Nicotine modulates prefrontal processing when tested with functional imaging. Previous studies on changes in regional brain volumes in small samples, reporting different life-time exposure to nicotine, identified reduced volume in smokers in prefrontal areas but reported controversial results for other areas. We investigated the association of cigarette smoking and regional gray and white matter volume by using voxel-based morphometry (VBM) for T1-weighted high-resolution magnetic resonance imaging in 315 current-smokers and 659 never-smokers from the representative Study of Health in Pomerania (SHIP). Our study showed that in current-smokers smoking is significantly associated with gray matter volume loss in the prefrontal cortex, the anterior cingulate cortex, the insula, and the olfactory gyrus. White matter volumes were not relevantly reduced in current-smokers. In current-smokers, we found associations of gray matter loss and smoking exposure (pack-years) in the prefrontal cortex, the anterior and middle cingulate cortex, and the superior temporal and angular gyrus, which however did not stand corrections for multiple testing. We confirmed associations between smoking and gray matter differences in the prefrontal cortex, the anterior cingulate cortex and the insula in the general population of Pomerania (Germany). For the first time, we identified differences in brain volumes in the olfactory gyrus. Other cerebral regions did not show significant differences when correcting for multiple comparisons within the whole brain. The regions of structural deficits might be involved in addictive behavior and withdrawal symptoms, whereas further investigations have to show if the observed atrophies were caused by smoking itself or are preexisting differences between smoking and non-smoking individuals.

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The cholinergic basal forebrain (CBF), comprising different groups of cortically projecting cholinergic neurons, plays a crucial role in higher cognitive processes and has been implicated in diverse neuropsychiatric disorders. A distinct corticotopic organization of CBF projections has been revealed in animal studies, but little is known about their organization in the human brain. We explored regional differences in functional connectivity (FC) profiles within the human CBF by applying a clustering approach to resting‐state functional magnetic resonance imaging (rs‐fMRI) data of healthy adult individuals (N = 85; 19–85 years). We further examined effects of age on FC of the identified CBF clusters and assessed the reproducibility of cluster‐specific FC profiles in independent data from healthy older individuals (N = 25; 65–89 years). Results showed that the human CBF is functionally organized into distinct anterior‐medial and posterior‐lateral subdivisions that largely follow anatomically defined boundaries of the medial septum/diagonal band and nucleus basalis Meynert. The anterior‐medial CBF subdivision was characterized by connectivity with the hippocampus and interconnected nodes of an extended medial cortical memory network, whereas the posterior‐lateral subdivision was specifically connected to anterior insula and dorsal anterior cingulate components of a salience/attention network. FC of both CBF subdivisions declined with increasing age, but the overall topography of subregion‐specific FC profiles was reproduced in independent rs‐fMRI data of healthy older individuals acquired in a typical clinical setting. Rs‐fMRI‐based assessments of subregion‐specific CBF function may complement established volumetric approaches for the in vivo study of CBF involvement in neuropsychiatric disorders.

Highlights Multimodal MRI analysis of cholinergic basal forebrain (cBF) changes in AD spectrum. Robust changes in cBF volume and diffusivity in MCI and AD dementia. Only minimal changes in cBF functional connectivity across the AD spectrum. No imaging modality detects significant cBF changes in subjective cognitive decline. Similar results in subset analysis of patients with biomarker-confirmed Aβ-pathology.