Correspondence of Basal Forebrain Resting-State Functional Connectivity and Cerebral Glucose Metabolism Alterations...

To investigate alterations in basal forebrain (BF) subregional functional connectivity (FC), cerebral glucose metabolism, and their spatial correspondence with atlas-based neurotransmitter distributions in Alzheimer's disease (AD).

Forty-two Aβ-PET-positive AD patients and forty-one matched healthy controls (HC) underwent simultaneous PET/MRI. We analyzed resting-state FC of BF subregions (Ch1-3, Ch4) and measured cerebral glucose metabolism using ¹⁸F-FDG PET standardized uptake value ratio (SUVR). Spatial correlations with neurotransmitter maps were assessed using the JuSpace toolbox.

Compared with HC, AD patients showed decreased FC between the left Ch4 and hippocampus/posterior cingulate gyrus, and increased FC between the right Ch4 and precentral/postcentral gyrus. Additionally, AD patients showed increased FC between the left Ch1-3 and superior temporal gyrus/insula, decreased FC between the right Ch1-3 and the orbitofrontal gyrus, and increased FC between the right Ch1-3 and the left temporal lobe (voxel-level p < 0.001, cluster-level p < 0.05, GRF correction). These FC changes were spatially correlated with serotonergic (5HT1a, 5HT4, SERT) and dopaminergic (D1, D2, DAT) receptor distributions (p < 0.05, FDR corrected). Widespread cerebral hypometabolism in temporoparietal and frontal regions was spatially correlated with serotonin, dopamine, GABA, glutamate, and kappa-opioid systems (p < 0.05, FDR corrected).

The FC of BF and cerebral metabolic changes in AD show distinct spatial correspondence with specific neurotransmitter systems, highlighting the crucial involvement of serotonin and dopamine in AD pathophysiology.