Study author Ying Duan, Ph.D.
Featured Paper of the Month – June 2025
Published in Neuropsychopharmacology by Ying Duan and Yihong Yang of the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.
Summary
Being able to adapt behavior in response to changing situations—known as cognitive or behavioral flexibility—is often impaired in people with neuropsychiatric disorders including substance use disorders. The medial prefrontal cortex (mPFC)-nucleus accumbens (NAc) pathway plays a critical role in behavioral flexibility. However, how this pathway interacts with other brain regions to modify behavior remains poorly understood.
In this study, we first confirmed the role of the mPFC-NAc pathway in behavioral flexibility using a set-shifting task in rats. We then evaluated the causal effects of mPFC-NAc activation on whole-brain activity and functional connectivity measured by functional MRI. Activation of mPFC-NAc via chemogenetic techniques improved performance on the set-shifting task by reducing perseverative errors. Additionally, stimulation of this pathway increased activity in a set of brain regions within the basal ganglia-thalamus-cortical loop network, while decreased functional connectivity strength of NAc-mPFC, NAc-secondary motor cortex, and other cortical circuits. Critically, performance on a set-shifting task was related to the functional connectivity strength of these frontostriatal and cortical-cortical circuits.
These findings provide insights into the link between specific frontostriatal circuits and behavioral flexibility, which may inform potential future interventions for flexibility deficits.
Publication Information
Frontostriatal regulation of brain circuits contributes to flexible decision making Journal Article
In: Neuropsychopharmacology, vol. 50, no. 7, pp. 1156–1166, 2025, ISSN: 1740-634X.
