Mean Motor Evoked Potentials Amplitude Research Articles

Reducing motor evoked potential amplitude variability through normalization.

BackgroundTranscranial Magnetic Stimulation (TMS) is used for in vivo assessment of human motor cortical excitability, with application of TMS pulses over the motor cortex resulting in muscle responses that can be recorded with electromyography (EMG) as Motor Evoked Potentials (MEPs). These have been widely explored as potential biomarkers for neuropsychiatric disorders but methodological heterogeneity in acquisition, and inherent high variability, have led to constraints in reproducibility. Normalization, consisting in scaling the signal of interest to a known and repeatable measurement, reduces variability and is standard practice for between-subject comparisons of EMG. The effect of normalization on variability of MEP amplitude has not yet been explored and was assessed here using several methods.MethodsThree maximal voluntary isometric contractions (MVICs) and 40 MEPs were collected from the right hand in healthy volunteers, with a retest session conducted 4 to 8 weeks later. MEP amplitude was normalized using either external references (MVICs) or internal references (extreme MEPs). Iterative re-sampling of 30 normalized MEPs per subject was repeated 5,000 times to define, for each normalization method, distributions for between-subject coefficients of variation (CV) of the mean MEP amplitude. Intra-class correlation coefficients (ICC) were used to assess the impact of normalization on test–retest stability of MEP amplitude measurements.ResultsIn the absence of normalization, MEPs collected from the right hand of 47 healthy volunteers were within reported values regarding between-subject variability (95% confidence intervals for the CV: [1.0567,1.0577]) and showed good temporal stability (ICC = 0.77). Internal reference normalization substantially reduced between-subject variability, by values of up to 64%, while external reference normalization had no impact or increased between-subject variability. Normalization with the smallest references reduced test–retest stability, with use of the largest references resulting in slight reduction or improvement of ICCs. Internal reference normalization using the largest MEPs was found to be robust to several sensitivity analyses.ConclusionInternal, but not external, reference normalization reduces between-subject variability of MEP amplitude, and has a minimal impact on within-subject variability when conducted with the largest references. Additional research is necessary to further validate these normalization methods toward potential use of MEPs as biomarkers of neuropsychiatric disorders.

Mirror neuron activity depending on the content and stage of the observed action: a TMS study.

The firing rate of the mirror neuron system in monkeys decreases systematically with more repetitions. The aim of this study is to investigate whether the activity of the mirror neuron system varies based on the observed movement and the contents of the action, as well as whether there is inhibition in the mirror neuron system when humans observe repeated actions. If inhibition is present, the second question of the study is whether it is related to the organization of the observed action. Fourteen healthy volunteers participated in the study. Transcranial magnetic stimulation was applied to the left primary motor cortex and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous and abductor pollicis brevis muscles while the participants were watching videos specially prepared for the study. There were no significant changes in MEP amplitudes compared to baseline MEPs while observing aimless action. However, while participants watched the repeated action video, the mean MEP amplitude increased at the beginning of the movement, but neither facilitation nor inhibition was detected when the participants watched the phase of grasping the object of the action compared to the baseline MEP amplitude. On the other hand, while participants were watching different activities, an increased MEP amplitude was observed at the beginning of the movement and in the grasping of the object of the action. Additionally, there was no significant reduction in MEP amplitude during any movement stages while observing the repeated action video. The findings of this study suggest that the activation of the mirror neuron system in humans depends on the content and stages of the observed movement. Additionally, there was no inhibition or systematic reduction in MEP amplitudes while watching a repeated action.

Paired Associative Stimulation with Interstimulus Intervals of Short-latency Afferent Inhibition on Motor Plasticity

ABSTRACT Background: Short-latency afferent inhibition (SAI) is a method used to assess sensorimotor integration. Inhibition typically occurs at an interstimulus interval (ISI) of 20–22 ms or N20 + 2 ms. Paired associative stimulation (PAS) applied at certain ISIs consecutively can induce changes in corticospinal excitability. Usually, ISIs of 10 and 25 ms are applied in PAS. In this study, we aimed to investigate the relationship between ISIs of SAI and PAS, a neuromodulation paradigm. To achieve this, we first identified the optimal ISIs that produced maximum inhibition and facilitation during SAI by evaluating multiple ISIs. Subsequently, we applied the PAS paradigm with these ISIs. Materials and Methods: Twelve healthy participants were recruited for the study conducted over three sessions. During the first session, we examined the ISI of maximum inhibitory and ISI of facilitatory or minimum inhibitory (if facilitation was absent) in each participant at multiple ISIs. In the other two sessions, we applied PAS at the ISI of maximum inhibitory and the ISI of facilitatory or minimum inhibitory. We compared the motor-evoked potential (MEP) amplitudes before PAS, immediately after PAS, and 30 min after PAS. Results: The highest inhibition in SAI was observed at an ISI of 22 ms. In 60% of the participants, inhibition was most prominent at this ISI. Facilitation was not observed in 50% of the participants. During the PAS paradigm, which used the ISI of maximum inhibitory, significant facilitation was observed 30 min after the procedure compared with baseline (P = 0.011) and immediately post-PAS (P = 0.026). The mean MEP amplitude decreased significantly 30 min after the procedure compared with the baseline in ISI of only detected facilitation (P = 0.041). Conclusion: Our findings suggest that the ISI of maximum inhibition can vary among individuals, and that facilitation may not be observed in everyone within the ISI range of 22 ms to 40 ms. The results indicate that paired stimuli at ISI of maximum inhibitory in SAI increase corticospinal excitability. In addition, PAS at ISI of only facilitation decreases excitability. These changes in excitability may be explained by spike-timing-dependent plasticity.

Multimodal Assessment of Precentral Anodal TDCS: Individual Rise in Supplementary Motor Activity Scales With Increase in Corticospinal Excitability.

BackgroundTranscranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) 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 (10 women) received 20 min of real (0.75 mA) 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 (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) 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 (AP-LM MEP latency).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.

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

ObjectiveSub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS15ms) would exert a lasting inhibitory effect on corticospinal excitability. Methods20 healthy volunteers received two minutes of 5 Hz-rPAS15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS15ms. ResultsSubthreshold 5-Hz rPAS15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle. ConclusionsSubthreshold 5-Hz rPAS15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex. SignificanceThe results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.

The effect of dexmedetomidine on motor-evoked potentials during pediatric posterior spinal fusion surgery: a retrospective case-control study.

Motor-evoked potentials (MEPs) are frequently used in pediatric posterior spinal fusion surgery (PSFS) to detect spinal cord ischemia. Dexmedetomidine is increasingly being used as an adjunct to total intravenous anesthesia, but its effect on MEP amplitude has been variably reported. The purpose of this study was to evaluate the effect of an infusion of dexmedetomidine on the amplitude of MEPs. We performed a retrospective case-control study of 30 pediatric patients who received a 0.5 µg·kg-1·hr-1 infusion of dexmedetomidine, ten patients who received 0.3 µg·kg-1·hr-1 dexmedetomidine, and 30 control patients who did not receive dexmedetomidine during PSFS. Two neurophysiologists reviewed the MEP amplitudes in six muscle groups at three time points: when the patient was turned prone (baseline; T1), one hour after incision (T2), and after exposure of the spine but before insertion of the first screw (T3). In all muscles tested, the mean MEP amplitude was reduced by T3 when dexmedetomidine was infused at 0.5 µg·kg-1·hr-1. The greatest reduction from baseline MEP amplitude was 829 µV (95% confidence interval, 352 to 1230; P < 0.001) seen in first right dorsus interosseous. When dexmedetomidine was infused at 0.3 µg·kg-1·hr-1, there was a significant reduction in MEP amplitude in four of the six muscles tested at T3 compared with the control group. Dexmedetomidine at commonly used infusion rates of 0.3 µg·kg-1·hr-1 or 0.5 µg·kg-1·hr-1 causes a significant decrease in MEP amplitude during pediatric PSFS. We suggest that dexmedetomidine should be avoided in children undergoing PSFS so as not to confuse the interpretation of this important neurophysiological monitor.

Global Corticospinal Excitability as Assessed in A Non-Exercised Upper Limb Muscle Compared Between Concentric and Eccentric Modes of Leg Cycling

This study investigated the effects of eccentric (ECC) and concentric (CON) semi-recumbent leg cycling on global corticospinal excitability (CSE), assessed through the activity of a non-exercised hand muscle. Thirteen healthy male adults completed two 30-min bouts of moderate intensity ECC and CON recumbent cycling on separate days. Power output (POutput), heart rate (HR) and cadence were monitored during cycling. Global CSE was assessed using transcranial magnetic stimulation to elicit motor-evoked potentials (MEP) in the right first dorsal interosseous muscle before (‘Pre’), interleaved (at 10 and 20 mins, t10 and t20, respectively), immediately after (post, P0), and 30-min post exercise (P30). Participants briefly stopped pedalling (no more than 60 s) while stimulation was applied at the t10 and t20 time-points of cycling. Mean POutput, and rate of perceived exertion (RPE) did not differ between ECC and CON cycling and HR was significantly lower during ECC cycling (P = 0.01). Group mean MEP amplitudes were not significantly different between ECC and CON cycling at P0, t10, t20, and P30 and CON (at P > 0.05). Individual participant ratios of POutput and MEP amplitude showed large variability across the two modes of cycling, as did changes in slope of stimulus-response curves. These results suggest that compared to ‘Pre’ values, group mean CSE is not significantly affected by low-moderate intensity leg cycling in both modes. However, POutput and CSE show wide inter-participant variability which has implications for individual neural responses to CON and ECC cycling and rates of adaptation to a novel (ECC) mode. The study of CSE should therefore be analysed for each participant individually in relation to relevant physiological variables and account for familiarisation to semi-recumbent ECC leg cycling.

P79-F Disrupted muscle cortical representations in amyotrophic lateral sclerosis studied by navigated TMS mapping

Background The search for biomarkers in amyotrophic lateral sclerosis (ALS) can provide pathophysiological insights and is important for early diagnosis and monitoring of the disease progression. Mapping muscle cortical representations using navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for probing corticospinal excitability. We aimed at studying nTMS map parameters as potential biomarkers in ALS. Methods We examined 12 ALS patients (4 women, age median 49, quartiles 40, 55) and 7 healthy controls (5 women, age median 37, quartiles 35, 41). Navigated TMS mapping was performed at the intensity of 110% of the resting motor threshold (RMT) with motor evoked potentials (MEPs) recorded from the abductor pollicis brevis muscle (APB). We used a 7 × 7 stimulation point grid, with 5 stimuli per cell in a pseudorandom order. We analyzed the RMT, the area of cells with at least one suprathreshold MEP, the area weighted by the probability of a suprathreshold MEP, and the area weighted by the mean MEP amplitude. Results The groups were not significantly different in age. The RMT was higher in ALS (p = 0.01, Mann-Whitney). Among the studied representation parameters, only the area weighted by the mean MEP amplitude showed a significant difference, with lower values in ALS patients than in controls (p = 0.02). Conclusions The results suggest that the extent of the APB motor representation in ALS patients is not significantly altered, whereas the excitability and amplitude-weighted area are reduced. Thus, it is important to study motor representation parameters other than the extent as potential ALS biomarkers. Funding RSF17-75-10062.

P77-S Early results of rTMS application in the recovery of motor function in the iSCI subjects

Background Patients with incomplete spinal cord injuries (iSCI) present impairment of motor and sensory functions associated with increased spasticity. The repetitive transcranial magnetic stimulation (rTMS) becomes widely used to potentiate the effects of long-lasting physical rehabilitation in the iSCI subjects. The purpose of this study was ascertaining the early changes in activity of motor muscles units and spinal cord efferent transmission studied with surface electromyography (sEMG) and motor evoked potentials (MEPs) recordings after five repeated sessions of rTMS applied every month to the iSCI subjects along with rehabilitation. Material and methods Twenty-eight subjects with iSCI at C2-Th12 levels were subjected to twenty sessions of rTMS for five months (three to four sessions every month). Subjects received 800 biphasic pulses (20 Hz, 2s trains, 28s ITI, 36–38% MSO) per day bilaterally over the primary motor cortex areas (MagVenture). sEMG at rest and during attempts of maximal contraction lasting five seconds and MEPs recordings from five observation periods were analyzed before and after rTMS. Results After five rTMS meetings a significant decrease in sEMG amplitudes recorded at rest and increase of mean sEMG amplitudes recorded during maximal contraction were observed. A moderate increase of mean MEPs amplitudes was observed on certain observation period. Conclusions rTMS provided decrease of spasticity as evaluated in sEMG recordings at rest and evoked simultaneous improvement of muscle’s motor units’ contractions as well as the efferent transmission in spinal pathways in the iSCI subjects. The study was supported by the Nicholls Spinal Injury Foundation, UK .

P44-S Sensorimotor integration in fibromyalgia

Background Fibromyalgia, is a chronic pain disorder, especially common in women, characterised by widespread pain, fatigue, sleep disorders and cognitive dysfunction. Recently prolonged somatosensory temporal discrimination values was shown in fibromyalgia patients compatible with impaired central sensory processing. However knowledge about sensorimotor integration in fibromyalgia is still lacking. Short latency afferent inhibition (SAI) is a phenomenon in which sensory stimulus modulates motor response. SAI is associated with cholinergic system, cognitive functions and sensorimotor integrity. In this study, sensorimotor integration is assessed with SAI paradigm in fibromyalgia patients for the first time. Methods 15 fibromyalgia patients and age-gender matched 15 healthy subjects were included in the study. Severity of pain and other symptoms were evaluated with visual analogue-scale and symptom severity scale respectively, cognitive functions were assessed with neuropsychological tests. Basal motor evoked potential (MEP) was recorded from right abductor pollicis brevis muscle at rest. SAI was obtained by right median nerve direct electrical current stimulation at twice the intensity of sensory threshold, 21 ms in advance of left motor cortical magnetic stimulation. Mean MEP amplitude ratio, recorded after single and conditioned stimulations, were calculated as SAI. Results No significant difference was found between the groups in terms of SAI values (Control group: 40.3 ± 23.4% inhibition; fibromyalgia group: 34.3 ± 25.6% inhibition, p = 0.51). There was no correlation between SAI values and severity of pain and other symptoms and cognitive function scores in the fibromyalgia group. Conclusion Even though sensory processing is impaired, sensorimotor integration and neural pathways that generate and modulate SAI remain intact in fibromyalgia.

P42-F New mobile application for adaptive threshold hunting in transcranial magnetic stimulation

Background Use of transcranial magnetic stimulation (TMS) in clinical neurophysiology has expanded as navigated TMS and repetitive TMS therapies have gained popularity. Clinical applications and scientific studies often apply adaptive threshold hunting (ATH) to determine motor threshold (MT). MT expresses corticospinal excitability, and it is used as a baseline stimulation intensity (SI) for modulatory, therapeutic and mapping procedures. Currently available tools for ATH are system-integrated tools and stand-alone software. System-integrated tools are rare, and the available stand-alone software require a dedicated computer adding to laboratory space-requirements. Material and methods I programmed an Android-based “bestPEST” mobile application for ATH to allow for a simple recording of MTs with sharing capabilities and logging. The application applies parameter estimation by sequential testing and was named after Pentlands BestPEST-routine ( Pentland , 1980 ). The application is free through Google Play. For comparison I applied Motor Threshold Assessment Tool 2.0 ( Awiszus and Borckardt, 2012 ) as a reference method. I used data gathered from 15 healthy volunteers to simulate realistic motor evoked potentials (MEPs) utilizing random generator which considered the experimentally measured individual mean MEP amplitude and variation at different SIs ( Kallioniemi et al., 2018 ). Results The MTs of the different methods agreed well (ICC ⩾ 0.989, p Conclusions The bestPEST application produced similar MTs with the reference method, and will help investigators to determine MTs and to log results.

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.

Comparing the effect between continuous infusion and intermittent bolus of rocuronium for intraoperative neurophysiologic monitoring of neurointervention under general anesthesia.

Background:Medical researchers have been reluctant to use neuromuscular blocking drugs (NMBD) during the use of intraoperative motor evoked potential (MEP) monitoring despite the possibility of patient movement. In this study, we compared the effects of no NMBD and continuous rocuronium infusion on the incidence of patient involuntary movement and MEP monitoring.Methods:In this study, 80 patients who underwent neuro intervention with MEP monitoring were randomly assigned into 2 groups. After an anesthetic induction, bolus of rocuronium 0.1 mg/kg was injected when it was needed (for patient involuntary movement or at the request of the surgeon) in group B, and 5 mcg/kg/min of rocuronium were infused in group I study participants. The incidence of patient involuntary movement and spontaneous respiration, the mean MEP amplitude, coefficient of variation (CV), the incidence of MEP stimulus change and train-of-four (TOF) count were compared.Results:The incidence of involuntary movement and spontaneous movement were measured as significantly lower in group I (P < .05). The incidence of undetectable MEP did not differ as measured in both groups. The means and CVs of MEP amplitude in all limbs were significantly lower in group I. The mean TOF counts from 30 to 80 min of operation were significantly higher in group B.Conclusion:We conclude that the continuous infusion of rocuronium effectively inhibited the involuntary movement and spontaneous respiration of the patient while enabling MEP monitoring.

S146. Does the mean MEP amplitude scale with the phase of pericentral μ-rhythm? A state-informed open-loop EEG-TMS study

The large trial-to-trial variability of MEP amplitude in response to TMS may be caused by fluctuations of the endogenous brain state at the time of stimulation. The phase of pericentral m-oscillations is thought to reflect pulsed inhibition at the positive peak, and facilitation (increased excitability) at the negative peak (Jensen and Mazaheri, 2010). Using state-informed EEG-TMS of the left motor hand area, we targeted the pericentral μ-rhythm at four different phases of the endogenous m-oscillations to investigate the state dependency of stimulation. We used real-time EEG analysis to perform state informed TMS, triggering single TMS pulses at a specific phase of the intrinsically expressed pericentral m-rhythm. Endogenous m- activity in the dominant left primary motor hand area was determined based on radial source projection using subject-specific head models and the EEG signal recorded from 63 surface electrodes. Corticospinal excitability was assessed by recording the motor evoked potential (MEP) of the right FDI muscle. Mean MEP amplitudes were compared for stimulation at low (positive peak, 0°) and high (trough, 180°) excitability states, as well as for rising (90°) and falling (270°) phase of the μ-oscillations (60 MEPs per condition). We investigated phase-dependent changes in MEP amplitude, using both biphasic (16 healthy young subjects; 14 females; age range: 20–34 years) and monophasic (15 healthy young subjects; 12 females; age range: 20–39 years) TMS. No pre-selection of subjects was performed to test the applicability of our setup to a general sample. Our state-informed open-loop EEG-TMS setup enabled successful state-informed TMS, hitting the desired phase with a mean absolute error of 48.6° across all trials. Using the MEP amplitude, we tested for differences between high (trough) and low (peak) excitability states, as well as between the rising and falling phase of the μ-oscillation. Neither monophasic TMS nor biphasic TMS yielded significant phase-dependent differences in mean MEP amplitude (two-sided t-tests, p > 0.4 for all comparisons). In a non-preselected sample of healthy young individuals, we did not observe any consistent modulation in mean MEP amplitude depending on the phase of the endogenous m-oscillation at the time of stimulation. Stringent pre-selection of subjects who have a strong and stable pericentral μ-rhythm or a restriction of TMS to periods during which μ-power is even higher, might reveal a significant modulation of MEP amplitude. Acknowledgements: Funded by the Novo Nordisk Foundation Interdisciplinary Synergy Program 2014 (“Biophysically adjusted state-informed cortex stimulation (BASICS); NNF14OC0011413).

S147. Effect of 1 Hz and 5 Hz rTMS over supplementary motor area on motor cortical excitability

Recent clinical trial of repetitive transcranial magnetic stimulation (rTMS) in Parkinson’s disease (PD) showed that both 1 Hz and 5 Hz rTMS over supplementary motor cortex (SMA) are effective for motor symptoms in PD. Previous studies have also indicated 1 Hz rTMS over primary motor cortex (M1) induces an inhibition whereas 5 Hz rTMS produce facilitation in excitability. Our aim is to clarify why both 1 Hz and 5 Hz rTMS, which have the opposite effects in cortical excitability, show the similar beneficial effects for PD. Recent clinical trial of repe. Subjects are twelve right-handed healthy volunteers (10 men, mean age 30.9 ± 6.5 years). rTMS consists of total 1000 pulses of 1 Hz, 5 Hz rTMS and realistic sham stimulation over SMA at intensity of 110% active motor threshold for the tibialis anterior (TA). We recorded motor-evoked potentials (MEP) from the right first dorsal interosseous (FDI) muscle and measured MEPs, short-intercortical inhibition (SICI) and intercortical facilitation (ICF) before, immediately (0), 15 and 30 min after the end of each condition. A two-way repeated measures ANOVA demonstrated a significant main effect of ‘condition’ (1 Hz, 5 Hz and sham) on the mean MEP amplitude (F2,87 = 4.72, P = 0.0113), whereas no significant effect on ‘time’ (T0-T30) (F2,87 = 0.589, P = 0.56) and ‘time’ × ‘condition’ interaction (F2,87=0.79. P = 0.535). Post hoc t tests revealed that decrease in MEP amplitude lasted at least for 15 min after the end of stimulation (0 min P = 0.0048; 15 min P = 0.0047). SICI and ICF did not show significant changes after 1 Hz rTMS. There were no significant changes either in MEP, SICI and ICF after 5 Hz rTMS and sham stimulation. 1 Hz SMA-rTMS decreased the amplitude of MEP evoked by a single-pulse TMS, whereas 5 Hz SMA-rTMS did not show significant changes. We suggest that 1 Hz and 5 Hz SMA-rTMS show different physiological after-effects, even though both conditions have a similar therapeutic effect for PD. It is presumable that these two rTMS have different mechanism for improving motor symptoms of PD. Further investigation is required to clarify the precise physiological effects of SMA-rTMS.

Analysis of mirror neuron system activation during action observation alone and action observation with motor imagery tasks.

This study aimed to explore the relationship between action observation (AO)-related corticomotor excitability changes and phases of observed action and to explore the effects of pure AO and concurrent AO and motor imagery (MI) state on corticomotor excitability using TMS. It was also investigated whether the mirror neuron system activity is muscle-specific. Fourteen healthy volunteers were enrolled in the study. EMG recordings were taken from the right first dorsal interosseous and the abductor digiti minimi muscles. There was a significant main effect of TMS timing (after the beginning of the movement, at the beginning of motor output state, and during black screen) on the mean motor evoked potential (MEP) amplitude. Mean MEP amplitudes for AO combined with MI were significantly higher than pure AO session. There was a significant interaction between session and TMS timing. There was no significant main effect of muscle on MEP amplitude. The results indicate that corticomotor excitability is modulated by different phases of the observed motor movement and this modulation is not muscle-specific. Simultaneous MI and AO enhance corticomotor excitability significantly compared to pure AO.

FV 5 Quadri-pulse theta burst stimulation using ultra-high frequency bursts at I-wave periodicity induces direction dependent bi-directional plasticity in human primary motor cortex

Background/Question Long-term potentiation (LTP) and long-term depression (LTD) are forms of cortical plasticity and are considered to be synaptic processes underlying learning and memory. Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce LTP-like and LTD-like effects in human primary motor cortex (M1), displayed by an increase or decrease in cortico-spinal excitability. Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS – so called quadri-pulse theta burst stimulation (qTBS) – at interstimulus intervals (ISI) that mimic I-wave periodicity (i.e. 1.5 ms/666 Hz) with an effective anterior-posterior (AP) and posterior-anterior (PA) current flow in the brain. Methods We investigated healthy volunteers (n = 12 per protocol) with 360 bursts of qTBS that was continuously given to M1 (i.e. 1440 full-sine pulses). QTBS consisted of repeated bursts of four biphasic TMS pulses (duration: 160 μ s) separated by ISI of 1.5 ms (666 Hz) and inter-burst intervals of 200 ms. (5 Hz). TMS was applied by a custom-made magnetic stimulator (IMETUM, Munich). Resting motor threshold (rMT), and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1mv (SI1mV) were measured before (Pre) qTBS, directly after (Post1), after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4). Results PA-qTBS at 666 Hz caused a decrease in mean MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean MEP amplitudes outlasting for approximately 60 min. As expected, baseline data of rMT prior to qTBS differed significantly, with higher thresholds in AP direction. Discussion/Conclusion Continuous qTBS at 666 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1.

Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents.

The objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS) to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment). We recruited 34 healthy adolescents (aged 13-19, 13 males, 21 females). To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP) elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min. All participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01) at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females. PAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

Corticospinal excitability predicts antidepressant response to rTMS

Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. Here we report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. Fifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. We measured MEP's to single pulse TMS using surface electromyography, before and after MC rTMS, and calculated MEP modulation as the change of mean MEP amplitude after MC rTMS. MEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. These findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS, and could inform future developments of rTMS to treat depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Modulation of motor cortex excitability predicts antidepressant response to prefrontal cortex repetitive transcranial magnetic stimulation

BackgroundRepetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. ObjectiveWe report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. MethodsFifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. MEP's were induced with single TMS pulses and measured using surface electromyography. MEP modulation was calculated as the change of mean MEP amplitude after MC rTMS. ResultsMEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. This was found both in univariate analyses (Spearman regression: rho = 0.43, p < 0.005) and a multivariable linear regression model (β = 0.25, p < 0.0001) controlling for baseline depression severity, age and resting motor threshold. ConclusionsThese findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS.