Limbic and Executive Meso- and Nigrostriatal Tracts Predict Impulsivity Differences in Attention-Deficit/Hyperactivity Disorder

Abstract

BackgroundImpulsivity is a defining characteristic of attention-deficit/hyperactivity disorder (ADHD), which has been associated with substance use disorders, higher accident rates, and lower educational and occupational outcomes. The meso- and nigrostriatal pathways of the dopamine system are hypothesized to be functionally heterogeneous, supporting diverse cognitive functions and impairments, including those associated with ADHD. We tested whether human midbrain pathways (where dopaminergic cell bodies originate) between the substantia nigra (SN) and ventral tegmental area (VTA) and the striatum differed between participants with ADHD and typically developing adolescent and young adult participants. We also assessed whether pathway connectivity predicted impulsivity regardless of diagnosis. MethodsDiffusion tensor imaging data were used to predict impulsivity (parent and self-report ratings, task-based behavioral measures) from participants with ADHD and typically developing adolescent and young adult participants (n = 155; 86 male, 69 female). Using probabilistic tractography, we mapped these pathways and divided the tracts into limbic, executive, and sensorimotor based on frontostriatal connectivity. ADHD and typically developing participants differed on all behavioral measures of impulsivity. We used correlation and machine learning analyses to test for a relationship between tract probabilities and impulsivity regardless of diagnosis. ResultsParticipants with ADHD had stronger structural connectivity between SN/VTA regions and the limbic striatum, weaker connectivity with the executive striatum, and no significant differences in sensorimotor tracts. Increased tract integrity between the limbic striatal and SN/VTA regions predicted greater impulsivity, while increased integrity between executive striatal and SN/VTA regions predicted reduced impulsivity. ConclusionsThese findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD.