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 ¼ 41.9; range ¼ 17 e82; females ¼ 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 cTBSinduced 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.

Objective Identify the optimal number of pulses necessary to achieve reliable measures of motor evoked potentials (MEPs) in transcranial magnetic stimulation (TMS) studies. Methods Retrospective data was obtained from 54 healthy volunteers (30 men, mean age 61.7±13.1 years) who as part of prior studies had completed three blocks of 30 consecutive TMS stimuli using neuronavigation. Data from four protocols were assessed: single-pulse TMS for measures of amplitude and latency of MEPs; paired-pulse TMS for short-interval intracortical inhibition (sICI) and intracortical facilitation (ICF); and single-pulse TMS to assess the effects of intermittent theta burst stimulation (iTBS). Two statistical methods were used: an internal consistency analysis and probability of inclusion in the 95% confidence interval (CI) around the mean MEPs amplitude. Results For single-pulse TMS, the minimum number of pulses needed to achieve reliable amplitude and latency MEPs measures was 21 and 23, respectively. For paired-pulse TMS, the minimum number of pulses needed to achieve reliable sICI and ICF measures was 20 and 25, respectively. Finally, the minimum number of pulses needed to achieve reliable amplitude and latency MEPs measures after iTBS was 22 and 23, respectively. Conclusions This study provides guidelines regarding the minimum number of pulses needed to achieve reliable MEPs measurements in various study protocols using neuronavigated TMS. Significance Results from this study have the potential to increase the reliability and quality of future neuronavigated TMS studies.

There is a strong link between the practice of regular physical exercise and maintenance of cognitive brain health. Animal and human studies have shown that exercise exerts positive effects on cognition through a variety of mechanisms, such as changes in brain volume and connectivity, cerebral perfusion, synaptic plasticity, neurogenesis, and regulation of trophic factors. However, much of this data has been conducted in young humans and animals, raising questions regarding the generalizability of these findings to aging adults. Furthermore, it is not clear at which doses these effects might take place, and if effects would differ with varying exercise modes (such as aerobic, resistance training, combinations, or other). The purpose of this review is to summarize the evidence on the effects of exercise interventions on various mechanisms believed to support cognitive improvements: cerebral perfusion, synaptic neuroplasticity, brain volume and connectivity, neurogenesis, and regulation of trophic factors. We synthesized the findings according to exposure to exercise (short-[1 day-16 weeks], medium-[24-40 weeks], and long-term exercise [52 weeks and beyond]) and have limited our discussion of dose effects to studies in aging adults and aged animals (when human data was not available).

Meaningful improvements in aspects of hand-related function that persisted at least 30 minutes after intervention were observed with transcutaneous electrical nerve stimulation and transcranial direct current stimulation, when combined with functional task practice.

Background and Purpose Evidence suggests the use of stimulation to increase corticomotor excitability improves hand function in persons with cervical spinal cord injury (SCI). We assessed effects of multi-day application of 10Hz repetitive transcranial magnetic stimulation (rTMS) applied to the corticomotor hand area combined with repetitive task practice (RTP) in participants with tetraplegia and neurologically healthy participants. Methods Using a double-blind randomized crossover design, 11 participants with chronic tetraplegia and 10 neurologically healthy participants received 3 sessions of 10Hz rTMS+RTP and 3 sessions of sham-rTMS+RTP to the corticomotor hand region controlling the weaker hand. RTMS was interleaved with RTP of a skilled motor task between pulse trains. Hand function (Jebsen-Taylor Hand Function Test [JTT], pinch, and grasp strength) and corticomotor excitability (amplitude of motor-evoked potential) were assessed prior to and following the rTMS+RTP and sham-rTMS+RTP phases. We assessed significance using paired t-tests on pre-post differences and effect sizes using standardized response mean (SRM). Results RTMS+RTP was associated with larger effect sizes compared to sham-rTMS+RTP for improvement in JTT for both the trained hand (SRM=0.85 and 0.42, respectively), non-trained hand (0.55, 0.31, respectively), and for grasp strength of the trained hand in the SCI group (0.67, 0.39, respectively) alone. Effect sizes for all other measures were small and there were no statistical between-condition differences in the outcomes assessed. Discussion and Conclusions RTMS may be a valuable adjunct to RTP for improving hand function in persons with tetraplegia. Higher stimulation dose (frequency, intensity, number of sessions) may be associated with larger effects. Video Abstract available (See Supplemental Digital Conent 1) for more insights from the authors.

We found that exercising for at least 52 hours is associated with improved cognitive performance in older adults with and without cognitive impairment. Exercise modes supported by evidence are aerobic, resistance (strength) training, mind-body exercises, or combinations of these interventions.

Background Physical exercise and cognitive training have been recommended to improve cognitive outcomes poststroke, but a multifaceted strategy including aerobic, resistance, and cognitive training to facilitate poststroke recovery has not been investigated. We aimed to assess the feasibility, adherence, and safety of a combined aerobic, resistance, and cognitive training intervention ( CARET + CTI ) after stroke. Methods and Results We prospectively randomized patients presenting with recent stroke to a comparison of a supervised 12‐week CARET + CTI program and a control group receiving sham CARET + CTI . Participants were scheduled for 3 weekly CARET and CTI sessions. All participants underwent pre‐ and postintervention assessments of strength, endurance, and cognition. The primary outcomes were feasibility and adherence, defined as the ratio of scheduled and observed visits, and safety. We enrolled 131 participants, of whom 37 withdrew from the study. There were 17 (20%) withdrawals in the CARET + CTI and 20 (44%) in the control group. The observed‐over‐expected visit ratio was significantly higher in the intervention than in the control group (0.74±0.30 versus 0.54±0.38; P =0.003). A total of 99 adverse events were reported by 59 participants, none of which were serious and related to the intervention. Greater gains in physical, cognitive, and mood outcomes were found in the CARET + CTI group than in the control group, but were not statistically significant after adjustments. Conclusions A CARET + CTI intervention, after stroke, is safe, feasible, and has satisfactory participant adherence over 12 weeks. REGISTRATION URL : https://www.clini​caltr​ials.gov . Unique identifier: NCT 02272426.

While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words ''spinal cord injury motor recovery'' identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase (clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic interventions).