Functional segregation of the human basal forebrain using resting state neuroimaging

The basal forebrain (BF) is poised to play an important neuromodulatory role in brain regions important to cognition due to its broad projections and complex neurochemistry. While significant in vivo work has been done to elaborate BF function in nonhuman rodents and primates, comparatively limited work has examined the in vivo function of the human BF. In the current study we used multi-echo resting state functional magnetic resonance imaging (rs-fMRI) from 100 young adults (18-34 years) to assess the potential segregation of human BF nuclei as well as their associated projections. Bottom-up clustering of voxel-wise functional connectivity maps yielded adjacent functional clusters within the BF that closely aligned with the distinct, hypothesized nuclei important to cognition: the nucleus basalis of Meynert (NBM) and the medial septum/diagonal band of Broca (MS/DB). Examining their separate functional connections, the NBM and MS/DB revealed distinct projection patterns, suggesting a conservation of nuclei specific functional connectivity with homologous regions known to be anatomically innervated by the BF. Specifically, the NBM demonstrated coupling with a widespread cortical network as well as the amygdala, whereas the MS/DB revealed coupling with a more circumscribed network, including the orbitofrontal cortex and hippocampal complex. Collectively, these in vivo rs-fMRI data demonstrate that the human BF nuclei support functional networks distinct aspects of resting-state functional networks, suggesting the human BF may be a neuromodulatory hub important for orchestrating network dynamics.