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PubMed2006

Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI.

Loss of function and subsequent spontaneous recovery after stroke have been associated with physiological and anatomical alterations in neuronal networks in the brain. However, the spatiotemporal pattern of such changes has been incompletely characterized. Manganese-enhanced MRI (MEMRI) provides a unique tool for in vivo investigation of neuronal connectivity. In this study, we measured manganese-induced changes in longitudinal relaxation rate, R(1), to assess the spatiotemporal pattern of manganese distribution after focal injection into the intact sensorimotor cortex in control rats (n=10), and in rats at 2 weeks after 90-min unilateral occlusion of the middle cerebral artery (n=10). MEMRI data were compared with results from conventional tract tracing with wheat-germ agglutinin horseradish peroxidase (WGA-HRP). Distinct areas of the sensorimotor pathway were clearly visualized with MEMRI. At 2 weeks after stroke, manganese-induced changes in R(1) were significantly delayed and diminished in the ipsilateral caudate putamen, thalamus and substantia nigra. Loss of connectivity between areas of the sensorimotor network was also identified from reduced WGA-HRP staining in these areas on post-mortem brain sections. This study demonstrates that MEMRI enables in vivo assessment of spatiotemporal alterations in neuronal connectivity after stroke, which may lead to improved insights in mechanisms underlying functional loss and recovery after stroke.

Animals↗
PubMed1998

A visuo-somatomotor pathway through superior parietal cortex in the macaque monkey: cortical connections of areas V6 and V6A.

This report addresses the connectivity of the cortex occupying middle to dorsal levels of the anterior bank of the parieto-occipital sulcus in the macaque monkey. We have previously referred to this territory, whose perimeter is roughly circumscribed by the distribution of interhemispheric callosal fibres, as area V6, or the 'V6 complex'. Following injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP) into this region, we examined the laminar organization of labelled cells and axonal terminals to attain indications of relative hierarchical status among the network of connected areas. A notable transition in the laminar patterns of the local, intrinsic connections prompted a sub-designation of the V6 complex itself into two separate areas, V6 and V6A, with area V6A lying dorsal, or dorsomedial to V6 proper. V6 receives ascending input from V2 and V3, ranks equal to V3A and V5, and provides an ascending input to V6A at the level above. V6A is not connected to area V2 and in general is less heavily linked to the earliest visual areas; in other respects, the two parts of the V6 complex share similar spheres of connectivity. These include regions of peripheral representation in prestriate areas V3, V3A and V5, parietal visual areas V5A/MST and 7a, other regions of visuo-somatosensory association cortex within the intraparietal sulcus and on the medial surface of the hemisphere, and the premotor cortex. Subcortical connections include the medial and lateral pulvinar, caudate nucleus, claustrum, middle and deep layers of the superior colliculus and pontine nuclei. From this pattern of connections, it is clear that the V6 complex is heavily engaged in sensory-motor integration. The specific somatotopic locations within sensorimotor cortex that receive this input suggest a role in controlling the trunk and limbs, and outward reaching arm movements. There is a secondary contribution to the brain's complex oculomotor circuitry. That the medial region of the cortex is devoted to tightly interconnected representations of the sensory periphery, both visual and somatotopic-which are routinely stimulated in concert-would appear to be an aspect of the global organization of the cortex which must facilitate multimodal integration.

Animals↗
PubMed2005

Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization.

Our work has shown that following focal ischemic lesion in adult rats, neutralization of the axon growth inhibitor Nogo-A with the monoclonal antibody (mAb) IN-1 results in functional recovery. Furthermore, new axonal connections were formed from the contralesional cortex to subcortical areas corresponding to the observed functional recovery. The present study investigated whether dendritic changes, also known to subserve functional recovery, paralleled the axonal plasticity shown after ischemic lesion and treatment with mAb IN-1. Golgi-Cox-stained layer V pyramidal neurons in the contralesional sensorimotor cortex were examined for evidence of dendritic sprouting. Results demonstrated increased dendritic arborization and spine density in the mAb IN-1-treated animals with lesion. Interestingly, administration of mAb IN-1 without lesion resulted in transient dendritic outgrowth with no change in spine density. These results suggest a novel role for Nogo-A in limiting dendritic plasticity after stroke.

Animals↗
PubMed2000

The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease, there can be substantial axonal injury and loss. We therefore hypothesized that adaptive cortical changes may contribute to limiting functional impairment, particularly in the early stages of the disease. To test our hypothesis, we used functional magnetic resonance imaging (MRI) to characterize the localization and volumes of activation in the motor cortex during simple flexion-extension finger movements. There were differences in the patterns of cortical activation with movement between the 12 MS patients and the 12 normal controls. All patients showed greater relative supplementary motor area activation than did the normal controls. The relative hemispheric lateralization of sensorimotor cortex (SMC) activation decreased in direct proportion to the total cerebral T2-weighted MRI hyperintense lesion load. This appeared to be due primarily to increases in ipsilateral SMC activation with increasing lesion load in white matter of the hemisphere contralateral to the limb moved. The center of activation in the contralateral SMC was shifted a mean of 8.8 mm posterior in patients relative to controls, providing additional evidence for cortical adaptive responses to injury. The magnitude of this posterior shift in the SMC activation increased with greater T2 lesion loads. These observations demonstrate that cortical recruitment for simple finger movements can change both quantitatively and qualitatively in the SMCs of MS patients, suggesting that cortical reorganization or "unmasking" of latent pathways can contribute to functional recovery. These adaptive changes are another factor potentially limiting the strength of the relationship between MRI measures of pathology and clinical measures of disability.

Adaptation, Physiological↗
PubMed1997

Functional magnetic resonance imaging of the somatosensory cortex.

Functional magnetic resonance (fMR) imaging, like positron emission tomography (PET), shows regions of activation in the brain resulting from the neuronal activity associated with cognitive, sensory, or motor function. An advantage of fMR imaging is that the functional and the reference anatomic images are acquired simultaneously. Additionally, fMR imaging is generally more available than PET or magnetoencephalography. This article reviews the applications of fMR imaging for studying the sensorimotor cortex prior to craniotomy.

Brain Diseases↗
PubMed2003

Cerebral and cerebellar activation in power and precision grip movements: an H2 15O positron emission tomography study.

SUMMARY: Most human manual grip movements can be divided into power gripping and precision gripping, but central neural control during these tasks remains unclear. We investigated activation of the whole brain to analyze how simple hand movements are performed. The cerebral blood flow of seven healthy right-handed volunteers was measured by H2 15O positron emission tomography during right grip tasks without gripping a target object. Auditory-cued, repetitive power grips (i.e., fist making) and repetitive precision grips (i.e., opposition of the tip of the index finger and the tip of the thumb) were performed at 1.26 Hz. The areas activated during both tasks were the left primary sensorimotor cortex, caudal portion of the dorsal premotor, caudal portion of the supplementary motor area, cingulate motor area, and the right spinocerebellum and intermediate region of the cerebrocerebellum in comparison with the rest state. The analysis of power grip-precision grip tasks showed the activated peaks in the upper portion of the left sensorimotor area and right cerebellar vermis, but these areas were activated in both the tasks [(power grip-rest) and (precision grip-rest)] with uncorrected P < 0.001 as the statistical criterion. With P < 0.05 corrected as the statistical criterion, the results showed no significant activated peaks in regional cerebral blood flow. Our findings indicate no difference in brain activation between the acts of power grip and precision grip without a target object.

Adult↗
PubMed2005

Sensorimotor rhythm-based brain-computer interface (BCI): feature selection by regression improves performance.

People can learn to control electroencephalogram (EEG) features consisting of sensorimotor rhythm amplitudes and can use this control to move a cursor in one or two dimensions to a target on a screen. In the standard one-dimensional application, the cursor moves horizontally from left to right at a fixed rate while vertical cursor movement is continuously controlled by sensorimotor rhythm amplitude. The right edge of the screen is divided among 2-6 targets, and the user's goal is to control vertical cursor movement so that the cursor hits the correct target when it reaches the right edge. Up to the present, vertical cursor movement has been a linear function of amplitude in a specific frequency band [i.e., 8-12 Hz (mu) or 18-26 Hz (beta)] over left and/or right sensorimotor cortex. The present study evaluated the effect of controlling cursor movement with a weighted combination of these amplitudes in which the weights were determined by an regression algorithm on the basis of the user's past performance. Analyses of data obtained from a representative set of trained users indicated that weighted combinations of sensorimotor rhythm amplitudes could support cursor control significantly superior to that provided by a single feature. Inclusion of an interaction term further improved performance. Subsequent online testing of the regression algorithm confirmed the improved performance predicted by the offline analyses. The results demonstrate the substantial value for brain-computer interface applications of simple multivariate linear algorithms. In contrast to many classification algorithms, such linear algorithms can easily incorporate multiple signal features, can readily adapt to changes in the user's control of these features, and can accommodate additional targets without major modifications.

Adult↗
PubMed2004

A critical period for prevention of posttraumatic neocortical hyperexcitability in rats.

Penetrating cortical trauma frequently results in delayed development of epilepsy. In the rat undercut model of neocortical posttraumatic hyperexcitability, suppression of neuronal activity by exposing the injured cortex to tetrodotoxin (TTX) in vivo for approximately 2 weeks prevents the expression of abnormal hypersynchronous discharges in neocortical slices. We examined the relationship between neuronal activity during the latent period after trauma and subsequent expression of hyperexcitability by varying the timing of TTX treatment. Partially isolated islands of rat sensorimotor cortex were treated with Elvax polymer containing TTX to suppress cortical activity and slices obtained for in vitro experiments 10 to 15 days later. TTX treatment was either started immediately after injury and discontinued after a variable number of days or delayed for a variable time after the lesion was placed. Immediate treatment lasting only 2 to 3 days and treatment delayed up to 3 days prevented hyperexcitability. Thus, there is a critical period for development of hyperexcitability in this model that depends on cortical activity. We propose that the hyperexcitability caused by partial cortical isolation may represent an early stage of posttraumatic epileptogenesis. A hypothetical cascade of events leading to subsequent pathophysiological activity is likely initiated at the time of injury but remains plastic during this critical period.

Anesthetics, Local↗
PubMedDate not supplied

The chemical nature of the hypothalamocortical activation underlying drinking behavior.

The injection of cholinergic substances (carbocholine, carbathin [karbatin], acetylcholine) into the lateral field of the hypothalamus of cats is accompanied by the appearance in the electrohypothalamogram of characteristic hypersynchronized activity and drinking behavior. The swallowing of water temporarily stops the hypersynchronized activity; the injection of adrenaline into the hypothalamus elicits the same effect. The injection of the same cholinergic preparations into the posterior sigmoid gyrus of the cerebral cortex is accompanied by similar, but less pronounced bioelectrical and behavioral effects. The presentation of a closed drink dispenser containing water to the animals against the background of cholinergic activation of the hypothalamus or cortex leads to desynchronization of the bioelectrical activity and suppression of the bursts of hypersynchronized activity. The drinking behavior of cats which appears on the basis of centrally created thirst motivation reflects the activity of a primary dominant focus in the hypothalamus and of a secondary dominant focus in the sensorimotor cortex. These foci are cholinergic in nature. The cessation of the drinking behavior may be related to the activation of adrenergic mechanisms of the same brain structures.

Acetylcholine↗
PubMed1994

Tropism and corticospinal target selection in the rat.

Layer V pyramidal cells in the intermediate part of the cerebral cortex enter the lumbar spinal gray, but not the cervical spinal gray matter, during the first postnatal week. To study if the ingrowth of intermediate corticospinal axons into the lumbar spinal gray is guided by a diffusible tropic factor, we co-cultured explants of the intermediate part of the sensorimotor cortex and of the lumbar spinal gray matter in 3-D collagen gels. Using this test system, a target specific directional growth of cortical axons towards the lumbar spinal gray explant can be demonstrated in vitro. Retrograde labeling indicates that most labeled cell bodies were located in layer V of the cortex explant and were characterized by a pyramidal cell shape. Furthermore, axon behavior of retrogradely labeled neurons within the cortical explant is considerably affected by the presence of lumbar spinal gray target tissue. In contrast to lumbar spinal gray innervation, intermediate corticospinal tract axons do not enter the cervical spinal gray in vivo. Is it the inability of intermediate corticospinal tract axons to respond to cervical target-derived influences? In the current study we co-cultured explants of the intermediate cortex and cervical spinal gray matter in 3-D collagen gels. Our data indicate that in vitro axons from layer V neurons in the intermediate part of the cortex are capable of recognizing and responding to a diffusible factor released by the cervical spinal cord target area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Epilepsia partialis continua: active cortical spike discharges and high cerebral blood flow in the motor cortex and enhanced transcortical long loop reflex.

We report a patient suffering from persistent myoclonic jerks in the right forearm without any definite EEG abnormality under routine recording conditions. By computer summation, using the jerk-locked averaging technique, a sharp spike was recognized as a precisely time-locked event in relation to myoclonic twitches. A cranial CT scan revealed a small cortical lesion, which was found very close to the sensorimotor cortex of the right arm. Cerebral blood flow study using the xenon inhalation method revealed a discrete focus of high flow, which corresponded well with the CT lesion. On electrical stimulation of the right median nerve, a large somatosensory evoked potential and an enhanced transcortical long loop reflex were observed. Electrocorticogram showed active focal spike discharges localized at the left precentral gyrus. We postulate that an epileptogenic focus in the motor cortex and an enhanced transcortical long loop reflex appear to be important for the occurrence of epilepsia partialis continua in this patient.

Cerebrovascular Circulation↗
PubMed1993

Functional significance of the mu rhythm of human cortex: an electrophysiologic study with subdural electrodes.

The existence of the mu rhythm and its general anatomical and physiological relationships are well known. There are few data, however, regarding the details of its anatomical and physiological specificity. We implanted fronto-temporal subdural electrode grids in 9 patients with intractable epilepsy to facilitate their surgical management. A 7-11 Hz cortical mu rhythm was observed in 5-16 electrodes located over the sensorimotor cortex as mapped by electrical stimulation. The mu rhythm was blocked by contralateral face and arm movements, passive movements of contralateral arm, and by ipsilateral arm movements. There was correspondence between the body area movement of which blocked the mu at a given site and the body region that was affected by stimulation at the same site. Power spectral analysis showed an overall decrease in power in all frequency bands. This was less prominent in the 14-100 Hz band resulting in a relative increase in high frequency power in association with movement. We conclude that both the presence and blocking of mu rhythm are specific to the somatic representation of the cortex from which it is recorded. Its functional significance may be similar to other sensory rhythms like the occipital alpha rhythm.

Adolescent↗
PubMedDate not supplied

Neurochemical mechanisms of the involvement of cortical sensorimotor neurons in alimentary and orientational behavior.

The object of these experiments was the study of the features of the neurochemical mechanisms of the involvement of individual neurons of the sensorimotor cortex of the rabbit brain the orienting reaction and the goal-oriented alimentary behavior elicited by stimulation of the "hunger center" of the lateral hypothalamus using electrical current of varying intensity. It is demonstrated that the neurotransmitters acetylcholine and norepinephrine, in approximately equal percentages, reorganize the reaction of neurons at the subthreshold as much as at the threshold level of stimulation. The microiontophoretic application to cortical sensorimotor neurons of the protein synthesis blocker, cycloheximide, also elicits alterations in their reactions to threshold and subthreshold stimulation of the lateral hypothalamus which are apparently linked to the suppression of synthesis of neuropeptides specific to both behaviors. It is proposed that the orienting, and especially the alimentary, motivational reactions are achieved by the activation of the synthesis of specific peptide molecules in the cortical sensorimotor neurons, which in fact may induce a change in their sensitivity to neurotransmitters.

Acetylcholine↗
PubMed1983

Origin and sagittal termination areas of cerebro-cerebellar climbing fibre paths in the cat.

Climbing fibre responses were recorded in the cerebellar anterior lobe on stimulation of the cerebral cortex. A zonal pattern was demonstrated in the cortical projection, which was related to the cerebellar sagittal zones, as identified from peripheral climbing fibre input. In all zones, except c2, a co-variation of the responses evoked on peripheral nerve stimulation and on stimulation of the corresponding part of the sensorimotor cortex was found. There was a bilateral projection to the a, b, c2 and d1 zones which also, to a varying extent, receive a bilateral peripheral input. The x, c1 and c3 zones, receiving an ipsilateral peripheral input, were activated exclusively from the contralateral cortex. Stimulation of the posterior sigmoid gyrus (p.s.g.) evoked responses in all the zones. These responses had, in all zones except d1, lower thresholds and shorter latencies than the responses from other cortical areas. Two separate p.s.g. areas were shown to project to the pars intermedia zones (c1, c2, c3 and d1), the lateral area to the caudal parts and the medial area to the rostral parts of the zones. In contrast, the b zone received a projection from only one p.s.g. area, centred between, but overlapping, the two areas projecting to the pars intermedia zones. Stimulation of the anterior sigmoid gyrus evoked short-latency responses in the d1 zone and long-latency responses in all other zones. Stimulation of the first and second somatosensory areas (SI and SII) was generally less effective in evoking climbing fibre responses than was stimulation of the p.s.g. The only exception was the c2 zone, in which responses were evoked from the SII with nearly as low thresholds and short latencies as on p.s.g. stimulation. From the parietal cortex, long-latency responses were regularly evoked in the d1 zone and less frequently in the a, b and c2 zones.

Animals↗
PubMed1999

Spatiotemporal reorganization of electrical activity in the human brain associated with a timing transition in rhythmic auditory-motor coordination.

We used a 61-channel electrode array to investigate the spatiotemporal dynamics of electroencephalographic (EEG) activity related to behavioral transitions in rhythmic sensorimotor coordination. Subjects were instructed to maintain a 1:1 relationship between repeated right index finger flexion and a series of periodically delivered tones (metronome) in a syncopated (anti-phase) fashion. Systematic increases in stimulus presentation rate are known to induce a spontaneous switch in behavior from syncopation to synchronization (in-phase coordination). We show that this transition is accompanied by a large-scale reorganization of cortical activity manifested in the spatial distributions of EEG power at the coordination frequency. Significant decreases in power were observed at electrode locations over left central and anterior parietal areas, most likely reflecting reduced activation of left primary sensorimotor cortex. A second condition in which subjects were instructed to synchronize with the metronome controlled for the effects of movement frequency, since synchronization is known to remain stable across a wide range of frequencies. Different, smaller spatial differences were observed between topographic patterns associated with synchronization at low versus high stimulus rates. Our results demonstrate qualitative changes in the spatial dynamics of human brain electrical activity associated with a transition in the timing of sensorimotor coordination and suggest that maintenance of a more difficult anti-phase timing relation is associated with greater activation of primary sensorimotor areas.

Acoustic Stimulation↗
PubMed1990

[Sexual differences in the interhemispheric asymmetry of the transcallosal responses of the associative areas in the cat neocortex].

Sex differences of hemisphere asymmetry of homo- and heterotopic transcallosal responses in association cortex of 48 cats (24 male and 24 female) immobilized by tubocurarine have been studied by means of topographic EPs recordings in both hemispheres. In males left hemisphere dominates by the amplitude of homotopic and positive wave of heterotopic EPs and right hemisphere dominates by the amplitude of negative wave of heterotopic sensorimotor cortex EPs. The individual asymmetry of EPs has been observed in sensomotor cortex of females and in parietal cortex of animals of both sex. The interhemispheric asymmetry is expressed distinctly in females than in males. It is concluded that sex dimorphism is present in functional organization of associative system of (callosal and intracortical) connections in cat's neocortex projection and association areas which means its more expressed hemisphere lateralization in males with more expressed interhemispheric asymmetry of functional transcallosal connections in females.

Animals↗
PubMed2000

Independent component-cross correlation-sequential epoch (ICS) analysis of high field fMRI time series: direct visualization of dual representation of the primary motor cortex in human.

A new technique for functional magnetic resonance imaging (fMRI) time series analysis is presented. The technique referred to here as independent component-cross correlation-sequential epoch (ICS) analysis is a hybrid technique of two standard methodologies of biological signal analysis, namely, data driven methods, represented by independent component analysis, and hypothesis driven methods, represented by a general linear model. The technique successfully identified four functionally discrete areas within the primary sensorimotor cortex (SMI) in normal human subjects based on blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) time series performed on a high field (3.0 T) system. Each of the four areas identified corresponded to the four physiological subdivisions of SMI, recognized in primates to be essential for voluntary hand motion, namely, 4 anterior (MI-4a) and 4 posterior (MI-4p) of the primary motor cortex, and 3a and the 'classical' (Brodmann areas 1, 2, and 3b) primary sensory cortex, respectively. ICS analysis appears to be a highly reliable and versatile technique for fMRI time series analysis.

Algorithms↗
PubMed1993

Ipsilateral cortical projections to areas 3a, 3b, and 4 in the macaque monkey.

In the macaque monkey area 3a of the cerebral cortex separates area 4, a primary motor cortical field, from somatosensory area 3b, which has a subcortical input mainly from cutaneous mechanoreceptive neurons. That each of these cortical areas has a unique thalamic input was illustrated in the preceding paper. In the present experiments the cortical afferent projections to these 3 areas of the sensorimotor cortex monkey were visualized and compared, using 4 differentiable fluorescent dyes as axonal retrogradely transported labels. The cortical projection patterns to areas 3a, 3b, and 4 were similar in that they each consisted of (a) a "halo" of input from the immediately surrounding cortex, and (b) discrete projections from one or more remote cortical areas. However, the pattern of remote inputs from precentral, mesial, and posterior parietal cortex was different for each of the 3 cortical target areas. The cortical input configuration was least complex for area 3b, its remote input projecting mainly from insular cortex. The pattern of discrete cortical inputs to the motor area 4, however, was more complex, with projections from the cingulate motor area (24c/d), the supplementary motor area, postarcuate cortex, insular cortex, and postcentral areas 2/5. Area 3a, in addition to the proximal projections from the immediately surrounding cortex, also received input from the supplementary motor area, cingulate motor cortex, insular cortex, and areas 2/5. Thus, this pattern of cortical input to area 3a resembled more closely that of the adjacent motor rather than that of the somatosensory area 3b. Contrasting with this, however, the thalamic input to area 3a was largely from somatosensory VPLc (abbreviations from Olszewski [1952] The Thalamus of the Macaca mulatta. Basel: Karger) and not from VPLo (with input from cerebellum, and projecting to precentral motor areas).

Aging↗