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Changes in the discharge patterns of cat motor cortex neurones during unexpected perturbations of on-going locomotion.

1. The impulse activity of single neurones in the forelimb part of the motor cortex was recorded extracellularly in unrestrained cats during self-paced locomotion on a horizontal circular ladder. 2. Fifty-one cells (forty-nine of which discharged rhythmically in time with the step cycle) were recorded during encounters with a number of rungs that could be locked firmly in position or, alternatively, held in position by weak springs so that when stepped on they unexpectedly descended (under the weight of the animal) from 1 to 5 cm before contacting a mechanical stop. 3. In eleven cells (22%) including four fast-axon pyramidal tract neurones (PTNs), an increase in discharge occurred when the contralateral forelimb descended unexpectedly. Onset latency relative to the start of rung movement ranged from ca 20 to ca 100 ms. In eight cells latency was such that most of the response preceded contact of the rung with the stop; averaged over a number of trials the altered discharge in five of these cells (including two PTNs) represented an accurate profile of the averaged velocity of rung (and foot) descent. The three remaining cells appeared to be responding largely to the cessation of rung movement. 4. Thirty-six of the cells were also studied during unexpected descent of the ipsilateral forelimb and six (17%) displayed an increase in discharge (onset latency ca 35 to ca 80 ms); three of these were among those that also responded to contralateral descents. 5. These findings for skilled locomotion requiring a high degree of visuomotor coordination are discussed and it is concluded that the motor cortex is rapidly informed regarding unexpected perturbations delivered to the contralateral forelimb at the onset of stance and that changes are evoked in the pattern of impulse traffic descending via the pyramidal tract.

Animals↗

Transcranial stimulation of the leg area of the motor cortex in humans.

We used transcranial magnetic stimulation on nine normal volunteers to establish an effective way to stimulate the leg area of the motor cortex. Three types of coils: a large figure-eight coil, small figure-eight coil, and a round coil were used. Surface electromyographic activities were recorded from the left tibialis anterior muscle, and the latencies and amplitudes compared with those obtained by anodal electrical stimulation. The most stable responses were obtained when the large figure-eight coil was centered over the vertex and backward current was run through it or when the round coil was centered two to three centimeters anterior to the vertex with left-flowing current in it at the posterior widening. The latencies obtained under these stimulation conditions were the same as those obtained by electrical stimulation. We conclude that direct activation of the pyramidal cells occurs in the leg area of the motor cortex in all forms of magnetic and electrical stimulation.

Electric Stimulation↗

Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis.

Abnormal balance between intracortical inhibitory and excitatory mechanisms has been found to contribute to the genesis of motor cortex hyperexcitability in amyotrophic lateral sclerosis (ALS), but data are lacking on the role of these abnormalities in the pathophysiology of the disease. We evaluated the resting motor threshold (RMT), the cortical silent period (CSP) to single-pulse transcranial magnetic stimulation (TMS), early intracortical inhibition (ICI), early intracortical facilitation (ICF) and late ICI to paired-pulse TMS in 40 patients with ALS. These parameters were correlated with disease duration and clinical features. They were also monitored over time in selected patients. The main abnormal TMS findings were: (a). reduced or even absent early and late ICI; six out of 9 patients, with normal early ICI at the first recording, developed abnormal ICI after several months; (b). reduced cortical silent period duration with increasing TMS intensity. ICF and RMT were not affected. Impairment of early and late ICI correlated significantly with disease duration, the diagnostic categories and the clinical evidence of upper motor neuron involvement. The alteration of different cortical inhibitory functions seems to take place with disease progression, rather than being the primary event in the pathogenesis of ALS. The impaired inhibition is considered as being due to both depletion of specific subpopulations of intracortical GABAergic neurons and mechanisms involved in motor cortex reorganization following progressive neuronal loss. Clarification of the importance of these factors in the pathogenesis of the disease may have diagnostic and therapeutic implications.

Adult↗

Rate-coding of spinal motoneurons with high-frequency magnetic stimulation of human motor cortex.

Rate-coding in spinal motoneurons was studied using high-frequency magnetic stimulation of the human motor cortex. The subject made a weak contraction to cause rhythmic (i.e., tonic) discharge of a single motor unit in flexor (or extensor) carpi radialis or tibialis anterior, while the motor cortical representation of that muscle was stimulated with brief trains of pulses from a Pyramid stimulator (4 Magstim units connected by 3 BiStim modules). An "m@n" stimulus train consisted of m number of pulses (1-4), with an interpulse interval (IPI) of n ms (1-6). Peristimulus time histograms were constructed for each stimulus condition of a given motor unit, and related to the average rectified surface electromyography (EMG) from that muscle. Surface EMG responses showed markedly more facilitation than single-pulse stimulation, with increasing numbers of pulses in the train; responses also tended to increase in magnitude for the longer IPI values (4 and 6 ms) tested. Motor-unit response probability increased in a manner comparable to that of surface EMG. In particular, motoneurons frequently responded twice to a given stimulus train. In addition to recruitment of new motor units, the increased surface EMG responses were, in part, a direct consequence of short-term rate-coding within the tonically discharging motoneuron. Our results suggest that human corticomotoneurons are capable of reliably following high-frequency magnetic stimulation rates, and that this activity pattern is carried over to the spinal motoneuron, enabling it to discharge at extremely high rates for brief periods of time, a pattern known to be optimal for force generation at the onset of a muscle contraction.

Action Potentials↗

Functional magnetic resonance imaging is more reliable than somatosensory evoked potential or mapping for the detection of the primary motor cortex in proximity to a tumor.

The accurate localization of the primary motor cortex (M1) is critical for the preservation of motor function during resection of brain tumors in and around the M1. The goal of the present study was to determine which technique provided the most accurate localization of M1. The accuracy of preoperative functional magnetic resonance imaging (fMRI), intraoperative somatosensory evoked potential (SEP) and cortical mapping for the localization of M1 was determined in 17 patients with brain tumors in and around the M1. Because localization of the M1 is typically symmetrical in the cerebral hemispheres, the M1 on the affected side was localized by determination of the M1 location on the unaffected side using fMRI with patient hand clenching. The location of M1 was successfully determined by SEP in 5 of 11 cases. In the remainder of cases, the sulcus at which phase reversal occurred during SEP was shifted 1 or 2 gyri rostral to the central sulcus. The location of M1 was successfully determined by brain mapping in 9 of 15 cases. In the remainder of cases, stimulation failed to elicit a motor response. Finally, the location of M1 was successfully determined by fMRI in 16 of 17 cases. These data indicate that fMRI was more reliable than SEP or brain mapping for the detection of M1 in proximity to a tumor.

Adult↗

One-hertz subthreshold rTMS increases the threshold for evoking inhibition in the human motor cortex.

Despite indisputable evidence that repetitive transcranial magnetic stimulation (rTMS) modulates motor cortical excitability, the effects of subthreshold low-frequency rTMS on intracortical inhibition (ICI) are controversial. In this paper we investigated whether increasing the level of baseline ICI increases the sensitivity of ICI for disclosing the after-effects of rTMS on cortical excitability. In experiment 1, we studied changes in ICI, tested at two different baseline levels, after a train of 900 subthreshold rTMS pulses delivered at 1 Hz. In experiment 2, we studied whether the same conditioning rTMS train changed the ICI threshold, and in experiment 3 whether it changed the facilitatory I-wave interaction. Conditioning rTMS reduced ICI tested at a baseline level of 75% but left ICI tested at a baseline level of 50% unchanged. It also increased the ICI threshold but left the facilitatory I-wave interaction unchanged. These findings suggest that conditioning rTMS selectively reduced ICI tested at a baseline level of 75% by increasing the threshold for evoking inhibition in the motor cortex. The inhibitory system mediating ICI may therefore be more efficient than other motor cortical systems in reducing high cortical excitability after external intervention. Hence studies investigating the after-effects of rTMS should standardize ICI levels at baseline.

Adult↗

Painful supernumerary phantom arm following motor cortex stimulation for central poststroke pain. Case report.

In this report, the authors describe a case in which the patient began to experience a supernumerary phantom arm after she received motor cortex stimulation for central pain. The patient had a history of right thalamocapsular stroke. It is speculated that the motor cortex activation triggered a response in the patient's parietal lobe, precipitating perception of the phantom limb. To the authors' knowledge this is the first reported case of its kind.

Cerebrovascular Disorders↗

Neuronal plasticity induced by self-stimulation rewarding experience in rats--a study on alteration in dendritic branching in pyramidal neurons of hippocampus and motor cortex.

Self-stimulation rewarding experience promoted structural changes in pyramidal neurons of the CA3 region of the hippocampus and the Vth layer of the motor cortex in adult male Wistar rats. Self-stimulation experience was allowed for 1 h daily for a duration of 10 days through bipolar electrodes placed bilaterally in lateral hypothalamus and substantia nigra--ventral tegmental area. At the end of 10 days, rats were sacrificed, and rapid Golgi examination of the CA3 hippocampal and layer V pyramidal neurons of the motor cortex was made for a grand total of 1600 neurons from 80 rats divided into 4 groups. The neurons of the self-stimulation experienced (SS) group revealed a significant (ANOVA, F-test) increase in dendritic branching in the perisomatic domains. Such changes were not observed in neurons of sham control (SH), experimenter administered stimulation (EA) and normal control (NC) groups. SS animals also showed a significant increase in the thickness of lacunosum and radiatum laminae of CA3 neurons of the hippocampus. Our results reveal that both limbic and neocortical neurons undergo changes in dendritic branching patterns due to self-stimulation rewarding experience. It is tempting to hypothesize that neuronal plasticity is the result of motivation and learning experienced by rats which underwent self-stimulation.

Animals↗

Two modes of corticospinal reinnervation occur close to spinal targets following unilateral lesion of the motor cortex in neonatal hamsters.

Although it has been shown that unilateral neonatal cortical ablation induces bilateral corticospinal projections, the explanation for the pathways responsible for this bilateral innervation remains controversial. We hypothesized that such reinnervation may be supplied from newly formed fibers sprouting at the level rostral to, or at, or caudal to the pyramidal decussation. In order to test our hypothesis, we examined the brain and spinal cord of young hamsters which had a unilateral ablation of the right motor cortex at six days postnatally, and then received an injection of an anterograde neuronal lectin tracer, Phaseolus vulgaris-leucoagglutinin, into the hindlimb area of the left motor cortex at 21 days postnatally. For the identification of motoneurons in the lumbar spinal cord, some of these animals also received an injection of cholera toxin subunit B, a retrograde tracer, into the gastrocnemius muscle. A quantitative analysis in the left gray matter of the lumbar spinal cord indicated that the lectin labeling was two to eight times higher in cortically ablated animals than in intact animals. Immunohistochemical detection of the lectin revealed that innervation of the left spinal cord occurred close to targets at lower levels in the spinal cord. Two modes of reinnervation (types I and II) by the intact corticospinal tract were recognized. The type I fibers consisted of recrossing axon collaterals sprouted from the intact dorsal funiculus near their targets, while the type II fibers were recrossing parent axons which entered the intact, right gray matter several levels rostral to their targets, and then changed direction toward the targets. The recrossing at lower spinal levels yielded a large number of ipsilaterally labeled axons and their terminals in the gray matter of the denervated lumbar cord, with a distribution pattern similar to that seen on the intact side. The present results indicate that such ipsilateral innervation may play an important role in the sparing and recovery of function following neonatal hemicortical injury.

Animals↗

Dexterity is not affected by fatigue-induced depression of human motor cortex excitability.

Following a fatiguing muscle contraction, motor evoked potentials (MEPs) evoked by transcranial magnetic brain stimulation remain depressed for many minutes, reflecting a reduction in the excitability of the corticospinal projection. No functional significance has been linked to this observation. We postulated that dexterity would be affected when MEPs are depressed. MEPs were recorded from the first dorsal interosseous muscle of 11 healthy subjects in resting muscles before and after a fatiguing maximum voluntary contraction. This induced significant MEP depression in all subjects. No change in dexterity was seen when MEPs were depressed or at any time point throughout the experiment. We conclude that fatigue-induced MEP depression is not associated with a decline in dexterity.

Adult↗

Motor cortex excitability in patients with cerebellar degeneration.

OBJECTIVES: To study motor cortex (M1) excitability and the effect of subthreshold transcranial magnetic stimulation (TMS) in patients with cerebellar degeneration and normals performing a reaction time (RT) task. METHODS: Time to wrist flexion after a visual go-signal was measured. TMS was always delivered at 90% of resting motor evoked potential (MEP) threshold. In one experiment, test TMS was delivered at various intervals after the go-signal. In half the trials priming TMS was also given with the go-signal. A second experiment examined the effect on RT of M1 and occipital priming stimulation alone. RESULTS: M1 excitability, measured as the likelihood of producing MEPs in the wrist flexor muscles, increased immediately after the go-signal in the patients and stayed high until movement. In controls, excitability rose gradually. This difference was largely eliminated by priming TMS. RT was longer in the patient group, but improved with priming TMS. Occipital priming produced less effect on RT than M1 stimulation in both controls (P=0.008) and patients (P=0.0004). CONCLUSIONS: M1 excitability prior to movement in an RT task increases abnormally early in cerebellar patients. This may reflect compensation for deficient thalamocortical drive. Subthreshold TMS can partially normalize the prolonged RT and abnormal excitability rise in cerebellar patients.

Adult↗

Functional imaging of human motor cortex at high magnetic field.

1. We used conventional gradient echo magnetic resonance imaging (MRI) at high field strength (4 Tesla) to functionally image the right motor cortex in six normal human subjects during the performance of a sequence of self-paced thumb to digit oppositions with the left hand (contralateral task), the right hand (ipsilateral task), and both hands (bilateral task). 2. A localized increase in activity in the lateral motor cortex was observed in all subjects during the task. The area of activation was similar in the contralateral and bilateral tasks but 20 times smaller in the ipsilateral task. The intensity of activation was 2.3 times greater in the contralateral than the ipsilateral task.

Adult↗

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study.

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.

Journal Article↗

Distribution of cortical fibers and fos immunoreactive neurons in ventrolateral medulla and in nucleus tractus solitarius following the motor cortex stimulation in the rat.

The present study demonstrates that the motor cortex (MC) stimulation induces expression of Fos-like immunoreactivity (FLI) in the rostro-caudal parts of ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). The coupling of biotinylated dextran (BD) injections with the MC stimulation also permits to identify cortical labeled fibers in the vicinity of FLI neurons in the VLM. Results suggest that the MC is involved in a direct and an indirect modulation of bulbar cardiovascular nuclei.

Animals↗

Segregation of lemniscal inputs and motor cortex outputs in cat ventral thalamic nuclei: application of a novel technique.

A double labeling method that permits accurate delineation of the terminals of medial lemniscal fibers was used to determine whether thalamic neurons projecting to motor cortex in the cat are in a position to be contacted by such terminals. Thalamic neurons in the VL nucleus were retrogradely labeled by injections of fluorogold placed in the cytoarchitectonically defined area 4, while lemniscal axons and their terminal boutons were anterogradely labeled, in a Golgi-like manner, from injections of Fast Blue placed under physiological control in different parts of the contralateral dorsal column nuclei. In additional experiments, spinothalamic fibers were similarly labeled by injections of Fast Blue in the spinal cord. The results reveal that there is no significant overlap in the distributions of lemniscal terminals and motor cortex-projecting neurons and that no somata or proximal dendrites of motor cortex-projecting neurons are in a position to receive lemniscal terminals. Spinothalamic terminals, on the other hand, end in clusters around motor cortex-projecting neurons in the VL nucleus as well as in other nuclei and are a more likely route for short latency somatosensory inputs to the motor cortex.

Amidines↗

Modulation of primary orthostatic tremor by magnetic stimulation over the motor cortex.

OBJECTIVES: To study the role of corticomotor neuronal pathways in primary orthostatic tremor. METHODS: Transcranial magnetic stimuli at an intensity 10% above the resting motor threshold were delivered over the leg motor cortex in two patients with primary orthostatic tremor while standing still. Electromyographic responses in both tibialis anterior muscles were recorded after 20 stimuli given randomly at intervals of 120 to 180 seconds. Differences between predicted and actual times of occurrence of tremor bursts after the stimuli were used to calculate a resetting index, with a value of 0 representing no resetting and a value of 1 representing complete resetting. RESULTS: Transcranial magnetic stimulation evoked EMG responses in both tibialis anterior muscles, followed by transient suppression of tremor before reappearance of rhythmic EMG activity. Analysis of the timing of tremor bursts from EMG recordings before and after the magnetic stimuli disclosed that the phase of orthostatic tremor could be reset by brain stimulation (mean resetting indices 0.93 and 0.82). CONCLUSION: The results suggest that a central oscillator, involving the motor cortex, has a crucial role in either the generation or modulation of orthostatic tremor.

Electromyography↗

Spatial segregation of different modes of movement control in the whisker representation of rat primary motor cortex.

What is mapped on the surface of the primary motor cortex (M1)? The classic somatotopic map holds true on the level of limb representations. However, on the small scale (at within-limb representations), neither somatotopy nor movement dynamics/kinematics seem to be organizational principles. We investigated the hypothesis that integrated into the body representation of M1 there may be separate representation of different modes of motor control, using different subcortical computations but sharing the same motor periphery. Using awake rats and long intracortical stimulation trains in M1 whisker representation (wM1) revealed that natural-like, rhythmic whisking (normally used for tactile exploration) can be evoked from a posteromedial subregion of wM1. Nonrhythmic whisker retraction, on the other hand, was evoked in an adjacent but more anterolaterally located region within wM1. Evoked whisker retraction was always accompanied by complex movements of the face, suggesting that the respective subregion is able to interact with other representations in specific behavioral contexts. Such associations were absent for evoked rhythmic whisking. The respective subregion rather seemed to activate a downstream central pattern generator, the oscillation frequency of which was dependent on the average evoked cortical activity. Nevertheless, joint stimulation of the two neighboring subregions demonstrated their potency to interact in a functionally useful way. Therefore, we suggest that the cause of cortical separation is the specific drive of subcortical structures needed to generate different types of movements rather than different behavioral contexts in which the movements are performed.

Animals↗

Interhemispheric asymmetries of motor cortex excitability in the postacute stroke stage: a paired-pulse transcranial magnetic stimulation study.

BACKGROUND AND PURPOSE: Changes in the intracortical inhibition (ICI) and facilitation (ICF) of motor cortex paired-pulse transcranial magnetic stimulation were reported in the affected (AH) and unaffected (UH) hemispheres of stroke patients and reflect some of the mechanisms related to motor cortex plasticity and different degrees of functional recovery. The interhemispheric differences of the ICI/ICF slopes have been found to have a nearly identical time course in the 2 hemispheres of healthy subjects, and whether such symmetry is modified after monohemispheric stroke has not yet been examined. Our goal was to investigate the interhemispheric asymmetries of the time course of ICI/ICF between the AH and UH of stroke patients in the postacute phase of recovery. METHODS: ICI/ICF recovery curves to subthreshold-conditioning suprathreshold-test magnetic stimuli were recorded from the paretic and nonparetic hand muscles of 10 well-recovered stroke patients and compared with those of a population of 10 control subjects. RESULTS: In the healthy subjects, ICI/ICF showed a symmetrical time evolution between the 2 hemispheres. In stroke patients, the ICI/ICF slopes were significantly different between the UH and AH; the intracortical inhibition was reduced in the AH and normal in the UH. CONCLUSIONS: The defective AH ICI associated with the effective UH ICI could represent a marker of poststroke cortical plasticity implicated as a mechanism relevant to functional recovery. Analysis of the interhemispheric asymmetries of the ICI/ICF recovery curves might provide a valuable neurophysiological parameter in the prognosis and follow-up of patients with monohemispheric stroke.

Acute Disease↗