The corticotopic organization of the human basal forebrain as revealed by regionally selective functional...

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.