Increase In Motor Evoked Potentials Amplitude Research Articles

Physiological processes influencing motor-evoked potential duration with voluntary contraction.

Voluntary contraction leads to facilitation of motor-evoked potentials (MEPs) producing greater amplitude, shorter onset latency, and prolonged duration of the electromyography potential. Whereas hyperexcitability of spinal motoneurons and changes in descending corticospinal volleys have been proposed as putative mechanisms for changes in MEP amplitude and onset latency, a contribution of propriospinal interneurons, exerting modulatory effects on α-motoneurons, has been proposed as a potential explanation for prolongation of MEP duration. The aim of the present study is to gain further insight into the physiological processes underlying changes in MEP duration. Transcranial magnetic stimulation (TMS) studies were undertaken on 30 healthy controls, using a 90-mm circular coil, with MEPs recorded at rest and during facilitation, produced by contraction of abductor pollicis brevis. In the same experiment, short interval-intracortical inhibition (SICI) was recorded at rest. Facilitation resulted in a significant prolongation of MEP duration, which increased with stimulus intensity and was accompanied by an increase in MEP amplitude. The main effect (TMS intensity × activation state) was correlated with MEP duration (F = 10.9, P < 0.001), whereas TMS intensity (F = 30.5, P < 0.001) and activation state (F = 125.8, P < 0.001) in isolation were correlated with MEP amplitude. There was a significant inverse relationship between SICI and MEP duration at rest (R2 = 0.141, P = 0.041) and during facilitation (R2 = 0.340, P = 0.001). The present findings suggest that similar physiological processes mediate changes in the facilitated MEP duration and amplitude and that both cortical and nonpropriospinal spinal mechanisms contribute to changes in MEP duration.NEW & NOTEWORTHY Muscle contraction is associated with a significant increase in motor-evoked potential (MEP) duration and amplitude. Whereas the increase in MEP duration was linear, the amplitude increase exhibited a ceiling effect. Importantly, the MEP duration increase strongly correlated with short interval-intracortical inhibition, a biomarker of motor cortical function. This suggests that whereas similar physiological processes contribute to changes in facilitated MEP duration and amplitude, cortical mechanisms appear to contribute to MEP duration changes.

The Time-Course of Acute Changes in Corticospinal Excitability, Intra-Cortical Inhibition and Facilitation Following a Single-Session Heavy Strength Training of the Biceps Brachii.

Objective: The current understanding of acute neurophysiological responses to resistance training remains unclear. Therefore, we aimed to compare the time-course of acute corticospinal responses following a single-session heavy strength training (HST) of the biceps brachii (BB) muscle and provide quantifiable evidence based on the super-compensation model in an applied setting.Methods: Fourteen participants completed a counter-balanced, cross-over study that consisted of a single HST session (5 sets × 3 repetition maximum [RM]) of the BB and a control session (CON). Single- and paired-pulse transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude, intra-cortical facilitation (ICF), short-interval intra-cortical inhibition (SICI) and long-interval intra-cortical inhibition (LICI). Additionally, maximal muscle compound wave (MMAX) and maximal voluntary isometric contraction (MVIC) of the BB were taken. All measures were taken at baseline, immediately post and at 10, 20, 30 min and 1, 2, 6, 24, 48 and 72 h post-training.Results: A significant reduction in MEP amplitude was observed immediately post training (P = 0.001), while MVIC (P < 0.001) and MMAX (P = 0.047) were reduced for up to 30 min post-training. An increase in MVIC (p < 0.001) and MMAX (p = 0.047) was observed at 6 h, while an increase in MEP amplitude (p = 0.014) was only observed at 48 and 72 h. No changes in SICI, ICF and LICI were observed.Conclusion: Our results suggest that: (1) acute changes in corticospinal measures returned to baseline in a shorter timeframe than the current super-compensation model (24–48 h) and (2) changes in corticospinal excitability post-HST may be modulated “downstream” of the primary motor cortex (M1).

State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major Depression.

The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that alterations in synaptic plasticity represent a final common pathway underlying the clinical symptoms of the disorder. This study tested the hypotheses that patients with MDD show an attenuation of cortical synaptic long-term potentiation (LTP)-like plasticity in comparison with healthy controls, and that this attenuation recovers after remission. Cortical synaptic LTP-like plasticity was measured using a transcranial magnetic stimulation protocol, ie, paired associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10 criteria and 27 sex- and age-matched healthy controls. The amplitude of motor-evoked potentials was measured before and after PAS. Patients were assessed during the acute episode and at follow-up to determine the state- or trait-character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in motor-evoked potential amplitudes, was significantly attenuated in patients with an acute episode of MDD compared with healthy controls. Patients with remission showed a restoration of synaptic plasticity, whereas the deficits persisted in patients without remission, indicative for a state-character of impaired LTP-like plasticity. The results provide first evidence for a state-dependent partial occlusion of cortical LTP-like plasticity in MDD. This further identifies impaired LTP-like plasticity as a potential pathomechanism and treatment target of the disorder.

Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor.

Parkinson’s disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET.

EP 134. Effect of transcranial random noise stimulation depends on sensitivity to sham stimulation

Introduction Tranccranial random noise stimulation (tRNS) induces a consistent excitability increase lasting at least 60 min after 10 min of stimulation, as demonstrated by both physiological measures and behavioural Tasks ( Terney et al., 2008 ). The present study tests whether the tRNS-induced changes in corticospinal excitability varies as a function of individual differences in sensitivity to sham stimulation. Methods The study was approved by the Ethic Committee of the Faculty of Medicine Christian-Albrechts University Kiel. 24 participants, aged between 18 and 30 years, participated in the study. All subjects were right-handed according to the Edinburgh handedness inventory ( Oldfield, 1971 ). Stimulation techniques : tRNS (1 mA, 10 min) was applied through a pair of saline-soaked surface sponge electrodes (5 × 7 cm). The minimum period between sessions for a single subject was 7 days, and sessions were applied in randomized order. Monitoring of motor cortical excitability: To examine changes in corticospinal excitability, motor evoked potentials (MEPs) of the right first dorsal interosseous muscle (FDI) were recording following stimulation of its motor-cortical representation field by single-pulse TMS. For further analysis we divided three subgroups according to excitatory (‘Excitatory group’, n = 9), inhibitory (‘Inhibitory group’, n = 7) or no respond (‘Non responder group’, n = 8) to sham- stimulation (Wilcoxon signed-rank test for dependent sampling). For this, we compared the MEP-amplitude in mean of the three time points after stimulation with the MEP-amplitude in mean before. Results In all subjects the tRNS was well tolerated. The general finding of present study is that sensitivity to sham stimulation has impact on effect of tRNS; namely, ‘Excitatory group’ resulted in inhibition of tRNS, whereas inhibitory group shows excitation of tRNS. For ‘Non responder group’ the 1 mA tRNS resulted in a significant increase of MEP amplitudes compared to sham stimulation, which is consistent with the literature Conclusion Accounting for variation in individual sensitivity to sham stimulation, stimulation may influence the utility of tRNS as a tool for understanding brain-behavior interactions and as a method for clinical interventions.

113. Spinal Direct Current Stimulation modulates short intracortical inhibition

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We evaluated healthy subjects before (T0) and at different intervals (T1 and T2) after anodal, cathodal and sham tsDCS (20 ′ ,2.0 mA) applied over the thoracic spinal cord (T10–T12). We assessed changes in cortical Silent Period (cSP), paired-pulse short intracortical inhibition (SICI, interstimulus interval, ISI = 3 ms) and intracortical facilitation (ICF, ISI = 10 ms). Motor Evoked Potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. Cathodal tsDCS increased MEP amplitudes at ISI of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper ( p = 0.81) and lower limb ( p = 0.33). tsDCS modulates inhibitory GABA(A) ergic drive, as assessed by SICI, without interfering with cSP and ICF. tsDCS may be helpful to modulate spinal drive through non spinal mechanisms. tsDCS could represent an early rehabilitation strategy in patients with acute brain lesions and in the treatment of spinal diseases or pain syndromes.

Effects of negative autobiographical memories retrieval on corticospinal excitability and sensorimotor integration

IntroductionPrevious transcranial magnetic stimulation (TMS) studies indicate that exposing the subjects to an emotionally valent stimulus results in larger motor evoked potentials (MEP). Up to date, no TMS studies have been conducted in order to investigate the effect of personal memories with emotional value on corticospinal excitability.ObjectsTo investigate changes in corticospinal excitability and sensorimotor integration induced by retrieval of negative or neutral autobiographical memories (AM).AimsTo contribute to a further characterization of neural circuits involved during the evocation of negative AM.MethodsIn 12 healthy volunteers, we recorded motor evoked potentials (MEPs) elicited by TMS pulses during the retrieval of negative AM or neutral AM. Furthermore, we also tested Short-interval Intracortical Inhibition (SICI), Intracortical facilitation (ICF), Short and Long afferent Inhibition (SAI and LAI) in the two different experimental conditions.ResultsRetrieval of negative AM induced a larger increase in MEP amplitude (35.01%) compared to neutral AM (F(1,22) = 7.04, P = 0.013). Furthermore we showed that retrieval of Negative AM increasedn ICF (F(1,22) = 5, P = 0.03) and decrease SAI (F(1,22) = 7.04, P = 0.039). The other TMS parameters were different between conditions.ConclusionsOur results indicate that evocation of negative AM induce a complex modulation of excitatory and inhibitory sensorimotor networks. Further studies are needed to explore the link of these electrophysiological biomarkers with the strength, valence and specificity of negative AM.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols.

Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.

ID 394 – Polarity independent suppression of long-term associative plasticity in the human SMA–M1 network by simultaneous tDCS

Introduction Excitability and connectivity of the supplementary motor area (SMA) and primary motor cortex (M1) are important for motor rehabilitation after stroke. Previously, we demonstrated that paired associative stimulation of SMA and M1 (SMA–M1-PAS) by dual coil transcranial magnetic stimulation (TMS) may induce STDP-like plasticity in this network. Here, we tested the influence of transcranial direct current stimulation (tDCS) on SMA–M1 plasticity. Methods 15 healthy right-handed men participated in this pseudo-randomized, double-blinded, crossover study. Subjects received simultaneously two blocks of neuronavigated SMA–before-M1 PAS and anodal, cathodal or sham tDCS over the left M1 in three different sessions. Motor-evoked potentials (MEP) quantified changes in SMA–M1-Plasticity. Results SMA–M1-PAS resulted in an LTP-like MEP amplitude increase 60% of the subjects in the sham tDCS condition (‘responders’), but LTD-like MEP decreases in 15 subjects (‘non-responders’). In 7 of the 9 responders, the LTP-like MEP increase was suppressed or even turned into MEP depression both in the anodal and cathodal tDCS condition. In contrast, in all 6 non-responders anodal and cathodal tDCS led to less MEP suppression or even turned it into facilitation. Conclusion Our results demonstrate a negative interaction between tDCS-induced excitability modulation and PAS-induced associative plasticity in the human SMA–M1 network, independent of tDCS-polarity.

Abstract WP154: Bihemispheric Modulation of the Motor Cortex by Single-session Transcranial Direct Current Stimulation During Training in Subacute Stroke Patients

Introduction: Non-invasive transcranial direct current stimulation (tDCS) can induce polarity-specific changes in cortical excitability. Compared to unilateral anodal tDCS over the non-dominant motor cortex (M1), dual-hemispheric tDCS to the M1 may further accelerate motor reaction of the target hand and alter excitability of the corticospinal tract (CST). However, the effects and individual variability of bi-hemispheric tDCS to the M1 during motor training remain largely unclear in healthy and stroke subjects. Purpose: We assessed the hypothesis that bi-hemispheric tDCS during single-session motor training alter inter-hemispheric inhibition, CST excitability and bilateral cortical oscillations. Methods: We enrolled first-time, unilateral ischemic stroke patients between two and four weeks after stroke and matched healthy controls. They were subjected to two 20 min-sessions of dual-hemispheric tDCS (anode over non-dominant or ipsilesional M1, cathode over dominant or contralesional M1; 2mA for 20 mins) and sham tDCS (2mA for 2 mins) in a randomized crossover design during repetitive extension of the non-dominant or paretic extensor carpi radialis muscle. We compared the post-stimulation changes of motor evoked potentials (MEPs), ipsilateral silent period (iSP), short interval intracoritcal inhibition (SICI), as well as resting and unilateral finger lifting-related cortical oscillations by magnetoencephalography (MEG). Results: Compared to the sham tDCS, the dual-hemispheric tDCS significantly increased MEP amplitudes and reduced SICI at the anodal-stimulated M1, as well as decreased inter-hemispheric inhibition from the cathodal-stimulated M1 with shortened iSP for about 30 mins in healthy controls (n=8). In contrast, reduced MEP amplitudes were observed at the cathodal-stimulated M1. The tDCS effects on cortical oscillations and in stroke patients are currently under investigation. Conclusions: Task-concurrent dual tDCS may enhance activity-dependent motor plasticity in subacute stroke.

Cortical Hyperexcitability in Amyotrophic Lateral Sclerosis

Amyotrophiclateralsclerosis(ALS) isadevastatingdiseaseofthe motornervoussystem.Whilemost casesare sporadic, approximately5%to10%ofcasesare familial andresult frommutation in1ofmorethan25knownALS genes.Thesegenesspanasurprisingly broad range of molecular functions, including RNA metabolism, oxidative stress, axonal transport, autophagy, excitability, and immunity.Oneof thegreatmysteries in the field is thatmotorneurondiseaseresultsasaconvergentphenotypefrommutations in this diverse group of genes. Understanding this puzzle is likely keytooptimizingbothclinicaltrialsandpatienttreatmentbecause differentdrugsmayultimatelybenecessaryfortargetingspecific disease variants. Despitethemolecularheterogeneity, theclinicalmotorneuronphenotypesresultingfromthevariousgeneticmutationsand sporadic casesdifferonlymodestly. So toohasbeen thecaseon theneurophysiological level, inwhichBaeandcolleagues1have performedanimpressiveassemblyofstudiesshowingaxonaland cortical hyperexcitability in ALS. Lowermotor neuron studies useaspecializednerveconductionstudyprotocolcalled threshold tracking,whichwasdevelopedbyMogyoroset al.2Changes instimulus intensitynecessarytogeneratecompoundmotoractionpotentialsofapredeterminedamplitudearemonitoredduring the course of a recording, andprepulses and recovery cycle analysisareusedtomeasuredifferentcomponentsofaxonalexcitability.Cortical hyperexcitability inALShasbeen repeatedly demonstrated using transcranial magnetic stimulation (TMS), bothusing the traditional constant stimulus technique toelicit motor-evokedpotentials (MEPs)andbyadaptingthethresholdtracking approach to TMS. Inthis issueofJAMANeurology,Geevasingaandcolleagues3 extendedtheirobservationstoshowcorticalhyperexcitability in patients with familial ALS due to chromosome 9 open reading frame72(c9orf72)hexanucleotidegenerepeatexpansion,which is themost commongenetic causeofALSand is responsible for about5%ofapparentsporadicALSand40%offamilialALScases. The findings are quite similar to those in sporadic and superoxidedismutase(SOD1)genefamilialALS,with increasedexcitabilitymanifestedmost clearlyusingpaired testing. Short intracortical inhibitionreferstotheincreaseinMEPthreshold(ordecrease inMEPamplitude) resulting fromaconditioningprepulsea few millisecondsbefore a test pulse. In contrast, intracortical facilitationisthereductioninthreshold(orincreaseinMEPamplitude) whentheconditioningprepulseprecedesthetestpulsebyabout 15milliseconds.4The reduction in short intracortical inhibition and increase in intracortical facilitationare2of themostprominentTMSfindings inALS.Otherdisease featuressharedbyboth sporadicandc9orf72 familialALS includereducedrestingmotor threshold, increased MEP amplitude, decreased cortical silent periodduration, and increased centralmotor conduction time. Thecorticalandaxonalexcitabilitystudieshaveshownaremarkableconsistencyof findings inbothpatientswithsporadic ALSandpatientswithfamilialALSand,thus,raisequestionsabout how different molecular mechanisms converge to produce changes inneuronalexcitability inALSandwhether researchers can leverage the consistent neurophysiological hyperexcitabilityphenotypetoreveal informationandpotential targetsthatare broadlyrelevantacrossALSvariants.Theclinical resultssuggest anopportunitytoreexaminehyperexcitabilityusinganimalmodelsandmore-reductionistsystemstoaddressexcitabilitymechanisms.Suchworkcouldpotentially reveal specific ionchannels or cellular pathways that underlie the neurophysiological phenotype.Thecomplexityofdifferentneuronal andnonneuronal cellularsubtypesthatgiverisetoandmodulatethedifferentTMS and nerve conduction study measurements justify additional basic exploration.However, technical considerationshave limited theuseof theneurophysiological techniques inmice, both with regard to challenges inperforming tests aswell as artifacts owing to sedation in interpreting test results. In animalmodels of SOD1 ALS, most studies have supported increased motor neuronactivity5;however,others, includingastudyusinginvivo recordings of specificmotor neuron pools, have not.6 Inmotor neuronsmadefromALS-inducedpluripotent stemcells,hyperexcitability ispresentbut thendecreaseswith longcultureperiods, potentially because of worsening neuronal health and a depolarization-inducedblockofmotorneuronfiring.7-9 Invitro studies have identified roles of persistent sodium currents and delayed-rectifierpotassiumcurrents in increasingmotorneuron excitability in ALS. Futurework using specific channelmodifiers may help elucidate the channels, receptors, andmolecular scaffolding underlying clinical neurophysiological cortical and axonal hyperexcitability. Webelievethebulkoftheevidencesupportshyperexcitability as aprimaryprocess inALSasopposed toanadaptiveone.10 Thepresenceofsignsofhyperexcitability,suchasfasciculations, beforeotherclinicalsymptomsismoreconsistentwithaprimary roleforhyperexcitability.Similarly,thehyperexcitabilityobserved inbothprenatalSOD1motorneuronsandALSstemcell–derived motorneuronsofmultiplegeneticvariants, inwhichdecreasing excitability improvesmotorneuronsurvival andreducesendoplasmicreticulumstressinvitro,bothsupportaprimaryupstream Author Audio Interview at jamaneurology.com

State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major Depression.

The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that alterations in synaptic plasticity represent a final common pathway underlying the clinical symptoms of the disorder. This study tested the hypotheses that patients with MDD show an attenuation of cortical synaptic long-term potentiation (LTP)-like plasticity in comparison with healthy controls, and that this attenuation recovers after remission. Cortical synaptic LTP-like plasticity was measured using a transcranial magnetic stimulation protocol, ie, paired associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10 criteria and 27 sex- and age-matched healthy controls. The amplitude of motor-evoked potentials was measured before and after PAS. Patients were assessed during the acute episode and at follow-up to determine the state- or trait-character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in motor-evoked potential amplitudes, was significantly attenuated in patients with an acute episode of MDD compared with healthy controls. Patients with remission showed a restoration of synaptic plasticity, whereas the deficits persisted in patients without remission, indicative for a state-character of impaired LTP-like plasticity. The results provide first evidence for a state-dependent partial occlusion of cortical LTP-like plasticity in MDD. This further identifies impaired LTP-like plasticity as a potential pathomechanism and treatment target of the disorder.

Ipsilateral M1 transcranial direct current stimulation increases excitability of the contralateral M1 during an active motor task: Implications for stroke rehabilitation

Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) elicits an increase in cortical excitability that outlasts the period of stimulation. However, little is known about effects of a-tDCS on the contralateral M1 during and after ipsilateral M1 stimulation. Therefore, we investigated the changes in corticospinal excitability and inhibition of the left M1 during and after 20 min of a-tDCS to the right M1. Eight healthy participants received real (2 mA) and SHAM a-tDCS to the right M1 randomized across 2 testing sessions. Single- and paired-pulse transcranial magnetic stimulation (TMS) was applied to the left M1 to measure changes motor-evoked potential (MEP) amplitude from the right extensor carpi radialis (ECR) at 130% of resting and active motor threshold, cortical silent period (CSP) and short-interval cortical inhibition (SICI). Active motor threshold was measured during a wrist extension contraction that was less than 5% of maximal electromyographic activation of the ECR. TMS measurements were recorded at baseline, every 5 min for 20 min during and 10 min after a-tDCS. The results showed a significant ( P < 0.05) increase in left M1 MEP amplitude and reduction in CSP duration during (10 and 15 min) and after (immediately and 10 min post) a-tDCS to the right M1, only during the active motor task. A significant reduction ( P < 0.05) in SICI during the active task was also found immediately and 10 min post a-tDCS. No significant changes in MEP amplitude, CSP and SICI were observed in the resting or active task during SHAM tDCS. The increase in left M1 MEP amplitude and reduction in CSP and SICI during and after 20 min of right M1 a-tDCS is most likely to be attributed to a reduction in interhemispheric inhibition that is modulated by a-tDCS during the performance of an active task. Our findings may have significant implications for stroke rehabilitation whereby the application of a-tDCS on the contralesional M1 during neurorehabilitation of the paretic limb may be beneficial for inducing neuroplasticity of the ipsilesional M1 to improve motor function.

P67. Effects of static magnetic fields on the human motorcortex

Transcranial static magnetic field stimulation (tSMS) has been introduced as an easy applicable, non-invasive neurostimulation technique with no side-effects like pain, discomfort or risks of seizures. Up to now, the two studies applying tSMS to the human motor cortex (Oliviero et al., 2011; Silbert et al., 2013) showed inhibitory effects on cortical excitability. In both experiments, decreased motor evoked potentials (MEPs) for a time period lasting 3–6min following stimulation were reported. In our study we aimed to replicate the results in the motor system. Twelve healthy, right-handed subjects (5 men, mean age 22.9years) participated in the study. Motor cortex excitability was measured using single- pulse transcranial magnetic stimulation (TMS) before and after a 15min period of tSMS application. Surface electromyography (EMG) was recorded from the right first dorsal interosseous (FDI). First, a coil position was defined on the left M1 to evoke the largest MEP. Then, a TMS intensity was defined to elicit MEPs of about 1mV. As a baseline measurement, 100 MEPs were recorded with an interval of 5–8s between pulses, covering about 12min. For tSMS, a cylindrical Neodym magnet of 30mm height and 45mm diameter (150mT at 2cm distance) was held over the left M1 for 15min. During stimulation, participants performed an acoustic oddball task to standardize brain activity. Following tSMS, 100 MEPs were recorded to evaluate possible long-lasting after-effects. Pre- and post-stimulation pulses were grouped together in blocks of 2min each. Time point post1 started 2min after SMS application. Data were subjected to an rmANOVA with the within factors STIMULATION (pre, post) and TIME (1, 2, 3, 4, 5, 6). There was a main effect of the factor TIME ( F 5,55 =2.56, p F 5,50 =3.84, p The expected inhibitory effect of the stimulation could not be shown in our experiment. We found an unspecific increase in MEP amplitude of male subjects after about 50 single pulses (8min) that occurred both in the control measurement (pre) as well as after tSMS exposure. We are planning to replicate both aspects of the present study in order to clarify the postulated tSMS effect as well as the observed sex-specific MEP increase over time.

P149. Suppression of LTP-like associative plasticity in the human SMA–M1 network by simultaneous tDCS

Introduction Excitability and connectivity in the human motor network comprising the supplementary motor area (SMA) and primary motor cortex (M1) are important for voluntary movement generation and rehabilitation of lost motor function after stroke. Previously, we demonstrated that paired associative stimulation of SMA and M1 (SMA–M1-PAS) by dual coil transcranial magnetic stimulation (TMS) may induce LTP-like plasticity in this network (Arai et al., 2011. J Neurosci 31:15376–83). Here, we tested the influence of simultaneous modulation of general network excitability by transcranial direct current stimulation (tDCS) on associative SMA–M1 plasticity. Methods 12 healthy right-handed male subjects took part in this pseudo-randomized,single-blinded, crossover study. Subjects received two blocks (spaced by 5 min) of 50 pairs of neuronavigated SMA-before-M1 PAS at an interstimulus interval of 6 ms and intertrial interval of 5 s. Simultaneously we applied anodal, cathodal, or sham tDCS over the left M1 in three different sessions, at least 1 week apart. Associative SMA–M1 plasticity was quantified by changes in (i) motor-evoked potentials (MEP) in the right first dorsal interosseus muscle, and (ii) SMA-to-M1 connectivity (ratio of SMA-conditioned/unconditioned MEPs), at baseline versus for up to two hours after the intervention. Results SMA–M1-PAS resulted in an expected LTP-like MEP amplitude increase in 9 of 12 subjects in the sham tDCS condition. In 7 of these 9 SMA–M1-PAS responders, the LTP-like MEP amplitude increase was suppressed or even turned into depression both in the anodal and cathodal tDCS condition. In contrast, in all three non-responders anodal and cathodal tDCS led to less MEP suppression or even turned it into facilitation. Likewise, in 7 (anodal tDCS) and 6 (cathodal tDCS) of the 8 subjects who showed a facilitation of SMA-to-M1 connectivity in the sham tDCS condition this connectivity was reduced in the anodal and cathodal tDCS conditions, whereas it was less reduced or even facilitated in 2 (anodal tDCS) and all (cathodal tDCS) of the 4 subjects showing a reduction of SMA-to-M1 connectivity in the sham condition. Conclusion Our results demonstrate a reversing interaction between general network excitability modulation by tDCS and associative plasticity in the human SMA–M1 network, independent of the polarity of tDCS.

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition.

Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF). Healthy subjects were studied before (T0) and at different intervals (T1 and T2) after anodal, cathodal, and sham tsDCS (20', 2.0 mA) applied over the thoracic spinal cord (T10-T12). We assessed changes in cSP, SICI (interstimulus interval, ISI = 3 ms) and ICF (ISI = 10 ms). Motor-evoked potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. Cathodal tsDCS increased MEP amplitudes at interstimulus interval of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper limb (p = 0.81) and lower limb (p = 0.33). tsDCS modulates inhibitory GABA(A)ergic drive, as assessed by SICI, without interfering with cSP and ICF. The possibility to interfere with cortical processing makes tsDCS a useful approach to modulate spinal drive through nonspinal mechanisms. tsDCS could also represent an early rehabilitation strategy in patients with acute brain lesions, when other noninvasive brain stimulation (NIBS) tools are not indicated due to safety concerns, as well as in the treatment of spinal diseases or pain syndromes.

Effects of Hand Vibration on Motor Output in Chronic Hemiparesis

Background.Muscle vibration has been shown to increase the corticospinal excitability assessed by transcranial magnetic stimulation (TMS) and to change voluntary force production in healthy subjects.Objectives.To evaluate the effect of vibration on corticospinal excitability using TMS and on maximal motor output using maximal voluntary contraction (MVC) in individuals with chronic hemiparesis.Methodology.Nineteen hemiparetic and 17 healthy control subjects participated in this study. Motor evoked potentials (MEPs) and MVC during lateral pinch grip were recorded at first dorsal interosseous muscle in a single session before, during, and after one-minute trials of 80 Hz vibration of the thenar eminence.Results.In hemiparetic subjects, vibration increased MEP amplitudes to a level comparable to that of control subjects and triggered a MEP response in 4 of 7 patients who did not have a MEP at rest. Also, vibration increased the maximal rate of force production (dF/dtmax⁡) in both control and hemiparetic subjects but it did not increase MVC.Conclusion.Motor response generated with a descending cortical drive in chronic hemiparetic subjects can be increased during vibration. Vibration could be used when additional input is needed to reveal motor responses and to increase rate of force generation.

Enhanced motor cortex excitability after spinal cord injury.

Enhanced motor cortex excitability after spinal cord injury.

Differential modulation of motor cortex plasticity in skill- and endurance-trained athletes.

Extensive evidence exists that regular physical exercise offers neuroplastic benefits to the brain. In this study, exercise-specific effects on motor cortex plasticity were compared between 15 skilled and 15 endurance trained athletes and 8 controls. Plasticity was tested with a paired associative stimulation (PAS) protocol. PAS is a non-invasive stimulation method developed to induce bidirectional changes in the excitability of the cortical projections to the target muscles. Motor cortex excitability was assessed by motor-evoked potentials (MEPs) in the task-relevant soleus muscle, elicited with transcranial magnetic stimulation, before and following PAS. To test for changes at the spinal level, soleus short latency stretch reflexes (SLSR) were elicited before and after PAS. PAS induced a significant (76 ± 83 %) increase in MEP amplitude in the skill group, without significant changes in the endurance (-7 ± 35 %) or control groups (21 ± 30 %). Baseline MEP/post MEP ratio was significantly different between the skill and endurance groups. SLSR remained unchanged after the PAS intervention. The possible reason for differential motor cortex plasticity in skill and endurance groups is likely related to the different training-induced adaptations. The findings of the current study suggest that long-term skill training by skill group induced preferable adaptations in the task-related areas of the motor cortex because increased plasticity is known to enhance motor learning.

Brain-state-dependent non-invasive brain stimulation and functional priming: a hypothesis.

Brain-state-dependent non-invasive brain stimulation and functional priming: a hypothesis.