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Effect of unilateral motor cortex ablation on activity of choline acetyltransferase and levels of amino acid transmitter candidates in the spinal cord of adult monkeys.

Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function in discrete regions of spinal cord after ablation of sensorimotor cortex in monkeys. One and five weeks after unilateral cortical ablation, samples from six areas of spinal cord (ventral, lateral and dorsal regions of the left and right sides) were analysed for choline acetyltransferase (ChAT) activity and contents of amino acid transmitter candidates-glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA). During one to five weeks after unilateral cortical ablation of the monkey, prolonged hemiplegia in the contralateral side was observed. Histological examination of the spinal cord 5 weeks after unilateral (left) cortical ablation showed no apparent change in either control (ipsilateral, left) or affected (contralateral, right) sides of the cord as examined by the Klüver-Barrera method. The ChAT activity as a cholinergic marker was scarcely changed in any region of either left (control) or right (affected) side of the spinal cord at one and five weeks after unilateral (left side) ablation of the motor cortex. Amino acid levels in each region of the spinal cord were not significantly changed one week after unilateral ablation of the motor cortex. However, a significant decrease of Glu content was observed in the lateral column of the affected (right) side compared to the control (left) side of cervical and lumbar cord five weeks after cortical ablation of the left motor area. No concomitant alterations of other amino acids were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

[Exhaustion of motor cortex after head injury--revealed by transcranial magnetic stimulation].

We evaluated the pattern of motor evoked potentials elicited by single-pulse and slow-rate (1 Hz) repetitive, transcranial, magnetic stimulation (RTMS) in minor head injuries. The motor response to a single magnetic stimulus in patients with minor head injury was characterized by a significantly higher threshold than in healthy subjects. However, central and peripheral motor conduction was normal in all patients. A stable pattern of MEP throughout the RTMS session was the most prominent feature in the control group. A progressive decrease in MEP amplitude and irregular alternation of large and very small MEPs over the course of RTMS was observed in minor head injury. The higher threshold of the motor response and the abnormal patterns of MEP behavior revealed by RTMS may reflect impaired excitability and enhanced exhaustion of the motor cortex in patients with minor head injuries, which improve with time.

Adolescent↗

Possible involvement of primary motor cortex in mentally simulated movement: a functional magnetic resonance imaging study.

The role of the primary motor cortex (M1) during mental simulation of movement is open to debate. In the present study, functional magnetic resonance imaging (fMRI) signals were measured in normal right-handed subjects during actual and mental execution of a finger-to-thumb opposition task with either the right or the left hand. There were no significant differences between the two hands with either execution or simulation. A significant involvement of contralateral M1 (30% of the activity found during execution) was detected in four of six subjects. Premotor cortex (PM) and the rostral part of the posterior SMA were activated bilaterally during motor imagery. These findings support the hypothesis that motor imagery involves virtually all stages of motor control.

Adult↗

Transcranial magnetic stimulation mapping of the motor cortex in normal subjects. The representation of two intrinsic hand muscles.

The TMS-mapped representations of two intrinsic hand muscles, abductor pollicis brevis (APB) and abductor digiti minimi (ADM), were quantified using a transcranial magnetic stimulation (TMS) mapping technique in 10 right handed and 6 left handed subjects. A 50 mm diameter figure eight coil was used. Stimulus sites were located using a latitude/longitude based coordinate system, stimulus intensity was threshold-adjusted and stimuli were applied during controlled low-level (10%) voluntary contraction of the target muscles. Maps of the corticomotor representation were generated by fitting a continuously defined three dimensional function to the data obtained from stimulation at specific scalp sites, and projecting this function onto a two dimensional surface using a radial projection. It was found that the mapped representations of APB and ADM were large and overlapping but that there was a statistically significant separation of the two areas, the APB area being more laterally placed than the ADM area. The TMS-mapped representations of the two muscles showed no significant interhemispheric differences and were similar in left and right handed subjects. Rotation of the magnetic coil through 90 degrees resulted in medial shift and elongation of the TMS-mapped representations but there was no change in the relative positions of the two areas. The TMS-mapped representations were found to be very reproducible when mapping was repeated after intervals of up to 181 days. The present technique of TMS mapping allows the representation of individual hand muscles in the primary motor cortex to be reliably and reproducibly mapped and should prove useful for further studies of the physiology and pathophysiology of the motor cortex in man.

Adult↗

Electrophysiological considerations regarding electrical stimulation of motor cortex and brain stem in humans.

OBJECTIVE: To provide information about activation of descending motor pathways in humans, motor evoked potentials were obtained from 16 patients without any sensorimotor deficit, after both cortical and brain stem stimulation. METHOD: Total anesthesia was achieved in all patients through intravenous administration. Short trains of one to five electrical pulses were delivered separately to the motor cortex and the brain stem. Compound muscle action potentials were recorded from the contralateral upper extremity. Threshold intensity, stimulus polarity, latencies, and effect of increased stimulus intensity on latencies were analyzed. RESULTS: The threshold intensity was significantly lower when stimulating the brain stem than when stimulating the cortex. A monophasic anodal stimulus was better for cortical stimulation than for brain stem stimulation. Conversely, a monophasic cathodal stimulus was more effective for brain stem stimulation. The rate of unsuccessful stimulations was higher with brain stem stimulation and with increased stimulation intensity. The variability of latencies was so high that a calculation of the conduction velocity of the motor pathways was not possible. CONCLUSION: The results indicate that cortical surface and brain stem stimulation act on different nervous elements. Because of the condensation of motor pathway fibers at the brain stem level, much less stimulus intensity for eliciting compound muscle action potentials was necessary. On the other hand, the higher rate of unsuccessful brain stem stimulations may be caused by a block of conduction at either the anterior horn cell pool or the neuromuscular junction. Thus, for cortical and for brain stem stimulation, different stimulating parameters seemed to be necessary with the patient under general anesthesia.

Action Potentials↗

Contrasting properties of neurons in two parts of the primary motor cortex of the awake rat.

Features of neuronal activity in two subdivisions of primary motor cortex (MI) were recorded in awake rats. Neurons in the caudal part of MI, which overlaps part of the somatic sensory cortex, discharge with brief bursts in conjunction with isometric bar pressing with the forelimb. Cells in this caudal region are activated by cutaneous stimuli. In the rostral part of MI, neurons discharge prior to and during forelimb force changes, begin to discharge earlier than in the caudal zone, and have non-cutaneous or unidentifiable receptive fields. These results suggest separate motor control functions for rostral and caudal parts of rat MI.

Animals↗

Functional properties of the primary motor cortex and ventral premotor cortex in the monkey during a visually guided jaw-movement task with a delay period.

This study investigated single neuronal activity in the face area of the primary motor cortex (MI) and ventral part of the premotor cortex (PMv) while a monkey performed a visually guided jaw-movement task with a delay period. When the monkey executed the jaw movements, 48 MI and 53 PMv neurons showed statistically significant activities time-locked to jaw movements and were defined as movement-related neurons. The activities of movement-related neurons could be classified into phasic, phasic-tonic and tonic patterns based on the changes in discharge rate. Most of the neurons exhibiting phasic and phasic-tonic activities probably contributed to the initiation of jaw movements, since they exhibited transient responses immediately after the onset of the go-cue indicating the jaw movement. In contrast, the sustained activity of the movement-related neurons exhibiting phasic-tonic and tonic activities may be involved in controlling and/or maintaining jaw position. Sustained activity was also detected during the delay period in 4 MI and 29 PMv neurons and these neurons were defined as set-related neurons. It is thought that these set-related neurons are involved in the preparation for the subsequent jaw movement, since the masticatory muscles showed no significant changes during the delay period. These findings suggest that the MI may be involved predominantly in the initiation and control of jaw movements, and that the PMv may be involved in motor preparation, and may play a role as a higher-order motor area related to the initiation and control of jaw movements.

Animals↗

Extradural motor cortex stimulation as a method to treat advanced Parkinson's disease: new perspectives in geriatric medicine.

Motor fluctuations not controlled by pharmacological therapy are often encountered in long-term Parkinson's disease (PD). Neurosurgery treatment represented by deep brain stimulation (DBS) was considered a valid alternative to pharmacological treatment. Unfortunately this method is most effective in patients under age of 70. Recently it has been suggested that extradural motor cortex stimulation (EMCS) could be a valid cost-effective alternative to DBS to control motor symptoms in patients affected by Parkinson's disease. The relevant non-invasive surgical technique makes this treatment particularly indicated in geriatric patients. Brain atrophy, cognitive impairment, psychiatric symptoms are not an absolute contraindication to the treatment. We submitted to EMCS an outpatient afferent to our geriatric department, a woman 68 yrs old. The patient showed an improvement of 35% as measured by the Unified Parkinson Disease Rating Scale (UPDRS) scale after the surgery. If our findings will be confirmed in larger series, a new dimension will be added to the treatment of PD.

Aged↗

Riluzole suppresses motor cortex facilitation in correlation to its plasma level. A study using transcranial magnetic stimulation.

The aim of our study was to measure the effects of the glutamate antagonist riluzole on different parameters of motor excitability, using transcranial magnetic stimulation (TMS) during 7 days of riluzole administration, and to correlate these effects with riluzole plasma levels. Nine healthy volunteers received a dose of 100 mg riluzole from day 1 to 7 of the study period. Electrophysiological examinations were performed on day 1 before and 2 h, 5 h and 8 h after riluzole administration, on day 2, day 3 and day 5 before riluzole administration, and on day 8. Plasma samples were taken simultaneously. The excitability of the motor cortex, supraspinal and spinal motor pathways was tested by studying intracortical facilitation and inhibition, the cortical silent period and motor threshold after TMS, as well as the peripheral silent period and F-wave amplitudes after electrical peripheral nerve stimulation. We found a significant reduction of intracortical facilitation, which correlated significantly with riluzole plasma levels. To a lesser extent, intracortical inhibition was enhanced on day 1, motor threshold was increased on day 8 and F-wave amplitudes were reduced. These changes did not correlate with riluzole plasma levels. We conclude that the main effect of riluzole in vivo is a reduction of intracortical facilitation, which is closely related to the drug's level in the plasma. The most probable mechanism involves an effect on glutamatergic synaptic transmission.

Adult↗

Transient changes in cortical distribution of S100 proteins during reorganization of somatotopy in the primary motor cortex induced by facial nerve transection in adult rats.

In adult rats, the primary motor cortex (MI) comprises a somatotopic map of muscle representations. This somatotopy is modified after transection of the facial nerve (N7x). Mapping with cortical stimulation revealed that the underlying cortical reorganization is biphasic. Primary changes cause a transient disinhibition of long cortico-cortical connections in both hemispheres. While the first reaction vanishes within a few hours, short intra-areal connections are disinhibited within MI contralateral to N7x. The resulting co-operation between adjacent parts of MI persists as long as peripheral reinnervation is prevented. Cellular mechanisms underlying this cortical reorganization are largely unknown. Here, we utilized changes in immunoreactivity of S100 proteins (S100-IR) known as a sensitive indicator of astroglial reactions during plastic reactions in the central nervous system. Within 1 h of N7x, zones with enhanced S100-IR appeared in both hemispheres. Between 3. 5 and 18 h, reaction patterns with changing topography were transiently prominent in many cortical areas including parts of MI which surrounded the facial muscle representation fields. After 24 h, the facial muscle representation contralateral to N7x became labelled while S100-IR enhancement disappeared in most of the cortex. S100-IR-enhancement vanished completely during the next day of survival. Data presented suggest that (i) enhancement of S100-IR labels cortical tissue during the functional reorganization that is induced by N7x, (ii) large parts of the cerebral cortex participate in the reorganization, before it is finally focused on the representation field of MI that corresponds with contralateral N7x, and (iii) temporo-spatial patterns of astrocytic reactions apparently play a role in the underlying plasticity reaction.

Animals↗

Two different areas within the primary motor cortex of man.

The primary motor area (M1) of mammals has long been considered to be structurally and functionally homogeneous. This area corresponds to Brodmann's cytoarchitectural area 4. A few reports showing that arm and hand are doubly represented in M1 of macaque monkeys and perhaps man, and that each subarea has separate connections from somatosensory areas, have, with a few exceptions, gone largely unnoticed. Here we show that area 4 in man can be subdivided into areas '4 anterior' (4a) and '4 posterior' (4p) on the basis of both quantitative cytoarchitecture and quantitative distributions of transmitter-binding sites. We also show by positron emission tomography that two representations of the fingers exist, one in area 4a and one in area 4p. Roughness discrimination activated area 4p significantly more than a control condition of self-generated movements. We therefore suggest that the primary motor area is subdivided on the basis of anatomy, neurochemistry and function.

Autoradiography↗

Increased uptake of [3H]deoxyglucose and [14C]deoxyglucose in localized regions of the brain during stimulation of the motor cortex.

A part of the motor area which evokes short-latency activity in jaw-opening muscles was stimulated for 30-45 min in guinea pigs which had received an injection of [3H]deoxyglucose or [14C]deoxyglucose. In a number of specific regions of the upper brainstem and basal ganglia, bilateral increases of metabolic activity were demonstrated by autoradiography. These included the putamen, globus pallidus, substantia nigra, subthalamic nucleus, dorsomedial region of red nucleus, deep layers of the superior colliculus, and pretectal nuclei. A ventral region of the thalamus was labeled ipsilateral to the stimulation. It is suggested that these regions represent stations in the circuits involved in the production of the evoked muscular activity. Using [3H]deoxyglucose instead of [14C]deoxyglucose as a tracer improved the quality of the autoradiographic images.

Animals↗

Visuomotor processing as reflected in the directional discharge of premotor and primary motor cortex neurons.

Premotor and primary motor cortical neuronal firing was studied in two monkeys during an instructed delay, pursuit tracking task. The task included a premovement "cue period," during which the target was presented at the periphery of the workspace and moved to the center of the workspace along one of eight directions at one of four constant speeds. The "track period" consisted of a visually guided, error-constrained arm movement during which the animal tracked the target as it moved from the central start box along a line to the opposite periphery of the workspace. Behaviorally, the animals tracked the required directions and speeds with highly constrained trajectories. The eye movements consisted of saccades to the target at the onset of the cue period, followed by smooth pursuit intermingled with saccades throughout the cue and track periods. Initially, an analysis of variance (ANOVA) was used to test for direction and period effects in the firing. Subsequently, a linear regression analysis was used to fit the average firing from the cue and track periods to a cosine model. Directional tuning as determined by a significant fit to the cosine model was a prominent feature of the discharge during both the cue and track periods. However, the directional tuning of the firing of a single cell was not always constant across the cue and track periods. Approximately one-half of the neurons had differences in their preferred directions (PDs) of >45 degrees between cue and track periods. The PD in the cue or track period was not dependent on the target speed. A second linear regression analysis based on calculation of the preferred direction in 20-ms bins (i.e., the PD trajectory) was used to examine on a finer time scale the temporal evolution of this change in directional tuning. The PD trajectories in the cue period were not straight but instead rotated over the workspace to align with the track period PD. Both clockwise and counterclockwise rotations occurred. The PD trajectories were relatively straight during most of the track period. The rotation and eventual convergence of the PD trajectories in the cue period to the preferred direction of the track period may reflect the transformation of visual information into motor commands. The widely dispersed PD trajectories in the cue period would allow targets to be detected over a wide spatial aperture. The convergence of the PD trajectories occurring at the cue-track transition may serve as a "Go" signal to move that was not explicitly supplied by the paradigm. Furthermore, the rotation and convergence of the PD trajectories may provide a mechanism for nonstandard mapping. Standard mapping refers to a sensorimotor transformation in which the stimulus is the object of the reach. Nonstandard mapping is the mapping of an arbitrary stimulus into an arbitrary movement. The shifts in the PD may allow relevant visual information from any direction to be transformed into an appropriate movement direction, providing a neural substrate for nonstandard stimulus-response mappings.

Animals↗

Selective output-discriminative signals in the motor cortex of waking monkeys.

Monkeys and humans have similar capacities to discriminate between the frequencies of mechanical sinusoids delivered to the glabrous skin of their hands. Combined psychophysical-electrophysiological experiments in monkeys discriminating in the range of flutter provided evidence that this capacity depends upon differences in the cycle lengths in the sets of periodically entrained activity, evoked by the stimuli discriminated, in neurons of areas 3b and 1 of the (sensory) hemisphere opposite the stimulated hand. Identical experiments have now been made, in similarly trained and discriminating monkeys, in the motor cortex (area 4) of the hemisphere opposite the arm projecting selectively to one of two targets, to indicate discrimination (five hemispheres, 1137 neurons studied). We observed a selective signal of the upcoming correct discrimination in about 25% of the neurons of area 4 active in the task. The neuronal discharge occurs selectively for stimuli either lower or higher in frequency than that of the base stimulus, and commonly begins within 200-300 msec after onset of the comparison stimulus. These neuronal discharges are aperiodic, with no sign of the stimulus frequencies. EMG recording during performance of the discrimination showed that the muscles of the arm opposite the side of recording were silent during the period of stimulus presentations. Recordings during trials in which the animal made errors showed most commonly that the output of the discrimination operation was itself in error, followed by an appropriate arm projection to the wrong target. We interpret the selective response during the comparison stimulus to be a postdiscrimination signal projected transcallosally from the sensory hemisphere to the motor area of the hemisphere controlling the responding arm. We obtained no evidence that the discrimination operation is localized to any particular area, and we surmise it to occur in the dynamic activity within the distributed system linking the sensory cortex of one hemisphere and the motor cortex of the other. One-third of the neurons of the motor cortex responded to indentation of the skin of the ipsilateral hand, at trial onset. These responses varied from those closely linked to that sensory stimulus to those linked to the upcoming movement of the contralateral hand. These onset responses did not occur when similar sequences of mechanical stimuli were delivered to alert but idling monkeys.

Animals↗

Two different effects of transcranial magnetic stimulation to the human motor cortex during the pre-movement period.

A single-pulse TMS to the human motor cortex (M1) influences reaction time (RT). We may summarize from previous studies where different groups of subjects participated in various types of RT tasks that TMS above motor threshold (MT) delays RT, whereas TMS below MT shortens RT and that these RT changes depends on TMS timings during RT period. However, these effects have never been systematically investigated in a single study where an identical group of subjects participated. The purpose of this study is to test previous TMS effects in a study of simple RT task. Seven subjects isometrically abducted their right index fingers as quickly as possible when a visual stimulus appeared. A single-pulse TMS was randomly delivered over the left M1 at various timings during RT period in a single trial (at 0, 40, 60, 80 or 100 ms after the visual stimulus). Motor-evoked potential (MEP) and EMG activity for response were recorded from the right finger muscles. Only the TMS above MT delivered at 80 or 100 ms, which increased MEP amplitude, significantly delayed RT and increased the size of response EMG activities that may reflect contents of central motor commands. The TMS below MT at these timings, which occasionally evoked MEP, exclusively shortened RT despite the fact that the response EMG size was unchanged. A single-pulse TMS has different effects on the ongoing neuronal processes in M1 during the pre-movement period: TMS above MT may temporally retard the processes and also affect contents of central motor commands, whereas TMS below MT may simply facilitate its processes without affecting motor commands.

Adult↗

[Motor cortex functions in the reorganization of postural coordinations].

A well-known function of the motor cortex (MCx) is control of the limb distal musculature, in particular, isolated finger movements during precise and fine hand movements. However, MCx has another function connected with the motor learning process, namely, a suppression of synergies and coordinations interfering with a movement being elaborated. This was shown for various limb movements. However, majority of movements is accompanied by postural adjustment as well. Two experimental models of rearrangement of an innate pattern of the postural adjustment were developed, and MCx was shown during such kind of learning to suppress the activity of structures providing the innate postural patterns. In contrast to the control of limb movements, the MCx influences were found to be bilateral for the postural pattern reorganization. It was revealed recently, however, that a possibility of recovery for the sequential MCx lesions depends on the sequence of the lesions, so, perhaps the role of MCx of different hemispheres in the compensation is different.

Animals↗

Reorganization of primary motor cortex in adult macaque monkeys with long-standing amputations.

The organization of primary motor cortex (M1) of adult macaque monkeys was examined years after therapeutic amputation of part of a limb or digits. For each case, a large number of sites in M1 were electrically stimulated with a penetrating microelectrode, and the evoked movements and levels of current needed to evoke the movements were recorded. Results from four monkeys with the loss of a forelimb near or above the elbow show that extensive regions of cortex formerly devoted to the missing hand evoked movements of the stump and the adjoining shoulder. Threshold current levels for stump movements were comparable to those for normal arm movements. Few or no sites in the estimated former territory of the hand evoked face movements. Similar patterns of reorganization were observed in all four cases, which included two monkeys injured as adults, one as a juvenile, and one as an infant. In a single monkey with a hindlimb amputation at the knee as an infant, stimulation of cortex in the region normally devoted to the foot moved the leg stump, again at thresholds in the range for normal movements. Finally, in a monkey that had lost digit 5 and the distal phalanges of digits 2-4 at 2 yr of age, much of the hand portion of M1 was devoted to movements of the digit stumps.

Amputation, Surgical↗

Time is a rubberband: neuronal activity in monkey motor cortex in relation to time estimation.

Anticipation of predictable events is crucial for organizing motor performance. Using instructed delay tasks, it has been shown that even when delay duration is kept constant, reaction time fluctuates from trial to trial. As time estimation is at the core of anticipatory behavior, it is reasonable to speculate whether neuronal delay activity correlates with the subjective estimate of time. As a consequence of the scalar property of time estimation processes, the variability in time estimation increases continuously as time passes during the delay. This scalar property may then be reflected in the increasing variability in neuronal delay activity. We thus studied the influence of temporal prior information on neuronal delay activity in monkey motor cortex in two conceptually different tasks in which two equally probable delay durations were randomly presented. We hypothesized that if one considers the animal's subjective time as the time which elapses between the first (instruction) signal and movement onset, then, by suppressing this temporal variability, across-trial variability in neuronal discharge should decrease. We thus defined a new time scale in each trial such that, after rescaling, the time between the instruction signal and movement onset was identical in all trials. Each spike was then displaced in time accordingly. As expected, the variability in the timing of neuronal peak discharges no longer increased during the trial. This suggests a direct link between the temporal profile of spiking activity and time estimation. The timing of motor cortical activity reflected the 'elasticity' of the animal's subjective time.

Action Potentials↗