Cytoarchitecture of the Ferret Suprasylvian Gyrus Correlated with Areas Containing Multiunit Responses Elicited by Stimulation of the Face

The cytoarchitecture was studied in a segment of the ferret suprasylvian gyrus containing at least two and possibly four somesthetic representations of the face that were observed in the primary somatosensory cortex. These representations were restricted to the crown of the gyrus and were surrounded by somesthetically unresponsive cortex that extended down both sides to the base of adjacent sulci. Numerous cytoarchitectonic subdivisions were found on a qualitative basis, and were confirmed quantitatively by cluster analyses and relevant statistical tests of 10 prominent features from layers III, IV, and V. Four distinct cytoarchitectonic subdivisions, each with a well-developed and homogeneous granular layer IV, were found distributed from anterior to posterior along the crown of the gyrus at sites corresponding to the locations of the four facial representations. The surrounding unresponsive cortex had a fragmented cytoarchitecture, especially along the medial bank and base of the coronal sulcus. This unresponsive cortex separated the facial representations from the body representations, which were located on the adjacent posterior cruciate gyrus. Most of the unresponsive subdivisions had a heterogeneous or agranular layer IV and fairly well-developed sublamination in layer III, which may be indicative of extensive corticocortical connections. One set of unresponsive subdivisions had comparable cytoarchitectures that directly bordered the facial representations. Another set of unresponsive subdivisions with comparable architectures occupied most of the lateral bank of the gyrus. The implications of multiple representations and cytoarchitectonic fragmentation of the ferret primary somatosensory cortex are discussed in relation to the organization of the primary somatosensory cortex in other species.     

Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity

Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience-dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.     

Involvement of Adenosine-Sensitive Cyclic AMP-Generating Systems in Cobalt-Induced Epileptic Activity in the Rat

An injection of cobalt chloride solution into the unilateral sensorimotor cortex of rats induced electrographic epileptic activity, which was followed by a peripheral motor disturbance. Brain slices were prepared from the cortical region including the injection site and from the other cortical regions of rats between 8 and 50 days after the injection. In the cortical slices, we examined cyclic AMP accumulations elicited by adenosine and its stable analogue 2-chloroadenosine. Adenosine and 2-chloroadenosine at their maximal dose increased cyclic AMP accumulation six- to 10-fold and 10–15-fold, respectively, and the elicitation was markedly inhibited by the adenosine antagonist 8-phenyltheophylline. The cyclic AMP accumulation was increased in the primary epileptic region of the cortex adjacent to the injection site of cobalt chloride solution, whereas it was unchanged in the other cortical regions. The increase in cyclic AMP accumulation was observed regardless of the presence or absence of the adenosine uptake inhibitor dipyridamole, the phosphodiesterase inhibitor DL-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, and adenosine deaminase. Such an increased accumulation of cyclic AMP in the primary epileptic cortex was detected as early as 8 days after the injection. The cyclic AMP accumulation continued to increase and reached a peak level 17–19 days after the injection, and it returned to the control levels after 40–50 days, in correspondence with the electrographic and behavioral findings. It is concluded that alterations in adenosine receptormediated generation of cyclic AMP in the primary epileptic cortex are closely associated with the central process of cobalt-induced epilepsy. In general, the adenosine-sensitive cyclic AMP-generating systems may serve as a common mechanism in experimental models of epilepsy.     

Areal Distributions of Cortical Neurons Projecting to Different Levels of the Caudal Brain Stem and Spinal Cord in Rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Ag_m), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb.

The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI. Injections in lateral SI representing the face produced dense terminal label in the contralateral trigeminal complex. Injections in cortex devoted to the forelimb and forepaw labeled the contralateral cuneate nucleus and parts of the dorsal horn of the spinal cord. The cortical injections also demonstrated interconnections of parts of SI with some of the other regions of cortex with projections to the spinal cord, and provided further evidence for the existence of PV in rats.     

Acute Effects of Total or Partial Digit Denervation on Raccoon Somatosensory Cortex

The immediate effects of total or partial denervation of single digits (0-16 hr after nerve transection) on primary somatosensory cortex were studied electrophysiologically. Comparisons of response properties and cortical somatotopy were made between intact raccoons and four groups of raccoons with transection of some or all of the nerves innervating the fourth or fifth digit. Animals with all four digital nerves cut (amputation of the digit) were most different from normal. Approximately half of the penetrations in the affected cortical region showed inhibitory responses to stimulation of adjacent skin regions. These consisted of a strong response to stimulus offset and/or a suppression of spontaneous activity during indentation. Since these responses were substantially different from those recorded several months after digit amputation, additional changes in connectivity and synaptic strength must occur with chronic denervation. These inhibitory responses were not seen in animals with one, two, or three nerves cut per digit.

In the animals with partial denervation of a digit, the greatest disruption occurred when both ventral nerves to the glabrous skin were transected. This yielded cell clusters with abnormally large receptive fields, disruptions in somatotopic organization, and a decreased occurrence of low-threshold responses. If only one nerve to glabrous skin was transected, there was less change, even if it was combined with transection of both nerves to hairy skin. These results suggest that the release of inhibitory responses in a cortical digital region by amputation is prevented by the retention of even one ventral nerve. None of the denervation conditions produced large nonresponsive areas of cortex, which would have indicated a loss of all inputs.     

大鼠初级听皮层神经元对声音空间信息的编码

尽管大脑听皮层神经元对声音空间信息的编码已有不少的研究报道,但其编码机制并不十分清楚,相关研究在大鼠的初级听皮层也未见详细的研究报道．用神经电生理学方法在大鼠初级听皮层考察了151个听神经元的听空间反应域,分析了神经元对来自不同空间方位声刺激反应的放电数和平均首次发放潜伏期的关系．结果表明,多数(52.32%)神经元对来自对侧听空间的声刺激反应较强,表现为对侧偏好型特征,其他神经元分别归类为同侧偏好型(18.54%)、中间偏好型(18.54%)、全向型(3.31%)和复杂型(7.28%)．多数神经元偏好的听空间区域的几何中心位于记录部位对侧听空间的中部和上部．绝大多数初级听皮层神经元对来自偏好听空间的声刺激反应的放电数较多、反应潜伏期较短,对来自非偏好听空间的声刺激反应的放电数较少、反应潜伏期较长,放电数与平均首次发放潜伏期呈显著负相关．在对声音空间信息的编码中,大脑初级听皮层可能综合放电数和潜伏期的信息以实现对声源方位的编码．     

Gene Expression Profiling of Rat Cerebral Cortex Development Using cDNA Microarrays

A large amount of genetic information is devoted to brain development. In this study, the cortical development in rats at eight developmental time points (four embryonic [E15, E16, E18, E20] and four postnatal [P0, P7, P14, P21]) was studied using a rat brain 10K cDNA microarray. Significant differential expression was observed in 467 of the 9,805 genes represented on the microarray. Two major Gene Ontology classes—cell differentiation and cell–cell signaling—were found to be important for cortical development. Genes for ribosomal proteins, heterogeneous nuclear ribonucleoproteins, and tubulin proteins were up-regulated in the embryonic stage, coincidently with extensive proliferation of neural precursor cells as the major component of the cerebral cortex. Genes related to neurogenesis, including neurite regeneration, neuron development, and synaptic transmission, were more active in adulthood, when the cerebral cortex reached maturity. The many developmentally modulated genes identified by this approach will facilitate further studies of cortical functions. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Astroglia demonstrate regional differences in their ability to maintain primary dendritic outgrowth from mouse cortical neurons in vitro

To determine whether glia from different regions of the central nervous system (CNS) initiate or maintain primary dendritic growth, embryonic day 18 mouse cortical neurons were co-cultured with rat (postnatal day 4) astroglial cells derived from retina, spinal cord, mesencephalon, striatum, olfactory bulb, retina, and cortex. Axon and dendrite outgrowth from isolated neurons was quantified using morphological and immunohistochemical techniques at 18 h and 1, 3, and 5 days in vitro. Neurons initially extend the same number of neurites, regardless of the source of glial monolayer; however, glial cells differ in their ability to maintain primary dendrites. Homotypic cortical astrocytes maintain the greatest number of primary dendrites. Glia derived from the olfactory bulb and retina maintained intermediate numbers of dendrites, whereas only a small number of primary dendrites were maintained by glia derived from striatum, spinal cord, or mesencephalon. Longer axons were initially observed from neurons grown on glia that did not maintain dendrite number. Axonal length, however, was similar on the various monolayers after 5 days in vitro. Neurons that were grown in media conditioned by either mesencephalic or cortical glia for the first 24 h followed by culture media from glia of the alternate source for 4 days in vitro confirmed that glia maintained, rather than initiated, the outgrowth of the primary dendritic arbor. These results indicate that glial cells derived from various CNS regions differ in their ability to maintain the primary dendritic arbor from mouse cortical neurons in vitro. © 1995 John Wiley & Sons, Inc.     

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCK_B antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCK_B antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.     

Binaural and frequency representation in the primary auditory cortex of the big brown bat, Eptesicus fuscus

This study examines the binaural and frequency representation in the primary auditory cortex (AC) of the big brown bat, Eptesicus fuscus, by using an ear-phone stimulation system. All 306 cortical neurons studied were excited by contralateral sound stimulation but they were either excited, inhibited or not affected by ipsilateral sound stimulation. These cortical neurons were columnarly organized according to their binaural and frequency-tuning properties. The excitation-excitation columns which occupy about 15% of the AC are mainly aggregated within an oval-shaped area of the central AC. The excitation-inhibition neurons and binaural neurons with mixed properties are distributed in the remaining 85% of the surrounding primary AC. Although the best frequency (BF) of these neurons shows a tendency to decrease from high to low along the anteroposterior axis of the primary AC, systematic variation in BF is not always consistent across the entire mapping area. In particular, BFs of cortical neurons isolated in the anterior AC vary quite unsystematically such that neurons with similar BFs are aggregated in isolated patches. Isofrequency and binaural columns are segregated into bands that intersect each other. Accepted: 13 August 1997     

Specific [3H]SCH23390 Binding to Dopamine D1 Receptors in Cerebral Cortex and Neostriatum: Evidence for Heterogeneities in Affinity States and Cortical Distribution

The tritiated antagonist SCH23390 was used to identify dopamine D1 receptors in the cerebral cortex and neostriatum. The kinetic properties of binding were investigated in parallel experiments with membrane preparations from both tissues. The densities of receptors (Bmax) and the dissociation constants (KD) were determined from saturation curves, and the specificity of binding verified in competition experiments using agonists and antagonists. The cortical D1 receptor displays the same pharmacological selectivity (including stereospecificity) and kinetic properties as the neostriatal D1 receptor. From both the dissociation kinetics by dilution and the competition curves, it could be established that there is an heterogeneity of binding probably due to high- and low-affinity states. Endogenous dopamine, 4-hydroxy-3-methoxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine contents, as well as D1 receptor distribution, were measured for the neostriatum and four localized cortical areas: anterior cingulate, primary somatosensory, primary visual, and piriform-entorhinal. For the regions examined, the distribution of D1 receptors is heterogeneous, but correlates very well (r greater than 0.98) with the endogenous levels of dopamine and its major metabolites.     

Responsiveness of Reorganized Primary Somatosensory (SI) Cortex after Local Inactivation of Normal SI Cortex in Chronic Spinal Cats

The cortical map of adult cats that sustained spinal cord transection at T₁₂ when they were 2 weeks old is characterized by a clear duplication of the representation of the forelimb, rostral trunk, and neck. The novel representation is located in the cortical region that is, in nonoperated animals, normally devoted to the hindlimb representation. We have investigated the possibility that the reactivation of the deprived hindlimb cortex may be mediated by corticocortical projections from normal to reorganized cortex. The primary somatosensory (SI) cortex was initially mapped to determine the boundaries of the normal and reorganized cortical representations. Somatotopically corresponding regions in both normal and reorganized cortex representing the trunk, the web space, or the shoulder were more precisely mapped. Inactivation of normal cortex was achieved by the nanoinjection of a solution of lidocaine hydrochloride stained with Chicago sky blue. Two major findings are described. First, inactivation of a circumscribed region of normal cortex representing a given receptive field (RF) failed to reduce or inhibit the responsiveness of a somatotopically corresponding RF represented in reorganized cortex. Therefore, it is unlikely that intracortical connections between normal and reorganized cortex could account for the reorganizational processes observed in cats that sustained spinal cord transection at 2 weeks of age. Second, the chemical blockade of normal cortex provoked an increase of the responsiveness and of the size of the peripheral RFs represented in reorganized cortex. This finding suggests that there are corticocortical connections (possibly topographically organized) between normal and reorganized cortex, and that these connections are inhibitory.     

Topographic Organization of Baboon Primary Motor Cortex: Face,Hand, Forelimb,and Shoulder Representation

(1) The fine details of the motor organization of the forelimb, face, and tongue representation of the baboon (Papio h. anubis)primary motor cortex were studied in four adult animals, using intracortical microstimulation (ICMS). (2) A total of 293 electrode penetrations were made. ICMS was delivered to 10,052 sites, and of these, 6,186 sites were verified to have been located within the grey matter. Motor effects were evoked from 30% of these sites. (3)The baboon motor cortex is confined, in large part, to the cortical tissue lying along the anterior bank of the central sulcus. When the electrode penetrations were confined to the precentral gyrus, few sites were capable of evoking movement when stimulated by currents of 40 μA or less. (4)The details of the motor maps varied among the four animals; nonetheless, a general topographic organization existed, with the tongue musculature being represented most laterally, followed by a medial progression of the face, digits, wrist, forearm, and shoulder. Within the representation of a given body part, the muscles were organized as a mosaic, wherein the same muscle was multiply represented. (5) A zone of unresponsive cortex was observed to lie consistently between the face and forelimb representation in all four animals. Repeated electrode penetrations within the unresponsive zone failed to elicit muscle contractions even with stimulating currents as high as 80 μA. (6) Our results suggest that the baboon motor cortex is topographically organized; however, embedded within this overall pattern lies a fine-grained mosaic incorporating multiple representations of the same muscle.     

Characterization of l-[3H]Nicotine Binding in Human Cerebral Cortex: Comparison Between Alzheimer''s Disease and the Normal

Putative nicotine receptors in the human cerebral cortex were characterized with L-[3H]nicotine, L-[3H]Nicotine binding was enhanced by the addition of Ca2+ and abolished in the presence of Na3EDTA. Association and dissociation of the ligand were rapid at 25 degrees C with t1/2 values of 2 and 3 min, respectively. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 5.6 nM and a Hill coefficient of 1.05. There was no effect of postmortem interval on the density of binding sites assayed up to 24 h in rat frontoparietal cortex. Nicotine binding in human cortical samples was also unaltered by increasing sampling delay. In human cortical membranes, binding site density decreased with normal aging. Receptor affinity and concentration in samples of frontal cortex (Brodmann area 10) from patients with Alzheimer's disease were comparable to age-matched control values. Samples of infratemporal cortex (Brodmann area 38) from patients with Alzheimer's disease had a 50% reduction in the number of L-[3H]nicotine sites. Choline acetyltransferase activity was significantly decreased in both cortical areas. Enzyme activities in the temporal pole were reduced to 20% of control values. These data indicate that postsynaptic nicotine receptors are spared in the frontal cortex in Alzheimer's disease. In the infratemporal cortex, significant numbers of receptors remain despite the severe reduction in choline acetyltransferase activity. Replacement therapy directed at these sites may be warranted in Alzheimer's disease.     

Organization of the Connections between the Parietal Associative Zone and the Primary Sensory Zones in the Cat Neocortex

In acute experiments on cats, we studied the impulse activity of 262 neurons of the parietal associative zone (PAZ, field 5). Among them, 129 cells [100 silent units and 29 units generating background activity (BA)] were identified as output neurons, while 133 cells with the BA were interneurons of the intrinsic cortical neuronal circuits. Electrical stimulation of the primary visual, auditory, or somatosensory cortices evoked no impulse responses in silent output PAZ neurons, while output neurons with the BA and interneurons (more than 65 and 80% of the cell units, respectively) generated clear responses (more frequently, phasic). Stimulation of the auditory and visual cortices exerted mostly inhibitory effects, while stimulation of the somatosensory cortex provided mostly excitatory influences. The ratios of neurons generating primary excitatory and inhibitory responses to stimulation of the visual, auditory, and somatic cortices were 0.3:1, 0.6:1, and 3.2:1, respectively. More than 95% of the field-5 neurons were influenced from the primary sensory zones via di- and/or polysynaptic pathways. Monosynaptic excitatory inputs from the visual cortex were identified for 3.8% of interneurons and 6.9% of output PAZ neurons; for the auditory cortical inputs, the respective figures were 1.7 and 3.5%. Monosynaptic connections with the somatic cortex were found only for 4% of the interneurons under study. It has been concluded that interaction of heteromodal signals coming to the PAZ via the corticopetal and associative inputs occurs on neurons of all the cortical layers.     

BAX敲除对小鼠大脑皮层和海马星形胶质细胞分布的影响

星形胶质细胞是大脑中一类高度异质的重要大胶质细胞,不仅在脑的发育和功能中起到重要作用,也参与多种神经病理生理学过程.多项研究表明B淋巴细胞瘤-2相关X蛋白(B-cell lymphoma-2 associated X protein,BAX)依赖性凋亡通路参与调控正常发育过程中脑内神经元的数量与分布,但是对其调控星形胶...     

Modification of callosal afferents of the primary visual cortex ipsilateral to the remaining eye in rats monocularly enucleated at different stages of ontogeny

Summary Callosal afferents to the primary visual cortex (area Oc1) mainly originate in the border region between the lateral portion of the primary visual cortex (area Oc1) and the laterally positioned secondary visual cortex (area Oc2L) of the contralateral hemisphere. The extent of this region has been determined by retrograde labeling with horseradish peroxidase (HRP). In normal rats the width of the retrogradely labeled cortical strip is about 0.3 mm. In rats monocularly enucleated from the 23rd up to the 44th ontogenetic day and subsequently injected as adults with HRP into Oc1 ipsilateral to the remaining eye, the perikarya of the callosal afferents from the opposite hemisphere are labeled in the form of significantly wider columns (about 0.8 mm) than in animals enucleated from the 50th ontogenetic day onwards. The latter do not differ from controls.     

GABA(A) receptor alpha-subunit proteins in human chronic alcoholics

Antibodies were raised against specific peptides from N-terminal regions of the alpha1 and alpha3 isoforms of the GABA(A) receptor, and used to assess the relative expression of these proteins in the superior frontal and primary motor cortices of 10 control, nine uncomplicated alcoholic and six cirrhotic alcoholic cases were matched for age and post-mortem delay. The regression of expression on post-mortem delay was not statistically significant for either isoform in either region. In both cortical areas, the regression of alpha1 expression on age differed significantly between alcoholic cases, which showed a decrease, and normal controls, which did not. Age had no effect on alpha3 expression. The alpha1 and alpha3 isoforms were found to be expressed differentially across cortical regions and showed a tendency to be expressed differentially across case groups. In cirrhotic alcoholics, alpha1 expression was greater in superior frontal than in motor cortex, whereas this regional difference was not significant in controls or uncomplicated alcoholics. In uncomplicated alcoholics, alpha3 expression was significantly lower in superior frontal than in motor cortex. Expression of alpha1 was significantly different from that of alpha3 in the superior frontal cortex of alcoholics, but not in controls. In motor cortex, there were no significant differences in expression between the isoforms in any case group.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4γ, 4δ, 6aα, 6aγ, 3a. The lesions were mainly in area 4γ. In the lesioned hemisphere there were many points around the lesion site (in areas 4γ and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6aγ) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4γ, 6aγ and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.