title: Insula's functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving.
abstract: BACKGROUND
  Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking.
  
  
  OBJECTIVE
  We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC).
  
  
  METHODS
  Overnight-deprived smokers (n = 24) and nonsmokers (n = 20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC.
  
  
  RESULTS
  Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI-vmPFC circuit fully mediated this alexithymia-craving relation. That is, elevated alexithymia predicted decreased aI-vmPFC rsFC and, in turn, decreased aI-vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI-vmPFC mediational effect was not observed following drug administration.
  
  
  CONCLUSIONS
  These results suggest that a weakened right aI-vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI-vmPFC functional coupling may be relevant factors for smoking cessation success.
authors: Department of Psychology, Florida International University, Miami, FL, USA. masuther@fiu.edu
authors: Matthew T
authors: MT
authors: Sutherland
authors: Allison J
authors: AJ
authors: Carroll
authors: Betty Jo
authors: BJ
authors: Salmeron
authors: Thomas J
authors: TJ
authors: Ross
authors: Elliot A
authors: EA
authors: Stein
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000523:psychology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism*; D003463:Cues; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D012907:Smoking / Q000523:psychology*; D016540:Smoking Cessation / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D014029:Tobacco Use Disorder / Q000523:psychology