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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]

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. [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 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]