Non-Invasive Brain Stimulation to Improve Language in Down Syndrome.

Down syndrome (DS) is associated with cognitive deficits, caused by alterations in neuroplasticity and synaptic transmission. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), can modulate the brain's plasticity mechanisms and neurotransmitter balance. Anodal tDCS increases cortical excitability by depolarizing neurons, while cathodal tDCS decreases it through hyperpolarization. When combined with cognitive training, tDCS may produce faster and longer-lasting therapeutic effects. Although most of the neurorehabilitation studies have applied anodal excitatory stimulation, recent evidence suggests the potential cathodal inhibitory stimulation in neurodevelopmental disorders with alteration of synaptic transmission, as people with DS. Potentially both anodal and cathodal stimulation protocols could lead to positive clinical effects in DS. This proof-of-concept study is a double-blind, placebo-controlled, clinical trial aiming to evaluate the efficacy of two active tDCS protocols (anodal and cathodal) targeting the left inferior frontal gyrus (IFG) versus sham stimulation tDCS, combined with speech and language training, to improve language skills in adolescents and young adults with DS. The study also aims to identify the most effective parameters of tDCS treatment, for customization in adolescents and young adults with DS. Thirty-six participants, aged 12 to 21 years, will be randomly assigned to three groups receiving anodal, cathodal, or sham tDCS. Each participant will undergo 10 sessions of tDCS at 1 mA for 20 minutes, alongside speech and language training five times for two weeks. Neuropsychological, behavioral, biomarker (including brain-derived neurotrophic factor and neurofilament light chain), and electroencephalogram assessments will be performed at baseline, post-treatment, and three months after treatment completion. The study hypothesizes that tDCS will enhance language abilities, particularly expressiv