Suppression Of Corticospinal Excitability Research Articles

Subthalamic DBS does not restore deficits in corticospinal suppression during movement preparation in Parkinson’s disease

ObjectiveParkinson’s disease (PD) patients exhibit changes in mechanisms underlying movement preparation, particularly the suppression of corticospinal excitability – termed “preparatory suppression” – which is thought to facilitate movement execution in healthy individuals. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to study the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics. MethodsOn two consecutive days, we applied single-pulse transcranial magnetic stimulation to the primary motor cortex of 20 advanced PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials (MEPs) were elicited at rest or during movement preparation in an instructed-delay choice reaction time task including left- or right-hand responses. Preparatory suppression was assessed by expressing MEPs during movement preparation relative to rest. ResultsPD patients exhibited a deficit in preparatory suppression when it was probed on the responding hand side, particularly when this corresponded to their most-affected hand, regardless of their STN-DBS status. ConclusionsAdvanced PD patients displayed a reduction in preparatory suppression which was not restored by STN-DBS. SignificanceThe current findings confirm that PD patients lack preparatory suppression, as previously reported. Yet, the fact that this deficit was not responsive to STN-DBS calls for future studies on the neural source of this regulatory mechanism during movement preparation.

The influence of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation in healthy participants: A cross sectional study

ObjectivesSeveral studies suggest that acute pain decreases corticomotor excitability. However, the variability between individuals remains important and unexplained. The aim of this study was to unveil potential sources of variation by looking at the effect of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation. MethodsCorticomotor excitability was assessed with the slopes of recruitment curves measured from the first dorsal interosseous elicited by transcranial magnetic stimulation before and during pain induced by capsaicin application on the forearm. Participants completed the Tampa Scale for Kinesiophobia (TSK) and the Pain Catastrophizing Scale (PCS). ResultsTwenty-four persons participated in the study. There was a moderate and positive correlation between individual changes in the slope of the recruitment curves and TSK questionnaire scores (rs=0.47; p = 0.02). During the painful condition, unlike those with higher TSK scores, participants with lower TSK scores demonstrated recruitment curves with reduced slopes compared to baseline. There was a difference between changes in the slopes of recruitment curves between individuals with “highest” vs. “lowest” kinesiophobia scores (p = 0.01). No relationship was observed between changes in the slopes of the recruitment curves and PCS scores (p = 0.20). DiscussionThe results suggest that kinesiophobia may affect neuromotor processes and influence the corticomotor pain response. ConclusionsHigher kinesiophobia scores during experimental induced pain were associated with smaller decreases in the slopes of recruitment curves. These findings suggest that there is less inhibition of corticospinal excitability in participants with greater TKS scores.

A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition

Common cortico-basal ganglia models of motor control suggest a key role for the subthalamic nucleus (STN) in motor inhibition.1-3 In particular, when already-initiated actions have to be suddenly stopped, the STN is purportedly recruited via a hyperdirect pathway to net inhibit the cortico-motor system in a broad, non-selectivefashion.4 Indeed, the suppression of cortico-spinal excitability (CSE) during rapid action stopping extends beyond the stopped muscle and affects even task-irrelevant motor representations.5,6 Although such non-selective CSE suppression has long been attributed to the broad inhibitory influence of STN on the motor system, causal evidence for this association is hitherto lacking. Here, 20 Parkinson's disease patients treated with STN deep-brain stimulation (DBS) and 20 matched healthy controls performed a verbal stop-signal task while CSE was measured from a task-unrelated hand muscle. DBS allowed a causal manipulation of STN, while CSE was measured using transcranial magnetic stimulation (TMS) over primary motor cortex and concurrent electromyography. In patients OFF-DBS and controls, the CSE of the hand was non-selectively suppressed when the verbal response was successfully stopped. Crucially, this effect disappeared when STN was disrupted via DBS in the patient group. Using this unique combination of DBS and TMS during human behavior, the current study provides first causal evidence that STN is likely involved in non-selectively suppressing the physiological excitability of the cortico-motor system during action stopping. This confirms a core prediction of long-held cortico-basal ganglia circuit models of movement. The absence of cortico-motor inhibition during STN-DBS may also provide potential insights into the common side effects of STN-DBS, such as increased impulsivity.7-11.

Tactile Perception of Right Middle Fingertip Suppresses Excitability of Motor Cortex Supplying Right First Dorsal Interosseous Muscle

The present study examined whether tactile perception of the fingertip modulates excitability of the motor cortex supplying the intrinsic hand muscle and whether this modulation is specific to the fingertip stimulated and the muscle and hand tested. Tactile stimulation was given to one of the five fingertips in the left or right hand, and transcranial magnetic stimulation eliciting motor evoked potential in the first dorsal interosseous muscle (FDI) or abductor digiti minimi was given 200 ms after the onset of tactile stimulation. The corticospinal excitability of the FDI at rest was suppressed by the tactile stimulation of the right middle fingertip, but such suppression was absent for the other fingers stimulated and for the other muscle or hand tested. The persistence and amplitude of the F-wave was not significantly influenced by tactile stimulation of the fingertip in the right hand. These findings indicate that tactile perception of the right middle fingertip suppresses excitability of the motor cortex supplying the right FDI at rest. The suppression of corticospinal excitability was absent during tonic contraction of the right FDI, indicating that the motor execution process interrupts the tactile perception-induced suppression of motor cortical excitability supplying the right FDI. These findings are in line with a view that the tactile perception of the right middle finger induces surround inhibition of the motor cortex supplying the prime mover of the finger neighboring the stimulated finger.

Adaptation of the Corticomuscular and Biomechanical Systems of Pianists.

Independent control of movements between the fingers plays a role in hand dexterity characterizing skilled individuals. However, it remains unknown whether and in what manner neuromuscular and biomechanical constraints on the movement independence of the fingers depend on motor expertise. Here, we compared motor dexterity, corticospinal excitability of multiple muscles, muscular activation, and anatomical features of the fingers between the pianists and nonpianists. When the ring finger was passively moved by a robot, passive motions produced at the adjacent fingers were smaller for the pianists than the nonpianists, indicating reduced biomechanical constraint of fingers in the pianists. In contrast, when the ring finger moved actively, we found no group difference in passive motions produced at the adjacent fingers; however, reduced inhibition of corticospinal excitability of the adjacent fingers in the pianists compared with the nonpianists. This suggests strengthened neuromuscular coupling between the fingers of the pianists, enhancing the production of coordinated finger movements. These group differences were not evident during the index and little finger movements. Together, pianists show expertise-dependent biomechanical and neurophysiological adaptations, specifically at the finger with innately low movement independence. Such contrasting adaptations of pianists may subserve dexterous control of both the individuated and coordinated finger movements.

Premovement inhibition can protect motor actions from interference by response‐irrelevant sensory stimulation

Suppression of corticospinal excitability is reliably observed during preparation for a range of motor actions, leading to the belief that this preparatory inhibition is a physiologically obligatory component of motor preparation. The neurophysiological function of this suppression is uncertain. We restricted the time available for participants to engage in preparation and found no evidence for preparatory inhibition. The function of preparatory inhibition can be inferred from our findings that sensory stimulation can disrupt motor output in the absence of preparatory inhibition, but enhance motor output when inhibition is present. These findings suggest preparatory inhibition may be a strategic process which acts to protect prepared actions from external interference. Our findings have significant theoretical implications for preparatory processes. Findings may also have a pragmatic benefit in that acoustic stimulation could be used therapeutically to facilitate movement, but only if the action can be prepared well in advance. Shortly before movement initiation, the corticospinal system undergoes a transient suppression. This phenomenon has been observed across a range of motor tasks, suggesting that it may be an obligatory component of movement preparation. We probed whether this was also the case when the urgency to perform a motor action was high, in a situation where little time was available to engage in preparatory processes. We controlled the urgency of an impending motor action by increasing or decreasing the foreperiod duration in an anticipatory timing task. Transcranial magnetic stimulation (TMS; experiment 1) or a loud acoustic stimulus (LAS; experiment 2) were used to examine how corticospinal and subcortical excitability were modulated during motor preparation. Preparatory inhibition of the corticospinal tract was absent when movement urgency was high, though motor actions were initiated on time. In contrast, subcortical circuits were progressively inhibited as the time to prepare increased. Interestingly, movement force and vigour were reduced by both TMS and the LAS when movement urgency was high, and enhanced when movement urgency was low. These findings indicate that preparatory inhibition may not be an obligatory component of motor preparation. The behavioural effects we observed in the absence of preparatory inhibition were induced by both TMS and the LAS, suggesting that accessory sensory stimulation may disrupt motor output when such stimulation is presented in the absence of preparatory inhibition. We conclude that preparatory inhibition may be an adaptive strategy which can serve to protect the prepared motor action from external interference.

Non-selective inhibition of the motor system following unexpected and expected infrequent events.

Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a two-alternative forced-choice reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression-but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression relative to frequent, expected events even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection.

Human Theta Burst Stimulation Combined with Subsequent Electroacupuncture Increases Corticospinal Excitability.

Objective Intermittent theta burst stimulation (iTBS) is a widely used noninvasive brain stimulation for the facilitation of corticospinal excitability (CSE). Previous studies have shown that acupuncture applied to acupoints associated with motor function in healthy people can reduce the amplitude of the motor-evoked potentials (MEPs), which reflects the inhibition of CSE. In our work, we wanted to test whether the combination of iTBS and electroacupuncture (EA) would have different effects on CSE in humans. Methods A single-blind sham-controlled crossover design study was conducted on 20 healthy subjects. Subjects received 20 minutes' sham or real EA stimulation immediately after sham or real iTBS. MEPs, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), cortical silent period (CSP), and central motor conduction time (CMCT) were recorded before each trial, and immediately, 20 minutes, and 40 minutes after the end of stimulation. Results In the sham iTBS group, EA produced a reduction in MEPs amplitude, lasting approximately 40 minutes, while in the real iTBS group, EA significantly increased MEPs amplitude beyond 40 minutes after the end of stimulation. In sham EA group, the recorded MEPs amplitude showed no significant trend over time compared to baseline. Among all experiments, there were no significant changes in SICI, ICF, CSP, CMCT, etc. Conclusion These data indicate that immediate application of EA after iTBS significantly increased corticospinal excitability. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR1900025348).

Motor Task-Dependent Dissociated Effects of Transcranial Random Noise Stimulation in a Finger-Tapping Task Versus a Go/No-Go Task on Corticospinal Excitability and Task Performance.

Background and Objective: Transcranial random noise stimulation (tRNS) is an emerging non-invasive brain stimulation technique to modulate brain function, with previous studies highlighting its considerable benefits in therapeutic stimulation of the motor system. However, high variability of results and bidirectional task-dependent effects limit more widespread clinical application. Task dependency largely results from a lack of understanding of the interaction between externally applied tRNS and the endogenous state of neural activity during stimulation. Hence, the aim of this study was to investigate the task dependency of tRNS-induced neuromodulation in the motor system using a finger-tapping task (FT) versus a go/no-go task (GNG). We hypothesized that the tasks would modulate tRNS’ effects on corticospinal excitability (CSE) and task performance in opposite directions.Methods: Thirty healthy subjects received 10 min of tRNS of the dominant primary motor cortex in a double-blind, sham-controlled study design. tRNS was applied during two well-established tasks tied to diverging brain states. Accordingly, participants were randomly assigned to two equally-sized groups: the first group performed a simple motor training task (FT task), known primarily to increase CSE, while the second group performed an inhibitory control task (go/no-go task) associated with inhibition of CSE. To establish task-dependent effects of tRNS, CSE was evaluated prior to- and after stimulation with navigated transcranial magnetic stimulation.Results: In an ‘activating’ motor task, tRNS during FT significantly facilitated CSE. FT task performance improvements, shown by training-related reductions in intertap intervals and increased number of finger taps, were similar for both tRNS and sham stimulation. In an ‘inhibitory’ motor task, tRNS during GNG left CSE unchanged while inhibitory control was enhanced as shown by slowed reaction times and enhanced task accuracy during and after stimulation.Conclusion: We provide evidence that tRNS-induced neuromodulatory effects are task-dependent and that resulting enhancements are specific to the underlying task-dependent brain state. While mechanisms underlying this effect require further investigation, these findings highlight the potential of tRNS in enhancing task-dependent brain states to modulate human behavior.

Perceptual Surprise Improves Action Stopping by Nonselectively Suppressing Motor Activity via a Neural Mechanism for Motor Inhibition.

Motor inhibition is a cognitive control ability that allows humans to stop actions rapidly even after initiation. Understanding and improving motor inhibition could benefit adaptive behavior in both health and disease. We recently found that presenting surprising, task-unrelated sounds when stopping is necessary improves the likelihood of successful stopping. In the current study, we investigated the neural underpinnings of this effect. Specifically, we tested whether surprise-related stopping improvements are due to a genuine increase in motor inhibition. In Experiment 1, we measured motor inhibition in primary motor cortex of male and female humans by quantifying corticospinal excitability (CSE) via transcranial magnetic stimulation and electromyography during a hybrid surprise-Go/NoGo task. Consistent with prior studies of motor inhibition, successful stopping was accompanied by nonselective suppression of CSE; that is, CSE was suppressed even in task-unrelated motor effectors. Importantly, unexpected sounds significantly increased this motor-system inhibition to a degree that was directly related to behavioral improvements in stopping. In Experiment 2, we then used scalp encephalography to investigate whether unexpected sounds increase motor-inhibition-related activity in the CNS. We used an independent stop-signal localizer task to identify a well characterized frontocentral low-frequency EEG component that indexes motor inhibition. We then investigated the activity of this component in the surprise-Go/NoGo task. Consistent with Experiment 1, this signature of motor inhibition was indeed increased when NoGo signals were followed by unexpected sounds. Together, these experiments provide converging evidence suggesting that unexpected events improve motor inhibition by automatically triggering inhibitory control.SIGNIFICANCE STATEMENT The ability to stop ongoing actions rapidly allows humans to adapt their behavior flexibly and rapidly. Action stopping is important in daily life (e.g., stopping to cross the street when a car approaches) and is severely impaired in many neuropsychiatric disorders. Therefore, finding ways to improve action stopping could aid adaptive behaviors in health and disease. Our current study shows that presenting unexpected sounds in stopping situations facilitates successful stopping. This improvement is specifically due to a surprise-related increase in a neural mechanism for motor inhibition, which rapidly suppresses the excitability of the motor system after unexpected events. These findings suggest a tight interaction between the neural systems for surprise processing and motor inhibition and yield a promising avenue for future research.

Distinct modulation of interhemispheric inhibitory mechanisms during movement preparation reveals the influence of cognition on action control

When selecting actions based on visual warning stimuli (WS), corticospinal excitability (CSE) is initially suppressed, consistent with a neural mechanism to prevent premature release of the competing responses. Despite being implicated in between-hand movement selection and preparation, the role that interhemispheric inhibition (IHI) may play in this ‘impulse control’ mechanism is not known. Participants performed a warned, between-hand, choice reaction time (RT) task in which the informativeness of the WS (with regards to which hand would be required to respond) was manipulated. Transcranial magnetic stimulation (TMS) assessed CSE of the right primary motor cortex (M1) and IHI from left to right M1 with 10 (IHI10) and 40 (IHI40) msec interstimulus intervals during movement selection and preparation.Consistent with impulse control, CSE was initially suppressed prior to both left and right hand actions, irrespective of WS informativeness. Subsequent CSE increases occurred in the responding hand which were larger, and occurred earlier, following an informative WS. Importantly, these increases strongly predicted response times. In contrast to the generic CSE suppression, an informative WS permitted a hand-specific release of IHI10 in the responding hand, whereas IHI40 was released in both hands. As releases of IHI cannot explain a simultaneous suppression of CSE, this suggests several distinct movement preparation mechanisms are at play with IHI modulation occurring independently from impulse control. Notably, the findings support the notion that IHI10 and IHI40 between contralateral motor regions are mediated by discrete transcallosal pathways, and are differently modulated by specific motor and cognitive attributes of a rapid choice task.

P159 Specific and non-specific inhibition of interneurons circuits during motor preparation and suppression

Introduction Corticospinal excitability is transiently suppressed during motor preparation (Greenhouse et al., 2015 ) and when cancelling a prepared movement (Hoshiyama et al., 1997 ). Because MEPs are suppressed even in task-irrelevant muscles Greenhouse et al., 2015 , Hoshiyama et al., 1997 ), it has been proposed that there is a “global” inhibitory signal (Greenhouse et al., 2015) . Objectives We tested the whether the inhibition is global or specific to different excitatory interneuron circuits in primary motor cortex (M1). Materials & methods A controllable pulse parameter TMS (cTMS; Rogue Resolutions Ltd.) device was used to activate distinct interneuron circuits in M1 by changing the coil orientation (posterior–anterior, PA; anterior–posterior, AP) and TMS pulse width (30–120 μs). Motor evoked potentials (MEPs) were elicited in the first dorsal interosseous muscle(s) using short AP- (AP30) and long PA-directed (PA120) pulses at various stages during: (1) a left/right choice reaction time task (CRTT) in which a non-informative warning cue appeared 0.5 s prior to the imperative signal indicated the required response; and (2) a Go/No-Go task in which a non-informative warning cue appeared 2 s prior to a Go or No-Go signal indicating to respond or not respond. Because TMS pulse specificity is greatest at low stimulus intensities, experiments were conducted with weak voluntary contraction (5–10% maximum) to reduce stimulus threshold. Results AP30 pulses evoked MEPs with a longer latency than PA120 pulses, confirming that different excitatory interneurons were recruited by the different pulse. [RH1] In the CRTT, the amplitude of AP30-evoked MEPs was suppressed at the time of the imperative stimulus in both responding and non-responding hands, whereas responses to PA120 stimuli were unaffected (Fig. 1A) Download : Download high-res image (366KB) Download : Download full-size image .[RH2] In the Go/No-Go task, AP30 and PA120 MEPs were suppressed to a similar extent in the No-Go condition near to the expected onset of movement (Fig. 1B). Conclusion During motor preparation for the CRTT there was a selective suppression of one interneuron circuit in M1. In contrast, a global inhibition of corticospinal excitability was observed following a decision not to move. The implication is that the mechanisms underlying each form of inhibition are at least partially distinct.

Interaction between the premotor processes of eye and hand movements: Possible mechanism underlying eye–hand coordination

Interaction between the execution process of eye movement and that of hand movement must be indispensable for eye–hand coordination. The present study investigated corticospinal excitability in the hand muscles during the premotor processes of eye and/or hand movement to elucidate interaction between these processes. Healthy humans performed a precued reaction task of eye and/or finger movement and motor-evoked potentials in the hand muscles were evoked in the reaction time. Leftward eye movement suppressed corticospinal excitability in the right abductor digiti minimi muscle only when little finger abduction was simultaneously executed. Corticospinal excitability in the first dorsal interosseous muscle was not suppressed by eye movement regardless of whether or not it was accompanied by finger movement. Suppression of corticospinal excitability in the hand muscles induced by eye movement in the premotor period depends on the direction of eye movement, the muscle tested, and the premotor process of the tested muscle. The suppression may reflect interaction between the motor process of eye movement and that of hand movement particularly active during eye–hand coordination tasks during which both processes proceed.

P 52. Corticospinal activity during the preparation of bimanual and unimanual movements: Investigating the neural mechanisms of bimanual coupling

Previous research has demonstrated that the movements produced by each hand are correlated and have a tendency to converge during bimanual actions, a phenomenon referred to as bimanual coupling. Bimanual coupling appears to depend on excitatory and inhibitory transcallosal circuits although it is not presently clear specifically which circuits contribute to this effect or the stage of motor preparation or execution at which they act. The current study aimed to determine whether corticospinal excitability (CSE) is suppressed during the preparation of unimanual forces and simultaneous bimanual forces where the hands produce unequal forces, compared to the production of forces of equal magnitude with each hand. Single-pulse transcranial magnetic stimulation (TMS) was used to measure CSE during the preparation of bimanual and unimanual pinch forces that were synchronized with an auditory tone. Bimanual coupling was observed across all bimanual conditions and was stronger in equal-force conditions than unequal-force conditions. TMS of either motor cortex significantly expedited forces onsets for both hands, with left motor cortex (M1) TMS producing a greater effect than right M1 TMS. Significantly greater CSE was observed when the primary motor cortex contralateral to the hand preparing a force was stimulated. However, no differences in corticospinal excitability were observed between unimanual and bimanual force conditions or between different bimanual conditions. The present study did not find any support for the hypothesis that suppression of force coupling to produce strictly unimanual forces or bimanual forces of unequal magnitude results in corticospinal inhibition. These results suggest that the inhibition of CSE during the production of unequal bimanual forces does not occur until motor execution [2] . The bimanual coupling dependent modulation of CSE during motor preparation may be confined to specific movement parameters such as movement direction [1] . The strong effect of left M1 TMS on force onset times suggests a role of the left M1 in the control of motor timings.

Electrophysiological correlates of motor conversion disorder

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age-matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder.

CS11 Pain in the absence of nociception: example from empathy

CS11 Pain in the absence of nociception: example from empathy

Stimulus intensity, coil characteristics and peripheral reafferent activation contribute to the suppressive effects of 1Hz rTMS on cortical excitability

Objective: Low-frequency (1Hz) repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) can suppress corticospinal excitability. Here we examined whether these inhibitory after effects depend on the stimulus intensity, the type of TMS coil and peripheral reafferent activation. Methods: In fifteen healthy volunteers, 900 biphasic pulses of 1Hz rTMS were given to the left M1 at an intensity of 90% or 115% of the individual resting motor threshold (subthreshold vs. suprathreshold intensity) using two commercially available 'figure-of-eight' shaped TMS coils (Magstim or Dantec coil) attached to the same magnetic stimulator. Before and twice after intervention we recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEPrTMS). Using a Magstim coil connected to two Magstim 200 stimulators, we also gave monophasic single and paired pulses to the M1 and assessed unconditioned MEPs (MEPtest), paired-pulse excitability and cortical silent period (cSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve at the wrist using a suprathreshold intensity. Results: We found that the suppressive effect on MEPrTMS depended on the intensity and the type of coil used for rTMS conditioning. The suppression of corticospinal excitability was more pronounced and lasted longer when a suprathreshold intensity and a Dantec coil was used. The intensity but not the type of coil also had an effect on time-dependent changes in intracortical facilitation and cSP. Suprathreshold 1Hz rENS also induced a short lasting inhibition of MEPrTMS. Conclusions: Both, the stimulation intensity and the type of TMS coil have an impact on the suppressive after effects of 1Hz rTMS. The stronger suppression of suprathreshold 1Hz rTMS can at least in part be attributed to repetitive peripheral stimulation caused by reafferent feedback. Significance: These data should be taken into account when rTMS is used for therapeutic means.

Suppression of corticospinal excitability during negative motor imagery.

To investigate the effect of negative motor imagery on corticospinal excitability, we performed transcranial magnetic stimulation (TMS) studies in seven healthy subjects during imagination of suppressing movements. Subjects were asked to imagine suppression of TMS-induced twitching movement of their nondominant left hands by attempting to increase the amount of relaxation after receiving an auditory NoGo cue (negative motor imagery), but to imagine squeezing hands after a Go cue (positive motor imagery). Single- and paired-pulse TMS were triggered at 2 s after Go or NoGo cues. Motor-evoked potentials (MEPs) were recorded in the first dorsal interosseus (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles of the left hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals of 2 (short intracortical inhibition) and 15 ms (intracortical facilitation) and that with suprathreshold conditioning stimuli at interstimulus interval of 80 ms (long intracortical inhibition) were performed in both negative motor imagery and control conditions. Compared with the control state (no imagination), MEP amplitudes of FDI (but not APB and ADM) were significantly suppressed in negative motor imagery, but those from all three muscles were unchanged during positive motor imagery. F-wave responses (amplitudes and persistence) were unchanged during both negative and positive motor imagery. During negative motor imagery, resting motor threshold was significantly increased, but short and long intracortical inhibition and intracortical facilitation were unchanged. The present results demonstrate that excitatory corticospinal drive is suppressed during imagination of suppressing movements.

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex

Objective: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. Background: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. Methods: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. Results: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. Conclusions: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.