Impulsivity 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 nigro-striatal 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 substantia nigra and ventral tegmental area (SN/VTA) and striatum differed between ADHD and typically developing (TD) adolescent and young adult participants (AYA). We also assessed whether pathway connectivity predicted impulsivity regardless of diagnosis.
Diffusion tensor imaging data were used to predict impulsivity (parent and self-report ratings, task-based behavioral measures) from ADHD and TD AYA 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 TD 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.
Participants with ADHD had stronger structural connectivity between SN/VTA regions and limbic striatum, weaker connectivity with executive striatum, and no significant differences in sensorimotor tracts. Increased tract integrity between limbic striatal and SN/VTA regions predicted greater impulsivity, while increased integrity between executive striatal and SN/VTA regions predicted reduced impulsivity.
These findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD.

Copyright © 2021. Published by Elsevier Inc.