Biomedical subjects

K Zilles

Publications and source records attributed to K Zilles.

At least 109 records · Page 6Linked to original sources

PubMed2000

Simultaneous movements of upper and lower limbs are coordinated by motor representations that are shared by both limbs: a PET study.

The purpose of this study was to examine the cerebral control of simultaneous movements of the upper and lower limbs. We examined two hypotheses on how the brain coordinates movement: (i) by the involvement of motor representations shared by both limbs; or (ii) by the engagement of specific neural populations. We used positron emission tomography to measure the relative cerebral blood flow in healthy subjects performing isolated cyclic flexion-extension movements of the wrist and ankle (i.e. movements of wrist or ankle alone), and simultaneous movements of the wrist and ankle (a rest condition was also included). The simultaneous movements were performed in the same directions (iso-directional) and in opposite directions (antidirectional). There was no difference in the brain activity between these two patterns of coordination. In several motor-related areas (e.g. the contralateral ventral premotor area, the dorsal premotor area, the supplementary motor area, the parietal operculum and the posterior parietal cortex), the representation of the isolated wrist movement overlapped with the representation of the isolated ankle movement. Importantly, the simultaneous movements activated the same set of motor-related regions that were active during the isolated movements. In the contralateral ventral premotor cortex, dorsal premotor cortex and parietal operculum, there was less activity during the simultaneous movements than for the sum of the activity for the two isolated movements (interaction analysis). Indeed, in the ventral premotor cortex and parietal operculum, the activity was practically identical regardless whether only the wrist, only the ankle, or both the wrist and the ankle were moved. Taken together, these findings suggest that interlimb coordination is mediated by motor representations shared by both limbs, rather than being mediated by specific additional neural populations.

Adult↗

PubMed2000

Neural consequences of acting in near versus far space: a physiological basis for clinical dissociations.

We used PET to determine which brain regions are implicated when normal volunteers bisect horizontal lines and point to dots in near (peripersonal) or far (extrapersonal) space. Studies of line bisection in patients with right hemisphere lesions have shown that bisection performance can be severely impaired in either near or far space while remaining within normal limits in the other spatial domain. Likewise, clinical dissociations between pointing to objects in near and far space have been reported. The normal functional anatomy of these dissociations has not been demonstrated convincingly. Regional cerebral blood flow measurements using PET were carried out in 12 healthy right-handed male volunteers who bisected lines or pointed to dots in near or far space, using a laser pen. Subjects performing either task in near space showed neural activity in the left dorsal occipital cortex, left intraparietal cortex, left ventral premotor cortex and left thalamus. In far space, subjects performing either task showed activation of the ventral occipital cortex bilaterally and the right medial temporal cortex. These data provide physiological support for the clinically observed dissociations demonstrating that attending to and acting in near space differentially employs dorsal visuomotor processing areas, whereas attending to and acting in far space differentially draws on ventral visuoperceptual processing areas, even when the motor components of the tasks are identical when performed in the two spaces.

Adult↗

PubMed2000

Functional delineation of the human occipito-temporal areas related to face and scene processing. A PET study.

By measuring regional cerebral blood flow using PET, we delineated the roles of the occipito-temporal regions activated by faces and scenes. We asked right-handed normal subjects to perform three tasks using facial images as visual stimuli: in the face familiar/unfamiliar discrimination (FF) task, they discriminated the faces of their friends and associates from unfamiliar ones; in the face direction discrimination (FD) task, they discriminated the direction of each unfamiliar face; in the dot location discrimination (DL) task, they discriminated the location of a red dot on a scrambled face. The activity in each task was compared with that in the control fixation (CF) task, in which they fixated on the centre of a display without visual stimuli. The DL task activated the occipital cortices and posterior fusiform gyri bilaterally. During the FD task, the activation extended anteriorly in the right fusiform gyrus and laterally to the right inferior temporal cortex. The FF task further activated the right temporal pole. To examine whether the activation due to faces was face-specific, we used a scene familiar/unfamiliar discrimination (SF) task, in which the subjects discriminated familiar scenes from unfamiliar ones. Our results suggest that (i) the occipital cortices and posterior fusiform gyri non-selectively respond to faces, scrambled faces and scenes, and are involved mainly in the extraction of physical features of complex visual images; (ii) the right inferior temporal/fusiform gyrus responds selectively to faces but not to non-face stimuli and is involved in the visual processing related to face perception, whereas the bilateral parahippocampal gyri and parieto-occipital junctions respond selectively to scenes and are involved in processing related to scene perception; and (iii) the right temporal pole is activated during the discrimination of familiar faces and scenes from unfamiliar ones, and is probably involved in the recognition of familiar objects.

Adult↗

PubMed2000

Fast reaction to different sensory modalities activates common fields in the motor areas, but the anterior cingulate cortex is involved in the speed of reaction.

We examined which motor areas would participate in the coding of a simple opposition of the thumb triggered by auditory, somatosensory and visual signals. We tested which motor areas might be active in response to all three modalities, which motor structures would be activated specifically in response to each modality, and which neural populations would be involved in the speed of the reaction. The subjects were required to press a button with their right thumb as soon as they detected a change in the sensory signal. The regional cerebral blood flow (rCBF) was measured quantitatively with (15)O-butanol and positron emission tomography (PET) in nine normal male subjects. Cytoarchitectural areas were delimited in 10 post mortem brains by objective and quantitative methods. The images of the post mortem brains subsequently were transformed into standard anatomic format. One PET scanning for each of the sensory modalities was done. The control condition was rest with the subjects having their eyes closed. The rCBF images were anatomically standardized, and clusters of significant changes in rCBF were identified. These were localized to motor areas delimited on a preliminary basis, such as supplementary motor area (SMA), dorsal premotor zone (PMD), rostral cingulate motor area (CMAr), and within areas delimited by using microstructural i.e., cytoarchitectonic criteria, such as areas 4a, 4p, 3a, 3b, and 1. Fields of activation observed as a main effect for all three modalities were located bilaterally in the SMA, CMAr, contralateral PMD, primary motor (M1), and primary somatosensory cortex (SI). The activation in M1 engaged areas 4a and 4p and expanded into area 6. The activation in SI engaged areas 3b, 1, and extended into somatosensory association areas and the supramarginal gyrus posteriorly. We identified significant activations that were specific for each modality in the respective sensory association cortices, though no modality specific regions were found in the motor areas. Fields in the anterior cingulate cortex, rostral to the CMAr, consistently showed significant negative correlation with mean reaction time (RT) in all three tasks. These results show that simple reaction time tasks activate many subdivisions of the motor cortices. The information from different sensory modalities converge onto the common structures: the contralateral areas 4a, 4p, 3b, 1, the PMD, and bilaterally on the SMA and the CMAr. The anterior cingulate cortex might be a key structure which determine the speed of reaction in simple RT tasks.

Acoustic Stimulation↗

PubMed2000

Functional mapping of human brain in olfactory processing: a PET study.

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.

Adolescent↗

PubMed1999

Widespread up-regulation of N-methyl-D-aspartate receptors after focal photothrombotic lesion in rat brain.

Following focal brain lesions, complex adaptive processes take place in remote intact areas. The present study examines changes in NMDA (N-methyl-D-aspartate), AMPA ((+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate receptors following focal photothrombotic ischemic lesions using quantitative receptor autoradiography. Increases in binding density of NMDA receptors were seen in both hemispheres for up to 30 days. In the contralateral hemisphere, this increase of NMDA receptors occurred as early as 4 h after lesion whereas it appeared with a delay for 14 days on the lesioned side. Binding density of [3H]AMPA and [3H]kainate was unchanged. We suggest that the translational process is differentially regulated by spreading depressions. The delayed up-regulation of NMDA receptor binding on the lesioned side may be due to a translation block similar to that previously described for GABA(A) receptor subunits.

Animals↗

PubMed1999

Broca's region revisited: cytoarchitecture and intersubject variability.

The sizes of Brodmann's areas 44 and 45 (Broca's speech region) and their extent in relation to macroscopic landmarks and surrounding areas differ considerably among the available cytoarchitectonic maps. Such variability may be due to intersubject differences in anatomy, observer-dependent discrepancies in cytoarchitectonic mapping, or both. Because a reliable definition of cytoarchitectonic borders is important for interpreting functional imaging data, we mapped areas 44 and 45 by means of an observer-independent technique. In 10 human brains, the laminar distributions of cell densities were measured vertical to the cortical surface in serial coronal sections stained for perikarya. Thousands of density profiles were obtained. Cytoarchitectonic borders were defined as statistically significant changes in laminar patterns. The analysis of the three-dimensional reconstructed brains and the two areas showed that cytoarchitectonic borders did not consistently coincide with sulcal contours. Therefore, macroscopic features are not reliable landmarks of cytoarchitectonic borders. Intersubject variability in the cytoarchitecture of areas 44 and 45 was significantly greater than cytoarchitectonic differences between these areas in individual brains. Although the volumes of area 44 differed across subjects by up to a factor of 10, area 44 but not area 45 was left-over-right asymmetrical in all brains. All five male but only three of five female brains had significantly higher cell densities on the left than on the right side. Such hemispheric and gender differences were not detected in area 45. These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production.

Adult↗

PubMed1999

Prostacyclin synthase is localized in rat, bovine and human neuronal brain cells.

Using a new polyclonal antibody against prostacyclin (PGI2)-synthase this enzyme was shown to be present in neuronal cells of bovine, rat and human brain, most abundantly in Purkinje cells of the cerebellum and cortical neurons, but not in glial cells. Western blots confirmed the specificity of the antibody and applied to enriched neuronal and astrocyte cultures supported these immunohistochemical data. It was further shown that staining with an anti-nitrotyrosine antibody was positive for PGI2-synthase containing cells. Possible physiological and/or pathophysiological functions of the enzyme in brain are discussed.

Aged↗

PubMed1999

Illusory arm movements activate cortical motor areas: a positron emission tomography study.

Vibration at approximately 70 Hz on the biceps tendon elicits a vivid illusory arm extension. Nobody has examined which areas in the brain are activated when subjects perceive this kinesthetic illusion. The illusion was hypothesized to originate from activations of somatosensory areas normally engaged in kinesthesia. The locations of the microstructurally defined cytoarchitectonic areas of the primary motor (4a and 4p) and primary somatosensory cortex (3a, 3b, and 1) were obtained from population maps of these areas in standard anatomical format. The regional cerebral blood flow (rCBF) was measured with (15)O-butanol and positron emission tomography in nine subjects. The left biceps tendon was vibrated at 10 Hz (LOW), at 70 or 80 Hz (ILLUSION), or at 220 or 240 Hz (HIGH). A REST condition with eyes closed was included in addition. Only the 70 and 80 Hz vibrations elicited strong illusory arm extensions in all subjects without any electromyographic activity in the arm muscles. When the rCBF of the ILLUSION condition was contrasted to the LOW and HIGH conditions, we found two clusters of activations, one in the supplementary motor area (SMA) extending into the caudal cingulate motor area (CMAc) and the other in area 4a extending into the dorsal premotor cortex (PMd) and area 4p. When LOW, HIGH, and ILLUSION were contrasted to REST, giving the main effect of vibration, areas 4p, 3b, and 1, the frontal and parietal operculum, and the insular cortex were activated. Thus, with the exception of area 4p, the effects of vibration and illusion were associated with disparate cortical areas. This indicates that the SMA, CMAc, PMd, and area 4a were activated associated with the kinesthetic illusion. Thus, against our expectations, motor areas rather than somatosensory areas seem to convey the illusion of limb movement.

Adult↗

PubMed1999

Observer-independent method for microstructural parcellation of cerebral cortex: A quantitative approach to cytoarchitectonics.

We describe a new, observer-independent procedure for identifying boundaries between cortical areas. The method is useful for images obtained from sections which provide microstructural information on the cortical laminar pattern, e.g., Nissl-, myelin-, or immunohistochemically stained sections or receptor autoradiographs. The laminar pattern is represented by profile curves extending from the cortical surface to the white matter boundary. These profiles are constructed from digitized images. Digitization is based on the grey level index (Nissl) or densitometry (myelin, immunohistochemistry, receptor autoradiography). The shapes of neighboring profiles are compared by calculating their distances according to feature vectors extracted from the profiles. Profiles derived from a homogeneous area can be expected to be similar in shape and hence show low distance values between each other. Maximum distances can be found between profiles which lie on opposite sides of a structural boundary. The Mahalanobis distance was found to be more sensitive and to yield greater spatial resolution than other distance measures such as the Euclidean distance. Cell-stained sections of the human neocortex were analyzed. The method not only verified boundaries which had been defined by visual inspection, it also revealed new ones which had not been detected visually. The procedure offers an important supplement to the traditional methods based on visual inspection which, for the first time, is based on quantitative data and therefore offers a new level of reproducibility and observer independence. Anatomical atlases based on this procedure thus provide a new tool for the interpretation of structural data obtained from functional imaging techniques.

Brain Mapping↗

PubMed1999

Measuring in vivo myelination of human white matter fiber tracts with magnetization transfer MR.

Precise characterization of white matter pathways is important for the understanding of structural-functional relationships in the human brain. While it is known from postmortem studies that the connectivity of cortical areas is conveyed by projection, commissural, and association fibers, most clinical studies disregard useful information about specific fiber tracts. Magnetization transfer (MT) MR detects the relative proportion of free mobile protons and immobile protons bound to macromolecules. MT values correlate with histopathology and it has been proposed that in the white matter, the amount of magnetization transfer correlates with the degree of myelination. Thus, MT-MR provides measures that may reflect more accurately the physiology and natural course of diseases involving the white matter. We applied this quantitative in vivo method to five children at different ages to determine whether the maturational changes of distinct fiber tracts could be measured. All regions of interest were localized by means of Brodmann's original descriptions and the additional use of reconstructed 3D-matched data from 10 myelin-stained human brain specimens. With this atlas-guided approach we localized and measured 26 supratentorial white matter fiber tracts in each hemisphere, connecting to primary as well as association cortices. All fiber tracts showed consistent age-related MT changes and the strongest effects were found in those tracts projecting to the primary cortical areas. These results suggest that our method is suitable for in vivo MT measurements in specific fiber tracts. It can provide data that relate to myelination during ontogenesis or myelination delays in myelin disorders. In the clinical domain, the focus on specific fiber tracts appears to be advantageous over standard approaches, because such system of parcellation is based on the functional anatomy of the white matter. Consequently, it may be especially useful for topical analysis in neurology allowing the assessment of the functional consequences of white matter damage as well as the effectiveness of treatments in patients with any lesion that can be visualized by MRI.

Acoustic Stimulation↗

PubMed1999

Optimal staining methods for delineation of cortical areas and neuron counts in human brains.

For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas.

Adult↗

PubMed1999

Areas 3a, 3b, and 1 of human primary somatosensory cortex.

This study defines cytoarchitectonic areas 3a, 3b, and 1 of the human primary somatosensory cortex by objective delineation of cytoarchitectonic borders and ensuing cytoarchitectonic classification. This avoids subjective evaluation of microstructural differences which has so far been the only way to structurally define cortical areas. Ten brains were fixed in formalin or Bodian's fixative, embedded in paraffin, sectioned as a whole in the coronal plane at 20 microm, and cell stained. Cell bodies were segmented from the background by adaptive thresholding. Equidistant density profiles (125 microm wide, spacing 300 or 150 microm) were extracted perpendicularly to the pial surface across cortical layers II-VI and processed with multivariate statistical procedures. Positions of significant differences in shape between adjacent groups of profiles were correlated with the cytoarchitectonic pattern. Statistically significant borders can be reproduced at corresponding positions across a series of nearby sections. They match visible changes in cytoarchitecture in the cell-stained sections. Area 3a lies in the fundus of the central sulcus, and area 3b in the rostral bank of the postcentral gyrus. Area 1 lies on its crown and reaches down into the postcentral sulcus. Interareal borders, however, do not match macrostructural landmarks of the postcentral gyrus, and they considerably vary in their positions relative to these landmarks across different brains. Hence, only genuine microstructural analysis can define the borders between these cortical areas. Additional significant borders which do not correlate with visible changes in cytoarchitecture can be found within areas 3b and 1. They may represent somatotopy and/or cortical representations of different somatosensory receptors.

Adult↗

PubMed1999

Mapping of histologically identified long fiber tracts in human cerebral hemispheres to the MRI volume of a reference brain: position and spatial variability of the optic radiation.

The interpretation of the anatomical basis of functional deficits after subcortical infarcts could be considerably improved, if the precise topography and interindividual variability in size and course of long fiber tracts in adult human cerebral hemispheres were available in a spatial reference system. We therefore developed a method enabling the mapping of long fiber tracts to the volume of a standard reference brain. The examined fiber tracts were identified in myelin-stained histological serial sections of 10 human brains. The reference brain is a 3-D reconstruction of in vivo obtained magnetic resonance images (MRIs). The warping of histological volumes with the labeled fiber tracts to the reference brain by means of linear and nonlinear transformation procedures results in population maps that demonstrate the interindividual variability in position, size, and course of fiber tracts. In this paper, we present population maps of the optic radiation and the lateral geniculate body as a first example of this mapping strategy. Both structures present a considerable interindividual variability. Furthermore, voxel-based morphometry shows significant side differences with larger volumes of both structures in the left hemisphere than in the right hemisphere. A more than twofold variability of size in the interhemispheric extension of the optic radiation and the lateral geniculate body is found even after normalization of absolute brain size. Our observations demonstrate that the present approach based on population maps of fiber tracts and nuclei can improve the anatomical localization and interpretation of brain lesions visible in MRIs at the level of microstructurally identified architectonical units.

Adult↗

PubMed1999

Connectivity in the somatosensory cortex of the adolescent rat: an in vitro biocytin study.

A promising way to elucidate neuronal information processing is to establish detailed structure-function relationships of identified single neurons or populations of nerve cells, especially their synaptic connectivity. This has been greatly improved by the development of acute brain slice preparations. The cellular physiology of the rodent primary somatosensory (barrel) cortex has been extensively studied. However, for a meaningful interpretation of physiological experiments the degree and pattern of connectivity has to be known for the particular preparation. Since such studies are not available for rat (P15-25) barrel cortex in vitro, we have traced the cortico-cortical and thalamo-cortical connections in 400-microm-thick slices with biocytin. In coronal slices, a wealth of axonal connections in retrograde and anterograde directions were heavily labeled, resembling the full pattern of cortico-cortical projections described in vivo. The most striking connections were vertical and horizontal connections within the primary somatosensory cortex, as well as a columnar projection to the secondary somatosensory cortex and beyond (mainly the parietal ventral area). Electron microscopic extensions of the study indicated that the full possible set of synaptic contacts with an adult-like appearance was already established in these connections. In thalamo-cortical slices, strong reciprocal connections with the ventrobasal (and to a much lesser extent also the posterior) thalamic nucleus were always observed, together with an intensive ramification of fibers in the reticular nucleus. A striatal terminal field was also consistently found. We conclude that all major intracortical and thalamo-cortical connection are richly preserved in the in vitro slice preparations of rats. Thus, these preparations are suitable for elucidation of the functional interaction of the most crucial brain structures involved in somatosensory information processing combining an in vivo-like anatomical structure with the controlled environment of an in vitro slice.

Animals↗

PubMed1999

Differential maturational patterns of nitric oxide synthase-I and NADPH diaphorase in functionally distinct cortical areas of the mouse cerebral cortex.

Nitric oxide (NO) regulates several functions both in the developing and the adult central nervous systems (CNS). During development, NO is assumed to contribute to the histogenetic differentiation of the CNS especially through the modulation of programmed neuronal death. The embryonal and postnatal changes in the distribution of the cortical NO producing system were studied in Balb/c mice using immunocytochemistry for nitric oxide synthase-I (NOS-I) and NADPH-diaphorase (NADPH-d) enzyme histochemistry. NOS-I reactive neurons (RN) appeared first at embryonic day 14 (E14) in the spinal cord in the vicinity of the central canal, and later, at E16-18, in the thalamus and striatum. The first cortical region to present NOS-I reactivity was the parietal cortex, which happened at E18-20. After E20 the number of NOS-I RN increased in every cortical area, plateauing at postnatal day 4 (P4). In parietal regions, however, the highest density of NOS-I RN was observed already at P1. The neuronal packing density (PD) of NOS-I RN declined until adulthood, interrupted by a transient increase in some cortical areas at the onset of puberty. The heterochronous appearance of NOS-I during pre- and postnatal development of different brain regions and the sequence of up- and downregulation of expression until adult stages points to an important role of NO in brain development and functional differentiation.

Animals↗

PubMed1999

Neuronal and glial structures of the superficial layers of the human superior colliculus.

We studied neuronal and glial elements in the superficial layers of the human superior colliculus by means of Nissl stains, Golgi impregnations, histochemical demonstration of NADPH-d activity and immunohistochemistry for glial fibrillary acidic protein (GFAP) in astrocytes. The glia-neuron interface was visualized with Wisteria floribunda agglutinin (WFA), which is a marker for perineuronal nets. The laminar pattern and the morphology of the major cell types closely resembled that found in other species although the thickness of the stratum zonale varied and the diversity of interneurons was greater than in other mammals. Furthermore, the stratum griseum superficiale showed a characteristic clustering of cells, the surfaces of which were intensely labeled by WFA. The clusters disappeared when GFAP expression increased.

Aged↗

PubMed1999

Changes in GABA(A) and GABA(B) receptor binding following cortical photothrombosis: a quantitative receptor autoradiographic study.

Experimental cortical photothrombosis leads to pronounced alterations in the binding density of [3H]muscimol and [3H]baclofen to GABA(A) and GABA(B) receptors, both in the lesioned and the structurally intact cortex. The binding density of [3H]muscimol to GABA(A) receptors was markedly increased in the "core" of the lesion during the first week, reaching a maximum on the third day post-lesion. Simultaneously, it dropped in the exofocal primary somatosensory cortex. Reductions in the binding density of [3H]muscimol were also found in remote cortical areas of the contralateral hemisphere and lasted for several weeks. In contrast to the down-regulation of apparent binding density of [3H]muscimol, a long-lasting up-regulation of that of [3H]baclofen to GABA(B) receptors was measured in the exofocal primary somatosensory cortex and in remote cortical areas of both hemispheres. The greatest increase in the binding density of [3H]baclofen was seen on the seventh day in the surroundings of the lesion. Our findings indicate that widespread alterations in the concentrations of GABA(A) and GABA(B) receptors are induced in remote cortical areas by a focal ischaemic lesion. Since GABA(A) receptor affinity is regulated by nitric oxide, we suggest that the observed down-regulation of GABA(A) receptors may be correlated with a lesion-induced increase in nitric oxide, whereas the up-regulation of GABAB receptors might be caused by other mechanisms, e.g., compensatory processes. In the centre of the lesion, however, a GABA(A) receptor-mediated mechanism, which limits the spread of lesion-induced hyperexcitability, is thought to be involved.

Animals↗