TY - JOUR
T1 - Limbic and Executive Meso- and Nigrostriatal Tracts Predict Impulsivity Differences in Attention-Deficit/Hyperactivity Disorder
AU - Elliott, Blake L.
AU - D'Ardenne, Kimberlee
AU - Mukherjee, Prerona
AU - Schweitzer, Julie B.
AU - McClure, Samuel M.
N1 - Funding Information:
This work was supported by the National Science Foundation Graduate Research Fellowships Program (to BLE), National Science Foundation Grant No. 1634179 (to SMM), and National Institute of Mental Health Grant No. 2 R01 MH091068 (to JBS and SMM). The authors thank J. Faye Dixon, Ph.D. for assistance with the diagnostic procedure and Murat Pakyurek for screening for medical concerns. The authors acknowledge the kind support of all their research participants, as well as of Catherine Fassbender, Ph.D.; Tadeus Arthur Hartanto, M.B.A.; Catrina A. Calub, M.A.; Amrita Ramakrishnan; Erin Calfee, M.A.; Lauren Boyle, Ph.D.; Laurel Cavallo; Maria B.E. Menor; Jessica Nguyen; and Steven J. Riley, M.A. The authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This work was supported by the National Science Foundation Graduate Research Fellowships Program (to BLE), National Science Foundation Grant No. 1634179 (to SMM), and National Institute of Mental Health Grant No. 2 R01 MH091068 (to JBS and SMM).
Publisher Copyright:
© 2021
PY - 2022/4
Y1 - 2022/4
N2 - Background: 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 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. Methods: Diffusion 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. Results: Participants 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. Conclusions: These findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD.
AB - Background: 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 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. Methods: Diffusion 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. Results: Participants 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. Conclusions: These findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD.
KW - ADHD
KW - DTI
KW - Dopamine
KW - Impulsivity
KW - MRI
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U2 - 10.1016/j.bpsc.2021.05.002
DO - 10.1016/j.bpsc.2021.05.002
M3 - Article
C2 - 34051394
AN - SCOPUS:85126908513
SN - 2451-9022
VL - 7
SP - 415
EP - 423
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 4
ER -