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Introduction: Perinatal stroke (PS) is a focal vascular brain injury and the leading cause of hemiparetic cerebral palsy. Motor impairments last a lifetime but treatments are limited. Transcranial direct-current stimulation (tDCS) may enhance motor learning in adults but tDCS effects on motor learning are less studied in children. Imaging-based simulations of tDCS-induced electric fields (EF) suggest differences in the developing brain compared to adults but have not been applied to common pediatric disease states. We created estimates of tDCS-induced EF strength using five tDCS montages targeting the motor system in children with PS [arterial ischemic stroke (AIS) or periventricular infarction (PVI)] and typically developing controls (TDC) aged 6-19 years to explore associates between simulation values and underlying anatomy. Methods: Simulations were performed using SimNIBS https://simnibs.github.io/simnibs/build/html/index.html using T1, T2, and diffusion-weighted images. After tissue segmentation and tetrahedral mesh generation, tDCS-induced EF was estimated based on the finite element model (FEM). Five 1mA tDCS montages targeting motor function in the paretic (non-dominant) hand were simulated. Estimates of peak EF strength, EF angle, field focality, and mean EF in motor cortex (M1) were extracted for each montage and compared between groups. Results: Simulations for eighty-three children were successfully completed (21 AIS, 30 PVI, 32 TDC). Conventional tDCS montages utilizing anodes over lesioned cortex had higher peak EF strength values for the AIS group compared to TDC. These montages showed lower mean EF strength within target M1 regions suggesting that peaks were not necessarily localized to motor network-related targets. EF angle was lower for TDC compared to PS groups for a subset of montages. Montages using anodes over lesioned cortex were more sensitive to variations in underlying anatomy (lesion and tissue volumes) than those using cathodes over non-lesioned cortex. Discussion: Individualized patient-centered tDCS EF simulations are prudent for clinical trial planning and may provide insight into the efficacy of tDCS interventions in children with PS. [ABSTRACT FROM AUTHOR]

Introduction: Symptoms following a mild traumatic brain injury (mTBI) usually resolve quickly but may persist past 3 months in up to 15% of children. Mechanisms of mTBI recovery are poorly understood, but may involve alterations in cortical neurophysiology. Transcranial Magnetic Stimulation (TMS) can non-invasively investigate such mechanisms, but the time course of neurophysiological changes in mTBI are unknown. Objective/Hypothesis: To determine the relationship between persistent post-concussive symptoms (PPCS) and altered motor cortex neurophysiology over time. Methods: This was a prospective, longitudinal, controlled cohort study comparing children (8–18 years) with mTBI (symptomatic vs. asymptomatic) groups to controls. Cortical excitability was measured using TMS paradigms at 1 and 2 months post injury. The primary outcome was the cortical silent period (cSP). Secondary outcomes included short interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval cortical inhibition (LICI). Generalized linear mixed model analyses were used to evaluate the effect of group and time on neurophysiological parameters. Results: One hundred seven participants (median age 15.1, 57% female) including 78 (73%) with symptomatic PPCS and 29 with asymptomatic mTBI, were compared to 26 controls. Cortical inhibition (cSP and SICI) was reduced in the symptomatic group compared to asymptomatic group and tended to increase over time. Measures of cortical facilitation (SICF and ICF) were increased in the asymptomatic group and decreased over time. TMS was well tolerated with no serious adverse events. Conclusions: TMS-assessed cortical excitability is altered in children following mild TBI and is dependent on recovery trajectory. Our findings support delayed return to contact sports in children even where clinical symptoms have resolved. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13–21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678 [ABSTRACT FROM AUTHOR]

Transcranial direct-current stimulation (tDCS) is a form of non-invasive brain stimulation that induces electric fields in neuronal tissue, modulating cortical excitability. Therapeutic applications of tDCS are rapidly expanding, and are being investigated in pediatrics for various clinical conditions. Anatomical variations are among a host of factors that influence the effects of tDCS, and pronounced anatomical differences between children and adults suggest that induced electric fields may be substantially different across development. The aim of this study was to determine the strength and distribution of tDCS-induced electric fields across development. Typically developing children, adolescents, and adults were recruited. Individualized finite-element method modeling of primary motor cortex (M1) targeting tDCS was performed. In the largest pediatric sample to date, we found significantly higher peak and mean M1 electric field strength, and more expansive electric field spread for children compared to adults. Electric fields were often comparable between adolescents and adults. Our results suggest that these differences may be associated with age-related differences in skull and extra-axial space thickness, as well as developmental changes occurring in gray and white matter. Individualized current modeling may be a valuable tool for personalizing effective doses of tDCS in future pediatric clinical trials. [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]

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]