Stimulating the Lip Motor Cortex with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.     

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging

The activation of listener''s motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners’ tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker''s ongoing motor plan.     

Visual Word Recognition in Deaf Readers: Lexicality Is Modulated by Communication Mode

Evidence indicates that adequate phonological abilities are necessary to develop proficient reading skills and that later in life phonology also has a role in the covert visual word recognition of expert readers. Impairments of acoustic perception, such as deafness, can lead to atypical phonological representations of written words and letters, which in turn can affect reading proficiency. Here, we report an experiment in which young adults with different levels of acoustic perception (i.e., hearing and deaf individuals) and different modes of communication (i.e., hearing individuals using spoken language, deaf individuals with a preference for sign language, and deaf individuals using the oral modality with less or no competence in sign language) performed a visual lexical decision task, which consisted of categorizing real words and consonant strings. The lexicality effect was restricted to deaf signers who responded faster to real words than consonant strings, showing over-reliance on whole word lexical processing of stimuli. No effect of stimulus type was found in deaf individuals using the oral modality or in hearing individuals. Thus, mode of communication modulates the lexicality effect. This suggests that learning a sign language during development shapes visuo-motor representations of words, which are tuned to the actions used to express them (phono-articulatory movements vs. hand movements) and to associated perceptions. As these visuo-motor representations are elicited during on-line linguistic processing and can overlap with the perceptual-motor processes required to execute the task, they can potentially produce interference or facilitation effects.     

Transpinal and Transcortical Stimulation Alter Corticospinal Excitability and Increase Spinal Output

The objective of this study was to assess changes in corticospinal excitability and spinal output following noninvasive transpinal and transcortical stimulation in humans. The size of the motor evoked potentials (MEPs), induced by transcranial magnetic stimulation (TMS) and recorded from the right plantar flexor and extensor muscles, was assessed following transcutaneous electric stimulation of the spine (tsESS) over the thoracolumbar region at conditioning-test (C-T) intervals that ranged from negative 50 to positive 50 ms. The size of the transpinal evoked potentials (TEPs), induced by tsESS and recorded from the right and left plantar flexor and extensor muscles, was assessed following TMS over the left primary motor cortex at 0.7 and at 1.1× MEP resting threshold at C-T intervals that ranged from negative 50 to positive 50 ms. The recruitment curves of MEPs and TEPs had a similar shape, and statistically significant differences between the sigmoid function parameters of MEPs and TEPs were not found. Anodal tsESS resulted in early MEP depression followed by long-latency MEP facilitation of both ankle plantar flexors and extensors. TEPs of ankle plantar flexors and extensors were increased regardless TMS intensity level. Subthreshold and suprathreshold TMS induced short-latency TEP facilitation that was larger in the TEPs ipsilateral to TMS. Noninvasive transpinal stimulation affected ipsilateral and contralateral actions of corticospinal neurons, while corticocortical and corticospinal descending volleys increased TEPs in both limbs. Transpinal and transcortical stimulation is a noninvasive neuromodulation method that alters corticospinal excitability and increases motor output of multiple spinal segments in humans.     

Whole-Body Water Flow Stimulation to the Lower Limbs Modulates Excitability of Primary Motor Cortical Regions Innervating the Hands: A Transcranial Magnetic Stimulation Study

Whole-body water immersion (WI) has been reported to change sensorimotor integration. However, primary motor cortical excitability is not affected by low-intensity afferent input. Here we explored the effects of whole-body WI and water flow stimulation (WF) on corticospinal excitability and intracortical circuits. Eight healthy subjects participated in this study. We measured the amplitude of motor-evoked potentials (MEPs) produced by single transcranial magnetic stimulation (TMS) pulses and examined conditioned MEP amplitudes by paired-pulse TMS. We evaluated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using the paired-TMS technique before and after 15-min intervention periods. Two interventions used were whole-body WI with water flow to the lower limbs (whole-body WF) and whole-body WI without water flow to the lower limbs (whole-body WI). The experimental sequence included a baseline TMS assessment (T0), intervention for 15 min, a second TMS assessment immediately after intervention (T1), a 10 min resting period, a third TMS assessment (T2), a 10 min resting period, a fourth TMS assessment (T3), a 10 min resting period, and the final TMS assessment (T4). SICI and ICF were evaluated using a conditioning stimulus of 90% active motor threshold and a test stimulus adjusted to produce MEPs of approximately 1–1.2 mV, and were tested at intrastimulus intervals of 3 and 10 ms, respectively. Whole-body WF significantly increased MEP amplitude by single-pulse TMS and led to a decrease in SICI in the contralateral motor cortex at T1, T2 and T3. Whole-body WF also induced increased corticospinal excitability and decreased SICI. In contrast, whole-body WI did not change corticospinal excitability or intracortical circuits.     

Motor cortex excitability during unilateral muscle activity.

The effect of unilateral tonic muscle activity with and without co-activation of the antagonists on motor cortex excitability has been studied. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseus muscles of both hands in response to transcranial magnetic stimulation (TMS) during relax, isometric index finger abduction and antagonistic co-activation. The intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated by paired-pulse TMS with interstimulus intervals of 3 and 13 ms. The unilateral tonic activation of the right hand facilitated contralateral and ipsilateral responses (cMEP and iMEP) recorded from both hands with an exception of iMEPs recorded from the left hand. During paired-pulse TMS ICI for cMEPs was not influenced by the unilateral tonic activity in both hands, while ICF was suppressed when MEPs were recorded from the active right hand. The effect of unilateral tonic activity on iMEP in response to paired-pulse TMS was essentially different: generally, ICI was greater for iMEPs and ICF was completely abolished with an exception of iMEPs recorded from the left hand during right finger isometric abduction when a strong ICF was evident. The decreased ICF and/or increased ICI are assumed to reflect mechanisms underlying the co-activation of antagonists.     

Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.     

Different motor learning effects on excitability changes of motor cortex in muscle contraction state

Abstract

We aimed to investigate whether motor learning induces different excitability changes in the human motor cortex (M1) between two different muscle contraction states (before voluntary contraction [static] or during voluntary contraction [dynamic]). For the same, using motor evoked potentials (MEPs) obtained by transcranial magnetic stimulation (TMS), we compared excitability changes during these two states after pinch-grip motor skill learning. The participants performed a force output tracking task by pinch grip on a computer screen. TMS was applied prior to the pinch grip (static) and after initiation of voluntary contraction (dynamic). MEPs of the following muscles were recorded: first dorsal interosseous (FDI), thenar muscle (Thenar), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles. During both the states, motor skill training led to significant improvement of motor performance. During the static state, MEPs of the FDI muscle were significantly facilitated after motor learning; however, during the dynamic state, MEPs of the FDI, Thenar, and FCR muscles were significantly decreased. Based on the results of this study, we concluded that excitability changes in the human M1 are differentially influenced during different voluntary contraction states (static and dynamic) after motor learning.     

Motor Properties of Peripersonal Space in Humans

Background

A stimulus approaching the body requires fast processing and appropriate motor reactions. In monkeys, fronto-parietal networks are involved both in integrating multisensory information within a limited space surrounding the body (i.e. peripersonal space, PPS) and in action planning and execution, suggesting an overlap between sensory representations of space and motor representations of action. In the present study we investigate whether these overlapping representations also exist in the human brain.

Methodology/Principal Findings

We recorded from hand muscles motor-evoked potentials (MEPs) induced by single-pulse of transcranial magnetic stimulation (TMS) after presenting an auditory stimulus either near the hand or in far space. MEPs recorded 50 ms after the near-sound onset were enhanced compared to MEPs evoked after far sounds. This near-far modulation faded at longer inter-stimulus intervals, and reversed completely for MEPs recorded 300 ms after the sound onset. At that time point, higher motor excitability was associated with far sounds. Such auditory modulation of hand motor representation was specific to a hand-centred, and not a body-centred reference frame.

Conclusions/Significance

This pattern of corticospinal modulation highlights the relation between space and time in the PPS representation: an early facilitation for near stimuli may reflect immediate motor preparation, whereas, at later time intervals, motor preparation relates to distant stimuli potentially approaching the body.     

Impaired motor facilitation during action observation in individuals with autism spectrum disorder

It has been suggested that social impairments observed in individuals with autism spectrum disorder (ASD) can be partly explained by an abnormal mirror neuron system (MNS) 1., 2.. Studies on monkeys have shown that mirror neurons are cells in premotor area F5 that discharge when a monkey executes or sees a specific action or when it hears the corresponding action-related sound 3., 4., 5.. Evidence for the presence of a MNS in humans comes in part from studies using transcranial magnetic stimulation (TMS), where a change in the amplitude of the TMS-induced motor-evoked potentials (MEPs) during action observation has been demonstrated 6., 7., 8., 9.. These data suggest that actions are understood when the representation of that action is mapped onto the observer's own motor structures [10]. To determine if the neural mechanism matching action observation and execution is anomalous in individuals with ASD, TMS was applied over the primary motor cortex (M1) during observation of intransitive, meaningless finger movements. We show that overall modulation of M1 excitability during action observation is significantly lower in individuals with ASD compared with matched controls. In addition, we find that basic motor cortex abnormalities do not underlie this impairment.     

Rules from Words: A Dynamic Neural Basis for a Lawful Linguistic Process

Listeners show a reliable bias towards interpreting speech sounds in a way that conforms to linguistic restrictions (phonotactic constraints) on the permissible patterning of speech sounds in a language. This perceptual bias may enforce and strengthen the systematicity that is the hallmark of phonological representation. Using Granger causality analysis of magnetic resonance imaging (MRI)- constrained magnetoencephalography (MEG) and electroencephalography (EEG) data, we tested the differential predictions of rule-based, frequency–based, and top-down lexical influence-driven explanations of processes that produce phonotactic biases in phoneme categorization. Consistent with the top-down lexical influence account, brain regions associated with the representation of words had a stronger influence on acoustic-phonetic regions in trials that led to the identification of phonotactically legal (versus illegal) word-initial consonant clusters. Regions associated with the application of linguistic rules had no such effect. Similarly, high frequency phoneme clusters failed to produce stronger feedforward influences by acoustic-phonetic regions on areas associated with higher linguistic representation. These results suggest that top-down lexical influences contribute to the systematicity of phonological representation.     

Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity.

Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to alpha-motoneuron activity than to motor cortical neuron activity, an idea that has important methodological implications.     

The effects of short-term hypoxia on motor cortex excitability and neuromuscular activation.

The effects of acute hypoxia on motor cortex excitability, force production, and voluntary activation were studied using single- and double-pulse transcranial magnetic stimulation techniques in 14 healthy male subjects. Electrical supramaximal stimulations of the right ulnar nerve were performed, and transcranial magnetic stimulations were delivered to the first dorsal interosseus motor cortex area during short-term hypoxic (HX) and normoxic (NX) condition. M waves, voluntary activation, F waves, resting motor threshold (rMT), recruitment curves (100-140% of rMT), and short-interval intracortical inhibition and intracortical facilitation were measured. Moreover, motor-evoked potentials (MEPs) and cortical silent periods were determined during brief isometric maximum right index finger abductions. Hypoxia was induced by breathing a fraction of inspired oxygen of 12% via a face mask. M waves, voluntary activation, and F waves did not differ between NX and HX. The rMT was significantly lower in HX (55.79 +/- 9.40%) than in NX (57.50 +/- 10.48%) (P < 0.01), whereas MEP recruitment curve, short-interval intracortical inhibition, intracortical facilitation, maximum right index finger abduction, and MEPs were unaffected by HX. In contrast, the cortical silent periods in HX (158.21 +/- 33.96 ms) was significantly shortened compared with NX (169.42 +/- 39.69 ms) (P < 0.05). These data demonstrate that acute hypoxia results in increased cortical excitability and suggest that acute hypoxia alters motor cortical ion-channel function and GABAergic transmission.     

Selective increase in corticospinal excitability in the context of tactile exploration

In this study, we compared changes in corticomotor excitability under various task conditions engaging the index finger of each hand. Functional demands were varied, from simple execution to demanding sensory exploration. In a first experiment, we contrasted facilitation in the first dorsal interosseus (FDI) by monitoring changes in motor evoked potentials (MEPs) when participants (young adults, n = 18) performed either a simple button pressing (BP) task or a more demanding tactile exploration (TE) task (i.e., discrimination of raised letters). This experiment showed a large effect of task conditions (p < 0.01) on MEP amplitude but no effect of “Hand”, while latency measurements were unchanged. In fact, MEPs were on average 40% larger during TE (2410 ± 1358 µV) than during BP (1670 ± 1477 µV). The two tasks produced, however, different patterns of electromyographic (EMG) activity, which could have accounted for some of the differences observed. A second experimental session involved a subset of participants (10/18) tested in third task condition: finger movement (FM). The latter task consisted of scanning a smooth surface with the tip of the index finger to reproduce the movements seen with the TE task. The addition of this third condition task confirmed that MEP facilitation seen during TE reflected task-specific influences and not differences in background EMG activity. These results, altogether, provide further insights into the effect of task conditions on corticomotor excitability. Our findings, in particular, stress the importance of behavioural context and tactile exploration in leading to selective increase in corticomotor excitability during finger movements.     

Activation of the Left Inferior Frontal Gyrus in the First 200 ms of Reading: Evidence from Magnetoencephalography (MEG)

Background

It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question.

Methodology/Principal Findings

MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100–250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at ∼130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at ∼115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at ∼140 ms, at a location coincident with the fMRI–defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus.

Conclusions/Significance

These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code.     

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.     

Dissociation of motor task-induced cortical excitability and pain perception changes in healthy volunteers

Background

There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks.

Methodology/Principal Findings

Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements.

Conclusions/Significance

Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training.     

Task-guided selection of the dual neural pathways for reading

The visual perception of words is known to activate the auditory representation of their spoken forms automatically. We examined the neural mechanism for this phonological activation using transcranial magnetic stimulation (TMS) with a masked priming paradigm. The stimulation sites (left superior temporal gyrus [L-STG] and inferior parietal lobe [L-IPL]), modality of targets (visual and auditory), and task (pronunciation and lexical decision) were manipulated independently. For both within- and cross-modal conditions, the repetition priming during pronunciation was eliminated when TMS was applied to the L-IPL, but not when applied to the L-STG, whereas the priming during lexical decision was eliminated when the L-STG, but not the L-IPL, was stimulated. The observed double dissociation suggests that the conscious task instruction modulates the stimulus-driven activation of the lateral temporal cortex for lexico-phonological activation and the inferior parietal cortex for spoken word production, and thereby engages a different neural network for generating the appropriate behavioral response.     

Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction

The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory “GO” signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90?ms) after the “GO” signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60?ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.