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PubMed2004

Spinal cord plasticity in response to unilateral inhibition of the rat motor cortex during development: changes to gene expression, muscle afferents and the ipsilateral corticospinal projection.

In developing Wistar albino rats, ventral horn muscle afferent boutons are lost following corticospinal innervation. Motor cortex lesions rescue a proportion of these boutons and perturb activity dependent expression of cJun and parvalbumin (PV) in the spinal cord. Therefore, we tested whether activity-dependent competition between corticospinal and proprioreceptive afferents determines the balance of these inputs to motor output pathways by delivering the inhibitory GABA agonist muscimol unilaterally to the forelimb motor cortex using slow release polymer implants from postnatal day 7 (P7) coincident with corticospinal synaptogenesis. Controls received saline. Inhibition of immature cortical neurons by muscimol was confirmed with separate in vitro electrophysiological recordings. After P28, spinal cord sections were immunostained for PV, cJun and muscle afferents transganglionically labelled with cholera toxin-B (CTB). Unilateral inhibition reduced contralaterally the number of PV positive spinal cord neurons and muscle afferent boutons in the dorsolateral ventral horn, compared to controls, and significantly altered the distribution of motoneuronal cJun expression. Separately, descending tracts were retrogradely traced with CTB from the cervical hemicord contralateral to implants. Forelimb sensorimotor cortex sections were immunostained for either CTB or PV. In muscimol treated animals, significantly fewer neurons expressed PV in the inhibited hemicortex, but as many CTB labelled corticospinal neurons were present as in controls, along with an equally large corticospinal projection from contralateral to the implant, significantly greater than in controls. Unexpectedly, unilateral inhibition of the motor cortical input did not lead to an expanded muscle afferent input. Instead, this was reduced coincident with development of a bilateral corticospinal innervation.

Age Factors↗
PubMed2006

Preparatory activity in premotor and motor cortex reflects the speed of the upcoming reach.

Neurons in premotor and motor cortex show preparatory activity during an instructed-delay task. It has been suggested that such activity primarily reflects visuospatial aspects of the movement, such as target location or reach direction and extent. We asked whether a more dynamic feature, movement speed, is also reflected. Two monkeys were trained to reach at different speeds ("slow" or "fast," peak speed being approximately 50-100% higher for the latter) depending on target color. Targets were presented in seven directions and at two distances. Of 95 neurons with tuned delay-period activity, 95, 78, and 94% showed a significant influence of direction, distance, and instructed speed, respectively. Average peak modulations with respect to direction, distance and speed were 18, 10, and 11 spikes/s. Although robust, modulations of firing rate with target direction were not necessarily invariant: for 45% of neurons, the preferred direction depended significantly on target distance and/or instructed speed. We collected an additional dataset, examining in more detail the effect of target distance (5 distances from 3 to 12 cm in 2 directions). Of 41 neurons with tuned delay-period activity, 85, 83, and 98% showed a significant impact of direction, distance, and instructed speed. Statistical interactions between the effects of distance and instructed speed were common, but it was nevertheless clear that distance "tuning" was not in general a simple consequence of speed tuning. We conclude that delay-period preparatory activity robustly reflects a nonspatial aspect of the upcoming reach. However, it is unclear whether the recorded neural responses conform to any simple reference frame, intrinsic or extrinsic.

Algorithms↗
PubMed1990

Magnetoelectric stimulation of human motor cortex: normal values and potential safety issues in spinal cord injury.

Upon magnetoelectric stimulation (MES) of the motor cortex, maximal amplitude and minimal latency of compound muscle action potentials were recorded for four limbs in 20 able-bodied volunteers after ten sequential stimulations. The ratio of maximal cortical to maximal peripheral compound muscle action potential was calculated. Standard statistical parameters were calculated for values from each limb. A paired t-test revealed a statistically significant difference in lower extremity side-to-side amplitude. Regression analysis of patient height vs upper extremity and lower extremity latency demonstrated a strong correlation: r = .720 and r = .601, respectively. A pendulum model demonstrated that a miniscule amount of energy is imparted onto metallic fixation devices by the magnetic coil, but no significant paraspinal activity could be measured in any of five volunteers upon stimulation of the motor cortex. This study has established a normal MES data base that might be useful in evaluating spinal cord injured patients. It has also demonstrated that initial safety concerns about the use of MES in this population are likely unfounded.

Adult↗
PubMed1975

Recovery of motor function after lesions in motor cortex of monkey.

This behavioural study concerns the contribution of active retraining to motor recovery after a standard lesion in the motor cortex, and includes an evaluation of various retraining procedures. These problems have not previously been experimentally analysed in man or animal. Rhesus monkeys (27) were initially trained on two motor tasks which consisted of a pulling task, involving the proximal muscles of the upper limb, and a hand-grip task for the distal musculature. Strength of pulling and hand-grip were measured quantitatively. For brevity, only the hand grip data are described. After a plateau of proficient performance was achieved in both hands (usually 6-8 months), the cortical precentral forelimb area was surgically ablated on one side. Each animal was then randomly assigned to one of four experimental groups or to a sham operative control group. The groups differed with respect to the use of the contralateral and/or ipsilateral forelimb(s) in post-operative motor training on the same task. In addition, to evaluate the contribution of spontaneous post-operative recovery independent of retraining, we started to train two groups immediately after surgery; in the other two experimental groups the weak forelimb remained idle for the first four post-operative months. Combined training of the weak and normal limb, which resulted in 85% recovery in the weak limb, did not differ statistically from training the weak limb alone (79% recovery). This suggests that the critical factor in promoting recovery is training of the weak forelimb, presumably by 'activation' of the damaged hemisphere. The role of the ipsilateral (strong) limb appears negligible. When post-operative training in the weak limb was delayed four months, spontaneous recovery noted one week after the start of delayed training was about 50% compared with 9% recovery after one week in the groups retrained immediately after surgery (P less than 0.001). The 'immediate' groups, however, continued to improve over a six-month period to about 82% of their pre-operative performance. The 'delay' groups, by contrast, exhibited only slight further improvement, reaching a plateau of 67% recovery six months after the start of retraining (10 months post-operatively). This difference in recovery between the immediate and delay groups was significant at the 0.05 level. This confirms that active physical retraining facilitates motor recovery, although the mechanism remains obscure. The data also suggest that, to be most effective, the training should begin as soon as possible after the insult to the brain has occurred.

Animals↗
PubMed1984

Caudal cuneate nucleus projection to the direct thalamic relay to motor cortex in cat: an electrophysiological and anatomical study.

The input to the border region between the ventrolateral nucleus (VL) and ventroposterolateral nucleus (VPL) of the thalamus, VL-VPL, was studied in cats using a combined electrophysiological and anatomical technique. Neurons within this border region receive somatic afferent input and project to a region of the motor cortex having similar receptive fields. In this study we asked the question whether neurons in the VL-VPL border receive input from the dorsal column nuclei (DCN). To answer this question we delivered intra-cortical microstimulation (ICMS) to the motor cortex while a second electrode inserted into the VL-VPL border, filled with a 20% solution of HRP dissolved in KCl, was used to record antidromically activated neurons. When an antidromically activated neuron was encountered and the neuron responded to natural peripheral stimulation, HRP was iontophoretically injected through the recording electrode. After a 48-72 h survival time, cats were sacrificed, and the brain tissue processed according to the method of Hardy and Heimer. Labeled cell bodies were found in the caudal cuneate nucleus (CCN) in all injected animals. These results suggested that neurons in CCN project to cells in VL-VPL which in turn project to the motor cortex.

Animals↗
PubMed2003

Evaluations of inhibitory effect on the motor cortex by cutaneous pain via application of capsaicin.

To evaluation the effect of experimental tonic cutaneous pain on motor cortex excitability by means of transcranial magnetic stimulation (TMS). Thirty healthy adults (male: 12, female: 18) were tested with TMS. Cutaneous pain was induced by topical application of capsaicin cream (0.025%) on the skin overlying the flexor carpi radialis of dominant limb. And the cream had been under an occlusive dressing for 40 minutes until we removed it. Magnetic stimulation was performed to the contralateral cortex with a circular coil at 80% intensity of maximum stimulator output. MEPs were recorded at flexor carpi radialis (FCR), extensor carpi radialis (ECR) and opponens pollicis (OP) with constant isometric contraction of 10%, 30% maximal voluntary contraction (MVC). Main outcome measures the intensity of pain by visual analog scale (VAS). The latency, amplitude and silent period of motor evoked potentials (MEPs). Values at baseline and 20, 40, 60, 80 minutes from applying capsaicin were compared. VAS score reached the peak value at 40 minutes. Amplitudes of MEPs at FCR progressively decreased up to 40 minutes than returned to nearly baseline value at 80 minutes. The decrease in MEP amplitude at FCR was accompanied by the increase in VAS score significantly and sustained for 20 min after washing out capsaicin cream. At ECR & OP, we could not demonstrate any changes in amplitude with time. Silent period at FCR only was significantly prolonged with the increase in VAS score. The present findings support that noxious cutaneous stimulation inhibit motor cortex excitability by so-called cortico-cortical circuits.

Administration, Cutaneous↗
PubMed1985

The effect of cooling of the supplementary motor cortex and adjacent cortical areas.

The medial surface of the rostral part of frontal agranular cortex, largely corresponding to the supplementary motor area, was rapidly and reversibly cooled while a monkey was performing a trained motor task requiring a premovement selection process of determining sensory signals as movement triggering or non-triggering. During cooling, the motor task was poorly performed with grossly altered reaction times and variable amount of force, along with erroneous responses. Neuronal activity in the precentral motor cortex in response to sensory signals was also found to be altered.

Animals↗
PubMed2000

Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement.

RATIONALE AND OBJECTIVES: The relatively high temporal and spatial resolution of functional MR imaging was used to compare the blood oxygenation level dependent (BOLD) response associated with movement induced by transcranial magnetic stimulation (TMS) with that for a similar movement executed volitionally (VOL). METHODS: Seven healthy adults were studied in a 1.5-T MR scanner. One hertz TMS at 110% of motor threshold was applied over the motor cortex for the thumb in 21-pulse trains in alternation with VOL every 63 seconds and interleaved with functional MR imaging. RESULTS: BOLD increases in motor cortex associated with TMS and VOL movement were similar (2%-3%). Mean separation of their centers of activity was 3.7 + 1.9 mm (mean displacement: left/right = 0.3 +/- 4.1 mm; superior/inferior = 0.7 +/- 1.9 mm). There was no indication of supraphysiological brain activity. CONCLUSIONS: Motor cortex BOLD response associated with thumb movement induced by 1-Hz TMS at 110% motor threshold is similar in both location and level to that caused by a similar movement executed volitionally.

Adult↗
PubMed2002

[Synaptic plasticity in the motor cortex].

Horizontally-oriented intracortical connections have been proposed to serve as a substrate for plastic reorganizations of adult motor cortex. N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) of synaptic efficacy is a candidate mechanism of these reorganizations in mammalian species ranging from rats to humans. The acquisition of a motor skill is accompanied by increased strength of synaptic connections within adult rat primary motor cortex, most likely due to LTP-like mechanisms.

Animals↗
PubMed2006

Disruption of primary motor cortex before learning impairs memory of movement dynamics.

Although multiple lines of evidence implicate the primary motor cortex (M1) in motor learning, the precise role of M1 in the adaptation to novel movement dynamics and in the subsequent consolidation of a memory of those dynamics remains unclear. Here we used repetitive transcranial magnetic stimulation (rTMS) to dissociate the contribution of M1 to these distinct aspects of motor learning. Subjects performed reaching movements in velocity-dependent force fields over three epochs: a null-field baseline epoch, a clockwise-field learning epoch (15 min after the baseline epoch), and a clockwise-field retest epoch (24 h after the learning epoch). Half of the subjects received 15 min of 1 Hz rTMS to M1 between the baseline and learning epochs. Subjects given rTMS performed identically to control subjects during the learning epoch. However, control subjects performed with significantly less error than rTMS subjects in the retest epoch on the following day. These results suggest that M1 is not critical to the network supporting motor adaptation per se but that, within this network, M1 may be important for initiating the development of long-term motor memories.

Adaptation, Physiological↗
PubMed1999

Increased numerical density of synapses in CA3 region of hippocampus and molecular layer of motor cortex after self-stimulation rewarding experience.

Self-stimulation has been considered as an intensely rewarding behavioural experience, being perhaps even more influential than feeding or sexual behaviour. Our earlier studies have demonstrated a self-stimulation rewarding experience-induced increase in dendritic branching points, intersections and spine densities in CA3 hippocampal and layer V motor cortical pyramidal neurons. In the present study, we report self-stimulation-induced alterations in the numerical density of synapses in the hippocampus and motor cortex. A self-stimulation experience was provided 1 h daily for a period of 10 days through bipolar electrodes, implanted bilaterally in the lateral hypothalamus and substantia nigra-ventral tegmental area, stereotaxically. The results revealed a significant (P < 0.001) increase in the number of synapses in the CA3 region of hippocampus and the molecular layer of the motor cortex in self-stimulation-experienced rats. The increased synaptic number may be due to the activation of afferent pathways to the hippocampus and motor cortex following self-stimulation, which may lead to the induction of long-term potentiation. Long-term potentiation is known to cause structural changes by strengthening the existing synapses or resulting in the formation of new synapses. These changes may be related to the improved cognitive functions observed in self-stimulation-experienced rats.

Animals↗
PubMed1992

The role of motor cortex in the pathophysiology of voluntary movement deficits associated with parkinsonism.

The characteristic motor deficits of parkinsonism result from dysfunction of the nigrostriatal dopaminergic system of the basal ganglia. These subcortical deficits must ultimately be expressed at the cortical and spinal motoneuron levels to result in the difficulty with initiation and execution of movements seen in parkinsonism. This article describes the neuronal activity of two motor cortical regions, the primary motor cortex (MI) and supplementary motor area (SMA), which receive the majority of basal ganglia outputs related to movement control through the ventral lateral thalamus. The kinematics and electromyographic characteristics of stimulus-initiated and self-initiated normal and parkinsonian movements are described, and the possible relation of SMA and MI task-related neuronal activity to the parkinsonian movement deficits is reviewed.

Animals↗
PubMed2001

Motor cortex stimulation.

In 1991 Tsubokawa and colleagues first published their landmark results from a series in which epidural motor cortex stimulation (MCS) was used in the treatment of eight patients with central and neuropathic pain. In ensuing studies authors have elaborated on the indications, technique, hypotheical mechanisms, and beneficial results of this treatment. Epidural MCS is effective for trigeminal neuropathy, lateral medullary and thalamic infarction, anesthesia dolorosa, postherpetic neuralgia, spinal cord injury, and limb stump pain. Postoperative outcomes are better when patients present with only mild or absent motor weakness in the region of pain and when there is pain in the trigeminal region. It is hypothesized that MCS is effective because it increases regional cerebral blood flow in the ipsilateral ventrolateral thalamus in which corticothalamic connections from the motor and premotor areas predominate. The extent of pain alleviation also correlates with the increase of blood flow in the cingulate gyrus. This suggests that stimulation reduces the suffering experienced by a patient with chronic pain. Procedure-related morbidity has included epidural hematoma, subdural effusion, gradual diminution of benefit, and painful stimulation. Although of concern, treatment-induced chronic seizure disorders have not occurred as a complication or in animal models of chronic cortical stimulation. Stimulation-induced pain relief occurs within minutes. There are no associated paresthesias or muscle contractions that confirm function. Pain relief may last for hours after electrical stimulation is discontinued. Motor cortex stimulation is an established therapy for the treatment of complex central and neuropathic pain syndromes that have proved refractory to medical treatment.

Electric Stimulation Therapy↗
PubMed1986

Synaptic connections of callosal projection neurons in the vibrissal region of mouse primary motor cortex: an electron microscopic/horseradish peroxidase study.

Reciprocal axonal projections between homotypic areas of the vibrissal region of mouse primary motor cortex (MsI) (Porter and White: Neurosci. Lett. 47:37-40, '84) suggested the existence of reciprocal synaptic connections between callosal projection neurons and callosal afferents. In the present study, the retrograde transport of horseradish peroxidase (HRP) was combined with lesion-induced degeneration to identify synapses between callosal afferents and callosal neurons in the corresponding region of the contralateral cortex. The procedure was as follows: MsI was injected with HRP and aspirated on the following day. After 4 days, the animals were perfused and motor cortex was processed for HRP according to a variation of the Adams (Brain Res. 176:33-47,'77) technique, and postfixed in OsO4. The methods used consistently filled fine dendritic branches and spines with dense reaction product, thus allowing examination of synaptic contacts with these processes. All callosal projection neurons were identified as pyramidal neurons, having somata in cortical layers II/III and V. Labeled cells from each of the two levels were prepared for electron microscopy, and that part of each cell's apical dendrite that traversed the superficial cortical layers, where most callosal axons terminate, was cut in an unbroken series of thin sections. Micrographs were taken of all labeled profiles in each thin section, and tracings of the profiles were assembled to reconstruct the apical dendrites. Data on the distribution, type, and amount of callosal and other synapses with the shaft and spines of the apical dendrites were obtained by examining the reconstructions. In addition, profiles of basal dendrites of layer II/III cells were examined in thin sections to ascertain the numbers of callosal and other synapses formed with their shafts and spines. The proportion of synapses that each dendrite formed with callosal axon terminals was compared to the concentration of callosal afferents in the neuropil. Dendrites of both layer II/III and layer V pyramidal cells synapsed with callosal axon terminals. The apical and basal dendrites of layer II/III neurons formed a similar proportion of their synapses with callosal afferents, and this was similar to the concentration of callosal synapses in the surrounding neuropil. Segments of apical dendrites belonging to layer V and layer II/III neurons course through neuropil containing nearly the same concentration of degenerating callosal terminals, but the layer V cells form fewer callosal synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson's disease.

According to the classical model of basal ganglia organization, deep brain stimulation (DBS) in the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD) blocks overactive excitatory projections to inhibitory basal ganglia output structures. This would release the break on thalamofrontal neurons alleviating the poverty of movement, the hallmark of PD. Such parallels to a functional lesion certainly simplify the mechanism of STN DBS. Here, we applied parametric analyses of H2(15)O positron emission tomography (PET) scans at rest while systematically varying stimulation frequency in 6 patients with STN DBS for akinetic PD. A strong positive correlation of rCBF to increasing stimulation frequency was detected around the STN bilaterally. More importantly, we show that gradual increases in STN stimulation frequency are tightly correlated with decreases in motor cortex activity. This demonstrates an active modulation of resting activity within the subcortical stimulation target and within motor cortex by STN DBS. Rather than a possible downstream effect, we propose to consider the tight correlations between DBS frequency and motor cortex activity in the context of an upstream modulation of direct efferents to the STN from primary motor and premotor cortices.

Aged↗
PubMed2001

Neuronal correlates of motor performance and motor learning in the primary motor cortex of monkeys adapting to an external force field.

The primary motor cortex (M1) is known to control motor performance. Recent findings have also implicated M1 in motor learning, as neurons in this area show learning-related plasticity. In the present study, we analyzed the neuronal activity recorded in M1 in a force field adaptation task. Our goal was to investigate the neuronal reorganization across behavioral epochs (before, during, and after adaptation). Here we report two main findings. First, memory cells were present in two classes. With respect to the changes of preferred direction (Pd), these two classes complemented each other after readaptation. Second, for the entire neuronal population, the shift of Pd matched the shift observed for muscles. These results provide a framework whereby the activity of distinct neuronal subpopulations combines to subserve both functions of motor performance and motor learning.

Animals↗
PubMed1989

[Functional properties of efferent zones of the motor cortex which project to ipsilateral and contralateral face muscles].

In both intact (4 animals) and lesioned (2 preparations with contralateral motor cortex ablation and 1 animal with transection of the rostral two thirds of the corpus callosum) cats, three different types of efferent zones were identified in the face motor cortex by the technique of microstimulation: contralateral, ipsilateral and bilateral efferent zones. The three types of efferent zones had different organizational features such as location, thresholds of effective sites and latencies of motor responses. Mean thresholds of effective sites from ipsilateral and bilateral efferent zones in lesioned animals were not significantly higher than those in intact preparations. In both intact and lesioned animals, neurons endowed with contralateral, bilateral and ipsilateral receptive fields were isolated from the three types of efferent zones.

Animals↗