title: Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence.
abstract: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Duke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, USA.
authors.forename: F Joseph
authors.initials: FJ
authors.lastname: McClernon
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Conklin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Rachel V
authors.initials: RV
authors.lastname: Kozink
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Center for Cognitive Neuroscience, Duke University, Durham, NC, USA.
authors.forename: R Alison
authors.initials: RA
authors.lastname: Adcock
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Sweitzer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Duke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Merideth A
authors.initials: MA
authors.lastname: Addicott
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Duke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ying-hui
authors.initials: YH
authors.lastname: Chou
authors.affiliation: Duke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, USA.|Department of Radiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Nan-kuei
authors.initials: NK
authors.lastname: Chen
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hallyburton
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeVito
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D066249:Craving / Q000502:physiology; D003463:Cues; D004777:Environment; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D012907:Smoking / Q000503:physiopathology* / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000523:psychology; D014029:Tobacco Use Disorder / Q000503:physiopathology* / Q000523:psychology; D014796:Visual Perception / Q000502:physiology*; D055815:Young Adult