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Specificity of sensorimotor learning and the neural code: neuronal representations in the primary motor cortex.

Human studies show that the learning of a new sensorimotor mapping that requires adaptation to directional errors is local and generalizes poorly to untrained directions. We trained monkeys to learn new visuomotor rotations for only one target in space and recorded neuronal activity in the primary motor cortex before, during and after learning. Similar to humans, the monkeys showed poor transfer of learning to other directions, as observed by behavioral aftereffects for untrained directions. To test for internal representations underlying these changes, we compared two features of neuronal activity before and after learning: changes in firing rates and changes in information content. Specific elevations of firing rate were only observed in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation; namely cells only showed plasticity if their preferred direction was near the training one. We applied measures from information theory to probe for learning-related changes in the neuronal code. Single cells conveyed more information about the direction of movement and this specific improvement in encoding was correlated with an increase in the slope of the neurons' tuning curve. Further, the improved information after learning enabled a more accurate reconstruction of movement direction from neuronal populations. Our findings suggest a neural mechanism for the confined generalization of a newly acquired internal model by showing a tight relationship between the locality of learning and the properties of neurons. They also provide direct evidence for improvement in the neural code as a result of learning.

Action Potentials↗

[Characteristics and mechanisms of the interhemisphere synchronization in the rat motor cortex].

Synchronised activity of the callosal cells was studied in the rat motor cortex. Cross-correlation analysis revealed narrow symmetrical peaks (less than 20 ms) and intermediate ones (30-80 ms). Common neuron(s) located in one hemisphere reciprocally connected callosal cells can play the role of a "common input" that synchronises discharges of the cells in both hemispheres. The narrow and intermediate peaks seem to be mediated by mono- and polysynaptic connections, resp.

Action Potentials↗

Modulation of human motor cortex excitability by single doses of amantadine.

Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.

Adult↗

Facilitation of responses to motor cortex stimulation: effects of isometric voluntary contraction.

In 7 normal subjects we compared the facilitatory effect of isometric contraction of the tibialis anterior on the size of electromyographic responses evoked in this muscle by electric stimuli applied over the cervical column and by electric and magnetic percutaneous stimulation of the motor cortex. No significant difference was found between the degrees of facilitation of the responses to any of the stimuli. Using collision techniques, we also showed that the pyramidal fibers activated by spinal and cortical stimuli are the same. Facilitation induced by isometric contraction (20% maximum) was of similar or greater magnitude than that found with constant vibration of the tendon of the target muscle. In cases where vibration and contraction had equal facilitatory effects, there was no further facilitation of the responses when both conditions were applied together. These findings indicate that the facilitatory effect of isometric contraction of the target muscle essentially originates at a spinal level rather than in the motor cortex.

Adult↗

[The neuronal activity of the cat motor cortex during the differentiation between the reactions of placing support on the right and left paws acquired by stimulation of the parietal cortex of either hemisphere].

Cats were simultaneously trained to differentiate two conditioned reflexes: conditions placing of the right and the left forepaws electrical stimulation of the ipsilateral parietal cortices (area 5) serving as a conditioned stimulus (the right and the left areas correspondingly). Single unit responses of the shortest latencies in the motor cortex did not depend upon the cases whether parietal stimulation evoked placing or did not. Excitatory single unit responses occurring within 20-200 ms latency period from the stimulation onset were observed to be present only if the placing reaction was performed on the side controlled by the motor cortex of the given hemisphere. In the absence of conditioned placing after satiation of an animal or if the conditioned placing was performed by the other forepaw these excitatory responses were replaced by inhibitory pauses within the same time limits.

Animals↗

Topographic distribution of connections from the primary motor cortex to the corpus striatum in Aotus trivirgatus.

Connections between the primary motor cortex (MI) and the corpus striatum were studied in the owl monkey. Representations of specific body movements were elicited in MI by microstimulation techniques, and the efferent projections from these stimulation sites were labeled with wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP). Dense projections were found in the putamen ipsilateral to the injection site and sparser projections occupied comparable areas in the contralateral putamen. Representations of hindpaw regions projected to the dorsomedial portion of the putamen with only slight extensions across cell bridges into the caudate nucleus. Representations of the forepaw and head projected to progressively more ventrolateral zones of the dorsal two-thirds of the putamen. Projections from injections of cortex representing discrete body movements terminated in an irregular or patchy distribution over a relatively large portion of the putamen. Extensive projections from relatively discrete injections in MI are indicative of a large degree of divergence and provide evidence for possible overlap from representations of relatively disparate body parts. The results are consistent with observations reported in other species of primates, but different from those seen in carnivores. This difference is discussed with regard to possible general features of corticostriate organization.

Animals↗

The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Adult↗

[Motor cortex stimulation in the treatment of the central pain: a case report].

Motor cortex stimulation (MCS) is one of the methods of treatment in chronic pain syndromes. According to recent clinical studies effectiveness of this mode of treatment in the central pain has been proved. This article reports the first case of a patient with the thalamic syndrome treated with MCS in the Clinical Department of Neurosurgery in Military Clinical Hospital in Bydgoszcz. The procedure of implantation was performed with the guidance of a frameless neuronavigation system which served for localization of the precentral gyrus. Correct placement of the electrode was confirmed by intraoperative stimulation. As a result of the treatment a decrease of pain and improvement of psychosocial state has been achieved.

Chronic Disease↗

[Quantitative study on cerebral motor cortex structure of kindling rat induced by coriaria lactone].

Ten male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly every 3.5 days to induce kindling seizures. The controls were injected with normal saline. Cerebral motor cortex of kindling rats was taken at the time between seizures and layer V was compared morphologically with that of the control. The number of neurons and neuroglias was counted from light micrographs. The numerical density and length fraction of boutons on the surface of pyramidal somata were measured from electron micrographs with MIAS 300 type image analyser. The number of synapses in neuropil was counted directly and the areal fraction of various constitute in neuropil was measured stereologically from EM photos. In the experimental rats, the number of neurons remained unchanged and the numerical density and length fraction of boutons on the surface of pyramidal somata showed no change, either. The number of synapses (or presynaptic terminals) decreased significantly in neuropil, but the areal fraction of synaptic terminals had no change and the areal fraction of dendrites and unmyelinated fibers decreased. The areal fraction of myelinated fibers increased significantly. The number of neuroglias and the areal fraction of neuroglial processes increased significantly in the experimental rats. The data suggest that the major morphological changes are manifested as a decline in the pyramidal dendritic components, especially dendritic spines, and the axons with its terminals from superficial neurons in motor cortex layer V of the kindling rats induced by coriaria lactone, besides the neurogliosis which is similar to that occurring in other long-term seizures.

Animals↗

Chemically-induced long-term potentiation in rat motor cortex involves activation of extracellular signal-regulated kinase cascade.

The involvement of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in long-lasting potentiation of synaptic transmission, induced by tetraethylammonium (TEA) or by elevated extracellular calcium concentration, was investigated in layer V horizontal connections within motor cortex in rat brain slices. Brief application of TEA (25 mM) resulted in a long-lasting potentiation of field potentials by 54+/-12%. A transient exposure of slices to elevated extracellular calcium (5 mM) induced long-lasting potentiation of responses reaching 30+/-8%. The induction of both forms of potentiation was prevented by the exposure of slices to inhibitors of the upstream activator of ERK 1/2, MEK (ERK kinase), U0126 (20 microM) and PD 98059 (50 microM). PhosphoERK2 immunoreactivity was transiently increased above baseline levels 15 min after termination of the exposure of slices to either TEA or elevated calcium concentration. Both forms of potentiation were partially occluded by Sp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Sp-cAMPS; 100 microM), an activator of cAMP-dependent protein kinase (PKA), and they were blocked after preincubation with Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS; 100 microM), a specific inhibitor of PKA activation by cAMP. It has previously been shown that TEA-induced potentiation represents a N-methyl-d-aspartate (NMDA) receptor-independent form of persistent synaptic enhancement, and, on the contrary, calcium-induced potentiation depends on NMDA receptors. Thus, the activation of PKA and the ERK1/2 cascade are required for two forms of chemically induced long-lasting increases of synaptic efficacy in slices of rat motor cortex.

Animals↗

Making arm movements within different parts of space: dynamic aspects in the primate motor cortex.

The activity of 176 individual cells in the arm area of motor cortex (areas 4 and 6) was studied while monkeys made arm movements of similar direction within different parts of extrapersonal space. The behavioral paradigm used was a 3-dimensional reaction-time task aimed at dissociating the direction of movement, which remained similar across the work space, from the patterns of muscular activity and the angular joint excursions necessary to perform these movements. In agreement with other studies (Georgopoulos et al., 1982; Schwartz et al., 1988), we found that, within a given part of space, the activity of 169 (96.0%) cells studied increased most for a given preferred direction and less for other directions of movement. This change was graded in an orderly fashion. We further analyzed the orientation in space of the cells' preferred directions under the differing conditions of the task. We found that, as movements with similar trajectories were made within different parts of space, the cells' preferred directions changed spatial orientation. This change was of different magnitudes for different cells, but at the level of the population, it followed closely the changes in orientation of the arm necessary to perform the movements required by the task. Movement population vectors (Georgopoulos et al., 1983, 1986, 1988) computed from cell activity proved to be good predictors of movement direction regardless of where in space the movements were performed. These results indicate that motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space. The data are discussed in relation to the existence of mechanisms which facilitate the transformation between extrinsic and intrinsic coordinates. These transformations are necessary to perform arm movements to visual targets in space.

Animals↗

Two types of TMS-induced movement variability after stimulation of the primary motor cortex.

Using transcranial magnetic stimulation, we studied the role of the primary motor cortex (M1) in repetitive movements, examining whether the functional contribution of this region is associated with controlling response timing, response implementation, or both. In two experiments, participants performed a rhythmic tapping task, attempting to produce isochronous intervals (range of 350-550 ms) while stimulation was applied over M1 or a control site. M1 stimulation was associated with increased variability of the inter-tap intervals (ITI), and, by manipulating stimulation intensity, we identified two distinct changes in performance: a generalized increase in ITI variability and a delay in the subsequent response when the pulse fell within a restricted window prior to movement onset. Using a series of simulations, we demonstrate that the general increase in variability and the temporally specific delay reflect disruption of response implementation processes rather than an increase in noise associated with response timing.

Evoked Potentials↗

Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by migraine with aura.

We previously showed paradoxical facilitatory effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of patients suffering migraine with aura. In this study we evaluated the effects of 1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor cortex to explore whether the abnormal pattern of excitability extends beyond the sensory cortex also involving motor areas in migraine with aura. Nine patients affected by migraine with aura and eight healthy controls entered into the study. The hot spot for activation of the right abductor pollicis brevis (APB) was checked by means of a figure-of-eight coil and motor threshold (MT) recorded on this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity were delivered at the hot spot. Before and after rTMS, intracortical inhibitory and facilitatory circuit excitability was assessed by means of a paired pulse paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed that in basal condition migraineurs present significantly reduced levels of intracortical inhibition (ICI) compared to controls. More importantly, opposite results were obtained in migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically, whereas intracortical facilitation (ICF) significantly decreased in controls, it significantly increased in migraineurs. ICI levels were not significantly affected by low-frequency stimulation. Our results showed that motor as well as sensory cortex of migraine patients present an abnormal modulation of cortical excitability, where a relevant role is likely played by the inefficiency of inhibitory circuits.

Adult↗

Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study.

BACKGROUND: The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections. METHODS: Intracortical excitatory and inhibitory systems were tested in three individuals with complete agenesis of the corpus callosum and sixteen healthy individuals. These systems were assessed using transcranial magnetic stimulation (TMS) protocols: motor threshold at rest, paired-pulse curve, and cortical silent period. RESULTS: TMS revealed no difference between the patient and control groups on the motor threshold measure, as well as intracortical facilitation and intracortical inhibition systems as tested by paired stimulation. However, intrahemispheric inhibitory function was found to be abnormal in participants without callosal projections, as the cortical silent period duration was significantly increased in the patient group. CONCLUSION: These data suggest that in addition to previously reported impaired interhemispheric function, patients lacking the entire corpus callosum also display abnormal intrahemispheric excitability of the primary motor cortex.

Adult↗

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo.

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.

Adult↗

Intracortical distribution of axonal collaterals of pyramidal tract cells in the cat motor cortex.

Slow and fast pyramidal tract cells (Pt cells) from the cat motor cortex were identified antidromically and injected with horseradish peroxidase (HRP). The axonal collaterals of these cells were mapped following HRP histochemistry with benzidine di-hydrochloride. All cells, slow or fast, show a similar arrangement of their collaterals. A proximal axonal network of 0.5-0.8 mm in diameter delimits a local field of action for collaterals in layers V and VI. The tangential expansion of this local field corresponds to that of the basal dendritic domain of Pt neurons. Much longer collaterals running for millimeters in the lower gray or white matter were observed in all cells. They form at a cortical level a distal field of action for Pt neurons. Many of these long branches were traced to other regions of area 4 or toward other cytoarchitectonic areas. In one case a collateral was seen entering and dividing in area 3a. Due to limitations of the HRP technique most of these long branches could not be followed to their terminals. On the basis of the laminar distribution of Pt cell collaterals (mostly in layers V and VI) synaptic sites where recurrent excitation and inhibition are produced on Pt neurons are discussed.

Animals↗

Changes in excitability in motor cortex (representation of foreleg) of the dog depending on signal signification of flexor reaction during elaboration of transswitching.

Excitability in a cortical representation of a foreleg was determined during elaboration of transswitching in dogs in three variations depending upon the stimulus used as a Conditioned stimulus (CS). If the flexor reaction to direct stimulation of the motor cortex was used as a CS, excitability changes of opposite signs appeared in the cortical representation of the foreleg, the threshold of flexion decreased in the alimentary situation and increased in the defense situation. Such changes in excitability were observed during instrumental conditioned transswitching. If subthreshold stimulation of the motor cortex was used as the CS, the threshold of flexion increased in both situations in approximately equal degree.

Animals↗

The antalgic efficacy of chronic motor cortex stimulation is related to sensory changes in the painful zone.

Epidural motor cortex stimulation (MCS) could achieve good pain control in patients with drug-resistant chronic neurogenic pain. In the search for parameters associated with the favourable outcome of this surgical procedure, quantitative sensory testing was performed in a series of 31 patients treated by MCS for chronic pain. Non-nociceptive and nociceptive sensory thresholds were measured in the painful area and its contralateral homologous zone with the stimulator in 'off' and in 'on' position. All 13 patients who exhibited normal or quite normal non-nociceptive thermal thresholds within the painful area benefited from MCS. Of the remaining 18 patients with altered thermal sensory thresholds, eight patients nevertheless experienced good pain control by MCS. In these eight 'good responders', sensory thresholds were improved by switching 'on' MCS. In contrast, the last 10 patients showed abnormal thermal thresholds that were not modified by switching 'on' MCS, and did not respond clinically to MCS. Therefore, 'good responders' to MCS could be identified by the absence of alteration of non-nociceptive sensory modalities within the painful area, or by abnormal sensory thresholds that could be improved by MCS. These results additionally suggest that MCS acts on neural pathways involved in sensory discrimination that, in turn, are able to modulate the transmission of pain signals.

Adult↗