Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

Abstract

Familial vulnerability to attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to atypical prefrontal activity during cognitive control tasks. However, ADHD is associated with deficits in the cerebellum as well as deficits in frontostriatal circuitry and associated cognitive control. In this study, we investigated whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. We used an event-related, rapid mixed-trial functional magnetic resonance imaging design. The paradigm was a variation on a go/no-go task, with expected (go) and unexpected (no-go) events at expected and unexpected times. A total of 36 male children and adolescents completed the study, including 12 sibling pairs discordant for ADHD and 12 matched controls. Children and adolescents with ADHD were less accurate on unexpected events than control subjects. Performance by unaffected siblings was intermediate, between that of children and adolescents with ADHD and controls. Functional neuroimaging results showed dissociation between activation in the cerebellum and anterior cingulate cortex: Activity in the anterior cingulate cortex was decreased for subjects with ADHD and their unaffected siblings compared with controls for manipulations of stimulus type (no-go trials), but not timing. In contrast, cerebellar activity was decreased for subjects with ADHD and their unaffected siblings for manipulations of timing, but not stimulus type. These findings suggest that activity in both the prefrontal cortex and cerebellum is sensitive to familial vulnerability to ADHD. Unaffected siblings of individuals with ADHD show deficits similar to affected probands in prefrontal areas for unexpected events and in cerebellum for events atunexpected times.