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Protracted Maturation of Proactive and Reactive Systems Predicts Cognitive Stability and Psychopathology : A longitudinal multi-cohort study

Gao, Z.; Zheng, L.; Banaschewski, T.; Barker, G. J.; Bokde, A. L. W.; Bruehl, R.; Desrivieres, S.; Gowland, P.; Grigis, A.; Heinz, A.; Nees, F.; Papadopoulos Orfanos, D.; Poustka, L.; Smolka, M. N.; Hohmann, S.; Holz, N.; Vaidya, N.; Walter, H.; Whelan, R.; Wirsching, P.; Schumann, G.; Garavan, H.; Menon, V.; Cai, W.; IMAGEN Consortium,

2026-07-10 neuroscience
10.64898/2026.07.07.736457 bioRxiv
Show abstract

Inhibitory control matures progressively from childhood to early adulthood, yet the neural mechanisms driving this development and their relevance to psychiatric risk remain poorly understood. Guided by the Dual Cognitive Control model, we leveraged longitudinal fMRI from two independent cohorts in the US (ABCD, ages 9-12) and Europe (IMAGEN, ages 14-22) to map the spatiotemporal dynamics of reactive and proactive control using novel single-trial modeling and representational similarity analysis. We found both reactive and proactive stopping networks stabilize after mid-adolescence, tracking the developmental patterns of inhibitory control and behavioral stability. By decoding trial-by-trial fluctuations along a speed-caution continuum, we demonstrate that brain-behavior coupling to a proactive "Safe state" tightens progressively with age. Furthermore, network-level representational coherence of this Safe state emerged as a scanner-invariant, trait-like biomarker that robustly predicted inhibitory control, behavioral stability, and transdiagnostic psychopathology across multiple developmental windows, providing a validated neural phenotype for precision psychiatry.

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