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Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy. NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy. [ABSTRACT FROM AUTHOR]

• Application of anodal tDCS concurrent to surgical training enhances unimanual skill acquisition compared to training alone. • Changes in delta EEG activity in the sensorimotor network are associated with surgical skill improvement. • EEG patterns of unimanual and bimanual surgical skill performance differ, primarily within the parietal cortex. • Anodal tDCS modulated alpha frequency band activity during bimanual surgical skill performance. Transcranial direct-current stimulation (tDCS), an increasingly applied form of non-invasive brain stimulation, can augment the acquisition of motor skills. Motor learning investigations of tDCS are limited to simple skills, where mechanisms are increasingly understood. Investigations of meaningful, complex motor skills possessed by humans, such as surgical skills, are limited. This replication and extension of our previous findings used electroencephalography (EEG) to determine how tDCS and complex surgical training alters electrical activity in the sensorimotor network to enhance complex surgical skill acquisition. In twenty-two participants, EEG was recorded during baseline performance of simulation-based laparoscopic surgical skills. Participants were randomized to receive 20 min of primary motor cortex targeting anodal tDCS or sham concurrent to 1 h of surgical skill training. EEG was reassessed following training, during a post-training repetition of the surgical tasks. Our results replicated our previous study suggesting that compared to sham, anodal tDCS enhanced the acquisition of unimanual surgical skill. Surgical training modulated delta frequency band activity in sensorimotor regions. Next, the performance of unimanual and bimanual skills evoked unique EEG profiles, primarily within the beta frequency-band in parietal regions. Finally, tDCS-paired surgical training independently modulated delta and alpha frequency-bands in sensorimotor regions. Application of tDCS during surgical skill training is feasible, safe and tolerable. In conclusion, we are the first to explore electrical brain activity during performance of surgical skills, how electrical activity may change during surgical training and how tDCS alters the brain to enhance skill acquisition. The results provide preliminary evidence of neural markers that can be targeted by neuromodulation to optimize complex surgical training. [ABSTRACT FROM AUTHOR]

Background Recent changes in surgical training environments may have limited opportunities for trainees to gain proficiency in skill. Complex skills such as neurosurgery require extended periods of training. Methods to enhance surgical training are required to overcome duty-hour restrictions, to ensure the acquisition of skill proficiency. Transcranial direct-current stimulation (tDCS) can enhance motor skill learning, but is untested in surgical procedural training. We aimed to determine the effects of tDCS on simulation-based neurosurgical skill acquisition. Methods Medical students were trained to acquire tumor resection skills using a virtual reality neurosurgical simulator. The primary outcome of change in tumor resection was scored at baseline, over 8 repetitions, post-training, and again at 6 weeks. Participants received anodal tDCS or sham over the primary motor cortex. Secondary outcomes included changes in brain resected, resection effectiveness, duration of excessive forces (EF) applied, and resection efficiency. Additional outcomes included tDCS tolerability. Results Twenty-two students consented to participate, with no dropouts over the course of the trial. Participants receiving tDCS intervention increased the amount of tumor resected, increased the effectiveness of resection, reduced the duration of EF applied, and improved resection efficiency. Little or no decay was observed at 6 weeks in both groups. No adverse events were documented, and sensation severity did not differ between stimulation groups. Conclusions The addition of tDCS to neurosurgical training may enhance skill acquisition in a simulation-based environment. Trials of additional skills in high-skill residents, and translation to nonsimulated performance are needed to determine the potential utility of tDCS in surgical training. [ABSTRACT FROM AUTHOR]

Objective Brain stimulation and constraint therapy may enhance function after perinatal stroke but mechanisms are unknown. We characterized interhemispheric interactions (IHI) in hemiparetic children and explored their relationship to motor function and neuromodulation. Methods Forty-five hemiparetic perinatal stroke subjects aged 6–19 years completed a clinical trial of repetitive-transcranial magnetic stimulation (rTMS) and constraint therapy. Paired-pulse TMS measured IHI in cases and normal controls. Suprathreshold conditioning stimuli preceded contralateral test stimuli bidirectionally: stroke to non-stroke (SNS) and non-stroke to stroke (NSS). Primary outcome was the interhemispheric ratio (IHR) between conditioned and test only MEP amplitudes X100 (<100 implied inhibition). Motor outcomes at baseline and post-intervention were compared to IHR. Results Procedures were well tolerated. IHI occurred bidirectionally in controls. Eighteen stroke participants had complete data. IHR were increased in stroke participants in both directions. SNS IHR was >100 (facilitation) in 39% of measurements and correlated with better motor function. NSS IHR correlated with poorer motor function. Intervention-induced clinical change was not associated with IHR. Conclusions Interhemispheric interactions are altered and related to clinical function, but not necessarily neuromodulation, in children with perinatal stroke. Significance Adding interhemispheric interactions to evolving models of developmental plasticity following early injury may advance neuromodulation strategies. [ABSTRACT FROM AUTHOR]

Introduction Perinatal stroke causes hemiparetic cerebral palsy (CP) and lifelong disability. Treatments are limited but non-invasive brain stimulation, such as transcranial direct-current stimulation (tDCS) can alter cortical excitability, providing a unique opportunity for therapeutic neuromodulation in CP. We have demonstrated that application of tDCS can enhance motor skill acquisition in children. Growing evidence suggests that tDCS is safe in pediatrics, however refined forms of stimulation such as high-definition (HD)-tDCS have not been applied in children. The KINARM robot objectively quantifies sensorimotor function and holds potential to examine functional changes associated with tDCS-paired motor learning. We aimed to characterize changes in sensorimotor function induced by tDCS and HD-tDCS paired motor learning in children. We hypothesized that application of tDCS and HD-tDCS will improve motor function (visually-guided reaching; VGR), but only tDCS will improve sensory function (position matching). Methods AMPED (Accelerated motor learning in pediatrics) is a randomized, sham-controlled trial (ClinicalTrials.gov: NCT03193580). Healthy, right-handed children (12–18y) were recruited. A validated 4-stage KINARM protocol and a series of motor function assessments [Purdue Pegboard Test (PPT), Jebsen Taylor Test, and Serial Reaction Time Task] were completed at baseline, post-training, and six weeks later. Participants were randomized to receive sham tDCS, anodal tDCS, or anodal HD-tDCS targeting the right primary motor cortex. Over five consecutive days, participants trained their left hand on the PPT during stimulation. Safety and tolerability was assessed daily. Group differences were explored using repeated measure ANOVA with post hoc correcting for multiple comparisons. Results To date, 15 of 24 participants have completed the study (median 16.4y, range 12–18y, 67% female). Blinded interim analysis of cases grouped by intervention (group A, B, C) was performed on an exploratory basis. All participants improved their left hand PPT scores ( p  < 0.001) regardless of intervention. The mean improvement in left hand PPT scores was 3.93 ± 1.33 pegs and was comparable across the groups: A 4.33 ± 1.78, B 3.08 ± 1.15, C 3.67 ± 1.18. No difference was observed between the groups. Right hand PPT scores increased (Group A p = 0.009) or were unchanged (both p > 0.06). Position matching performance did not change from baseline to post-training. Group A demonstrated improvements in left hand reaction (p = 0.03) and movement time (p = 0.04) in VGR tasks between baseline and post-training. All procedures were well tolerated with no adverse events reported. Conclusion Application of tDCS and HD-tDCS in healthy children is safe, feasible, and tolerable. Sensorimotor function may be altered by tDCS and HD-tDCS paired with motor training. Optimizing tDCS and HD-tDCS protocols while exploring mechanisms of action is essential to advance therapeutic applications of tDCS in children with CP and other motor disabilities. [ABSTRACT FROM AUTHOR]

Introduction Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP). We have shown non-invasive brain stimulation enhances motor learning in healthy and hemiparetic children using transcranial-direct-current-stimulation (tDCS). High-definition (HD-tDCS) may offer additional potential but is unstudied in pediatrics. Motor maps are individualized representations of primary motor cortex (M1) topography measurable with single pulse TMS. Advances in MRI-guided imaging and robotic TMS may facilitate rapid and accurate motor mapping. How motor maps are altered by motor learning and tDCS are unknown. We aimed to determine the effects of tDCS/HD-tDCS enhanced motor learning on motor maps in children, hypothesizing tDCS-enhanced learning is associated with motor map enlargement. Methods AMPED (Accelerated Motor learning in PEDiatrics) is a randomized, sham-controlled trial (NCT03193580). Participants are healthy, right handed children aged 12–18 years. TMS motor mapping is performed using neuronavigated (Brainisght2), robotic (Axilum) TMS. A 10 × 10, 7 mm grid is placed over M1 with 4 stimulations per point generating motor evoked potentials (MEP) of individual hand muscles. Primary outcome is motor map area (volume, center of gravity, cortical excitability are secondary). Motor function is assessed with Purdue Pegboard (primary), Jebsen-Taylor Test, and Serial Reaction Time Task. Participants are randomized into three groups: right M1 1 mA tDCS, HD-tDCS, or sham. All practiced the PPT daily (8 trails) during stimulation with the left hand for 5 consecutive days. Safety and tolerability is assessed daily. All outcomes are repeated on day 5 and at 6 weeks. Two-way repeated measure ANOVA examined changes in performance and motor maps across groups and sessions. Results Fifteen of 24 participants have completed the study (median age 16.4, 67% female). Blinded interim analysis grouped interventions as A, B, or C. PPT scores improved across all groups (p < 0.001) mean improvement was 3.93(SD:1.3) and comparable across groups: A 4.3(SD 1.7), B 3.1(SD 1.2), C 3.7(SD 1.2). Motor maps were obtained without complication except two subjects could not complete bi-hemispheric mapping due to time constraints. Motor map outcomes differed at baseline between hemispheres −109.31 mm 2 (SD 675.46). Following intervention, map area decreased in group C(−147 ± 65.7), p < 0.04) but change in area was not different between groups. Similar findings were observed for secondary outcomes. Procedures were well tolerated with no adverse events. Conclusion Trials combining tDCS or HD-tDCS enhanced motor learning with robotic TMS motor mapping are feasible in children. Completion of the sample will determine how HD-tDCS enhancement of motor learning compares to tDCS, with potential to advance therapeutic applications in children with CP. [ABSTRACT FROM AUTHOR]

Background. Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their activity and impairing motor function. Current intervention for the lower limb emphasizes passive approaches (stretching, braces, botulinum toxin injections). The study hypothesis was that intensive, early, child-initiated activity during the critical period will enhance connectivity of motor pathways to the legs and improve motor function. Objective. The study objective was to determine whether early intervention with intensive activity is better than standard care, intervention delivered during the proposed critical period is better than after, and the outcomes are different when the intervention is delivered by a physical therapist in an institution vs. a parent at home. Design. A prospective, delay-group, single-blind, randomized controlled trial (RCT) and a parallel, cohort study of children living beyond commuting distance and receiving an intervention delivered by their parent. Setting. The RCT intervention was provided in university laboratories, and parent training was provided in the childs home. Participants. Children 8 months to 3 years old with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. Intervention. Intensive, play-based leg activity with weights for the affected leg and foot, 1 hour/day, 4 days/week for 12 weeks. Measurements. The primary outcome was the Gross Motor Function Measure-66 score. Secondary outcomes were motion analysis of walking, full-day step counts, motor evoked potentials from transcranial magnetic stimulation, and patellar tendon reflexes. Limitations. Inter-individual heterogeneity in the severity of the stroke and behavioral differences are substantial but measurable. Differences in intervention delivery and assessment scoring are minimized by standardization and training. Conclusions. The intervention, contrary to current practice, could change physical therapy interventions for children with perinatal stroke. [ABSTRACT FROM AUTHOR]