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Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES., Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided., Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity., Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases., Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials., (Copyright © 2022 International Federation of Clinical Neurophysiology. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Perinatal stroke causes lifelong motor disability, affecting independence and quality of life. Non-invasive neuromodulation interventions such as transcranial direct current stimulation (tDCS) combined with intensive therapy may improve motor function in adult stroke hemiparesis but is under-explored in children. Measuring cortical metabolites with proton magnetic resonance spectroscopy (MRS) can inform cortical neurobiology in perinatal stroke but how these change with neuromodulation is yet to be explored., Methods: A double-blind, sham-controlled, randomized clinical trial tested whether tDCS could enhance intensive motor learning therapy in hemiparetic children. Ten days of customized, goal-directed therapy was paired with cathodal tDCS over contralesional primary motor cortex (M1, 20 min, 1.0 mA, 0.04 mA/cm 2 ) or sham. Motor outcomes were assessed using validated measures. Neuronal metabolites in both M1s were measured before and after intervention using fMRI-guided short-echo 3T MRS., Results: Fifteen children [age(range) = 12.1(6.6-18.3) years] were studied. Motor performance improved in both groups and tDCS was associated with greater goal achievement. After cathodal tDCS, the non-lesioned M1 showed decreases in glutamate/glutamine and creatine while no metabolite changes occurred with sham tDCS. Lesioned M1 metabolite concentrations did not change post-intervention. Baseline function was highly correlated with lesioned M1 metabolite concentrations (N-acetyl-aspartate, choline, creatine, glutamate/glutamine). These correlations consistently increased in strength following intervention. Metabolite changes were not correlated with motor function change. Baseline lesioned M1 creatine and choline levels were associated with clinical response., Conclusions: MRS metabolite levels and changes may reflect mechanisms of tDCS-related M1 plasticity and response biomarkers in hemiparetic children with perinatal stroke undergoing intensive neurorehabilitation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aims to determine the effects of transcranial direct-current stimulation (tDCS) on motor learning in healthy school-aged children. Safety, tolerability, and translation of effects to untrained tasks were also explored. We recruited 24 right-handed children for a randomized, sham-controlled, double-blinded trial to receive: right primary motor cortex (M1) 1 mA anodal (1A-tDCS), left M1 1 mA cathodal (1C-tDCS), left M1 2 mA cathodal tDCS (2C-tDCS), or sham tDCS over 3 consecutive days of motor task practice. Participants trained their left hand to perform the Purdue Pegboard Test (PPT) during tDCS application. Right hand and bimanual PPT, the Jebsen-Taylor Test (JTT), and the Serial Reaction Time Task (SRTT) were tested at baseline and post-training. All measures were retested 6 weeks later. Active tDCS montages enhanced motor learning compared with sham (all P < 0.002). Effects were sustained at 6 weeks. Effect sizes were large and comparable across montages: contralateral 1A-tDCS (Cohen's d = 2.58) and ipsilateral 1C-tDCS (3.44) and 2C-tDCS (2.76). Performance in the untrained hand PPT, bilateral JTT, and SRTT often improved with tDCS. tDCS was well-tolerated and safe with no adverse events. These first principles will advance the pairing of tDCS with therapy to enhance rehabilitation for disabled children such as those with cerebral palsy., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine whether the addition of transcranial direct current stimulation (tDCS) to intensive therapy increases motor function in children with perinatal stroke and hemiparetic cerebral palsy., Methods: This was a randomized, controlled, double-blind clinical trial. Participants were recruited from a population-based cohort with MRI-classified unilateral perinatal stroke, age of 6 to 18 years, and disabling hemiparesis. All completed a goal-directed, peer-supported, 2-week after-school motor learning camp (32 hours of therapy). Participants were randomized 1:1 to 1 mA cathodal tDCS over the contralesional primary motor cortex (M1) for the initial 20 minutes of daily therapy or sham. Primary subjective (Canadian Occupational Performance Measure [COPM]), objective (Assisting Hand Assessment [AHA]), safety, and secondary outcomes were measured at 1 week and 2 months after intervention. Analysis was by intention to treat., Results: Twenty-four participants were randomized (median age 11.8 ± 2.7 years, range 6.7-17.8). COPM performance and satisfaction scores doubled at 1 week with sustained gains at 2 months (p < 0.001). COPM scores increased more with tDCS compared to sham control (p = 0.004). AHA scores demonstrated only mild increases at both time points with no tDCS effects. Procedures were safe and well tolerated with no decrease in either arm function or serious adverse events., Conclusion: tDCS trials appear feasible and safe in hemiparetic children. Lack of change in objective motor function may reflect underdosing of therapy. Marked gains in subjective function with tDCS warrant further study., Clinicaltrialsgov Identifier: NCT02170285., Classification of Evidence: This study provides Class II evidence that for children with perinatal stroke and hemiparetic cerebral palsy, the addition of tDCS to moderate-dose motor learning therapy does not significantly improve motor function as measured by the AHA., (© 2016 American Academy of Neurology.)

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]

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]

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]