title: Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations.
abstract: BACKGROUND
  Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations.
  
  
  METHODS
  We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural-functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding.
  
  
  RESULTS
  Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural-functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula's task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum's interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing.
  
  
  CONCLUSIONS
  Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum).
authors.affiliation: Department of Psychology, Florida International University, AHC-4, RM 312, 11200 S.W. 8th St, Miami, FL, 33199, USA. masuther@fiu.edu.
authors.forename: Matthew T
authors.identifier: http://orcid.org/0000-0002-6091-4037
authors.initials: MT
authors.lastname: Sutherland
authors.affiliation: Department of Psychology, Florida International University, AHC-4, RM 312, 11200 S.W. 8th St, Miami, FL, 33199, USA.|Department of Physics, Florida International University, Miami, FL, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Riedel
authors.affiliation: Department of Psychology, Florida International University, AHC-4, RM 312, 11200 S.W. 8th St, Miami, FL, 33199, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Flannery
authors.affiliation: Department of Psychology, Auburn University, Auburn, AL, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Yanes
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.|South Texas Veterans Health Care System, San Antonio, TX, USA.|State Key Laboratory for Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, China.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.affiliation: Department of Physics, Florida International University, Miami, FL, USA.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Laird
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D059906:Neuroimaging; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology*; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology
keywords: Addiction; Cerebellum; Cigarettes; Gray matter; Insula; Mediodorsal thalamus; Morphometry; Nicotine; Ventromedial prefrontal cortex