Comprehensive mapping of cognitive and emotion networks in stress, anxiety, and depression implicates the precuneus...

Stress-related conditions disrupt cognition and emotion regulation and can result in psychiatric illness, but the neural circuit-level changes that can explain these broad effects remain unclear. To address this issue, we paired population-grounded discovery with out-of-sample testing. Using resting-state fMRI from > 14,000 healthy adults in the UK Biobank, we derived connectivity profiles tied to cognition (reaction time, numeric memory), and proxies of emotion dysregulation (neuroticism, anhedonia). We then applied the profiles to a trauma-exposed cohort (N = 306) to assess symptom relevance. Associations with stress, anxiety, and depression concentrated in a subset of circuit motifs, two of which recurred: (1) hyperintegration between the default mode and control/limbic interfaces, as well as (2) hypointegration between the default mode and visual interfaces, both tracked higher symptom burden. Static and dynamic analyses converged on the precuneus as a critical hub: stronger precuneus-visual coupling and greater occupancy of a precuneus-engaged dynamic state were related to lower symptoms, whereas the opposing state was related to higher burden. This novel hybrid approach-discover-thenproject-thus yielded interpretable markers of circuit dysfunction that generalized to post-trauma psychopathology. Furthermore, the approach identified the precuneus as a potential target for mechanistically informed interventions.