Single-pulse Motor Evoked Potential Research Articles

Covariation of the amplitude and latency of motor evoked potentials elicited by transcranial magnetic stimulation in a resting hand muscle

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to study human neurophysiology. A single TMS pulse delivered to the primary motor cortex can elicit a motor evoked potential (MEP) in a target muscle. MEP amplitude is a measure of corticospinal excitability and MEP latency is a measure of the time taken for intracortical processing, corticofugal conduction, spinal processing, and neuromuscular transmission. Although MEP amplitude is known to vary across trials with constant stimulus intensity, little is known about MEP latency variation. To investigate MEP amplitude and latency variation at the individual level, we scored single-pulse MEP amplitude and latency in a resting hand muscle from two datasets. MEP latency varied from trial to trial in individual participants with a median range of 3.9 ms. Shorter MEP latencies were associated with larger MEP amplitudes for most individuals (median r = − 0.47), showing that latency and amplitude are jointly determined by the excitability of the corticospinal system when TMS is delivered. TMS delivered during heightened excitability could discharge a greater number of cortico-cortical and corticospinal cells, increasing the amplitude and, by recurrent activation of corticospinal cells, the number of descending indirect waves. An increase in the amplitude and number of indirect waves would progressively recruit larger spinal motor neurons with large-diameter fast-conducting fibers, which would shorten MEP onset latency and increase MEP amplitude. In addition to MEP amplitude variability, understanding MEP latency variability is important given that these parameters are used to help characterize pathophysiology of movement disorders.

Operant Conditioning of the Motor Evoked Potentials for Sensorimotor Rehabilitation

<h3>Research Objectives</h3> The corticospinal pathway and its plasticity are essential in sensorimotor function recovery after neuromuscular injuries. To determine if operant up-conditioning of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) can increase corticospinal excitability and enhance sensorimotor rehabilitation, we are testing this neuromodulation approach in three different ongoing subprojects. We hypothesized that MEP up-conditioning can improve corticospinal activation of the targeted muscle and thereby improve functions in which that muscle participates. <h3>Design</h3> Each subproject utilizes operant MEP up-conditioning methodology. Standard MEP conditioning protocol consists of 6 baseline and 24 conditioning sessions (3/week, 30-45 min each). In each session, 250 single-pulse MEPs are elicited using TMS with or without operant conditioning (i.e., feedback on performance). Before and after conditioning, electrophysiological, kinematic, and functional assessments are performed. <h3>Setting</h3> Controlled laboratory. <h3>Participants</h3> Volunteers with chronic incomplete spinal cord injury (SCI), or with early-stage knee osteoarthritis (OA). <h3>Interventions</h3> See Design. <h3>Main Outcome Measures</h3> Target muscle MEP size, EMG, kinematics. <h3>Results</h3> Dorsiflexor MEP conditioning in people with chronic incomplete SCI: We hypothesize up-conditioning of the tibialis anterior (TA) MEP induces CNS plasticity that affects TA activation and improves locomotion. Initial studies found up-conditioning can increase TA MEP size and improve locomotion. Our current work aims to characterize cortical and corticospinal mechanisms of changes in MEP, locomotor EMG, and kinematics. Forearm extensor MEP conditioning in people with SCI: We hypothesize that corticospinal excitability for the wrist extensors can be increased through MEP conditioning and that it will help improve forearm motor function. Initial results support such possibilities in individuals with chronic incomplete cervical SCI. Quadriceps MEP conditioning in people with knee OA: We hypothesize that up-conditioning can increase quadriceps MEP size and improve quadriceps activation in individuals with early-stage knee OA. We are developing a protocol to examine the effects of MEP up-conditioning on quadriceps activation and function. <h3>Conclusions</h3> These projects will facilitate the dissemination of MEP conditioning as a neurorehabilitation tool to enhance functional recovery after neuromuscular injuries. <h3>Author(s) Disclosures</h3> Authors listed have no conflicts of interest to declare.

The Effects of 1 mA tACS and tRNS on Children/Adolescents and Adults: Investigating Age and Sensitivity to Sham Stimulation.

The aim of this study was to investigate the effect of transcranial random noise (tRNS) and transcranial alternating current (tACS) stimulation on motor cortex excitability in healthy children and adolescents. Additionally, based on our recent results on the individual response to sham in adults, we explored this effect in the pediatric population. We included 15 children and adolescents (10–16 years) and 28 adults (20–30 years). Participants were stimulated four times with 20 Hz and 140 Hz tACS, tRNS, and sham stimulation (1 mA) for 10 minutes over the left M1HAND. Single-pulse MEPs (motor evoked potential), short-interval intracortical inhibition, and facilitation were measured by TMS before and after stimulation (baseline, 0, 30, 60 minutes). We also investigated aspects of tolerability. According to the individual MEPs response immediately after sham stimulation compared to baseline (Wilcoxon signed-rank test), subjects were regarded as responders or nonresponders to sham. We did not find a significant age effect. Regardless of age, 140 Hz tACS led to increased excitability. Incidence and intensity of side effects did not differ between age groups or type of stimulation. Analyses on responders and nonresponders to sham stimulation showed effects of 140 Hz, 20 Hz tACS, and tRNS on single-pulse MEPs only for nonresponders. In this study, children and adolescents responded to 1 mA tRNS and tACS comparably to adults regarding the modulation of motor cortex excitability. This study contributes to the findings that noninvasive brain stimulation is well tolerated in children and adolescents including tACS, which has not been studied before. Finally, our study supports a modulating role of sensitivity to sham stimulation on responsiveness to a broader stimulation and age range.

Muscle-selective disinhibition of corticomotor representations using a motor imagery-based brain-computer interface

Bridging between brain activity and machine control, brain-computer interface (BCI) can be employed to activate distributed neural circuits implicated in a specific aspect of motor control. Using a motor imagery-based BCI paradigm, we previously found a disinhibition within the primary motor cortex contralateral to the imagined movement, as evidenced by event-related desynchronization (ERD) of oscillatory cortical activity. Yet it is unclear whether this BCI approach does selectively facilitate corticomotor representations targeted by the imagery. To address this question, we used brain state-dependent transcranial magnetic stimulation while participants performed kinesthetic motor imagery of wrist movements with their right hand and received online visual feedback of the ERD. Single and paired-pulse magnetic stimulation were given to the left primary motor cortex at a low or high level of ERD to assess intracortical excitability. While intracortical facilitation showed no modulation by ERD, short-latency intracortical inhibition was reduced the higher the ERD. Intracortical disinhibition was only found in the agonist muscle targeted by motor imagery at high ERD level, but not in the antagonist muscle. Single pulse motor-evoked potential was also increased the higher the ERD. However, at high ERD level, this facilitatory effect on overall corticospinal excitability was not selective to the agonist muscle. Analogous results were found in two independent experiments, in which participants either performed kinesthetic motor imagery of wrist extension or flexion. Our results showed that motor imagery-based BCI can selectively disinhibit the corticomotor output to the agonist muscle, enabling effector-specific training in patients with motor paralysis.

Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Transcranial focused ultrasound is an emerging form of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. The effect of ultrasound on human motor cortical excitability and behavior is currently unknown. We apply ultrasound to the primary motor cortex in humans using a novel simultaneous transcranial ultrasound and magnetic stimulation paradigm that allows for concurrent and concentric ultrasound stimulation with transcranial magnetic stimulation (TMS). This allows for non-invasive inspection of the effect of ultrasound on motor neuronal excitability using the motor evoked potential (MEP). We test the effect of ultrasound on single pulse MEP recruitment curves and paired pulse protocols including short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). In addition, we test the effect of ultrasound to motor cortex on a stimulus response reaction time task. Results show ultrasound inhibits the amplitude of single-pulse MEPs and attenuates intracortical facilitation but does not affect intracortical inhibition. Ultrasound also reduces reaction time on a simple stimulus response task. This is the first report of the effect of ultrasound on human motor cortical excitability and motor behavior and confirms previous results in the somatosensory cortex that ultrasound results in effective neuronal inhibition that confers a performance advantage.

P142 Reliability of MEP when using the 1 mV MEP standard to set TMS intensity

The inherent variability of motor evoked potential (MEP) recordings is an important consideration when drawing conclusions from studies in which transcranial magnetic stimulation (TMS) is used to assess central nervous system plasticity. Single-pulse TMS assessments have been made at various points on the stimulus intensity – MEP response curve, and MEP variability is dependent on the where one stimulates on this curve. Whilst many studies use the traditional approach of applying stimulation at 120% of the resting motor threshold, another technique that is becoming increasingly common is to set the stimulation intensity to evoke a 1 mV peak-to-peak amplitude MEP. The aim of the present study was to investigate the reliability of single-pulse MEPs elicited at the stimulation intensity set which produce a 1 mV peak-to-peak amplitude response. 52 participants were recruited to the study. MEPs were recorded from the First Dorsal Interosseous (FDI) muscle of the right hand in response to magnetic stimuli delivered over the hand area of the motor cortex. Stimulation intensity was set to evoke an MEP with a 1 mV peak-to-peak amplitude when the muscle was at rest. MEPs were recorded in 8 sets of 30 stimuli with an inter-stimulus interval of 4 s, with 2-min breaks between sets. Coil position and orientation was held constant with frameless stererotaxy. Reliability was assessed using Bland–Altman plots to compare the mean MEP recorded from sets 2–8 with that of the first set. This analysis revealed a consistent deviation from MEPs in the first set with a tendency for MEP amplitude to increase (rmANOVA, p We have demonstrated that stimulation delivered with an intensity to produce 1 mV MEPs results in highly variable MEPs with a tendency for the MEPs to increase. Given the intensity to induce 1 mV MEPs differs relative to threshold for every participant this might inflate variability. This result highlights the importance MEP variability and re-emphasises the importance of taking care in concluding changes in MEP amplitude are indeed the result of the intervention as opposed to natural variation of participant attention over time.

Motor evoked potential polyphasia: a novel endophenotype of idiopathic generalized epilepsy.

Objective:We compared the motor evoked potential (MEP) phases using transcranial magnetic stimulation in patients with idiopathic generalized epilepsy (IGE), their relatives, and healthy controls, hypothesizing that patients and their unaffected relatives may share a subtle pathophysiologic abnormality.Methods:In a cross-sectional study, we investigated 23 patients with IGE, 34 first-degree relatives, and 30 matched healthy controls. Transcranial magnetic stimulation was performed to produce a series of suprathreshold single-pulse MEPs. A semiautomated method was used to count phases. We compared between groups the mean number of MEP phases, the stimulus-to-stimulus variability in MEP phases, and the proportion of polyphasic MEPs within subjects.Results:Patients with IGE and their relatives had a significantly increased number of MEP phases (median for patients 2.24, relatives 2.17, controls 2.01) and a significantly higher proportion of MEPs with more than 2 phases than controls (median for patients 0.118, relatives 0.088, controls 0.013). Patients had a greater stimulus-to-stimulus variability in number of MEP phases than controls. There were no differences between patients and relatives.Conclusion:Increased MEP polyphasia in patients with IGE and their first-degree relatives may reflect transient abnormal evoked oscillations. The presence of polyphasic MEPs in relatives as well as patients suggests that MEP polyphasia is not related to treatment, and is in isolation insufficient to predispose to epilepsy. Polyphasic MEP may be a novel endophenotype in IGE.

Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex

A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS(1.5)) or not coincide (2-ms IPI, ITMS(2)) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS(1.5) corticomotor excitability was increased by ~60% for 15 min (P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (~35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS(2) did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal resolution of the order of a few hundreds of microseconds.

Pharmacological Modulation of the Short-Lasting Effects of Antagonistic Direct Current-Stimulation Over the Human Motor Cortex

Combined administration of transcranial direct current-stimulation (tDCS) with either pergolide (PER) or d-cycloserine (d-CYC) can prolong the excitability-diminishing effects of cathodal, or the excitability enhancing effect of anodal stimulation for up to 24 h poststimulation. However, it remains unclear whether the potentiation of the observed aftereffects is dominated just by the polarity and duration of the stimulation, or the dual application of combined stimulation and drug administration. The present study looks at whether the aftereffects of oral administration of PER (a D1/D2 agonist) or d-CYC (a partial NMDA receptor agonist), in conjunction with the short-duration antagonistic application of tDCS (either 5 min cathodal followed immediately by 5 min anodal or vice versa), that alone only induces short-lasting aftereffects, can modulate cortical excitability in healthy human subjects, as revealed by a single-pulse MEP (motor-evoked-potential) paradigm. Results indicate that the antagonistic application of tDCS induces short-term neuroplastic aftereffects that are dependent upon the order of the application of short-duration stimulation. The administration of d-CYC resulted in a marked inhibition of cortical excitability under the application of tDCS in both stimulation orders. Intake of PER resulted in an increase in cortical excitability in both stimulation orientations, but was non-significant compared to the placebo condition. These results indicate that the aftereffects of tDCS are dependent upon the order of stimulation applied, and also demonstrate the prolongation of tDCS aftereffects when combined with the administration of CNS active drugs.

Cortical activation during temporal preparation assessed by transcranial magnetic stimulation

Preparatory modulations relative to the timing of upcoming stimuli may involve activation or suppression mechanisms. Here, we assessed the interplay between these mechanisms with transcranial magnetic stimulation (TMS) of the motor cortex. Single- or paired-pulse TMS with 3- or 15-ms interstimulus intervals was delivered during the interval between the warning and the imperative stimuli (i.e., the foreperiod) of a choice reaction time task. Temporal uncertainty was manipulated through between-block variation of the foreperiod duration (500 or 2500 ms). The shortening of reaction time for the short foreperiod was accompanied with a decrease in amplitude of the single-pulse motor evoked potential (MEP), indicating corticospinal suppression. The co-occurring increase in amplitude of both paired-pulse MEPs (3 and 15 ms) expressed relative to single-pulse MEPs reveals released short intracortical inhibition (SICI) and enhanced intracortical facilitation (ICF). These results suggest that temporal preparation is associated with both corticospinal suppression and cortical activation.

Selective suppression of the incorrect response implementation in choice behavior assessed by transcranial magnetic stimulation

Selecting the adequate alternative in choice situations may involve an inhibition process. Here we assessed response implementation during the reaction time of a between-hand choice task with single- or paired-pulse (3 or 15 ms interstimulus intervals [ISIs]) transcranial magnetic stimulation of the motor cortex. The amplitude of the single-pulse motor evoked potential (MEP) initially increased for both hands. At around 130 ms, the single-pulse MEP kept increasing for the responding hand and decreased for the nonresponding hand. The paired-pulse MEP revealed a similar pattern for both ISIs with no effect on short intracortical inhibition and intracortical facilitation measures. The results suggest that the incorrect response implementation was selectively suppressed before execution of the correct response, preventing errors in choice context. The results favor models assuming that decision making involves an inhibition process.

Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: A new technique for modulating synaptic plasticity

Objective We hypothesised that facilitatory I-wave interaction set up by paired-pulse transcranial magnetic stimulation delivered with I-wave periodicity (iTMS) may reinforce trans-synaptic events and provide a means for modulating synaptic plasticity and cortical excitability. Our objective was to determine whether prolonged iTMS can increase corticospinal excitability, and whether this form of stimulation can have lasting aftereffects. Methods Paired stimuli of equal strength with a 1.5 ms inter-stimulus interval were delivered for 30 min at a rate of 0.2 Hz. Motor threshold and motor evoked potential (MEP) amplitude to single-pulse TMS was compared before and after intervention. Results Paired-pulse MEP amplitude increased linearly throughout the period of iTMS, and had increased five-fold by the end of the stimulation period. Single-pulse MEP amplitude was increased a mean of four-fold for 10 min after stimulation. Motor threshold was unaffected. Conclusions iTMS is an effective method for increasing excitability of the human motor cortex, and probably acts by increasing synaptic efficacy. Significance Reinforcement of trans-synaptic events by iTMS may provide a means to investigate and modulate synaptic plasticity in the brain.