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Suppression of the motor cortex by magnetic stimulation of the cerebellum.

Conditioning magnetic stimulation of the cerebellum suppresses the motor cortex 5-8 ms later, probably through activation of cerebellar Purkinje cells, which inhibit the dentatothalamocortical pathway. To further characterize this pathway, we examined several factors that may modulate its excitability. We tested the effects of different test motor evoked potential (MEP) amplitudes, voluntary activation of the target muscle, and arm extension that required activation of proximal arm muscles while maintaining relaxation of hand muscles. Surface electromyography was recorded from the right first dorsal interosseous (FDI) muscle. A double-cone coil centered 3 cm lateral to the inion was used for right cerebellar stimulation. The stimulus intensity was set at 5% below the threshold for activation of the corticospinal tract. A figure-of-eight coil was used for left motor cortex stimulation. Interstimulus intervals (ISIs) between 3 and 15 ms were studied. Small test MEPs of about 0.5 mV were markedly inhibited at ISIs of 5-8 ms, but there was much less inhibition for test MEPs of about 2 mV. There was no significant MEP suppression during voluntary activation of the FDI muscle or during right arm extension. Left arm extension did not affect inhibition. Our findings indicate that cerebellar stimulation has a much stronger effect on motor cortex neurons activated near threshold intensities than those activated at higher intensities. Activation of contralateral but not ipsilateral proximal arm muscles during arm extension reduced the excitability of the cerebellothalamocortical projections to the hand area of the motor cortex.

Adult↗

Role of motor cortex in coordinating multi-joint movements: is it time for a new paradigm?

Reaching movements to spatial targets require motor patterns at the shoulder to be coordinated carefully with those at the elbow to smoothly move the hand through space. While the motor cortex is involved in this volitional task, considerable debate remains about how this cortical region participates in planning and controlling movement. This article reviews two opposing interpretations of motor cortical function during multi-joint movements. On the one hand, studies performed predominantly on single-joint movement generally support the notion that motor cortical activity is intimately involved in generating motor patterns at a given joint. In contrast, studies on reaching demonstrate correlations between motor cortical activity and features of movement related to the hand, suggesting that the motor cortex may be involved in more global features of the task. Although this latter paradigm involves a multi-joint motor task in which neural activity is correlated with features of movement related to the hand, this neural activity is also correlated to other movement variables. Therefore it is difficult to assess if and how the motor cortex contributes to the coordination of motor patterns at different joints. In particular, present paradigms cannot assess whether motor cortical activity contributes to the control of one joint or multiple joints during whole-arm tasks. The final point discussed in this article is the development of a new experimental device (KINARM) that can both monitor and manipulate the mechanics of the shoulder and elbow independently during multi-joint motor tasks. It is hoped that this new device will provide a new approach for examining how the motor cortex is involved in motor coordination.

Animals↗

Distribution of calbindin-D28K immunoreactive neurons in rat primary motor cortex.

Distribution of calbindin-D28K immunoreactive cells in the primary motor area of the adult rat neocortex was studied in the present experiment. In the primary motor cortex, calbindin-D28K immunoreactivity was found in two populations of cortical neurons. One was composed of neurons heavily labeled with anti-calbindin antibody, which were present in two bands corresponding to cortical layers II-III, and V. The morphological types of these cells were varied; they had oval, fusiform or mutiangular somata. The proximal dendrites of the heavily stained cells showed that these cells were non-pyramidal neurons, and they were either bitufted or multipolar cells. The other was a weakly stained population, mainly concentrated in layers II and III, that also contained pyramidal neurons. In addition, one outstanding feature of the neuropil staining deep to layer II was the labeling of the long, vertically oriented bundles of immunoreactive processes. Such a distinct pattern of calbindin-D28K immunoreactive neurons in the primary motor cortex suggests a relatively high density of calcium channels exists in the superficial layers of the rat primary motor cortex.

Animals↗

Further evidence to support different mechanisms underlying intracortical inhibition of the motor cortex.

Paired-pulse magnetic stimulation has been widely used to study intracortical inhibition of the motor cortex. Inhibition at interstimulus intervals (ISIs) of 1-5 ms is ascribed to a GABAergic inhibitory system in the motor cortex. However, Fisher et al. have proposed that different mechanisms are operating at an ISI of 1 ms and 2.5 ms. In order to confirm their concept and clarify whether inhibition at all these intervals is produced by a single mechanism, we compared effects of paired-pulse stimulation at ISIs of 1 ms, 2 ms, and 3-5 ms. We evaluated how intracortical inhibition affected the I3-wave, I1-wave, magnetic D-wave, and anodal D-wave components of electromyographic (EMG) responses using previously reported methods. The data suggest that three separate effects occur within these ISIs. At ISIs of 3-5 ms, inhibition was evoked only in responses to I3-waves, whereas no inhibition was elicited in responses to I1-waves or magnetic D-waves. In contrast, at an ISI of 1 ms, responses to I3-waves and I1-waves were moderately suppressed. Moreover, even magnetic D-waves were slightly suppressed, whereas anodal D-waves were unaffected. At an ISI of 2 ms, none of the descending volleys were inhibited. We propose that we should use ISIs of 3-5 ms for estimating function of the GABAergic inhibitory system of the motor cortex by paired-pulse transcranial magnetic stimulation (TMS). Our results support the idea of Fisher et al. that the mechanism responsible for the inhibition at an ISI of 1 ms is not the same as that responsible for suppression at ISIs of 3-5 ms (GABAergic inhibitory circuits in the motor cortex). At an ISI of 2 ms, we suggest that the inhibitory influence evoked by the first stimulus (S1) should collide with or be occluded by the second stimulus (S2), which leads to the lack of inhibition when the subjects make a voluntary contraction of the target muscle.

Adult↗

Resection of intrinsic tumors from nondominant face motor cortex using stimulation mapping: report of two cases.

We report two right-handed patients who underwent resection of intrinsic glial tumors from the nondominant hemisphere, face motor cortex. Both patients underwent preoperative assessment with computed tomography and magnetic resonance imaging localizing the tumor in the inferior region of the Rolandic cortex. With the patients under general anesthesia and without muscular paralysis, the tumor volume was determined by intraoperative ultrasound and resective surgery accomplished with the aid of cortical and subcortical stimulation mapping techniques. Radical resection of the tumor from the face motor cortex was achieved in both patients. A transient contralateral facial weakness and apraxia were noted in each patient, and this resolved within 6 to 8 weeks following surgery. Removal of intrinsic tumors involving the nondominant face motor cortex may be safely achieved using brain mapping techniques to localize inferior Rolandic cortex and avoid resection of the hand motor cortex and descending subcortical motor pathways. Permanent disability will be prevented due to the bilateral representation of face motor function at the neocortical level. However, due to language localization in cortical zones contiguous with the dominant hemisphere, face motor cortex, we do not recommend resection of this region.

Adolescent↗

[The spike reactions of the motor cortex neurons of old rabbits to specific stimuli].

Spike reactions of motor cortex neurons to tactile and electrocutaneous stimulation of a forelimb were studied in aged (6-7-year old) rabbits. As compared with young adult animals, the neuronal reactions to afferent stimuli were rarely recorded in the motor cortex of aged rabbits (66.7 and 50%, respectively). The activation manifested in increasing firing rate over its spontaneous level was less intensive than in young animals. The neuronal reactions of aged animals were characterized by the slower activation with longer latencies and slower development of spike responses. The parameters of slow activation could be partly corrected by the iontophoretic application of acetylcholine to the soma region. Neuronal inhibition recorded in the motor cortex of aged rabbits was not markedly changed compared to inhibition reactions in young animals. It is suggested that impairment of the functional state of dendrites in aging is responsible for the changes observed.

Acetylcholine↗

Modulation of motor cortex excitability by median nerve and digit stimulation.

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200-600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation.

Adult↗

Epidural motor cortex stimulation with functional imaging guidance.

Chronic epidural motor cortex stimulation (MCS) has been shown to have promise in the treatment of patients with refractory deafferentation pain. Precise placement of the electrode over the motor cortex region corresponding to the area of pain is essential for the success of this procedure. Whereas standard anatomical landmarks have been used in the past in conjunction with image guidance, the use of functional brain imaging can be beneficial in the precise surgical planning. The authors report the use of functional imaging-guided frameless stereotactic surgery for epidural MCS. Five patients underwent MCS in which functional imaging guidance was used. Prior to surgery, patients underwent magnetic resonance (MR) imaging with skin fiducial markers placed on standard anatomical reference prints, followed by magnetoencephalography (MEG) mapping of the sensory and motor cortices. In two patients, functional MR imaging was also performed using a motor task paradigm. The functional imaging data were integrated into a frameless stereotactic database by using a three-dimensional coregistration algorithm. Subsequently, a frameless stereotactic craniotomy was performed using the integrated anatomical and functional imaging data for surgical planning. Intraoperative somatosensory evoked potentials (SSEPs) and direct stimulation were used to confirm the target and final placement of the electrode. Direct stimulation and SSEPs performed intraoperatively confirmed the accuracy of the functional imaging data. Trial periods of stimulation successfully reduced pain in three of the five patients who then underwent permanent internal placement of the system. At a mean 6-month follow up, these patients reported an average reduction in pain of 55% on a visual analog scale. The integration of functional and anatomical imaging data allows for precise and efficient surgical planning and may reduce the time necessary for intraoperative physiological verification.

Humans↗

Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain.

OBJECTIVE: To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. METHODS: In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz. RESULTS: At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief. CONCLUSION: Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.

Adult↗

Somatotopic mapping of the primary motor cortex in humans: activation studies with cerebral blood flow and positron emission tomography.

1. The somatotopic representation of the human primary motor cortex was examined noninvasively with estimates of cerebral blood flow (CBF) obtained with positron emission tomography. Twelve normal subjects performed a motor tracking task with the arm, first finger, tongue, and great toe commensurate with the bolus injection of radioactive H215O. Images of the relative percent increase of blood flow, compared with control studies, demonstrated reproducible foci of CBF increases in the motor cortex in every subject. Each motor task could be localized to a predictable site on a coronal section containing the precentral gyrus. 2. In reproducibility experiments of repeated measures, it was determined that two foci of activation in the primary motor cortex could be discriminated with a 95% confidence if they were separated by 5.4 mm. 3. In five subjects with matched magnetic resonance imaging studies, the sites of activation were variable with respect to surface anatomy and could be found at the depth of sulci or the surface of gyri. The findings were similar to previously reported electrophysiological studies using direct cortical stimulation. 4. The method may be applied to the in vivo functional mapping of the primary motor cortex in patients with cerebral disorders.

Adult↗

Effect of isoflurane on motor-evoked potentials induced by direct electrical stimulation of the exposed motor cortex with single, double, and triple stimuli in rats.

BACKGROUND: The clinical application of intraoperative motor-evoked potentials (MEPs) has been hampered by their sensitivity to anesthetics. Recently, to overcome anesthetic-induced depression of myogenic MEPs, multiple stimulus setups with a paired or a train of pulses for stimulation of the motor cortex were reported. However, the effects of anesthetics on MEPs induced by these stimulation techniques are unknown. METHODS: Bipolar electrical stimulation of the left motor cortex was carried out in 15 rats anesthetized with thiopental while the compound muscle action potentials were recorded from the contralateral hind limb. After recording of the MEP in response to the single-shock stimulation of the motor cortex, paired pulses (double pulses) or a train of three pulses (triple pulses) with an interstimulus interval of each pulse at 0.3, 0.5, 1.0, 1.5, and 2.0 ms were applied. After control MEP recording, isoflurane was administered at a concentration of 0.25 minimum alveolar anesthetic concentration (MAC), 0.5 MAC, 0.75 MAC, and 1.0 MAC, and the effects of isoflurane on the MEPs induced by single, double, and triple pulses were evaluated. RESULTS: In all animals, distinct baseline MEPs were recorded. During the administration of 0.25 MAC and 0.5 MAC isoflurane, MEPs induced by stimulation with a single pulse could be recorded in 87% and 33% of animals, respectively, and MEP amplitude was significantly reduced in a dose-dependent manner. During the administration of 0.75 MAC isoflurane, MEPs after single-pulse stimulation could not be recorded in any animals. By stimulating with paired or triple pulses, the success rate of MEP recording and MEP amplitude significantly increased compared with those after single pulse before and during the administration of isoflurane. Both the success rate of MEP recording and MEP amplitude after double- and triple-pulse stimulation decreased significantly in a dose-dependent manner during the administration of isoflurane. CONCLUSIONS: Application of double or triple stimulation of the motor cortex increases the success rate of MEP recording and its amplitude during isoflurane anesthesia in rats. However, these responses are suppressed by isoflurane in a dose-dependent manner.

Action Potentials↗

Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans.

We explored the aftereffects of two premotor 1 Hz rTMS sessions on motor cortex excitability in healthy humans. In experiment 1, 11 healthy right-handed volunteers received 20-min submotor threshold 1 Hz rTMS trains over the left premotor cortex on 2 consecutive days. Left motor cortex excitability was determined at baseline, immediately after, 30, 60, 120 min, and 24 h after each rTMS session. We measured motor thresholds, amplitudes of motor-evoked potentials, silent periods, and paired-pulse excitability at interstimulus intervals (ISI) of 3-7, 10, and 15 ms. In experiment 2, 5 volunteers received two identical rTMS trains on Days 1 and 7. Measurements were carried out on Day 1 (first rTMS train), Day 2, and Day 7 (second rTMS train). In experiment 1 there was a selective increase of paired pulse facilitation at an ISI of 7 ms after rTMS lasting for less than 30 min on Day 1. This effect was also present after rTMS on Day 2. However, it persisted for at least 2 h. In experiment 2 the same extra facilitation was induced by rTMS on Days 1 and 7 but not on Day 2. It lasted for less than 30 min on both Day 1 and Day 7. We conclude that 1 Hz premotor rTMS leads to cumulative plastic changes of intrinsic motor cortex excitability when repeated within 24 h but not after 1 week, implying the formation of memory after the first rTMS train lasting more than a day but less than a week.

Adult↗

A frequency analysis of neuronal activity in monkey thalamus, motor cortex and electromyograms in wrist oscillations.

1. Extracellular recordings were made in three monkeys while recording from neurones in the motor cortex (eighty-four cells), ventro-posterior lateralis pars caudalis (VPLc, forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. This experiment was designed to produce active and reflex movements of varying velocities in order to study the relationship between amplitude of velocity and magnitude of neuronal discharge of thalamic neurones. The active movements were voluntary rapid alternating movements (RAMs) of the wrist and the reflex movements were produced by forcibly oscillating the wrist joint between frequencies of 1 and 7 Hz (forced oscillations). 3. This study was also designed to examine cerebellar influences on a reflex path, namely the transcortical reflex loop. Forced oscillations were predicted to provide circumstances where active damping was required to prevent excessive oscillations in the reflex path. Rapid alternating movements of the wrist were predicted to provide circumstances where oscillations at the natural frequency in that reflex path would support and propagate the movements. 4. Forced oscillations from 1 to 7 Hz produced movements of different velocities. VPLc and cerebellar thalamic neurones discharged in relation to the duration of movement in a particular direction, but their discharge levels were unrelated to the magnitude of the velocity. Motor cortex neurones fired in a pattern which was related to the timing but not the magnitude of the acceleration. 5. In forced oscillations of the wrist the resonant frequency was between 3 and 7 Hz. They may be controlled in part by a transcortical reflex. The cerebellar thalamic neurones did not fire before motor cortex neurones. Therefore, it is unlikely that the cerebello-thalamo-cortical pathway is necessary to damp these potentially unstable oscillations by an effect on antagonist-related cortical neurones. 6. Rapid alternating movements (RAMs) of monkeys' wrists were performed in a stereotyped fashion over a narrow range of frequencies with the greatest displacement in joint angle and peak velocity at the natural frequency of 3-5 Hz. 7. During the performance of RAMs, neuronal discharge modulated sinusoidally in the VPLc, cerebellar thalamus and motor cortex. There was no relationship between velocity and neuronal discharge of the cerebellar thalamic and motor cortical neurones but there did appear to be a relationship between velocity and VPLc neuronal discharge. 8. The onset of electromyogram (EMG) discharge changed earlier than neuronal discharge in the motor cortex and thalamus during the performance of RAMs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Task-related coding of stimulus and response in cat motor cortex.

In a previous study in the cat, we have reported that motor cortex neurons discharging before the initiation of an aimed forearm response (lead cells) are better timed to movement of a display (stimulus) than to the response. The present study was done to distinguish the coding of stimulus and response features in the discharge patterns of such early activity in motor cortex. Single neurons were recorded in the arm area of motor cortex in three cats performing the same pair of responses (forearm flexion and extension) but to display movements in either of the two directions by changing display polarity. The modulation of lead cell activity was contingent on the occurrence of the learned motor response and timed to the stimulus in all conditions. The majority of lead cells (88%, n = 50) fell into one of two distinct classes. In one class of neurons, force-direction (56%, n = 32), activity was contingent on a single direction of forelimb response (flexion or extension) and was thus independent of the direction of the display stimulus. The only muscles whose patterns matched the activity of this class of response-related neurons were forelimb flexors and extensors. In these neurons, the onset of modulation was timed to one or the other of the two stimuli according to the stimulus direction which elicited the appropriate response. Thus, the display-related input to these neurons varied according to the response required. In the second class of neurons, stimulus-direction (32%, n = 18), modulation was associated with a specific stimulus direction rather than the response direction. The pattern of activity of these neurons was similar to the pattern of EMG signals of shoulder and neck muscles during the different task conditions. The contraction of proximal and axial muscles corresponded to a second response elicited by the stimulus, namely attempts at head rotation towards the moving display and was independent of the conditioned forelimb response in both time of onset and direction. To test the possibility that stimulus-direction neurons participated in the control of head rotation we trained two of the animals to also produce isometric changes in neck torque in the direction of the moving display without making the forelimb response. The activity of stimulus-direction neurons was similarly modulated during performance of the neck task. By contrast, force-direction neurons examined during the neck task were either unmodulated or discharged after the neck response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Motor cortex changes in a patient with hemicerebellectomy.

To evaluate reorganisation of motor pathways following a cerebellar lesion, we studied motor cortex excitatory responses and inhibitory effects after transcranial stimulation, together with segmental spinal cord excitability, in one patient who had undergone hemicerebellectomy. We compared the results obtained using different forms of stimulation capable of activating the cortico-spinal tract at different sites. Results were compared between sides. We previously reported that the threshold for responses is higher in the motor cortex contralateral to the impaired hemicerebellum and the right/left threshold asymmetry is clearly greater than normal when a circular coil centred over the vertex is used. In the present study, using electrical anodal stimulation, no side difference was observed. Significant interside differences were absent also when the durations of the silent periods or the mean amplitude of the flexor carpi radialis H reflex between the two sides were compared. The outcome is that the interside differences previously observed are mainly due to reduction in the intrinsic excitability properties of the motor cortex functionally related to the impaired hemicerebellum and not to modification of the inhibitory properties of the cortex or to spinal mechanisms.

Cerebellum↗

[Jacksonian seizure model induced by a kainic acid microinjection into unilateral sensori-motor cortex].

Kainic acid microinjection into unilateral sensori-motor cortex induced focal seizure status and secondarily generalized seizure status for about 4 hours. After these seizure status, focal myoclonic jerkings were induced for about 2 days. EEG demonstrated generalized synchronous periodic spikes with these myoclonic jerkings. This phenomenon was very similar to those symptoms of epilepsia partialis continua in man. During focal seizure status, autoradiographic study with 14C-deoxyglucose demonstrated increased local cerebral glucose utilizations in the injected site of the sensori-motor cortex, ipsilateral caudate nucleus, globus pallidus, substantia nigra and thalamic nuclei. The result suggested that subcortical pathways played an important roles in the seizure propagation from the cortical epileptogenic focus.

Animals↗

Thalamic projections to the feline motor cortex studied with horseradish peroxidase.

Cells in the thalamus projecting to the distal forelimb regions of the motor cortex, area 3a, and the sensory cortex were identified with horseradish peroxidase (HRP). These cortical areas were defined by mapping evoked potentials from superficial and deep radial nerve stimulation. Following injections into the motor cortex, the labelled cells were distributed throughout a large region (greater than 2 mm wide) in the ventral portion of the ventral lateral nucleus (VL). The border area between VL and the ventral posterolateral nucleus (VPL) also contained labelled cells. The region containing labelled cells following injections into area 3a was in the rostral, dorsal VPL, and overlapped with the region containing cells labelled by injections into the motor cortex. Cells labelled by injections into the sensory cortex were near the center of VPL distinctly separated from those labelled after injections into either area 3a or the motor cortex.

Animals↗

Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke.

BACKGROUND AND PURPOSE: Skilled reaching movements are an important aspect of human motor behavior but are impaired after motor system stroke. The purpose of this study was to document skilled movements in mice before and after a focal motor cortex stroke for the purpose of developing a mouse model of human stroke. METHODS: Male C57/BL6 mice were trained to reach with a forelimb for food pellets and then given a motor cortex stroke, induced by pial stripping, contralateral to their preferred reaching limb. Reaching success and the movements used in reaching were analyzed by frame-by-frame inspection of presurgical and postsurgical video records. RESULTS: Reaching success was severely impaired after the stroke. Improvement in success over 2 postsurgical weeks was moderate. Analysis of 10 movement components comprising reaches pre- and postsurgically indicated that most of the rotatory movements of the limb used for aiming, advancing, pronating, and supinating the paw were impaired. When successful reaches did occur, body movements that compensated for the impairments in limb rotatory movements aided them. CONCLUSIONS: The results indicate that skilled reaching in the mouse is impaired by focal motor cortex stroke and they suggest that the mouse, and the skilled reaching task, provides an excellent model for studying impairments, compensation, and recovery after motor system stroke.

Animals↗