Effect of Precision-based HD-tDCS Over Conventional HD-tDCS in Young-onset Mania: Protocol for an Active Comparison...

As more accurate neuromodulation systems combining high-resolution electroencephalogram (EEG) and anatomical biomarkers develop, it is prudent to evaluate how refined and effective precision neuromodulation is compared to conventional techniques. Considering the growing incidence and the lack of studies outlining an optimal treatment approach, which often leads to a poorer prognosis, young-onset mania presents an ideal challenge for such a comparison.

This study aims to be the first to directly compare precision and conventional neuromodulation in child and adolescent populations. It also seeks to study and compare, for the first time, changes in neuroimaging parameters caused by precision and conventional techniques. By correlating perturbation-induced changes in cortical inhibition paradigms and functional connectivity of cerebral circuits, we aim to introduce a more objective measure of therapeutic efficacy and response, as opposed to relying solely on subjective clinical scales. Furthermore, we aim to study, for the first time, task-based differential activation of brain areas in young-onset mania.

Participants would be randomly allocated to the intervention group 1 (G1) or the active control treatment group 2 (G2). Baseline assessments of both groups will include evaluations using clinical scales (Clinical Global Impression [CGI], Brief Psychiatric Rating Scale-Child [BPRS], Young Mania Rating Scale [YMRS], Barratt's Impulsivity Scale [BIS], and Affectivity Reactivity Index [ARI]), task-based and resting-state functional magnetic resonance imaging (rs-fMRI), and transcranial magnetic stimulation (TMS)-based cortical inhibition paradigms (cortical silent period [CSP], short interval intracortical inhibition [SICI], and long interval intracortical inhibition [LICI]). G1 would receive precision-based high-definition transcranial direct current stimulation (HD-tDCS) over the right ventromedial prefrontal cortex (VMPFC) daily for 10 days with 2 sessions spaced 4 h apart. G2 would receive conventional HD-tDCS over the right VMPFC daily for 10 days with sessions spaced 4 h apart. Participants would undergo reassessment at 2 weeks following the completion of 20 sessions, using scales, task-based and rs-fMRI, and cortical inhibition paradigms, as well as at 6 weeks. Data would be analyzed using the Statistical Package for the Social Sciences (SPSS) for outcome variables as defined for the study. The primary outcome variable would be the improvement in the severity of young-onset mania, as measured by YMRS and CGI scale scores, using precision over conventional HD-tDCS. The secondary outcome would be an improvement in functional connectivity, as measured by neuroimaging, and enhancement of cortical inhibition, as measured by cortical inhibition paradigms, in young-onset mania after receiving adjunctive precision over conventional HD-tDCS.

This study protocol aims to explore the effect of novel precision-based HD-tDCS in young-onset mania compared to conventional HD-tDCS, thereby allowing for the examination of precision neuromodulation in young-onset mania.