RT Journal Article SR Electronic T1 Differential impact of transdiagnostic, dimensional psychopathology on multiple scales of functional connectivity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.05.434151 DO 10.1101/2021.03.05.434151 A1 Seok, Darsol A1 Beer, Joanne A1 Jaskir, Marc A1 Smyk, Nathan A1 Jaganjac, Adna A1 Makhoul, Walid A1 Cook, Philip A1 Elliott, Mark A1 Shinohara, Russell A1 Sheline, Yvette I. YR 2021 UL http://biorxiv.org/content/early/2021/03/07/2021.03.05.434151.abstract AB Introduction Dimensional psychopathology strives to associate different domains of cognitive dysfunction with brain circuitry. Connectivity patterns as measured by functional magnetic resonance imaging (fMRI) exist at multiple scales, with global networks of connectivity composed of microscale interactions between individual nodes. It remains unclear how separate dimensions of psychopathology might differentially impact these different scales of organization.Methods Patients experiencing anxious misery symptomology (depression, anxiety and trauma; n = 192) were assessed for symptomology and received resting-state fMRI scans. Three modeling approaches (seed-based correlation analysis [SCA], support vector regression [SVR] and Brain Basis Set Modeling [BSS]), each relying on increasingly dense representations of functional connectivity patterns, were used to associate connectivity patterns with six different dimensions of psychopathology: anxiety sensitivity, anxious arousal, rumination, anhedonia, insomnia and negative affect. Importantly, a full 50 patients were held-out in a testing dataset, leaving 142 patients as training data.Results Different symptom dimensions were best modeled by different scales of brain connectivity: anhedonia and anxiety sensitivity were best modeled with single connections (SCA), insomnia and anxious arousal by mesoscale patterns (SVR) and negative affect and ruminative thought by broad, cortex-spanning patterns (BBS). Dysfunction within the default mode network was implicated in all symptom dimensions that were best modeled by multivariate models.Conclusion These results suggest that symptom dimensions differ in the degree to which they impact different scales of brain organization. In addition to advancing our basic understanding of transdiagnostic psychopathology, this has implications for the translation of basic research paradigms to human disorders.Competing Interest StatementThe authors have declared no competing interest.