Background: Current diagnostic systems for neurodevelopmental disorders do not have clear links to underlying neurobiology, limiting their utility in identifying targeted treatments for individuals. Here, we aimed to investigate differences in functional brain network integrity between traditional diagnostic categories (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], typically developing [TD]) and carefully consider the impact of comorbid ASD and ADHD on functional brain network integrity in a sample adequately powered to detect large effects. We also assess the neurobiological separability of a novel, potential alternative categorical scheme based on behavioral measures of executive function. Method: Five-minute resting-state fMRI data were obtained from 168 children (128 boys, 40 girls) with ASD, ADHD, comorbid ASD and ADHD, and TD children. Independent component analysis and dual regression were used to compute within- and between-network functional connectivity metrics at the individual level. Results: No significant group differences in within- or between-network functional connectivity were observed between traditional diagnostic categories (ASD, ADHD, TD) even when stratified by comorbidity (ASD + ADHD, ASD, ADHD, TD). Similarly, subgroups classified by executive functioning levels showed no group differences. Conclusions: Using clinical diagnosis and behavioral measures of executive function, no differences in functional connectivity were observed among the categories examined. Despite our limited ability to detect small- to medium-sized differences between groups, this work contributes to a growing literature suggesting that traditional diagnostic categories do not define neurobiologically separable groups. Future work is necessary to ascertain the validity of the executive function-based nosology, but current results suggest that nosologies reliant on behavioral data alone may not lead to discovery of neurobiologically distinct categories.
Bibliographical noteFunding Information:
We thank Jeanette Mumford for her contribution to the statistical modeling of the group difference tests. This work was supported by the National Institute of Mental Health (R01MH107549) to LQU. This work was also funded by Autism Speaks and NIH: R01NS048527, R01 MH085328, R01 MH078160, the Johns Hopkins UniversitySchool of MedicineInstitute for Clinical and Translational Research, and NIH/NCRR CTSA Program, UL1-RR025005, to S.H.M.
We thank Jeanette Mumford for her contribution to the statistical modeling of the group difference tests. This work was supported by the National Institute of Mental Health ( R01MH107549 ) to LQU. This work was also funded by Autism Speaks and NIH : R01NS048527 , R01 MH085328 , R01 MH078160 , the Johns Hopkins University School of Medicine Institute for Clinical and Translational Research , and NIH/NCRR CTSA Program, UL1-RR025005, to S.H.M.
- Functional connectivity
- Research domain criteria