Biomedical subjects

K Zilles

Publications and source records attributed to K Zilles.

At least 145 records · Page 8Linked to original sources

PubMed1998

Characterization of neuronal migration disorders in neocortical structures: extracellular in vitro recordings.

The majority of patients showing neuronal migration disorders in cortical structures suffer from pharmaco-resistant epilepsy. In order to study the molecular and cellular mechanisms underlying this pronounced hyperexcitability, we used an animal model of focal cortical dysplasia demonstrating structural malformations which resemble the human pathology of microgyria. Neocortical slices prepared from adult rats, which at the day of birth received a cortical freeze lesion, were analysed in vitro with an array of eight extracellular recording electrodes to investigate the pattern and pharmacology of propagating epileptiform activity in microgyric cortex. In cortical slices exhibiting neuronal migration disorders, orthodromic synaptic stimulation elicited late recurrent activity and early epileptiform responses that spread with 0.06 m/s over > or = 3.5 mm across the cortex. Application of a N-methyl-D-aspartate (NMDA) antagonist blocked the late recurrent activity, but not the propagation of the early epileptiform responses. The latter were blocked by an (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, indicating that the spread of this activity was predominantly mediated by activation of AMPA receptors. A very similar response pattern could be observed in neocortical slices obtained from untreated age-matched control rats, when the slice was partially disinhibited by bath-application of 5 microM bicuculline methiodide. Stimulus-evoked epileptiform signals recorded in disinhibited slices propagated with 0.08 m/s across the cortex and showed the same sensitivity to ionotropic glutamate antagonists as in dysplastic cortex. Our results indicate that widespread structural and/or functional modifications of the AMPA receptor and possibly also of the gamma-amino-butyric acid type A receptor contribute to the pronounced hyperexcitability in dysplastic cortex.

Animals↗

PubMed1998

Characterization of neuronal migration disorders in neocortical structures: quantitative receptor autoradiography of ionotropic glutamate, GABA(A) and GABA(B) receptors.

Epileptiform activity was previously described [Luhmann et al. (1998) Eur. J. Neurosci., 10, 3085-3094] in the neocortex of the adult rat following freeze lesioning of the newborn neocortex. After a survival time of 3 months, a small area of dysplastic cortex surrounded by histologically normal (exofocal) neocortex was observed. The dysplastic cortex is characterized by the formation of a small sulcus and a three- to four-layered architecture. Two questions are addressed here: (i) is the hyperexcitability associated with changes in binding to major excitatory and inhibitory transmitter receptors in the dysplastic cortex?; and (ii) do such changes also occur in the exofocal cortex? Alterations in binding to glutamatergic N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and GABA(A) and GABA(B) (gamma-aminobutyric acid) receptors are demonstrated with quantitative in vitro receptor autoradiography by using the ligands [3H]MK-801, [3H]AMPA, [3H]kainate, [3H]muscimol and [3H]baclofen, respectively. In the dysplastic cortex, the binding to NMDA, AMPA and kainate receptors is significantly increased, whereas the binding to GABA(A) and GABA(B) receptors is reduced. Exofocal areas of the lesioned hemisphere show an imbalance between excitatory and inhibitory receptor binding with an up-regulation of the binding to AMPA and kainate, and a down-regulation to GABA(A) receptors. The binding to GABA(B) and NMDA receptors is not significantly changed in the exofocal areas. The imbalance between excitatory and inhibitory receptors may cause the hyperexcitability, as previously found in the identical experimental model, and may also induce epileptiform activity in the human cortex with migration disorders.

Animals↗

PubMed1998

Characterization of neuronal migration disorders in neocortical structures. II. Intracellular in vitro recordings.

Neuronal migration disorders (NMD) are involved in a variety of different developmental disturbances and in therapy-resistant epilepsy. The cellular mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are not well understood and demand further clinical and experimental analyses. We used a focal freeze-lesion model in cerebral cortex of newborn rats to study the functional consequences of NMD. Intracellular recordings from supragranular regular spiking cells in cortical slices from adult sham-operated rats revealed normal passive and active intrinsic membrane properties and normal stimulus-evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively). Regular spiking neurons recorded in rat dysplastic cortex showed on average a significantly smaller action potential amplitude, a slower spike rise, and a less steep primary frequency-current relationship. Stimulus-elicited EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which coincided with extracellular field potentials and lasted 150-800 ms. These epileptiform responses could be recorded at membrane potentials between -50 and -110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV, suggesting that NMDA receptors are activated at relatively negative membrane potentials. In comparison with the controls, polysynaptic IPSPs mediated by the gamma-aminobutyric acid (GABA) type A and B receptor were either absent or reduced in peak conductance in microgyric cortex by 27% (P < 0.05) and 17%, respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic glutamate receptor antagonists revealed a similar efficacy in NMD and control cortex, indicating that GABAergic neurons in microgyric cortex get a weaker excitatory input. Our data indicate that the expression of epileptiform activity in NMD-affected cortex rather results from an imbalance between excitatory and inhibitory synaptic transmission than from alterations in the intrinsic membrane properties. This imbalance is caused by an increase in NMDA-receptor-mediated excitation in pyramidal neurons and a concurrent decrease of glutamatergic input onto inhibitory interneurons.

2-Amino-5-phosphonovalerate↗

PubMed1998

Transient increase of manganese-superoxide dismutase in remote brain areas after focal photothrombotic cortical lesion.

BACKGROUND AND PURPOSE: Free radicals including superoxide are responsible for postlesional cytotoxicity. In contrast to the constitutive CuZn-superoxide dismutases (SODs), manganese-superoxide dismutase (Mn-SOD) is inducible and has the potential to protect neurons by its superoxide dismutating activity. Therefore, we studied the presence and the regional changes in Mn-SOD within the brain after focal cortical ischemia. METHODS: Focal cortical photothrombotic lesions were produced in the hindlimb region of rat brains. Animals were anesthetized and transcardially perfused with Zamboni's fixative. Mn-SOD was immunohistochemically localized using an antiserum against rat-Mn-SOD. Changes in Mn-SOD immunoreactivity were quantified by image analysis. RESULTS: Focal photothrombosis caused a perilesional increase in Mn-SOD after 24 hours, followed by a further significant increase at 48 hours in perilesional cortex, ipsilateral corpus callosum, hippocampus, and thalamus, as well as in a homotopic cortical area within the nonlesioned hemisphere. At day 2, Mn-SOD was present in neurons and astrocytes. Up to day 7, Mn-SOD increased in the entire ipsilateral and contralateral cortex but remained higher elevated in the ipsilateral hippocampus and thalamus. Thereafter, Mn-SOD decreased globally but remained elevated in some cortical neurons up to day 60. CONCLUSIONS: The early transient increase of Mn-SOD in distinct brain regions, which are functionally connected via afferents and efferents, suggests that these regions are affected by the injury. It suggests that Mn-SOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.

Animals↗

PubMed1998

The size of the middle temporal area in primates.

The increase in the size of the lateral geniculate body and the primary visual cortex from prosimians to apes and man reflects at an anatomical level the importance of the visual system in primates. In the prestriate cortex visual modalities are processed separately in specialized pathways and areas. This arrangement facilitates the allometric analysis of cortical areas subserving defined visual modalities. Its heavy myelination makes the middle temporal area, a visual cortical field specialized for the detection of moving stimuli, an easily detectable and reliably delineable area in histological sections. The size and position of the middle temporal area can therefore be compared between species, in order to collect quantitative data about the development of a defined visual submodality during primate evolution. The volume of the middle temporal area was measured in 27 primate species. Allometric comparisons show that the middle temporal area is larger in simians than in most prosimians. In Callitrichidae, both the middle temporal area and the striate cortex are well developed. In cebids and cercopithecids, however, the sizes of the middle temporal area and primary visual cortex show divergent trends. Whereas the striate cortex is still enlarging, the size of the middle temporal area is reduced as compared to callitrichids. Previous studies have revealed a close correlation between area striata and neocortex sizes, as well as area striata and lateral geniculate sizes. Such a close correlation does not exist for the middle temporal area versus neocortex or area striata. Therefore, the size of a visual structure serving a special submodality (e.g., the middle temporal area for the detection of moving stimuli) may develop in a species relatively independently from the lateral geniculate and primary visual cortex sizes.

Animals↗

PubMed1998

The distribution of nitric oxide synthase-I and NADPH-diaphorase containing neurons in the cerebral cortex of different strains of mice and its association with learning and memory.

We investigated the distribution of nitric oxide synthase-I (NOS-I) containing neurons within the neocortex of inbred mice belonging to the Balb/c, NMRI and DBA/2 strains which differ in learning and memory performance. The NOS-I positive neurons were detected immunohistochemically with antibodies against NOS-I and enzyme histochemically using their NADPH-diaphorase (NADPH-d) activity. The qualitative and quantitative evaluation of cortical NADPH-d and NOS-I containing neurons revealed that more than 95% of these cells contained both enzymes. Therefore, we combined the NADPH-d with the WFA-staining to evaluate and parcellate at one section. The specific differences in learning and memory tasks of the three mouse strains have been tested in previous studies. Our investigation test the hypothesis that differences in various aspects of eight-arm radial maze learning are associated with differences in the density of NOS-I positive neurons in cytoarchitectonically and functionally identified cortical areas. We found an increased density of NADPH-d neurons within the whole neocortex in the DBA/2 strain, which reached a lower learning score than the Balb/c and NMRI strains. Significantly higher densities of NADPH-d neurons appeared in the areas of the gustatory cortex, the piriform cortex, the entorhinal cortex and in area 1 of the temporal cortex in DBA/2 mice. A negative correlation exists between the learning scores and the number of NADPH-d positive neurons. If NOS-I activity influences spatial learning as determined in the eight-arm radial maze, the areas with strongly elevated NADPH-d positive neurons may demarcate task-related cortical areas affected in mice with a reduced learning capacity.

Animals↗

PubMed1998

Comparison of iodotyrosines and methionine uptake in a rat glioma model.

UNLABELLED: This study compares brain tumor imaging with 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT) and 3-[123I/125I]iodo-O-methyl-alpha-methyl-L-tyrosine (OMIMT) to that with [methyl-3H]-L-methionine (Met) in a rat glioma model by double-tracer autoradiography. METHODS: Cells of the glioma clone F-98 were implanted stereotactically into the right basal ganglia of 22 Fischer 344 rats. After 8 days of tumor growth, the animals simultaneously were injected with a mixture of either 123I-IMT and 3H-Met (n=5), 123I-OMIMT and 3H-Met (n=8) or 123I-IMT and 125I-OMIMT (n=9). The animals were killed 15 min after the tracer injection and cryosections of the tumor-bearing brain area were exposed to phosphor-imaging plates both immediately and after the decay of 123I. Tumor-to-brain ratios (T/B) and intratumoral distribution of the different tracers and of the cresyl violet staining of the tissue were compared. RESULTS: There was a significant correlation of the T/B ratios between all tracers (IMT versus Met: r=0.97, n=5, p < 0.01; OMIMT versus Met: r=0.94, n=8, p < 0.001; OMIMT versus IMT: r=0.95, n=9, p < 0.001). Intratumoral tracer distribution was similar for all tracers and the extent of tumor labeling was identical to that of the histological tumor extent. Mean values of the T/B ratios, however, were lower for IMT (2.81+/-0.78, n=14, mean+/-s.d., p < 0.01 compared with Met) and for OMIMT (2.03+/-0.57, n=17, p < 0.01 compared with Met) than for Met (3.86+/-1.12, n=13). CONCLUSION: This study confirms that tumor imaging with IMT is similar to that of Met but T/B ratios of IMT are lower. OMIMT intratumoral tracer distribution and tumor size are similar to Met and IMT, but the T/B contrast is rather low and makes this amino acid less suitable for clinical application.

Animals↗

PubMed1998

Three-dimensional linear and nonlinear transformations: an integration of light microscopical and MRI data.

The registration of image volumes derived from different imaging modalities such as MRI, PET, SPECT, and CT has been described in numerous studies in which functional and morphological data are combined on the basis of macrostructural information. However, the exact topography of architectural details is defined by microstructural information derived from histological sections. Therefore, a technique is developed for integrating micro- and macrostructural information based on 1) a three-dimensional reconstruction of the histological volume which accounts for linear and nonlinear histological deformations, and 2) a two-step procedure which transforms these volumes to a reference coordinate system. The two-step procedure uses an extended principal axes transformation (PAT) generalized to affine transformations and a fast, automated full-multigrid method (FMG) for determining high-dimensional three-dimensional nonlinear deformations in order to account for differences in the morphology of individuals. With this technique, it is possible to define upwards of 1,000 times the resolution of approximately 1 mm in MRI, making possible the identification of geometric and texture features of microscopically defined brain structures.

Brain Mapping↗

PubMed1997

Copper-zinc superoxide dismutase and isolectin B4 binding are markers for associative and transhemispheric diaschisis induced by focal ischemia in rat cortex.

Copper/zinc-superoxide dismutase (Cu/Zn-SOD) belongs to a class of enzymes, identified as essential and highly effective endogenous scavengers of cytotoxic oxygen radicals. These radicals contribute to postlesional neurotoxicity. In order to determine the superoxide-scavenging potential of regions affected by unilateral cortical photothrombosis, we studied the changes in the distribution of Cu/Zn-SOD and the appearance of activated microglia by immunohistochemistry and isolectin B4 binding. Four hours postlesion, Cu/Zn-SOD increased significantly within a homotopic area of the contralateral hemisphere and in ipsilateral thalamic nuclei, whereas isolectin B4-positive microglia were upregulated at days 5 and 7 postlesion within the same regions. The contralateral increase in the amount of the superoxide-scavenging Cu/Zn-SOD indicates that this enzyme is induced by a retrograde reaction carried through callosal connections.

Animals↗

PubMed1997

Geniculo-cortical afferents form synaptic contacts with vasoactive intestinal polypeptide (VIP) immunoreactive neurons of the rat visual cortex.

The lateral geniculate nucleus of the rat was injected with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) to see if geniculo-cortical axons terminate on vasoactive intestinal polypeptide immunoreactive (VIP-IR) neurons of the primary visual cortex. PHA-L-labelled boutons attached to VIP-IR perikarya and dendrites were identified as presynaptic parts of asymmetrical synapses. This geniculo-cortical projection to VIP-IR cells in the visual cortex and comparable findings in the somatosensory cortex suggest that sensory input from specific thalamic nuclei may influence local circuit inhibition and the metabolic state within the cortical domain via VIP-IR neurons.

Animals↗

PubMed1997

Co-localization of vasoactive intestinal polypeptide, gamma-aminobutyric acid and choline acetyltransferase in neocortical interneurons of the adult rat.

Interneurons immunoreactive for vasoactive intestinal polypeptide (VIP) are integral elements of columnar organization patterns in the rat cerebral cortex. By application of the sensitive mirror technique, the co-localization of VIP with the classical inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT), was investigated in neocortical neurons. Furthermore, the frequency of co-localization of ChAT with GABA was determined. In a sample of 118 VIP-immunoreactive neurons, mostly from the primary somatosensory cortex, it was demonstrated that virtually all of them reveal immunoreactivity for GABA and, therefore, are to be GABAergic. Moreover, 34% of mostly bipolar, VIP-positive neurons contained ChAT and are, thus, supposedly cholinergic as well. Co-localization of VIP and ChAT varied according to cortical laminae. Finally, 88% of a total of 60 ChAT-immunoreactive neurons were also immunostained for GABA. It is concluded that almost all VIP-immunoreactive neurons and most of the cholinergic neurons in rat neocortex represent partly overlapping subpopulations of inhibitory interneurons utilizing GABA.

Animals↗

PubMed1997

The somatosensory cortex of human: cytoarchitecture and regional distributions of receptor-binding sites.

The aim of this study is to characterize the regional and laminar distribution patterns of various neurotransmitter binding sites in areas 3a, 3b, 1, and 2 of the human primary somatosensory cortex, and to compare these receptor-based "maps" with the cytoarchitectonic parcelation. Cryostat sections from a dorsomedial region of the postcentral gyrus close to the interhemispheric fissure and from a ventrolateral region close to the Sylvian fissure were examined. Neurotransmitter-binding sites were analyzed with quantitative in vitro receptor autoradiography. Different muscarinic-binding sites were labeled with [3H]pirenzepine and [3H]oxotremorine-M, noradrenergic-binding sites with [3H]prazosin, different serotoninergic-binding sites with [3H]5-hydroxytryptamine and [3H]ketanserine, glutamate-binding sites with l-[3H]glutamate, and GABA-binding sites with [3H]muscimol. Adjacent sections were stained with a modified Nissl method for cytoarchitectonic analysis. The binding sites either were preferentially localized in the superficial layers ([3H]5-hydroxytryptamine, [3H]prazosin, l-[3H]glutamate, [3H]muscimol, and [3H]pirenzepine) or were more homogeneously distributed with highest densities in layers III-V ([3H]oxotremorine-M and [3H]ketanserine). Changes in the distribution patterns of [3H]oxotremorine-M- and [3H]ketanserine-binding sites precisely matched the borders between areas 4/3a, 3b/1, and 1/2, as defined cytoarchitectonically. In addition, the autoradiographs showed that area 1 possibly consists of two subregions which cannot be distinguished cytoarchitectonically. The results demonstrate that the regional and laminar distribution patterns of some, but not all, transmitter-binding sites are precisely correlated with the cytoarchitectonic parcelation of the human primary somatosensory cortex. In addition, binding sites may reveal new borders not detectable in Nissl-stained sections. Finally, the human primary somatosensory cortex differs clearly from the primary motor cortex due to higher densities of l-[3H]glutamate-, [3H]muscimol-, [3H]pirenzepine-, [3H]oxotremorine-M-, and [3H]ketanserine-binding sites.

Aged↗

PubMed1997

Postnatal development of interhemispheric asymmetry in the cytoarchitecture of human area 4.

The postnatal development of interhemispheric asymmetry was analyzed in the primary motor cortex (area 4) of 20 human brains with quantitative cytoarchitectonic techniques. The volume fraction of cortical tissue occupied by cell bodies (grey level index) was determined by automated image analysis. In children as well as in adults, the volume fraction of cell bodies averaged over all cortical layers was greater on the right than on the left. Thus, the space between cell bodies, i.e. the volume fraction of neuropil containing axons, dendrites and synapses, was greater in the left than in the right primary motor cortex. At the level of single layers, however, interhemispheric asymmetry of the neuropil volume fraction differed between age groups. The supragranular layers were significantly less asymmetrical in children than in adults, whereas the infragranular layers showed a similar degree of asymmetry in both age groups. Thus, the postnatal development of the architectonic asymmetry in the supra- and infragranular layers of area 4 follows the same sequence of maturation as found during neuronal migration, i.e. an inside-to-outside gradient. Comparing the layer-specific developmental pattern with available functional data, it was found that the structural maturation of interhemispheric asymmetry in the supragranular layers correlates with the development of hand preference.

Adult↗

PubMed1997

Nitric oxide synthase-expressing neurons are area-specifically distributed within the cerebral cortex of the rat.

Neuronal nitric oxide synthase produces nitric oxide, a radical involved in neurotransmission as well as in cytotoxicity during stroke and neurodegenerative diseases. In the adult Wistar rat neuronal nitric oxide synthase-positive neurons are inhomogenously distributed along defined cortical areas, with highest densities (18 cells/mm2) in cingular area 1, piriform cortex, frontal motor area Fr 2 and in the medial visual association area Oc 2MM. A medium packing density of neuronal nitric oxide synthase neurons (10/mm2) characterizes primary sensory areas, whereas retrosplenial cortices contain lowest cell numbers (3-5/mm2). The data suggest that functions of certain cortical areas are more dependent on intracortically produced nitric oxide than others, and that cortical injury may cause more severe nitric oxide related cytotoxicity in areas with higher numbers of neuronal nitric oxide synthase-positive neurons.

Animals↗

PubMed1997

Neurobiological bases of behavioral development in the first year.

This review summarizes the temporal relations between selected psychological milestones in the first year of the human infant and theoretically relevant developmental neurobiological changes in the brain, supplemented where appropriate, with evidence from the non-human primate. The disappearance of the palmar grasp reflex and the decrease in endogenous smiling and spontaneous crying, which occur at 2-3 months, are correlated to emergent cortical inhibition of brainstem circuits. In addition, the improved ability to recognize an event experienced in the immediate past (recognition memory) is related to growth of the hippocampus and adjacent structures at this age. The behavioral developments at 7-10 months include an enhanced ability to retrieve stored representations of the past and to compare past and present (working memory), along with the emergence of the universal fears of strangers and separation from the caretaker. These milestones are correlated in time with maturational changes in the prefrontal and rhinal cortices and hippocampal formation, the integration of the limbic system and increased responsiveness of the hypothalamus-pituitary-adrenal axis. Knowledge of age-dependent correlations of brain and behavioral maturation is a basis for the investigation of causal relationships between brain development and behavior. A close collaboration of pediatricians, psychologists and neuroscientists is, therefore, necessary.

Age Factors↗

PubMed1997

Limitations of the principal-axes theory.

The classical principal-axes transformation (PAT) has been used in numerous publications for three-dimensional (3-D) reconstructions by sequential alignment of histological sections. However, the PAT can determine at most 1/2n(n + 1) parameters (scaling-rotation) in n dimensions. Distortions (shearing) of histological sections can be described by an affine transformation with n2 parameters. An analytical model is devised for calculating rotational and scaling errors which can be determined by relating the transformation parameters of the PAT to the exact solution of a singular value decomposition (SVD) of the perturbation matrix. The results show that form and deformation of the form are intertwined and that these results can be transferred to real data. The model is important for assessing the quality that can be expected with the PAT for 3-D reconstructions if no multimodality reference is available (rigid transformation) and reveals the misalignment in terms of rotational and scaling errors resulting from the PAT as derived in a previously published paper.

Diagnostic Imaging↗

PubMed1997

Interneurons immunoreactive for vasoactive intestinal polypeptide (VIP) are extensively innervated by parvalbumin-containing boutons in rat primary somatosensory cortex.

Sensory perception results from the synchronized action of large ensembles of cortical neurons. Receptive field properties of such neurons in sensory areas strongly depend on circuits utilizing the inhibitory amino acid transmitter gamma-aminobutyric acid (GABA). GABAergic neurons often co-localize neuropeptides and/or calcium-binding proteins in a cell-type specific manner. We have taken advantage of this fact to study the synaptic circuitry involving presynaptic parvalbumin-containing boutons (originating from horizontally extensive basket cells) and postsynaptic VIP-immunoreactive GABAergic targets which mostly have a vertically oriented axonal field. Abundant appositions between parvalbumin-immunoreactive boutons and all VIP-stained neurons were observed at the light microscopic level. The numbers of contacts ranged between three and well over 20 for single VIP cells. The higher numbers were especially frequent in the supragranular and granular layers contacting the numerous bipolar, as well as multipolar VIP cells located there; but the VIP-immunoreactive neurons in the infragranular layers were also targeted by parvalbumin-immunoreactive boutons without exception, albeit in more variable, mostly lower numbers. Correlated electron microscopic investigations revealed that virtually all of these light microscopically observed appositions resembled symmetric synaptic specializations. The vast majority were located on the soma or proximal dendrites of the VIP-positive neurons. Since pyramidal cells, in turn, represent a major target for the parvalbumin and VIP synapses, the activation of these synapses may lead to coherent oscillations providing the necessary clock function to synchronize pyramidal cell discharges, both across and within cortical columns.

Animals↗

PubMed1997

Persistence of layer IV in the primary motor cortex (area 4) of children with cerebral palsy.

The normal development of the human primary motor cortex is characterized by a cytoarchitectonic transformation from the fetal, six-layered cortex to the adult, five-layered agranular cortex. The present study examines whether this transformation also occurs in children with cerebral palsy. Nissl-stained, serial sections through the left precentral gyrus of 14 children (age: 3-13 years) with cerebral palsy and from a control group without any clinically manifested disturbances of the motor system were analyzed. The widths of cortical layers, the laminar distributions of area 1 fractions occupied by cell bodies and neuropil, and the numerical densities and mean sizes of cell bodies were measured. In 5 cases of cerebral palsy, an inner granular layer (IV) persisted up to ages between 3 and 9 years. Layer IV was absent in other cases and in the controls. The persistence of layer IV was closely related to severe impairments of posture: all children with persistent layer IV were unable to maintain an upright posture. Cytoarchitectonic differences to controls were also found in other layers. Layer V, the major source of the pyramidal tract, was more narrow in children with cerebral palsy. The ratio between average cell body size for layers III and V was changed in the group of cerebral palsy. Thus, severe impairment of posture can be associated with disturbed cytoarchitectonic development of the motor cortex.

Adolescent↗