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

Research output: Contribution to journalReview articlepeer-review


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 stress-related 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.

Original languageEnglish (US)
Pages (from-to)443-469
Number of pages27
JournalAnnual Review of Clinical Psychology
StatePublished - 2022

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants U01DA041120 (M.L. and P.F.C.) and R01 1R01MH122473 (M.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
Copyright © 2022 by Annual Reviews. All rights reserved.


  • dopamine
  • executive function
  • externalizing
  • internalizing
  • neurodevelopment
  • neuroimaging

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural


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