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[Instrumentalization of movements induced by stimulation of motor cortex with food reinforcement in dogs].

Contrary to some literature data, the possibility to instrumentalize the movements (liftings) of the hind limb elicited by stimulation of the corresponding contralateral area of the motor cortex was shown. The instrumental reflex (spontaneous high lifting of the hind limb) was acquired after a number of uniform trials: cortical stimulation--movement--food. Food delivery was preceded by a click, which was presented during the hind limb lifting and served as a secondary reinforcement. The acquisition was rather prolonged (50-200 trials) and demanded some special conditions. The results count in favor of the viewpoint that the motor cortex can directly participate in establishing the instrumental conditioned connection (motivation--movement), and simple instrumental movements can be initiated through this connection.

Animals↗

Magnetic stimulation of the motor cortex in cervical spondylosis.

We report a new technique of transcranial magnetic stimulation of the motor cortex to measure conduction within central motor pathways of 67 patients with cervical spondylosis or disk herniation. There were upper motor neuron signs in 34 patients (51%) and x-ray evidence of cervical cord compression in 44 (66%). Muscle action potentials (MAPs) to cortical stimulation were abnormal in 84% of patients with, and 22% of those without, radiologic signs of cervical cord compression. Median nerve somatosensory evoked potentials were altered in only 25% of patients. The frequency of MAP alterations correlated with upper motor neuron signs. In 5 (11%) of the 44 patients with x-ray evidence of cervical cord compression, subclinical cord compression was disclosed by cortical stimulation. In 10 patients restudied 3 months after surgical decompression, normalization of central motor conduction time did not occur, indicating permanent damage to the cervical cord.

Action Potentials↗

On variability and use of rat primary motor cortex responses in behavioral task discrimination.

The success of a cortical motor neuroprosthetic system will rely on the system's ability to effectively execute complex motor tasks in a changing environment. Invasive, intra-cortical electrodes have been successfully used to predict joint movement and grip force of a robotic arm/hand with a non-human primate (Chapin J K, Moxon K A, Markowitz R S and Nicolelis M A L 1999 Real-time control of a robotic arm using simultaneously recorded neurons in the motor cortex Nat. Neurosci. 2 664-70). It is well known that cortical encoding occurs with a high degree of cortical plasticity and depends on both the functional and behavioral context. Questions on the expected robustness of future motor prosthesis systems therefore still remain. The objective of the present work was to study the effect of minor changes in functional movement strategies on the M1 encoding. We compared the M1 encoding in freely moving, non-constrained animals that performed two similar behavioral tasks with the same end-goal, and investigated if these behavioral tasks could be discriminated based on the M1 recordings. The rats depressed a response paddle either with a set of restrictive bars ('WB') or without the bars ('WOB') placed in front of the paddle. The WB task required changes in the motor strategy to complete the paddle press and resulted in highly stereotyped movements, whereas in the WOB task the movement strategy was not restricted. Neural population activity was recorded from 16-channel micro-wire arrays and data up to 200 ms before a paddle hit were analyzed off-line. The analysis showed a significant neural firing difference between the two similar WB and WOB tasks, and using principal component analysis it was possible to distinguish between the two tasks with a best classification at 76.6%. While the results are dependent upon a small, randomly sampled neural population, they indicate that information about similar behavioral tasks may be extracted from M1 based on relatively few channels of neural signal for possible use in a cortical neuroprosthetic system.

Algorithms↗

Altered pyramidal cell dendritic development in the motor cortex of lead intoxicated neonatal rats. A Golgi study.

Neonatal Long-Evans rat pups were given the standard dose, 600 mg of lead acetate per kg of body weight every 24 hours beginning one day after birth until a cumulative dose of 2400 mg/kg (4 doses) had been administered via stomach intubation. Blood lead levels in lead treated rats averaged 526.35 micrograms/dl at 10 days of age. Blood lead values in age-matched controls averaged 0.079 microgram/dl. The body weights of the lead treated rats were not significantly different than control rats at 30 days of age. The brain weights were significantly greater than those of control rats at 30 days. Camera lucida drawings of pyramidal cells from motor cortex of control rats contained significantly (54%) more secondary and tertiary branches extending laterally from the primary apical dendrite than pyramidal cells of lead treated rats. The dendritic branches were numbered according to their branching point away from the soma. There was a significant reduction in the number of 4, 5, 6, and 7th order branches extending from the apical dendrite and 3 and 4th order branches extending from the basal dendrites in the leaded-rats. The mean dendritic length was reduced by 19% in basal dendrites and by 28% in apical dendrites. Measurements of dendritic material by the Scholl method revealed 17% reduction in the basal dendrites and a 36% reduction in the apical dendritic material in treated rats. These results suggest that neonatal lead exposure alters the dendritic development of pyramidal cells of rat motor cortex.

Animals↗

Regional (14C) 2-deoxyglucose uptake during vibrissae movements evoked by rat motor cortex stimulation.

Repetitive left mystacial vibrissae movements were produced by electrical stimulation of right motor cortex (MI) were a bipolar electrode in the alert, unanesthetized rat. Regional increases of (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically during these left vibrissae movements. Uptake of 2DG increased in a 2-4-mm-diameter area about the stimulating electrode in right MI and in a smaller region in left MI cortex. Columnar increases of 2DG uptake occurred bilaterally in somatosensory cortex in the face region of somatosensory cortex (SI). Bilateral increases of 2DG uptake occurred subcortically in dorsolateral caudate-putamen (CP) and subthalamic nucleus. Primary right-sided increases of 2DG uptake occurred in other basal ganglia structures including dorsal globus pallidus (GP), posterior, entopeduncular nucleus (EPN), ventrolateral substantia nigra pars reticulata (SNr), and anterolateral substantia nigra pars compacta (SNc). Uptake of 2DG increased on the right side of the following thalamic regions: much of the ventrolateral (VL) nucleus, particularly dorsally; the anterodorsal reticular nucleus; dorsolateral posteromedial (POm) nucleus; the ventromedial nucleus; and dorsolateral parafasicular nucleus. The anterior and ventral posterior portions of VL were not activated. Caudal to thalamus right-sided 2DG uptake increased in the medial, ventral, and lateral pontine nuclei, deep layers of superior colliculus, lateral deep mesencephalic nucleus (DMN), and nucleus cuneiformis (NCU). UPtake of 2DG increased in right rostral parvocellular and red nucleus in a few animals. Discrete portions of the right internal capsule and right medial pyramidal tract increased 2DG uptake during MI stimulation. Uptake of 2DG increased on the left side of the brain during right MI stimulation in the left lateral nucleus (NL) of cerebellum and in several discrete regions of left cerebellar hemisphere granule cells including anterior paravermis, lobulus simplex, crus II, and the paramedian lobule. Uptake of 2DG increased in left nucleus of the spinal tract of the trigeminal nerve (ntV) ventrally in subnuclei interpolaris and oralis. Left lateral portions of the facial nucleus were activated in a few animals. The lateral portions of the facial nucleus are known to project to vibrissae musculature. All of the above structures may be involved in the motor-sensory processing responsible for vibrissae movements. Regions not previously suggested to play a major role in vibrissae movements include DMN and NCU. Though NCU has been called the "locomotor center" it may play a role in facial movements as well. Polysynaptic activation of GP, EPN, NL, and cerebellar hemisphere occurred since no connections between MI and these regions exist. A pathway from ntV to POm to MI and SI is suggested to provide proprioceptive input to motor-sensory cortex from the moving vibrissae since neither the principal trigeminal sensory nucleus nor the ventrobasal nucleus of the thalamus increased 2DG uptake during MI stimulation.

Animals↗

Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8 Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other secondary effect of levodopa administration psychiatric symptoms - are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

Aged↗

Surgery of lesions in the motor strip combining a stereotactically-guided mini-craniotomy with electrophysiological mapping of the motor cortex.

The removal of space-occupying lesions in the sensori-motor cortex carries a considerable risk of postoperative palsy. Therefore subcortical lesions located in the sensori-motor strip are often considered to be inoperable. Treatment options are stereotactic biopsy and radiosurgery beside radiological control examinations without surgery or surgery with a higher risk of postoperative deficits. The following article focusses on a combined approach involving a stereotactically guided and electrophysiologically controlled surgery. The instruments used (stereotactical system and electric stimulator) are available in almost every neurosurgical department in the Western and Eastern world and had been the first navigation systems in the human brain.

Brain Neoplasms↗

Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study.

Using multichannel electroencephalography (EEG), we investigated temporal dynamics of the cortical response to transcranial magnetic stimulation (TMS). TMS was applied over the left primary motor cortex (M1) of healthy volunteers, intermixing single suprathreshold pulses with pairs of sub- and suprathreshold pulses and simultaneously recording EEG from 60 scalp electrodes. Averaging of EEG data time locked to the onset of TMS pulses yielded a waveform consisting of a positive peak (30 ms after the pulse P30), followed by two negative peaks [at 45 (N45) and 100 ms]. Peak-to-peak amplitude of the P30-N45 waveform was high, ranging from 12 to 70 microV; in most subjects, the N45 potential could be identified in single EEG traces. Spectral analysis revealed that single-pulse TMS induced a brief period of synchronized activity in the beta range (15-30 Hz) in the vicinity of the stimulation site; again, this oscillatory response was apparent not only in the EEG averages but also in single traces. Both the N45 and the oscillatory response were lower in amplitude in the 12-ms (but not 3-ms) paired-pulse trials, compared with the single-pulse trials. These findings are consistent with the possibility that TMS applied to M1 induces transient synchronization of spontaneous activity of cortical neurons within the 15- to 30-Hz frequency range. As such, they corroborate previous studies of cortical oscillations in the motor cortex and point to the potential of the combined TMS/EEG approach for further investigations of cortical rhythms in the human brain.

Adult↗

Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation.

The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons.

Animals↗

The effect of acupuncture on motor cortex excitability and plasticity.

Acupuncture has been used extensively in facilitating motor recovery after stroke. Its mechanism of action remains uncertain. In this sham-controlled study, we demonstrate for the first time that acupuncture has a real and enduring effect on motor cortex functional changes, in terms of cortical excitability and output mapping using transcranial magnetic stimulation.

Acupuncture↗

Long-Evans rats have a larger cortical topographic representation of movement than Fischer-344 rats: a microstimulation study of motor cortex in naïve and skilled reaching-trained rats.

Intracortical microstimulation of the frontal cortex evokes movements in the contralateral limbs, paws, and digits of placental mammals including the laboratory rat. The topographic representation of movement in the rat consists of a rostral forelimb area (RFA), a caudal forelimb area (CFA), and a hind limb area (HLA). The size of these representations can vary between individual animals and the proportional representation of the body parts within regions can also change as a function of experience. To date, there have been no investigations of strain differences in the cortical map of rats, and this was the objective of the present investigation. The effect of cortical stimulation was compared in young male Long-Evans rats and Fischer-344 rats. The overall size of the motor cortex representation was greater in Long-Evans rats compared to Fischer-344 rats and the threshold required to elicit a movement was higher in the Fischer-344 rats. An additional set of animals were trained in a skilled reaching task to rule out the possibility that experiential differences in the groups could account for the result and to examine the relationship between the differences in topography of cortical movement representations and motor performance. The Long-Evans rats were quantitatively and qualitatively better in skilled reaching than the Fischer-344 rats. Also, Long-Evans rats exhibited a relatively larger area of the topographic representation and lower thresholds for eliciting movement in the contralateral forelimb. This is the first study to describe pronounced strain-related differences in the microstimulation-topographic map of the motor cortex. The results are discussed in relation to using strain differences as a way of examining the behavioral, the physiological, and the anatomical organization of the motor system.

Animals↗

Somatotopic arrangement and corticocortical inputs of the hindlimb region of the primary motor cortex in the macaque monkey.

Using Japanese monkeys, we examined the somatotopic organization of the hindlimb region of the primary motor cortex (MI) with intracortical microstimulation. In the hindlimb region of the MI, areas representing distal movements (digits and ankle joints) were basically surrounded by those representing proximal movements (knee and hip joints). Thus, the hindlimb region of the MI has a nested or horseshoe-like somatotopic representation. We then examined the topographic organization of corticocortical projections to the hindlimb region of the MI by the retrograde double-labeling technique: one monkey received paired injections of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb representation of the MI, respectively, while two monkeys received those of FB and DY into proximal or distal representation of the hindlimb region of the MI, respectively. The neurons projecting to the hindlimb region of the MI were located in cortical areas largely separate from those projecting to the forelimb region of the MI. On the other hand, we found a substantial overlap of corticocortical neurons projecting to the proximal and distal parts of the hindlimb region of the MI in the dorsal division of the premotor cortex and the cingulate motor areas.

Animals↗

Influence of dopamine on ventrolateral thalamic inputs in cat motor cortex.

Neuronal activity in several brain regions is modulated by dopaminergic inputs. When single neuronal activity/20 trials of single-pulse ventrolateral thalamic (VL) stimulation was extracellularly recorded in the in vivo, anesthetized cat motor cortex, iontophoretic application of dopamine (DA) elicited either suppression or, in a fewer instances, facilitation of evoked unitary responses. The predominant inhibition exerted by DA appeared to be consistent for successive trials, and a D(1), D(2), and D(1)/D(2) receptor antagonist restored the effect, thereby reflecting a possible coexistence of two DA receptors. By contrast, only a fewer neurons' response to DA displayed facilitation, which was not attenuated by DA antagonists. Moreover, subsequent trials with receptor agonist and antagonists induced inconsistent effects. Except for the jitters, single unit spikes showed invariant latency, which was constant during all recording parameters, and the mean latency remained unchanged. The modulatory effects mediated by DA did not reveal any substantial difference between short- and long-latency responses. Both pyramidal tract neurons and non-pyramidal tract neurons, determined on the basis of antidromic potentials from the pyramidal tract, responded to DA essentially in a similar manner. It appears that DA overall inhibits cat motor cortical neuronal activity in response to VL inputs. We propose that such DAergic inhibition of thalamocortical excitation in the motor cortex could be critical for ongoing sensorimotor transformation.

Animals↗

Properties of associative long-lasting potentiation induced by cellular conditioning in the motor cortex of conscious cats.

Mechanisms of long-lasting potentiation of synaptic responses induced in the thalamocortical and recurrent collateral pathways of the pyramidal tract were studied in intracellular recordings from the motor cortex of unanesthetized, chronically implanted cats. The observations provide the first description of long-lasting potentiation in the unanesthetized neocortex in vivo. Monosynaptic excitatory postsynaptic potentials of 2-5 mV in amplitude were evoked as test responses by stimulation of the pyramidal tract and thalamic ventrolateral nucleus at 0.1-0.5 Hz frequency. Pressure microinjections of drugs and ions were also performed during intracellular recordings. In the first series of experiments, test synaptic responses were paired with intracellular current injection-induced action potentials at an interstimulus interval set between 0-200 ms and 0.1-0.5 Hz frequency. Pairings (30-100 x) induced long-lasting potentiation of the test responses in 58% of cells. The increased synaptic responses typically initiated action potentials and their potentiation usually lasted over the period of recordings. Increases in amplitude of synaptic responses were not correlated with statistically significant changes in electrical membrane properties (resting potential, input resistance, time constant, spike threshold) or parameters of action potentials and their afterpotentials. The failure to induce increases in synaptic efficacy by unpaired stimuli (pseudoconditioning) demonstrated the associative property of the long-lasting potentiation. In a second series of experiments, differential cell conditioning was employed. This paradigm induced long-lasting potentiation of the explicitly paired synaptic response without noticeable modification of unpaired or pseudorandomly paired synaptic responses tested conjointly in the same neuron. These observations demonstrated the input-specificity of long-lasting potentiation. In a third series of experiments, subthreshold depolarizing current pulses were summated with synaptic responses to induce firing in the recorded neuron during pairing. Long-lasting potentiation occurred in 55% of the summated synaptic inputs. Pseudoconditioning did not induce synaptic potentiation in these cells. In a fourth series of experiments, conditioning was employed in neurons in which firing activity was suppressed by an intracellularly injected lidocaine derivative. Long-lasting potentiation was induced in 50% of the attempts when synaptic responses were paired with current-induced depolarizations greater than 30 mV. These results suggest that postsynaptic induction of long-lasting synaptic potentiation can be successful in the absence of postsynaptic sodium spikes in neurons of the motor cortex in vivo. In a fifth series of experiments, homosynaptic high-frequency tetanization (80-200 Hz for 5-15 s) was applied to the thalamocortical and recurrent pyramidal afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement.

We describe the relations between the neuronal activity in primate motor cortex and the direction of arm movement in three-dimensional (3-D) space. The electrical signs of discharge of 568 cells were recorded while monkeys made movements of equal amplitude from the same starting position to 8 visual targets in a reaction time task. The layout of the targets in 3-D space was such that the direction of the movement ranged over the whole 3-D directional continuum in approximately equal angular intervals. We found that the discharge rate of 475/568 (83.6%) cells varied in an orderly fashion with the direction of movement: discharge rate was highest with movements in a certain direction (the cell's "preferred direction") and decreased progressively with movements in other directions, as a function of the cosine of the angle formed by the direction of the movement and the cell's preferred direction. The preferred directions of different cells were distributed throughout 3-D space. These findings generalize to 3-D space previous results obtained in 2-D space (Georgopoulos et al., 1982) and suggest that the motor cortex is a nodal point in the construction of patterns of output signals specifying the direction of arm movement in extrapersonal space.

Animals↗

Contribution of the ipsilateral motor cortex to recovery after chronic stroke.

It has been proposed that the intact (ipsilateral) motor cortex play a significant role mediating recovery of motor function in the paretic hand of chronic stroke patients, but this hypothesis has not been tested experimentally. Here, we evaluated the effects of transcranial magnetic stimulation (TMS) on motor performance of the paretic hand of chronic stroke patients and healthy controls. We hypothesized that, if activity in the intact hemisphere contributes to functional recovery, TMS should result in abnormal motor behavior in the paretic hand. We found that stimulation of the intact hemisphere resulted in delayed simple reaction times (RTs) in the contralateral healthy but not in the ipsilateral paretic hand, whereas stimulation of the lesioned hemisphere led to a marked delay in RT in the contralateral paretic hand but not in the ipsilateral healthy hand. RT delays in the paretic hand correlated well with functional recovery. Finger tapping in the paretic hand was affected by TMS of the lesioned but not the intact hemisphere. These results are consistent with the idea that recovered motor function in the paretic hand of chronic stroke patients relies predominantly on reorganized activity within motor areas of the affected hemisphere.

Adult↗

Excitability of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine.

The pathophysiology underlying the involuntary tics of Gilles de la Tourette syndrome (GTS) remains unknown. Here we used transcranial magnetic stimulation (TMS) to examine the excitability of two different inhibitory systems in the human motor cortex: short interval intracortical inhibition (SICI) and short interval afferent inhibition (SAI) in 10 healthy non-smoking controls and eight untreated non-smoking patients with GTS. Compared with the healthy control group, both SICI (measured at a range of conditioning intensities) and SAI were reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output. A single dose of nicotine reduced tic severity as assessed by blind video scoring in the majority of patients. In addition, it abolished the difference between patients and controls in SICI and SAI. There was no effect of nicotine, and no difference between controls and patients in measures of motor or SICI threshold. This indicates that cholinergic input can modulate the efficiency of SICI and SAI differently in GTS and healthy controls.

Adult↗

Overlap of internal models in motor cortex for mechanical loads during reaching.

A hallmark of the human motor system is its ability to adapt motor patterns for different environmental conditions, such as when a skilled ice-hockey player accurately shoots a puck with or without protective equipment. Each object (stick, shoulder pad, elbow pad) imparts a distinct load upon the limb, and a key problem in motor neuroscience is to understand how the brain controls movement for different mechanical contexts. We addressed this issue by training non-human primates to make reaching movements with and without viscous loads applied to the shoulder and/or elbow joints, and then examined neural representations in primary motor cortex (MI) for each load condition. Even though the shoulder and elbow loads are mechanically independent, we found that some neurons responded to both of these single-joint loads. Furthermore, changes in activity of individual neurons during multi-joint loads could be predicted from their response to subordinate single-joint loads. These findings suggest that neural representations of different mechanical contexts in MI are organized in a highly structured manner that may provide a neural basis for how complex motor behaviour is learned from simpler motor tasks.

Action Potentials↗