Resting-State Functional Connectivity of the Basal Nucleus of Meynert in Cigarette Smokers: Dependence Level and Gender Differences.
BACKGROUND
Numerous studies have characterized impaired cerebral functioning in nicotine-addicted individuals. Whereas nicotine interacts with multiple neurotransmitters in cortical and subcortical circuits, it directly targets the cholinergic system, sourced primarily from the basal nucleus of Meynert (BNM). However, no studies have examined how this cholinergic system is influenced by cigarette smoking. Here, we addressed this gap of research.


METHODS
Using a dataset from the Functional Connectome Projects, we investigated this issue by contrasting seed-based BNM connectivity of 40 current smokers and 170 age- and gender-matched nonsmokers. We followed our data analytic routines in recent work and examined differences between smokers and nonsmokers in men and women combined as well as separately.


RESULTS
Compared to nonsmokers, female but not male smokers demonstrated greater positive BNM connectivity to the supplementary motor area, bilateral anterior insula, and right superior temporal/supramarginal gyri as well as greater negative connectivity to the posterior cingulate cortex and precuneus. Further, BNM connectivity to the supplementary motor area is negatively correlated to the Fagerström Test for Nicotine Dependence score in male but not female smokers.


CONCLUSIONS
Along with a previous report of upregulated nicotinic acetylcholine receptor in male but not female smokers, these new findings highlight functional changes of the cholinergic systems in cigarette smokers. The results suggest sex-specific differences in cholinergic dysregulation and a need for multiple imaging modalities to capture the neural markers of nicotine addiction.


CONCLUSIONS
Nicotine influences cognition via cholinergic projections of the basal forebrain to the cerebral cortex. This study examined changes in resting-state whole-brain functional connectivity of the BNM in cigarette smokers. The new findings elucidate for the first time sex differences in BNM-cerebral connectivity in cigarette smoking.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Sheng
S
Zhang
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Sien
S
Hu
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Lisa M
LM
Fucito
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Xingguang
X
Luo
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.|Women's Health Research, Yale University School of Medicine, New Haven, CT.
Carolyn M
CM
Mazure
Center for Molecular and Behavioral Neuroscience, Rutgers, NJ.
Laszlo
L
Zaborszky
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.|Department of Neuroscience, Yale University School of Medicine, New Haven, CT.|Interdepartmental Neuroscience Program, Yale University, New Haven, CT.
Chiang-Shan R
CR
Li
D000328:Adult; D020532:Basal Nucleus of Meynert / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D012146:Rest / Q000502:physiology*; D012907:Smoking / Q000503:physiopathology*; D014029:Tobacco Use Disorder / Q000503:physiopathology*