title: The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate-precuneus pathway.
abstract: BACKGROUND
  Perturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus.
  
  
  METHODS
  Using functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting-state functional connectivity analysis using the anterior cingulate cortex as a seed.
  
  
  RESULTS
  Independent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed-based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60-0.76; P < 0.05).
  
  
  CONCLUSIONS
  In concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting-state functional connectivity in this pathway increases during nicotine withdrawal in correlation with the intensity of withdrawal-induced craving. These findings suggest that smoking triggers structural and functional neural adaptations in the brain that support withdrawal-induced craving.
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: Jean A
authors.initials: JA
authors.lastname: King
authors.affiliation: Department of Family Medicine and Community Health, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: W W Sanouri
authors.initials: WW
authors.lastname: Ursprung
authors.affiliation: Department of Radiology, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01605.
authors.forename: Shaokuan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: Nanyin
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: David N
authors.initials: DN
authors.lastname: Kennedy
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: Douglas
authors.initials: D
authors.lastname: Ziedonis
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655 ; Department of Family Medicine and Community Health, University of Massachusetts Medical School 55 Lake Avenue North, Worcester, Massachusetts, 01655.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: DiFranza
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology*; D014029:Tobacco Use Disorder / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
keywords: Addiction; nicotine; resting-state functional connectivity