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Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging.

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.

Adult↗

Involvement of the motor cortex in pseudochoreoathetosis.

The pathophysiological background of involuntary movements in pseudochoreoathetosis is unclear. We therefore recorded in four patients with pseudochoreoathetosis and in six age-matched controls cortical activity with a whole-head magnetoencephalography (MEG) system and surface EMGs from hand muscles. Subjects performed the following tasks: 1) rest, and 2) constant finger stretch during forearm elevation; controls additionally simulated pseudochoreoathetotic finger movements. During rest, the patients showed involuntary finger movements associated with excessive MEG-EMG coherence at frequencies between 6 and 20 Hz, whereas coherence in controls simulating pseudochoreoathetotic movements did not exceed noise level (P < 0.02). During finger stretch, MEG-EMG coherence in patients was similar to that of controls. Cortical sources of MEG-EMG coherence in patients were localized in the contralateral motor cortex. We conclude that pseudochoreoathetosis is associated with pathologically increased corticomuscular coherence and thus differs, neurophysiologically, from voluntarily simulated pseudochoreoathetotic movements. The enhanced MEG-EMG coherence in pseudochoreoathetosis probably reflects a pathologically strong motor cortical drive of spinal motorneurons after deafferentation.

Adult↗

Reorganization in primary motor cortex of primates with long-standing therapeutic amputations.

Intracortical microstimulation was used to investigate the organization of primate primary motor cortex (M1) in three squirrel monkeys and two galagos years after the therapeutic amputation of an injured forelimb or hindlimb. In two squirrel monkeys with forelimb amputation, physiological results were correlated with the distribution of corticospinal neurons after injections of tracers into the lower cervical segments of the spinal cord. Distributions of labeled corticospinal neurons helped identify the locations of the former forelimb cortex in M1. Evoked movements from M1 ipsilateral to the missing limb were not obviously different from M1 of normal controls. Stimulation in the deefferented part of M1 contralateral to the missing limb elicited movements of the remaining proximal muscles as well as movements from adjacent body representations in all cases. Stimulation in the deefferented forelimb cortex evoked shoulder stump, trunk, and orofacial movements, whereas stimulation in the deefferented hindlimb cortex evoked hip stump, trunk, and tail movements. Movements were evoked from all sites in the deprived cortex, so that there were no unresponsive zones. Minimal levels of current necessary to evoke these movements varied from those in the normal range to those of much higher levels, with the average threshold higher than normal. Finally, multiunit recording from the two galagos revealed that the deprived portions of S1 were responsive to touch or taps on the stump and neighboring body parts.

Amputation, Surgical↗

Reversal of thalamic hand syndrome by long-term motor cortex stimulation.

The authors describe a case of complete recovery from the so-called "thalamic hand" syndrome following chronic motor cortex stimulation in a 64-year-old man suffering from poststroke thalamic central pain. As of the 2-year follow-up examination, the patient's dystonia and pain are still controlled by electrical stimulation. It is speculated that a common mechanism in which the thalamocortical circuit loops are rendered out of balance may sustain hand dystonia and central pain in this case of thalamic syndrome. To the authors' knowledge this is the first reported case of its kind.

Dystonia↗

[Evolution of the astroglial reaction in the pyramidal pathway after injury of the rat motor cortex].

Investigation of astrocytes in the pyramidal tract of the rat 2 to 100 days after a lesion of the motor cortex indicates that the glial reaction, with increase in size of astrocytes and in affinity for Cajal's gold-sublimate, begins at the lesion and extends to the distal segments of the spinal cord. But this reaction recedes and disappears in lumbar and dorsal cord about 70 days after the operation. It persists in the cervical cord and in the brain. On the other hand, a characteristic increase in activity of glutamate andglucose-6-phosphate dehydrogenases is restricted to the vicinity of the lesion and does not even encroach upon the posterior limb of the internal capsule.

Animals↗

[The differential effect of damage to the motor cortex on the precise reactions of avoidance and escape in dogs].

Effects of ablation of the forelimb area in the motor cortex on the precise lifting of this limb were studied. Even inaccurate avoidance reactions to the sound signal did not recover spontaneously. In the course of retraining irregular reactions of insufficient amplitude could be easily recovered but the precise reactions (both fast continuous and slow discontinuous) did not recover at least for half a year after the ablation. On the contrary, the fast precise escape reactions (to the shock applied to the "working" limb and eliciting its unconditioned flexion) remained essentially unchanged, i. a. the ability to stop movement in the correct (previously learnt) position persisted. The ability to fix position of the flexed limb retained but in was less perfect and did not improve. The ability to overcome unconditioned flexion (in order to perform discontinuous extensor escape reaction) was severely and continuously (for a year) decreased. Visually guided placings of the forepaw on a held out hand of an experimenter recovered essentially spontaneously and almost completely during a month.

Acoustic Stimulation↗

Effects of a primary motor cortex lesion on step-tracking movements of the wrist.

1. We lesioned the contralateral arm area of the primary motor cortex (M1) in a monkey that had been trained to make rapid step-tracking movements of the wrist in different directions. We examined movement kinematics and electromyographic (EMG) activity of forearm muscles both before and 3.5-5 mo after the lesion. 2. The lesion caused marked changes in movement kinematics and the patterns of activity in agonist, synergist, and antagonist muscles. 3. After the lesion, movements to all targets were performed more slowly. In addition, some movements were misdirected. For example, most movements to the target that required wrist flexion and radial deviation were made in two steps, instead of in a single smooth trajectory. 4. After the lesion, distinct bursts of muscle activity were no longer observed during step-tracking movements. In addition, suppression of antagonist activity at movement onset was abolished or reduced. The relative timing of agonist and synergist muscle activity was markedly altered. 5. We conclude that M1 contributes to the precise spatiotemporal patterning of muscle activity during step-tracking movements.

Animals↗

Phasic and tonic responses of premotor and primary motor cortex neurons to torque changes.

Responses to torque step perturbation of the wrist were compared in premotor area (PMA) and motor cortex (MI) neurons of the monkey. A substantial portion (39%) of cells recorded from the PMA had phasic responses with onset latencies as short as those found in MI (mostly between 15 and 50 ms). Responsiveness to small perturbations, directional specificity and linear correlation of phasic responses with the velocity of displacement are properties that were essentially present in the PMA. A role of somatosensory feedback to the PMA in accurate and fast up-dating of movement is suggested. Tonically sustained responses to torque change (mean latency around 60 ms) were encountered in both areas and preferentially in neurons that had a monotonic load-relationship under steady-state condition. Such cortical responses did not exhibit reflex-like features, i.e. no correlation with amplitude of torque step and resulting displacement. Instead, the new load condition seemed to be represented by the tonic response of any particular neuron in accordance with its individual firing rate-load characteristics. These tonic cortical responses may be involved in the swift and effective adaptation to the actual load.

Animals↗

Contrasting neuronal activity in supplementary and precentral motor cortex of monkeys. II. Responses to movement triggering vs. nontriggering sensory signals.

This report compares neuronal activity in the supplementary motor area (SMA) and the precentral motor cortex (PCM) in response to auditory and vibrotactile signals that required a monkey either to start a key-press movement or to refrain from initiating such a movement. Confirming previous reports (3, 9), a vibrotactile stimulus that triggered movement gave rise to two phases of neuronal activity in PCM neurons: a short-latency response time-locked to the occurrence of the vibrotactile stimulus, and a response related to the time of onset of the movement. When the animal was required to refrain from moving in response to the vibrotactile signal, the short-latency response was often attenuated and there was rarely any later activity. There was no attenuation of the short-latency response to the nontriggering vibrotactile stimulus in the anterior part of the postcentral somatosensory cortex. As reported previously (23), short-latency stimulus-locked responses of SMA neurons to a vibrotactile signals were less frequent and the magnitude of the responses was smaller than in the PCM. However, the properties of the later-occurring responses of SMA neurons were often different from those of PCM neurons. Many SMA neurons responded to both the triggering and nontriggering vibrotactile signals. Twenty-nine SMA neurons responded to the nontriggering signal only and not to the movement-triggering signal. Most of the PCM neurons were active after the auditory signal only when the signal was a trigger to start the key-press movement; three neurons exhibited a slight activity increase after the nontriggering auditory signal. In contrast, a number of SMA neurons responded to the nontriggering auditory signal as well as the movement-triggering auditory signal. Twenty-three neurons responded exclusively to the nontriggering auditory signal. These results indicate the extent to which SMA neuronal activity, in contrast to that of the PCM, is related to factors other than the execution of movement.

Animals↗

Effects of behaviorally rewarding hypothalamic electrical stimulation on intracellularly recorded neuronal activity in the motor cortex of awake monkeys.

Effects of hypothalamic stimulation (HS) were studied in intracellular recordings obtained from 125 neurons of the motor cortex (MC). HS that was effective in reinforcing bar-press behavior, i.e. satisfactory for intracranial self-stimulation (ICSS), evoked short-latency (less than 3 ms) activation of these cortical neurons more frequently (42% of cells tested) than did HS that was ineffective in reinforcing bar-press behavior (7% of cells tested). Longer latency activation (greater than 3 ms) and inhibition (of variable onset) also occurred, but their incidence was not significantly different when HS was effective or ineffective in producing ICSS. Effects of HS that was effective in producing ICSS were also examined in 23 cells in which the spikes were followed by afterhyperpolarization (AHP) of 1.4-10 mV amplitude and 1.7-54 ms duration. The amplitudes of AHPs of greater than 8 ms duration were reduced after presentations of HSs that were effective as a reinforcer for ICSS. These results suggest that: (1) MC neurons receive reward-related hypothalamic information through pathways sufficiently direct to produce short-latency activation; and (2) a modulation of spike afterhyperpolarization can be observed in conjunction with reception of this information.

Animals↗

Effects of small ischemic lesions in the primary motor cortex on neurophysiological organization in ventral premotor cortex.

After a cortical lesion, cortical areas distant from the site of injury are known to undergo physiological and anatomical changes. However, the mechanisms through which reorganization of distant cortical areas is initiated are poorly understood. In a previous publication, we showed that the ventral premotor cortex (PMv) undergoes physiological reorganization after a lesion destroying the majority of the primary motor cortex (M1) distal forelimb representation (DFL). After large lesions destroying >50% of the M1 DFL, the PMv DFL invariably increased in size, and the amount of the increase was positively correlated with the size of lesion. To determine whether lesions destroying <50% of the M1 DFL followed a similar trajectory, we documented PMv reorganization using intracortical microstimulation techniques after small, ischemic lesions targeting subregions within the M1 DFL. In contrast to earlier results, lesions resulted in a reduction of the PMv DFL regardless of their location. Further, because recent anatomical findings suggest a segregation of PMv connectivity with M1, we examined two lesion characteristics that may drive alterations in PMv physiological reorganization: location of the lesion with respect to PMv connectivity and relative size of the lesion. The results suggest that after a lesion in the M1 DFL, the induction of representational plasticity in PMv, as evaluated using intracortical microstimulation, is related more to the size of the lesion than to the disruption of its intracortical connections.

Animals↗

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects.

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.

Adult↗

Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.

Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate. Three glutamate transporters expressed in human motor cortex, termed EAAT1, EAAT2, and EAAT3 (for excitatory amino acid transporter), have been characterized by their molecular cloning and functional expression. Each EAAT subtype mRNA was found in all human brain regions analyzed. The most prominent regional variation in message content was in cerebellum where EAAT1 expression predominated. EAAT1 and EAAT3 mRNAs were also expressed in various non-nervous tissues, whereas expression of EAAT2 was largely restricted to brain. The kinetic parameters and pharmacological characteristics of transport mediated by each EAAT subtype were determined in transfected mammalian cells by radio-label uptake and in microinjected oocytes by voltage-clamp measurements. The affinities of the EAAT subtypes for L-glutamate were similar, with Km determinations varying from 48 to 97 microM in the mammalian cell assay and from 18 to 28 microM in oocytes. Glutamate uptake inhibitors were used to compare the pharmacologies of the EAAT subtypes. The EAAT2 subtype was distinguishable from the EAAT1/EAAT3 subtypes by the potency of several inhibitors, but most notably by sensitivity to kainic acid (KA) and dihydrokainic acid (DHK). KA and DHK potently inhibited EAAT2 transport, but did not significantly affect transport by EAAT1/EAAT3. Using voltage-clamp measurements, most inhibitors were found to be substrates that elicited transport currents. In contrast, KA and DHK did not evoke currents and they were found to block EAAT2-mediated transport competitively. This selective interaction with the EAAT2 subtype could be a significant factor in KA neurotoxicity. These studies provide a foundation for understanding the role of glutamate transporters in human excitatory neurotransmission and in neuropathology.

Amino Acid Sequence↗

Influence of the supplementary motor area on primary motor cortex excitability during movements triggered by neutral or emotionally unpleasant visual cues.

The stronger anatomo-functional connections of the supplementary motor area (SMA), as compared with premotor area (PM), with regions of the limbic system, suggest that SMA could play a role in the control of movements triggered by visual stimuli with emotional content. We addressed this issue by analysing the modifications of the excitability of the primary motor area (M1) in a group of seven healthy subjects, studied with transcranial magnetic stimulation (TMS), after conditioning TMS of SMA, during emotional and non-emotional visually cued movements. Conditioning TMS of the PM or of contralateral primary motor cortex (cM1) were tested as control conditions. Single-pulse TMS over the left M1 was randomly intermingled with paired TMS, in which a conditioning stimulation of the left SMA, left PM or right M1 preceded test stimulation over the left M1. The subjects carried out movements in response to computerised visual cues (neutral pictures and pictures with negative emotional content). The amplitudes of motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle after paired TMS were measured and compared with those obtained after single-pulse TMS of the left M1 under the various experimental conditions. Conditioning TMS of the SMA in the paired-pulse paradigm selectively enhanced MEP amplitudes in the visual-emotional triggered movement condition, compared with single-pulse TMS of M1 alone or with paired TMS during presentation of neutral visual cues. On the other hand, conditioning TMS of the PM or cM1 did not differentially influence MEP amplitudes under visual-emotional triggered movement conditions. This pattern of effects was related to the intensity of the conditioning TMS over the SMA, being most evident with intensities ranging from 110% to 80% of motor threshold. These results suggest that the SMA in humans could interface the limbic and the motor systems in the transformation of emotional experiences into motor actions.

Adult↗

[Facilitation and depression, under the influence of the iontophoretic application of acetylcholine, of the different components of the neuronal reactions in the cat motor cortex during the performance of a conditioned reflex of placing the paw on a lever].

The iontophoretic application of acetylcholine onto the motor cortex of cats during the execution of conditioned placing reaction caused an increase in neuronal excitability and facilitation of "extrinsic" connections (manifested as an enhancement of primary responses to electrical stimulation of the parietal cortex) and independent effect of suppression, which could be seen only in the response components with longer latency. The functional significance of these oppositely directed effects of acetylcholine application is corroborated by statistically significant changes in the motor response latency of the same directions as the changes in neuronal responses. Such a correlation was observed in a number of experiments.

Acetylcholine↗

'Direct' and 'crossed' modulation of human motor cortex excitability following exercise.

Rapid repetitive movements of the thumb (1 min duration) produce a reversible decrease in the activated primary motor cortex (MI) excitability to transcranial magnetic stimulation (TMS) with recovery within 35-40 min. In the present study we investigated (1) the role of peripheral sensory feedback in inducing such decrease and (2) possible effects of exercise on the non-activated MI. Stimulation of peripheral Ia afferent fibres, induced by 1 min vibration of thenar muscles and 2 Hz electrical stimulation of the median nerve at the wrist, have no effect on motor evoked potential (MEP) amplitude to TMS suggesting no role for sensory feedback to produce MI excitability modulation. Exercise produces a significant (P < 0.01) decrease of MEPs for homologous non-exercised muscles with concomitant contraction of corresponding motor cortical output maps, suggesting that changes in MI excitability also occur in the nonactivated hemisphere. This 'crossed' effect might relate to an interhemispheric transfer of information, via homotopic connections of the corpus callosum.

Adult↗

Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats.

Recent studies suggest that proliferation in the adult forebrain subventricular zone increases in response to a forebrain stroke and intraventricular infusions of growth factors enhance this response. The potential for growth factor infusions to regenerate the damaged motor cortex and promote recovery of motor function after stroke has not been examined. Here, we report that intraventricular infusions of epidermal growth factor and erythropoietin together, but not individually, promote substantial regeneration of the damaged cerebral cortex and reverse impairments in spontaneous and skilled motor tasks, in a rat model of stroke. Cortical regeneration and functional recovery occurred even when growth factor administration was delayed for up to 7 days after the stroke-induced lesion. Cell tracking demonstrated the contribution of neural precursors originating in the forebrain subventricular zone to the regenerated cortex. Strikingly, removal of the regenerated cortical tissue reversed the growth factor-induced functional recovery. These findings reveal that specific combinations of growth factors can mobilize endogenous adult neural stem cells to promote cortical tissue re-growth and functional recovery after stroke.

Animals↗

Structural study of the acute effect of Karwinskia humboldtiana on cerebral motor cortex, hippocampus, and caudate nucleus of the rat.

1. Acute effects of Karwinskia humboldtiana (Kh) ingestion were studied in some cerebral motor regions. 2. In motor cortex, widening of Virchow-Robin spaces and hyperchromasia occurred throughout the study. 3. In CA1 region of hippocampus, hyperchromasia, swelling of cell nuclei and neuronal shrinkage; were observed at the various stages. 4. In caudate nucleus, cell shrinkage and nuclear swelling occurred throughout the study. 5. Cell death images were observed in all areas studied. 6. It is suggested that a toxic effect is produced by Kh fruit, and that tissue damages may be closely related to the motor non-paralytic disturbances observed after its ingestion.

Animals↗