Regional differences in the stratified transitional field and the honeycomb matrix of the developing human cerebral cortex

The neurons of the cerebral cortex originate in the proliferative neuroepithelium and settle in the cortical plate during embryonic development. Interposed between these two sites is a large transitional field. We have earlier demonstrated experimentally in rats with ³H-thymidine autoradiography that this transitional field is a stratified structure composed of discrete layers of migrating and sojourning cells, and fiber bands. Here we show that the different layers of the stratified transitional field are identifiable without experimental procedures in the developing human cerebral cortex and that there are conspicuous regional differences in its stratification. At the peak of its development, the stratified transitional field contains three fibrous bands in an inside-out order: the commissural fibers of the corpus callosum, the thalamocortical and corticofugal projection fibers, and the expanding white matter. There are regional differences in the thickness of these fibrous layers as well as in the number and configuration of the perikaryal layers. This preview focuses on laminar differences of the transitional fields of the agranular frontal lobe and the granular parietal and occipital lobes. At the latter sites, but not in the frontal lobe, there is a distinctive multi-layered band, the honeycomb matrix, where radially oriented fiber columns are sandwiched between two perikaryal sublayers and are separated from one another by radially oriented cells. We postulate that the radial fiber columns of the honeycomb matrix are composed of topographically organized thalamocortical fibers and that the unspecified young neurons acquire their enduring topographic identity by making selective contacts with tagged fibers here before they resume their radial or tangential migration to the cortical plate.     

Neurono-glial ratios in the frontal cortex of the human cerebrum in normal and pathologic aging (Alzheimer's disease)

Structural organization of the frontal area cortex (fields 8 and 47) in the left and right cerebral hemispheres has been studied cytoarchitectonically in mentally sound and sick persons of various age groups (34-40, 50-60 and 80-90 years). In sections 20 mcm thick, stained with cresyl-violet, in 0.001 mm3 of the cerebral substance (layers III and V) arrangement density is estimated for all pyramidal neurons, for all gliocytes, neurons surrounded with satellite glia and separately for perineuronal gliocytes, as well as per cent ratio of all the parameters obtained. In the process of normal and pathological ageing certain changes, both common for these two processes and specific for each of them, take place in the structural organization of the fields 8 and 47. Under normal ageing the changes are more distinct in the field 8, in the layer III, and at Alzheimer's disease there is a slight prevalence of them in the associative field 47, in the layer V.     

Microstructural Damage of the Posterior Corpus Callosum Contributes to the Clinical Severity of Neglect

One theory to account for neglect symptoms in patients with right focal damage invokes a release of inhibition of the right parietal cortex over the left parieto-frontal circuits, by disconnection mechanism. This theory is supported by transcranial magnetic stimulation studies showing the existence of asymmetric inhibitory interactions between the left and right posterior parietal cortex, with a right hemispheric advantage. These inhibitory mechanisms are mediated by direct transcallosal projections located in the posterior portions of the corpus callosum. The current study, using diffusion imaging and tract-based spatial statistics (TBSS), aims at assessing, in a data-driven fashion, the contribution of structural disconnection between hemispheres in determining the presence and severity of neglect. Eleven patients with right acute stroke and 11 healthy matched controls underwent MRI at 3T, including diffusion imaging, and T1-weighted volumes. TBSS was modified to account for the presence of the lesion and used to assess the presence and extension of changes in diffusion indices of microscopic white matter integrity in the left hemisphere of patients compared to controls, and to investigate, by correlation analysis, whether this damage might account for the presence and severity of patients'' neglect, as assessed by the Behavioural Inattention Test (BIT). None of the patients had any macroscopic abnormality in the left hemisphere; however, 3 cases were discarded due to image artefacts in the MRI data. Conversely, TBSS analysis revealed widespread changes in diffusion indices in most of their left hemisphere tracts, with a predominant involvement of the corpus callosum and its projections on the parietal white matter. A region of association between patients'' scores at BIT and brain FA values was found in the posterior part of the corpus callosum. This study strongly supports the hypothesis of a major role of structural disconnection between the right and left parietal cortex in determining ‘neglect’.     

Organization of Regional Interactions of the Brain Cortical Activity during the Common-root Word Derivation Task

This study analyzed specificities in the activity of the neurophysiological mechanisms underlying the organization of active word-derivation processes. The regularities in the reorganization of the spatial structure for the systemic interaction of bioelectrical activity between different cortical areas of the cerebral hemispheres were studied in adult subjects during the test for mental derivation of common root words (i.е., using the modern methods of the so-called “functional connectome” investigations). Сross-correlation and coherent analysis of EEG has shown that the ipsilateral statistical EEG interactions in the left hemisphere, including Broca’s and Wernicke’s areas, were significantly increased in adults during mental derivation of common root words and, simultaneously, the interhemispheric connectivity and the EEG interactions in the right hemisphere were reduced. Comparison of our results with the previous data of verbal activity associated with speech perception and production has revealed significant differences in the degree of involvement of the left and right hemisphere cortical activity in verbal processing. For example, unlike the data of current study, an equal involvement of both hemispheres cortical activity was recorded during the phoneme recognition in auditory perceived words, grammatical and semantic errors in sentences, as well as during mental formation of words from a set of phonemes and sentences from a set of words, which was particularly manifested in the increased of hemispheric interactions, predominantly, in the inferior frontal and temporal areas and the overlapped areas of the temporal, parietal, and occipital cortical zones (TPO) of both hemispheres. Thus, the data obtained in this study indicate the presence of expressed specificities in the lateralization of activity in the neurophysiological mechanisms underlying the processes of active word derivation and inflexion.     

The Lateralizer: a tool for students to explore the divided brain

Despite a profusion of popular misinformation about the left brain and right brain, there are functional differences between the left and right cerebral hemispheres in humans. Evidence from split-brain patients, individuals with unilateral brain damage, and neuroimaging studies suggest that each hemisphere may be specialized for certain cognitive processes. One way to easily explore these hemispheric asymmetries is with the divided visual field technique, where visual stimuli are presented on either the left or right side of the visual field and task performance is compared between these two conditions; any behavioral differences between the left and right visual fields may be interpreted as evidence for functional asymmetries between the left and right cerebral hemispheres. We developed a simple software package that implements the divided visual field technique, called the Lateralizer, and introduced this experimental approach as a problem-based learning module in a lower-division research methods course. Second-year undergraduate students used the Lateralizer to experimentally challenge and explore theories of the differences between the left and right cerebral hemispheres. Measured learning outcomes after active exploration with the Lateralizer, including new knowledge of brain anatomy and connectivity, were on par with those observed in an upper-division lecture course. Moreover, the project added to the students' research skill sets and seemed to foster an appreciation of the link between brain anatomy and function.     

带状疱疹后遗神经痛患者脑基础活动改变的功能核磁共振研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是临床上一种慢性顽固性神经病理性疼痛,然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨带状疱疹后遗神经痛患者的相关脑区活动,利用功能核磁共振成像低频振幅振荡(ALFF)技术观察带状疱疹后遗神经痛患者的基础脑区活动.8名带状疱疹后遗神经痛患者与8名性别、年龄相匹配的健康者行静息态功能磁共振(f MRI)成像扫描,用SPM8中的多重回归分析,在控制被试年龄、性别、教育年限的影响下,将每个体素的ALFF值同每个被试的病程、视觉模拟评分(visual analog scale,VAS)进行相关分析.与健康志愿者相比,PHN组与VAS评分相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA11/46/47)、右侧顶叶(BA40)、右侧舌回(BA17/18/19);与VAS评分相关的ALFF值降低的脑区有:右侧颞中回(BA21)、左侧舌回(BA17/18)、右侧小脑前叶、左侧后扣带回(BA30/19)和右侧中央前回(BA3/4/6);PHN组与病程相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA9/10/11/47)、左侧颞上回(BA38)、右侧顶叶和右侧舌回(BA17/18/19);与病程相关ALFF值降低的脑区有:左侧海马旁回(BA28)、右侧小脑前叶、左侧扣带回(BA24)、右侧颞上回(BA13)、左侧中央前回和右侧顶下小叶(BA39/40).研究结果提示,涉及疼痛的情绪、警觉行为、注意的脑区在带状疱疹后遗痛慢性疼痛的产生和维持中发挥重要作用.     

Characteristics of the structural organization of the phylogenetically new fields in the human neocortex

The myeloarchitectonics of the specific human fields 40, 39, 37c, 37b of neocortex and also fields 17 and 19 which are the cortex end of visual analyzer has been studied with the help of neurohistological and quantitative methods. According to the character of the fibrous bundles, their diameter, the quantity of the fibrous in them and the diameter of the fibrous gradual changes from field 17 to field 19 and further to field 39 have been shown. It is an evidence of the succession between phylogenetically older and younger fields of the cortex. The peculiarities of the field quantitative myeloarchitectonics differing in the function and genesis are marked by heterochronous growth of these fields square in the process of evolution.     

Relationship of squamosal suture to asterion on external skull surfaces versus endocasts of pongids: Implications for Hadar early hominid AL 162-28

The relationship between the squamosal suture and asterion was quantified in 15 hemispheres of eight chimpanzee endocasts that were aligned in the conventional lateral view (i.e., with frontal pole [FP]–occipital pole [OP] horizontal). Using a three-dimensional digitizer, x, y, and z coordinates were collected for the highest and lowest points of the squamosal suture, and the most rostral point of the suture approximate to the coronal suture. Our results were compared to a similar study of the squamosal suture on the external surfaces of chimpanzee skulls that were oriented in the Frankfurt horizontal (Holloway and Shapiro, 1992). The relationship between the squamosal suture and asterion differs markedly between the outsides of skulls and endocasts. Whereas the squamosal suture is very rarely below asterion on the external skull, we found that most of the squamosal suture is located inferior to asterion on endocasts. We also found that the squamosal suture courses approximately 2.0 mm lower on the right side than the left. (An asymmetry of the same magnitude was reported for the external skull but, curiously, in the opposite direction.) It may be that a lowered right squamosal endosuture on chimpanzee endocasts is associated with earlier closure on that side. The discrepancy in results for the external skull versus endocast is partially attributable to orienting chimpanzee skulls in the Frankfurt horizontal, which usually results in the endocasts being tilted so that FP is above OP, i.e., FP-OP is not parallel with the Frankfurt horizontal. Falk's (1985) orientation of the early hominid endocast from Hadar (AL 162-28) is consistent with data determined from endocasts of chimpanzees. © 1994 Wiley-Liss, Inc.     

A cross correlation analysis of the electrical activity of different regions of the cerebral cortex during visual pattern recognition in children]

Characteristics of spatial-temporal organization of brain biopotentials were examined in one to 2.5 year old children during recognition of visual images. Crosscorrelation EEG analysis of frontal, motor, inferior parietal, temporal and occipital cortical zones has shown that recognition of familiar visual objects is accompanied by an increase in spatial synchronization of biopotentials, especially in the inferior parietal zones of both hemispheres and occipital centres of the left hemisphere. There is a considerable increase in the number of highly synchronous synphasic oscillations at the 4--5 per sec frequency with an intensified periodicity of processes. Recognition of unfamiliar objects does not produce a similar effect. Temporal organization of biopotentials of the associative (frontal and inferior parietal) and projection visual areas in the course of recognition of images depends on the existence of a notion of the whole object in the child's memory.     

Electrophysiologic analysis of the process of recognizing target and non-target stimuli in healthy and oligophrenic children

In an automatized experiment, with a computer on line, amplitude-temporal parameters of evoked potentials (EPs) to purposive and non-purposive stimuli (digits), were analyzed in normal and mental retarded children. At unilateral stimuli presentation to the left or right visual half-fields EPs were recorded simultaneously in projection, TPO, parietal and central areas of the left and right hemispheres. It has been shown that in normal children, differential involvement of projection and associative structures in the analysis of sensory information takes place in both hemispheres. The amplitudes of most EP components in the range of 100-400 ms to the purposive stimuli are higher than to the non-purposive ones. Considerable similarity of EPs developing in response to ipsi- and contralateral stimulations of visual fields ("direct" and "transmitted" EP) is observed. In mental retarded children significant changes are revealed in intra- and interhemisphere organization of the process of perception of purposive and non-purposive stimuli. In the right hemisphere structures there are no differential EP reactions to the two types of stimuli. Significant, in comparison with the norm, prolongation of the latencies of most EP components is noted, especially in the structures of the left hemisphere, to the purposive stimuli. In the process of perception, changes are seen of the integration of functions of both hemispheres. The totality of disturbances of systemic brain organization at perceptive activity in mental retarded children may reflect neurophysiological mechanisms of mental deficiency.     

Cerebral Activations Related to Writing and Drawing with Each Hand

BackgroundWriting is a sequential motor action based on sensorimotor integration in visuospatial and linguistic functional domains. To test the hypothesis of lateralized circuitry concerning spatial and language components involved in such action, we employed an fMRI paradigm including writing and drawing with each hand. In this way, writing-related contributions of dorsal and ventral premotor regions in each hemisphere were assessed, together with effects in wider distributed circuitry. Given a right-hemisphere dominance for spatial action, right dorsal premotor cortex dominance was expected in left-hand writing while dominance of the left ventral premotor cortex was expected during right-hand writing.MethodsSixteen healthy right-handed subjects were scanned during audition-guided writing of short sentences and simple figure drawing without visual feedback. Tapping with a pencil served as a basic control task for the two higher-order motor conditions. Activation differences were assessed with Statistical Parametric Mapping (SPM).ResultsWriting and drawing showed parietal-premotor and posterior inferior temporal activations in both hemispheres when compared to tapping. Drawing activations were rather symmetrical for each hand. Activations in left- and right-hand writing were left-hemisphere dominant, while right dorsal premotor activation only occurred in left-hand writing, supporting a spatial motor contribution of particularly the right hemisphere. Writing contrasted to drawing revealed left-sided activations in the dorsal and ventral premotor cortex, Broca’s area, pre-Supplementary Motor Area and posterior middle and inferior temporal gyri, without parietal activation.DiscussionThe audition-driven postero-inferior temporal activations indicated retrieval of virtual visual form characteristics in writing and drawing, with additional activation concerning word form in the left hemisphere. Similar parietal processing in writing and drawing pointed at a common mechanism by which such visually formatted information is used for subsequent sensorimotor integration along a dorsal visuomotor pathway. In this, the left posterior middle temporal gyrus subserves phonological-orthographical conversion, dissociating dorsal parietal-premotor circuitry from perisylvian circuitry including Broca''s area.     

The continuous Wagon wheel illusion and the 'when' pathway of the right parietal lobe: a repetitive transcranial magnetic stimulation study

A continuous periodic motion stimulus can sometimes be perceived moving in the wrong direction. These illusory reversals have been taken as evidence that part of the motion perception system samples its inputs as a series of discrete snapshots -although other explanations of the phenomenon have been proposed, that rely on the spurious activation of low-level motion detectors in early visual areas. We have hypothesized that the right inferior parietal lobe ('when' pathway) plays a critical role in timing perceptual events relative to one another, and thus we examined the role of the right parietal lobe in the generation of this "continuous Wagon Wheel Illusion" (c-WWI). Consistent with our hypothesis, we found that the illusion was effectively weakened following disruption of right, but not left, parietal regions by low frequency repetitive transcranial magnetic stimulation (1 Hz, 10 min). These results were independent of whether the motion stimulus was shown in the left or the right visual field. Thus, the c-WWI appears to depend on higher-order attentional mechanisms that are supported by the 'when' pathway of the right parietal lobe.     

Distribution of afferents from the association nuclei of the thalamus in the projection and association cortex in cats

Patterns of distribution of terminal degeneration in the parietal cortex (field 7) and in the occipital cortex (field 17) were studied after ultrasonic destruction of the pulvinar by the Fink-Heimer and electron microscopy methods. Degenerating fibers and their terminals were observed in the parietal cortex within all the layers; the greatest amount of degeneration was found in the III--V layers. In the occipital cortex the fibers from the pulvinar end predominantly in the IV layer. Degenerating axons end on the dendritic spines and thin dendritic branches both in the parietal and occipital cortex.     

Focusing Narrowly or Broadly Attention When Judging Categorical and Coordinate Spatial Relations: A MEG Study

We measured activity in the dorsal system of the human cortex with magnetoencephalography (MEG) during a matching-to-sample plus cueing paradigm, where participants judged the occurrence of changes in either categorical or coordinate spatial relations (e.g., exchanges of left versus right positions or changes in the relative distances) between images of pairs of animals. The attention window was primed in each trial to be either small or large by using cues that immediately preceded the matching image. In this manner, we could assess the modulatory effects of the scope of attention on the activity of the dorsal system of the human cortex during spatial relations processing. The MEG measurements revealed that large spatial cues yielded greater activations and longer peak latencies in the right inferior parietal lobe for coordinate trials, whereas small cues yielded greater activations and longer peak latencies in the left inferior parietal lobe for categorical trials. The activity in the superior parietal lobe, middle frontal gyrus, and visual cortex, was also modulated by the size of the spatial cues and by the type of spatial relation change. The present results support the theory that the lateralization of each kind of spatial processing hinges on differences in the sizes of regions of space attended to by the two hemispheres. In addition, the present findings are inconsistent with the idea of a right-hemispheric dominance for all kinds of challenging spatial tasks, since response times and accuracy rates showed that the categorical spatial relation task was more difficult than the coordinate task and the cortical activations were overall greater in the left hemisphere than in the right hemisphere.     

The number, size, and type of axons in rat subcortical white matter on left and right sides: A stereological, ultrastructural study

Abundant evidence indicates important functional differences between the two cerebral hemispheres of humans, although the cellular basis of these differences is unknown. A recent hypothesis proposes that these functional differences depend on differences between sides in the “repertoire” of axonal conduction delays for cortico-cortical axons. In morphological terms this corresponds to differences in caliber, or proportion, of myelinated versus unmyelinated axons. Several behavioural studies have indicated that cerebral asymmetry occurs in rodents, in which rigorous morphological analysis is possible. The hypothesis was therefore tested for the first time in adult male Wistar rats, using transmission electron microscopy and stereological methods. Subcortical white matter was compared between left and right sides in three regions (frontal, parietal, and occipital). The average caliber and numerical density of unmyelinated and myelinated axons was compared between sides and between regions. All data were corrected for shrinkage. No significant differences between sides were found in the average caliber of either type of axon in any region. The numerical density of either type of axon also yielded no significant differences between sides in any region. Significant differences were evident between regions in both caliber and numerical density of the two axonal types, and these quantitative data are reported. The proportion of unmyelinated axons in the lateral white matter was also higher than in previous studies of hemispheric white matter that studied the corpus callosum. The present study provides no evidence supporting the hypothesis that functional hemispheric specialization is due to differences in axonal number, caliber or type.     

MRI Markers for Mild Cognitive Impairment: Comparisons between White Matter Integrity and Gray Matter Volume Measurements

The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer''s disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.     

Structural and Diffusion Property Alterations in Unaffected Siblings of Patients with Obsessive-Compulsive Disorder

Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD.     

Substance P-like immunoreactivity in the parietal eye visual system of the lizard Uta stansburiana

Summary We examined the parietal eye visual system of the iguanid lizard Uta stansburiana for the presence of substance P-like immunoreactivity by use of both immunofluorescence and peroxidase-antiperoxidase techniques. In the parietal eye no substance P-containing somata were found; however, its plexiform layer contained small (ca. 1 m diam) immunoreactive fibers. These fibers apparently originate outside the parietal eye. Immunoreactive fibers also were found in the parietal nerve, the dorsal sac, and the leptomeninx of the pineal gland. No labeled somata were observed in any of these regions in either normal or colchicine treated animals. Previously we demonstrated that a system of centrifugal fibers to the parietal eye originates from neurons in the dorsal sac (Engbretson et al. 1981). The apparent absence of substance P-containing neurons in the dorsal sac suggests that the substance P-containing fibers in the parietal eye are not the previously observed centrifugal fibers. The source of the substance P-containing fibers in the parietal eye is unknown. The pars dorsolateralis of the left medial habenular nucleus receives a dense substance P-positive projection. No such projection was seen in the right habenula. Simultaneous visualization of the terminals of ganglion cells of the parietal eye (labeled with orthograde intraaxonally transported horseradish peroxidase) and substance P-like immunofluorescence showed that the locus of habenular immunoreactivity is distinct from the projection field of the parietal eye. Thus the substance P-positive terminals in the habenula do not originate in the parietal eye. Transection of the parietal nerve confirmed this conclusion.     

Cortico-cortical connections in the parietal area of the cerebral cortex

Layer-by-layer arrangement of the commissural and associative fibers has been studied in the cat parietal cortex. The commissural fibers are distributed in all the layers of the parietal cortex in the contralateral hemisphere, except the superficial part of the I layer. These fibers mainly terminate in the III, IV layers of the contralateral parietal cortex, though their termination in other layers is not excluded. The associative fibers of the parietal cortex are distributed in all the layers of the sensomotor area, except the superficial part of the I layer. They mainly terminate in the III, IV, V layers of the primary somatosensory and in the III, V layers of the motor cortex.     

Fronto-striatal correlations in normal and pathologic aging of the human brain

In psychically healthy persons of three age groups (30-40, 50-60, 80-90 years), as well as in those suffering from Alzheimer's disease (50-60 years) right and left hemispheres formations, including into a single functional system (fields 8, 10, 47 and the nucleus caudatus) have been investigated. Using the series of frontal paraffin sections 20 mcm thick, stained after Nissl and Bielschowsky methods, cyto-glioarchitectonics and neuronal composition of the structures mentioned have been studied. In 0.001 mm3 of the brain substance, in cortical layers II and V and in the nucleus caudatus head density of neurons, perineuronal glia, neurons with lipofuscin, size of the neurons have been calculated. Various degree of manifestation of morphological changes is revealed in different stages of the single functional system. These changes are directly proportional to the organizational level of the structures studied and depend on the stage of the process, on accompanying diseases and individual peculiarities of the person. They are more intensive in the frontal fields and weaker in the nucleus caudatus. At Alzheimer's disease they are more distinct in the associative fields 10 and 47, at normal ageing--in the motor structures--in the field 8 and then in the nucleus caudatus. Spreading of the pathological process occurs with a predominant damage of neurons of cholinergic origin.