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Time course of motor cortex reorganization following botulinum toxin injection into the vibrissal pad of the adult rat.

The present experiment studies representation patterns in the motor cortex (M1) of adult rats, 1, 3, 6, and 12 days after unilateral injection of Botulinum Toxin (BTX) into the vibrissa pad. Intracortical microstimulation (ICMS) was used to evidence changes in the representation over time and in the current thresholds required to evoke movements inside the disconnected vibrissa region. After 1 day, isolated as well as contiguous negative sites were observed within the motor cortex corresponding to the disconnected vibrissa region. Thereafter the percentage of unresponsive sites decreased so that after 6 days, the number of unresponsive sites was not significantly higher than those in the control hemispheres. Within the disconnected vibrissa region, electrical stimulation elicited forelimb, eye, ipsilateral vibrissa and neck movements. Following BTX injection, the enlargement of the forelimb representation into the disconnected vibrissa representation began during the first day and stabilized during the second week after injection. In the first days, stimulation thresholds in expanded forelimb sites were higher than those required for similar movement in normal M1 forelimb representation. These thresholds then declined so that in approximately 6 days they were similar to normal. There was no clear evidence that stimulation of sites in the medial part of disconnected vibrissa-cortex evoked eye movements during the first 6 days after BTX injection. After this time, thresholds required to evoke eye movement in expanded sites were generally similar to, and never higher than, those needed to evoke this movement in control sites. Intermingled ipsilateral vibrissa and neck movement occupies part of the medial vibrissa region. Over the 12 days, extension of the ipsilateral vibrissa representation shrank while the representation of neck movement remained unchanged. Throughout the entire time there was no change in the excitability of these sites and the thresholds remained higher than that needed to elicit the vibrissa movement normally represented in this cortical region. No significant differences in threshold were found over time for any of the other movement categories represented in M1. These results indicate that, over time, the new movements inside the disconnected vibrissa region develop differently in M1 following peripheral motor disconnection. The implications for mechanisms involved in cortical plasticity are discussed.

Animals↗

Instrumentalization of movements evoked by stimulation of the motor cortex by food reinforcement in dogs.

The possibility that hindlimb movements (elevations) evoked by stimulation of the corresponding contralateral area of the motor cortex could be instrumentalized by reinforcement with food was demonstrated, contradicting some previously published data. Operant movements (interstimulus voluntary high elevations of the hindlimb) were acquired as a result of consistent combinations: cortical stimulation - movement - food. Acquisition required more than 50-200 combinations. Delivery of food was accompanied by a click at exactly the moment at which the hindlimb reached the required height. The click became the food-related conditioned signal and served as a secondary operant reinforcement, which facilitated acquisition of the operant movement. These results support the view that the motor cortex can have an immediate role in forming "operant" temporary connections (motivation-movement) and that simple operant movements can be initiated via this arc.

Animals↗

Motor cortex excitability changes preceding voluntary muscle activity in simple reaction time task.

The effect of transcranial magnetic stimulation (TMS) on reaction time (RT) and motor cortex excitability in the premovement period was investigated. Single and paired-pulse TMS with 3 and 13 ms interstimulus intervals (ISI) were applied to the left motor cortex at different delays after a visual command for isometric right hand index finger abduction. Motor evoked potentials (MEPs) recorded from the right first dorsal interosseous (FDI) were analysed to assess cortex excitability. The MEPs in response to single pulse TMS were gradually increased in the premovement period in general, but strongly augmented in a period of 90-100 ms before the voluntary myoelectrical activity (EMG) onset. In paired-pulse TMS (13 ms ISI), the MEP augmentation was smaller but started earlier before the EMG burst, and a gradual increase of MEP amplitudes was not evident. In case of 3 ms ISI, the expected intracortical inhibition (ICI) was evident only when TMS preceded the voluntary EMG by an interval of more than 60 ms, but at shorter intervals, rather some MEP augmentation was observed. Generally, the augmentation of MEPs in the premovement period was more pronounced in single pulse TMS. Most strikingly, a dead band period without MEP occurrences was observed within an interval of 30-50 ms before the voluntary EMG. In conclusion, parallel action of intracortical facilitation (ICF) and ICI as well as different dynamic behaviour of ICF and pre movement facilitation may explain the earlier mentioned effects. Moreover, this leads to an extended description of the rather subtle TMS influence on RT.

Adaptation, Physiological↗

Unilateral lesions of the forelimb area of rat motor cortex: lack of evidence for use-dependent neural growth in the undamaged hemisphere.

Unilateral lesions of the forelimb area of the motor cortex have been reported to produce enhanced dendritic outgrowth in the undamaged hemisphere in response to the behavioral asymmetry produced by the lesions (e.g. Jones, T.A. and Schallert, T., Use-dependent growth of pyramidal neurons after neocortical damage, J. Neurosci, 14 (1994) 2140-2152). We attempted to replicate this result and to determine if there were sex differences in cortical plasticity using the Jones and Schallert model. Animals were given either unilateral aspiration or electrolytic lesions of the forelimb area of the motor cortex or a sham operation. Use of the forelimb ipsilateral to the lesion for postural support was assessed pre- and postsurgery. Eighteen days after surgery the animals were sacrificed. and the brains processed for Golgi-Cox staining or a series of other stains for acetylcholine, astrocytes (glial fibrillary acidic protein), and microglia (OX-42). Although the lesions produced significant behavioral asymmetry and enhanced glial response on the lesioned side, there was little evidence for use-dependent neural growth in the undamaged hemisphere in either sex.

Acetylcholine↗

Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.

OBJECTIVES: The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. METHODS: We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus). RESULTS: Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. CONCLUSIONS: The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.

Aged↗

Attention to movement modulates activity in sensori-motor areas, including primary motor cortex.

Attention to sensory stimulation modulates behavioural responses and cortical activity. Attention to movement can also modulate motor responses. For example, directing attention away from cued movements can increase reaction times. This study used fMRI to determine where in the motor cortex attention to movement modulates activity. Attention to movement was reduced by asking subjects to perform a concurrent distractor task (counting backwards). Sensori-motor areas showing a negative interaction between counting and movement (i.e. reduced activation in the dual task condition relative to the sum of the single task conditions) included the supplementary motor area (SMA), cingulate cortex, insula and post-central gyrus. A separate volumes-of-interest analysis revealed significant reductions in mean percent signal change in the dual task compared to the single task in a portion of the pre-central gyrus, deep in the central sulcus (thought to correspond to area 4p) and SMA. We conclude that the brain network for motor control is modulated by attention at multiple sites, including the primary motor cortex. These results are also discussed with reference to theories concerning the neural correlates of dual task performance and mental calculation and have implications for the interpretation of functional imaging studies of normal and impaired motor performance.

Adult↗

Modulation of parvalbumin expression in the motor cortex of parkinsonian rats.

Dopamine deficiency in Parkinson's disease leads to numerous molecular changes in basal ganglia. However, the consequences of these changes on the motor cortex remain unclear. Here we show that the immunoreactivity of parvalbumin, which is expressed in GABAergic interneurons, increases in the primary motor cortex of parkinsonian rats. This increase can be reversed by a subsequent lesion of the subthalamic nucleus. These results suggest that dopamine deficiency induces reversible changes in GABAergic cortical cells, which might be linked with parkinsonian symptoms.

Animals↗

Activation of human primary motor cortex during action observation: a neuromagnetic study.

The monkey premotor cortex contains neurons that discharge during action execution and during observation of actions made by others. Transcranial magnetic stimulation experiments suggest that a similar observation/execution matching system also is present in humans. We recorded neuromagnetic oscillatory activity of the human precentral cortex from 10 healthy volunteers while (i) they had no task to perform, (ii) they were manipulating a small object, and (iii) they were observing another individual performing the same task. The left and right median nerves were stimulated alternately (interstimulus interval, 1.5 s) at intensities exceeding motor threshold, and the poststimulus rebound of the rolandic 15- to 25-Hz activity was quantified. In agreement with previous studies, the rebound was strongly suppressed bilaterally during object manipulation. Most interestingly, the rebound also was significantly diminished during action observation (31-46% of the suppression during object manipulation). Control experiments, in which subjects were instructed to observe stationary or moving stimuli, confirmed the specificity of the suppression effect. Because the recorded 15- to 25-Hz activity is known to originate mainly in the precentral motor cortex, we concluded that the human primary motor cortex is activated during observation as well as execution of motor tasks. These findings have implications for a better understanding of the machinery underlying action recognition in humans.

Animals↗

[The formation of instrumental escape reactions based on movements induced by stimulation of the motor cortex in dogs].

The purpose of the study was to find out the possibility of instrumentalization of movements induced by stimulation of the motor cortex (MI) in dogs. The scheme of conditioning was as follows. The electrical shock applied to the right forepaw was used for a weak painful stimulation. In 3 s, the stimulation of the MI was added, which elicited the right hind limb flexion. The shock was switched off at the moment of the hind limb lifting. After several trials, the shock began to elicit the hind limb flexion before the cortical stimulation. The scheme of conditioning excluded the possibility of instrumentalization of irrelevant chance movements. Prolonging the shock by 2 s after the cortical stimulation led to extinction of acquired responses. Renewal of reinforcement of the hind limb movements by immediate switching off the shock led to recovery of conditioned reactions. Thus, the instrumental nature of the responses has been proved. The obtained results are of particular interest in connection with the findings that similar acquisition of instrumental reaction on the basis of food reinforcement is impossible. The results support the assumption that the "instrumental" conditioned connection can be addressed directly to the motor cortex.

Animals↗

Intracortical origin of the short latency facilitation produced by pairs of threshold magnetic stimuli applied to human motor cortex.

Under certain conditions, EMG responses evoked by pairs of transcranial magnetic stimuli over the motor cortex are larger than the sum of the responses to each stimulus given alone. This occurs with interstimulus intervals of around 1.3, 2.5 and 4.3 ms and could be due to interaction between the responses to each stimulus at either the cortex or spinal cord. We recorded the descending volleys set up by such pairs of stimuli from the cervical epidural space of five patients implanted with chronic stimulators for pain control. Interstimulus intervals of 1, 1.2, 1.4 and 2 ms were used to investigate the first peak of facilitation. Enhanced EMG responses occurred after pairs of stimuli at 1, 1.2 and 1.4 ms, and these were accompanied by larger and more numerous descending volleys than expected from the sum of each stimulus alone. We conclude that facilitatory interaction between the stimuli can occur within the cerebral cortex. This may involve elements that produce repetitive I-wave activity in response to a single stimulus.

Adult↗

Vibrissa movement elicited by rhythmic electrical microstimulation to motor cortex in the aroused rat mimics exploratory whisking.

The rhythmic motor activity of the vibrissae that rodents use for the tactile localization of objects provides a model system for understanding patterned motor activity in mammals. Evidence suggests that neural circuitry in the brain stem provides rhythmic drive to the vibrissae. Yet multiple brain structures at higher levels of organization, including vibrissa primary motor cortex (M1), have direct projections to brain stem nuclei that are implicated in whisking. We thus asked whether output from M1 can control vibrissa movement on the approximately 10-Hz scale of the natural rhythmic movement of the vibrissae. Our assay of cortical control made use of periodic intracortical microstimulation (ICMS) to excite a region of vibrissa M1 cortex in awake, behaving animals and measurements of the stimulus-locked electromyogram (EMG) in both the intrinsic and extrinsic muscles that drive the vibrissae. We observed that ICMS evoked a prompt activation of the extrinsic muscles and a delayed and prolonged response in the intrinsic muscles. The relative timing and shape of these waveforms approximates the EMG waveforms seen during natural exploratory whisking. We further observed prompt activation of the intrinsic muscles, an occurrence not seen during exploratory whisking. Despite the latter difference in muscular activation, the motion of the vibrissae evoked by periodic ICMS strongly resembled the motion during natural, exploratory whisking. Interestingly, the extent of the movement was proportional to the level of arousal, as quantified by the amplitude of hippocampal activity in the theta frequency band. We interpret these data as demonstrating that M1 cortex can, in principle, initiate the full pattern of whisking on a cycle-by-cycle basis in aroused animals. Beyond issues of natural motor control, our result may bear on the design of algorithms for neuroprosthetic control of motor output.

Animals↗

The origin of thalamic inputs to the "hand" representation in the primary motor cortex.

We used retrograde transport of WGA-HRP to examine the origin of thalamic inputs to the "hand" representation in the primary motor cortex of macaques (Macaca nemestrina). Injections were placed in either the crest of the precentral gyrus or the rostral bank of the central sulcus. The sites for injection in the sulcus were determined by using intracortical stimulation to map the location of hand representation. We found that the precentral gyrus and central sulcus receive their predominant input from different subdivisions of the ventrolateral thalamus. Ventralis posterior lateralis pars oralis (VPLo) provides the most substantial input to a portion of the hand representation on the gyrus. In contrast, Ventralis lateralis pars oralis (VLo) provides the most substantial input to a portion of the hand representation in the sulcus. Prior studies have shown that VPLo is a major site of termination of cerebellar efferents and that VLo is a major site of termination of pallidal efferents. Thus, our results indicate that both the basal ganglia and the cerebellum "directly" influence the "hand" representation of the primary motor cortex.

Amidines↗

Laminar differences in field potential morphology and long-term potentiation in motor cortex coronal slices from both unstimulated and previously potentiated rats.

We have reported that long-term potentiation (LTP) can be reliably induced in motor cortex of adult, freely moving rats by the application of spaced and repeated high frequency stimulating trains to the white matter. In the present study, we monitored field potentials (FPs) and LTP in both layer II/III and V in coronal slices of motor cortex taken from implanted control and previously potentiated Long-Evans rats. The baseline FP amplitudes were decreased in layer II/III, and the amplitude of small spikes was significantly increased in layer V in slices from previously potentiated rats compared to unpotentiated control rats. In response to high frequency stimulation applied to the slice itself, both implanted control and previously potentiated rats showed similar levels of LTP in layer II/III. LTP could not be induced in layer V. These results show that layer II/III and V respond differently to high frequency stimulation in vitro. In addition, layer II/III responds very differently in slice compared to chronic preparations.

Animals↗

Effects of aging on motor cortex excitability.

To determine whether aging is associated with changes in excitability of the cerebral cortex, we evaluated the excitability of the motor cortex with transcranial magnetic stimulation (TMS). We compared TMS related measures obtained in a group of young people with those of a group of old people. Motor evoked potential (MEP) amplitude was significantly smaller in older than in younger controls (1.3+/-0.8 mV versus 2.7+/-1.1 mV; p<0.0071). Mean cortical silent period (CSP) duration was shorter in older than in younger controls (87+/-29 ms versus 147+/-39 ms; p<0.0071). SP duration/MEP amplitude ratios were similar in both groups. Our results are consistent with an impaired efficiency of some intracortical circuits in old age.

Adult↗

[Bilateral motor cortex effects on interneurons of the ventral horn of the lumbar segments].

The ventral horn interneurons in the spinal cord L6-7 segments were recorded in anesthetized cats during stimulation of the pericruciate cortex of both cerebral hemispheres. The majority of ventral interneurons are activated by volleys from the contralateral motor cortex and nearly half of them--by volleys from the ipsilateral cortex as well. Two kinds of firing patterns occurred: separate spikes and bursts of spikes. The latency of the 1st type firing was significantly greater than that of the 2nd one. There was a close relation of convergence of the afferent and corticospinal volleys on ventral horn interneurons: neurons activated by ipsilateral afferents only received synaptic influence only from the contralateral motor cortex whereas neurons with ipsilateral as well as contralateral inputs were activated by corticospinal volleys from both hemispheres. The interneurons with bilateral segmental and supraspinal connections seem to be involved in integrative action as important elements of the neuronal mechanism of bilateral motor coordination.

Action Potentials↗

Influence of pulse configuration and direction of coil current on excitatory effects of magnetic motor cortex and nerve stimulation.

UNLABELLED: This paper describes the influence of pulse configuration and current direction on the excitation of the hand-associated motor cortex and the median nerve by magnetic stimulation. Monophasic and biphasic current pulses with the same peak rise time of 80 micros and a maximum rate of current change (dI/dt) were discharged through an eight-shaped coil of the stimulator used (Dantec MagPro). Two current directions with opposite orientation in the coil axis were studied. FINDINGS: (1) for both, cortex and nerve stimulation, biphasic stimuli were more effective and elicited compound muscle action potentials (CMAPs) with lower thresholds and larger amplitudes. (2) Using biphasic pulses the direction of the currents in the first phase of the pulse did not influence the CMAP amplitude. (3) Using monophasic pulses induced currents oriented postero-anteriorly in the motor cortex or orthodromically along the nerve axis elicited larger CMAPs than currents in the opposite orientation. (4) Pulse configuration did not influence the CMAP-latencies and by this the stimulation site (cortex, nerve). CONCLUSION: Monophasic stimuli are useful to investigate excitation effects which are dependent on the current direction. The application of biphasic stimuli with their stronger excitation effects might be advantageous when patients with high cortical thresholds or deep lying nerves shall be investigated.

Action Potentials↗

Localization of area prostriata and its projection to the cingulate motor cortex in the rhesus monkey.

Area prostriata is a poorly understood cortical area located in the anterior portion of the calcarine sulcus. It has attracted interest as a separate visual area and progenitor for the cortex of this modality. In this report we describe a direct projection from area prostriata to the rostral cingulate motor cortex (M3) that forms the fundus and lower bank of the anterior part of the cingulate sulcus. Injections of retrograde tracers in M3 resulted in labeled neurons in layers III, V and VI of prostriate cortex. However, injections of anterograde tracers in M3 did not demonstrate axon terminals in area prostriata. This connection was organized topographically such that the rostral part of M3 received input from the dorsal region of prostriate cortex, whereas middle and caudal levels of M3 received input from more ventral locations. Injections of retrograde and anterograde tracers in the caudal cingulate motor cortex (M4) did not produce labeling in prostriate cortex. Cytoarchitectural analysis confirmed the identity of area prostriata and further clarified its extent and borders with the parasubiculum of the hippocampal formation rostrally, and V1 of the visual cortex caudally. This linkage between cortex bordering V1 and cortex giving rise to a component of the corticofacial and corticospinal pathways demonstrates a more direct visuomotor route than visual association projections coursing laterally.

Animals↗

The after effects of motor cortex rTMS depend on the state of contraction when rTMS is applied.

OBJECTIVE: To test whether the after effects of 5 Hz focal rTMS over the primary motor cortex are modulated by the state of muscle contraction when the rTMS is applied. METHODS: Ten healthy volunteers gave informed consent to the studies. Fifty stimuli at active motor threshold intensity were applied at 5 Hz to the forearm motor area during 10% MVC isometric wrist flexion, 10% MVC wrist extension and at rest. Short interval intracortical inhibition (SICI: interstimulus intervals of 2-5 ms) and intracortical facilitation (interstimulus intervals of 7 and 10 ms) were recorded at rest before and after rTMS from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles with surface electrodes. RESULTS: rTMS during wrist flexion decreased SICI in the FCR whereas SICI was increased if rTMS was given during wrist extension. The opposite was true in ECR: SICI was increased if rTMS was applied during wrist flexion, whereas it was reduced if rTMS was given during wrist extension. rTMS applied at rest produced a small overall decrease of SICI in FCR and ECR but this was not individually significant in the FCR. The 10 s wrist flexion without any rTMS did not have any effect on SICI. CONCLUSIONS: The after effects of motor cortex rTMS can be selectively modulated by the pattern of muscle contraction.

Adult↗