1. ¹McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
2. ²Department of Psychology, McGill University, Montreal, QC, Canada

Correspondence: Dr A Dagher, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, 3801 University St., Montreal, QC, Canada H3A 2B4. Tel: +1 514 398 1726; Fax: +1 514 398 8948; E-mail: alain@bic.mni.mcgill.ca

Received 26 September 2005; Revised 1 February 2006; Accepted 27 February 2006; Published online 5 April 2006.

Abstract

Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.