Dorsal anterior cingulate glutamate is associated with engagement of the default mode network during exposure to smoking cues

Abstract

Background: When exposed to smoking cues, nicotine dependent individuals activate brain regions overlapping with the default mode network (DMN), a network of regions involved in internally-focused cognition. The salience network (SN), which includes the dorsal anterior cingulate cortex (dACC), is thought to interact with the DMN and aids in directing attention toward salient internal or external stimuli. One possibility is that neurochemical variation in SN regions such as the dACC impact DMN reactivity to personally relevant stimuli such as smoking cues. This is consistent with emerging evidence suggesting an association between midline cortical glutamate (Glu) and activity in brain regions overlapping with the DMN.

Methods: In 18 nicotine-dependent individuals, we assessed the relationship between DMN activation to smoking relative to neutral cues using functional magnetic resonance imaging and dACC Glu as measured by magnetic resonance spectroscopy. This association also was tested in a replication sample of 14 nicotine-dependent participants.

Results: Not only was the DMN significantly less suppressed during smoking cue exposure, but also there was a positive association between DMN reactivity to smoking relative to neutral cues and dACC Glu (r=0.56, p<0.02). This finding was confirmed in the independent replication cohort (r=0.64, p<0.02).

Conclusions: The current findings confirm that the DMN is less suppressed when smokers view smoking relative to neutral cues, suggesting that smoking cues engage self-relevant processing. Furthermore, these results indicate that dACC Glu is associated with enhanced DMN engagement when nicotine-dependent individuals are exposed to self-relevant smoking cues.

Keywords: Default mode network; Dorsal anterior cingulate cortex; Glutamate; Nicotine; fMRI.

Figure 1

Default mode network activation is significantly less suppressed when smokers view smoking cues. The green overlay on the brain images shows the DMN ROI taken from Smith et al 2009 used in all relevant analyses. The orange overlay shows the whole brain analysis results of the smoking vs. neutral contrast for the primary cohort, which significantly overlaps with the DMN ROI. The bar graph shows data from the primary cohort indicating that there is elevated DMN activity for the smoking > neutral contrast, which is driven by a lack of DMN suppression when smokers view smoking images. The asterisk indicates a significant difference between DMN reactivity to smoking cues and neutral cues (p < 0.001). This finding was confirmed by the replication cohort.

Figure 2

Representative J-resolved spectra showing the Glu and Cr peaks used in the analysis. Brain image shows the sagittal view of a representative T1-weighted image illustrating the 2 × 2 × 3cm voxel placement in the dACC.

Figure 3

There is a significant association between dACC Glu/Cr (y-axis) and the amount of DMN activation from the smoking > neutral contrast (x-axis) for both the primary and replication cohort.