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PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗
PubMed2000

Coherence between cerebellar thalamus, cortex and muscle in man: cerebellar thalamus interactions.

Local field potentials (LFPs) were recorded in seven unanaesthetized patients between the four adjacent contacts of a macroelectrode stereotactically implanted for the treatment of tremor. The LFPs were presumed to arise predominantly from the nucleus ventralis intermedius (Vim) of the thalamus, the implantation target. They were recorded simultaneously with the ipsilateral EEG and contralateral EMG during an isometric contraction or at rest. The patients had a history of either isolated tremor (essential tremor, n = 2; benign tremulous Parkinson's disease, n = 1) or tremor with signs of a cerebellar syndrome (multiple sclerosis, n = 3; essential tremor and ataxia, n = 1), although clinical tremor was absent at the time of recording because of a temporary microthalamotomy effect in four patients. In patients with isolated tremor, oscillatory activity picked up by contacts in Vim (cerebellar thalamus) was invariably coherent with that in the sensorimotor cortex or contracting muscle in the 8-27 Hz range. Such coherence was absent in two of the four subjects with tremor associated with a cerebellar syndrome. Coherence between LFPs recorded from more caudally placed contacts and the sensorimotor cortex or contracting muscle was negligible in all patients. These caudally placed contacts demonstrated the highest sensory evoked potential in response to median nerve stimulation. Oscillatory activity in the cerebellar thalamus (Vim) lagged behind that in both cortex and muscle. Coherent activity between the cerebellar thalamus (Vim) and the cortex persisted at rest. It is suggested that rhythmicities in the 8-27 Hz range could provide the basis for a temporal framework that is widely distributed within the motor system.

Aged↗
PubMed2004

Time course of changes in brain activity and functional connectivity associated with long-term adaptation to a rotational transformation.

The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was 1 week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within 3 days. During early stages of adaptation, better performance was associated with greater activity in brain areas related to attention including bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen, and a nonmotor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions toward the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus, and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions, but also in the strengthening and maintenance of specific functional connections.

Adaptation, Physiological↗
PubMed1997

Distributed neural systems underlying the timing of movements.

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).

Adolescent↗
PubMedDate not supplied

[Motor polarization dominance and "animal hypnosis"].

Two kinds of dominanta were simultaneously formed under conditions of chronic experiments in rabbits. The motor polarization dominanta was formed under exposure of the right sensorimotor cortex of an animal to direct anodic current, and the state of "animal hypnosis" (the second dominanta) was induced. Animal behavior and electrophysiological characteristics were recorded. It was shown that the "animal hypnosis" induced at the optimum of the right motor polarization dominanta inhibited the motor reaction of the "dominant" extremity to testing stimuli. After the "animal hypnosis session, exposure of the right sensorimotor cortex to anodic current produced the latent excitation focus, which did not reach the level of summation. Two days later, exposure to testing stimuli developed the latent foci at first in the right cortex and then in subcortical structures. In the course of recovery of the motor polarization dominanta and its further change for the state characteristic of the "animal hypnosis", the patterns of cortical EEG coherence in the delta range typical of each kind of dominanta alternated in parallel with the time course of state changes.

Animals↗
PubMed1984

Distribution of corticospinal neurons with collaterals to lower brain stem reticular formation in cat.

The fluorescent retrograde double-labeling technique has been used to determine whether corticospinal neurons in the cat sensorimotor cortex distribute collaterals to the lower brain stem reticular formation. In this study the fluorescent tracers Nuclear Yellow and Diamidino Yellow 2HCl were used in combination with Fast Blue. One tracer was injected unilaterally in the spinal cord and the other was injected ipsilaterally in the bulbar medial reticular formation. The distribution of the retrogradely labeled neurons was studied in the contralateral hemisphere. In the sensorimotor cortex a large population of neurons was found which were labeled from the spinal cord and were double-labeled from the brain stem. These branching neurons were concentrated in the rostromedial part of the area 4 and the adjoining lateral part of area 6. In this region the percentages of corticospinal neurons which were double-labeled from the brain stem ranged from 5% laterally to 30% medially. In two cats it was demonstrated by means of the anterograde transport of HRP that the corticobulbar fibers from this region which must include the corticospinal collaterals are distributed to the reticular formation of the lower brain stem. In view of the fact that the double-labeled neurons are concentrated in the anterior part of the motor cortex, those branching neurons are in all likelihood involved in the control of neck, back and shoulder movements. This control is probably exerted by way of two routes i.e. by way of the direct corticospinal connections to spinal interneurons, and by way of the indirect cortico-reticulospinal connections established by the cortical fibers to the bulbar reticular formation. The present findings suggest that this dual control may be exerted by one and the same cell.

Animals↗
PubMed2000

Organization of cortical activities related to movement in humans.

The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.

Arm↗
PubMed1995

Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy.

Intracortical injection of iron ions has been used as a model of posttraumatic epilepsy. Oxidation of lipids in neural membranes by reactive oxygen species, especially hydroxyl radicals (OH), is involved in the mechanisms responsible for iron-induced seizures. We examined the scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on OH radicals and superoxide (O2.-) using an electron spin resonance (ESR) spectrometer, and the occurrence of epileptic discharges in electrocorticogram (ECoG) induced by FeCl3 injection into the sensorimotor cortex of rats. Though DMPO-O2.- spin adducts generated by the hypoxanthine-xanthine oxidase system were not quenched by Ado or Cl-Ado, 5 mM of each showed a quenching effect on DMPO-OH spin adducts (5.3 x 10(16) spins/ml) generated by the Fenton reagent. In ECoG of rats, spike discharges appeared 15-45 min after FeCl3 injection (500 nmol) into the sensorimotor cortex, and polyspikes and/or ictal patterns were observed 70-90 min after the injection. Cl-Ado (1 mg/kg) or Ado (5 mg/kg) injected intraperitoneally 30 min prior to the FeCl3 injection suppressed or delayed the occurrence of epileptic discharges induced by FeCl3. Cl-Ado and Ado may suppress the occurrence of epileptic discharges by scavenging OH and by their anticonvulsant effect.

2-Chloroadenosine↗
PubMed1986

Modulation of transmission in rostral trigeminal sensory nuclei during chewing.

Eighty-one sensory neurons in the rostral trigeminal sensory nuclei (main sensory nucleus, nucleus oralis, and the lateral border zone of the motor nucleus) were recorded in urethan-anesthetized rabbits before and during mastication. Receptive-field characteristics were described, and responses evoked by electrical stimulation of the inferior alveolar and infraorbital nerves, sensorimotor cortex, and thalamus were recorded. Forty-four percent of neurons were stimulated by the movements of mastication; nevertheless, evidence is presented that the excitability of the 49 neurons that receive low-threshold mechanoreceptor inputs is depressed during mastication for the following reasons: The spontaneous activity of seven cells was inhibited during movement. The probability of firing in response to stimulation of the peripheral nerve on sensorimotor cortex was decreased during mastication. There was usually a corresponding increase in the latency of the action potentials. Injections of local anesthetic (prilocaine hydrochloride, 4%) into the receptive field of the neuron did not prevent the decrease in excitability during mastication. Fourteen neurons that received inputs from periodontal pressoreceptors were recorded medial to most of the low-threshold group. The excitability of six of these was reduced during jaw closure and during the occlusal phase of movement, that is, within the period in which they would be activated by pressure on the teeth. The rest were tonically suppressed. Eighteen neurons recorded in the lateral border zone of the motor nucleus had receptive fields that were of high threshold or were undefined. They responded to stimulation of the peripheral nerve at high threshold. The excitability of most of these neurons was strongly phase modulated during mastication. They were most excitable during jaw closure or during the occlusal phase of movement and inexcitable during opening. The excitability of the others was tonically depressed. In most cases, the changes in excitability described did not seem to be due to the patterns of activity of the neurons that were generated by the movements. We conclude that the pattern elaborated by the central pattern generator includes selective modifications of sensory transmission. One reason for this is to suppress reflex responses to low-threshold inputs while maintaining the protective response to tissue damage.

Alveolar Process↗
PubMed1997

[Functional brain mapping in motor task and somatosensory stimulation using echo planar MRI].

Functional brain mapping was performed with a 1.5T clinical MRI apparatus. Single shot gradient echo echo-planar imaging (EPI) sequence was employed. Normal volunteers were studied with the task of grasping hand or opposition of fingers at the frequency of 3 Hz, median nerve electro-stimulation, pure somatosensory stimulation by roller for acupuncture. Apparent signal increase was observed at contralateral sensorimotor cortex with motor task. Signal changes delayed about 5 seconds compared with the start and the cessation of the task, which may suggest that regional changes of CBF and blood oxygen level in capillary and/or in venule lag behind electrical excitation. It was hard to detect the activated area with median nerve electro-stimulation. On the other hand, roller stimulation provoked distinct activated areas at contralateral sensorimotor cortex. The activated areas caused by the roller stimulation and the motor task coincided entirely, which suggests the possibility of the intermixed localization of primary areas of motor and somatosensory. It was also clearly demonstrated that the activated area was broader with quick (3 Hz) and complicated motor task (finger opposition) than with slow (1Hz) and simple motor task (hand grasping).

Adult↗
PubMed2001

Functional magnetic resonance imaging of reorganization in rat brain after stroke.

Functional recovery after stroke has been associated with brain plasticity; however, the exact relationship is unknown. We performed behavioral tests, functional MRI, and histology in a rat stroke model to assess the correlation between temporal changes in sensorimotor function, brain activation patterns, cerebral ischemic damage, and cerebrovascular reactivity. Unilateral stroke induced a large ipsilateral infarct and acute dysfunction of the contralateral forelimb, which significantly recovered at later stages. Forelimb impairment was accompanied by loss of stimulus-induced activation in the ipsilesional sensorimotor cortex; however, local tissue and perfusion were only moderately affected and cerebrovascular reactivity was preserved in this area. At 3 days after stroke, extensive activation-induced responses were detected in the contralesional hemisphere. After 14 days, we found reduced involvement of the contralesional hemisphere, and significant responses in the infarction periphery. Our data suggest that limb dysfunction is related to loss of brain activation in the ipsilesional sensorimotor cortex and that restoration of function is associated with biphasic recruitment of peri- and contralesional functional fields in the brain.

Animals↗
PubMed2000

Cortical myoclonus and cerebellar pathology.

OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve the cerebellar system, but there has only been one report of cerebellar pathology in a patient in whom cortical myoclonus was physiologically characterized antemortem. METHODS: Cortical somatosensory evoked potentials (SEPs) were recorded and EEG activity was averaged preceding myoclonic electromyographic activity. In one patient cortico-cortical inhibition was tested using two paired ipsilateral magnetic stimuli over the motor strip. Neuropathologic examination was carried out, including linear Purkinje cell densities/millimeter calculations for different regions of the cerebellum. RESULTS: The electrophysiology showed evidence of dysfunction of the sensorimotor cortex with enlarged SEPs and a time-locked cortical potential preceding the action myoclonus. In addition, motor cortical inhibition was abnormal in one case. Pathology showed unremarkable primary sensory, motor, and premotor cerebral cortices, except for unilateral gliosis of the motor cortex in one case. The cerebellum showed patchy atrophy and ongoing degeneration. A striking feature was the greater severity of Purkinje cell loss and Bergmann gliosis in the outer aspects than in the depths of the folia. CONCLUSIONS: Pathologic abnormalities are paradoxically mainly located in the cerebellum in some patients with cortical myoclonus, despite clear electrophysiologic evidence of cortical dysfunction. This observation suggests that enhanced excitability of the sensorimotor cortex may arise as a distant effect of cerebellar pathology.

Adult↗
PubMed2005

Human brain structures related to plantar vibrotactile stimulation: a functional magnetic resonance imaging study.

The purpose of this study was to investigate the sensorimotor cortex response to plantar vibrotactile stimulation using a newly developed MRI compatible vibration device. Ten healthy subjects (20-45 years) were investigated. Vibrotactile stimulation of the sole of the foot with a frequency of 50 Hz and a displacement of 1 mm was performed during fMRI (echo-planar imaging sequence at 1.5 T) using an MRI compatible moving magnet actuator that is able to produce vibration frequencies between 0 and 100 Hz and displacement amplitudes between 0 and 4 mm. The fMRI measurement during vibrotactile stimulation of the right foot revealed brain activation contralaterally within the primary sensorimotor cortex, bilaterally within the secondary somatosensory cortex, bilaterally within the superior temporal, inferior parietal, and posterior insular region, bilaterally within the anterior and posterior cingular gyrus, bilaterally within the thalamus and caudate nucleus, contralaterally within the lentiform nucleus, and bilaterally within the anterior and posterior cerebellar lobe. The advantages of the new MRI compatible vibration device include effective transmission of the stimulus and controlled vibration amplitudes, frequencies, and intensities. The results indicate that plantar vibration can be a suitable paradigm to observe activation within the sensorimotor network in fMRI. Furthermore, the method may be used to determine the optimal responsiveness of the individual sensorimotor network.

Adult↗
PubMed1999

Activity-dependent competition between developing corticospinal terminations.

In cats, each sensorimotor cortex has bilateral corticospinal (CS) terminations during early postnatal life, with contralateral terminations denser than ipsilateral ones. Subsequent development depends on neural activity: silencing CS neurons on one side results in development of sparse terminations from that side and dense bilateral terminations from the active side. In this study we determined whether activity-dependent competition between CS terminations is important in shaping their development. We compared the effect of bilateral sensorimotor cortex activity blockade (activity deprivation alone, without competition) on CS development, with that produced by unilateral blockade (activity deprivation with competition). We found that the extent of the spinal gray matter labeled is substantially greater when the motor cortex on each side is silenced rather than when only one side is silenced. These findings support the hypothesis that competition between developing CS terminations is important in shaping the topography of CS connections.

Animals↗
PubMed1993

Immature corticospinal neurons respond to axotomy with changes in tubulin gene expression.

We have examined the expression of two different tubulin mRNAs in hamster corticospinal neurons that were axotomized at three different developmental stages; postnatal day 8 (P8), P20, and adult. In situ hybridization of histological sections of the sensorimotor cortex was done with 35S-labeled cDNA probes specific to alpha 1-tubulin and beta III-tubulin mRNAs at 2-14 days following unilateral transection of the corticospinal tract in the caudal medulla. Both film and emulsion autoradiography were used to detect changes in tubulin mRNA levels. Qualitative assessment indicated substantial decreases in both alpha 1-tubulin and beta III-tubulin mRNA levels in layer V neurons of the sensorimotor cortex following axotomy. The changes were apparent as early as 2 days postinjury for P20 and adult operates, but not for P8 operates. However, by 14 days postinjury, decreases in alpha 1-tubulin and beta III-tubulin gene expression were apparent in animals operated at all three developmental stages. These findings indicate that both immature and adult corticospinal neurons respond to axonal injury in a manner that is distinctly different from the peripheral neuron response.

Animals↗
PubMed1990

Neural damage in the rat thalamus after cortical infarcts.

Histopathologic changes in the thalamus of 23 rats after somatosensory cortical infarction produced by middle cerebral artery occlusion were examined using the Fink-Heimer silver staining method, immunohistochemistry with antibodies against glial fibrillary acidic protein and laminin, and conventional stains. Middle cerebral artery occlusion produced cortical infarcts in the lateral parietal region, with variable involvement of the frontoparietal parasagittal sensorimotor cortex. Within 3 days after occlusion, massive terminal degeneration but no neuronal changes were apparent in the ipsilateral thalamus. By 1 week after occlusion, abnormal neurons with darkly stained, shrunken nuclei and atrophic perikarya were present in the ipsilateral thalamic nuclei. These neurons were densely argyrophilic in Fink-Heimer sections. Rats with small lateral parietal cortical lesions had degenerating neurons limited to the medial ventroposteromedial nucleus. Large lesions involving the parasagittal sensorimotor cortex resulted in widespread neuronal damage in the ventroposteromedial, ventroposterolateral, intralaminar, and posterior nuclear regions but nowhere else. Immunoreactivity to laminin antibody decreased, and astrocytic proliferation was abundant in affected thalamic areas. These findings are consistent with retrograde neuronal degeneration due to thalamocortical fiber damage in ischemic cortical regions. Such lesions remote from the infarct may influence functional recovery in patients with stroke.

Animals↗
PubMed2000

The role of the supplementary motor area in externally timed movement: the influence of predictability of movement timing.

A significant role in the planning and preparation for voluntary movement has been ascribed to secondary motor areas located on the medial wall of the cerebral hemispheres, and in particular to the supplementary motor area (SMA). Within the SMA, rostral and caudal subdivisions have been described, and differential roles have been attributed to these regions in relation to movement planning, preparation and execution. We have used functional magnetic resonance imaging (fMRI) to investigate the role of the SMA in the timing of movement execution, by recording the fMRI signal from mesial pre-motor areas and primary sensorimotor cortex (SM1) during the execution of a simple motor task externally cued at predictable (regular) and unpredictable (irregular) time intervals. The mean rate of movement was matched in both experiments. There was a greater activation of caudal than rostral SMA with both predictably and unpredictably cued movements, and a doubling of the signal when the timing of the motor response was unpredictable. In contrast, there was no difference in the activation of primary sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA has an important role in the execution of externally cued movements. The results also suggest a greater role for this region in the performance of unpredictably timed compared with predictably timed movements, however a model is proposed (based on electrophysiological data) which shows how the difference in functional signal in these two situations can be explained on the basis of a difference in the time course of neuronal activation in the SMA, rather than in the overall degree of activation.

Adult↗
PubMed1986

The persistence of a normally transient cerebrocerebellar pathway in the cat.

A direct, although transient, projection from the sensorimotor cortex to the cerebellum has been described previously in the neonatal kitten. The present report demonstrates that this pathway can be induced to persist into juvenile stages of the cat by partially denervating the deep cerebellar nuclei. Most of the cerebellar cortex on one side was removed in kittens within the first week after birth, but the deep cerebellar nuclei were preserved, in an effort to destroy most of the input into the deep nuclei. After 6-11 weeks the remaining white matter and deep nuclei on the lesioned side were injected with WGA-HRP in most of the animals, while a few received injections of either WGA-HRP or HRP in the sensorimotor cortex ipsilateral to the lesion. Results from these experiments showed that the normally transient cerebrocerebellar pathway persisted to some degree in young adults lesioned as neonates. However, the functional significance of this pathway, as well as other transient pathways, is still unknown.

Animals↗