title: Progressive levels of physical dependence to tobacco coincide with changes in the anterior cingulum bundle microstructure.
abstract: BACKGROUND
  The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).
  
  
  METHODS
  Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation to two additional measures of dependence severity, the Hooked on Nicotine Checklist (HONC), and the Fagerström Test for Nicotine Dependence (FTND).
  
  
  RESULTS
  Among smokers, FA in the left anterior cingulate bundle (ACb) correlated negatively with the Level of PD (r = -0.68, p = 0.02) and HONC scores (r = -0.65, p = 0.03), but the correlation for the FTND did not reach statistical significance (r = -49, p = 0.12). With advancing Levels of PD, the density of streamlines between the ACb and precuneus increased (r = -0.67, p<0.05) and those between the ACb and white matter projecting to the superior-frontal cortex (r = -0.86, p = 0.0006) decreased significantly.
  
  
  CONCLUSIONS
  The correlations between neural structure and both the clinical Level of PD survey measure and the HONC suggest that the Level of PD and the HONC may reflect the microstructural integrity of white matter, as influenced by tobacco abuse. Given that the Level of PD is measuring a sequence of symptoms of neurophysiologic dependence that develops over time, the correlation between the Level of PD and neural structure suggests that these features might represent neuroplastic changes that develop over time to support the development of neurophysiologic dependence.
authors.affiliation: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Joseph R
authors.initials: JR
authors.lastname: DiFranza
authors.forename: David N
authors.initials: DN
authors.lastname: Kennedy
authors.forename: Nanyin
authors.initials: N
authors.lastname: Zhang
authors.forename: Douglas
authors.initials: D
authors.lastname: Ziedonis
authors.forename: Sanouri
authors.initials: S
authors.lastname: Ursprung
authors.forename: Jean A
authors.initials: JA
authors.lastname: King
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D003337:Corpus Callosum / Q000503:physiopathology* / Q000648:ultrastructure; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D011594:Psychometrics; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000503:physiopathology* / Q000523:psychology