Large-scale analysis of interindividual variability in single and paired-pulse TMS data.

OBJECTIVE: This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. METHODS: Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. RESULTS: 687 healthy participant's data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual's single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. CONCLUSIONS: This large-scale analysis has identified a number of factors influencing participants' responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. SIGNIFICANCE: This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.

Large-scale analysis of interindividual variability in theta-burst stimulation data: Results from the 'Big TMS Data Collaboration'.

BACKGROUND: Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. OBJECTIVE/HYPOTHESIS: This study brought together over 60 TMS researchers to form the 'Big TMS Data Collaboration', and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. METHODS: 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. RESULTS: 430 healthy participants' TBS data was pooled across 22 studies (mean age = 41.9; range = 17-82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. CONCLUSIONS: This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

Concussion incidence and time-loss in Australian football: A systematic review.

OBJECTIVES: Australian football is associated with a risk of concussion. However, despite the extensive and varied nature of literature devoted to this issue, concussion incidence has not been systematically evaluated. To address this, we aimed to conduct a meta-analysis of concussion incidence in Australian football. DESIGN: Systematic review. Prospero registration number: CRD42017064290. METHODS: A systematic search of 14 databases using the terms 'concussion', and 'Australian football' (and variations) was used to obtain records that reported concussion incidence per 1000 players hours across age, sex, and level-of-play. Data were grouped based on how time-loss was applied to the concussion definition. RESULTS: Forty-two studies met inclusion criteria. Incidence rates based on a possible time-loss definition per 1000 player hours, ranged from 2.24 to 17.63 at the elite level, and 0.35 to 14.77 at the community/amateur level. Return-to-play details were reported by six studies and only two studies measured head-impacts in real-time. Several limitations were identified with this literature. First, insufficient return-to-play details precluded a meta-analysis of incidence rates. Second, no longitudinal studies across levels-of-play were found. Third, concussion incidence data for junior and female players were notably scarce. CONCLUSIONS: There was limited scope to determine concussion burden (i.e., incidence and severity) and only preliminary data for player exposure to head-impacts. To address these limitations, injury surveillance should capture sufficient information to permit comparisons within and across levels-of-play. This will also help determine the influence of interventions aimed at reducing the frequency and severity of concussive-injuries.

Intra- and Inter-Regional Priming of Ipsilateral Human Primary Motor Cortex With Continuous Theta Burst Stimulation Does Not Induce Consistent Neuroplastic Effects.

Human responses to non-invasive brain stimulation (NIBS) techniques can be highly variable. Recently, priming protocols involving a conditioning round of NIBS applied to a target brain region prior to the application of a test protocol have shown promise in inducing more reliable effects. We investigated whether intra- or inter-regional priming of the left primary motor cortex (M1) using continuous theta burst stimulation (cTBS) can induce consistent, and reliable modulation of corticospinal excitability. Twenty healthy adults (six males) underwent four cTBS protocols. For intra-regional priming, cTBS was applied twice to the left M1 (M1-M1). For inter-regional M1 priming, cTBS was applied to the ipsilateral (left) dorsal premotor cortex (dPMC-M1), and ipsilateral (left) dorsolateral prefrontal cortex (DLPFC-M1). In the control condition, sham stimulation was applied to left M1, followed by active cTBS also applied to the left M1 (sham-M1). Each round of cTBS was separated by 10 min. Neuroplastic responses were indexed using motor evoked potentials (MEPs) elicited from the left M1 hand region, and measured from the contralateral first dorsal interosseous (right hand). MEP measurements were taken before the first round of cTBS priming, then immediately, 10, 20 and 30 min after the second test round of cTBS. The primary two-way repeated measures ANOVA revealed no significant differences in MEP responses across each condition (no main effects or interaction). Intra- and inter-regional priming of the left M1 using cTBS does not induce consistent neuroplastic effects. Further work is required to identify factors which contribute to such variability in human responses to NIBS.

Acute motor, neurocognitive and neurophysiological change following concussion injury in Australian amateur football. A prospective multimodal investigation.

OBJECTIVES: This multimodal study investigated the motor, neurocognitive and neurophysiological responses following a sports related concussion injury in the acute-phase (up to 10 days) in sub-elite Australian football players. DESIGN: Between-group, repeated measures. METHODS: Over the course of one season (six months), 43 male players from one football club (25.1 ± 4.5 years) were assessed for fine motor dexterity, visuomotor reaction time, implicit learning and attention. Motor cortex excitability and inhibition were assessed using transcranial magnetic stimulation. RESULTS: Of the 43 players, eight suffered concussion injuries, and were compared to 15 non-concussed players (active control) who returned for follow up testing. Post-concussion assessments using the aforementioned tests were carried out at 48 and 96 h, and 10 days. Compared to the non-concussed players, those who suffered concussion showed slowed fine dexterity (P = 0.02), response (P = 0.02) and movement times (P = 0.01) 48 h post-concussion. Similarly, attentional performance was reduced in the concussed group at all time points (48 h: P < 0.01; 96 h: P < 0.01; and 10 days: P = 0.02) post-concussion. TMS revealed significantly increased corticospinal inhibition at 48 (P = 0.04) and 96 h post concussion (P = 0.02) with significant correlations between increased corticospinal inhibition and response (r = 0.48; P < 0.01), movement time (r = 0.42; P = 0.02), and attention performance (r = 0.44; P = 0.01). CONCLUSIONS: This study has demonstrated that acutely concussed Australian football players show abnormalities in motor, cognitive and neurophysiological measures with variable rates of recovery. These findings suggest that measuring the recovery of concussed athletes should incorporate a range of testing modalities rather than relying on one area of measurement in determining return to play.