Improvement in Tics and Motor Impulsivity Is Associated With Functional and Receptor-Enriched Connectivity Changes in...

In Tourette disorder (TD), tics are frequently associated with impulsivity, but the mechanisms linking these dimensions and their evolution during adolescence remain unclear. We combined behavioral, clinical, and receptor-enriched analysis of functional connectivity by targets (REACT) functional connectivity imaging to examine tic severity and impulsivity over time in adolescents with TD.

A total of 64 adolescents with TD and 56 healthy control participants completed a saccadic motor waiting impulsivity (WI) task and resting-state functional magnetic resonance imaging at baseline. Participants with TD were reassessed 15 months later. REACT was used to examine dopamine transporter (DAT)- and serotonin 1B (5-HT_1B) receptor-weighted functional connectivity within frontostriatal motor and limbic networks. Longitudinal analyses focused on within-TD changes and their associations with clinical measures.

Behaviorally, no differences emerged between groups, but in the TD group, higher WI was associated with greater global tic severity (Yale Global Tic Severity Scale [YGTSS/100]). Longitudinally, both tics (YGTSS/50 and 100) and WI improved significantly. Compared with controls, adolescents with TD showed higher functional connectivity between the caudate and the anterior cingulate cortex (ACC) on the left. Longitudinally, tic reduction (YGTSS/50) was linked to increased connectivity between the nucleus accumbens (NAcc) and the ventral tegmental area on the left; reduced WI correlated with higher left caudate-subgenual ACC and bilateral putamen-supplementary motor area (SMA) connectivity. In patients with TD versus controls, REACT showed elevated DAT-weighted connectivity between the NAcc and SMA and 5-HT_1B-weighted connectivity between the raphe and the SMA. Longitudinally in TD, while 5-HT_1B-weighted connectivity declined, DAT-weighted connectivity remained stable.

Changes in motor and limbic frontostriatal functional connectivity were associated with longitudinal improvements in tics and WI in adolescents with TD.