrontal cortex is activated by language and music exposure. Some of this information should be complementary to fMRI based on the bold-paradigm (using images informed by de-oxygenated hemoglobin). striatum auditory area piriform (olfactory) cortex sensorimotor hand area cerebellar cortex NAVIGATOR several functional specialisations of the central and frontal neocortex may be targets for the study of neurovascular coupling with ultrasound 210 / 219 NAVIGATOR 211 / 219 Cerebellum Due to partial visualisation with ultrasound, a quantified analysis of cerebellum remains a challenge. But foliation starts to be visible at early preterm age and some measurements of cerebellar size are reproducible thoughout the preterm stay on the NICU. crl 54 mm pma 12 w crl 68 mm pma 13 w crl 80 mm pma 14 w crl 105 mm pma 16 w crl 111 mm pma 17 w crl 125 mm pma 18 w crl 143 mm pma 19 w numbers of folia per lobule of the human cerebellum (visual fit of the means) The gestational age at which a lobule attains half the adult average number of folia varies between 24 and 37 weeks. Anterior and posterior lobules mature earlier than the middle ones. The adult number of folia is reached around 2 months after term birth. From Loeser et al. 1972. crl 155 mm pma 20 w crl 200 mm pma 23 w crl 230 mm pma 26 w 26w coronal Bayer & Altman 2005 foliation at viable preterm age crl 250 mm pma 28 w EGL external granular layer IGL internal granular layer Pu purkinje cell layer Cerebellar developmental histology (Larroche 1977, Friede 1989) stage PMA weeks layers description 1 3-8 2 (sub)ventricular plus intermediate layer 2 8-20 3 formation of the EGL; condensation of the IGL starts 3 20-30 5 progressively thickening EGL: lamina dissecans (between Pu cell layer and IGL), dissappears around 28 w in vesticulo- en spinocerebellum, around 32 w in neocerebellum 4 30-term 4 IGL growing fast and Pu layer conspicuous 5 > term 4 - 3 thinning of EGL rapidly after 3 months of life; molecular layer starts to thicken around term and reaches adult size near end of the first year Loeser JD, Lemire RJ, Alvord EC (1972) The development of the folia in the human cerebellar vermis. Anat Rec 173:109-114. 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