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July 3rd, 2025
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Department of Psychiatry, The University of Melbourne, Parkville, Australia
neuroscience
biorxiv

Altered basal forebrain regulation of intrinsic brain networks in depressive and anxiety disorders

Jamieson, A. J.Open in Google Scholar•Steward, T.Open in Google Scholar•Davey, C. G.Open in Google Scholar•Ince, S.Open in Google Scholar•Agathos, J. A.Open in Google Scholar•Moffat, B. A.Open in Google Scholar•Glarin, R. K.Open in Google Scholar•Felmingham, K. L.Open in Google Scholar•Harrison, B. J.Open in Google Scholar

Depressive and anxiety disorders are marked by changes both within and between the default mode (DMN) and salience networks. Recent work has highlighted the importance of subcortical regions, including subdivisions of the basal forebrain, in coordinating the activity of these intrinsic networks. However, the precise influence of these basal forebrain subregions in healthy individuals, and whether these connections demonstrate alterations across depressive and anxiety disorders, remains unclear. Using ultra-high field (7-Tesla) functional magnetic resonance imaging, we examined the resting-state effective connectivity of three basal forebrain subregions, the medial septum/diagonal band (Ch1-3), nucleus basalis of Meynert (Ch4), and the ventral pallidum, with core regions of the salience network and DMN. This was investigated in a transdiagnostic sample of 70 individuals with mental health conditions, predominantly depressive and anxiety disorders, and 77 healthy controls. Consistent with previous research, healthy controls demonstrated an excitatory influence from Ch1-3 to DMN regions and from Ch4 to salience network regions. An inverse relationship was observed for the inhibitory influence from basal forebrain subregions to these networks. Compared to controls, clinical participants showed increased inhibitory connectivity from Ch4 to regions of the DMN and dorsal anterior cingulate cortex and greater excitatory connectivity to the anterior insula. Increased inhibitory connectivity was also observed from the ventral pallidum to regions of the posterior DMN. These alterations in the basal forebrain's regulation of large-scale cortical networks may suggest novel mechanistic avenues for pharmacological treatments targeting the cholinergic system.

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