tACS-combined motor training for the rehabilitation of the upper limb in children and adolescents with cerebral palsy: A randomized, sham-controlled trial protocol

Background: Children with cerebral palsy (CP) commonly face gross motor function impairments and manual dexterity deficits, significantly affecting their activity level and independence and, ultimately, quality of life. Rehabilitation often targets improving manual dexterity and activity levels, but standard therapies have limited efficacy. Hence, exploring novel methods to enhance upper limb functionality is crucial. Transcranial alternating current stimulation (tACS), by delivering currents oscillating at specific frequencies syncing with the brain's electrical rhythms, has been demonstrated to modulate neural oscillations and motor behavior. Method: This randomized, double-blind, sham-controlled, pre-post test study involves 44 children and adolescents (6-17 yo) with CP treated in pairs, which will be randomly allocated to the experimental or control group receiving, respectively, active or sham fronto-cerebellar tACS delivered at the individual gamma frequency. After tACS, both groups will undergo bimanual training, including lower extremities (HABIT-ILE). Primary outcome measures will include the Assisting Hand Assessment, Box and Block Test, and a Visuomotor Task administered via computer for manual visuomotor control evaluation. Secondary outcomes will encompass the Children's Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland version 2, Pediatric Quality of Life Inventory, and EEG power recorded in fronto-central regions at rest before (at T0), soon after (at T1), and 3 months after the end of (T2) the training. Safety and tolerability will be assessed by pre- and post-tACS recordings of oxygen saturation and heart rate, along with self-report questionnaires on sensations and side-effects. Discussion: This study investigates whether an intensive HABIT-ILE program combined with fronto-cerebellar gamma tACS can boost training effects on manual dexterity in children and adolescents with CP, while ensuring safety and tolerability throughout the intervention period. Trial registration: ClinicalTrials.gov NCT06372041.