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Cross-correlation analysis of interneuronal connectivity in the motor cortex of the monkey.

Pairs of neurones were recorded within the hand region of the precentral motor cortex of monkeys trained to squeeze a force transducer between the thumb and index finger. Neuronal discharges of a pair of cells, recorded through the same electrode, were first examined for their co-variation with force. The discharges of those pairs with a consistent co-variation were cross-correlated during periods of constant isometric force. Cross-correlograms in the majority of cases had either a sharp peak or trough at latencies suggesting monosynaptic causal relations between the cell discharges. A peak was associated with pairs of cells whose discharges co-varied similarly with force and when a trough was observed, the cell discharges of the pair generally differed in their force co-variation. It is concluded that the action of motor cortical neurones is linked by common and recurrent collateral inputs during isometric co-contraction of finger muscles.

Action Potentials↗

Task-dependent modulation of inhibitory actions within the primary motor cortex.

In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205+/-42 ms; FDI 213+/-47 ms). SP duration at tonic isometric contraction amounted to 172+/-35 ms in APB and 178+/-31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159+/-15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies -30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex.

Adult↗

Sensory response properties of pyramidal tract neurons in the precentral motor cortex and postcentral gyrus of the rhesus monkey.

Pyramidal tract neurons (PTNs) were identified in precentral motor cortex (MI) and in postcentral cortex (PoC) of a monkey trained to pronate and supinate its forearm. PTN responses to passive, ramp-form displacements of the forearm were examined in relation to the size of the neuron (as reflected by its antidromic latency). Larger PTNs tended to exhibit transient responses to passive limb displacement, whereas smaller PTNs more frequently showed sustained responses. These findings suggest that smaller PTNs, that make up the majority of the total PTN population, receive continuous feedback during posture as well as during the dynamic phase of movement.

Afferent Pathways↗

[The effect of the iontophoretic application of acetylcholine to the neurons of the rabbit motor cortex on the functioning of the intracortical connections].

The multiunit activity of the neurons in the motor cortex was recorded in 8 rabbits under conditions of acetylcholine (or physiological saline) iontophoretic application. Crosscorrelation analysis of pulse trains was carried out. It was found out that acetylcholine activated the intracortical connections. Its application led to an increase in intensity of permanently existing short-latency interneuronal connections (i.e. the stable ones). Moreover, it led to a formation of the long-latency unstable connections. However, the obtained data do not suggests that acetylcholine promotes the formation of new short-latency connections between neurons. The modulatory influence of acetylcholine is discussed on the network activity of cortical neurons.

Acetylcholine↗

Bicuculline and neuronal activity in motor cortex.

We have studied the effects of bicuculline applied in microgram quantities to the precruciate gyrus (motor cortex) of cat upon visually evoked and spontaneous single-unit and slow-wave activity. The bicuculline produced an increase in both the visually evoked and the spontaneous unit activity. A surface negative component of the slow-wave response was markedly enhanced by the bicuculline. This component was associated with an intense suppression of spontaneous single-unit activity. Therefore, we have found that bicuculline has a convulsant effect upon single-unit activity as previously reported by others. However, we also found that bicuculline potentiates a process which appears associated with an enhancement of inhibition.

Animals↗

[Dynamic characteristics of motor reactions induced by motor cortex stimulation of unanesthetized cats].

Temporal characteristics of muscle contraction evoked by bipolar macrostimulation of cat motor cortex were studied in chronic experiments. Cortically induced flexion of the contralateral hindlimb was recorded isometrically and in some cases isotonically. Latency of muscle contraction exceeded 100 ms when low frequency (100-150/s) stimulation was applied. An increase in the stimulation frequency and intensity led to the shortening of the latency: under "optimal" parameters of the stimulation the minimal values were 30-35 ms. Time constant of the contraction increment was 50-80 ms whereas that of the contraction decrement after stimulation cessation reached 150-300 ms. The results obtained are considered from the view point of automatic regulation theory.

Animals↗

[Properties of rhythmic discharge by cat motor cortex neurons evoked by a continuous current through their membranes].

The properties of rhythmic discharge of motor cortex neurons evoked by dc depolarizing current through the membrane were studied in acute experiments on immobilized cats. Linear relation between the rate of rhythmic discharge and the strength of current was revealed, the slope of this relation being 18-10.7 imp/s nA. Correlation between input resistance and the slope of the discharge frequency current curve was demonstrated. Two types of adaptation to current were observed: exponential and undamped oscillations. The relation of the latency of the first spike and first interspike interval to current was hyperbolic. The role of dendrites in the observed phenomena is discussed.

Action Potentials↗

Quantitative evidence for multiple widespread representations of individual muscles in the cat motor cortex.

We sought to determine why a given muscle appears represented in widespread loci in the motor cortex (MCx). To this end, we microstimulated every 500 microm along medio-lateral rows and recorded the evoked electromyographic (EMG) responses of up to a dozen forelimb muscles of the cat. A consistent finding in all animals studied was that along a given row, distal muscle responses could be elicited from medially situated cortical loci and conversely, proximal muscles responses from laterally situated cortical loci. In many such cases, the evoked EMG responses were such that the largest responses from a distal muscle were obtained by stimulation at a medially situated point and those of a proximal muscle from a laterally situated point. A Spearman correlation analysis showed that there was no correlation between cortical position and where the peak response of a given muscle occurred. These quantitative results strongly support the view that in the forelimb area of the cat MCx there exists widespread 'colonies' of corticospinal neurons with common spinal cord targets.

Animals↗

[Reactions of cat motor cortex neurons to stimulation of the pyramidal tract and ventroposterolateral thalamic nuclei].

Responses of neurons of motor cortex evoked by stimulations of pyramidal tract (PT) and ventroposterolateral (VPL) nucleus of thalamus were studied in cats immobilized by Myorelaxin. Antidromic spikes were found in 22.6% and in 9.9% of cortical cells when PT and VPL were stimulated, respectively. Fast- and slow-conducting PT-neurones could be differentiated according to antidromic excitation latencies. PT stimulation evoked EPSPs in 46.3% of studied neurones and VPL stimulation--in 48.2% ones. Monosynaptic EPSPs were identified in responses of fast- and slow-conducting PT-units and of neurones projecting in VPL; mechanisms and functional role of such reactions are discussed. Di- and polysynaptic IPSPs were evoked in 74.5% of units by PT stimulation and in 94.4%--by VPL stimulation. Three groups of IPSPs were classified with durations to 120, 130-280 and more than 300 ms. Duration of PT-evoked IPSPs was higher in cortical neurones from surface layers and VPL-evoked ones--in units localized in deep layers.

Action Potentials↗

[Changes in excitability in the motor cortex of the dog during switching-over conditioned escape and avoidance reflexes].

Excitability of the motor cortex (projection of the foreleg), judged by the threshold of flexion reaction to its stimulation during elaboration of conditioned transswitching (CT), was studied in dogs. CT was elaborated for instrumental reflexes of escape (1-st CT variant) and avoidance (2-nd CT variant). In the 1-st variant the dog escaped from the hydrochloric acid solution, if during its administration it produced an active flexion of the foreleg in situation A and an active extension of the same leg in situation B, with a permanent action of a switch (a fan). In the 2-nd CT variant, the dog avoided the acid, if in situation A, in response to a tone of 250 Hz, it actively lifted its foreleg, and if in situation B, it actively resisted a passive lift in response to the same stimulus. In escape CT as well as in avoidance CT, there was a statistically significant difference between the thresholds of flexion reaction. The threshold was lower in situation of instrumental flexion reflex formation in comparison to the situation of extension reflex formation.

Animals↗

MRI measurement of the functional blood flow changes in a large superficial vein draining the motor cortex.

In this study, phase-contrast MR techniques are applied in order to measure the blood flow changes induced by a motor task in a large superficial vein draining the motor cortex. The measurements were applied to six healthy volunteers, in motor rest conditions and during performance of a motor task. The latter consisted of sequential finger-to-thumb opposition. The task was actually executed and mentally simulated. Significant blood flow increases were found when changing from from mental simulation to actual execution of the motor task (increases ranging between 1.6 and 10.3 ml/min, i.e. 9% and 45%, respectively) and from resting conditions to actual execution of the motor task (increases ranging between 1.7 and 14.0 ml/min, i.e. 32% and 72%, respectively).

Adult↗

Cancellation of a planned movement in monkey motor cortex.

Abruptly stopping a planned movement before it has even begun can be crucial to retarding a premature action. In the monkey motor cortex, we report herein that rapid cancellation of a prepared motor act involved the brief activation of neurons representing a movement in the opposite direction (anti-directional activity). When an expected GO signal failed to occur, this opposing anti-directional discharge appeared. It coincided in time with the cessation of the motor cortical activity preparing the requested arm reach. We suggest that functional interactions between subpopulations of neurons eliciting movements in opposite directions could rapidly alter population dynamics, and therefore be used to abruptly cancel a planned movement.

Action Potentials↗

Effect of pimozide on the increase of muscarinic receptors caused by mazindol and apomorphine in the rat cerebral motor cortex.

The effects of pimozide, mazindol and apomorphine on muscarinic receptors in homogenates of rat cerebral motor cortex were measured by binding assays, using 3H-N-methylscopolamine (3H-NMS) alone as ligand (for the measurement of M1- and M2-like receptors) or in the presence of carbachol or pirenzepine for determination of M1- and M2-like receptors, respectively. Female Wistar rats (150 g) were treated daily for one week with pimozide, a dopaminergic antagonist (10 and 20 mg/kg, po, by gavage), or with apomorphine (1 mg/kg, ip). In another set of experiments, animals were treated with pimozide and 30 min later with mazindol (10 mg/kg, po, by gavage) or apomorphine. The drugs were administered daily for one week. Controls received the same volume of saline. 3H-NMS binding was increased from the control value of 418 +/- 17 to 548 +/- 42 fmol/mg protein by administration of mazindol (10 mg/kg) but binding was reduced to 360 +/- 11 fmol/mg protein upon administration of pimozide (20 mg/kg) plus mazindol (10 mg/kg). Similarly 10 mg/kg pimozide reduced the increase in M1-like receptors caused by mazindol from 262 +/- 31 to 220 +/- 20 fmol/mg protein. Although 20 mg/kg pimozide alone produced a decrease in M1- plus M2-like receptors (from 418 +/- 17 to 348 +/- 22 fmol/mg protein), its action was preferentially on M2-like receptors, decreasing them from 148 +/- 10 to 111 +/- 15 fmol/mg protein in the control and treated groups, respectively. At the higher dose, 20 mg/kg pimozide also inhibited the 3H-NMS binding (M1- plus M2-like receptors) in the presence of apomorphine (263 +/- 25 vs 418 +/- 17 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reinforcement of subliminal flexion reflexes by transcranial magnetic stimulation of motor cortex in subjects with spinal cord injury.

A 20 msec train (500 Hz; 0.1-0.2 msec duration) of percutaneous electrical stimulation (ES) applied to the plantar surface was used to condition muscle responses evoked in tibialis anterior (TA) by transcranial magnetic stimulation of the motor cortex in 8 subjects with traumatic spinal cord injury (SCI). The intensity of conditioning ES was adjusted to just subthreshold for evoking flexion reflexes in TA and was delivered at conditioning-test (C-T) intervals of 15-60 msec prior to cortical stimulation. Four subjects with clinically complete SCI revealed no muscle response to cortical stimulation or following combined subliminal percutaneous ES and cortical stimulation. Four subjects (3 clinically incomplete and 1 complete injury) demonstrated muscle responses with a latency of 70-80 msec time-locked to the percutaneous ES when the conditioning subliminal stimulation was delivered at C-T: 15-40 msec. These responses, resembling suprathreshold flexion reflexes, reflect the convergence of excitatory afferent and cortical inputs and provide evidence of preserved corticospinal innervation to the L4-5 segmental motoneuron or interneuron pools. In 3 of the subjects this preserved corticospinal influence was evident despite absence of motor evoked potentials (MEPs) following cortical stimulation. The effect of the combined electrical and cortical stimulation in yielding suprathreshold flexion reflexes, instead of the facilitated MEPs seen in control subjects, appears to be related to slowed central conduction, prolonged temporal dispersion of the motoneuron facilitation following cortical stimulation and segmental reflex changes associated with disrupted modulation of interneuronal pathways. The results show this conditioning paradigm to be useful in revealing preserved corticospinal innervation in some SCI subjects with absent MEPs.

Adaptation, Physiological↗

Lasting cortical activation after repetitive TMS of the motor cortex: a glucose metabolic study.

OBJECTIVE: Cerebral [18F]fluorodeoxy-D-glucose PET ([18F]FDG-PET) was used to visualize the lasting neuronal activation after repetitive transcranial magnetic stimulation (rTMS) over the left hand area of the primary motor cortex (M1HAND). BACKGROUND: Applied over M1HAND, rTMS has been shown to produce a modulation of corticomotor excitability beyond the time of stimulation itself. METHODS: Eight right-handed subjects underwent nonquantitative [18F]FDG-PET measurements during two experimental conditions: at rest and after focal subthreshold 5-Hz rTMS over the left M1HAND. In the post-rTMS condition, [18F]FDG was injected immediately after the administration of 1,800 magnetic pulses over the left M1HAND. Relative differences in normalized regional cerebral metabolic rate of glucose (normalized rCMRglc) between conditions were determined using a voxel-by-voxel Student's t-test and volume-of-interest (VOI) analysis. Analysis was a priori restricted to the M1HAND, the supplementary motor area (SMA), and the primary auditory cortex of both hemispheres. RESULTS: A 5-Hz rTMS of the left M1HAND caused a lasting relative increase in normalized rCMRglc within the M1HAND bilaterally and the SMA. The magnitude and the topographic pattern of persisting relative rCMRglc increases within these motor cortical areas demonstrated considerable interindividual variations. CONCLUSIONS: Subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the hand area of the primary motor cortex is associated with a persisting neuronal activation in a distinct set of motor cortical areas beyond the time of stimulation. The current findings demonstrate that [18F]FDG-PET can localize and quantify regional net changes in synaptic cortical activity after rTMS and thus might elucidate the mechanisms underlying rTMS-associated therapeutic effects.

Adult↗

Motor cortex stimulation for enhancement of recovery after stroke: case report.

We present a case report of a 65-year-old patient who had a subcortical infarct and a right spastic hemiparesis that occurred 19 months before being treated with an investigational therapy consisting of low frequency subthreshold epidural motor cortex electrical stimulation delivered during structured occupational therapy repeated daily for three weeks. Before treatment the patient's affected arm rested in a flexion posture and he was unable to flex or extend the fingers. After three weeks of treatment, the resting tone of his arm had improved and he was able to grasp a pen and write letters. The Fugl-Meyer motor scale score improved from 36 to 46 and this improvement was sustained for four weeks after the conclusion of rehabilitation therapy. This is the first patient to be entered into a randomized clinical feasibility and safety study assessing functional improvement in stroke patients treated with epidural cortical stimulation concurrent with occupational therapy (an investigational therapy).

Aged↗

Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements.

1. Single-cell activity was recorded from three different motor areas in the cerebral cortex: the primary motor cortex (MI), supplementary motor area (SMA), and premotor cortex (PM). 2. Three monkeys (Macaca fuscata) were trained to perform a sequential motor task in two different conditions. In one condition (visually triggered task, VT), they reached to and touched three pads placed in a front panel by following lights illuminated individually from behind the pads. In the other condition (internally guided task, IT), they had to remember a predetermined sequence and press the three pads without visual guidance. In a transitional phase between the two conditions, the animals learned to memorize the correct sequence. Auditory instruction signals (tones of different frequencies) told the animal which mode it was in. After the instruction signals, the animals waited for a visual signal that triggered the first movement. 3. Neuronal activity was analyzed during three defined periods: delay period, premovement period, and movement period. Statistical comparisons were made to detect differences between the two behavioral modes with respect to the activity in each period. 4. Most, if not all, of MI neurons exhibited similar activity during the delay, premovement, and movement periods, regardless of whether the sequential motor task was visually guided or internally determined. 5. More than one-half of the SMA neurons were preferentially or exclusively active in relation to IT during both the premovement (55%) and movement (65%) periods. In contrast, PM neurons were more active (55% and 64% during the premovement and movement periods) in VT. 6. During the instructed-delay period, a majority of SMA neurons exhibited preferential or exclusive relation to IT whereas the activity in PM neurons was observed equally in different modes. 7. Two types of neurons exhibiting properties of special interest were observed. Sequence-specific neurons (active in a particular sequence only) were more common in SMA, whereas transition-specific neurons (active only at the transitional phase) were more common in PM. 8. Although a strict functional dichotomy is not acceptable, these observations support a hypothesis that the SMA is more related to IT, whereas PM is more involved in VT. 9. Some indications pointing to a functional subdivision of PM are obtained.

Animals↗

The effect of motor cortex stimulation in deafferentated rats.

OBJECTIVES: The aim of the study was to describe the effect of motor cortex stimulation (MCS) on pain thresholds in deafferentated rats. SETTINGS AND DESIGN: The effect of MCS was studied in 18 deafferentated and 14 intact laboratory rats, using a standardised plantar test and tail-flick latencies. Two inoxious stimulation electrodes were implanted subdurally over the cerebral cortex and a C5-Th1 dorsal root rhizotomy was performed on the left side. Pain thresholds were measured before and after cortical stimulation. The data were analysed with ANOVA for repeated measures. RESULTS: MCS in intact animals evoked no changes in pain thresholds except for the contralateral forelimb, in which the pain threshold increased after MCS. Following deafferentation, pain thresholds increased in both plantar test and tail-flick in comparison to baseline values. When MCS was applied to the deafferentated animals, the pain thresholds returned to baseline levels. The effect of MCS disappeared within 24 hours. MAIN FINDINGS: 1. MCS in intact animals evoked hypoesthesia in the corresponding contralateral forelimb; 2. deafferentation itself increased pain thresholds in the unaffected limbs; 3. under MCS, pain thresholds in deafferentated rats were not different from pre-dafferentation values; 4. the effect of MCS disappeared in 24 hours and oscillated. CONCLUSIONS: Our results show a similar effect of the stimulation in man and experimental animals despite the differences in the organisation of the cerebral cortex. The use of laboratory animals is promising for further studies in the field of involved antalgic mechanisms of MCS.

Animals↗