TY - JOUR
T1 - Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms
AU - Mooney, Michael A.
AU - Hermosillo, Robert J.M.
AU - Feczko, Eric
AU - Miranda-Dominguez, Oscar
AU - Moore, Lucille A.
AU - Perrone, Anders
AU - Byington, Nora
AU - Grimsrud, Gracie
AU - Rueter, Amanda
AU - Nousen, Elizabeth
AU - Antovich, Dylan
AU - Feldstein Ewing, Sarah W.
AU - Nagel, Bonnie J.
AU - Nigg, Joel T.
AU - Fair, Damien A.
N1 - Publisher Copyright:
Copyright © 2024 the authors.
PY - 2024/3/6
Y1 - 2024/3/6
N2 - Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case–control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen’s d = −0.318, robust p = 5.5 × 10−4) than those with persistent ADHD (age 7–19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.
AB - Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case–control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen’s d = −0.318, robust p = 5.5 × 10−4) than those with persistent ADHD (age 7–19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.
KW - MRI
KW - attention-deficit hyperactivity disorder
KW - brain-wide association study
KW - polygenic score
KW - polyneuro score
KW - resting-state functional connectivity
UR - http://www.scopus.com/inward/record.url?scp=85187114028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85187114028&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1202-23.2023
DO - 10.1523/JNEUROSCI.1202-23.2023
M3 - Article
C2 - 38286629
AN - SCOPUS:85187114028
SN - 0270-6474
JO - Journal of Neuroscience
JF - Journal of Neuroscience
M1 - e1202232023
ER -