Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

Cognitive and behavioural flexibility permit the appropriate adjustment of thoughts and behaviours in response to changing environmental demands. Brain mechanisms enabling flexibility have been examined using non-invasive neuroimaging and behavioural approaches in humans alongside pharmacological and lesion studies in animals. This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan. Flexibility can be compromised in early-life neurodevelopmental disorders, clinical conditions that emerge during adolescence and late-life dementias. We critically evaluate evidence for the enhancement of flexibility through cognitive training, physical activity and bilingual experience. Flexibility is critical for the optimal adaptation of thoughts and actions under changing circumstances. In this Review, Uddin summarizes research that has identified cognitive processes and neural systems supporting flexibility and discusses ways to improve flexibility across the lifespan.