Cue-elicited craving, thalamic activity, and physiological arousal in adult non-dependent drinkers

Changes in physiological arousal frequently accompany cognitive and affective challenges. Many studies employed cue exposure paradigms to investigate the neural processes underlying cue-elicited drug and alcohol craving. However, whether cue-elicited craving relates to changes in physiological arousal and the neural bases underlying the potential relationship remain unclear. Here we examined cerebral cue-related activations in relation to differences in skin conductance responses (SCR) recorded during alcohol vs. neutral cue blocks in 61 non-dependent alcohol drinkers (30 men). Imaging and skin conductance data were collected and processed with published routines. Mediation analyses were conducted to examine the inter-relationship between regional activities, cue-elicited craving, and SCR. The results showed higher SCR during alcohol than during neutral cue exposure. Despite no differences in drinking characteristics, men as compared to women demonstrated higher craving rating, and men but not women demonstrated a positive correlation between alcohol (vs. neutral) cue-evoked craving and SCR. Further, across subjects, thalamic cue activity was positively correlated with differences in SCR between alcohol and neutral cue blocks in men but not in women. Mediation analyses suggested that thalamic activity mediated the correlation between craving and SCR across men and women, and in men but not women alone. These findings substantiate physiological and neural correlates of alcohol cue response and suggest important sex differences in the physiological and neural processes of cue evoked craving. Centered on the intralaminar and mediodorsal subregions, the thalamic correlate may represent a neural target for behavioral or pharmacological therapy to decrease cue-elicited arousal and craving.