Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms
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 eff...
Saved in:
| Published in | The Journal of neuroscience Vol. 44; no. 10; p. e1202232023 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Society for Neuroscience
06.03.2024
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Summary: | 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,
= 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (
= 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (
< 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
= -0.318, robust
= 5.5 × 10
) 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. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 D.A.F. is a patent holder on the Framewise Integrated Real-Time Motion Monitoring software. He is also a cofounder of Nous Imaging. The nature of this financial interest and the design of the study have been reviewed by two committees at the University of Minnesota. They have put in place a plan to help ensure that this research study is not affected by the financial interest. All other authors report no biomedical financial interests or potential conflicts of interest. Author contributions: M.A.M., R.J.M.H., E.F., O.M.-D., L.A.M., A.P., N.B., G.G., A.R., E.N., D.A., S.W.F.E., B.J.N., J.T.N., and D.A.F. designed research; M.A.M., R.J.M.H., E.F., O.M.-D., A.P., N.B., G.G., A.R., E.N., and D.A. performed research; M.A.M., R.J.M.H., E.F., and O.M.-D. analyzed data; M.A.M. wrote the first draft of the paper; all authors edited the paper. Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit >10,000 children aged 9–10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. The ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from the ABCD 2.0.1 data release (http://dx.doi.org/10.15154/1504041). This work was supported by funding from the National Institute of Mental Health of the National Institutes of Health under award numbers R01MH115357 (D.A.F. and J.T.N.), R37MH059105 (J.T.N.), R01MH131685 (M.A.M. and J.T.N.), U01DA041148 (D.A.F., B.J.N., and S.W.F.E.), and U24DA041123 (D.A.F.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The creation of genetic scores benefited from the collaboration of the OHSU Integrated Genomics Core (Chris Harrington, Ph.D., director) and Kristina Vartanian. Large-scale image processing across the data set greatly benefited from collaboration with the Masonic Institute for the Developing Brain Informatics Group (MIDB-IG, Thomas Pengo, Ben Lynch, Timothy Hendrickson, James Wilgenbusch). An earlier version of this paper was posted on the medRxiv preprint server (https://doi.org/10.1101/2021.11.16.21266121). |
| ISSN: | 0270-6474 1529-2401 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.1202-23.2023 |