Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence

Neuropsychopharmacology. 2016 Feb;41(3):877-85. doi: 10.1038/npp.2015.214. Epub 2015 Jul 16.


Environments associated with prior drug use provoke craving and drug taking, and set the stage for lapse/relapse. Although the neurobehavioral bases of environment-induced drug taking have been investigated with animal models, the influence of drug-environments on brain function and behavior in clinical populations of substance users is largely unexplored. Adult smokers (n=40) photographed locations personally associated with smoking (personal smoking environments; PSEs) or personal nonsmoking environment (PNEs). Following 24-h abstinence, participants underwent fMRI scanning while viewing PSEs, PNEs, standard smoking and nonsmoking environments, as well as proximal smoking (eg, lit cigarette) and nonsmoking (eg, pencil) cues. Finally, in two separate sessions following 6-h abstinence they viewed either PSEs or PNEs while cue-induced self-reported craving and smoking behavior were assessed. Viewing PSEs increased blood oxygen level-dependent signal in right posterior hippocampus (pHPC; F(2,685)=3.74, p<0.024) and bilateral insula (left: F(2,685)=6.87, p=0.0011; right: F(2,685)=5.34, p=0.005). In the laboratory, viewing PSEs, compared with PNEs, was associated with higher craving levels (F(2,180)=18.32, p<0.0001) and greater ad lib smoking (F(1,36)=5.01, p=0.032). The effect of PSEs (minus PNEs) on brain activation in right insula was positively correlated with the effect of PSEs (minus PNEs) on number of puffs taken from a cigarette (r=0.6, p=0.001). Our data, for the first time in humans, elucidates the neural mechanisms that mediate the effects of real-world drug-associated environments on drug taking behavior under conditions of drug abstinence. These findings establish targets for the development and evaluation of treatments seeking to reduce environment provoked relapse.

Trial registration: ClinicalTrials.gov NCT01840111.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Brain Mapping
  • Cerebral Cortex / physiopathology*
  • Craving / physiology
  • Cues
  • Environment*
  • Female
  • Hippocampus / physiopathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / physiopathology
  • Neuropsychological Tests
  • Photic Stimulation
  • Smoking / physiopathology*
  • Smoking / psychology
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / psychology
  • Tobacco Use Disorder / physiopathology*
  • Tobacco Use Disorder / psychology
  • Visual Perception / physiology*
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT01840111