Impaired fear recognition and attentional set-shifting is associated with brain structural changes in alcoholic patients

Alcoholic patients with multiple detoxifications/relapses show cognitive and emotional deficits. We performed structural magnetic resonance imaging and examined performance on a cognitive flexibility task (intra-extradimensional set shift and reversal; IED). We also presented subjects with fearful, disgust and anger facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social drinker controls (n = 31). Alcoholic patients were less able than controls to change their behavior in accordance with the changing of the rules in the IED and they were less accurate in recognizing fearful expressions in particular. They also showed lower gray matter volume compared with controls in frontal brain areas, including inferior frontal cortex (IFC) and insula that mediate emotional processing, inferior parietal lobule and medial frontal cortex that mediate attentional and motor planning processes, respectively. Impairments in performance and some of the regional decreases in gray matter were greater in MDTx. Gray matter volume in IFC in patients was negatively correlated with the number of detoxifications, whereas inferior parietal lobule was negatively correlated with the control over drinking score (impaired control over drinking questionnaire). Performance in IED was also negatively correlated with gray matter volume in IFC/BA47, whereas recognition of fearful faces was positively correlated with the IFC gray matter. Repeated episodes of detoxification from alcohol, related to severity of dependency, are coupled with altered brain structure in areas of emotional regulation, attention and motor planning. Such changes may confer increased inability to switch behavior according to environmental demands and social incompetence, contributing to relapse.