Background Cigarette smoking is associated with metabolite abnormalities in anterior brain regions, but it is unclear if these abnormalities are apparent in other regions. Additionally, relationships between regional brain metabolite levels and measures of decision-making, risk-taking, and impulsivity in smokers and non-smokers have not been investigated. Methods Young/middle-aged (predominately male) non-smokers (n=30) and smokers (n=35), were compared on N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-containing compounds (Cr), myo-Inositol (mI), and glutamate (Glu) levels in the anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) via 4 Tesla (T) proton magnetic resonance (MR) single volume spectroscopy. Groups were also compared on NAA, Cho, Cr, and mI concentrations in the gray matter (GM) and white matter (WM) of the four cerebral lobes and subcortical nuclei/regions with 1.5T proton MR spectroscopic imaging. Associations of regional metabolite levels with neurocognitive, decision-making, risk-taking, and self-reported impulsivity measures were examined. Results Smokers showed lower DLPFC NAA, Cr, mI and Glu concentrations, and lower lenticular nuclei NAA level; smokers also demonstrated greater age-related decreases of DLPFC NAA, and ACC and DLPFC Glu levels. Smokers exhibited poorer decision-making and greater impulsivity. Across the sample, higher NAA and Glu in the DLPFC and NAA concentrations in multiple lobar GM and WM regions and subcortical nuclei were associated with better neurocognition and lower impulsivity. Conclusions This study contributes additional novel evidence that chronic smoking in young/middle-aged individuals is associated with significant age-related neurobiological abnormalities in anterior frontal regions implicated in the development and maintenance of addictive disorders.

Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions.

The rhesus monkey is a useful model for examining age-related as well as other neurological and developmental effects on the brain, because of the extensive neuroanatomical homology to the human brain, the reduced occurrence of neurological diseases such as Alzheimer’s disease as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses. In this study, cortical thickness measurements based on a cortical surface modeling technique were applied for the first time to investigate cortical thickness patterns in the rhesus monkey brain, and were used to evaluate regional age related effects across a wide range of ages. Age-related effects were observed in several cortical areas, in particular in the somatosensory and motor cortices, where a robust negative correlation of cortical thickness with age was observed, similar to that found in humans. In contrast, results for monkeys compared to humans show significant inter-species differences in cortical thickness patterns in the frontal and the inferior temporal regions.