Neural substrates of smoking cue reactivity: a meta-analysis of fMRI studies.

Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity.