Generalizable prediction of stimulus-independent, task-unrelated thought from functional brain networks

Neural substrates of “mind wandering” have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering—stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling—dominated by default-frontoparietal control subnetwork interactions—that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of attention-deficit/hyperactivity disorder (ADHD) adults. In three additional resting-state fMRI studies (total n =1,115), including healthy and ADHD populations, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales, populations, and contexts. ### Competing Interest Statement A.K., M.E., E.M.V., J.C., A.G., M.U., J.D.E.G., and S.W.G. have no competing interests. Dr. Joseph Biederman is currently receiving research support from the following sources: AACAP, Feinstein Institute for Medical Research, Food and Drug Administration, Genentech, Headspace Inc., NIDA, Pfizer Pharmaceuticals, Roche TCRC Inc., Sunovion Pharmaceuticals Inc., Takeda/Shire Pharmaceuticals Inc., Tris, and NIH. He receives honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. Dr. Biederman's program has received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Biomarin, Bracket Global, Cogstate, Ingenix, Medavent Prophase, Shire, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. In 2020: Through MGH corporate licensing, Dr. Biederman has a US Patent (#14/027,676) for a non-stimulant treatment for ADHD, a US Patent (#10,245,271 B2) on a treatment of impaired cognitive flexibility, and a patent pending (#61/233,686) on a method to prevent stimulant abuse. In 2019, Dr. Biederman was a consultant for Akili, Avekshan, Jazz Pharma, and Shire/Takeda. He received research support from Lundbeck AS and Neurocentria Inc. Through MGH CTNI, he participated in a scientific advisory board for Supernus. In 2018, Dr. Biederman was a consultant for Akili and Shire. In 2017, Dr. Biederman received research support from the Department of Defense and PamLab. He was a consultant for Aevi Genomics, Akili, Guidepoint, Ironshore, Medgenics, and Piper Jaffray. He was on the scientific advisory board for Alcobra and Shire.