Normalization of Intrinsic Neural Circuits Governing Tourette’s Syndrome Using Cranial Electrotherapy Stimulation

Goal: The aim of this study was to investigate the normalization of the intrinsic functional activity and connectivity of TS adolescents before and after the cranial electrotherapy stimulation (CES) with alpha stim device. Methods: We performed restingstate functional magnetic resonance imaging on eight adolescents before and after CES with mean age of about nine-years old who had Tourette’s syndrome with moderate to severe tics symptom. Independent component analysis (ICA) with hierarchical partner matching method was used to examine the functional connectivity between regions within cortico-striato-thalamo-cortical (CSTC) circuit. Granger causality was used to investigate effective connectivity among these regions detected by ICA. We then performed pattern classification on independent components with significant group differences that served as endophenotype markers to distinguish the adolescents between TS and the normalized ones after CES. Results: Results showed that TS adolescents after CES treatment had stronger functional activity and connectivity in anterior cingulate cortex (ACC), caudate and posterior cingulate cortex while had weaker activity in supplementary motor area within the motor pathway compared with TS before CES. Conclusion: The results suggest that the functional activity and connectivity in motor pathway was suppressed while activities in the control portions within CSTC loop including ACC and caudate were increased in TS adolescents after CES compared with adolescents before CES. Significance: The normalization of the balance between motor and control portions of the CSTC circuit may result in the recovery of TS adolescents.