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Forms and spatial arrangement of neurons in the primary motor cortex of man.

The morphology and the spatial arrangement of neurons in the primary motor cortex (area 4) of the adult human brain have been investigated by the Golgi method. The human motor cortex displays a great variety of pyramidal and nonpyramidal cells, expressed as important differences in soma shape and size, and in the dimensions and the distribution of dendritic trees, which are described in detail. The neuronal composition of each layer and the white matter is analyzed. In sublayers III b and c, the somata and dendritic trees of pyramidal and nonpyramidal cells are grouped into columnar aggregations, 100-300 micron wide and separated by cell-sparse spaces of 50-100 micron width. Within the aggregations, the apical dendrites of pyramidal cells form several bundles. The dendrites of most nonpyramidal cells do not surpass the columnar width. Sections in different planes reveal that the columnar aggregations observed in sections perpendicular to the long axis of the precentral gyrus are actually the cross-sectioned representatives of elongate strips running parallel to the long axis of the gyrus. The dendrites and somata of pyramidal cells in layers III and V show a preferential orientation in the same direction, parallel to the main axis of the gyrus. In layers II, IV, and V, aggregations like those in layer III are not recognizable; however, in layer V, loose assemblages of neurons of all sizes group around the giant Betz cells. Layer VI has a radial appearance due to the radii of myelinated fibers entering and leaving the white matter. The vertical, columnar organization of layer III and the asymmetry of somata and dendritic trees are not observed consistently throughout area 4, but are more pronounced at the boundary of the precentral gyrus and the central sulcus.

Adult↗

Modelling motor cortex stimulation for chronic pain control: electrical potential field, activating functions and responses of simple nerve fibre models.

This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulation-induced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode.

Chronic Disease↗

Movement-related activity of thalamic neurons with input from the globus pallidus and projection to the motor cortex in the monkey.

Thalamic neurons projecting to the arm area of the motor cortex were identified by their antidromic response to stimulation of that area in two awake monkeys. Neurons were further identified as receiving inputs from the cerebellar nuclei or the internal segment of the globus pallidus by excitatory or inhibitory response to stimulation of these nuclei. Most (33/34) of the thalamic neurons in the cerebello-thalamo-cortical projection and more than half (12/18) of those in the pallido-thalamo-cortical projection changed their firing rate on the lever-lifting hand movement in the reaction-time task. A considerable number of neurons of both groups (14/23 and 3/10) changed their firing rate prior to the onset of the earliest EMG. These findings agree with the model that activities of pallidal as well as cerebellar nuclear neurons related to motor control are transmitted to the motor cortex through the thalamus.

Animals↗

Exercise increases metabolic capacity in the motor cortex and striatum, but not in the hippocampus.

Acute bouts of exercise have been shown to produce transient increases in regional cerebral glucose utilization, oxygen uptake, and cerebral blood flow in motor cortex, striatum, and hippocampus. The purpose of this study was to determine whether or not chronic exercise will cause long-term metabolic plasticity in brain structures activated during physical activity. The activity of cytochrome oxidase (COX), is coupled to the production of ATP, and reflects long-term plasticity in metabolic capacity. The present study examined whether or not 6 months of voluntary exercise would increase COX activity in the striatum, sensorimotor cortex, and three hippocampal subfields. Five-month-old, female Long-Evans hooded rats were randomly assigned to a control or exercise condition. Exercising rats had running wheels attached to their home cages. After the training period, fresh brains were rapidly frozen and sectioned with a cryostat. COX activity was measured using COX histochemical methods and optical densitometry. Rats in the exercise condition had significantly higher optical density in the hindlimb and forelimb motor cortices (18%, P<0.01) and dorsolateral caudate putamen (17%, P<0.01), but not in the ventrolateral caudate putamen or any subfield of the hippocampus. Although exercise is believed to increase neuronal activity in the hippocampus, motor cortex and striatum, only limb representations in the motor cortex and striatum increase bioenergetic capacity after regular exercise.

Animals↗

Corticospinal responses to electrical stimulation of motor cortex in the rat.

Direct and indirect corticospinal responses to electrical stimulation of motor cortex were identified in urethane-anesthetized rats. 'Killed-end' recordings were taken from the corticospinal tract at the level of the cervical cord (C1-C2) and from the medullary pyramid. The identities of direct (D) and indirect (I) corticospinal responses were confirmed by: (1) removing motor cortex to eliminate I activity, and (2) pharmacologically increasing neocortical excitability, prior to any lesions, to increase I activity. Our data indicate that the conduction velocity of the fastest corticospinal fibers is approximately 18 m/s. Our identification of the components of the corticospinal response will permit the interpretation of the more complicated surface or 'non-killed-end' depth recordings which have shown particular utility in evaluating spinal cord damage.

Action Potentials↗

Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements.

Previous studies have shown that unilateral finger movements are normally accompanied by a small activation in ipsilateral motor cortex. The magnitude of this activation has been shown to be altered in a number of conditions, particularly in association with stroke recovery. The site of this activation, however, has received limited attention. To address this question, functional magnetic resonance imaging (MRI) was used to study precentral gyrus activation in six control and three stroke patients during right index finger tapping, then during left index finger tapping. In each hemisphere, the most significantly activated site (P < 0.001 required) was identified during ipsilateral and during contralateral finger tapping. In the motor cortex of each hemisphere, the site activated during use of the ipsilateral hand differed from that found during use of the contralateral hand. Among the 11 control hemispheres showing significant activation during both motor tasks, the site for ipsilateral hand representation (relative to contralateral hand site in the same hemisphere) was significantly shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11 hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6 of 11 hemispheres, tapping of the contralateral finger simultaneously activated both the ipsilateral and the contralateral finger sites, suggesting bilateral motor control by the ipsilateral finger site. The sites activated during ipsilateral and contralateral hand movement showed similar differences in the unaffected hemisphere of stroke patients. The region of motor cortex activated during ipsilateral hand movements is spatially distinct from that identified during contralateral hand movements.

Brain Mapping↗

[Long-term rearrangements of the processing of kinesthetic afferentation at the neuronal level of the cat motor cortex after damage to the ventrolateral thalamic nucleus].

Single-unit recordings from motor cortex (area 4) were obtained in cats and under semichronic experimental conditions before and within various periods (from a week to five months) after the lesion in thalamic nucleus ventralis lateralis (n. VL). Neuronal responses to tactile stimulation of the contralateral forelimb and its passive movement in the wrist joint with the mean speed 170 degrees/s were studied. As it had been already reported by others, the magnitude and time course of averaged response histograms for some neurons, which were evoked by imposed displacements of the forelimb, were related to the velocity and/or acceleration components of the movements. Spontaneous firing and kinematic processing capabilities of motor cortical cells were affected by the lesion. The findings are in agreement with a hypothesis that n. VL is essential for encoding specific kinematic features of angular joint movements. Restoration of kinematic processing by cortical neurons in the course of post-traumatic period was characterized by facilitation of activatory reactions of the area 4 cortical cells to peripheral cutaneous stimulation. Some suggestions are made on the nature of plastic changes which develop in neuronal nets of the motor cortex after the lesion of n. VL.

Afferent Pathways↗

Changes of steady state activity in motor cortex consistent with the length-tension relation of muscle.

Steady state activity of motor cortex (MI) neurons and muscles was examined in relation to joint position. Two monkeys performed either isometric or load-bearing isotonic contractions, at different joint positions and during variation of steady torque. In either condition, MI steady state firing rate were found to be related to the amount of muscular excitation necessary to adjust muscle tension to length at any given position and load. The results obtained from 526 neurons (including pyramidal tract neurons) demonstrate for 206 neurons a correlate of the length-tension relation of muscle in the motor cortex.

Animals↗

Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey.

The terminal distribution of cortico-cortical connections was examined by autoradiography 7-8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200-500 mum wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retrosplenial limbic cortex and the motor cortex indicates that columination in the intracortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization. A columnar mode of distribution of cortico-cortical projections is present in monkeys at all ages investigated but is especially well delineated in the youngest of them. Thus, grain concentrations within columns are very high in monkeys injected at 4 days of age, somewhat lower in monkeys injected at 39-45 days of age, and least dense in those injected at 5.5 months. The distinctness of the spatially segregated pattern of innervation in the cortex of neonates indicates that the columnar organization of association-fiber systems in the frontal and limbic cortex is achieved before or shortly after birth.

Animals↗

Progressive plastic changes in the hand representation of the primary motor cortex parallel incomplete recovery from a unilateral section of the corticospinal tract at cervical level in monkeys.

After a sub-total hemisection of the cervical cord at level C7/C8 in monkeys, a paralysis of the homolateral hand is rapidly followed by an incomplete recovery of manual dexterity, reaching a plateau after about 40-50 days, whose extent appears related to the size of the lesion. During a few days after the lesion, the hand representation in the contralateral motor cortex disappeared, replaced by representations of either face or more proximal body parts. Later, however, following a time course (about 40 days) consistent with the functional recovery, progressive plastic changes in the contralateral motor cortex took place, as demonstrated by a progressive reappearance of digit movements elicited by intracortical microstimulation. These progressive plastic changes, which parallel the functional recovery, correspond to a reinstallation of a hand representation, though substantially diminished in size as compared to pre-lesion. Regarding the functional recovery, the motor cortex (including the reestablished hand area) contralateral to the unilateral cervical cord lesion played a crucial role in reestablishing control on finger movements, as assessed by reversible inactivation experiments. In contrast, the motor cortex ipsilateral to the cervical cord lesion, with largely intact projections to the spinal cord, did not contribute significantly to the recovered movements by the affected hand. These observations indicate that the CS fibers spared by the lesion are not sufficient, at least in their pre-lesion condition, to control the motoneurones innervating the digit muscles and that the pathways conveying signals from the contralateral M1 underwent reorganization.

Animals↗

Altered plasticity of the human motor cortex in Parkinson's disease.

Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long-term potentiation-like effect in the M1 in Parkinson's disease (PD) patients. Eighteen right-handed PD patients and 11 right-handed age-matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD-off). Ten patients were also evaluated after medication (PD-on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor-evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor-evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor-evoked potential amplitude before and after IPAS in PD-off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning.

Aged↗

Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson's disease.

BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found abnormalities in several excitatory and inhibitory circuits in the motor cortex in PD. These include motor evoked potential (MEP) recruitment curve, silent period duration (SP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI). METHODS: The authors studied the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on these circuits in 12 patients with PD treated with STN DBS. Data from nine patients who completed the study were analyzed. Patients remained on their usual medications. The stimulators were set at the optimal parameters (ON), half the optimal amplitude (HALF), and switched off (OFF) in random order. RESULTS: The Unified PD Rating Scale motor scores were significantly lower in the ON compared to the HALF and OFF conditions. Resting SICI, studied with paired-pulse TMS at interstimulus interval of 2 ms, was reduced in the OFF and HALF conditions compared to normal subjects. STN stimulation restored SICI to normal levels. STN stimulation had no effect on motor threshold, MEP recruitment curve, SP, active SICI, ICF, and LICI. CONCLUSIONS: Although restoration of short-interval intracortical inhibition by STN stimulation is similar to the effects of dopaminergic drugs, it has no effect on silent period duration and long-interval intracortical inhibition, which are also influenced by dopaminergic drugs. A previous study found that internal globus pallidus (GPi) stimulation reduced SP but did not change SICI. Thus, GPi and STN stimulation may affect different circuits in the motor cortex.

Adult↗

[A patient with focal dystonia induced by golf and presenting a decrease in activity of cerebral motor cortex on task].

We here report a 45-year-old man with left arm focal dystonia induced by golf. He was a swimming instructor. From 35 years of age, he swung a golf club for 4 hours everyday. At 37 years of age, he noted difficulties in moving left arm when swinging, and developed involuntary movement of left arm toward his back thereafter. His involuntary movement was exacerbated even in several years after stopping both golf and swimming. Neurologically, simultaneous contraction was observed in left triceps and biceps muscles and his left arm dropped when raising arm to front. A 'sensory trick' was also observed. Thus, he was diagnosed as having a rare focal dystonia, and its clinical characteristics and course were basically different from those of 'yips', a focal dystonia that is characterized by anxiety and distal dominant dystonia presenting only on golf. Magnetic resonance imaging (MRI), FDG-positron emission CT (FDG-PET), C11-Raclopride PET and 99mTc-single photon emission CT (SPECT) revealed no abnormality in cerebral cortex and basal ganglias. However, motor evoked potentials (MEPs) were not evoked bilaterally when magnetic stimulation was applied on primary motor cortex. On functional MRI (fMRI), 40 seconds raising left arm task-induced activation in the right primary motor, supplementary motor, and premotor areas was apparently decreased, while left motor areas, the normal side, were reasonably activated. Motor-associated areas are generally overactivated by task in focal dystonia patients whereas excitability in primary motor area is decreased in idiopathic generalized dystonia. Therefore, dystonia of the present case appears to be similar to focal dystonia clinically but may partly have a mechanism similar to idiopathic generalized dystonia as shown in the fMRI studies.

Arm↗

[The interaction in the motor cortex of 2 foci of a "polarization" dominant].

The effect of sequential applications of the weak anode DC (0.5-3 mcA) to the areas of fore- and hindlimb representation in the motor cortex was studied in waking unrestrained rabbits. This procedure formed two excitation foci with the dominant properties, i.e., different afferent stimuli (sound, light) produced the dominant behavioral reaction (limb movement). The cooperative inhibition of the dominant foci was observed in the process of formation of the second focus in different time intervals. The second focus inhibited the primary focus for a rather long-term period, and then the mutual inhibition of the foci acquired the reciprocal character. The obtained results testify to excitation redistribution in the motor cortex during the action of weak anode DC on the motor cortex.

Animals↗

Amyotrophic lateral sclerosis: T2 shortening in motor cortex at MR imaging.

PURPOSE: To determine whether decreased signal intensity of the motor cortex (T2 shortening) at magnetic resonance (MR) imaging is a useful finding for supporting the diagnosis of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: High-field-strength (1.5-T) MR images of 15 patients (seven men and eight women, aged 28-80 years) and 49 neurologically normal age-matched control patients were examined for T2 shortening in the motor cortex. In addition, brains of patients with ALS were examined at autopsy. RESULTS: The MR images of 14 of the 15 patients showed T2 shortening in precentral cortices, while the images of all but one of the control patients showed no such finding. In three of eight brains at autopsy, sections from the precentral cortex showed sparsely distributed, intensely stained astrocytes and macrophages. CONCLUSION: Abnormal iron deposition associated with the degenerative process could be the source of T2 shortening, which is a useful MR imaging finding in the diagnosis of ALS.

Amyotrophic Lateral Sclerosis↗

Mechanisms of use-dependent plasticity in the human motor cortex.

Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-d-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-d-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation.

Dextromethorphan↗

Motor cortex disinhibition in Alzheimer's disease.

OBJECTIVES: To explore subclinical disturbances in the motor cortex of patients with Alzheimer's disease (AD). METHODS: We used transcranial magnetic stimulation in a paired pulse technique to test intracortical inhibition (ICI) and intracortical facilitation in mildly to moderately demented AD patients with a normal neurological examination. Patients were studied before and during treatment with the cholinesterase inhibitor donepezil. RESULTS: AD patients had a reduced ICI compared to an age-matched control group. The amount of disinhibition correlated with the severity of dementia. Treatment with 10 mg donepezil daily was associated with an increase of ICI. CONCLUSIONS: The subclinical motor cortex disinhibition in AD patients indicates a functional disturbance, and is probably associated with a cholinergic deficit.

Aged↗

Simultaneous recording of slow brain potentials and transcranial magnetic stimulation of hand area in human motor cortex.

Recording of slow brain potentials (SPs) and transcranial magnetic stimulation (TCMS) of the human motor cortex were combined to probe the relationship between SP level and excitability of cortical neurons. In experiment 1, TCMS was applied during and shortly after the warning interval in a forewarned reaction time task. Electromyographic (EMG) responses to TCMS increased only slightly during the warning interval and were significantly elevated 150 ms after the imperative stimulus. In experiment 2, TCMS was applied during biofeedback-induced cortical positivity and negativity. In this non-motor task a dependence of TCMS response on SP amplitude was not significant. Results indicate higher local excitability of motor cortex during cortical negativity when a preparatory motor task is required. TCMS may better be suited to probe processes involved in motor tasks rather than non-motor and cognitive conditions.

Adult↗