The neuropathology of hereditary congenital facial palsy vs Möbius syndrome.

OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial patients were compared with those of patients with Möbius syndrome. RESULTS: The authors observed a marked decrease in the number of neurons in the facial motor nucleus with corresponding small facial nerve remnants. In the patients with congenital facial palsy the number of facial motoneurons ranged between 280 and 1,680 as compared to 5,030 and 8,700 for controls. No signs of neuronal degeneration or necrosis with neuronal loss, gliosis, or calcifications were present. There were no other abnormalities of the rhombencephalon and its associated structures. The corticospinal tracts were fully developed. In contrast, Möbius syndrome is part of a more complex congenital anomaly of the posterior fossa with hypoplasia of the entire brainstem, including the traversing long tracts, with signs of neuronal degeneration and other congenital brain abnormalities. CONCLUSION: Neuropathologic findings confirm clinical observations that hereditary congenital facial palsy and Möbius syndrome are two different entities with a different pathogenesis.

Differential gene expression in human brain pericytes induced by amyloid-beta protein.

Cerebral amyloid angiopathy is one of the characteristics of Alzheimer's disease (AD) and this accumulation of fibrillar amyloid-beta (Alphabeta) in the vascular wall is accompanied by marked vascular damage. In vitro, Abeta1-40 carrying the 'Dutch' mutation (DAbeta1-40) induces degeneration of cultured human brain pericytes (HBP). To identify possible intracellular mediators of Abeta-induced cell death, a comparative cDNA expression array was performed to detect differential gene expression of Abeta-treated vs. untreated HBP. Messenger RNA expression of cyclin D1, integrin beta4, defender against cell death-1, neuroleukin, thymosin beta10, and integrin alpha5 were increased in DAbeta1-40-treated HBP, whereas insulin-like growth factor binding protein-2 mRNA expression was decreased. Corresponding protein expression was investigated in AD and control brains to explore a potential role for these proteins in pathological lesions of the AD brain. Cyclin D1 expression was increased in cerebral amyloid angiopathy and cells in a perivascular position, suggesting that the cell cycle may be disturbed during Abeta-mediated degeneration of cerebrovascular cells. Moreover, cyclin D1 expression, but also that of integrin beta4, defender against cell death-1, neuroleukin and thymosin beta10 was found in a subset of senile plaques, suggesting a role for these proteins in the pathogenesis of senile plaques.

Development and malformations of the human pyramidal tract.

The corticospinal tract develops over a rather long period of time, during which malformations involving this main central motor pathway may occur. In rodents, the spinal outgrowth of the corticospinal tract occurs entirely postnatally, but in primates largely prenatally. In mice, an increasing number of genes have been found to play a role during the development of the pyramidal tract. In experimentally studied mammals, initially a much larger part of the cerebral cortex sends axons to the spinal cord, and the site of termination of corticospinal fibers in the spinal grey matter is much more extensive than in adult animals. Selective elimination of the transient corticospinal projections yields the mature projections functionally appropriate for the pyramidal tract. Direct corticomotoneuronal projections arise as the latest components of the corticospinal system. The subsequent myelination of the pyramidal tract is a slow process, taking place over a considerable period of time. Available data suggest that in man the pyramidal tract develops in a similar way. Several variations in the funicular trajectory of the human pyramidal tract have been described in otherwise normally developed cases, the most obvious being those with uncrossed pyramidal tracts. A survey of the neuropathological and clinical literature, illustrated with autopsy cases, reveals that the pyramidal tract may be involved in a large number of developmental disorders. Most of these malformations form part of a broad spectrum, ranging from disorders of patterning, neurogenesis and neuronal migration of the cerebral cortex to hypoxic-ischemic injury of the white matter. In some cases, pyramidal tract malformations may be due to abnormal axon guidance mechanisms. The molecular nature of such disorders is only beginning to be revealed.

Development and developmental disorders of the human cerebellum.

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

A spinal intradural enterogenous cyst with well-differentiated muscularis propria.

We report a case of a newborn presenting with severe compression of the spinal cord due to a large, solitary mass extending from C4 to T2. Neurosurgical exploration revealed a large intradural, extramedullary cystic lesion, compressing the spinal cord. Slowly progressive respiratory failure due to severe myelopathy led to the death of the child 19 days postpartum. At autopsy, a well-differentiated enterogenous cyst was found, the cyst wall containing gastric and esophageal type mucosa, and a bona fide muscularis propria. The gastrointestinal tract was completely normal. The possible developmental history of intradural enterogenous cysts is discussed.

Origin and development of descending catecholaminergic pathways to the spinal cord in amphibians.

The origin and development of the supraspinal catecholaminergic (CA) innervation of the spinal cord was studied in representative species of the three amphibian orders (Anura: Xenopus laevis and Rana perezi; Urodela: Pleurodeles waltl; Gymnophiona: Dermophis mexicanus). Using retrograde dextran amine tracing in combination with tyrosine hydroxylase (TH)-immunohistochemistry, we showed that only four brain centers contribute to the CA innervation of the adult spinal cord: (1) the ventrolateral component of the posterior tubercle, (2) the periventricular nucleus of the zona incerta, (3) the locus coeruleus, and (4) the nucleus of the solitary tract (except for gymnophionans). The pattern observed is largely similar in all amphibian species studied. The development of the CA innervation of the spinal cord was studied with in vitro double labeling methods in Xenopus laevis tadpoles. At stage 40/41, the first CA neurons projecting to the spinal cord were found to originate in the posterior tubercle. At stage 43, spinal projections were found from the periventricular nucleus of the zona incerta and the locus coeruleus, whereas spinal projections from the nucleus of the solitary tract were not observed before stage 53. These results demonstrate a temporal sequence in the appearance of the CA cell groups projecting to the anuran spinal cord, organized along a rostrocaudal gradient.

Intestinal mucosa on top of a rudimentary occipital meningocele in amniotic rupture sequence: disorganization-like syndrome, homeotic transformation, abnormal surface encounter or endoectodermal adhesion?

We present a case of a peculiar rudimentary occipital meningocele that was surgically removed when the patient (a boy) was 5 months of age. The patient also had distal transverse defects of both hands. The association of congenital scalp defects and distal congenital hand anomalies is relatively rare and one form is known as the Adams-Oliver syndrome. To our surprise, microscopic examination revealed intestinal mucosa on top of the skin tag containing the rudimentary meningocele. No comparable cases were found in the literature. We discuss the following possible explanations for this peculiar situation: 1) disorganization-like syndrome; 2) homeotic transformation; 3) abnormal surface encounter between the epidermis and remnants of the yolk sac or omphalo-enteric duct; and 4) endoectodermal adhesion in the presomite embryo.

Descending supraspinal pathways in amphibians. I. A dextran amine tracing study of their cells of origin.

The present study is the first of a series on descending supraspinal pathways in amphibians in which hodologic and developmental aspects are studied. Representative species of anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), urodeles (the Iberian ribbed newt, Pleurodeles waltl), and gymnophionans (the Mexican caecilian, Dermophis mexicanus) have been used. By means of retrograde tracing with dextran amines, previous data in anurans were largely confirmed and extended, but the studies in P. waltl and D. mexicanus present the first detailed data on descending pathways to the spinal cord in urodeles and gymnophionans. In all three orders, extensive brainstem-spinal pathways were present with only minor representation of spinal projections originating in forebrain regions. In the rhombencephalon, spinal projections arise from the reticular formation, several parts of the octavolateral area, the locus coeruleus, the laterodorsal tegmental nucleus, the raphe nucleus, sensory nuclei (trigeminal sensory nuclei and the dorsal column nucleus), and the nucleus of the solitary tract. In all species studied, the cerebellar nucleus and scattered cerebellar cells innervate the spinal cord, predominantly contralaterally. Mesencephalic projections include modest tectospinal projections, torospinal projections, and extensive tegmentospinal projections. The tegmentospinal projections include projections from the nucleus of Edinger-Westphal, the red nucleus, and from anterodorsal, anteroventral, and posteroventral tegmental nuclei. In the forebrain, diencephalospinal projections originate in the ventral thalamus, posterior tubercle, the pretectal region, and the interstitial nucleus of the fasciculus longitudinalis medialis. The most rostrally located cells of origin of descending spinal pathways were found in the suprachiasmatic nucleus, the preoptic area and a subpallial region in the caudal telencephalic hemisphere, probably belonging to the amygdaloid complex. Our data are discussed in an evolutionary perspective.

Descending supraspinal pathways in amphibians. II. Distribution and origin of the catecholaminergic innervation of the spinal cord.

Immunohistochemical studies with antibodies against tyrosine hydroxylase, dopamine, and noradrenaline have revealed that the spinal cord of anuran, urodele, and gymnophionan (apodan) amphibians is abundantly innervated by catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur in all three orders of amphibians CA, it is unclear to what extent the CA innervation of the spinal cord is of supraspinal origin. In a previous study, we showed that many cell groups throughout the forebrain and brainstem project to the spinal cord of two anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), a urodele (the Iberian ribbed newt, Pleurodeles waltl), and a gymnophionan (the Mexican caecilian, Dermophis mexicanus). To determine the exact site of origin of the supraspinal CA innervation of the amphibian spinal cord, retrograde tracing techniques were combined with immunohistochemistry for tyrosine hydroxylase in the same sections. The double-labeling experiments demonstrated that four brain centers provide CA innervation to the amphibian spinal cord: 1.) the ventrolateral component of the posterior tubercle in the mammillary region, 2.) the periventricular nucleus of the zona incerta in the ventral thalamus, 3.) the locus coeruleus, and 4.) the nucleus of the solitary tract. This pattern holds for all three orders of amphibians, except for the CA projection from the nucleus of the solitary tract in gymnophionans. There are differences in the strength of the projections (based on the number of double-labeled cells), but in general, spinal functions in amphibians are controlled by CA innervation from brain centers that can easily be compared with their counterparts in amniotes. The organization of the CA input to the spinal cord of amphibians is largely similar to that described for mammals. Nevertheless, by using a segmental approach of the CNS, a remarkable difference was observed with respect to the diencephalic CA projections.

The mitochondrial toxin 3-nitropropionic acid induces differential expression patterns of apoptosis-related markers in rat striatum.

The mitochondrial toxin 3-nitropropionic acid (3-NP) causes selective striatal lesions in rats and serves as an experimental model for the neurodegenerative disorder Huntington's disease (HD). Apoptotic cell death has been implicated for the neuronal degeneration that occurs in HD brains. The present study was designed to investigate whether the 3-NP-induced cell death in rats involves apoptosis and an altered expression of Bcl-2 family proteins. Systemic administration of 3-NP via subcutaneous Alzet pumps resulted in lesions of variable severity with neuronal loss and gliosis in the striatum. Using the terminal transferase-mediated biotinylated-UTP nick end-labelling (TUNEL) of DNA, TUNEL-positive cells exhibiting typical apoptotic morphology were detected only in the striatum of rats with a severe lesion. Furthermore, the neuronal expression of the pro-apoptotic protein Bax was strongly increased in the core of the severe lesion. Expression of the anti-apoptotic marker Bcl-2 was unchanged in this location, but was enhanced in the margins of the lesions. A moderately increased expression of both Bax and Bcl-2 was observed in dark neurones in the mild lesion and in the subtle lesion. The presence of nuclear DNA fragmentation, strong granular Bax expression and an increased Bax/Bcl-2 ratio in the centre of severe lesions suggests the occurrence of apoptotic cell death following 3-NP administration. In contrast, the dark compromised neurones observed in 3-NP-treated animals revealed an equally enhanced expression of both Bax and Bcl-2, but lacked TUNEL-labelling, and are therefore not apoptotic.

[Development and developmental disorders of the human brain. III. Neuronal migration disorders of the cerebrum]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. III. Neuronale migratiestoornissen van de grote hersenen.

Neuronal migration disorders of the cerebral cortex form a heterogeneous group of abnormalities, characterised by mental retardation, epilepsy and hypotonia. They are prevalent in 1% of the population and in 20-40% of the untreatable forms of epilepsy. Disorders at the start of the migration result in nodular heterotopias. Bilateral periventricular nodular heterotopias are X-linked disorders, in which cortical neurons are unable to leave their position at the ventricular surface due to the absence of filamin 1. The large group of lissencephalies can be divided into a number of syndromes, each of which is characterised by a gene mutation (LIS1, DCX, RELN). These mutations result in agyria and pachygyria, which are characteristic for this group. A number of these abnormalities, especially the smaller nodular heterotopias and focal cortical dysplasia, may be treated by neurosurgical excision.

[Development and developmental disorders of the human brain. II. Development of the cerebral cortex and major tract systems]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. II. Ontwikkeling van de hersenschors en de grote baansystemen.

In the development of the cerebral cortex, two phases can be distinguished: (a) the formation of the preplate, a superficial layer essential for a normal lamination of the cerebral cortex; (b) the formation of the cortical plate. The cortical plate divides the preplate into a superficial marginal zone (the future layer I) and the subplate. The transient subplate is important for the formation of thalamocortical projections. Most cortical neurons arise in the ventricular zone of the pallium and migrate along radial glial cells (radial migration) to the cortical plate. The gamma-aminobutyric acid (GABA)ergic cortical interneurons, however, originate from the ganglionic eminences and reach the cerebral cortex through tangential migration.

[Development and the developmental disorders of human brain. I. Early development of the cerebrum]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. I. Vroege ontwikkeling van de grote hersenen.

The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early development of mostly the spinal cord and the brain stem. Regionalization of the brain has been related to genes that play a part in it. A characteristic developmental disorder for this early phase in the development of the forebrain is holoprosencephaly, a brain patterning disorder. Numerous genes play a part in its occurrence; abnormal function of signal factors as well as of transcription factors may lead to holoprosencephaly.

A case of Joubert's syndrome with extensive cerebral malformations.

Joubert's syndrome is a relatively rare, autosomal-recessive syndrome defined by vermis hypoplasia, hypotonia, developmental delay and at least one of two additional manifestations: abnormal breathing pattern or abnormal eye movements. Detailed descriptions of the neuropathological findings in this syndrome are scarce. We present a radiological and pathological correlation of a case of Joubert's syndrome in which, apart from the classic vermis aplasia and some malformations of the brain stem and the spinal cord, extensive malformations of the cerebrum were found. The dentate nuclei were broken into islands and showed a few heterotopias within the superior cerebellar pedunculi, the inferior olives were plump and dysplastic, and an almost complete absence of the pyramidal decussation was found. In the spinal cord, the dorsal columns were located in a dorsal position within the spinal grey matter. In the cerebrum, absence of the corpus callosum was found. Many nodular heterotopias of the cerebral cortex and of the basal ganglia, the amygdala and the diencephalon were observed. The present case is compared to previous pathological descriptions of the Joubert syndrome and to other syndromes with comparable malformations of the posterior fossa.

The effect of electrolytic thalamic lesions on the NADPH-diaphorase activity of neurons of the laterodorsal tegmental and pedunculopontine nuclei in rats.

Cholinergic neurons of the mesopontine complex have extensive ascending projections to the forebrain: the laterodorsal tegmental nucleus extensively innervates the anterior thalamus, the anteroventral nucleus in particular, whereas the pedunculopontine nucleus has widespread projections to both the thalamus and extrapyramidal structures. Most of their neurons express nitric oxide synthase (NOS) activity. Following electrolytic lesions of the anteroventral thalamic nucleus, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) activity in neurons of the laterodorsal tegmental nucleus changed drastically. The intensity of NADPH-diaphorase staining increased in laterodorsal tegmental neurons ipsilateral to the lesion side, but decreased contralaterally. The intensity of the NADPH-diaphorase staining of neurons of the pedunculopontine nucleus, however, remained unchanged bilaterally. After partial lesions of the anteroventral thalamic nucleus a similar effect was noted. In contrast, large electrolytic lesions involving other thalamic nuclei or extrapyramidal structures did not change the number of NADPH-diaphorase neurons or their intensity of staining in the laterodorsal tegmental nuclei. These data show that electrolytic lesions of target areas can lead to an upregulation of NOS expression in the parent cell bodies, provided that there is no wide collateralization as found for the pedunculopontine nucleus.

Development and regenerative capacity of descending supraspinal pathways in tetrapods: a comparative approach.

Throughout tetrapods a basic pattern in the organization of descending supraspinal pathways is present. The most notable difference between nonmammalian tetrapods and mammals is the apparent absence of somatomotor cortical areas giving rise to long descending projections to the spinal cord. The phylogenetic constancy of descending supraspinal pathways, at least of those arising in the brain stem, probably implies a comparable pattern of development, presumably a developmental sequence in the formation of these central motor pathways. For studies on the development of motor systems, anurans such as the clawed toad, Xenopus laevis, chicken embryos, and opossums are very attractive animals. Moreover, in these species as well as in rodents in vitro approaches can be used. In the present survey, current knowledge on the neurogenesis, axonal outgrowth, synaptogenesis, and developmental plasticity of the central motor pathways in tetrapods including the sparse data available for man, is discussed. These data are placed in the perspective of the development of the spinal cord and, where possible, correlated with functional data. Emphasis is on the clawed toad, X. laevis, chicken embryos, and opossum and rodent data. The outgrowth of axons of descending supraspinal pathways can be regarded as the result of a series of distinct processes, which may be expressed in a coordinated program: (1) the outgrowth of axons and selection of pathways to their appropriate destination; (2) dendritic outgrowth and formation of specific dendritic morphology; (3) selection of specific targets and collateralization by axons; (4) elimination of incorrect and redundant synapses, axonal and dendritic branches, and of mismatched neurons; and (5) functional refinement of synaptic connections. Tracer and transmitter immunohistochemistry in Xenopus laevis showed that from the moment cell division stops, an axon is formed followed by dendrites which emerge from the cell body. At the beginning of the cell differentiation phase the production of the cell-specific neuroactive substances takes place. Initial outgrowth is in a specific direction for each class of neuron. It is likely that all descending supraspinal pathways arise in a similar way. In the spinal projections of each of the descending supraspinal pathways three stages can be distinguished: (1) an initial stage of outgrowth to the spinal cord, (2) a short "waiting" period after which collaterals enter the spinal gray matter, and (3) myelination of axons. An "overshoot" of spinal projections is particularly evident for the mammalian corticospinal tract. The pattern of early descending axonal tracts appears to be similar in all vertebrate groups. Early axons lay down an axonal scaffold containing guidance cues that are available to later generated growth cones. Throughout vertebrates including man, the fasciculus longitudinalis medialis (flm) is the first descending pathway to be formed. Interstitiospinal fibers "pioneer" this tract, and are joined by reticulospinal fibers. Vestibulospinal fibers (the medial vestibulospinal tract) follow much later. The lateral vestibulospinal tract takes a separate course through the brain stem. Late-arriving fiber tracts such as the rubrospinal and corticospinal tracts probably have their own mechanism of selecting the appropriate pathway. The formation of the descending supraspinal pathways occurs according to a developmental sequence. In all tetrapods studied, reticulospinal and interstitiospinal fibers reach the spinal cord first, followed by vestibulospinal fibers and, much later, by rubrospinal and, if present, corticospinal projections. A special case is presented by anurans which in fact have two motor systems, a primary, transient motor system and a secondary, definitive motor system. Reticulospinal, interstitiospinal and vestibulospinal fibers innervate the spinal cord very early in development, well before the development of the hindlimbs. Rubrospinal fibers in

Major events in the development of the forebrain.

The development of the central nervous system can be divided into a number of phases, each of which is characterized by particular developmental disorders. In recent years, much progress has been made in elucidating the mechanisms by which the forebrain develops and in our understanding of major developmental disorders such as holoprosencephaly and neuronal migration disorders. In this general introduction to this symposium the major stages in the development of the forebrain, its regionalization and the genes involved, and some of the developmental disorders derailing cortical development with subsequent damage to the main cortical fiber connections (pyramidal tract and corpus callosum) are discussed.

The cochlear nuclei in two patients with Usher syndrome type I.

HYPOTHESIS: Does long-term sound deprivation lead to degeneration of the cochlear nuclei in two Usher type I patients? METHODS: The cochlear nuclei of these patients were morphometrically analyzed and compared with two age-matched controls. Routine autopsy of the brainstems was performed before the design of this study was known. During this procedure, the ventral cochlear nucleus (VCN) can easily be damaged. Five partially damaged VCN could nevertheless be analyzed for this study, including the right VCN of Usher patient 1 and both VCN of Usher patient 2. Using 15 microm thick serial paraffine sections of the cochlear nuclei, estimates of volume, neuronal densities, number of cells and mean cell diameter of the dorsal cochlear nucleus (DCN) and VCN were obtained. RESULTS: This study presents unique material of the cochlear nuclei in two patients with Usher syndrome type I. Data regarding volume and total cell number of the VCN are influenced by the absence of a part of the VCN. Results suggest a decrease in mean cell diameter of the VCN in Usher patients. Other parameters of the VCN and DCN, however, showed no major differences between Usher type I patients and controls. CONCLUSION: Only minor degenerative changes are apparent in the cochlear nuclei of two patients with Usher type I, who were deprived of acoustic stimuli since birth.

Severe, non X-linked congenital microcephaly with absence of the pyramidal tracts in two siblings.

In two siblings (a female and a male neonate), severe microcephaly, bilateral absence of the pyramids, severe hypoplasia of the cerebral peduncles, and dysplasia of the inferior olives was found together with microphthalmia, facial malformations and multiple contractures of the extremities. In both cases, the cerebral hemispheres otherwise showed a more or less normal gyral pattern with the insula incompletely covered by the opercula, and a tom but otherwise intact corpus callosum. In case 2, congenital cataract was also observed. The present cases can be characterized as a rapidly fatal, familial syndrome, probably transmitted as an autosomal recessive trait, and have several features in common with the Neu-Laxova syndrome. They differ in having a less severe form of microcephaly, a rather normal cytoarchitecture of the cerebral cortex, an apparently normal corpus callosum, no gross cerebellar abnormalities, and no other organ malformations. The present cases belong to a group of heterogeneous syndromes which have microcephaly, ocular and facial malformations, multiple contractures, and ichthyosis-like skin in common.

Some introductory notes on the organization of the forebrain in tetrapods.

As an introduction to the main theme of this conference an overview of the organization of the tetrapod forebrain is presented with emphasis on the telencephalic representation of sensory and motor functions. In all classes of tetrapods, olfactory, visual, octavolateral, somatosensory and gustatory information reaches the telencephalon. Major differences exist in the telencephalic targets of sensory information between amphibians and amniotes. In amphibians, three targets are found: the lateral pallium for olfactory input, the medial pallium for visual and multisensory input, and the lateral subpallium for visual, octavolateral and somatosensory information. The forebrains of reptiles and mammals are similar in that the dorsal surface of their cerebral hemisphere is formed by a pallium with three major segments: (a) an olfactory, lateral cortex; (b) a 'limbic' cortex that forms the dorsomedial wall of the hemisphere, and (c) an intermediate cortex that is composed entirely of isocortex in mammals, but in reptiles (and birds) consists of at least part of the dorsal cortex (in birds the Wulst) and a large intraventricular protrusion, i.e. the dorsal ventricular ridge. In birds, the entire lateral wall of the hemisphere is involved in this expansion. The intermediate pallial segment receives sensory projections from the thalamus and contains modality-specific sensory areas in reptiles, birds and mammals. The most important differences between the intermediate pallial segment of amniotes concern motor systems.