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PubMed1985

[Activity of neurons of the motor cortex of the cat during inhibition of a postural change conditioned reflex].

Spike reactions were recorded from motor cortex neurons in cats in the forelimb projection area during external and internal inhibition of the conditioned postural adjustment (transfer of the body weight) of the same limb. Spike responses evoked by external stimulation were of the same character as the responses during conditioned stimulation. As a rule, they were determined by the state of the animal and its habituation to the applied stimulus. Duration of the responses during external stimulation was shorter in trained cats than in untrained ones. Late after-discharges of units and associated conditioned movements disappeared simultaneously during external and internal inhibition. Sometimes the external stimuli were able to depress after-discharges even when the conditioned movements appeared. External stimuli of various modalities inhibited the reflex in different manners. The changes of spike reactions during conditioned posture adjustment resembled those during well learned local conditioned events.

Animals↗

PubMed2003

Functional somatotopy of finger representations in human primary motor cortex.

To assess the degree of fine-scale somatotopy within the hand area of the human primary motor cortex (M1), functional mapping of individual movements of all fingers was performed in healthy young subjects (n = 7) using MRI at 0.8 x 0.8 mm2 resolution and 4 mm section thickness. The experimental design comprised both a direct paradigm contrasting single digit movements vs. motor rest and multiple differential paradigms contrasting single digit movements vs. the movement of another digit. Direct mapping resulted in largely overlapping activations. A somatotopic arrangement was only recognizable when considering the mean center-of-mass coordinates of individual digit representations averaged across subjects. In contrast, differential paradigms revealed more segregated and somatotopically ordered activations in single subjects. The use of center-of-mass coordinates yielded inter-digit distances ranging from 2.0 to 16.8 mm, which reached statistical significance for pairs of more distant digits. For the middle fingers, the functional somatotopy obtained by differential mapping was dependent on the choice of the digit used for control. These results confirm previous concepts that finger somatotopy in the human M1 hand area emerges as a functional predominance of individual digit representations sharing common areas in a distributed though ordered network.

Adult↗

PubMed2000

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

PubMed2004

fMRI signal decreases in ipsilateral primary motor cortex during unilateral hand movements are related to duration and side of movement.

Interactions between the primary motor cortices of each hemisphere during unilateral hand movements appear to be inhibitory, although there is evidence that the strengths of these interactions are asymmetrical. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of motor task duration and hand used on unilateral movement-related BOLD signal increases and decreases in the hand region of primary motor cortex (M1) of each hemisphere in six right-handed volunteers. Significant task-related BOLD signal decreases were observed in ipsilateral M1 during single and brief bursts of unilateral movements for both hands. However, these negative-to-baseline responses were found to intensify with increasing movement duration in parallel with greater task-related increases in contralateral M1. Movement-related BOLD signal decreases in ipsilateral M1 were also stronger for the right, dominant hand than for the left hand in our right-handed subjects. These findings would be consistent with the existence of interhemispheric interactions between M1 of each hemisphere, whereby increased neuronal activation in M1 of one hemisphere induces reduced neuronal activity in M1 of the opposite hemisphere. The observation of a hemispheric asymmetry in inhibition between M1 of each hemisphere agrees well with previous neuroimaging and electrophysiological data. These findings are discussed in the context of current understanding of the physiological origins of negative-to-baseline BOLD responses.

Adult↗

PubMed1986

A correlative electron microscopic study of basket cells and large GABAergic neurons in the monkey sensory-motor cortex.

Large basket cells were identified in Golgi and horseradish peroxidase labeled material from the sensory-motor cortex of adult monkeys. Their morphology was correlated at the light and electron microscopic level with large comparable cells stained immunocytochemically for glutamate decarboxylase. In Golgi-impregnated material these cells have a very large cell body and dendrites that extend through several layers of the cortex with a predominant vertical orientation. The axon is only stained for a few micrometers. The same cells studied electron microscopically in serial sections after gold-toning show very distinctive ultrastructural characteristics: the cell bodies contain a large number of organelles, the nuclei are rounded with homogeneously dispersed chromatin and synapsing onto the somata are many axon terminals, both symmetrical and asymmetrical but the symmetrical type forms 70-80% of the total; dendrites also receive a large number of both symmetrical and asymmetrical synaptic contacts. All the axons of basket cells become myelinated and the Golgi labeling of the initial segments is interrupted at the commencement of the first myelin internode. The axon initial segments receive several symmetrical synaptic contacts in the proximal one-third of their length. The axonal arborization of a basket cell retrogradely labeled in the somatosensory cortex after intracortical injection of horseradish peroxidase was analyzed in detail. The mainly horizontal axonal collaterals of this cell are myelinated for most of their trajectory and have a preferred orientation in the anteroposterior dimension. These axonal collaterals, although very long (more than 1.8 mm), at intervals give rise to a small number of short unmyelinated terminal branches that bear a series of boutons terminaux forming a multi-terminal ending. The multi-terminal endings surround somata and proximal dendrites of pyramidal and non-pyramidal cells. Dense pericellular terminations (baskets or nests) like those drawn by Ramón y Cajal and Marin-Padilla are not formed by the axon of a single basket cell. Thus, basket formations are presumably formed by converging axons from several basket cells. Immunocytochemical material was stained for glutamate decarboxylase, the enzyme involved in the synthesis of gamma-aminobutyrate (GABA). This shows that large glutamate decarboxylase-positive neurons of the same size as those positively identified as basket cells in the Golgi and horseradish peroxidase material have virtually the same morphological characteristics, at both the light and electron microscope levels, as the basket cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways.

We explored interhemispheric facilitation (IHF) between (a) left and right primary motor cortex (M1) and (b) left dorsal premotor (dPM) and right M1 in 20 right-handed healthy human subjects using a paired pulse transcranial magnetic stimulation (TMS) protocol. A conditioning TMS pulse (CP) applied to left M1 or dPM with an intensity of 80% and 60% active motor threshold (CP(80%AMT) and CP(60%AMT), respectively) was followed by a test pulse (TP) over right M1 induced by anterior-posterior- or posterior-anterior- (TP(AP), TP(PA)) directed currents in the brain at interstimulus intervals (ISIs) of 3-8 and 10 ms. EMG was recorded from left first dorsal interosseous muscle. In the main experimental condition IHF was evoked by CP(80%AMT) over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP(80%AMT) produced IHF at an ISI of 8 ms when applied over left dPM but only with TP(PA). In addition, when CP(60%AMT) was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TP(PA), indicating that IHF elicited over dPM was not caused by current spread of the conditioning pulse to M1. We conclude that IHF can be induced differentially by conditioning M1 and dPM using subthreshold CP. These facilitatory interactions depended on the intensity and ISI of the CP as well as the current flow direction of the TP. We suggest that not only do the CPs activate separate anatomical pathways but also that these pathways project to different populations ofinterneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.

Adult↗

PubMed1996

Conditioning lower limb H-reflexes by transcranial magnetic stimulation of motor cortex reveals preserved innervation in SCI patients.

Conditioning of lower limb H-reflexes by transcranial magnetic stimulation of motor cortex was used to detect preserved innervation in patients with long-standing spinal cord injury (SCI). Cortical stimulation was delivered at intensities suprathreshold or subthreshold for evoking motor evoked potentials (MEPs). The conditioning (C) cortical stimulation preceded the test (T) H-reflex stimulus at intervals between C-T: 10-300 msec. Conditioned H-reflex profiles in control subjects (n = 10), following both suprathreshold and subthreshold cortical conditioning, yielded evidence of early (C-T: 10-30 msec) and late arriving (C-T: 60-130 msec) excitatory inputs to the lateral gastrocnemius (LG) motoneuron pool. Demonstration of late inputs following subthreshold cortical conditioning suggested the inputs are mediated by slow conducting or oligosynaptic descending motor tracts, as distinct from afferent consequences of short latency MEPs. In SCI patients (n = 11) the conditioned H-reflex profile varied according to the patients' ASIA impairment rating. Higher functioning SCI patients (ASIA level C and D) revealed evidence of both early and late arriving inputs to the lumbosacral motoneuron pool whereas patients with more severe impairments (ASIA levels A and B) most often failed to exhibit early or late periods of H-reflex facilitation in LG. In three patients (i.e., 1 ASIA B; 2 ASIA C) the cortical modulation of H-reflex amplitudes yielded evidence of preserved corticospinal innervation that was not detectable by other MEP reinforcement procedures. These results introduce the cortical conditioning procedure as a sensitive means of detecting latent corticospinal and/or bulbospinal innervation in SCI patients consistent with the emerging neuropathological picture of preserved axonal integrity in descending motor tracts in the face of extensive functional loss.

Adult↗

PubMed2006

Nonuniform distribution of reach-related and torque-related activity in upper arm muscles and neurons of primary motor cortex.

The present study examined the activity of primate shoulder and elbow muscles using a novel reaching task. We enforced similar patterns of center-out movement while the animals countered viscous loads at their shoulder, elbow, both joints, or neither joint. Accordingly, we could examine reach-related activity during the unloaded condition and torque-related activity by comparing activity across load conditions. During unloaded reaching the upper arm muscles exhibited a bimodal distribution of preferred hand direction. Maximal reach-related activity occurred with hand movements mostly toward or away from the body. Arm muscles also exhibited a bimodal distribution of their preferred torque direction. Maximal torque-related activity typically occurred with shoulder-extension/elbow-flexion torque or shoulder-flexion/elbow-extension torque. Similar biases in reach-related and torque-related activity could be reproduced by optimizing a global measure of muscle activity. These biases were also observed in the neural activity of primary motor cortex (M1). The parallels between M1 and muscular activity demonstrate another link between motor cortical processing and the motor periphery and may reflect an optimization process performed by the sensorimotor system.

Algorithms↗

PubMed1997

The motor syndrome associated with exaggerated inhibition within the primary motor cortex of patients with hemiparetic.

Following transcranial magnetic stimulation (TMS) at stimulation strength of 1.5 times the resting motor threshold, a silent period (SP) of approximately 180 ms duration can be observed in surface EMG-registrations of tonically activated small hand muscles. This SP is believed to be generated cortically and can be prolonged in stroke patients, but it is not known whether a prolongation of the SP has any functional significance. In order to answer the question of whether enhanced cortical inhibition can contribute to pathophysiology of motor dysfunction we studied stroke patients with clearly prolonged SP durations in the first dorsal interosseus muscle (> 2 times that of the intact side), but with normal magnetically evoked motor potentials. Sixteen patients out of a cohort of 174 consecutive patients presenting with acute hemiparetic stroke fulfilled the inclusion criteria. Serial TMS investigations were performed for up to 2 years post-stroke. In all patients, the SP duration decreased in parallel with clinical improvement. In two patients, intermittent clinical deterioration was accompanied by an increase in the SP duration. In four patients, in addition to a markedly prolonged SP duration, the phenomenon of a complete inability to initiate voluntary muscle activity for several seconds, following TMS, could be observed in a number of trials ('motor arrest'). Detailed clinical analysis revealed that, in addition to hemiparesis, distinct motor disturbances in patients with SP prolongation could be observed. These motor disturbances resembled those of motor neglect and were characterized by motivationally dependent under-utilization of the affected arm, impairment of movement initiation, inability to maintain a constant force level and to scale forces, and impairment of individual finger movements. In 12 of the 16 patients at least one additional behavioural manifestation of neglect was present. We suggest that in stroke patients severe motor dysfunction may be caused by hyperactivity of cortical inhibitory interneurons rather than by direct lesions of descending motor tracts. Cortical hyperinhibition may, in turn, result from damage to any of a number of afferent pathways to the motor cortex which modulate local interneuronal activity.

Adult↗

PubMed2006

Mapping phantom movement representations in the motor cortex of amputees.

Limb amputation results in plasticity of connections between the brain and muscles, with the cortical motor representation of the missing limb seemingly shrinking, to the presumed benefit of remaining body parts that have cortical representations adjacent to the now-missing limb. Surprisingly, the corresponding perceptual representation does not suffer a similar fate but instead persists as a phantom limb endowed with sensory and motor qualities. How can cortical reorganization after amputation be reconciled with the maintenance of a motor representation of the phantom limb in the brain? In an attempt to answer this question we explored the relationship between the cortical representation of the remaining arm muscles and that of phantom movements. Using transcranial magnetic stimulation (TMS) we systematically mapped phantom movement perceptions while simultaneously recording stump muscle activity in three above-elbow amputees. TMS elicited sensations of movement in the phantom hand when applied over the presumed hand area of the motor cortex. In one subject the amplitude of the perceived movement was positively correlated with the intensity of stimulation. Interestingly, phantom limb movements that the patient could not produce voluntarily were easily triggered by TMS, suggesting that the inability to voluntarily move the phantom is not equivalent to a loss of the corresponding movement representation. We suggest that hand movement representations survive in the reorganized motor area of amputees even when these cannot be directly accessed. The activation of these representations is probably necessary for the experience of phantom movement.

Amputation Stumps↗

PubMed1999

Effects of voluntary contraction on descending volleys evoked by transcranial electrical stimulation over the motor cortex hand area in conscious humans.

The spinal volleys evoked by electric anodal and cathodal stimulation over the cerebral motor cortex hand area were recorded from a bipolar electrode inserted into the cervical epidural space of two conscious human subjects. We measured the size of volleys elicited by electric stimulation at active motor threshold and at 3% of maximum stimulator output above this value with subjects at rest and during maximum voluntary contraction of the contralateral first dorsal interosseous muscle. Surface EMG activity was recorded at the same time. Electrical anodal stimulation evoked a single negative wave that we termed D-wave in analogy with data in experimental animals. Cathodal stimulation evoked a single negative wave with a latency of 0.2 ms longer than the D-wave recruited by anodal stimulation. At both intensities tested, voluntary contraction did not modify the amplitude of the descending waves. We conclude that changes in cortical excitability induced by voluntary activity do not modify the corticospinal volley evoked by electric stimulation and that the D-waves evoked by both anodal and cathodal electric stimulation are probably initiated several nodes distant to the cell body.

Adult↗

PubMed2004

Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex.

OBJECTIVE: To study the after effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on corticospinal excitability. METHODS: Eight healthy volunteers received either 150 or 1800 stimuli of 5 Hz rTMS on two separate days in a counterbalanced order. rTMS was given over the 'motor hot spot' of the right first dorsal interosseus (FDI) muscle using an intensity of 90% of resting motor threshold (referred to as subthreshold rTMS). We evaluated the amplitude of the motor-evoked potential (MEP), short-latency intracortical inhibition (SICI), short-latency intracortical facilitation (SICF), and cortical silent period (CSP) before and for about 30 min after rTMS. MEPs were recorded from the right FDI muscle and abductor digiti minimi (ADM) muscle. RESULTS: 1800 stimuli induced an increase in MEP amplitude in the relaxed FDI muscle, but not in the relaxed ADM muscle. This facilitatory after effect was stable for at least 30 min. Prolonged 5 Hz rTMS had no effect on the relative magnitude of SICI and SICF. 150 stimuli caused no lasting modulation of MEP amplitudes in either muscle. In a subgroup of 5 subjects, 900 conditioning stimuli caused only a short-lived MEP facilitation. 5 Hz rTMS did not modify the duration of the CSP during tonic contraction. CONCLUSIONS: A single session of subthreshold 5 Hz rTMS to the M1 can induce a long-lasting and muscle-specific increase in resting corticospinal excitability. However, a sufficient number of conditioning stimuli is necessary to produce persistent corticospinal facilitation.

Adult↗

PubMed2003

Reorganization in the ipsilateral motor cortex of patients with lower limb amputation.

The aim of the present study was to assess reorganization in the motor cortex of patients with lower limb amputation. We studied seven patients with traumatic lower limb amputation, and six healthy controls, using transcranial magnetic stimulation mapping, with recordings from the quadriceps femoris muscle on both sides. Motor threshold, sum of amplitudes, area and the amplitude-weighted centre of gravity (COG) of the motor output map were assessed. We found a significant lateral displacement of the COG on the hemisphere contralateral to the healthy leg, whereas other parameters did not differ significantly between sides. This finding might be indicative of cortical reorganization in the hemisphere ipsilateral to the amputation. It is discussed with respect to an altered peripheral input to this hemisphere, and to transcallosal interactions from the deafferented hemisphere.

Adaptation, Physiological↗

PubMed2002

Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex.

OBJECTIVE: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability. METHODS: The study consisted of two separate experiments. Subjects received a 10 min long subthreshold 1 Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed. RESULTS: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10 min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15 min following the train. Intra-cortical inhibition was not significantly affected. CONCLUSIONS: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS.

Adult↗

PubMed1997

Positron emission tomography during motor cortex stimulation for pain control.

We studied regional changes in cerebral flood flow (rCBF) in 9 patients undergoing motor cortex stimulation (MCS) for pain control. Significant increase in rCBF was observed in the lateral thalamus ipsilateral to MCS probably reflecting corticothalamic connections from motor/premotor areas. Subsignificant increases were observed in the anterior cingulate, left insula and upper brainstem. Mean rCBF in the anterior cingulate increased during MCS in patients with good analgesic efficacy, while it decreased in those with poor clinical outcome; conversely, thalamic rCBF increased in the two groups, albeit to a greater extent in patients with good clinical results. Our results support a model of MCS action whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in other pain-related structures, including the anterior cingulate and the periaqueductal gray. MCS could influence the affective-emotional component of chronic pain by way of cingulate activation, and lead to descending inhibition of pain impulses by activation of the brainstem. Such effects may be obtained only if thalamic activation reaches a 'threshold' level, below which the analgesic cascade would not be successfully triggered.

Adult↗

PubMed1988

Topographical organization of the thalamic afferent connections to the motor cortex in the cat.

The topographical distribution of the cortical afferent connections to the different subdivisions of the motor cortex (MC) was studied in adult cats. The retrograde axonal transport of horseradish peroxidase technique was used. Small single injections of the enzyme were made in the entire MC, including the hidden regions in the depth of the sulcus cruciatus. The areal location and density of the subsequent thalamic neuronal labeling were evaluated in each case. Comparison of the results obtained in the various cases shows that the following: (1) The ventral anterior-ventral lateral complex is the principal thalamic source of afferents to the MC. (2) The ventral medial, dorsal medial, the different components of the posterior thalamic group (lateral, medial, and ventral posteroinferior and suprageniculate nuclei), and the intralaminar, lateral anterior, lateral intermediate, lateral medial, and anteromedial thalamic nuclei are also thalamic sites in which neural projections to the MC arise. (3) The thalamocortical projections to the MC are sequentially organized. The connections arising from the lateral part of the thalamus end in the region of area 4 that is situated medially in the superior lip of the sulcus cruciatus and in the posterior sigmoid gyrus. The projections originating in the most medial thalamic regions terminate in that region of area 6a beta which is located in the medial part of the inferior lip of the cruciate sulcus, and in the anterior sigmoid gyrus. Moreover, the ventral thalamic areas send connections to the most anteriorly located zones of the MC, while the most dorsal thalamic ones project to the most posteriorly located parts of the MC. (4) This shift in the thalamocortical connections is not restrained by cytoarchitectonic boundaries, either in the thalamus or in the cortex. (5) The populations of thalamocortical cells which project to neighboring MC subdivisions exhibit consistent overlapping among themselves. (6) These findings suggest, moreover, that the basal ganglia and the cerebellar projections to the MC through the thalamus are arranged in a number of parallel pathways, which may occasionally overlap.

Animals↗

PubMed1999

Facial nerve injury produces a latent somatosensory input through recruitment of the motor cortex in the rat.

Short-latency effects of unilateral facial nerve transection were studied on neuronal activation evoked in the primary motor cortex (MI) on both sides by vibrissa stimulation in adult rats. In the controls, unilateral trigeminal stimulation evoked activity in the whisker representation of both the contralateral somatosensory cortex (SI) and MI, but never in the ipsilateral MI. Unilateral transection of the facial motoric nerve facilitated evoked responses in the contralateral MI, and induced further neuronal activation (gross potentials and unit activity) in the MI ipsilateral to the stimulation. Since these changes appeared rapidly and could be mimicked by picrotoxin application onto the SI contralateral to the stimulation, they are considered to be based on the disinhibition of preexisting associative and commissural connections, which are unmasked by facial nerve transection.

Animals↗

PubMed2001

Neural activity in primary motor cortex related to mechanical loads applied to the shoulder and elbow during a postural task.

Whole-arm motor tasks performed by nonhuman primates have become a popular paradigm to examine neural activity during motor action, but such studies have traditionally related cell discharge to hand-based variables. We have developed a new robotic device that allows the mechanics of the shoulder and elbow joints to be manipulated independently. This device was used in the present study to examine neural activity in primary motor cortex (MI) in monkeys (Macaca mulatta) actively maintaining their hand at a central target as they compensated for loads applied to the shoulder and/or elbow. Roughly equal numbers of neurons were sensitive to mechanical loads only at the shoulder, only at the elbow, or loads at both joints. Neurons possessed two important properties. First, cell activity during multi-joint loads could be predicted from its activity during single-joint loads as a vector sum in a space defined by orthogonal axes for the shoulder and elbow. Second, most neurons were related to flexor torque at one joint coupled with extensor torque at the other, a distribution that paralleled the observed activity of forelimb muscles. These results illustrate that while MI activity may be described by independent axes representing each mechanical degree-of-freedom, neural activity is also strongly influenced by the specific motor patterns used to perform a given task.

Action Potentials↗