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Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.

The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.

Adult↗

[Effect of fenamin and haloperidol on conditioned activity of neurons of the motor cortex and striopallidal system].

The activity of neurones in the motor cortex, caudate nucleus, putamen and globus pallidus was studied during elaboration of motor conditioned reflexes to time in rabbits, treated with 1-amphetamine and haloperidol. Mechanisms of reproduction of cells trace activity in the reflex to time at the omission of trials, reacted to 1-amphetamine by increasing the intensity of reactions in the motor cortex and inactivation in putamen cells. The curve of dynamics of intensity changes of trace discharges in the course of a series of trials omissions remained unaltered only in motor cortex; in the other structures it significantly differed from the norm of intact animals. Haloperidol depressed the mechanisms of reproduction of trace reactions of the globus pallidus cells, and made them almost fully inactive in the motor cortex; the putamen neurones reacted to haloperidol by an increase of trace reactions intensity. Against the background of the animal chronic 1-amphetamine intoxication, haloperidol normalized the dynamics and intensity of trace activity. "Therapeutic" effect of haloperidol was most distinctly expressed in the motor cortex and putamen cells, less--in the caudate nucleus and was completely absent in the globus pallidus.

Amphetamine↗

Influence of task-related ipsilateral hand movement on motor cortex excitability.

OBJECTIVE: The time course of the right motor cortex excitability in relation to a task-related voluntary right thumb twitch was studied using sub-threshold transcranial magnetic stimulation (TMS) to the right motor cortex. METHODS: Motor excitability was studied in 8 adult subjects who made a brief right thumb twitch to the predictable omission of every fifth tone in a series of tones 2.5 s apart. This paradigm avoided an overt sensory cue, while allowing experimental control of TMS timing relative to both movement and the cue to move. Motor excitability was characterized by several measures of motor evoked potentials (MEPs) recorded from the left thenar eminence in response to TMS over the right scalp with a 9 cm coil: probability of eliciting MEPs, incidence of MEPs and amplitude of MEPs. RESULTS: All subjects showed suppression of motor excitability immediately following a voluntary right thumb twitch (ipsilateral response), and up to 1 s after it. However, two distinctly different effects on motor excitability were observed before the response: two subjects showed excitation, beginning about 500 ms before response until 300 ms after it, followed by the post-movement suppression; 6 subjects displayed pre-movement suppression, beginning about 600 ms before the response and persisting for the duration. CONCLUSIONS: The net effect of an ipsilateral response on motor cortex can be either inhibitory or excitatory, changing with time relative to the response. These findings are compatible with two separate processes, inhibitory and excitatory, which interact to determine motor excitability ipsilateral to the responding hand.

Adult↗

The importance of being agranular: a comparative account of visual and motor cortex.

The agranular cortex is an important landmark-anatomically, as the architectural flag of mammalian motor cortex, and historically, as a spur to the development of theories of localization of function. But why, exactly, do agranularity and motor function go together? To address this question, it should be noted that not only does motor cortex lack granular layer four, it also has a relatively thinner layer three. Therefore, it is the two layers which principally constitute the ascending pathways through the sensory (granular) cortex that have regressed in motor cortex: simply stated, motor cortex does not engage in serial reprocessing of incoming sensory data. But why should a granular architecture not be demanded by the downstream relay of motor instructions through the motor cortex? The scant anatomical evidence available regarding laminar patterns suggests that the pathways from frontal and premotor areas to the primary motor cortex actually bear a greater resemblance to the descending, or feedback connections of sensory cortex that avoid the granular layer. The action of feedback connections is generally described as "modulatory" at a cellular level, or "selective" in terms of systems analysis. By contrast, ascending connections may be labelled "driving" or "instructive". Where the motor cortex uses driving inputs, they are most readily identified as sensory signals instructing the visual location of targets and the kinaesthetic state of the body. Visual signals may activate motor concepts, e.g. "mirror neurons", and the motor plan must select the appropriate muscles and forces to put the plan into action, if the decision to move is taken. This, perhaps, is why "driving" motor signals might be inappropriate-the optimal selection and its execution are conditional upon both kinaesthetic and motivational factors. The argument, summarized above, is constructed in honour of Korbinian Brodmann's centenary, and follows two of the fundamental principles of his school of thought: that uniformities in cortical structure, and development imply global conservation of some aspects of function, whereas regional variations in architecture can be used to chart the "organs" of the cortex, and perhaps to understand their functional differences.

Brain Mapping↗

Propagating waves mediate information transfer in the motor cortex.

High-frequency oscillations in the beta range (10-45 Hz) are most active in motor cortex during motor preparation and are postulated to reflect the steady postural state or global attentive state of the animal. By simultaneously recording multiple local field potential signals across the primary motor and dorsal premotor cortices of monkeys (Macaca mulatta) trained to perform an instructed-delay reaching task, we found that these oscillations propagated as waves across the surface of the motor cortex along dominant spatial axes characteristic of the local circuitry of the motor cortex. Moreover, we found that information about the visual target to be reached was encoded in terms of both latency and amplitude of evoked waves at a time when the field phase-locked with respect to the target onset. These findings suggest that high-frequency oscillations may subserve intra- and inter-cortical information transfer during movement preparation and execution.

Animals↗

Early and late lower limb motor evoked potentials elicited by transcranial magnetic motor cortex stimulation.

Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism.

Adolescent↗

Handedness and asymmetry of hand representation in human motor cortex.

The cortical representation of five simple hand and finger movements in the human motor cortex was determined in left- and right-handed people with whole-head magnetoencephalography. Different movements were found to be represented by spatially segregated dipolar sources in primary motor cortex. The spatial arrangement of neuronal sources for digit and wrist movements was nonsomatotopic and varied greatly between subjects. As an estimator of hand area size in primary motor cortex, we determined the smallest cuboid volume enclosing the five dipole sources within the left and right hemisphere of each subject. Interhemispheric comparison revealed a significant increase of this volume in primary motor cortex opposite to the preferred hand. This asymmetry was due to a greater spatial segregation of neuronal dipole generators subserving different hand and finger actions in the dominant hemisphere. Mean Euclidean distances between dipole sources for different movements were 10.7 +/- 3.5 mm in the dominant and 9.4 +/- 3.5 mm in the nondominant hemisphere (mean +/- SD; P = 0. 01, two-tailed t-test). The expansion of hand representation in primary motor cortex could not simply be attributed to a greater number of pyramidal cells devoted to each particular movement as inferred from current source amplitudes. The degree of hemispheric asymmetry of hand area size in the primary motor cortex was correlated highly with the asymmetry of hand performance in a standardized handedness test (r = -0.76, P < 0.01). These results demonstrate for the first time a biological correlate of handedness in human motor cortex. The expansion of hand motor cortex in the dominant hemisphere may provide extra space for the cortical encoding of a greater motor skill repertoire of the preferred hand.

Adult↗

Morphology of identified corticospinal cells in the rat following motor cortex injury: absence of use-dependent change.

After unilateral injury to the forelimb area of the motor cortex, rats are reported to show relatively increased use of the ipsilateral forelimb during exploratory behavior and a concomitant transient increase in dendritic growth in neurons in the undamaged motor cortex. To identify the specific population of cells in motor cortex that undergo such use-dependent change, we examined the morphology of corticospinal pyramidal cells in the intact hemisphere 18 days following unilateral motor cortex damage. Corticospinal neurons in the motor cortex were retrogradely labeled with injections of the fluorescent tracer, DiO, into the cervical enlargement of the spinal cord. Seven days later, the rats received a lesion in the forelimb area of the contralateral motor cortex and 18 days following the lesion, limb use was assessed in two behavioral tests after which the rats were sacrificed. Under fluorescent light, corticospinal cells were visualized and injected with a horseradish peroxidase-fluorescein conjugate that was then reacted with diaminobenzidine. The labeled cells were reconstructed and the number and centrifugal order of the branches were analyzed. The increased use of the paw contralateral to the intact motor cortex was not associated with an increase in dendritic arborization in corticospinal motor neurons in the intact motor cortex. The results are discussed in light of methodological and theoretical considerations relevant to the study of neural plasticity in the motor system.

Animals↗

Effects of single intracortical microstimuli in motor cortex on activity of identified forearm motor units in behaving monkeys.

We examined the magnitude and extent of output effects elicited from focal cortical sites on the activity of individual motor units (MUs) by delivering single-pulse intracortical microstimuli (S-ICMS) (5-15 microA) during isometric wrist activity. Stimulation sites in the precentral gyrus (area 4) were chosen for study if stimulus-triggered averages (stimulus-TAs) of multiunit electromyograms (EMGs) revealed poststimulus facilitation (PStimF) of EMG activity in any of the coactivated wrist muscles. Single MUs were then isolated in the facilitated muscles with a remotely controlled tripolar microelectrode. MUs were identified by their signatures in their parent muscles (from MU-triggered averages of EMGs) and by their firing pattern during ramp-and-hold wrist responses. One objective was to quantify the magnitude and time course of the effects on single MUs by compiling peristimulus histograms of MU firing. The cross-correlation histograms between S-ICMS and MU action potentials showed peaks with onset latencies of 8.8 +/- 1.7 ms (mean +/- SD, n = 64) and durations of 1.8 +/- 1.2 ms (n = 104). The cumulative sums of the correlogram peaks resembled the rising phase of corticomotoneuronal excitatory postsynaptic potentials previously recorded in forelimb motoneurons. Comparison of correlogram peaks with stimulus-TAs of MU potentials suggests that the duration of PStimF of multiunit EMG can be accounted for, in approximately equal proportions, by l) the variation in firing time of single MUs (i.e., the width of the MU correlogram peaks), 2) the width of single MU potentials, and 3) the contribution of different MUs at different latencies. The sizes of the correlogram peaks relative to base line were larger than the PStimF of multiunit EMGs, and increased more rapidly with stimulus intensity, indicating appreciable cancellation in the multiunit records. A second objective was to determine whether S-ICMS affected all the MUs of a facilitated muscle, or only a particular subset. Of 104 MUs sampled in facilitated muscles, 99 (95%) were found to be individually facilitated (P less than 0.05). MU firing patterns during isometric ramp-and-hold torque responses were characterized as phasic, phasic-tonic, tonic, or decrementing; stimulation at a given cortical site was found to facilitate all four types of MUs. When more than one muscle showed PStimF from a site, MUs belonging to each of the facilitated muscles were facilitated individually by S-ICMS at that site.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

[Motor cortex neuron activity during elaboration of a motor conditioned reflex to electric stimulation of the ventrolateral nucleus of the thalamus].

Conditioned fore-leg movement was elaborated in cats to the electrical stimulation of the ventrolateral thalamic nucleus through one of the two chronically implanted electrodes (1+) and differentiation to a stimulation through the other electrode (2-). Then the signal meaning of the stimuli for the same animals was reversed (1-, 2+). Independently of the electrode through which the positive or differentiation stimulus was applied, the following was observed during the conditioned response: 1) in the biceps EMG a response to the conditioned stimulus was recorded with minimal latency of 8--12 ms; when the conditioned and differentiation stimuli were presented at random, the EMG response to the differentiation stimulation was considerably less pronounced or was totally absent: 2) Short-latency excitatory components of neuronal responses in the motor cortex to conditioned stimuli with a latency less than 6 and 12 ms were greater than the corresponding components of the response to differentiation stimuli.

Animals↗

Double magnetic stimulation of the motor cortex in amyotrophic lateral sclerosis.

OBJECTIVES: To study the motor cortex circuitry and the motor interhemispheric influences with double magnetic stimulation in patients affected by amystrophic lateral sclerosis. METHODS: We investigated the motor cortex in 21 amyotrophic lateral sclerosis patients (ALS, 10 with bulbar and 11 with spinal onset) with double magnetic stimulation (one shock in each hand area) with 2, 4, 6, 11 and 15 ms delay between shocks and paired magnetic stimulation (both shocks in the same area), with 4, 15, 25, 35, 55, 85, 100, 155, 200 and 255 ms delays, and compared the results with those obtained in normal subjects. RESULTS: Double magnetic stimulation showed reduced interhemispheric facilitatory influences (maximal at 4 ms delay between shocks) when the test shock was applied on the left hemisphere in all patients; whereas no significant differences were observed compared to control (P > 0.05) when it was applied on the right hemisphere in both forms. Inhibitory effects (maximal at 11 ms delay between shocks) were reduced in all patients for both hemispheres (P < 0.05). Paired magnetic stimulations showed decreased inhibitory influences at 100-155 ms delay between shocks. Compared to control, the difference was significant in bulbar (P < 0.05) and spinal onset, but not between onset forms (P > 0.05). Inhibitory effects recorded with a short delay between shocks (4 ms) were not significantly modified in both forms of onset (P > 0.05) as compared to control. There were no facilitatory influences at 15 and 35 ms delays between shocks. CONCLUSIONS: The results suggest that under these test conditions inhibition and facilitation were reduced in the motor cortex in ALS. As inhibitory effects were affected differently, two distinct cortical circuitries could be involved for short and long delays. As GABA neurons altered in ALS have been identified as a subpopulation reactive to parvalbumin, and since only inhibitory effects recorded with long delay between shocks were impaired in ALS, we suggest that this subpopulation of GABA neurons may be involved in the genesis of inhibitory effects recorded with a long delay between shocks.

Adult↗

Differential contributions of motor cortex, basal ganglia, and cerebellum to speech motor control: effects of syllable repetition rate evaluated by fMRI.

In order to delineate the neuroanatomical correlates of speech motor control, functional magnetic resonance imaging was performed during silent repetitions of the syllable "ta" at three different rates (2.5, 4.0, and 5.5 Hz). Spatial extent and magnitude of hemodynamic responses at the level of the motor cortex showed a positive correlation to production frequencies. As concerns the basal ganglia, the lower rates (2.5 and 4.0 Hz) gave rise to higher magnitudes of activation within the left putamen as compared to the 5.5 Hz condition. In contrast, cerebellar responses were rather restricted to fast performance (4.0 and 5.5 Hz) and exhibited a shift in caudal direction during 5.5 as compared to 4.0 Hz. These findings corroborate the suggestion of a differential impact of various cortical and subcortical areas on speech motor control.

Adult↗

[Influence of carbachol and atropine on the motor cortex neurons in cat operant reflex].

Effects of carbachol and atropine on the caused and background impulse neurons activity during operant reflex were studied on twenty motor cortex neurons. Motor cortex neurons in dependence of changes impulse neurons activity after carbachol administration have been divided into two groups; the first group includes neurons with a long influence on impulse activity and the second--with short. Carbachol applied by ionophoresis to motor cortex promoted authentic increase of background impulse activity and duration of the caused reaction in both groups. Abministration of atropine, an antagonist of m-cholinergic receptors significantly reduced parameters of background impulse activity and duration of the caused reaction. It was suggested that acetylcholine released by terminals of the cholinergic fibers in natural conditions takes part in maintenance of motor cortex neuron background activity and provides sufficient intensity of the motor commands generated by these cells; the given effects mediated by m-cholinergic receptors.

Animals↗

Does preoperative paresis influence intraoperative monitoring of the motor cortex?

Intraoperative monitoring of motor function by means of motor evoked potentials (MEPs) is a new method. The current study examines the influence of preoperative paresis on the feasibility and reliability of this method. Intraoperative monitoring of MEPs was performed in 58 patients during surgery in the central region. The patients were divided into three groups according to their preoperative strength (group I, muscle strength less than or equal to grade 4 according to the British Medical Research Council grading system [n = 17]; group II, normal strength (n = 36); and group III, muscle strength less than grade 5 but not worse than grade 4 [n = 5]). The motor cortex was stimulated directly with a high-frequency monopolar anodal train. In groups II and III, MEPs were elicited in all patients on cortical stimulation, whereas in group I a response was obtained in only 88% of patients. The MEP parameters in all groups had a broad interindividual range of variation. A correlation between individual intraoperative potential changes and surgical maneuvers was observed in seven patients in group II and in four patients in group I. No MEP changes were recorded in group III. Irreversible MEP changes (groups I and II) resulted in postoperative clinical deterioration. No postoperative deterioration of motor function was observed in patients with reversible MEP changes. Preoperative paresis reduces the feasibility of the method; however, it has no influence on the intraoperative pattern and reaction of the MEPs.

Adolescent↗

Specialization of motor cortex neurons in rabbits under normal conditions and after ablation of the visual cortex.

The activity of motor cortex neurons in instrumental food-acquisition behavior is compared in two control rabbits and in three rabbits after bilateral ablation of the visual cortex. Although the same types of neuron specialization were found in the experimental and control animals, their numerical ratio differed markedly in two out of the three experimental rabbits in comparison with the controls: the number of neurons activated in the act of seizing food was halved, while the number of neurons activated in connection with acts of instrumental behavior doubled. The similarity of the processes underlying behavior learning and recovery is discussed.

Animals↗

The mechanisms of interhemispheric inhibition in the human motor cortex.

Transcranial magnetic stimulation can be used to non-invasively study inhibitory processes in the human motor cortex. Interhemispheric inhibition can be measured by applying a conditioning stimulus to the motor cortex resulting in inhibition of the contralateral motor cortex. Transcranial magnetic stimulation can also be used to demonstrate ipsilateral cortico-cortical inhibition in the motor cortex. At least two different ipsilateral cortico-cortical inhibitory processes have been identified: short interval intracortical inhibition and long interval intracortical inhibition. However, the relationship between interhemispheric inhibition and ipsilateral cortico-cortical inhibition remains unclear. This study examined the relationship between interhemispheric inhibition, short interval intracortical inhibition and long interval intracortical inhibition. First, the effect of test stimulus intensity on each inhibitory process was studied. Second, the effects of interhemispheric inhibition on short interval intracortical inhibition and long interval intracortical inhibition on interhemispheric inhibition were examined. Motor evoked potentials were recorded from the right first dorsal interosseous muscle in 11 right-handed healthy volunteers. For interhemispheric inhibition, conditioning stimuli were applied to the right motor cortex and test stimuli to the left motor cortex. For short interval intracortical inhibition and long interval intracortical inhibition, both conditioning stimuli and test stimuli were applied to the left motor cortex. With increasing test stimulus intensities, long interval intracortical inhibition and interhemispheric inhibition decreased, while short interval intracortical inhibition increased. Moreover, short interval intracortical inhibition was significantly reduced in the presence of interhemispheric inhibition. Interhemispheric inhibition was significantly reduced in the presence of long interval intracortical inhibition when matched for test motor evoked potential amplitude but the difference was not significant when matched for test pulse intensity. These findings suggest that both interhemispheric inhibition and long interval intracortical inhibition are predominately mediated by low threshold cortical neurons and may share common inhibitory mechanisms. In contrast, the mechanisms mediating short interval intracortical inhibition are probably different from those mediating long interval intracortical inhibition and interhemispheric inhibition although these systems appear to interact.

Adult↗

The organization of the rat motor cortex: a microstimulation mapping study.

In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.

Animals↗