Improvement in Tics and Motor Impulsivity Is Associated with Functional and Receptor-Enriched Connectivity changes in Adolescents with Tourette Disorder

In Tourette Disorder (TD), tics are frequently associated with impulsivity, yet the mechanisms linking these dimensions and their evolution during adolescence remain unclear. We combined behavioral, clinical, and receptor-enriched by target (REACT) functional connectivity imaging to examine tic severity and impulsivity over time in TD adolescents. 64 TD adolescents and 56 healthy controls completed a saccadic motor waiting impulsivity (WI) task and resting-state fMRI at baseline. TD participants were reassessed 15 months later. REACT was used to examine dopamine transporter (DAT) - and serotonin 1B receptor (5-HT1B)-weighted functional connectivity within fronto-striatal motor and limbic networks. Longitudinal analyses focused on within-TD changes and their associations with clinical measures. Behaviorally, no differences emerged between groups, but within TD, higher WI was associated with greater global tic severity (YGTSS/100). Longitudinally, both tics (YGTSS/50 and /100) and WI improved significantly. Compared to controls, TD showed a higher functional connectivity between caudate and anterior cingulate cortex (ACC) on the left. Longitudinally, tic reduction (YGTSS/50) was linked to increased connectivity between nucleus accumbens (NAcc) - ventral tegmental area on the left; reduced WI correlated with a higher left caudate – subgenual ACC and bilateral putamen–supplementary motor area (SMA) connectivity. In TD versus controls, REACT showed elevated both DAT-weighted connectivity between the NAcc–SMA and 5-HT1B-weighted connectivity between the raphe–SMA. Longitudinally in TD, while 5-HT1B-weighted connectivity declined DAT-weighted connectivity remained stable. Changes in motor and limbic fronto-striatal functional connectivity were associated with longitudinal improvements in tics and WI in TD adolescents.