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Contributions of the motor cortex and the cerebellum to a simple learned movement in the monkey.

Monkeys were trained to perform isometric plantar flexions of the foot in a simple reaction time situation. In test sessions, the contralateral hindlimb area of the motor cortex was cooled by a cryode placed on the dura until somatosensory evoked potentials disappeared. Movement amplitude decreased to about 70% of initial size; reaction time which was measured on the EMG, and torque signals increased slightly; and the evoked response in the dentate nucleus of the cerebellum remained unchanged. An extensive lesion in the motor cortex by coagulation reduced the movement amplitude to 10% of its preoperational size, but again, did not change reaction time significantly. It is concluded that the motor cortex is not essential for the execution of this overtrained simple movement.

Animals↗

[Transformation of an afferent tactile signal into a motor command in the cat motor cortex].

The activity of 112 units of the cat precruciate motor cortex was studied simultaneously with the performance of a placing reaction of the foreleg to tactile stimulation of its distal parts. The response latency to the tactile stimulation of the foreleg was 30-40 ms for the electromyographic response of m. biceps brachii and 20 +/- 10 ms for the earliest-responses of the motor cortical neurons. The electrical reaction of m. biceps brachii occured 5-10 ms after the termination of the electrical stimulation of the cortex by a puls series (the series duration was 25 ms, the pulse duration 0.2 ms, frequency 400 per s). Two different types of excitatory reactions of the motor cortex units were found: the sensory (s) ones occured at each tactile stimulus and did not depend on the presence or absence of the foreleg motion; the motor (m) type of reactions developed simultaneously with the motor placing reaction of the foreleg only. The minimal latency of cortical m- and s-type discharge was 20 +/- 10 ms. Electrical stimulation (5-25 micronA) through the microelectrode placed in the locus of neuronal activity which increased during active flexion of the foreleg, provoked in 70% of cases the electrical response in m. biceps brachii.

Animals↗

Topographic mapping of somatosensory evoked potentials helps identify motor cortex more quickly in the operating room.

Median nerve somatosensory evoked potentials were recorded from exposed cerebral cortex during craniotomies. This technique is valuable when knowledge of the motor cortex location can influence surgical decisions about resection limits or biopsy sites. Two different recording techniques were compared: strips of electrodes and arrays of electrodes. The arrays recorded electrical potentials suitable for topographic mapping. We found that motor cortex could be identified more quickly when using the topographic mapping of SEPs from arrays. We conclude that topographic mapping of SEP from sensorimotor regions during craniotomies works well in general and can be done more quickly than the traditional electrode strip technique.

Adolescent↗

Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex.

Glutamate transport is critical for synaptic inactivation of glutamate and prevention of excitotoxicity. The following four glutamate transporters have been identified in human brain: EAAT1, EAAT2, EAAT3, and EAAT4. Deficient glutamate transport has been identified in the motor cortex and the spinal cord of tissue from amyotrophic lateral sclerosis (ALS) patients. The defect appears to be due to a selective loss of the astroglial specific glutamate transporter protein EAAT2. In these studies we sought to extend our understanding of glutamate transporters in ALS by examining the mRNA for each transporter subtype in ALS motor cortex. All tissue was matched for age and postmortem delay. There was no quantitative change in mRNA for EAAT1, EAAT2, or EAAT3 in ALS motor cortex, even in patients with a large loss of EAAT2 protein (95% decrease compared with control) and decreased tissue glutamate transport (73% decrease compared with control). These studies suggest that the dramatic abnormalities in EAAT2 may be due to translational or post-translational processes.

ATP-Binding Cassette Transporters↗

Use of motor cortex stimulation to measure simultaneously the changes in dynamic muscle properties and voluntary activation in human muscles.

Force responses to transcranial magnetic stimulation of motor cortex (TMS) during exercise provide information about voluntary activation and contractile properties of the muscle. Here, TMS-generated twitches and muscle relaxation during the TMS-evoked silent period were measured in fresh, heated, and fatigued muscle. Subjects performed isometric contractions of elbow flexors in two studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One study (n = 6) measured muscle contraction times and relaxation rates during brief maximal and submaximal contractions in fresh and fatigued muscle. Another study (n = 7) aimed to 1) assess the reproducibility of muscle contractile properties during brief voluntary contractions in fresh muscle, 2) validate the technique for contractile properties in passively heated muscle, and 3) apply the technique to study contractile properties during sustained maximal voluntary contractions. In both studies, muscle contractile properties during voluntary contractions were compared with the resting twitch evoked by motor nerve stimulation. Measurement of muscle contractile properties during voluntary contractions is reproducible in fresh muscle and reveals faster and slower muscle relaxation rates in heated and fatigued muscle, respectively. The technique is more sensitive to altered muscle state than the traditional motor nerve resting twitch. Use of TMS during sustained maximal contractions reveals slowing of muscle contraction and relaxation with different time courses and a decline in voluntary activation. Voluntary output from the motor cortex becomes insufficient to maintain complete activation of muscle, although slowing of muscle contraction and relaxation indicates that lower motor unit firing rates are required for fusion of force.

Adult↗

Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant.

Previous experiments from our laboratory have shown that application of brain-derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration-associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5-mm-long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation.

Animals↗

Motor cortex inhibition in patients with ataxia.

We studied the effects of a subthreshold magnetic stimulus over the motor cortex and an electrical stimulus over the cerebellum on EMG responses produced by a suprathreshold magnetic stimulus over the motor cortex. In normal subjects, both subthreshold conditioning stimuli and cerebellar stimuli could suppress responses to suprathreshold magnetic test stimuli when given at appropriate timings: "cortico-cortical" and "cerebellar" inhibition, respectively. In all patients with degenerative ataxias and patients with a lesion in the cerebellar thalamus, the "cortico-cortical" inhibition was normal and the "cerebellar" inhibition was absent. We conclude that cerebellar systems make no or little contribution to the above-mentioned "cortico-cortical" inhibition.

Adult↗

Magnetic transcranial and electric direct stimulation of the facial motor cortex in dogs.

Magnetic stimulation may allow noninvasive study of the entire course of the facial nerve. Our goal was to determine if evoked muscle action potentials can be obtained in facial musculature using electric direct cortical and noninvasive transcranial magnetic stimulation of the canine motor cortex. Thirty-four dogs were studied with electric direct cortical stimulation through a craniotomy and magnetic transcranial stimulation of the facial motor cortex. Facial nerve stimulation in the cerebellopontine angle allowed comparison to cortical responses. Latencies of 6.08 and 9.52 msec for orbicularis oculi and levator nasolabialis, respectively, were determined with magnetic transcranial stimulation, compared with 4.22 and 5.78 msec with electric direct cortical stimulation. In conclusion, magnetic stimulation of the facial motor cortex is possible in dogs, with longer central conduction times than with electric direct stimulation.

Action Potentials↗

N30 and the effect of explorative finger movements: a model of the contribution of the motor cortex to early somatosensory potentials.

OBJECTIVES: The source of the N30 potential in the median nerve somatosensory evoked potentials (SEP) has been previously attributed to a pre-central origin (motor cortex or the supplementary motor area, SMA) or a post-central located generator (somatosensory cortex). This attribution was made from results of lesion studies, the behavior of the potential under pathological conditions, and dipole source localization within spherical volume conductor models. METHODS: The present study applied dipole source localization and current density reconstruction within individual realistically shaped head models to median nerve SEPs obtained during explorative finger movements. RESULTS: The SEPs associated with movement of the stimulated hand showed a minor reduction of the N20 amplitude and a markedly reduced amplitude for the frontal N30 and parietal P27, exhibiting a residual frontal negativity around 25 ms. The brain-stem P14 remained unchanged. Mapping of the different SEPs (movement of the non-stimulated hand minus movement of the stimulated hand) showed a bipolar field pattern with a maximum around 30 ms post-stimulus. In eight out of ten normal subjects, both the N30 and the gN30 (subtraction data) sources resided within the pre-central gyrus, more medially than the post-centrally located N20. Two subjects, in contrast, showed rather post-centrally localized sources in this time range. A model of the cortical SEP sources is introduced, explaining the data with respect to previously described findings of dipole localization, and from lesion studies and the alterations seen in motor diseases. CONCLUSIONS: The results provide evidence for a pre-central N30 generator, predominantly tangentially oriented, located within the motor cortex, while no sources were detected elsewhere. It is suggested that the mechanisms underlying the 'gating' effect during explorative finger movements in the 30 ms time range predominantly arise in the motor cortex.

Adult↗

Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.

Adult↗

Effects of internal globus pallidus stimulation on motor cortex excitability.

BACKGROUND: Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD. METHODS: The physiologic effects of internal globus pallidus (GPi) stimulation in seven patients with PD and seven age-matched healthy volunteers were studied. The stimulators were set at the optimal parameters (ON), at half the optimal amplitude (Half-Amp), or switched off (OFF) in random order. Patients were taking their usual medications. Magnetic stimulation was applied to the motor cortex, and motor evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous muscle. Several excitatory and inhibitory pathways that have been found to be abnormal in PD were tested. RESULTS: The motor threshold (MT), MEP recruitment curve (stimulus intensities from 100 to 150% of MT), short and long interval intracortical inhibition, and intracortical facilitation were similar in the three stimulator conditions tested both at rest and during voluntary contraction. The silent period (SP) was longer in the OFF and Half-Amp conditions than in normal control subjects. In the stimulator ON condition, the SP was significantly reduced compared with the OFF condition and became similar to that in normal control subjects. CONCLUSIONS: GPi stimulation while on dopaminergic medications reduced the SP following magnetic stimulation but did not change corticospinal excitability or other measures of intracortical inhibition and facilitation. The reduction of SP may be related to the antidyskinetic and levodopa-blocking effects of ventral GPi stimulation.

Aged↗

Corticospinal volleys evoked by anodal and cathodal stimulation of the human motor cortex.

1. In fifteen neurologically normal subjects, corticospinal volleys evoked by transcranial stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes in the high-thoracic and low-thoracic regions during surgery to correct scoliosis. 2. Anodal stimulation at the vertex produced complex corticospinal volleys that could be recorded at both sites, with multiple waves analogous to the D and I waves documented in animal experiments. These volleys were of higher amplitude when the cathode was 7 cm lateral to the vertex rather than 7 cm anterior. There were no differences in conduction time between the two recording sites for D and I waves, when these waves could be identified at the low-thoracic site. 3. Anodal stimuli of 150 V commonly produced a descending volley containing a single peak at both recording sites. Modest increases in stimulus intensity to 225-375 V produced a peak 0.8 ms in advance of the wave of lowest threshold in thirteen subjects and, in seven subjects, further increases produced an additional peak 1.7 ms in advance of the first-recruited wave. The early peaks increased in size with stimulus intensity, replacing the first-recruited wave. These results suggest that the site of impulse initiation with electrical stimulation of the motor cortex shifts from superficial cortex to deep structures, approximately 5 and 10-11 cm below the cortex. These sites are probably the internal capsule and the cerebral peduncle. 4. With cathode at the vertex and anode over the 'hand area' the response of lowest threshold occurred at the latency of the anodal D wave but could not be recorded at the low-thoracic site, suggesting that it was generated by the anode over the 'hand area'. Slightly higher intensities induced a 'cathodal D wave' and still higher intensities produced late peaks at latencies of anodal I waves. These cathodal D and I waves involved axons innervating lumbar segments. There was no evidence that cathodal stimulation preferentially produced I waves. Cathodal stimulation at the vertex with the anode 7 cm anteriorly produced similar results: D waves were produced at relatively low intensities, but I waves appeared at relatively high stimulus intensities if at all.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Somatosensory responses in the cat motor cortex. I. Identification and course of an afferent pathway.

1. The main aim of the present series of experiments was to demonstrate with electrophysiological methods that the spinothalamocortical system may send somesthetic information to the pyramidal and corticospinal tract cells in the motor cortex of the cat. 2. Experiments were carried out on acutely prepared cats anesthetized with alpha-chloralose. Extra- and intracellular recordings were made from the cells located in the pericruciate motor cortex (the lateral portion of area 4 gamma). They were identified by their antidromic responses to pyramidal stimulation and/or stimulation of the dorsolateral funiculus of the spinal cord. The animals were subjected to a set of nervous tissue lesions to prevent any transit of extereoceptive information to the motor cortex via the cerebellum and the somatosensory cortex. A lesion of the dorsal part of the spinal cord was also made, leaving intact only the afferent inflow ascending in the spinal ventral half, i.e., the spinothalamic system. 3. In this cat preparation it was observed that both electrical and natural stimulation of the limbs still efficiently activated the motor cortical efferent cells. 4. The pathway was mapped by applying microstimulation along its whole course in the spinal cord and brain stem. Stimulation of the primary afferent fibers running in the dorsal columns caudally to the spinal cord lesion produced activation and/or inhibition of the cortical cells. The existence of these responses may be attributable to the existence of collaterals from primary afferent fibers located in the dorsal columns, which activate the spinothalamic tract cells either mono- or polysynaptically. In the brain stem the fibers join the medial lemniscus. 5. In view of the short latency of the responses (mean latency 10.5 ms from the spinal cord) it is suggested that this component of the spinothalamic system may play an important role in the sensory regulation of ongoing movements.

Afferent Pathways↗

Excitation of the motor cortex associated with the E2 phase of cutaneous reflexes in man.

We investigated excitability changes of the motor cortex associated with the E2 phase of cutaneous reflexes in the first dorsal interosseous muscle using transcranial electrical and magnetic stimulation of the motor cortex in humans. EMG responses to combined cutaneous and weak magnetic cortical stimulation, which were elicited during the E2 phase of cutaneous reflexes, were larger than those by the same magnetic cortical stimulation alone. This facilitatory effect was reduced or even inhibitory effect was seen when the intensity of cortical stimulation was increased. Responses to weak electrical cortical stimulation were less affected by the combined cutaneous stimulation. The same facilitatory effect on responses to weak magnetic cortical stimulation was also observed in single motor unit recordings, too. Dissociation between facilitatory effects on the responses evoked by weak magnetic and weak electrical cortical stimulations suggests that the motor cortical excitability is increased in association with the E2 phase. The present results are consistent with the hypothesis that the E2 phase is a kind of transcortical reflex.

Adult↗

Motor cortex plasticity induced by extensive training revealed by transcranial magnetic stimulation in human.

This study examines the effect of high-level skilled behaviour on motor cortex representations of upper extremity muscles of ten sportswomen. We used transcranial magnetic stimulation to map proximal medial deltoid and distal extensor carpi radialis muscle representations on both hemispheres during low-level voluntary contraction. We compared cortical representation areas between two groups of subjects and between hemispheres within subjects. The first group comprised five elite volleyball attackers and the second group five runners. Four stimuli were delivered on multiple scalp sites (1.5 cm apart) to induce motor-evoked potentials recorded by surface EMG. Maps were described in terms of excitable scalp positions and of motor-evoked potentials. We observed differences in map areas between the two groups. Volleyball players had larger cortical representations of the proximal medial deltoid muscle than runners. Furthermore, the volleyball players had larger map areas for dominant muscles compared with non-dominant muscles. There was no difference, however, in map area for either muscle between the dominant and non-dominant arm in the runner group. Our results show that heavy training in a specific skill induces an expansion of proximal muscle representation in the contralateral primary motor cortex. This enlarged map area for proximal muscle is accompanied by an increase in the overlapping of proximal and distal muscle representations. This could reflect the fact that motor learning of co-ordinated movement involves a common control of both muscles. This reorganization supports the hypothesis of a cortical plasticity driven by activity.

Adult↗

Role of the motor cortex in the control of visually triggered gait modifications.

One important aspect of locomotor control is the ability of an animal to make anticipatory gait modifications to avoid obstacles, by stepping either around them or over them. This paper reviews some of the evidence that suggests that the motor cortex is one of the principal structures involved in the control of such anticipatory gait modifications in cats, in particular when they are triggered by a visual signal. Evidence for this statement is provided both from experiments in which the motor cortex has been lesioned or inactivated and from studies in which the activity of motor cortical neurones has been recorded during locomotor tasks in which visual information is required to ensure the correct positioning of the paw or an appropriate modification of the limb trajectory. Inactivation of small regions of the motor cortex with the GABA agonist muscimol results in changes in the limb trajectory so that cats hit an obstacle instead of stepping over it as they do normally. A similar disruption of the hindlimb trajectory is seen following lesions of the spinal cord at T13 that interrupt the corticospinal tract. The results from cell recording studies are complementary in that they show that the activity of many identified pyramidal tract neurones increases when the cat is required to modify the forelimb or hindlimb trajectory to step over obstacles. We suggest that the major function of this increased discharge frequency is to regulate the amplitude, duration, and temporal pattern of muscle activity during the gait modification to ensure an appropriate modification of limb trajectory. We further suggest that different groups of pyramidal tract neurones are involved in regulating the activity of groups of synergistic muscles active at different times in the gait modification. For example, some groups of pyramidal tract neurones would be involved in ensuring the appropriate and sequential activation of the muscle groups involved in the initial flexion of the elbow, while others would be active prior to the repositioning of the paw on the support surface. We discuss the possibility that the motor cortical activity seen during locomotion is the sum result of a feedforward signal, which provides visuospatial information about the environment, and feedback activity, which signals, in part, the state of the interneuronal pattern generating networks in the spinal cord. The way in which the resulting descending command may interact with the basic locomotor rhythm to produce the gait modifications is discussed.

Animals↗

The comparable size and overlapping nature of upper limb distal and proximal muscle representations in the human motor cortex.

The purpose of this study was to determine the relative size and location of proximal and distal upper limb muscle representations in the human motor cortex. Motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded in the proximal muscle anterior deltoid (AD) and in the distal muscles extensor carpi radialis (ECR) and first dorsal interosseus (1DI). The coil was moved in steps of 1 cm along a grid drawn on a tight-fitting polyester cap placed on the subject's head. At each location, four stimuli were delivered at 1.2 times the active motor threshold (AMT), and MEPs averaged in real-time. The peak-to-peak amplitude of each muscle's mean MEP was measured at each stimulation site. The area of a muscle's representation was measured by a pixel-counting algorithm. The optimal point of each muscle's areal representation, which corresponds to the locus near which the largest MEPs are obtained, was determined by fitting a 3D Lorentzian function to the data points. The optimal point of distal muscles tended to be situated more laterally along the motor strip than that of proximal muscles. However, there was no statistically significant difference between the size of the areal representations and they overlapped considerably. Additionally, in another five subjects, using a small 45-mm coil placed in a hyper-focal orientation, maps were obtained at a stimulus intensity of 1.1-1.15 times the AMT of the muscle with the lowest threshold, usually the 1DI. Even in this very stringent condition, the mapped representations of the AD, ECR and 1DI overlapped, notwithstanding that sharp demarcations between borders were also apparent. These observations demonstrate that stimulus spread alone does not explain the overlap of muscle representations. These results show that commonly used proximal and distal upper-limb muscles, taken individually, are controlled by motor cortical territories of approximately equal size that significantly overlap despite differences in the location of their optimal points.

Adult↗

Motor cortex plasticity during forced-use therapy in stroke patients: a preliminary study.

Treatment-induced plastic changes were investigated in the brains of stroke patients in the subacute stage of illness. Nine patients participated in 1 week of conventional physiotherapy. In the subsequent week conventional physiotherapy was combined with forced-use therapy. Focal transcranial magnetic stimulation was used to determine the motor output areas of the abductor pollicis brevis muscles prior to the treatment and after the first and after the second week. Motor performance was evaluated using the Nine Hole Peg Test, the Frenchay Arm Test and vigorometry to measure the grip strength. Before treatment the cortical representation area of the paretic hand muscle was significantly smaller than the contralateral side. This difference persisted after the first week of physiotherapy. In contrast, the motor output map in the affected hemisphere was significantly enlarged after forced-use therapy. This increase in motor cortex excitability was accompanied by a significant improvement in dexterity. Across the two treatment weeks the centres of the motor output maps shifted significantly stronger in the affected hemisphere than in unaffected hemisphere, suggesting the recruitment of adjacent brain areas. We conclude that the combination of forced-use therapy and conventional physiotherapy enhances motor cortex excitability and improves motor performance compared to a preceding conventional physiotherapy alone. Due to the small number of patients and the lack of a control group, these results are preliminary observations and require replication in a larger sample.

Aged↗