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

Abstract

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.

Figure 1

Brain regions where the Smoking Cue > Neutral Cue contrast was consistently significant across fMRI studies, as determined by ALE meta-analysis. The color map indicates the value of the ALE statistic in regions that were found to be significantly active using a whole-brain false discovery rate of q < .05 and a minimum cluster size of 200 mm³. These data were obtained from 12 experiments in which cigarette smokers (n = 224) viewed smoking-related and neutral pictures or videos during an fMRI scan. ACC = Anterior Cingulate Cortex, MeFG = Medial Frontal Gyrus, PCC = Posterior Cingulate Cortex, PrC = Precuneus, CUN = Cuneus, LG = Lingual Gyrus, SFG = Superior Frontal Gyrus, BS = Brainstem, ALE = Activation Likelihood Estimate. The x coordinate refers to the placement of the sagittal slice in Talairach-Tournoux space, where negative coordinates indicate the left side of the brain.

Figure 2

Brain regions where the Smoking Cue > Neutral Cue contrast was more reliably significant in studies of non-deprived smokers than in studies of deprived smokers, as determined by subtraction ALE meta-analysis. The color map indicates the value of the ALE difference score between the deprived and non-deprived conditions in regions that were found to be significantly active using a whole-brain false discovery rate of q < .05 and a minimum cluster size of 200 mm³. These data were obtained from 8 studies of non-deprived smokers (n = 181) and 4 studies of deprived smokers (n = 43) who viewed smoking-related and neutral pictures or videos during an fMRI scan. LG = Lingual Gyrus, SFG = Superior Frontal Gyrus, ALE = Activation Likelihood Estimate, R = Right, L = Left. The z coordinate refers to the placement of the axial slice in Talairach-Tournoux space, where negative coordinates are inferior to the plane connecting the anterior and posterior commissures.

Figure 3

In the bilateral fusiform gyri, the Smoking Cue > Neutral Cue contrast was more reliably significant in studies that used short stimulus presentation times (≤ 5 s) than in studies that used long stimulus presentation times (≥ 18 s), as determined by subtraction ALE meta-analysis. The color map indicates the value of the ALE difference score between the two groups of studies in regions that were found to be significantly active using a whole-brain false discovery rate of q < .05 and a minimum cluster size of 200 mm³. There were 5 studies (n = 68) that used short stimulus presentation times, and 7 studies that used long stimulus presentation times (n = 156). ALE = Activation Likelihood Estimate, R = Right, L = Left. The z coordinate refers to the placement of the axial slice in Talairach-Tournoux space, where negative coordinates are inferior to the plane connecting the anterior and posterior commissures.