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Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm

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Published on: May 4, 2020

Flexible brain state engagement predicts cognitive control transdiagnostically.

Jean Ye, Saloni Mehta, Milana Khaitova

Biorxiv : the Preprint Server for Biology

|January 23, 2026

Summary

Flexible brain state engagement supports cognitive control across diverse psychiatric disorders. This brain network flexibility is key to adapting responses, offering insights into mental health variations.

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Area of Science:

Neuroscience
Psychiatry
Computational Psychiatry

Background:

Cognitive control is crucial for adaptation but its neural basis in psychiatric disorders is unclear.
Altered cognitive control is a common feature across various mental health conditions.
Understanding the neural mechanisms is vital for developing targeted interventions.

Purpose of the Study:

To investigate if flexible recruitment of brain states serves as an intermediate phenotype for cognitive control.
To examine this relationship across transdiagnostic psychiatric samples.
To identify shared neural networks supporting cognitive control flexibility.

Main Methods:

Utilized machine learning and external validation on three independent datasets (N>600).
Assessed cognitive control components (inhibition, shift) using task and questionnaire data.
Employed connectome-based predictive modeling and analyzed brain network dynamics.

Main Results:

Flexible brain state engagement robustly predicted cognitive control metrics across datasets and participant groups.
Shared brain networks underpinned flexible brain state engagement in a transdiagnostic manner.
Temporal alignment of flexible brain state engagement and network connectivity correlated with better cognitive control.

Conclusions:

Flexible engagement of brain states is a robust intermediate phenotype for cognitive control.
This flexibility supports both inter- and intra-individual differences in cognitive control.
Findings offer a transdiagnostic neural mechanism linking brain dynamics to cognitive function in mental health.