Association Between Nicotine Dependence Severity, BOLD Response to Smoking Cues, and Functional Connectivity

Enhanced motivational salience towards smoking cues is a consequence of chronic nicotine use, but the degree to which this value increases beyond that of other appetitive cues is unknown. In addition, it is unclear how connectivity between brain regions influences cue reactivity and how cue reactivity and functional connectivity are related to nicotine dependence severity. This study examined neural responses during the presentation of smoking cues and appetitive control cues, as well as functional connectivity in 116 smokers with a range of nicotine dependence severity. Smoking cues elicited greater response above baseline than food cues in orbitofrontal cortex (OFC) and supplementary motor area (SMA) and less deactivation below baseline in middle frontal gyrus, inferior parietal lobe, and middle temporal gyrus. Psychophysiological interaction (PPI) analysis using right OFC as a seed revealed increased connectivity with somatosensory cortex and lateral inferior parietal lobe during smoking cues compared with food cues. Similarly, a PPI analysis using left insula as a seed showed stronger connectivity with somatosensory cortex, right insula, OFC, and striatum. Finally, relationships with nicotine dependence scores showed enhanced response in insula and dorsal anterior cingulate cortex in the smoking vs food comparison, and increased connectivity between insula and circuits involved in motivated behavior. Combined, these results suggest that smokers engage attentional networks and default mode networks involved in self-referential processing to a greater degree during smoking cues. In addition, individuals with greater nicotine dependence severity show increased engagement of sensorimotor and motor preparation circuits, suggesting increased reliance on habitual behavior.