Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study

Background  

The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections.     

Anticipatory postural adjustment in bimanual unloading: role of the motor cortex in motor learning

The role of the motor cortex was investigated during learning unusual postural adjustment. Healthy subjects held their right (postural) forearm in a horizontal position while supporting a 1-kG load via an electromagnet. The postural forearm position was perturbed by the load release triggered by other elbow voluntary movement. Repetition of the imposed unloading test resulted in a progressive reduction of the maximal forearm rotation, accompanied by the anticipatory decrease in m. biceps brachii activity (learning). Control situation consisted of the voluntary forearm loading. Using the transcranial magnetic stimulation we examined changes in the motor evoked potential of the m. biceps brahii at the beginning and at the end of learning. The evoked potential amplitude did not significantly change in process of the decrease of m. biceps brachii activity. At the end of learning, motor evoked potential / baseline electromyogram ratio increased as compared to the beginning of learning and to the control situation. The results highlight the fundamental role of the motor cortex in suppression of synergies which interfere with formation of a new coordination during motor learning.     

Phonological and lexical motor facilitation during speech listening: a transcranial magnetic stimulation study.

In the present study, we used transcranial magnetic stimulation (TMS) to investigate the influence of phonological and lexical properties of verbal items on the excitability of the tongue's cortical motor representation during passive listening. In particular, we aimed to clarify if the difference in tongue motor excitability found during listening to words and pseudo-words [Fadiga, L., Craighero, L., Buccino, G., Rizzolatti, G., 2002. Speech listening specifically modulates the excitability of tongue muscles: a TMS study. European Journal of Neuroscience 15, 399-402] is due to lexical frequency or to the presence of a meaning per se. In order to do this, we investigated the time-course of tongue motor-evoked potentials (MEPs) during listening to frequent words, rare words, and pseudo-words embedded with a double consonant requiring relevant tongue movements for its pronunciation. Results showed that at the later stimulation intervals (200 and 300 ms from the double consonant) listening to rare words evoked much larger MEPs than listening to frequent words. Moreover, by comparing pseudo-words embedded with a double consonant requiring or not tongue movements, we found that a pure phonological motor resonance was present only 100 ms after the double consonant. Thus, while the phonological motor resonance appears very early, the lexical-dependent motor facilitation takes more time to appear and depends on the frequency of the stimuli. The present results indicate that the motor system responsible for phonoarticulatory movements during speech production is also involved during speech listening in a strictly specific way. This motor facilitation reflects both the difference in the phonoarticulatory characteristics and the difference in the frequency of occurrence of the verbal material.     

Application of transcranial magnetic stimulation for monitoring of the motor cortex condition in dynamics in healthy subjects

Transcranial magnetic stimulation (TMS) is used already for sixteen years for studying human central nervous system. The main objective of this work was to study motor thresholds and their hemispheric asymmetry in healthy subjects during TMS. We examined 31 righthanded healthy students. Their motor thresholds were measured in May (before vacations), September (immediately after vacations), and November (two months after vacations). Magnetic stimulator Neurosoft-MS (Ivanovo, Russia) was used for TNS of the motor cortex. It was shown that in the absence of regular active functional loads on the right hand, the motor thresholds in healthy righthanders significantly increased under the TMS of the left hemisphere, and hemispheric asymmetry disappeared under conditions both of muscle relaxation and voluntary contraction. Motor thresholds under the left-side TMS decreased and hemispheric asymmetry recovered with the restart of the regular active functional loads on the right hand.     

Perceiving what is reachable depends on motor representations: evidence from a transcranial magnetic stimulation study

Background

Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space.

Methodology

Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80% of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90% of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms).

Principal Findings

Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space.

Conclusion

This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possible interactions with nearby objects and thus may contribute to the perception of the boundary of peripersonal space.     

Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study

Background

Upper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls.

Methods

Motor evoked potentials of the genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls.

Main Results

In the sleep apnea patients: 1) combined genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls.

Conclusion

Sleep apnea patients and control subjects differ in the response pattern of the genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.     

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans.

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (approximately 1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5-20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for approximately 30 min (P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.     

Task-related functional magnetic resonance imaging-based neuronavigation for the treatment of depression by individualized repetitive transcranial magnetic stimulation of the visual cortex

To determine whether repetitive transcranial magnetic stimulation(rTMS) of the visual cortex(VC) provides effective and welltolerated treatment and whether magnetic resonance imaging(MRI) measures functional change of the VC as a biomarker of therapeutic effect in major depressive disorder(MDD), we performed a sham-controlled, double-blind, randomized, three-arm VC rTMS treatment study in 74 MDD patients. Neuronavigated rTMS(10 Hz, 90% of resting motor threshold, 1,600 pulses over20 min twice per day) was performed over the VC for five days. Clinical outcome was measured by Hamilton Depression Rating Scale(HAMD-24) at days 0, 1, 3, 5 and after terminating rTMS, with follow-up at four weeks. MRI was measured at days 0 and5. The individualized group exhibited the greatest change in HAMD-24 scores after VC rTMS for 5 days(F=5.53, P=0.005),which were maintained during follow-up period(F=4.22, P=0.016). All patients reported good tolerance. Changes in VC taskrelated functional MRI correlated with symptomatic reduction in the individualized group. Treatment reduced the initially abnormal increase in resting state functional connectivity from the VC to the pre/subgenual anterior cingulate cortex at day 5,especially in the individualized group. We demonstrated therapeutic potential and good tolerance of VC rTMS in MDD patients,indicated by biomarkers of f MRI measurement.     

The site of action of magnetic stimulation of human motor cortex in a patient with motor neuron disease

Cortical and spinal root (C₈-T₁) magnetic stimulation evoked single motor unit potentials in the abductor pollicis brevis and abductor digiti minimi muscles in a patient with chronic motor neuron disease. This patient was unique in that there were few surviving motoneurons in these muscles making it possible to record single motor units. Central motor conduction time was within normal limits. Cortical mapping of motor evoked potentials (MEPs) was carried out using a twin magnetic coil stimulating over the motor cortex at intervals of 1 cm along the coronal axis and 1–2 cm along the sagittal axis. As the site of cortical stimulation was moved from the centre, the latency of the MEPs increased by 0.7–0.8 ms suggesting one synaptic delay. This study provides further data that magnetic stimulation of the human cortex indirectly activates pyramidal cells via interneurons.     

Spike suppression in a local cortical circuit induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) noninvasively interferes with human cortical function, and is widely used as an effective technique for probing causal links between neural activity and cognitive function. However, the physiological mechanisms underlying TMS-induced effects on neural activity remain unclear. We examined the mechanism by which TMS disrupts neural activity in a local circuit in early visual cortex using a computational model consisting of conductance-based spiking neurons with excitatory and inhibitory synaptic connections. We found that single-pulse TMS suppressed spiking activity in a local circuit model, disrupting the population response. Spike suppression was observed when TMS was applied to the local circuit within a limited time window after the local circuit received sensory afferent input, as observed in experiments investigating suppression of visual perception with TMS targeting early visual cortex. Quantitative analyses revealed that the magnitude of suppression was significantly larger for synaptically-connected neurons than for isolated individual neurons, suggesting that intracortical inhibitory synaptic coupling also plays an important role in TMS-induced suppression. A conventional local circuit model of early visual cortex explained only the early period of visual suppression observed in experiments. However, models either involving strong recurrent excitatory synaptic connections or sustained excitatory input were able to reproduce the late period of visual suppression. These results suggest that TMS targeting early visual cortex disrupts functionally distinct neural signals, possibly corresponding to feedforward and recurrent information processing, by imposing inhibitory effects through intracortical inhibitory synaptic connections.     

Muscle afferent modulation by stimulation of motor and supplementary motor cortex in cats

Local stimulation in the zone of motor representation of the cat hind limb in the postcruciate cortex (area 4) modulates afferent activity of flexor spindles of the foot. An initial pause, connected with contraction of extrafusal fibers, is observed in this activity. After the muscle has returned to its original length, a sharp rise of discharge frequency develops followed by a return to its initial level. Similar phases, but less marked, are observed in secondary afferents. Stimulation of contralateral and ipsilateral regions of the medial precruciate cortex (area 6) causes selective, intensive, and prolonged facilitation of discharge of type Ia units followed by an after-effect, without involving extrafusal muscle fibers. Since influences of the premotor supplementary cortex on lumbar gamma motoneurons are relatively independent of influences coupled with activation of the alpha system on muscle afferents from the motor cortex, a specific role of area 6 in the regulation of segmental excitability of the gamma system can be postulated.     

Integration in working memory: a magnetic stimulation study on the role of left anterior prefrontal cortex

Integration is a fundamental working memory operation, requiring the insertion of information from one task into the execution of another concurrent task. Previous neuroimaging studies have suggested the involvement of left anterior prefrontal cortex (L-aPFC) in relation to working memory integration demands, increasing during presentation of information to be integrated (loading), throughout its maintenance during a secondary task, up to the integration step, and then decreasing afterward (unloading). Here we used short bursts of 5 Hz repetitive Transcranic Magnetic Stimulation (rTMS) to modulate L-aPFC activity and to assess its causal role in integration. During experimental blocks, rTMS was applied (N = 10) over L-aPFC or vertex (control site) at different time-points of a task involving integration of a preloaded digit into a sequence of arithmetical steps, and contrasted with a closely matched task without integration demand (segregation). When rTMS was applied during the loading phase, reaction times during secondary task were faster, without significant changes in error rates. RTMS instead worsened performance when applied during information unloading. In contrast, no effects were observed when rTMS was applied during the other phases of integration, or during the segregation condition. These results confirm the hypothesis that L-aPFC is causally and selectively involved in the integration of information in working memory. They additionally suggest that pre-integration loading and post-integration unloading of information involving this area may be active and resource-consuming processes.     

Effects of exhaustive incremental treadmill exercise on diaphragm and quadriceps motor potentials evoked by transcranial magnetic stimulation.

It is unknown whether changes in corticomotor excitability follow exercise in healthy humans. We hypothesized that a fall in the diaphragm and quadriceps motor-evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation of the motor cortex would occur after an incremental exercise task. In 11 healthy subjects, we measured transdiaphragmatic pressure and isometric quadriceps tension in response to supramaximal peripheral magnetic nerve stimulation. MEPs were recorded from these muscles in response to transcranial magnetic stimulation. After baseline measurements, subjects performed a period of submaximal exercise (gentle walking). Measurements were repeated 5 and 20 min after this. The subjects then exercised on a treadmill with an incremental protocol to exhaustion. Transcranial magnetic stimulation was performed at baseline and at 5, 20, 40, and 60 min after exhaustive exercise, and force measurements were obtained at baseline, 20 min, and 60 min. Mean exercise duration was 18 +/- 4 min, and mean maximum heart rate was 172 +/- 10 beats/min. Twitch transdiaphragmatic pressure and twitch isometric quadriceps tension were not different from baseline after exercise, but a significant decrease was observed in diaphragm MEP amplitude 5 and 20 min after exercise (60 +/- 38 and 45 +/- 24%, respectively, of baseline, P = 0.0001). At the same times, the mean quadriceps MEPs were 59 +/- 39 and 74 +/- 32% of baseline (P < 0.0001 and P < 0.01, respectively). Studies using paired stimuli confirmed a likely intracortical mechanism for this depression. Our data confirm significant depression of both diaphragm and quadriceps MEPs after incremental treadmill exercise.     

Frequency analysis of motor responses evoked in unanesthetized cats by stimulation of the motor cortex

Frequency characteristics of motor responses evoked by stimulation of the motor cortex by amplitude- and frequency-modulated stimulus sequences were investigated in chronic experiments on unanesthetized cats. The variable component of evoked muscular contraction was studied. Frequency characteristic curves were plotted by the harmonic linearization method. Transformation of controlling signals in the motor system was shown to take place by low-frequency filtration and to be characterized by nonstationary, nonlinear, and frequency-dependent properties. Phase delay of the principal harmonic of the variable component of evoked muscular contraction was minimal at a frequency of 0.2 Hz and it varied in different experiments from 40 to 90°. The increase in the phase delay and decline of the amplitude-frequency characteristic curves were particularly marked if the frequency exceeded 1–2 Hz. The mean phase delay at a frequency of 5 Hz was about 108°; the mean slope of the amplitude characteristic curves in the 2–10 Hz region was –12 dB/decade. It is suggested that definite correlation between the dynamic properties of the motor system may be determined, in particular, by the adaptive properties of the spike discharge of neurons concerned in the transmission of motor command signals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 571–579, November–December, 1980.     

Dynamic characteristics of motor responses evoked by stimulation of the motor cortex in unanesthetized cats

Temporal characteristics of motor responses evoked in unanesthetized cats by stimulation of the motor cortex through bipolar needle electrodes were investigated in chronic experiments. Isometric and isotonic contractions of the flexor muscles of the hip and knee joints of the limb contralateral to the point of stimulation were recorded. The latent period of response varied from 100 msec or more in the case of low-frequency (100–150 Hz) and low-threshold (1.1–1.2 thresholds) stimulation of the motor cortex to 30–35 msec in the case of "optimal" parameters of stimulation (300–400 Hz, 1.5–1.6 thresholds). If the intensity of stimulation was high enough the rising time constant of evoked contraction was 50–80 msec; values of the falling time constant of muscular contraction after cessation of stimulation were much greater, namely 150–300 msec. The rising time constant of contraction decreased with an increase in both the frequency and strength of motor cortical stimulation. The results are examined and discussed from the standpoint of methods of automatic control theory.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 451–458, September–October, 1980.     

Study of motor cortex excitability in the load holding task

Changes in the amplitude of hand muscle responses to a series of ten stimuli applied to the motor cortex has been studied in subjects holding a small load for 3 min. The amplitude of muscle responses and the background activity decreased with time as compared to the initial level. Regression analysis showed that the muscle response amplitude decreased with the number of stimuli to a greater extent than the background activity. Comparison of the parameters of hand muscle activity during load holding in the stable and unstable equilibrium positions showed that the decrease in the muscle response to motor cortex stimulation during load holding in a state of unstable equilibrium is less pronounced than during load holding in a state of stable equilibrium. For the forearm muscles, the muscle response amplitude and background activity decreased less with the number of stimuli, and this decrease did not depend on the stability of the load position. It may be supposed that the evoked responses decreased more rapidly than the background activity because the motor cortex is involved in the adjustment of the level of muscle activity at the stage of the development of the program for the performance of motor tasks and then transfers the control to subcortical structures.