Modulation Of Motor Evoked Potentials Research Articles

Probing the orientation specificity of excitatory and inhibitory circuitries in the primary motor cortex with multi-channel TMS

ObjectiveElectric-field orientation is crucial for optimizing neuronal excitation in transcranial magnetic stimulation (TMS). Yet, the stimulus orientation effects on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are poorly understood due to technical challenges in manipulating the TMS-induced stimulus orientation within milliseconds. We aimed to assess the orientation sensitivity of SICI and ICF paradigms and identify optimal orientations for motor evoked potential (MEP) facilitation and suppression. MethodsWe applied paired-pulse multi-channel TMS to 12 healthy subjects with conditioning and test stimuli in the same, opposite, and perpendicular orientations to each other at four interstimulus intervals (ISI) to generate refractoriness, SICI, and ICF. ResultsMEP modulation was affected by the conditioning- and test-stimulus orientation, being strongest when both pulses were in the same direction. MEP modulation with 2.5-ms and 6.0-ms ISIs were more sensitive to orientation changes than 0.5- and 8.0-ms ISIs. ConclusionSICI and ICF orientation sensitivity exhibit a complex dependence on the conditioning stimulus orientation, which might be explained by anatomical and morphological arrangements of inhibitory and excitatory neuronal populations. SignificanceDistinct mechanisms mediating SICI and ICF are sensitive to stimulus orientation at specific ISIs, describing a structural–functional relationship that maximizes each effect at the cortical level.

Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Investigating the Working Mechanism of Transcranial Direct Current Stimulation

BackgroundTranscranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability. Materials and MethodsIn a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS. ResultsA significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions. ConclusionsThe significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

Scale-invariant changes in corticospinal excitability reflect multiplexed oscillations in the motor output.

In the absence of disease, humans produce smooth and accurate movement trajectories. Despite such 'macroscopic' aspect, the 'microscopic' structure of movements reveals recurrent (quasi-rhythmic) discontinuities. To date, it is unclear how the sensorimotor system contributes to the macroscopic and microscopic architecture of movement. Here, we investigated how corticospinal excitability changes in relation to microscopic fluctuations that are naturally embedded within larger macroscopic variations in motor output. Participants performed a visuomotor tracking task. In addition to the 0.25Hz modulation that is required for task fulfilment (macroscopic scale), the motor output shows tiny but systematic fluctuations at ∼2 and 8Hz (microscopic scales). We show that motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) during task performance are consistently modulated at all (time) scales. Surprisingly, MEP modulation covers a similar range at both micro- and macroscopic scales, even though the motor output differs by several orders of magnitude. Thus, corticospinal excitability finely maps the multiscale temporal patterning of the motor output, but it does so according to a principle of scale invariance. These results suggest that corticospinal excitability indexes a relatively abstract level of movement encoding that may reflect the hierarchical organisation of sensorimotor processes. KEY POINTS: Motor behaviour is organised on multiple (time)scales. Small but systematic ('microscopic') fluctuations are engrained in larger and slower ('macroscopic') variations in motor output, which are instrumental in deploying the desired motor plan. Corticospinal excitability is modulated in relation to motor fluctuations on both macroscopic and microscopic (time)scales. Corticospinal excitability obeys a principle of scale invariance, that is, it is modulated similarly at all (time)scales, possibly reflecting hierarchical mechanisms that optimise motor encoding.

Modulation of lower limb muscle corticospinal excitability during various types of motor imagery

Motor imagery (MI) is used for rehabilitation and sports training. Previous studies focusing on the upper limb have investigated the effects of MI on corticospinal excitability in the muscles involved in the imagined movement (i.e., the agonist muscles). The present study focused on several lower-limb movements and investigated the influences of MI on corticospinal excitability in the lower limb muscles. Twelve healthy individuals (ten male and two female individuals) participated in this study. Motor-evoked potentials (MEP) from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles were elicited through transcranial magnetic stimulation (TMS) to the primary motor cortex during MI of knee extension, knee flexion, ankle dorsiflexion, and ankle plantarflexion and at rest. The results showed that the RF MEPs were significantly increased during MI in knee extension, ankle dorsiflexion, and ankle plantarflexion but not in knee flexion, compared with those at rest. The TA MEPs were significantly increased during MI in knee extension and foot dorsiflexion, while MEPs were not significantly different during MI in knee flexion and foot dorsiflexion than those at rest. For the BF and SOL muscles, there was no significant MEP modulation in either MI. These results demonstrated that corticospinal excitability of the RF and TA muscles was facilitated during MI of movements in which they are active and during MI of lower-limb movements in which they are not involved. On the contrary, corticospinal excitability of the BF and SOL muscles was not facilitated by MI of lower-limb movements. These results suggest that facilitation of corticospinal excitability depends on the muscle and the type of lower-limb MI.

Disinhibition of short-latency but not long-latency afferent inhibition of the lower limb during upper-limb muscle contraction.

Research has demonstrated that motor and sensory functions of the lower limbs can be modulated by upper-limb muscle contractions. However, whether sensorimotor integration of the lower limb can be modulated by upper-limb muscle contractions is still unknown. [AQ: NR Original articles do not require structured abstracts. Hence, abstract subsections have been deleted. Please check.]Human sensorimotor integration has been studied using short- or long-latency afferent inhibition (SAI or LAI, respectively), which refers to inhibition of motor-evoked potentials (MEPs) elicited via transcranial magnetic stimulation by preceding peripheral sensory stimulation. In the present study, we aimed to investigate whether upper-limb muscle contractions could modulate the sensorimotor integration of the lower limbs by examining SAI and LAI. Soleus muscle MEPs following electrical tibial nerve stimulation (TSTN) during rest or voluntary wrist flexion were recorded at inter-stimulus intervals (ISIs) of 30 (i.e. SAI), 100, and 200 ms (i.e. LAI). The soleus Hoffman reflex following TSTN was also measured to identify whether MEP modulation occurred at the cortical or the spinal level. Results showed that lower-limb SAI, but not LAI, was disinhibited during voluntary wrist flexion. Furthermore, the soleus Hoffman reflex following TSTN during voluntary wrist flexion was unchanged when compared with that during the resting state at any ISI. Our findings suggest that upper-limb muscle contractions modulate sensorimotor integration of the lower limbs and that disinhibition of lower-limb SAI during upper-limb muscle contractions is cortically based.

No robust online effects of transcranial direct current stimulation on corticospinal excitability

Transcranial direct current stimulation (tDCS) has been used for over twenty years to modulate cortical (particularly motor corticospinal) excitability both during (online) and outlasting (offline) the stimulation, with the former effects associated to the latter. However, tDCS effects are highly variable, partially because stimulation intensity is commonly not adjusted individually (in contrast to transcranial magnetic stimulation, TMS). In Experiment 1, we therefore explored an empirical approach of personalizing tDCS intensity for the primary motor cortex (M1) based on dose-response curves (DRCs), individually relating tDCS Intensity (in steps from 0.3 to 2.0 mA) and Polarity (anodal, cathodal) to the online modulation of concurrent TMS motor evoked potentials (MEP), assessing DRC reliability across two separate days. No robust DRCs could be observed, neither at the individual nor at the group level, with the only robust effect being a (paradoxical) MEP facilitation during cathodal tDCS at 2.0 mA, but no modulation at traditional intensities of or near 1 mA. In Experiment 2, we therefore attempted to replicate the classical bidirectional online MEP modulation during 1 mA tDCS that had been reported by several of the early seminal tDCS papers. We either closely recreated stimulation parameters and temporal protocol of these original studies (Experiment 2A) or slightly modernized them according to current standards (Experiment 2B). In neither experiment did we observed any significant online MEP modulation. We conclude that an empirical titration of individually effective tDCS intensities may not be feasible as online tDCS effects do not appear to be sufficiently robust.

Postural support requirements preferentially modulate late components of the gastrocnemius response to transcranial magnetic stimulation

Mounting evidence suggests that motor evoked potentials (MEPs) recorded in upper limb muscles with postural support roles following transcranial magnetic stimulation receive contributions from both corticospinal and non-corticospinal descending pathways. We tested the hypothesis that neural structures responsible for regulating upright balance are involved in transmitting late portions of TMS-induced MEPs in a lower limb muscle. MEPs were recorded in the medial gastrocnemius muscles of each leg, while participants supported their upright posture in five postural conditions that required different levels of support from the target muscles. We observed that early and late portions of the MEP were modulated independently, with early MEP amplitude being reduced when high levels of postural support were required from a target muscle. Independent modulation of early and late MEPs by altered postural demand suggests largely separable transmission of each part of the MEP. The early component of the MEP is likely generated by fast-conducting corticospinal pathways, whereas the later component may be primarily transmitted along a polysynaptic cortico-reticulospinal pathway.

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males

ObjectivesAs a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms. Materials and MethodsIn this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current. ResultsMEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components. ConclusionstaVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.

Sharing motor plans while acting jointly: A TMS study

When acting together, we may represent not only our own individual goals but also a collective goal. Although behavioural evidence suggests that agents' motor plans might be related to collective goals, direct neurophysiological evidence of whether collective goals are motorically represented is still scarce. The aim of the present transcranial magnetic stimulation (TMS) study is to begin to fill this gap. A participant and a confederate were asked to sequentially perform a two-choice reaction time task by acting on pressure sensors. In their own turn, they saw a cue indicating whether to lift their fingers from (or to press them on) a pressure sensor to shoot a ball across the screen as fast as possible. The confederate responded with the right hand, the participant with the left hand. While the confederate acted on the sensor, the participant's motor evoked potentials (MEPs) were collected from the right Extensor Carpi Ulnaris. If participants represent their own and the confederate's actions as being directed to a collective goal, MEPs amplitude should be modulated according to the action the confederate should perform. To test this conjecture, we contrasted three conditions: a Joint condition, in which both players worked together with their collective goal being to shoot the ball to get it to a common target, a Parallel condition, in which the players performed exactly the same task but received independent outcomes for their performance, and a Competitive condition, in which the outcome of the game still depended on the other player performance, but without the collective goal feature. Results showed no MEPs modulation according to the confederate's action in the Joint condition. Post-hoc exploratory analyses both provide some hints about this negative finding and also suggest possible improvements (i.e., adopting a different dependent variable, avoiding task-switching between conditions) for testing our hypothesis that collective goal can be represented motorically.

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1). MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects. ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS. ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations. SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.

Comparison of the on-line effects of different motor simulation conditions on corticospinal excitability in healthy participants

In healthy participants, corticospinal excitability is known to increase during motor simulations such as motor imagery (MI), action observation (AO) and mirror therapy (MT), suggesting their interest to promote plasticity in neurorehabilitation. Further comparing these methods and investigating their combination may potentially provide clues to optimize their use in patients. To this end, we compared in 18 healthy participants abductor pollicis brevis (APB) corticospinal excitability during MI, AO or MT, as well as MI combined with either AO or MT. In each condition, 15 motor-evoked potentials (MEPs) and three maximal M-wave were elicited in the right APB. Compared to the control condition, mean normalized MEP amplitude (i.e. MEP/M) increased during MI (P = .003), MT (P < .001) and MT + MI (P < .001), without any difference between the three conditions. No MEP modulation was evidenced during AO or AO + MI. Because MI provided no additional influence when combined with AO or MT, our results may suggest that, in healthy subjects, visual feedback and unilateral movement with a mirror may provide the greatest effects among all the tested motor simulations.

Involvement of the primary motor cortex in the early processing stage of the affective stimulus-response compatibility effect in a manikin task

Compatible (positive approaching and negative avoiding) and incompatible (positive avoiding and negative approaching) behavior are of great significance for biological adaptation and survival. Previous research has found that reaction times of compatible behavior are shorter than the incompatible behavior, which is termed the stimulus-response compatibility (SRC) effect. However, the underlying neurophysiological mechanisms of the SRC effect applied to affective stimuli is still unclear. Here, we investigated preparatory activities in both the left and right primary motor cortex (M1) before the execution of an approaching-avoiding behavior using the right index finger in a manikin task based on self-identity. The results showed significantly shorter reaction times for compatible than incompatible behavior. Most importantly, motor-evoked potential (MEP) amplitudes from left M1 stimulation were significantly higher during compatible behavior than incompatible behavior at 150 and 200 ms after stimulus presentation, whereas the reversed was observed for right M1 stimulation with lower MEP amplitude in compatible compared to incompatible behavior at 150 ms. The current findings revealed the compatibility effect at both behavioral and neurophysiological levels, indicating that the affective SRC effect occurs early in the motor cortices during stimulus processing, and MEP modulation at this early processing stage could be a physiological marker of the affective SRC effect.

Deficits in corticospinal control of stretch reflex thresholds in stroke: Implications for motor impairment

ObjectivesThe corticospinal system (CS) regulates muscle activation through shifts in muscle-level tonic stretch-reflex thresholds (TSRT). This ability is impaired in stroke and contributes to sensorimotor impairments such as spasticity. We determined the role of CS in elbow flexor activity regulation in healthy and post-stroke subjects. We also determined whether CS modulation deficits were related to sensorimotor impairment intensity in post-stroke individuals. MethodsSeventeen healthy (59.8 ± 12.2 yr) and 27 stroke subjects (58.7 ± 10.1 yr) had transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) flexor representation to elicit motor-evoked potentials (MEPs) in elbow flexors in different angular positions. In a subset of post-stroke subjects (n = 12), flexor TSRTs were measured in passive and active conditions, and TSRT modulation was determined. ResultsPosition-related MEP amplitude modulation was similar in healthy and mild stroke subjects, while subjects with more severe stroke exhibited less consistent modulation. MEP modulation in stroke was related to clinical upper limb motor impairment, spasticity, and the ability to modulate TSRTs between passive and active elbow movements. ConclusionsCS output was closely related to TSRT modulation. Impairments in TSRT regulation may underlie motor deficits in moderate-to-severe post-stroke individuals. SignificanceTranslation of these neurophysiological findings to clinical applications may enhance post-stroke motor recovery.

Do nociceptive stimulation intensity and temporal predictability influence pain-induced corticospinal excitability modulation?

Temporal predictability and intensity of an impending nociceptive input both shape pain experience and modulate laser-evoked potentials (LEPs) amplitude. However, it remains unclear whether and how these two factors could influence pain-induced corticospinal excitability modulation. The current study investigated the influence of nociceptive stimulation intensity and temporal predictability on motor-evoked potentials (MEPs) modulation, in parallel to their effect on pain perception and LEPs amplitude. Twenty participants completed electroencephalographic and transcranial magnetic stimulation experiments during which two laser nociceptive stimulation intensities (high and low) were either unpredictably delivered (random delay) or preceded by a fixed-timing cue (fixed delay). The amplitude of the conditioned MEPs was significantly reduced only for the high nociceptive stimulation and was not affected by the temporal predictability of pain (despite the fact that temporal predictability modulated the amplitude of P2 LEP component amplitude). However, a posteriori analyses based on patterns of pain-induced MEPs modulation revealed that participants in which nociceptive stimulation resulted in an increase in corticospinal excitability were more affected by the predictability of pain (i.e. increasing corticospinal excitability even more when pain occurrence was predictable), regardless of the nociceptive stimulation intensity; whereas participants in which nociceptive stimulation resulted in a decrease in corticospinal excitability were sensitive to the intensity of the stimulation but not its predictability. These results suggest a potential influence of cognitive factors such as temporal predictability on the response of the motor system in the presence of pain for some participants, contributing to explain, at least in part, the high variability highlighted in a number of previous studies.

Using Cutaneous Receptor Vibration to Uncover the Effect of Transcranial Magnetic Stimulation (TMS) on Motor Cortical Excitability.

BackgroundLittle is known about how vibrational stimuli applied to hand digits affect motor cortical excitability. The present transcranial magnetic stimulation (TMS) study investigated motor evoked potentials (MEPs) in the upper extremity muscle following high-frequency vibratory digit stimulation.Material/MethodsHigh-frequency vibration was applied to the upper extremity digit II utilizing a miniature electromagnetic solenoid-type stimulator-tactor in 11 healthy study participants. The conditioning stimulation (C) preceded the test magnetic stimulation (T) by inter-stimulus intervals (ISIs) of 5–500 ms in 2 experimental sessions. The TMS was applied over the primary motor cortex for the hand abductor pollicis-brevis (APB) muscle.ResultsDunnett’s multiple comparisons test indicated significant suppression of MEP amplitudes at ISIs of 200 ms (P=0.001), 300 ms (P=0.023), and 400 ms (P=0.029) compared to control.ConclusionsMEP amplitude suppression was observed in the APB muscle at ISIs of 200–400 ms, applying afferent signaling that originates in skin receptors following the vibratory stimuli. The study provides novel insight on the time course and MEP modulation following cutaneous receptor vibration of the hand digit. The results of the study may have implications in neurology in the neurorehabilitation of patients with increased amplitude of MEPs.

Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients

ObjectivesSkill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS. MethodsEighteen relapsing-remitting (RR)-MS patients and eighteen healthy controls performed 600 fast abductions of index finger in 30 blocks of 20 movements. Before and after practice, transcranial magnetic stimulation (TMS) was delivered over the hot spot of the trained first dorsal interosseous muscle. Movements kinematics, measures of cortical excitability, and the input/output curves of motor evoked potentials (MEPs) were assessed. ResultsKinematic variables of movement improved with practice in patients and controls to a similar extent, although patients showed lower MEPs amplitude increase after practice. Practice did not change the difference in resting motor threshold values observed between patients and controls, nor did modulate short-interval intracortical inhibition. Clinical/radiological characteristics were not associated to practice-dependent effects. ConclusionsPractice-induced reorganization of M1 is altered in non-disabled RR-MS patients, as shown by impaired MEPs modulation after motor learning. SignificanceThese findings suggest that in RR-MS physiological mechanisms of practice-dependent plasticity are altered.

Aftereffects of Intermittent Theta-Burst Stimulation in Adjacent, Non-Target Muscles

To assess motor cortex neurophysiology, including the mechanisms of neuroplasticity, transcranial magnetic stimulation (TMS) is typically applied to the motor “hotspot”— the optimal site for inducing a twitch in a given target muscle. It is known that the effects of suprathreshold repetitive TMS (rTMS) spread along functional connections beyond the specific cortical stimulation target, and yet, it is unknown whether the aftereffects of subthreshold intermittent theta-burst stimulation (iTBS), an ultra-high frequency patterned rTMS protocol, extend beyond the targeted muscle.We investigated whether and to what extent iTBS induces changes in the cortical output to other intrinsic hand muscles with adjacent cortical representation to the target. Sixteen healthy adults underwent neuronavigated TMS-iTBS targeting the first dorsal interosseus (FDI) hotspot. Proportion of motor evoked potentials (MEPs) at the resting motor threshold (RMT), baseline MEP amplitude, and iTBS-induced changes in MEP amplitude were compared between FDI, abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. MEP amplitudes recorded from the three muscles at RMT and suprathreshold intensities indicated the chosen hotspots were relatively selective for FDI. Nevertheless, iTBS induced significant facilitation of MEPs recorded from both FDI and APB, but not ADM. Surprisingly, the MEP modulation was greater in APB, even when controlling for the baseline MEP amplitude. These results indicate that iTBS modulation of cortico-spinal excitability extends beyond the representation of the targeted muscle. Results have implications both for how iTBS may be used in clinical treatment and for the safety guidelines for the application of iTBS.

Short-latency afferent-induced facilitation and inhibition as predictors of thermally induced variations in corticomotor excitability.

Recently (Ansari et al., PeerJ 6:e6163, 2018a; Somatosens Mot Res 35:69-79, 2018b), we showed using transcranial magnetic stimulation (TMS) that focal application of innocuous thermal stimuli to the distal hand produced variable responses in terms of motor-evoked potential (MEP) suppression or enhancement. Here, we sought to investigate possible causes of this variability by examining circuits mediating sensorimotor integration and intra-cortical inhibition. Participants (n = 21) first underwent TMS to assess baseline corticomotor excitability by measuring MEPs at rest with the index finger wrapped in a gel pack at room temperature (24°C). Then, conditioned protocols were applied to assess short-latency afferent inhibition (SAI), short-latency afferent facilitation (SAF) and short-interval intra-cortical inhibition (SICI). Following baseline measures, MEP modulation in response to distal cooling was recorded with the index finger wrapped ina gel pack at ~ 10°C. At baseline, participants exhibited variable levels of SAI, SAF and SICI. Participant also exhibited variable responses to cooling with about half of them (11/21) showing suppressed excitability and one-third showing enhanced excitability (7/21). A linear regression analysis revealed that SAI and SAF proved to be good predictors of cooling-induced variations in corticomotor excitability but not SICI. These results provide novel evidence linking variations in SAI and SAF with those in corticomotor excitability elicited in response to focal thermal stimulation, suggesting that these markers could be used to predict responses to sensory stimulation protocols.

Attention and cognitive load modulate motor resonance during action observation

Observation of others’ actions evokes a motor resonant (MR) response, in the parieto-frontal Action Observation Network (AON, comprising BA40, BA6, BA4). In order to investigate the effect of cognitive processes on the AON we manipulated attention and cognitive load during central and peripheral observation of hand grasping actions with three experiments. Motor Evoked Potentials (MEPs) were elicited in the opponent of the thumb (OP) and abductor of the little finger (ADM) by Transcranial Magnetic Stimulation (TMS) of the primary motor cortex. First, we investigated the role of selective attention by asking subjects to focus their attention on the thumb of the moving hand in central vision. A selective facilitation of OP MEPs was recorded, without the expected ADM MEPs modulation. Second, a “covert attention” paradigm was used to investigate the role of attention in peripheral vision. Surprisingly, MEP modulation was virtually abolished. In the third experiment we tested the hypothesis that the higher cognitive load introduced by the covert attention instruction had interfered with MR. We allowed subjects to view the action before its peripheral presentation with covert attention, thereby decreasing the cognitive effort necessary to decode the grasping action. The accuracy of motor resonant response was restored.