Repeated detoxification of alcohol-dependent patients impairs brain mechanisms of behavioural control important in resisting relapse

Alcohol abuse is frequently characterised by cycles of heavy drinking, detoxification, and relapse. We review evidence that multiple detoxifications are associated with impaired ability to control reward seeking, and with exaggerated responses to negative emotional stimuli. Under conditions of incentive conflict and in intra-extra dimensional shift and reversal tasks, deficits are found that are consistent with impaired executive control of behaviour by prefrontal cortical mechanisms. Correspondingly, alcoholics who have undergone multiple detoxifications show loss of grey matter in prefrontal regions associated with accurate performance of these tasks, the extent correlating with numbers of detoxifications. The ability to respond appropriately to certain emotional stimuli (e.g., fearful faces) is also impaired following multiple detoxifications. Such impairments are associated with reduced connectivity between insula and prefrontal areas but increased connectivity between insula and subcortical regions (colliculus), and between amygdala and other subcortical regions (bed nucleus of stria terminalis, BNST). Such changes may increase vulnerability to stress-induced relapse, and disrupt social abilities, contributing to social isolation.