Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder

Background: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. Methods: We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. Results: Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. Conclusions: Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD.