Introduction: Motor evoked potentials (MEPs) to transcranial magnetic stimulation are known to be susceptible to several sources of variability. However, conflicting evidences on individual characteristics in relatively small sample sizes have been reported. We investigated the effect of age, height, and sex on MEPs of the motor cortex and spinal roots in a large cohort. Methods: A total of 587 subjects clinically and neuroradiologically intact were included. MEPs were recorded during mild tonic contraction through a circular coil (...) applied over the “hot spot” of the first dorsal interosseous and tibialis anterior muscles, bilaterally. Central motor conduction time (CMCT) was estimated as the difference between MEP cortical latency and the peripheral motor conduction time by cervical or lumbar magnetic stimulation. Peak-to-peak MEP amplitude to cortical stimulation and right-to-left difference of each parameter were also measured. Results: After Bonferroni correction, general linear (multiple) regression analysis showed that both MEP cortical latency and peripheral motor conduction time at four limbs positively correlated with age and height. At lower limbs, an independent effect of sex on the same measures was also observed (with females showing smaller values than males). CMCT correlated with both age (negatively) and height (positively) when analyzed by a single regression; however, with a multiple regression analysis this significance disappeared, due to the correction for the multicollinearity within the dataset. Conclusions: Physical individual features need to be considered for a more accurate and meaningful MEPs interpretation. Both in clinical practice and in research setting, patients and controls should be matched for age, height, and sex. (shrink)

This study aimed to investigate whether the effect of mental practice can be enhanced by providing neurofeedback based on transcranial magnetic stimulation -induced motor evoked potentials. Twenty-four healthy, right-handed subjects were enrolled in this study. The subjects were randomly allocated into two groups: a group that was given correct TMS feedback and a group that was given randomized false TMS feedback. The subjects imagined pushing the switch with just timing, when the target circle overlapped a cross at the (...) center of the computer monitor. In the Real-FB group, feedback was provided to the subjects based on the MEP amplitude measured in the trial immediately preceding motor imagery. In contrast, the subjects of the Sham-FB group were provided with a feedback value that was independent of the MEP amplitude. TMS was applied when the target, moving from right to left, overlapped the cross at the center of the screen, and the MEP amplitude was measured. The MEP was recorded in the right first dorsal interosseous muscle. We evaluated the pre-mental practice and post-mental practice motor performance in both groups. As a result, a significant difference was observed in the percentage change of error values between the Real-FB group and the Sham-FB group. Furthermore, the MEP was significantly different between the groups in the 4th and 5th sets. Therefore, it was suggested that TMS-induced MEP-based neurofeedback might enhance the effect of mental practice. (shrink)

ObjectiveThe time interval between transcranial magnetic stimulation pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals. However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials.MethodsIn our study, we delivered sets of 30 TMS pulses with three different IPIs to the left (...) primary motor cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants. MEP amplitudes were recorded through electromyography.ResultsWe found that the IPI had no significant effect on the MEP amplitudes in the active muscle, whereas in the resting muscle, the IPI significantly affected the MEP amplitudes, decreasing the MEP amplitude of the 2 s IPI.ConclusionsThese results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies. (shrink)

Short-term limb immobilization results in skeletal muscle decline, but the underlying mechanisms are incompletely understood. This study aimed to determine the neurophysiologic basis of immobilization-induced skeletal muscle decline, and whether repetitive Transcranial Magnetic Stimulation could prevent any decline. Twenty-four healthy young males underwent unilateral limb immobilization for 72 h. Subjects were randomized between daily rTMS using six 20 Hz pulse trains of 1.5 s duration with a 60 s inter-train-interval delivered at 90% resting Motor Threshold, or Sham rTMS throughout (...) immobilization. Maximal grip strength, EMG activity, arm volume, and composition were determined at 0 and 72 h. Motor Evoked Potentials were determined daily throughout immobilization to index motor excitability. Immobilization induced a significant reduction in motor excitability across time. The rTMS intervention increased motor excitability at 0 h. Despite daily rTMS treatment, there was still a significant reduction in motor excitability, loss in EMG activity, and a loss of maximal grip strength after immobilization. Interestingly, the increase in biceps and posterior forearm skinfold thickness with immobilization in Sham treatment was not observed following rTMS treatment. Reduced MEPs drive the loss of strength with immobilization. Repetitive Transcranial Magnetic Stimulation cannot prevent this loss of strength but further investigation and optimization of neuroplasticity protocols may have therapeutic benefit. (shrink)

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to its antagonist. (...) The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS. (shrink)

Paired associative stimulation at the spinal cord has been shown to increase muscle force and dexterity by strengthening the corticomuscular connection, through spike timing dependent plasticity. Typically, transcranial magnetic stimulation and transcutaneous peripheral nerve electrical stimulation are often used in spinal PAS. PNS targets superficial nerve branches, by which the number of applicable muscles is limited. Alternatively, a muscle can be activated by positioning the stimulation electrode on the “motor point”, which is the most sensitive location of a muscle (...) to electrical stimulation. Although this can increase the number of applicable muscles for spinal PAS, nobody has tested whether MPS can be used for the spinal PAS to date. Here we investigated the feasibility of using MPS instead of PNS for spinal PAS. Ten healthy male individuals received spinal PAS on two separate days with different stimulation timings expected to induce facilitation of corticospinal excitability or no effect on the soleus. The motor evoked potentials response curve in the soleus was measured prior to the spinal PAS, immediately after and at 10, 20, 30 min post-intervention as a measure of corticospinal excitability. The post-intervention MEP response curve areas were larger in the REAL condition than the CONTROL conditions. Further, the post-intervention MEP response curve areas were significantly larger than pre-intervention in the REAL condition but not in the CONTROL condition. We conclude that MPS can facilitate corticospinal excitability through spinal PAS. (shrink)

Short-term motor practice leads to plasticity in the primary motor cortex. The purpose of this study is to investigate the factors that determine the increase in corticospinal tract excitability after motor practice, with special focus on two factors; “the level of muscle activity” and “the presence/absence of a goal of keeping the activity level constant.” Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the “comfortable task” and “forceful task”, the subjects adducted (...) their thumb using comfortable and strong forces. In the “comfortable with a goal task” and “forceful with a goal task”, subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation, which combines peripheral nerve stimulation and transcranial magnetic stimulation, with an inter-stimulus interval of 25 ms was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant. (shrink)

BackgroundTranscranial direct current stimulation targeting the primary motor hand area may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging can probe after-effects of TDCS on regional neural activity on a whole-brain level.ObjectiveUsing a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas.MethodsSeventeen healthy volunteers received 20 min of real or sham TDCS (...) on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob.ResultsReal TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency.ConclusionFunctional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability. (shrink)

GraphicalThirty healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA. Motor cortical excitability was assessed using TMS-induced MEPs acquired across different oscillatory phases during and outlasting tACS, as well as at the start and end of the stimulation session. Mean MEP amplitude increased by ∼41% from pre- to post-tACS ; however, MEP amplitudes were not modulated with respect to the tACS phase.Converging evidence suggests that transcranial alternating current stimulation may entrain endogenous neural oscillations (...) to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation. However, observing entrainment in the electroencephalograph during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory tACS by measuring motor cortical excitability across different oscillatory phases during and outlasting stimulation. 30 healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation of the hand region of the primary motor cortex to induce motor evoked potentials in the contralateral thumb. MEPs were acquired at four time-points within each trial – early online, late online, early offline, and late offline – as well as at the start and end of the overall stimulation period. A significant increase in MEP amplitude was observed from pre- to post-tACS and from the first to the last tACS block. However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism. (shrink)

Previous studies on body ownership illusions have shown that under certain multimodal conditions, healthy people can experience artificial body-parts as if they were part of their own body, with direct physiological consequences for the real limb that gets ‘substituted’. In this study we wanted to assess (a) whether healthy people can experience ‘missing’ a body-part through illusory ownership of an amputated virtual body, and (b) whether this would cause corticospinal excitability changes in muscles associated with the ‘missing’ body-part. Forty right-handed (...) participants saw a virtual body from a first person perspective but for half of them the virtual body was missing a part of its right arm. Single pulse transcranial magnetic stimulation was applied before and after the experiment to left and right motor cortices. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and the extensor digitorum communis (EDC) of each hand. We found that the stronger the illusion of amputation and arm ownership, the more the reduction of MEP amplitudes of the EDC muscle for the contralateral sensorimotor cortex. In contrast, no association was found for the EDC amplitudes in the ipsilateral cortex and for the FDI amplitudes in both contralateral and ipsilateral cortices. Our study provides evidence that a short-term illusory perception of missing a body-part can trigger inhibitory effects on corticospinal pathways and importantly in the absence of any limb deafferentation or disuse. (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% resting motor (...) threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)