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PubMed1996

Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study.

The effect of a single oral dose of various antiepileptic drugs on the excitability of the motor system was studied in healthy volunteers by means of transcranial magnetic stimulation. Motor threshold, duration of the cortical silent period, and intracortical excitability after double-shock transcranial stimulation were tested before and at defined intervals after drug intake. Antiepileptic drugs that support the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold. Gabapentin, whose mechanism of action has not yet been unequivocally identified, showed a similar profile. By contrast, sodium and calcium channel blockers without considerable neurotransmitter properties (carbamazepine, lamotrigine, losigamone) elevated motor threshold but did not change intracortical excitability. The cortical silent period was lengthened by gabapentin and carbamazepine. Changes in peripheral motor excitability (maximum M wave, peripheral silent period) were not observed. We conclude that the changes in intracortical excitability are caused by GABA-controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability. Transcranial magnetic stimulation may be a promising noninvasive approach to study the selective effects of antiepileptic drugs on brain function.

4-Aminobutyrate Transaminase↗

PubMed2001

Postoperative changes on functional mapping of the motor cortex in patients with brachial plexus injury: comparative study of magnetoencephalography and functional magnetic resonance imaging.

Using magnetoencephalography (MEG) and functional magnetic resonance imaging (f-MRI), we investigated the areas of the cerebral cortex that were activated when patients with brachial plexus injuries performed elbow flexion, a motion re-acquired through nerve transfer surgery. In all patients, elbow flexion on the operated side and on the unaffected side led to the activation of an area in the motor cortex, with these areas being located almost symmetrically on either side of the sagittal midline. These findings suggest that the activity center for the transferred intercostal nerves shifted to the motor cortex for the elbow, from the original intercostal nerve site.

Adolescent↗

PubMed2004

Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I.

In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.

Adult↗

PubMed1986

Representation of movements and muscles within the primate precentral motor cortex: historical and current perspectives.

A major problem with the study of the control of movement and posture is to determine how specific brain areas contribute to the selection of those particular muscle patterns that underlie a coordinated movement. With this problem in mind, a selective review is presented of mapping studies of the primate motor cortex, whose results bear on the question of how the spatial organization of cortical efferent cells might contribute to the production of organized muscle synergies. More recent findings are also summarized, which appear to resolve previous controversies on the question of whether movements or muscles are the primary units of motor cortex organization. These same findings suggest also a form of spatial organization within the primate precentral gyrus that would allow spatially simple afferent inputs to evoke the muscle synergies that are necessary for a variety of simple movements of the arm and hand.

Animals↗

PubMed2001

Dissociation between hand motion and population vectors from neural activity in motor cortex.

The population vector hypothesis was introduced almost twenty years ago to illustrate that a population vector constructed from neural activity in primary motor cortex (MI) of non-human primates could predict the direction of hand movement during reaching. Alternative explanations for this population signal have been suggested but could not be tested experimentally owing to movement complexity in the standard reaching model. We re-examined this issue by recording the activity of neurons in contralateral MI of monkeys while they made reaching movements with their right arms oriented in the horizontal plane-where the mechanics of limb motion are measurable and anisotropic. Here we found systematic biases between the population vector and the direction of hand movement. These errors were attributed to a non-uniform distribution of preferred directions of neurons and the non-uniformity covaried with peak joint power at the shoulder and elbow. These observations contradict the population vector hypothesis and show that non-human primates are capable of generating reaching movements to spatial targets even though population vectors based on MI activity do not point in the direction of hand motion.

Animals↗

PubMed2002

Noradrenergic innervation of the developing and mature visual and motor cortex of the rat brain: a light and electron microscopic immunocytochemical analysis.

The noradrenergic (NA) innervation of the developing and adult visual and motor cortex of the rat was examined with light and electron microscopic immunocytochemistry by using antibodies against dopamine-beta-hydroxylase. At birth, NA fibers were present in both cortical areas, appearing as two tangential streams, one above and the other below the cortical plate. During the subsequent weeks, these two streams arborized gradually innervating all cortical layers. The adult pattern of distribution was attained by postnatal day 14, but the density of innervation, which was higher in the motor than in the visual cortex, appeared similar to the adult by the end of the third postnatal week. Electron microscopic analysis revealed that a low proportion of NA varicosities (the highest value was 12% in the adult motor cortex in single sections) were engaged in synaptic contact, throughout development, in both areas examined. The overwhelming majority of these synapses were symmetrical, involving predominantly small or medium dendrites. This evidence suggests that transmission by diffusion is the major mode of NA action in the developing and adult cerebral cortex. Noradrenaline released in the rare synaptic junctions may act mainly to reduce the activity of its cortical targets. The results altogether provide morphologic evidence for an involvement of noradrenaline in the development of the neocortex and, along with earlier data on the serotonergic system, indicate that the monoaminergic systems are endowed with a specific anatomic organization in various areas of the brain.

Aging↗

PubMed1988

Primate motor cortex and free arm movements to visual targets in three-dimensional space. III. Positional gradients and population coding of movement direction from various movement origins.

In one experiment, we studied the relations between the frequency of discharge of 274 single cells in the arm area of the motor cortex of the monkey and the actively maintained position of the hand in space. We found that the frequency of discharge of 63.9% of the cells studied was a multilinear function of the position of the hand in space according to the following equation (multiple linear regression): d = f + fxsx + fysy + fzsz, where d is the discharge rate of a single cell, f, fx, fy, fz are regression coefficients, and sx, sy, sz are the coordinates of the position of the hand. The equation above defines a positional gradient which implies that the frequency of cell discharge will increase at a maximum rate when the position of the hand changes along a certain direction; we call this direction of orientation of the positional gradient, and the rate of change in discharge rate along this orientation, the magnitude of the gradient. The orientations of the positional gradients were distributed throughout three-dimensional (3-D) space and their magnitudes differed among different cells. In a different experiment, we studied the changes in activity of 289 cells in the arm area of the motor cortex when the monkeys made equal-amplitude movements that started from different points in space, were in the same direction, and traveled along parallel trajectories in 3-D space. Four pairs of such movement directions (i.e., a total of 8 movement directions) were studied for every cell, and the changes in cell activity associated with movements within each pair were compared. We found that these changes in cell activity did not differ statistically for 68.4% of the movement pairs studied but did differ for the remaining 31.6%. The data from the whole population of cells studied in this experiment were analyzed using the population vector analysis described in the preceding paper (Georgopoulos et al., 1988). Thus, 8 population vectors were calculated, 1 for each of the 8 movement directions studied. We found that the direction of the population vector was close to the direction of the corresponding movement. These results indicate that the population vector provides unique information concerning the direction of the movement even when the point of origin of the movement varies in 3-D space.

Animals↗

PubMed2006

Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias.

Experimental models of Parkinson's disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson's disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP) like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson's disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motor-evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8% of baseline at T30) but not in patients off medication (T30: +0.07% of baseline in the non-dyskinetic, +27% in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9% of baseline MEP) but not in the dyskinetic group (T30: -9.2% of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson's disease off medications and is restored by levodopa in non-dyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.

Aged↗

PubMed1978

Properties of the pyramidal tract neuron system within the precentral wrist and hand area of primate motor cortex.

1. To obtain basic anatomical data that will be useful in interpreting the results of studies of primate pyramidal tract neurons (PTNs), extracellular, single-unit recording techniques were used to determine a number of the properties of the PTN population within the electrically defined, precentral wrist zone of the monkey's motor cortex. 2. Recordings were obtained from a total of 1,375 antidromically identified PT and corticospinal tract (CST) cells. A mathematical model was then used to correct the statistics of the sample for variations in the probability of unit detection, which arise from variations in neuronal size and extracellular field dimensions. 3. Both the experimentally observed and theoretically corrected results suggest that the PT projection from this cortical zone is derived principally from slowly conducting, and presumably small to medium-sized cells (an estimated 85% of the resident PTN population). 4. Both the fast and slow cell subpopulations were found to be concentrated within cortical layer V, where they tend to congregate in small, mixed clusters of 2 to 5 neurons. Estimates of the total packing density of PTNs within layer V of this cortical zone suggest that they account for only 10-20% of the neurons within this major efferent layer. 5. 70% of the slow and 82% of the fast PT neurons within this cortical area were found to send their axons into the contralateral, lateral corticospinal tract. Thus, in futur functional studies of PTNs in this cortical area, it can be assumed that three of every four neurons will in fact influence segmental cells of one category or another directly. 6. Extensive data are also presented on the incidence of axon collateral branching from PT and CST cells to the red nucleus, the medial medullary reticular formation and the cuneate nucleus. 7. Some general implications of these findings for the design of future functional studies of anatomically identified motor cortex cell systems are then discussed.

Action Potentials↗

PubMed1994

[The electrophysiological characteristics of long-term homo- and heterotopic cortical transplants in the rat motor cortex].

Microelectrode experiments were performed on the transplants (TPs) in the motor cortex, MI, of adult rats 2 to 6 mo and 8 to 11 mo after grafting TPs taken from one of hemispheres of newborn rat. Within TPs, latencies of neuronal responses evoked by means of electrocutaneous stimulation of forelimbs, hindlegs and vibrissal pads were ranged, from 13 to 30 ms, 17 to 38 ms and 10 to 15 ms, respectively. The values are similar with those in intact MI in both experimental and normal rats. A trend to widening receptive fields was observed in many neurons recorded in long-surviving TPs. In some units, a predominance of ipsilateral somesthetic inputs over contralateral ones was demonstrated which is more usual phenomenon for immature neurons in MI during early normal development. It indicates on the deficiency of maturation's mechanisms for synaptic inputs into the TPs. No motor responses were induced by low-threshold microstimulation in TPs and only on the depths lower than 2000 microns motor responses were obtained in a few cases, presumably due to the activation of white matter axons.

Animals↗

PubMed1977

[Cortico-cortical connections in the motor cortex of the brain; a study using the peroxidase method].

Using a method based on retrograde axonal transport of horse-radish peroxidase (HRP), the cortico-cortical afferents of the motor cortex were studied. After enzyme injection into the posterior sigmoideus gyrus, the HRP product was found in the first and the second somatic sensory areas and in parietal cortex (fields 5a, 5b). The HRP-positive neurons occurred in layers II, III and V of the cortex and belonged to the pyramidal cells.

Afferent Pathways↗

PubMed1994

8-12 Hz rhythmic oscillations in human motor cortex during two-dimensional arm movements: evidence for representation of kinematic parameters.

Direct cortical recordings were taken from 12 patients with implanted subdural electrode arrays during performance of a 2-dimensional, multi-joint, visually guided arm movement task. Task-related changes in the amplitude of the motor cortex 8-12 Hz surface local field oscillations were evaluated for the encoding of direction and amplitude of movement in the 6 patients in whom no epileptogenic or ECoG background abnormalities were detected over the motor-sensory cortical areas under the recording electrode array. The topography, time of onset and duration of these responses were evaluated in the context of motor cortex somatotopy, as defined by cortical stimulation delivered through the electrode array. Multi-joint arm movements were accompanied by a decrease in the power of the 8-12 Hz frequency components of the ECoG signal. These power changes were spatially distributed over the upper extremity, motor-sensory representation. Movement amplitude influenced the magnitude, duration, and extent of the spatial distribution of ECoG power changes in the 8-12 Hz band. These effects occurred predominantly over cortical areas corresponding to the upper extremity motor-sensory representations. Direction of movement had a weaker influence on the 8-12 Hz frequency components of the ECoG over the upper extremity motor-sensory representations, but influenced the patterns of 8-12 Hz ECoG response on adjacent cortical regions. These results show that the amplitude of surface electrical oscillations generated over the rolandic cortex are correlated with the kinematics of multi-joint arm movements. These changes in the ECoG signal appear to reflect shifts in the functional state of neuronal ensembles involved in the initiation and execution of motor tasks.

Adult↗

PubMed2005

Theta burst stimulation of the human motor cortex.

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.

Adult↗

PubMed2003

Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand.

BACKGROUND: Complex regional pain syndrome type I (CRPS I) develops as a consequence of trauma affecting the limbs, without obvious nerve lesion. Its features include pain, edema, autonomic dysfunction, movement disorder, and trophic changes. CNS involvement is suggested by the symptoms, but the pathophysiology of CRPS I is unknown. OBJECTIVE: To assess excitability changes in the motor cortex in patients with CRPS I. METHODS: The authors studied 25 patients with unilateral CRPS I involving the hand by means of transcranial magnetic stimulation using a paired-pulse paradigm. Motor threshold (MT) and intracortical inhibition and facilitation were determined on the affected and the clinically unaffected side. A control group of 20 healthy subjects was studied. RESULTS: The authors found a significant reduction of intracortical inhibition on both sides of patients with CRPS compared with control subjects, whereas intracortical facilitation and MT did not differ significantly. However, in the patients' group, the presence of allodynia significantly decreased MT. CONCLUSIONS: The authors showed a bilateral disinhibition of the motor cortex in patients with complex regional pain syndrome.

Adult↗

PubMed1997

Developmental expression of parvalbumin by rat lower cervical spinal cord neurones and the effect of early lesions to the motor cortex.

Expression of calcium binding proteins (CaBPs), increasing neuronal activity and phases of synapse elimination are widely believed to be linked during development. We have employed immunocytochemistry to study the expression of the CaBP parvalbumin (PV) during the postnatal development of the lower cervical spinal cord and investigated how early lesions to the motor cortex, at the onset of corticospinal synaptogenesis, perturb the normal pattern of PV expression. This study confirms previous observations that in normal rats PV-like immunoreactivity is confined to large sensory afferents for at least 10 days postnatally (P10) and that the adult pattern of expression emerges from about P18 and involves mainly dorsal horn neurones. However, the study has also demonstrated a transient wave of expression in ventral horn neurones which reaches a maximum between P14-18 and declines thereafter. Unilateral lesions made at P7 to the forelimb motor cortex, which sends an almost completely crossed projection to the spinal cord, resulted in reduced neuronal expression of PV in the lower cervical spinal cord contralaterally at a range of ages (P14-31). The median ratio of PV positive neurones contralateral/ipsilateral to the lesion in spinal cord segments C7 and C8 was significantly lower (p < 0.01) at 56.0% (34.5-76.8 95% confidence limits, n = 14) than in sham operated controls (99.7%, range 93.7-113.6, n = 5). The lesion affected the transient wave of expression seen in ventral horn neurones during the third postnatal week as well as dorsal horn expression at older ages. We conclude that there is considerable plasticity in PV immunoreactivity during spinal cord development. PV is transiently expressed by ventral horn neurones at an age when movement control is functionally maturing. Early cortical lesions disrupt this transient phase of expression but also alter mature patterns of PV localisation. This suggests a critical role for corticospinal pathways in guiding maturation of segmental spinal cord circuitry.

Animals↗

PubMed2001

Impairment of motor cortex activation and deactivation in Parkinson's disease.

OBJECTIVES: To examine the time course of corticospinal excitability before and after voluntary movement in Parkinson's disease (PD). METHODS: We studied 9 mild PD patients at least 12 h off medications and 11 healthy volunteers in a simple reaction time (RT) paradigm. Suprathreshold transcranial magnetic stimulation was delivered to the left motor cortex at intervals covering the periods before and after movement. RESULTS: PD patients (284+/-90 ms) and normal subjects (282+/-56 ms) had similar median RT. The time courses of both the premovement increase and the postmovement decrease in corticospinal excitability were significantly different between PD patients and normal subjects. The increase in motor-evoked potential (MEP) amplitudes began earlier for PD patients (200 ms before electromyographic (EMG) onset) than for normal subjects (150 ms before EMG onset), but the rate of increase was slower in PD patients than controls. After EMG offset, MEP amplitudes were increased for about 150 ms in normal subjects, but in PD patients this period was prolonged to about 350 ms. CONCLUSIONS: Impairment of motor cortex activation and deactivation is an early feature of PD and may be a physiological correlate of bradykinesia. The normal RT in our patients may be related to the earlier occurrence of the premovement increase in corticospinal excitability compensating for the slower rate of rise.

Adult↗

PubMed1988

Sustained excitatory synaptic input to motor cortex neurons in awake animals revealed by intracellular recording of membrane potentials.

1. Most of the intracellular electrophysiological data on cortical neurons has been obtained in anesthetized or reduced preparations, and differs from observations in awake, intact animals. To determine whether these differences are due to experimental techniques or physiological factors, we recorded membrane potentials intracellularly from motor cortex neurons in chronically prepared cats and monkeys under Nembutal-anesthetized, Halothane-anesthetized, and unanesthetized conditions, or during transitions between anesthetized and awake conditions. 2. Resting membrane potentials were found to depend on the anesthetic state of the animal. Membrane potentials of neurons recorded in awake animals were more depolarized than those recorded in the anesthetized state. In the awake state membrane potentials were all less than -65 mV. 3. The input resistance of neurons recorded in awake animals were significantly smaller than those measured in the anesthetized state. Action potentials recorded in awake animals typically showed an undershoot (i.e. negative values at peak), implying that voltage-dependent conductances may be altered. Undershoot of the action potential was more prominent in pyramidal tract neurons (PTNs) than non-PTNs. 4. These data suggested that in awake animals motor cortex neurons, especially PTNs, receive sustained excitatory synaptic input or neuro-modulatory activities.

Action Potentials↗

PubMed2004

Modification of the human motor cortex by associative stimulation.

Manipulation of afferent input is capable of inducing reorganisation of the motor cortex. For example, following 1 h of paired electrical stimulation to the motor point of two hand muscles ("associative stimulation") the excitability of the corticospinal projection to the stimulated muscles is increased. Here we investigated the mechanisms responsible for such change using transcranial magnetic stimulation (TMS). Cortical excitability changes were investigated by measuring motor evoked potentials (MEPs), intracortical inhibition (ICI), intracortical facilitation (ICF), and short-interval intracortical facilitation (SICF). Following 1 h of associative stimulation MEP amplitudes in the stimulated muscles significantly increased. Additionally, there was a significant increase in ICF and of SICF at interstimulus intervals in the range of 2.3-3.3 ms. There was no significant change in ICI. These findings confirm previous observations that a 1-h period of associative stimulation can increase the excitability of the cortical projection to stimulated muscles. Additionally, these results suggest that the observed modifications of excitability are due to changes in intracortical excitatory circuits.

Adult↗