Accelerating Motor Learning in Pediatrics

Background \& rationale: Plasticity may be enhanced in the developing brain but mechanisms are poorly understood. Brain stimulation technologies such as transcranial direct-current stimulation (tDCS) modulate motor cortex excitability and plasticity. Studies by our group and others suggest that neuromodulation trials with tDCS are both safe and feasible in children. Recently the investigators demonstrated that conventional tDCS can enhance motor learning in healthy children. Additionally, recent advances in high-definition tDCS (HD-tDCS) have presented an opportunity to focally stimulate regions of the brain. HD-tDCS has not been investigated to date in children.

Establishing an ability of tDCS to enhance motor learning has therapeutic implications for children with motor disabilities. Perinatal stroke is the leading cause of hemiparetic cerebral palsy and most survivors suffer lifelong physical disability. Emerging models from our lab and others have defined central therapeutic targets whereby brain stimulation may enhance motor learning and function. Understand the effects of tDCS on motor learning, and it's underlying changes within the brain, is essential to advancing such interventions.

Research question \& objectives: Here the investigators propose to characterize the effects of tDCS on motor learning in healthy children. The primary objective of this study is to determine changes in acquisition of motor skill, when training is paired with conventional anodal tDCS, HD-tDCS, or sham tDCS. Multiple secondary objectives will describe biochemical and sensorimotor changes in the brain that take place during motor learning paired with tDCS. Secondary objectives will also assess the safety of HD- tDCS in healthy children.

Ethics: This study has been approved by the University of Calgary Research Ethics Board.

Design: Randomized, double blind, sham-controlled trial to evaluate the ability of tDCS and HD-tDCS to enhance motor learning.

Methods: Children will be recruited through the Healthy Infants and Children Clinical Research Program.

The training task will consists of performing the Purdue Pegboard Test (PPTL) with their left hand. This simple motor learning task is a well-validated task for complex, functionally relevant motor learning. The PPTL has demonstrated good sensitivity to change in both healthy and disease motor learning studies in adults and school-aged children. The PPTL will be performed over five consecutive days to monitor motor learning.

Children will attend the Alberta Children's Hospital Non-Invasive Brain Stimulation Laboratory. Subjects will be randomized to one of three stimulation groups (sham tDCS, conventional anodal tDCS, HD-tDCS). Baseline measures will be performed, including: magnetic resonance neuroimaging (anatomical imaging, functional neuroimaging and magnetic resonance spectroscopy), transcranial magnetic stimulation neurophysiology (motor mapping of the left and right motor cortex), sensorimotor functional changes assessed using the Kinesiological Instrument for Normal and Altered Reaching Movements (KINARM; arm positioning matching, kinesthesia, visually guided reaching, and object hit task), motor function changes (PPT, Jebsen-Taylor Test, Serial Reaction Time Task), and sensory discrimination measures (amplitude discrimination, temporal order judgment, temporal order judgment task, duration discrimination task, duration discrimination with confound, and single site adaptation task.

Following baseline measures, subjects will be seating in a comfortable chair with the PPTL test in front of them on a table. Participant randomized to sham or conventional anodal tDCS will be fitted with two 25cm2 electrodes (anode over the right primary motor cortex, cathode over the contralateral supraorbital area) or an EEG cap containing four small circular electrode (HD-tDCS, 1 anode centered over the right primary motor cortex, 4 cathodes surround the anode in a ring-like fashion). Three pre-intervention trials of the PPTL will be performed. All subjects will then have the tDCS ramped up to 1milliamp over 45 seconds. After 120 seconds the current will either be ramped down to 0milliamp (sham tDCS) or continue for a total of 20 minutes. The PPTL will be performed 5, 10, and 15 minutes following stimulation commencement, and after stimulation has ended (3 repetitions per time point). A tDCS safety and tolerability questionnaire will then be completed.

The same tDCS-treatment, PPTL training and safety and tolerability questionnaires will be performed over the next three consecutive days. On study day 5 participants will again repeat PPTL training paired with tDCS-treatment. Following tDCS and PPTL training, magnetic resonance neuroimaging, transcranial magnetic stimulation neurophysiology, sensorimotor functional changes, motor function changes, and sensory discrimination measures will be repeated to assess changes induced by motor learning and tDCS.

Participants will return six weeks following training, where magnetic resonance neuroimaging, transcranial magnetic stimulation neurophysiology, sensorimotor functional changes, motor function changes, and sensory discrimination measures will be repeated to assess long-term changes.

Data analysis: All outcome variables will be compared across the three intervention groups (sham tDCS, conventional tDCS, HD- tDCS) using a two-way repeated measures ANOVA with appropriate post-hoc analysis. The repeated measures ANOVA will distinguish the influence of intervention (stimulation type) and time (baseline, post-training, 1 month post- training). Pearson's correlations will be performed between the primary outcome measure and secondary outcome measures. Secondary statistical analysis will be performed as warranted.