The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability

BackgroundNeural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8–13 Hz) and beta (14–30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown.ObjectiveHere, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0°, 90°, 180°, and 270°) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study.ResultsMixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations.ConclusionOur results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.     

Effects of Different Electrical Brain Stimulation Protocols on Subcomponents of Motor Skill Learning

BackgroundNoninvasive electrical brain stimulation (NEBS) with transcranial direct current (tDCS) or random noise stimulation (tRNS) applied to the primary motor cortex (M1) can augment motor learning.ObjectiveWe tested whether different types of stimulation alter particular aspects of learning a tracing task over three consecutive days, namely skill acquisition (online/within session effects) or consolidation (offline/between session effects).MethodsMotor training on a tracing task over three consecutive days was combined with different types and montages of stimulation (tDCS, tRNS).ResultsUnilateral M1 stimulation using tRNS as well as unilateral and bilateral M1 tDCS all enhanced motor skill learning compared to sham stimulation. In all groups, this appeared to be driven by online effects without an additional offline effect. Unilateral tDCS resulted in large skill gains immediately following the onset of stimulation, while tRNS exerted more gradual effects. Control stimulation of the right temporal lobe did not enhance skill learning relative to sham.ConclusionsThe mechanisms of action of tDCS and tRNS are likely different. Hence, the time course of skill improvement within sessions could point to specific and temporally distinct interactions with the physiological process of motor skill learning. Exploring the parameters of NEBS on different tasks and in patients with brain injury will allow us to maximize the benefits of NEBS for neurorehabilitation.     

Individual differences in TMS sensitivity influence the efficacy of tDCS in facilitating sensorimotor adaptation

BackgroundTranscranial direct current stimulation (tDCS) can enhance cognitive function in healthy individuals, with promising applications as a therapeutic intervention. Despite this potential, variability in the efficacy of tDCS has been a considerable concern.Objective/Hypothesis: Given that tDCS is always applied at a set intensity, we examined whether individual differences in sensitivity to brain stimulation might be one variable that modulates the efficacy of tDCS in a motor learning task.MethodsIn the first part of the experiment, single-pulse transcranial magnetic stimulation (TMS) over primary motor cortex (M1) was used to determine each participant's resting motor threshold (rMT). This measure was used as a proxy of individual sensitivity to brain stimulation. In an experimental group of 28 participants, 2 mA tDCS was then applied during a motor learning task with the anodal electrode positioned over left M1. Another 14 participants received sham stimulation.ResultsM1-Anodal tDCS facilitated learning relative to participants who received sham stimulation. Of primary interest was a within-group analysis of the experimental group, showing that the rate of learning was positively correlated with rMT: Participants who were more sensitive to brain stimulation as operationalized by our TMS proxy (low rMT), showed faster adaptation.ConclusionsMethodologically, the results indicate that TMS sensitivity can predict tDCS efficacy in a behavioral task, providing insight into one source of variability that may contribute to replication problems with tDCS. Theoretically, the results provide further evidence of a role of sensorimotor cortex in adaptation, with the boost from tDCS observed during acquisition.     

Transcranial magnetic stimulation has no placebo effect on motor learning

ObjectiveMotor learning is the core cognitive function in neurorehabilitation and in various other skill-training activities (e.g. sport, music). Therefore, there is an increasing interest in the use of transcranial magnetic stimulation (TMS) methods for its enhancement. However, although usually assumed, a potential placebo effect of TMS methods on motor learning has never been systematically investigated.MethodsImprovement of performance on the Purdue Pegboard Task over three test-blocks (T0, T1, and T2), separated by >20 min, was used to evaluate motor learning. In Experiment-1, two groups of 10 participants each were compared: one group immediately before T1 received a sham intermittent theta burst stimulation procedure (P-iTBS group), while another did not have any intervention at all (control – CON group). In Experiment-2, a third group of participants (six subjects) who received sham high-frequency repetitive TMS procedure before T1 (P-rTMS group) was compared with P-iTBS group.ResultsAll three groups showed significant learning over time, but without any difference between them, either in Experiment-1 between P-iTBS and CON, or in Experiment-2 between P-rTMS and P-iTBS.ConclusionThe results suggest lack of any placebo effect of TMS on motor learning.SignificanceThe results may help in designing further TMS–motor learning studies and in interpreting their results.     

Neurophysiology of motor skill learning in chronic stroke

ObjectiveMotor learning is relevant in chronic stroke for acquiring compensatory strategies to motor control deficits. However, the neurophysiological mechanisms underlying motor skill acquisition with the paretic upper limb have received little systematic investigation. The aim of this study was to assess the modulation of corticomotor excitability and intracortical inhibition within ipsilesional primary motor cortex (M1) during motor skill learning.MethodsTen people at the chronic stage after stroke and twelve healthy controls trained on a sequential visuomotor isometric wrist extension task. Skill was quantified before, immediately after, 24 hours and 7 days post-training. Transcranial magnetic stimulation was used to examine corticomotor excitability and short- and long-interval intracortical inhibition (SICI and LICI) pre- and post-training.ResultsThe patient group exhibited successful skill acquisition and retention, although absolute skill level was lower compared with controls. In contrast to controls, patients’ ipsilesional corticomotor excitability was not modulated during skill acquisition, which may be attributed to excessive ipsilesional LICI relative to controls. SICI decreased after training for both patient and control groups.ConclusionsOur findings indicate distinct inhibitory networks within M1 that may be relevant for motor learning after stroke.SignificanceThese findings have potential clinical relevance for neurorehabilitation adjuvants aimed at augmenting the recovery of motor function.     

Primary motor and premotor cortex in implicit sequence learning - evidence for competition between implicit and explicit human motor memory systems

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1‐AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd‐AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1‐AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd‐AtDCS during practice attenuated offline stabilization compared with M1‐AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition.     

Effects of anodal transcranial direct current stimulation over lower limb primary motor cortex on motor learning in healthy individuals

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which alters motor functions in healthy humans and in neurological patients. Most studies so far investigated the effects of tDCS on mechanisms underlying improvements in upper limb performance. To investigate the effect of anodal tDCS over the lower limb motor cortex (M1) on lower limb motor learning in healthy volunteers, we conducted a randomized, single‐blind and sham‐controlled study. Thirty‐three (25.81 ± 3.85, 14 female) volunteers were included, and received anodal or sham tDCS over the left M1 (M1‐tDCS); 0.0625 mA/cm² anodal tDCS was applied for 15 min during performance of a visuo‐motor task (VMT) with the right leg. Motor learning was monitored for performance speed and accuracy based on electromyographic recordings. We also investigated the influence of electrode size and baseline responsivity to transcranial magnetic stimulation (TMS) on the stimulation effects. Relative to baseline measures, only M1‐tDCS applied with small electrodes and in volunteers with high baseline sensitivity to TMS significantly improved VMT performance. The computational analysis showed that the small anode was more specific to the targeted leg motor cortex volume when compared to the large anode. We conclude that anodal M1‐tDCS modulates VMT performance in healthy subjects. As these effects critically depend on sensitivity to TMS and electrode size, future studies should investigate the effects of intensified tDCS and/or model‐based different electrode positions in low‐sensitivity TMS individuals.     

Posttraining transcranial magnetic stimulation of striate cortex disrupts consolidation early in visual skill learning

Practice-induced improvements in skilled performance reflect "offline " consolidation processes extending beyond daily training sessions. According to visual learning theories, an early, fast learning phase driven by high-level areas is followed by a late, asymptotic learning phase driven by low-level, retinotopic areas when higher resolution is required. Thus, low-level areas would not contribute to learning and offline consolidation until late learning. Recent studies have challenged this notion, demonstrating modified responses to trained stimuli in primary visual cortex (V1) and offline activity after very limited training. However, the behavioral relevance of modified V1 activity for offline consolidation of visual skill memory in V1 after early training sessions remains unclear. Here, we used neuronavigated transcranial magnetic stimulation (TMS) directed to a trained retinotopic V1 location to test for behaviorally relevant consolidation in human low-level visual cortex. Applying TMS to the trained V1 location within 45 min of the first or second training session strongly interfered with learning, as measured by impaired performance the next day. The interference was conditional on task context and occurred only when training in the location targeted by TMS was followed by training in a second location before TMS. In this condition, high-level areas may become coupled to the second location and uncoupled from the previously trained low-level representation, thereby rendering consolidation vulnerable to interference. Our data show that, during the earliest phases of skill learning in the lowest-level visual areas, a behaviorally relevant form of consolidation exists of which the robustness is controlled by high-level, contextual factors.     

Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning

BackgroundNon-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability and thereby influencing motor behaviour and learning.HypothesisWhile there is increasing knowledge about the importance of the primary motor cortex (M1) in short- and long-term motor skill learning, little is known about the role of secondary motor areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA) especially in short-term motor performance. Since SMA but not pre-SMA is directly connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will facilitate visuomotor learning.MethodsWe applied anodal tDCS (tDCS_anodal) over left SMA, pre-SMA or M1 (n = 12 in each group) while subjects performed a visuomotor pinch force task (VPFT) with their right hand and compared VPFT performance relative to sham (tDCS_sham).ResultsFor the first time, we could show that apart from tDCS_anodal over left M1 also SMA but not pre-SMA stimulation promotes short-term improvements in visuomotor learning relative to tDCS_sham.ConclusionsOur findings provide novel evidence about the role of SMA in short-term visuomotor performance. This knowledge might be beneficial in developing hypothesis-driven clinical studies in neurorehabilitation.     

Utilizing transcranial direct current stimulation to enhance laparoscopic technical skills training: A randomized controlled trial

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability. Prior work suggests it may enhance motor learning giving it the potential to augment surgical technical skill acquisition.ObjectivesThe aim of this study was to test the efficacy of tDCS, coupled with motor skill training, to accelerate laparoscopic skill acquisition in a pre-registered (NCT03083483), double-blind and placebo-controlled study. We hypothesized that relative to sham tDCS, active tDCS would accelerate the development of laparoscopic technical skills, as measured by the Fundamentals of Laparoscopic Surgery (FLS) Peg Transfer task quantitative metrics.MethodsIn this study, sixty subjects (mean age 22.7 years with 42 females) were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the FLS Peg Transfer Task during six 20-min training blocks, which were preceded and followed by a single trial pre-test and post-test. The primary outcome was changes in laparoscopic skill performance over time, quantified by group differences in completion time from pre-test to post-test and learning curves developed from a calculated score accounting for errors.ResultsLearning curves calculated over the six 20-min training blocks showed significantly greater improvement in performance for the bM1 group than the sham group (t = 2.07, p = 0.039), with the bM1 group achieving approximately the same amount of improvement in 4 blocks compared to the 6 blocks required of the sham group. The SMA group also showed greater mean improvement than sham, but exhibited more variable learning performance and differences relative to sham were not significant (t = 0.85, p = 0.400). A significant main effect was present for pre-test versus post-test times (F = 133.2, p < 0.001), with lower completion times at post-test, however these did not significantly differ for the training groups.ConclusionLaparoscopic skill training with active bilateral tDCS exhibited significantly greater learning relative to sham. The potential for tDCS to enhance the training of surgical skills, therefore, merits further investigation to determine if these preliminary results may be replicated and extended.     

No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm

BackgroundThe motor potentials evoked by transcranial magnetic stimulation (TMS) over the motor hand area (M1-HAND) show substantial inter-trial variability. Pericentral mu-rhythm oscillations, might contribute to inter-trial variability. Recent studies targeting mu-activity based on real-time electroencephalography (EEG) reported an influence of mu-power and mu-phase on the amplitude of motor evoked potentials (MEPs) in a preselected group with strong pericentral mu-activity. Other studies that determined mu-power or mu-phase based on post-hoc trial sorting according in non-preselected individuals were largely negative.ObjectivesTo reassess if cortico-spinal activity is modulated by the mu-rhythm, we applied single-pulse TMS to the M1-HAND conditional on the phase of the intrinsically expressed pericentral mu-rhythm in 14 non-preselected healthy young participants.MethodsTMS was given at 0, 90, 180, and 270° of the mu-phase. Based on the absence of effects of mu-phase or mu-power when analyzing the mean MEP amplitudes, we also computed a linear mixed effects model, which included mu-phase, mu-power, inter-stimulus interval (ISIs) as fixed effects, treating the subject factor as a random effect.ResultsMixed model analysis revealed a significant effect of mu-power and ISI, but no effect of mu-phase and no interactions. MEP amplitude scaled linearly with lower mu-power or longer ISIs, but these modulatory effects were very small relative to inter-trial MEP variability.ConclusionOur largely negative results are in agreement with previous offline TMS-EEG studies and point to a possible influence of ISI. Future research needs to clarify under which circumstances the responsiveness of human the M1-HAND to TMS depends on the synchronicity with mu-power and mu-phase.     

Paired Associative Stimulation drives the emergence of motor resonance

BackgroundAssociative plasticity, the neurophysiological bases of Hebbian learning, has been implied in the formation of the association between sensory and motor representations of actions in the Mirror Neuron System; however, such inductor role still needs empirical support.Objective/hypothesisWe have assessed whether Paired Associative Stimulation (PAS), known to activate Hebbian associative plasticity, can induce the formation of atypical (absent in normal conditions), visuo-motor associations, reshaping motor resonance.MethodsHealthy participants underwent a novel PAS protocol (mirror-PAS, m-PAS), during which they were exposed to repeated pairings of transcranial magnetic stimulation (TMS) applied over the right primary motor cortex (M1), time-locked with the view of index-finger movements of the right (ipsilateral) hand. In a first experiment, the inter-stimulus interval (ISI) between visual-action stimuli and TMS pulses was varied. Before and after each m-PAS session, motor resonance was assessed by recording Motor Evoked Potentials induced by single-pulse TMS applied to the right M1, during the observation of both contralateral (left) and ipsilateral (right) index-finger movements. In the second experiment, the specificity of the m-PAS was assessed by presenting a visual stimulus depicting a non-biological movement.ResultsBefore m-PAS, the facilitation of corticospinal excitability occurred only during the view of contralateral (with respect to the TMS side) index-finger movements. The m-PAS induced new ipsilateral motor resonance responses, indexed by atypical facilitation of corticospinal excitability by the view of ipsilateral hand movements. This effect occurred only if the associative stimulation followed the chronometry of motor control (ISI of 25 ms) and if the visual stimulus of the m-PAS depicts a biological movement (human hand action).ConclusionsThe present findings provide the first empirical evidence that Hebbian learning induced by a PAS protocol shapes the visual-motor matching properties of the human Mirror Neuron System.     

Behavioral and neurophysiological mechanisms underlying motor skill learning in patients with post-stroke hemiparesis

Objective

Given the presence of execution deficits after stroke, it is difficult to determine if patients with stroke have deficits in motor skill learning with the paretic arm. Here, we controlled for execution deficits while testing practice effects of the paretic arm on motor skill learning, long-term retention, and corticospinal excitability.

Modulation of motor learning by a paired associative stimulation protocol inducing LTD-like effects

BackgroundPaired associative stimulation (PAS) induces long-term potentiation (LTP)-like effects when interstimulus intervals (ISIs) between electrical peripheral nerve stimulation and transcranial magnetic stimulation (TMS) to M1 are approximately 21–25 ms (PAS_LTP). It was previously reported that two forms of motor learning (i.e., mode-free and model-based learning) can be differentially modulated by PAS_LTP depending on the different synaptic inputs to corticospinal neurons (CSNs), which relate to posterior-to-anterior (PA) or anterior-to-posterior (AP) currents induced by TMS (PA or AP inputs, respectively). However, the effects of long-term depression (LTD)-inducing PAS with an ISI of approximately 10 ms (PAS_LTD) on motor learning and its dependency on current direction have not yet been tested.ObjectiveTo investigate whether, and how, PAS_LTD affects distinct types of motor learning.MethodsEighteen healthy volunteers participated. We adopted the standard PAS using suprathreshold TMS with the target muscle relaxed, as well as subthreshold PAS during voluntary contraction, which was suggested to selectively recruit PA or AP inputs depending on the orientation of the TMS coil. We examined the effects of suprathreshold and subthreshold PAS_LTD on the performance of model-free and model-based learning, as well as the corticospinal excitability, indexed as the amplitudes of motor evoked potentials (MEPs).ResultsPAS_LTD inhibited model-free learning and MEPs only when subthreshold AP currents were applied. The PAS_LTD protocols tested here showed no effects on model-based learning.ConclusionsPAS_LTD affected model-free learning, presumably by modulating CSN excitability changes, rather than PA inputs, which are thought to be related to model-free learning.     

Cell type-specific excitability probed by optogenetic stimulation depends on the phase of the alpha oscillation

BackgroundAlpha oscillations have been proposed to provide phasic inhibition in the brain. Yet, pinging alpha oscillations with transcranial magnetic stimulation (TMS) to examine phase-dependent network excitability has resulted in conflicting findings. At the cellular level, such gating by the alpha oscillation remains poorly understood.ObjectiveWe examine how the excitability of pyramidal cells and presumed fast-spiking inhibitory interneurons depends on the phase of the alpha oscillation.MethodsOptogenetic stimulation pulses were administered at random phases of the alpha oscillation in the posterior parietal cortex (PPC) of two adult ferrets that expressed channelrhodopsin in pyramidal cells. Post-stimulation firing probability was calculated as a function of the stimulation phase of the alpha oscillation for both verum and sham stimulation.ResultsThe excitability of pyramidal cells depended on the alpha phase, in anticorrelation with their intrinsic phase preference; pyramidal cells were more responsive to optogenetic stimulation at the alpha phase with intrinsically low firing rates. In contrast, presumed fast-spiking inhibitory interneurons did not show such a phase dependency despite their stronger intrinsic phase preference.ConclusionsAlpha oscillations gate input to PPC in a phase-dependent manner such that low intrinsic activity was associated with higher responsiveness to input. This finding supports a model of cortical oscillation, in which internal processing and communication are limited to the depolarized half-cycle, whereas the other half-cycle serves as a signal detector for unexpected input. The functional role of different parts of the alpha cycle may vary across the cortex depending on local neuronal firing properties.     

Bihemispheric sensorimotor oscillatory network states determine cortical responses to transcranial magnetic stimulation

BackgroundBrain responses to external stimuli vary with fluctuating states of neuronal activity. Previous work has demonstrated effects of phase and power of the ongoing local sensorimotor μ-alpha-oscillation on responses to transcranial magnetic stimulation (TMS) of motor cortex (M1). However, M1 is part of a distributed network, and the effects of oscillatory activity in this network on TMS-evoked EEG responses (TEPs) have not been explored.ObjectivesTo determine the effects of oscillatory activity in the bihemispheric sensorimotor network on TEPs.Methods31 healthy subjects received single-pulse TMS of the left M1 hand area during EEG recording. Ongoing bihemispheric sensorimotor cortex oscillatory states were reconstructed from the EEG directly preceding TMS, and inferred by a data-driven method combining a multivariate autoregressive model and a Hidden Markov model. TEP amplitudes (P25, N45, P70, N100 and P180) were then compared between different bihemispheric sensorimotor cortex oscillatory states.ResultsFour bihemispheric sensorimotor cortex oscillatory states were identified, with different interhemispheric expressions of theta and alpha oscillations. High alpha-power states in the stimulated sensorimotor cortex increased P25 amplitude. Alpha power in the alpha-alpha state (stimulated - non-stimulated hemisphere) correlated in both hemispheres with N45 amplitude. Theta power in the alpha-theta state correlated in the non-stimulated hemisphere with P70 amplitude.ConclusionsBihemispheric sensorimotor cortex oscillatory states contribute to TEPs, with a relevance shift from stimulated to non-stimulated M1 from P25 over N45 to P70. This significantly extends previous findings: not only ongoing local oscillations but distributed network oscillatory states determine cortical responsiveness to external stimuli.     

Median nerve stimulation induced motor learning in healthy adults: A study of timing of stimulation and type of learning

Median nerve stimulation (MNS) has been shown to change brain metaplasticity over the somatosensory networks, based on a bottom‐up mechanism and may improve motor learning. This exploratory study aimed to test the effects of MNS on implicit and explicit motor learning as measured by the serial reaction time task (SRTT) using a double‐blind, sham‐controlled, randomized trial, in which participants were allocated to one of three groups: (a) online active MNS during acquisition, (b) offline active MNS during early consolidation and (c) sham MNS. SRTT was performed at baseline, during the training phase (acquisition period), and 30 min after training. We assessed the effects of MNS on explicit and implicit motor learning at the end of the training/acquisition period and at retest. The group receiving online MNS (during acquisition) showed a significantly higher learning index for the explicit sequences compared to the offline group (MNS during early consolidation) and the sham group. The offline group also showed a higher learning index as compared to sham. Additionally, participants receiving online MNS recalled the explicit sentence significantly more than the offline MNS and sham groups. MNS effects on motor learning have a specific effect on type of learning (explicit vs. implicit) and are dependent on timing of stimulation (during acquisition vs. early consolidation). More research is needed to understand and optimize the effects of peripheral electrical stimulation on motor learning. Taken together, our results show that MNS, especially when applied during the acquisition phase, is a promising tool to modulate motor leaning.     

Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition,consolidation, and interlimb transfer of motor skills in healthy young adults

Objective

Plasticity of the central nervous system likely underlies motor learning. It is however unclear, whether plasticity in cortical motor networks is motor learning stage-, activity-, or connectivity-dependent.

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans

ObjectiveQuadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1).MethodsOne burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5 s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs).ResultsQPS-5 over M1 or dPMC enhanced the P25–N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs.ConclusionsQPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations.SignificanceQPSs induced heterotopic LTP or LTD-like cortical excitability changes.     

Mobile Phone Emissions Modulate Brain Excitability in Patients with Focal Epilepsy

BackgroundElectromagnetic fields (EMFs) emitted by mobile phones had been shown to increase cortical excitability in healthy subjects following 45 min of continuous exposure on the ipsilateral hemisphere.ObjectiveUsing Transcranial Magnetic Stimulation (TMS), the current study assessed the effects of acute exposure to mobile phone EMFs on the cortical excitability in patients with focal epilepsy.MethodsTen patients with cryptogenic focal epilepsy originating outside the primary motor area (M1) were studied. Paired-pulse TMS were applied to the M1 of both the hemisphere ipsilateral (IH) and contralateral (CH) to the epileptic focus before and immediately after real/sham exposure to the GSM-EMFs (45 min). The TMS study was carried out in all subjects in three different experimental sessions (IH and CH exposure, sham), 1 week apart, according to a crossover, double-blind and counter-balanced paradigm.ResultsThe present study clearly demonstrated that an acute and relatively prolonged exposure to GSM-EMFs modulates cortical excitability in patients affected by focal epilepsy; however, in contrast to healthy subjects, these effects were evident only after EMFs exposure over the hemisphere contralateral to the epileptic focus (CH). They were characterized by a significant cortical excitability increase in the exposed hemisphere paired with slight excitability decrease in the other one (IH). Both sham and real EMFs exposure of the IH did not affect brain excitability.ConclusionPresent results suggest a significant interaction between the brain excitability changes induced by EMFs and the epileptic focus, which eliminated the excitability enhancing effects of EMFs evident only in the CH.