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Limited generalizability of dynamic fMRI correlates of adolescent rumination

Treves, I. N.; Park, M. S.; Spence, J.; Jaffe, N.; Pidvirny, K.; Tierney, A. O.; Kucyi, A.; Gabrieli, J. D. E.; Auerbach, R. P.; Webb, C. A.

2025-09-03 neuroscience
10.1101/2025.08.29.673124 bioRxiv
Show abstract

Rumination, or perseverative negative self-referential thinking, is a hallmark of depression. In adults, a dynamic resting-state fMRI model of trait rumination was recently identified through predictive modelling. In adolescents, a development period during which rumination and depression increase, the neurobiological correlates of ruminative thinking are less clear. In the current preregistered study, we examine dynamic connectivity correlates of self-reported rumination in the largest sample of adolescents to date (n = 443, containing clinical and non-clinical individuals). Notably, the adult model failed to generalize to our sample. In addition, linear models trained on default-mode network (DMN) connectivity, as well as whole-brain connectome models, failed to generalize to held-out data. In an exploratory random forest analysis, we found significant prediction performance of a model where increased variability between DMN-cerebellum, DMN-dorsal attention network, and DMN-DMN connections was nominally associated with higher rumination. However, the model did not generalize to an external sample with lower rumination scores and a distinct scanner protocol. Our findings illustrate the difficulty of characterizing the neurodevelopment of risk factors for depression.

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