Plasticity in cerebellar tactile maps in the adult rat.

We previously demonstrated that the fractured tactile cerebellar map within the crus IIa folia of the cerebellar hemispheres reorganizes after deafferentation of the upper lip in neonatal rats (postnatal day [PND] 1-30). The present study examined the capacity of this map to reorganize after deafferentation in adults and animals late in development (PND 30-89). Several months after cauterization of the infraorbital branch of the trigeminal nerve, the tactile map in the granule cell layer of crus IIa reorganized, with representations of intact structures expanding into the denervated area. The pattern of reorganization was similar to reorganization after neonatal lesions in that (1) all representations were from perioral structures, (2) the reorganized map maintained a fractured somatotopy, and (3) the denervated area was predominantly and consistently invaded by the upper incisor representation. We conclude that the spatial pattern of reorganization is essentially the same regardless of the age of deafferentation. However, we also observed developmental differences in reorganization. First, more areas of crus IIa were nonresponsive in animals lesioned later in development (PND 30-89). Second, we found a surprising degree of variability in the pattern of tactilely evoked cerebellar field potentials of PND 30-40 animals compared with neonates and adults, suggesting that this time period differs from other stages. The pattern of evoked potentials reflects the two primary inputs to the map. Our data show that, although both afferent pathways are capable of reorganization throughout development, their relative contribution to the map appears to differ, depending on the age at which lesion occurs.     

Silent cortical neuronal damage in atherosclerotic disease of the major cerebral arteries

In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, hemodynamic compromise may cause selective neuronal damage manifested as loss of central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex, without overt episode of stroke. To investigate the association of decreases in cortical BZRs with hemodynamic compromise and the effect of angiotensin receptor blockers (ARBs) on these receptors in patients whose atherosclerotic ICA or MCA disease is asymptomatic, we measured BZRs using positron emission tomography and ¹¹C-flumazenil in 79 patients with asymptomatic atherosclerotic ICA or MCA disease and no cortical infarction. Three-dimensional stereotactic surface projections were used to calculate the BZR index, a measure of abnormally decreased BZRs in the cerebral cortex within the MCA distribution. Multiple regression analysis showed this index to be positively correlated with the value of oxygen extraction fraction, with the presence of silent subcortical infarcts, and with the presence of ischemic heart disease, whereas it was negatively correlated with the treatment of hypertension with ARBs. In asymptomatic atherosclerotic ICA or MCA disease, hemodynamic compromise is associated with selective neuronal damage manifested as decreases in cortical BZRs in the noninfarcted cerebral cortex, whereas ARBs are associated with preservation of cortical BZRs.     

The organization of the neuronal activity of the cortical cingulate gyrus in the waking-sleep cycle

Dynamics of the neuronal activity of the cingulate gyrus (CG) in the sleep-wakefulness cycle (SWC) was studied in free-moving cats. Most of neurons (65.4) discharged with high frequency during active wakefulness (AW) and emotional stage of paradoxical sleep (PS); the frequency of discharges decreased during the passive wakefulness (PW) and slow-wave sleep (SWS). 15% of neurons showed opposite dynamics of the activity. They fired more intensively during the SWS. 19.6% of neurons showed no statistically significant difference in the discharge frequency of different phases of the SWC. Most of neurons (75.2%) regularly changed the pattern of discharges at a chang of the phases of the SWC. In particular, those neurons discharged by single spikes, more or less uniformly distributed in time, against the background of AW and PS. With the development of the SWS neurons began to discharge according to the cluster-pause principle. During the development of the short fragments of the EEG arousal, most of neurons either decrease (42.6%) or did not change (50.4%) the activity. The involvement of the CG in the regulation of the SWC is discussed.     

Developmental plasticity in cerebellar tactile maps: Fractured maps retain a fractured organization

Plasticity following deafferentation has been repeatedly demonstrated in topographic sensory maps in the mammalian brain. In this paper we investigated the developmental plasticity of the fractured somatotopic map found in the tactile regions of the rat cerebellum. At various stages of postnatal development between postnatal days 1 and 30, we cauterized the infraorbital branch of the trigeminal nerve, which innervates the upper lip, furry buccal pad, and vibrissae that are represented within cerebellar folium crus IIa. The organization of the crus IIa map was then examined 2 to 3 months after denervation. We found that tactile receptive fields had reorganized throughout the denervated area but maintained a fractured somatotopy. Comparison of the reorganization in different animals showed that the denervated upper lip region was consistently and predominantly replaced by representation of the upper incisors. Analysis of evoked field potentials revealed an alteration, in denervated animals, of the response of the granule cell layer to brief tactile stimulation. This response in normal animals consists of two components at different latencies. Animals lesioned later in development were less likely to have the short latency component. This result suggests a difference in the developmental sensitivity of different cerebellum-related pathways to nerve lesions.     

Plasticity of auditory maps in the brain.

The central auditory pathway contains maps of sound frequency that reflect the functional organization of the cochlea, as well as topographic representations of other stimulus features, such as sound location, that are synthesized within the brain. Both types of map undergo changes during development and are shaped by experience. This is particularly true of the representation of auditory space in the superior colliculus, which can be modified by alteration of auditory and visual inputs early in life. Although experience-induced plasticity in this map is restricted primarily to the developmental period, the frequency representation in the cortex of adult animals can re-organize following partial deafness.     

Ischemic cortical neuronal damage and cognitive impairments in atherosclerotic occlusive disease of the major cerebral artery: a PET study

In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, selective neuronal damage can be detected as a decrease in central benzodiazepine receptors (BZRs) in an apparently normal cerebral cortex. To investigate the association between cortical BZRs decreases and executive dysfunctions, we measured BZRs using positron emission tomography (PET) and (11)C-flumazenil in 60 non-disabled patients with unilateral atherosclerotic ICA or MCA disease and no cortical infarction. Using 3-dimensional stereotactic surface projections, we calculated the BZR index, a measure of abnormally decreased BZRs in the cerebral cortex within the anterior cerebral artery (ACA) or MCA territory, and found that it to be correlated with the patient's score on the Wisconsin Card Sorting Test (WCST). Based on the WCST results, 39 patients were considered abnormal (low categories achieved) for their age. The BZR index of the ACA territory in the hemisphere affected by arterial disease was significantly higher in abnormal patients than in normal patients. The BZR index of the MCA territory differed significantly between the 2 groups when patients with left arterial disease (n = 28) were analyzed separately. The BZR indices of the anterior cingulate gyrus and the middle frontal gyrus carrelated significantly and positively with the total number of WCST errors. In atherosclerotic ICA or MCA disease, selective neuronal damage that is manifested as a decrease in BZRs in the non-infarcted cerebral cortex is associated with executive dysfunction. PET imaging of BZRs is useful as an objective measure of cognitive impairments in atherosclerotic occlusive disease of the major cerebral artery.     

Plasticity in the tonotopic organization of the medial geniculate body in adult cats following restricted unilateral cochlear lesions

To investigate subcortical contributions to cortical reorganization, the frequency organization of the ventral nucleus of the medial geniculate body (MGv) in six normal adult cats and in eight cats with restricted unilateral cochlear lesions was investigated using multiunit electrophysiological recording techniques. The tonotopic organization of MGv in the lesioned animals, with severe mid-to-high frequency hearing losses, was investigated 40-186 days following the lesioning procedure. Frequency maps were generated from neural responses to pure tone bursts presented separately to each ear under barbiturate anesthesia. Consideration of the frequency organization in normal animals, and of the apparently normal representation of the ipsilateral (unlesioned) cochlea in lesioned animals, allowed for a detailed specification of the extent of changes observed in MGv. In the lesioned animals it was found that, in the region of MGv in which mid-to-high frequencies are normally represented, there was an "expanded representation" of lesion-edge frequencies. Neuron clusters within these regions of enlarged representation that had "new" characteristic frequencies displayed response properties (latency, bandwidth) very similar to those in normal animals. Thresholds of these neurons were not consistent with the argument that the changes merely reflect the residue of prelesion responses, suggesting a dynamic process of reorganization. The tonotopic reorganization observed in MGv is similar to that seen in the primary auditory cortex and is more extensive than the reorganization found in the auditory midbrain, suggesting that the auditory thalamus plays an important role in cortical plasticity.     

Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex

Light and electron microscopic methods were used to examine the neurons in the monkey cerebral cortex labeled autoradiographically following the uptake and transport of [3H]-gamma-aminobutyric acid (GABA). Nonpyramidal cell somata in the sensory-motor areas and primary visual area (area 17) were labeled close to the injection site and at distances of 1 to 1.5 mm beyond the injection site, indicating labeling by retrograde axoplasmic transport. This labeling occurred preferentially in the vertical dimension of the cortex. Prior injections of colchicine, an inhibitor of axoplasmic transport, abolished all labeling of somata except those within the injection site. In each area, injections of superficial layers (I to III) produced labeling of clusters of cell somata in layer V, and injections of the deep layers (V and VI) produced labeling of clusters of cell somata in layers II and III. In area 17, injections of the superficial layers produced dense retrograde cell labeling in three bands: in layers IVC, VA, and VI. Vertically oriented chains of silver grains linked the injection sites with the resulting labeled cell clusters. In all areas, the labeling of cells in the horizontal dimension, i.e., on each side of an injection, was insignificant. Electron microscopic examination of labeled neurons confirms that the neurons labeled at a distance from an injection site are nonpyramidal neurons, many with somata so small that they would be mistaken for neuroglial cells light microscopically. They receive few axosomatic synapses, most of which have symmetric membrane thickenings. The vertical chains of silver grains overlie neuronal processes identifiable as both dendrites and myelinated axons, but unmyelinated axons may also be included. The clusters of [3H]GABA-labeled cells are joined to one another and to adjacent unlabeled cells by many junctional complexes, including puncta adherentia and multi-lamellar cisternal complexes. We conclude that groups of GABA-transporting neurons are likely to use GABA as a transmitter and form an inhibitory, bidirectional system of connections that join together cells in superficial and deep layers of functional cortical columns; intrinsic, horizontal GABAergic connections are either far less significant in the organization of the cerebral cortex or are not labeled by this method.(ABSTRACT TRUNCATED AT 400 WORDS)     

Decision-making in refractory epilepsy: an analysis based on computer simulation.

A program developed to simulate management of patients with recurrent seizures was tested in 24 subjects, including 13 experienced neurologists. Identifiable errors included excessive reliance on plasma anticonvulsant levels, misinterpretation of random effects, inefficiency in selection of follow-up intervals, and undue reference to arbitrary data, such as the initial dose, in the selection of "optimum" drug dosage.     

Integration of distributed cortical systems by reentry: a computer simulation of interactive functionally segregated visual areas

A computer model based on visual cortex has been constructed to analyze how the operations of multiple, functionally segregated cortical areas can be coordinated and integrated to yield a unified perceptual response. We propose that cortical integration arises through the process of reentry--the ongoing, parallel, recursive signaling between separate maps along ordered anatomical connections. To test the efficacy of this reentrant cortical integration (RCI) model, we have carried out detailed computer simulations of 3 interconnected cortical areas in the striate and extrastriate cortex of the macaque. The simulated networks contained a total of over 222,000 units and 8.5 million connections. The 3 modeled areas, called VOR, VOC, and VMO, incorporate major anatomical and physiological properties of cortical areas V1, V3, and V5 but are vastly simplified compared with monkey visual cortex. Simulated area VOR contains both orientation and directionally selective units; simulated area VMO discriminates the direction of motion of arbitrarily oriented objects; and simulated area VOC responds to both luminance and occlusion boundaries in the stimulus. Area VOC is able to respond to illusory contours (Kanizsa, 1979) by means of the same neural architecture used for the discrimination of occlusion boundaries. This architecture also generates responses to structure-from-motion by virtue of reentrant connections from VMO to VOC. The responses of the simulated networks to these illusions are consistent with the perceptual responses of humans and other species presented with these stimuli. The networks also respond in a consistent manner to a novel illusion that combines illusory contours and structure-from-motion. The response synthesized to this combined illusion provides a strong argument supporting the need for a recursive reentrant process in the cortex. Functional integration of the simulated areas in the RCI model were found to depend upon the combined action of 3 reentrant processes: (1) conflicting responses among segregated areas are competitively eliminated, (2) outputs of each area are used by other areas in their own operations, and (3) outputs of an area are "reentered" back to itself (through lower areas) and can thus be used iteratively to synthesize responses to complex or illusory stimuli. Transection of the reentrant connections selectively abolished these integrative processes and led to failure of figural synthesis. The proposed model of reentry suggests a basis for understanding how multiple visual areas as well as other cortical areas may be integrated within a distributed system.     

Disturbances in neuronal migration and laminar cortical organization associated with multicystic encephalopathy in the Pena-Shokeir syndrome

Summary The Pena-Shokeir syndrome is characterized by intrauterine growth retardation, camptodactyly, multiple ankyloses, facial anomalies and pulmonary hypoplasia. The condition is thought to be inherited in an autosomal recessive fashion. A detailed neuropathological analysis of the brain of a stillborn full-term male infant who exhibited the gross features of the Pena-Shokeir syndrome revealed diffuse bilateral cerebral polymicrogyria associated with multicystic encephalopathy. Abnormal brain development, which was characterized by disturbances in neuronal migration and laminar cortical organization, was clearly associated with changes of an encephaloclastic nature, namely reactive gliosis and infiltration by macrophages. These findings suggest strongly that the Pena-Shokeir syndrome may also result from teratogenic factors such as intrauterine ischemic and/or hypoxic insults to the developing brain.Supported in part by USPHS NIEHS grant ES 02928     

Thalamo-telencephalic connections: new insights on the cortical organization in reptiles

Tracer injections into the dorsal tier of the lacertilian dorsal thalamus revealed an extensive innervation of the cerebral cortex. The medial cortex, the dorsomedial cortex, and the medial part of the dorsal cortex received a bilateral projection, whereas the lateral part of dorsal cortex and the dorsal part of the lateral cortex received only an ipsilateral thalamic projection. Thalamocortical fibers were found superficially in all cortical regions, but in the dorsal part of the lateral cortex, varicose axons within the cellular layer were also observed. The bilateral thalamocortical projection originates from a cell population located throughout the dorsolateral anterior nucleus, whereas the ipsilateral input originates mainly from a rostral neuronal subpopulation of the nucleus. This feature suggests that the dorsolateral anterior nucleus consists of various parts with different projections. The dorsal subdivision of the lateral cortex displayed hodological and topological (radial glia processes) features of a dorsal pallium derivative. After tracer injections into the dorsal cortex of lizards, we found long descending projections that reached the striatum, the diencephalic basal plate, and the mesencephalic tegmentum, which suggests that it may represent a sensorimotor cortex.     

Polymicrogyria includes fusion of the molecular layer and decreased neuronal populations but normal cortical laminar organization

Malformations of cortical development are frequently identified in surgical resections for intractable epilepsy. Among the more frequently identified are cortical dysplasia, pachygyria, and polymicrogyria. The pathogenesis of these common developmental anomalies remains uncertain. Polymicrogyria is particularly vexing because there are multiple described forms (2, 4, and 6 layers) that have been attributed to multiple etiologies (e.g. ischemic, genetic, infectious, and toxic). We reviewed the pathology in 19 cases and performed cortical laminar analysis in 10 of these cases. Our data indicate that a defining feature of polymicrogyriais fusion of the molecular layer and that most often there is a well-defined gray matter-white matter junction. Unexpectedly, the cortical laminae were normally positioned, but there were reduced neuronal populations within these laminae, particularly in the subgranular layers. On the basis of these data, we propose that the categorization of polymicrogyria according to the number of lamina is artificial and should be abandoned, and polymicrogyria should be defined according to the presence or absence of coexisting neuropathological features. Furthermore, our data indicate that polymicrogyria is not a cell migration disorder, rather it should be considered a postmigration malformation of cortical development.     

Ethanol induces a reduction in cortical thickness,neuronal density and somatic shrinkage in the cerebellar cortex of adult mice

Ethanol-induced impairments to the structure of the cerebellar cortex were investigated in adult mice treated with ethanol. Alcohol (15%) was given to a group of mice (Group E), and the mice in the control group (Group C) were allowed to drink pure tap water. After 3 months, animals were sacrificed and processed for histological observations of the cerebellar cortex using Nissl staining. The thickness of each cortical layer, the density of neurons and the diameter of Purkinje cell (PC) soma were measured under light microscope. The results showed that the cerebellar cortex in Group E exhibited a significant decline in the thickness of the cortical cortex and neuronal density, and remarkable atrophy in PC soma occurred when compared to the control group. Our findings indicate that ethanol induces a decline in cortical thickness, loss of cortical neurons and atrophy in neuron volume, which might lead to cerebellar shrinkage after long-term alcohol abuse. Neuronal atrophy may be caused by loss of cytoplasmic matrix and cellular organelle degeneration, resulting in a reduction in substance synthesis and energy supply in neurons. A decrease in cerebellar circuitry due to neuronal loss might mediate a decline in cerebellar function in ethanol-treated mice.     

Plasticity of motor maps in primates: recent advances and therapeutical perspectives

In the past decade, there have been considerable advances in understanding the neuronal bases of sensory and motor map reorganisation in adults and it is now clear that cortical representations are not invariant and stable, but rather, are dynamic and can continuously be modified. In human subjects, substantial advances in this field have been possible because of the spectacular development of non-invasive imaging and brain stimulation techniques. This review addresses specific questions about the capacity of motor maps in adult primates, including man, to change in response to behaviourally relevant experiences or as a result of central or peripheral lesion. The first part of this review deals with recent progress in understanding the role of the primary motor cortex (M1) in both motor control and cognition. The organisation and function of multiple "non-primary" motor areas located rostrally to the primary motor cortex and in the cingulate cortex are also discussed. This review then focuses on advances made in understanding motor cortex plasticity in different conditions. Firstly, since representations in M1 have been shown to change after motor learning, the contribution of M1 in motor learning has been insinuated; arguments against and in favour of this view are discussed. In addition, data suggesting that intracortical circuitry of M1 may play a role in map reorganisation following motor learning are also evaluated. Secondly, a large body of evidence from both animal and human observations is reviewed that confirms that M1 representations can also be altered as a result of changes in availability of effectors or following sensory deprivation. The mechanisms underlying such a plasticity of cortical maps following peripheral lesions are increasingly well understood. Thirdly, we discuss data showing that a corticospinal system lesion can lead to a complete reorganisation of the area allocated to the hand representation in the primary motor cortex or to a reorganization of the whole network of motor areas responsible for voluntary movements. As a conclusion, therapeutical perspectives that result from a better understanding of those various mechanisms responsible for motor map plasticity are briefly discussed.     

Spontaneous neuronal unit activity in the primate basal ganglia and the effects of precentral cerebral cortical ablations

The discharge properties of single neuronal units in the putamen, caudate nucleus, and globus pallidus were studied in awake primates. The effects of restricted deafferentation of the striatum were determined by recording single unit activity in animals with unilateral ablation of areas 4 and 6 of Brodmann. The most striking change was on the regularity of unit firing in the putamen. Units in the normal putamen exhibited a wide range of firing rates and variability. In many units discharge rate was very slow. After the lesion, putaminal units discharged in steady spike trains with highly regular patterns of interspike intervals having on average a 63% reduction in the coefficient of variation. Contrary to expectations, average firing rates actually increased slightly (22%) from a median value of 4.88 Hz in controls to 5.95 Hz in lesioned animals. Although the rates and variability observed in lesioned animals completely overlapped the range of the sample observed in controls, the distributions were shifted such that there were more units with regular discharge patterns and slightly faster firing rates. The caudate nucleus showed no significant change in firing rate or variability. In the globus pallidus, firing rate decreased significantly in the internal segment, and both segments showed an increase in discharge variability. The findings demonstrate that the cerebral cortex strongly influences the spontaneous discharge properties in the basal ganglia. The effects on the variability of spontaneous activity are greater than on the maintenance of tonic firing.