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PubMed2000

Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Adult↗

PubMed2002

A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia.

It has been proposed that inhibitory deficits play a crucial role in the pathophysiological process of schizophrenia as suggested by post-mortem, neuropsychological and neurophysiological evidence. We hypothesised that patients with schizophrenia would demonstrate abnormalities of cortical inhibition in the motor cortex with single and paired pulse transcranial magnetic stimulation (TMS). Patients with DSM-IV schizophrenia (n=22) and normal volunteers (n=21) participated in the study. Electromyographic recordings from the abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the contra-lateral motor cortex. The threshold intensity to produce a motor response, the size of the motor evoked potential, the duration of the silent period, and the cortical inhibition and facilitation to paired pulse TMS were measured. The patient group demonstrated a reduction in length of the silent period and a reduction in cortical inhibition with paired stimuli. No changes were found in motor threshold, motor evoked potential size, or cortical facilitation. The study demonstrated deficits of cortical inhibition in the motor cortex of patients with schizophrenia. These deficits appear to be of cortical origin. Their relationship to dysfunction in other cortical networks requires further elucidation.

Adolescent↗

PubMed1977

Reversibility of lipofuscin accumulation caused by protein malnutrition in the motor cortex of squirrel monkeys, Saimiri scireus.

Lipofuscin pigment has been demonstrated histochemically in the motor cortex by the use of several histochemical and cytochemical methods in the healthy (maintained on a diet with 25% protein content) and protein malnourished (maintained on a diet with 2% protein content) adult animals. 4 animals in the latter category were rehabilitated over a period of 11 months and various histochemical techniques were repeated on the motor cortex of these animals. The healthy animals showed a somewhat uniform distribution of lipofuscin pigment in the neuronal perikarya with the perineuronal glia showing only slight occurrence of pigment bodies. The malnourished animals exhibited a significantly larger number of lipofuscin bodies in the neuronal as well as glial perikarya. The neurons, especially, showed aggregations of lipofuscin bodies characterized by a large increase in the activity of acid phosphatase and simple esterases. The rehabilitated animals, however, showed a decrease of lipofuscin pigment in the neuronal perikarya with a concomitant loss of lysosomal enzymes, while a significant increase of these bodies was observed in the perineuronal glial cells. It is evident that the formation of lipofuscin pigment gets accelerated under the extrinsic influence of dietary protein deprivation in the adult animals, but the process is reversed at least to some extent by halting the dietary deficiency or its correction by rehabilitation. The perineuronal glial cells appear to play a significant role in the removal of lipofuscin bodies from the neuronal perikarya. The significance of these observations has been discussed.

Animals↗

PubMed2001

Integrating the work of D. Denny-Brown and some of his contemporaries into current studies of the primate motor cortex.

Most contemporary investigators who study the behavioral effects of lesions of the primate motor cortex evaluate their findings in comparison to those of other recent investigators, but not in relation to the experimental neurologists who dominated this field around the mid-part of the 20th century. Utilizing selected recent reports, we demonstrate that these earlier papers, primarily those by D. Denny-Brown, provide valuable insights into the interpretation of some modern studies. Thus, we suggest that contemporary investigators of the primate motor cortex thoroughly review articles by the mid-20th century experimental neurologists. In addition, Denny-Brown and his contemporaries studied the effects of lesions in many other parts of the primate nervous system, and the associated reports are presumably also relevant to current investigations of these areas of the CNS.

Animals↗

PubMed2006

Changes in motor cortex excitability with stimulation of anterior thalamus in epilepsy.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders and pain. Recently, bilateral DBS of the anterior nucleus of thalamus (AN) was performed for the treatment of intractable epilepsy. This surgery reduced seizure frequency in an initial group of patients. However, its physiologic effects on the cortex and mechanisms of action remain poorly understood. Different classes of antiepileptic drugs (AEDs) have distinct effects on the excitatory and inhibitory circuits in the motor cortex, which can be studied noninvasively by transcranial magnetic stimulation (TMS). OBJECTIVE: To examine the effects of bilateral AN DBS on motor cortex excitability in epilepsy and compare these to the known effects of AEDs. METHODS: Cortical excitability was assessed in five medicated epilepsy patients with bilateral stimulators implanted in the anterior thalamus and nine healthy controls. Single and paired TMS were used to examine cortical inhibitory and facilitatory circuits. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex. Patients were studied during DBS turned off (OFF condition), DBS with cycling stimulation mode (1 minute on, 5 minutes off; CYCLE), and DBS with continuous stimulation (CONTINUOUS) in random order on 3 consecutive days. RESULTS: Motor thresholds were increased in the patients regardless of DBS condition. Active short-interval intracortical inhibition (SICI) was significantly reduced in the OFF and CYCLE conditions but returned toward normal levels in the CONTINUOUS condition. Rest SICI, long interval intracortical inhibition, and silent period duration were unchanged. CONCLUSIONS: Increased short-interval intracortical inhibition with continuous deep brain stimulation (DBS) suggests that thalamic DBS might drive cortical inhibitory circuits, similar to antiepileptic drugs that enhance gamma-aminobutyric acid inhibition.

Adult↗

PubMed2002

Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Adult↗

PubMed1998

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques.

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high-resolution fast low-angle shot (FLASH) technique (matrix size 1282). The FLASH technique was applied additionally with a 64(2) matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64(2) matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and posterior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 1282 compared to FLASH 64(2) and EPI 64(2), whereas the activated areas proved to be smaller in FLASH 1282 functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 1282. Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.

Adult↗

PubMed2006

The imprint of action: motor cortex involvement in visual perception of handwritten letters.

Humans are able to recognize handwritten texts accurately despite the extreme variability of scripts from one writer to another. This skill has been suggested to rely on the observer's own knowledge about implicit motor rules involved in writing. To investigate the possible neural correlates of such an ability, we monitored with magnetoencephalography (MEG) the approximately 20-Hz oscillations originating from the motor cortex. The oscillations were more suppressed after visual presentation of handwritten than printed letters, indicating stronger excitation of the motor cortex to handwritten scripts. These results support the idea of embodied visual perception of handwritten scripts and the involvement of the motor cortex in the underlying action-perception link.

Adult↗

PubMed1986

Long-range focal collateralization of axons arising from corticocortical cells in monkey sensory-motor cortex.

Small extracellular injections of HRP were placed into a stratum of corticocortical axons situated immediately deep to area 3b of the monkey somatic sensory cortex. This stratum had previously been demonstrated to contain corticocortical fibers linking the cytoarchitectonic fields of the somatic sensory cortex to one another and certain of them to the motor cortex. This method resulted in extremely successful filling of pyramidal cells, their axons, collateral axon branches, and terminations in areas 3b, 1, and 2 posterior to the injection and in areas 3a and 4 anterior to it. The major finding was that cells with somata situated in any one of these fields and with principal axons traversing the injection site have long collaterals, primarily in layers III and V, which can extend throughout their own cytoarchitectonic field and into one or more other fields. In these fields they give off focused, columnlike concentrations of terminal boutons, which can be separated from one another by 800 micron or more. The anterogradely labeled, primary corticocortical fibers, traced forwards into areas 3a and 4, have virtually identical focal terminations. These findings indicate that interareal connectivity in the sensory-motor cortex can be effected by the axon branches of single cells rather than by separate groups of cells, and this may form a basis for the convergence of place and modality information on single cells in the sensorimotor cortex, a convergence that is not seen in the thalamic input to this cortex.

Animals↗

PubMed2002

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

Algorithms↗

PubMed1995

The relation between bradykinesia and excitability of the motor cortex assessed using transcranial magnetic stimulation in normal and parkinsonian subjects.

The response of single motor units in the first dorsal interosseus (FDI) muscle to transcranial magnetic stimulation (TMS) of the motor cortex has been assessed using the post-stimulus time histogram during weak voluntary contraction in patients with parkinsonian symptoms and in age-matched, normal subjects. Patients and subjects were required to maintain the discharge of a motor unit at a steady rate during TMS. Responses were evident in post-stimulus time histograms of motor unit discharges as single or double peaks at mean (+/- S.E.) latencies of 23.4 msec (+/- 0.7) for normal subjects and 24.9 msec (+/- 0.9) for parkinsonian patients. There were no significant differences in latency or tendency to double peaks in the responses of motor units when normal subjects and parkinsonian patients were compared. The group data showed no significant difference between the threshold TMS for modulation of the discharge of single motor units in patients and normal subjects. However, 7 of the 15 parkinsonian patients, but only 1 of 15 normal subjects, had thresholds to TMS greater than or equal to 45% of the maximum output of the magnetic stimulator. Speed of movement was measured by 3 tasks: (1) timed stand/walk/sit, (2) timed peg-board test, (3) frequency of 2-point table taps. In the parkinsonian group there was a positive linear correlation between threshold to TMS and degree of bradykinesia for each individual score and the average score on the tests of speed of movement. This was not evident for the normal group. The results are discussed in the light of current views on the mode of action of TMS. The findings are consistent with the conclusion that parkinsonian patients exhibiting pronounced bradykinesia have a lowered excitability of the motor cortex.

Aged↗

PubMed1997

Persistence of layer IV in the primary motor cortex (area 4) of children with cerebral palsy.

The normal development of the human primary motor cortex is characterized by a cytoarchitectonic transformation from the fetal, six-layered cortex to the adult, five-layered agranular cortex. The present study examines whether this transformation also occurs in children with cerebral palsy. Nissl-stained, serial sections through the left precentral gyrus of 14 children (age: 3-13 years) with cerebral palsy and from a control group without any clinically manifested disturbances of the motor system were analyzed. The widths of cortical layers, the laminar distributions of area 1 fractions occupied by cell bodies and neuropil, and the numerical densities and mean sizes of cell bodies were measured. In 5 cases of cerebral palsy, an inner granular layer (IV) persisted up to ages between 3 and 9 years. Layer IV was absent in other cases and in the controls. The persistence of layer IV was closely related to severe impairments of posture: all children with persistent layer IV were unable to maintain an upright posture. Cytoarchitectonic differences to controls were also found in other layers. Layer V, the major source of the pyramidal tract, was more narrow in children with cerebral palsy. The ratio between average cell body size for layers III and V was changed in the group of cerebral palsy. Thus, severe impairment of posture can be associated with disturbed cytoarchitectonic development of the motor cortex.

Adolescent↗

PubMed1984

Specialized subregions in the cat motor cortex: anatomical demonstration of differential projections to rostral and caudal sectors.

Ipsilateral cortico-cortical and thalamo-cortical projections to the cat motor cortex were determined from the locations of retrogradely labeled neurons following single small intracortical injections of HRP in area 4 gamma. These projections were also examined by studying the distribution of anterogradely transported axonal label following multiple injections of HRP or of tritiated amino acids in areas 1-2 of SI and in area 2pri (SII). The number of retrogradely labeled cells in areas 1-2 and in area 2pri differed markedly between HRP injection sites located in the precruciate (anterior sigmoid gyrus) and postcruciate (posterior sigmoid gyrus) subregions of area 4 gamma. These associational projections from primary and secondary somatosensory cortices were dense to postcruciate subregions but weak to the precruciate subregions. The associational projections from areas 1-2 and from area 2pri to the postcruciate subregion of area 4 gamma were topographically organized, but no clear topographic organization could be demonstrated for the precruciate projection. Anterograde terminal labeling following injection of either HRP or tritiated amino acids into areas 1-2 and area 2pri confirmed the preferential projection of somatosensory cortex to the postcruciate subregion of motor cortex. The projection from somatosensory areas 1-2 was uniform over its terminal field, but that from area 2pri was more patchy and complex. HRP injections in area 4 gamma gave rise to lamellae of labeled neurons in the ventrolateral nucleus of thalamus (VL). A topographic relationship was found between the site of injection and the location of the lamella of labeled neurons. The percentage of retrogradely labeled neurons in the shell zone surrounding the border of the ventrolateral nucleus and the ventrobasal complex (VB) was greater following postcruciate than precruciate injections, whereas fewer retrogradely labeled neurons were found in central lateral nucleus (CL) after postcruciate injections than after precruciate injections. These observations support the hypothesis that differential cortical and thalamic projections to different subregions of area 4 gamma may give rise to the different physiological properties of neurons observed in these subregions (Vicario et al. 1983; Martin et al. 1981).

Afferent Pathways↗

PubMed2000

Single- and multiple-event paradigms for identification of motor cortex activation.

BACKGROUND AND PURPOSE: The "single-event" technique has been used as an alternative to the "block-trial" method to detect activation that may be accompanied by head motion. The purpose of this study was to compare the two methods for measuring activation in the sensorimotor cortex secondary to motor tasks. METHODS: Functional MR imaging data were acquired from six participants as they performed tasks with their fingers, tongues, and toes in a block-trial and a single-event paradigm. For the block trial, the participant was instructed to perform the task when cued at a rapid self-timed rate for 15 seconds, alternating with 15 seconds of rest. Five periods of task performance and six rest periods were included in one acquisition. For the single-event method, the participant performed the task a single time every 15 seconds when cued by the investigator, for a total of 21 times. Using conventional parcellation methods, activation was detected by a cross-correlation technique and was classified as occurring in the sensorimotor cortex, supplementary motor area (SMA), or as nonspecific. Differences between the two acquisition paradigms were tested using the standard t test at a significance level of P < .05. RESULTS: Activation was identified by both the block-trial and the single-event methods for the finger task, for the tongue task, and inconsistently for the toe task. More motion artifact occurred in conjunction with the toe and tongue tasks than with the finger tasks. On average, more activated pixels were identified by the single-event method than by the block-trial method. For these motor tasks, however, a larger percentage of pixels detected by the block-trial method than by the single-event method were specific for the sensorimotor cortex or SMA as sites of activation. CONCLUSION: For the tongue and the toe movement tasks, which may produce some head motion artifacts, the single-event paradigm provides a useful alternative to the block-trial method for identifying the sensorimotor cortex or SMA. It does not achieve a greater percentage of activation within primary motor areas. For the finger movement task, which does not usually produce head motion artifacts, the block-trial method generally produced a greater percentage of activated pixels in the sensorimotor cortex or SMA than did the single-event method.

Adult↗

PubMed1998

Long-term reorganization of human motor cortex driven by short-term sensory stimulation.

Removal of sensory input can induce changes in cortical motor representation that reverse when sensation is restored. Here we ask whether manipulation of sensory input can induce long-term reorganization in human motor cortex that outlasts the initial conditioning. We report that for at least 30 minutes after pharyngeal stimulation, motor cortex excitability and area of representation for the pharynx increased, while esophagus representation decreased, without parallel changes in the excitability of brainstem-mediated reflexes. Therefore increased sensory input can drive long-term cross-system changes in motor areas of the cerebral cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a frequent consequence of cerebral injury.

Adult↗

PubMed2002

Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex.

The regional specificity and functional significance of learning-dependent synaptogenesis within physiologically defined regions of the adult motor cortex are described. In comparison to rats in a motor activity control group, rats trained on a skilled reaching task exhibited an areal expansion of wrist and digit movement representations within the motor cortex. No expansion of hindlimb representations was seen. This functional reorganization was restricted to the caudal forelimb area, as no differences in the topography of movement representations were observed within the rostral forelimb area. Paralleling the physiological changes, trained animals also had significantly more synapses per neuron than controls within layer V of the caudal forelimb area. No differences in the number of synapses per neuron were found in either the rostral forelimb or hindlimb areas. This is the first demonstration of the co-occurrence of functional and structural plasticity within the same cortical regions and provides strong evidence that synapse formation may play a role in supporting learning-dependent changes in cortical function.

Animals↗

PubMed1981

Anatomical demonstration of multiple representation in the forelimb region of the cat motor cortex.

Retrograde transport of HRP was employed to examine the pattern of callosal connections in the forelimb region of area 4 gamma in the cat. According to the conventional view, areas of the motor cortex which contain the representation of distal body parts neither send nor receive callosal fibers. If this is true, then an absence of callosal connections would define the sites of distal forelimb representation. Following multiple injections of HRP into the contralateral motor cortex, many labeled neurons were found in the forelimb region of area 4 gamma. However, within this region, two spatially separate areas were found where labeled neurons were either absent or present in very low density ("callosal holes"). The anatomically defined callosal holes corresponded in size, shape, and location to the physiologically defined digit zones. To provide direct evidence for this correspondence, retrograde HRP transport was combined with intracortical stimulation in the same animal. Small lesions placed in physiologically identified digit zones were located within the anatomically defined callosal holes. Thus, a double representation of the distal forelimb can be defined in area 4 gamma of the cat motor cortex using both anatomical and physiological methods.

Animals↗

PubMed1999

Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats.

To assess behavioral experience effects on synaptic plasticity after brain damage, the present study examined the effects of complex motor skills training (the acrobatic task) on synaptic changes in layer V of the motor cortex opposite unilateral damage to the forelimb sensorimotor cortex (FLsmc). Adult male rats were given lesions or sham operations followed by 28 d of training on the acrobatic task [acrobat condition (AC)]. As a motor activity control [motor control (MC)], lesion and sham animals were given simple repetitive exercise. Previously, FLsmc lesions and acrobatic training have independently been found to result in increases in synapse to neuron ratios in the intact motor cortex relative to controls, and both of these effects were replicated in the present study. In addition, acrobat training after lesions significantly increased layer V synapses per neuron relative to sham-AC and lesion-MC rats. Thus, the combination of acrobatic training and lesions resulted in an enhanced synaptogenic response. Synapse subtypes were also differentially affected by the conditions. Lesion-MC and sham-AC primarily had increases in the number of synapses per neuron formed by multiple synaptic boutons in comparison to sham-MC. In contrast, lesion-AC had increases in both multiple and single synapses. Multiple synaptic spines and perforated synapses were also differentially affected by training versus lesions. On tests of coordinated forelimb use, lesion-AC rats performed better than lesion-MC rats. In addition to supporting a link between behavioral experience and structural plasticity after brain damage, these findings suggest that adaptive neural plasticity may be enhanced using behavioral manipulations as "therapy."

Animals↗