Neural Circuits of Cognitive Flexibility

Cognitive flexibility is a higher-order executive function that is necessary to flexibly adapt previously learned behaviors to a changing environment. This cognitive function enables an individual to “look at things differently” and to adapt to one’s environment, instead of engaging in perseverative thinking that can lead to rumination and mental rigidity. Cognitive flexibility is impaired in several psychiatric disorders, including major depression, generalized anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder. A major risk factor for the pathogenesis of these disorders is chronic stress, which has been shown to reduce cognitive flexibility. In addition, a higher propensity for cognitive flexibility can promote stress resilience, possibly by enabling flexible adjustment of cognitive or behavioral coping strategies. Here, we aim to understand which corticolimbic neural circuits regulate cognitive flexibility and how they are affected by stress. We are particularly interested in the role of neural projections from the hippocampus to the prefrontal cortex regulate, and if these projections can be targeted to promote active stress coping and stress resilience.