Neuroplasticity, the Prefrontal Cortex, and Psychopathology-Related Deviations in Cognitive Control

A basic survival need is the ability to respond to, and persevere in the midst of, experiential challenges. Mechanisms of neuroplasticity permit this responsivity via functional adaptations (flexibility), as well as more substantial structural modifications following chronic stress or injury. This review focuses on prefrontally based flexibility, expressed throughout large-scale neuronal networks through the actions of excitatory and inhibitory neurotransmitters and neuromodulators. With substance use disorders and stressrelated internalizing disorders as exemplars, we review human behavioral and neuroimaging data, considering whether executive control, particularly cognitive flexibility, is impaired premorbidly, enduringly compromised with illness progression, or both. We conclude that deviations in control processes are consistently expressed in the context of active illness but operate through different mechanisms and with distinct longitudinal patterns in externalizing versus internalizing conditions.