Shankar Vallabhajosula

MRI and FDG-PET changes in normal aging across the adult lifespan

which can be combined with novel in vivo markers of BFCS degeneration. Methods: Structural MRI and rs-fMRI scans were retrieved for 70 healthy subjects (age range: 20-85 years) from the International Neuroimaging Data-sharing Initiative (INDI). Rs-fMRI data was preprocessed using the DPARSFA toolbox in SPM8. Localizations of the rostral cholinergic nuclei Ch1-2, as well as the anterior-to-intermediate (Ch4a-i) and posterior (Ch4p) sections of the nucleus basalis, were identified using a newly created subregion-specific atlas of the BFCS based on combined histology and post mortem MRI in-cranio. Seed-to-voxel FC analysis was used to reveal nucleus-specific networks of interconnected brain regions, independently of age and gender (p(FWE)<0.05). Cross-sectional voxel-wise regression analyses were used to assess age-effects on connectivity strength within these networks (p(FDR)<0.05). Results: The different cholinergic nuclei showed distinct but partially overlapping FC networks. The Ch12 region showed prominent FC with the ventromedial prefrontal cortex (vmPFC), hippocampus and posterior cingulate (PC), resembling midline components of the default mode network (DMN). In contrast, the Ch4a-i nucleus appeared to be selectively connected to inferior parietal nodes of the DMN, in addition to vmPFC and anterior medial temporal regions. The Ch4p section also showed FC with medial temporal regions, but also to lateral temporal areas, as well as insular and dorsal anterior cingulate components of a previously described salience network. Marked changes in FC with age were only detected for the Ch12 region, which showed age-related decreases in FC within the whole network. Conclusions: The BFCS may sit at an interface between neuronal networks subserving internal memory processing and stimulus-induced shifts in attention. In-vivo detection of changes in FC of the BFCS may become a useful tool to study ageand AD-related cholinergic deficits.