Motor Corticospinal Excitability Research Articles

The effect of transcranial ultrasound pulse repetition frequency on sustained inhibition in the human primary motor cortex: A double-blind, sham-controlled study

BackgroundNon-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. ObjectiveTo investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. MethodsT1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. ResultsA significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. ConclusionThis study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications.

Prolonged continuous theta burst stimulation increases motor corticospinal excitability and intracortical inhibition in patients with neuropathic pain: An exploratory, single-blinded, randomized controlled trial

ObjectivesA new paradigm for Transcranial Magnetic Stimulation (TMS), referred to as prolonged continuous theta burst stimulation (pcTBS), has recently received attention in the literature because of its advantages over high frequency repetitive TMS (HF-rTMS). Clinical advantages include less time per intervention session and the effects appear to be more robust and reproducible than HF-rTMS to modulate cortical excitability. HF-rTMS targeted at the primary motor cortex (M1) has demonstrated analgesic effects in patients with neuropathic pain but their mechanisms of action are unclear and pcTBS has been studied in healthy subjects only. This study examined the neural mechanisms that have been proposed to play a role in explaining the effects of pcTBS targeted at the M1 and DLPFC brain regions in neuropathic pain (NP) patients with Type 2 diabetes. MethodsForty-two patients with painful diabetic neuropathy were randomized to receive a single session of pcTBS targeted at the left M1 or left DLPFC. pcTBS stimulation consisted of 1,200 pulses delivered in 1 min and 44 s with a 35–45 min gap between sham and active pcTBS stimulation. Both the activity of the descending pain system which was examined using conditioned pain modulation and the activity of the ascending pain system which was assessed using temporal summation of pain were recorded using a handheld pressure algometer by measuring pressure pain thresholds. The amplitude of the motor evoked potential (MEP) was used to measure motor corticospinal excitability and GABA activity was assessed using short (SICI) and long intracortical inhibition (LICI). All these measurements were performed at baseline and post-pcTBS stimulation. ResultsFollowing a single session of pcTBS targeted at M1 and DLPFC, there was no change in BPI-DN scores and on the activity of the descending (measured using conditioned pain modulation) and ascending pain systems (measured using temporal summation of pain) compared to baseline but there was a significant improvement of >13% in perception of acute pain intensity, increased motor corticospinal excitability (measured using MEP amplitude) and intracortical inhibition (measured using SICI and LICI). ConclusionIn patients with NP, a single session of pcTBS targeted at the M1 and DLPFC modulated the neurophysiological mechanisms related to motor corticospinal excitability and neurochemical mechanisms linked to GABA activity, but it did not modulate the activity of the ascending and descending endogenous modulatory systems. In addition, although BPI-DN scores did not change, there was a 13% improvement in self-reported perception of acute pain intensity.

Parkinson's Disease-related Pains are Not Equal: Clinical, Somatosensory and Cortical Excitability Findings in Individuals With Nociceptive Pain

Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = −.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PerspectiveThis work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS

BackgroundIntermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). ObjectiveUsing pTMS, we tested the hypothesis that monophasic iTBS would induce a stronger plasticity effect than biphasic, measured as induced increases in motor corticospinal excitability. MethodsIn a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as increases in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 min after iTBS. ResultsBoth monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, linear mixed effects (LME) models showed that the iTBS condition had a significant effect on the MEP amplitude (χ2 (1) = 27.615, p < 0.001) with monophasic iTBS leading to significantly stronger plasticity than biphasic iTBS (t (693) = 2.311, p = 0.021). Control vertex iTBS had no effect. ConclusionsIn this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.

Motor corticospinal excitability abnormalities differ between distinct chronic low back pain syndromes

ObjectivesIt is not known whether cortical plastic changes reported in low-back pain (LBP) are present in all etiologies of LBP. Here we report on the assessment of patients with three LBP conditions: non-specific-LBP (ns-LBP), failed back surgery syndrome (FBSS), and sciatica (Sc). MethodsPatients underwent a standardized assessment of clinical pain, conditioned pain modulation (CPM), and measures of motor evoked potential (MEPs)-based motor corticospinal excitability (CE) by transcranial magnetic stimulation, including short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Comparisons were also made with normative data from sex- and age-matched healthy volunteers. Results60 patients (42 women, 55.1±9.1 years old) with LBP were included (20 in each group). Pain intensity was higher in patients with neuropathic pain [FBSS (6.8±1.3), and Sc (6.4±1.4)] than in those with ns-LBP (4.7±1.0, P<0.001). The same was shown for pain interference (5.9±2.0, 5.9±1.8, 3.2±1.9, P<0.001), disability (16.4±3.3, 16.3±4.3, 10.4±4.3, P<0.001), and catastrophism (31.1±12.3, 33.0±10.4, 17.4±10.7, P<0.001) scores for FBSS, Sc, and ns-LBP groups, respectively. Patients with neuropathic pain (FBSS, Sc) had lower CPM (-14.8±1.9, -14.1±16.7, respectively) compared to ns-LBP (-25.4±16.6; P<0.02). 80.0% of the FBSS group had defective ICF compared to the other two groups (52.5% for ns-LBP, P=0.025 and 52.5% for Sc, P=0.046). MEPs (140%-rest motor threshold) were low in 50.0% of patients in the FBSS group compared to 20.0% of ns-LBP (P=0.018) and 15.0% of Sc (P=0.001) groups. Higher MEPs were correlated with mood scores (r=0.489), and with lower neuropathic pain symptom scores(r=-0.415) in FBSS. ConclusionsDifferent types of LBP were associated with different clinical, CPM and CE profiles, which were not uniquely related to the presence of neuropathic pain. These results highlight the need to further characterize patients with LBP in psychophysics and cortical neurophysiology studies.

Transcranial Magnetic Stimulation Following a Paired Associative Stimulation Protocol Based on a Video Game Neuromodulates Cortical Excitability and Motor Behavior.

Transcranial Magnetic Stimulation (TMS) can be used to modulate cortico-spinal excitability following a paired associative stimulation (PAS) protocol. Movement-related cortical stimulation (MRCS) is a PAS protocol based on the synchronization of a single-pulse TMS with a movement task. However, plasticity and motor performance potentiation due to MRCS has been related exclusively to single-movement tasks. In order to unveil the effects of an MRCS protocol in complex movements, we applied PAS synchronized with a movement-related dynamic task (MRDT) with a customized video game. In 22 healthy subjects, we measured the reaction time (RT), trajectory error (TE), and the number of collected and avoided items when playing the custom video game to evaluate the task motor performance. Moreover, we assessed the recruitment curve of Motor Evoked Potentials (MEPs) with five different intensities to evaluate the motor corticospinal excitability. MEPs were recorded in Abductor Pollicis Brevis (APB) and Abductor Digiti Minimi (ADM), before, right after, and 30 min after the PAS intervention, in an active versus sham experimental design. The MRCS PAS intervention resulted in RT reduction, and motor corticospinal excitability was modulated, reflected as significant MEP amplitude change at 110% RMT intensity in ADM and at 130% RMT intensity in APB. RTs and ADM MEP amplitudes correlated positively in specific time and intensity assessments. We conclude that the proposed PAS protocol facilitated RT performance in a complex task. This phenomenon might be useful to develop neurorehabilitation strategies with complex movements, similar to activities of daily living.

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

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

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.

Early Right Motor Cortex Response to Happy and Fearful Facial Expressions: A TMS Motor-Evoked Potential Study.

The ability to rapidly process others’ emotional signals is crucial for adaptive social interactions. However, to date it is still unclear how observing emotional facial expressions affects the reactivity of the human motor cortex. To provide insights on this issue, we employed single-pulse transcranial magnetic stimulation (TMS) to investigate corticospinal motor excitability. Healthy participants observed happy, fearful and neutral pictures of facial expressions while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed an enhancement of corticospinal excitability for the observation of happy and fearful emotional faces compared to neutral expressions specifically in the right hemisphere. Interindividual differences in the disposition to experience aversive feelings (personal distress) in interpersonal emotional contexts predicted the early increase in corticospinal excitability for emotional faces. No differences in corticospinal excitability were observed at the later time (300 ms) or in the left M1. These findings support the notion that emotion perception primes the body for action and highlights the role of the right hemisphere in implementing a rapid and transient facilitatory response to emotional arousing stimuli, such as emotional facial expressions.

Impact of a Carbohydrate Mouth Rinse on Quadriceps Muscle Function and Corticomotor Excitability.

The purpose of this investigation is to determine the effects of different forms of a CHO MR on quadriceps muscle performance and corticospinal motor excitability. Ten subjects (5 females, 5 males; 25±1 years; 1.71±0.03 m 73±5 kg) completed 4 trials. A different MR condition was applied during each trial (Placebo (PLA), 6.4% glucose (GLU), 6.4% maltose (MAL), 6.4% maltodextrin (MDX)). Maximal voluntary contraction (MVIC) of the right quadriceps and motor-evoked potential (MEP) of the right rectus femoris was determined pre (10 min), immediately after, and post (10 min) MR. MEP was precipitated by transcranial magnetic stimulation (TMS) during muscle contraction (50% of MVIC). MR was held in the mouth for 20 s and treatments were applied using a Latin square design. The relative change in MEP from pre-measures was different across treatments (p=0.025) but was not different across time (p=0.357). Relative change in MEP was greater for all CHO conditions immediately after (GLU=2.58±5.33%; MAL=3.92±3.90%; MDX=18.28±5.57%) and 10 min after (GLU=14.09±13.96%; MAL=8.64±8.67%; MDX=31.54±12.77%) MR compared to PLA (Immediately after=-2.19±4.25%, 10 min=-13.41±7.46%). The relative change in MVC was greater for CHO conditions immediately (GLU=3.98±2.49%; MAL=5.89±2.29.90%; MDX=7.66±1.93%) and 10 min after (GLU=7.22±2.77%; MAL=10.26±4.22%; MDX=10.18±1.50%) MR compared to PLA (Immediately after=-3.24±1.50%, 10 min=-6.46±2.22%). CHO MR increased corticospinal motor excitability and quadriceps muscle performance immediately and 10 min after application; however, the form of CHO used did not influence this response.

Motor corticospinal excitability: a novel facet of pain modulation?

Introduction:Increase in excitability of the primary motor cortex (M1) is associated with pain inhibition by analgesics, which is, in turn, associated with the psychophysical antinociceptive pain modulation profile. However, the relationship between neurophysiological M1 excitability and psychophysical pain modulation has not yet been explored.Objectives:We aim to study these relationships in healthy subjects.Methods:Forty-one young healthy subjects (22 women) underwent a wide battery of psychophysical testing that included conditioned pain modulation (CPM) and pain temporal summation, and a transcranial magnetic stimulation neurophysiological assessment of the motor corticospinal excitability, including resting motor threshold, motor-evoked potentials (MEPs), and cortical silent period.Results:Increased motor corticospinal excitability in 2 parameters was associated with more efficient CPM: (1) higher MEP amplitude (r = −0.574; P_Bonferroni = 0.02) and (2) longer MEP duration (r = −0.543; P_Bonferroni = 0.02). The latter also correlated with the lower temporal summation magnitude (r = −0.421; P = 0.007); however, on multiplicity adjustment, significance was lost.Conclusions:Increased corticospinal excitability of the primary motor cortex is associated with more efficient inhibitory pain modulation as assessed by CPM, in healthy subjects. Motor-evoked potential amplitude and duration may be considered as an additional, objective and easy to measure parameter to allow for better individual assessment of pain modulation profile.

Impact of a Carbohydrate Mouth Rinse on Motor Performance and Corticospinal Motor Excitability

Application of a carbohydrate (CHO) mouth rinse (MR) prior to exercise has been shown to improve physical performance and facilitate corticospinal motor excitability. It is unclear if different forms of CHO impact this phenomenon. PURPOSE: The purpose of this investigation is to determine the effects of different forms of a CHO MR on muscular performance and corticospinal motor excitability. METHODS: Ten normal healthy subjects (5 females, 5 males; 25±1 years; 1.71±0.03 m 73±5 kg) completed 4 trials each separated by at least 48 hours. A different MR condition was applied during each trial (Placebo (PLAC), 6.4% glucose (GLU), 6.4% maltose (MAL), 6.4% maltodextrin (MDX)). Maximal voluntary contraction (MVC) of the right knee extensors and motor-evoked potential (MEP) of the right vastus medialis was determined pre (10 min before), immediately after, and post (10 min after) application of the MR. MEP was precipitated by applying transcranial magnetic stimulation (TMS) during muscle contraction (50% of MVC). The MR was held in the mouth for 20 sec and MR treatments were applied using a Latin square design. RESULTS: No differences were found in the change of MEP from pre to immediately after the MW across the conditions (PLAC=1.5±4.4%; GLU=-6.2±11.2%; MAL=3.9±3.4%; MDX=8.9±7.9%). In contrast, the increase in MEP was greater at the post time point in CHO conditions (GLU=-11.3±14.7%, p=0.01; MAL=12.9±7.9%, p=0.07; MDX=28.0±14.4%, p=0.02) as compared to PLAC (PLAC=-14.3±7.8%). MVC was similar at pre (PLAC=260±26 Nm; GLU=241±19 Nm MAL=245±21 Nm; MDX=248±25 Nm), after (PLAC=269±26 Nm; GLU=249±18 Nm MAL=257±19 Nm; MDX=250±23 Nm), and 10 min after (PLAC=262±28 Nm; GLU=256±17 Nm MAL=269±25 Nm; MDX=253±21 Nm) the MW. CONCLUSIONS: CHO MR increased corticospinal motor excitability 10 min after application; however, the form of CHO used did not influence this response. The increase in corticospinal motor excitability did not translate into an improvement in motor performance.

Development of corticospinal motor excitability and cortical silent period from mid-childhood to adulthood – a navigated TMS study

We characterized the maturation of the excitability of the motor cortex and corticospinal tract from childhood to adulthood using electric field (EF) navigated TMS and correlated the results with manual dexterity. Both hemispheres of healthy right-handed children (6-9 years, n=10), preadolescents (10-12 years, n=13), adolescents (14-17 years, n=12) and young adults (22-34 years, n=12) of both genders were examined. The optimal cortical representation site and resting motor threshold (rMT) were determined for the abductor pollicis brevis muscle. Motor-evoked potential (MEP) latencies and amplitudes in relaxed and active states, input-output curves and silent period (SP) durations were determined. Manual dexterity was assessed with the Box and Block Test. rMT (in terms of maximal stimulator output or EF strength) decreased with age (P<0.001) and stabilized when reaching adolescence. The MEP amplitude (P=0.037) and latency increased (P<0.001) with age. Input-output curves showed age-dependent changes in several parameters. SP duration decreased with age (P<0.001), and demonstrated hemispheric asymmetry in the children (P=0.030). Manual dexterity correlated negatively with rMT (P<0.001). The excitation/inhibition balance develops with age and correlates with manual dexterity. Strong corticospinal inhibition was observed in the children and this was found to decrease with age. Interhemispheric asymmetry was only observed for SP duration in the children. Knowledge of normal development is crucial for the understanding of developmental disabilities and using estimates of effective EF may be advantageous in future pediatric studies.

P181 tACS frequency dependent changes in corticospinal excitability revealed using TMS mapping

Transcranial alternating current stimulation (tACS) has been suggested to entrain neuronal oscillations leading to changes in motor behaviour and corticospinal excitability (CSE). Reports characterising the effect of tACS on CSE are equivocal despite tACS after-effects being ascribed to changes in synaptic plasticity. All studies to date assessing tACS-induced CSE have used single pulse TMS at a single intensity. However, this method might not reveal shifts in the corticospinal representation or unequal expansion of the cortical representation. The present study aimed to investigate the effect of tACS on CSE using TMS maps, with a stimulation frequency within (20 Hz) and outside (140 Hz) the traditional beta band for the motor system. Eleven participants visited the lab on three separate occasions to receive 10 min of sham stimulation or tACS at 1 mA and either 20 or 140 Hz. Stimulating electrodes (4 × 4 cm) were placed over the motor representation of the first dorsal interosseous (FDI) muscle and contralateral orbit. A novel rapid TMS mapping method was employed to assess the FDI motor representation before and 10–35 min after tACS. The difference in TMS map area and centre of gravity (COG) before and after stimulation were analysed. On average, map area increased after 140 Hz and decreased after 20 Hz tACS. A repeated measures ANOVA revealed no significant effect for either FREQUENCY (P = 0.07), TIME (P = 0.86) or a FREQUENCY’TIME interaction (P = 0.34). Based on variability in the baseline measures we identified five participants with increased map area following 140 Hz tACS, whilst following 20 Hz tACS map area decreased for three participants. On average COG was displaced 5 ± 3 mm in the post maps compared to the baseline map. However, COG were not systematically displaced in either the x (xDisp: FREQUENCY: P = 0.38, TIME: P = 0.83, FREQUENCY’TIME: P = 0.83) or y direction (yDisp: FREQUENCY: P = 0.23, TIME: P = 0.97, FREQUENCY’TIME: P = 0.94) In conclusion, no main effect of tACS was found on CSE using TMS mapping. Nonetheless, these pilot data suggest that 10 min of 20 Hz stimulation may inhibit excitability and 140 Hz stimulation may facilitate excitability, in line with our hypothesis. This effect is masked by significant variability in the response with only a third to a half of the participants showing a changes in CSE following tACS, which is in line with reports for tDCS.

When anger dominates the mind: Increased motor corticospinal excitability in the face of threat

Threat demands fast and adaptive reactions that are manifested at the physiological, behavioral, and phenomenological level and are responsive to the direction of threat and its severity for the individual. Here, we investigated the effects of threat directed toward or away from the observer on motor corticospinal excitability and explicit recognition. Sixteen healthy right‐handed volunteers completed a transcranial magnetic stimulation (TMS) task and a separate three‐alternative forced‐choice emotion recognition task. Single‐pulse TMS to the left primary motor cortex was applied to measure motor evoked potentials from the right abductor pollicis brevis in response to dynamic angry, fearful, and neutral bodily expressions with blurred faces directed toward or away from the observer. Results showed that motor corticospinal excitability increased independent of direction of anger compared with fear and neutral. In contrast, anger was better recognized when directed toward the observer compared with when directed away from the observer, while the opposite pattern was found for fear. The present results provide evidence for the differential effects of threat direction on explicit recognition and motor corticospinal excitability. In the face of threat, motor corticospinal excitability increases independently of the direction of anger, indicative of the importance of more automatic reactions to threat.

Personal distress and the influence of bystanders on responding to an emergency.

Spontaneous helping behavior during an emergency is influenced by the personality of the onlooker and by social situational factors such as the presence of bystanders. Here, we sought to determine the influences of sympathy, an other-oriented response, and personal distress, a self-oriented response, on the effect of bystanders during an emergency. In four experiments, we investigated whether trait levels of sympathy and personal distress predicted responses to an emergency in the presence of bystanders by using behavioral measures and single-pulse transcranial magnetic stimulation. Sympathy and personal distress were expected to be associated with faster responses to an emergency without bystanders present, but only personal distress would predict slower responses to an emergency with bystanders present. The results of a cued reaction time task showed that people who reported higher levels of personal distress and sympathy responded faster to an emergency without bystanders (Exp. 1). In contrast to our predictions, perspective taking but not personal distress was associated with slower reaction times as the number of bystanders increased during an emergency (Exp. 2). However, the decrease in motor corticospinal excitability, a direct physiological measure of action preparation, with the increase in the number of bystanders was solely predicted by personal distress (Exp. 3). Incorporating cognitive load manipulations during the observation of an emergency suggested that personal distress is linked to an effect of bystanders on reflexive responding to an emergency (Exp. 4). Taken together, these results indicate that the presence of bystanders during an emergency reduces action preparation in people with a disposition to experience personal distress.Electronic supplementary materialThe online version of this article (doi:10.3758/s13415-016-0423-6) contains supplementary material, which is available to authorized users.

Relationship between motor corticospinal excitability and ventilatory response during intense exercise.

Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3min of cycling exercise at 75-85% of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60min of resting recovery following 45min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0±5.6) was significantly greater than that (25.1±5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25±0.89) than in IE1st (4.67±0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66±22%) than in IE1st (77±24%). The difference in mean ESL between the two IEs was significantly (p<0.05, r=-0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

Stage dependent alteration of cortical excitability in patients with hepatic encephalopathy

Question Altered cortical excitability is supposed to play a relevant role in the pathophysiology of hepatic encephalopathy (HE). However, most data is based on animal studies and only limited data of patients with HE is available. We therefore investigated cortical excitability in HE-patients at different disease stages using transcranial magnetic stimulation. Methods In eleven patients with HE stage 1, ten patients with HE stage 2 and ten age matched healthy control subjects several measures for cortical excitability of the primary motor cortex, i. e. motor threshold, motor evoked potential recruitment curve (MEP-RC), short interval intracortical inhibition (SICI), long interval intracortical inhibition, intracortical facilitation and short interval intracortical facilitation were compared. The critical flicker frequency (CFF) was also measured as one marker of disease severity. Results In HE-patients the slope of the MEP-RC was shallower compared to healthy controls. Moreover SICI was significantly reduced in HE stage 2 patients compared to healthy controls and a relevant correlation between SICI and CFF was found. No differences were found in the other measures. Conclusion Our results suggest a disease stage dependent alteration of motor cortical and corticospinal excitability in patients with HE.

TMS over M1 Reveals Expression and Selective Suppression of Conflicting Action Impulses

Goal-directed action control comes into play when selecting between competing action alternatives. Response capture reflects the susceptibility of the motor system to incitement by task-irrelevant action impulses; the subsequent selective suppression of incorrect action impulses aims to counteract response capture and facilitate the desired response. The goal of this experiment was to clarify physiological mechanisms of response capture and suppression of action impulses during conflict at the level of the motor system. We administered single-pulse TMS at various intervals preceding speeded choice responses. The correct response side was designated by stimulus color, whereas stimulus location (which could match or conflict with response side) was to be ignored. TMS pulses triggered motor evoked potential and silent period, providing sensitive indices of cortico-spinal excitation and inhibition. Motor evoked potential data showed the typical progressive increase in cortico-spinal motor excitability leading up to the imminent (correct) response, which started earlier on nonconflict than on conflict trials. On conflict trials, the irrelevant stimulus location captured the incorrect response, as expressed by an early and transient rise in excitability. Silent period data showed that, already early during the response process, inhibition of the incorrect response was stronger for conflict than for nonconflict trials. Furthermore, inhibition decreased over time for nonconflict trials facilitating the imminent correct response while maintaining higher levels of inhibition on conflict trials. In conclusion, dynamic patterns of cortico-spinal excitability provide unique physiological evidence for the expression and selective suppression of action impulses captured by competing action alternatives.

P 128. Predicting behavioural response to TDCS in chronic motor stroke

Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1–M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients’ behavioural response to TDCS. There were three main findings: (1) Unlike Anodal and Cathodal TDCS, Bilateral M1–M1 TDCS (1 mA, 20 min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; (2) GABA levels in ipsilesional M1 predicted patients’ behavioural gains from Anodal TDCS; (3) Although patients were in the chronic phase, time since stroke (and its combination with Fugl-Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor corticospinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.