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

Abstract

Depressive and anxiety disorders are characterized by altered connectivity within and between the default mode (DMN) and salience networks. Basal forebrain subdivisions, critical for regulating network activity, remain understudied across these conditions. To address this gap, we analyzed 7-Tesla resting-state functional magnetic resonance imaging data from a transdiagnostic sample (n = 70), primarily with depressive and anxiety disorders, and healthy controls (n = 77). We used spectral dynamic causal modelling to assess effective connectivity between the medial septum/diagonal band (Ch1-3), nucleus basalis of Meynert (Ch4), ventral pallidum, and DMN and salience networks. Healthy participants showed excitatory connectivity from Ch1-3 to the DMN and from Ch4 to the anterior insula. In contrast, clinical participants exhibited greater inhibitory Ch4 to DMN connectivity and increased excitatory connectivity from Ch4 to the anterior insula. Wide-spread Ch4 connectivity dysfunction may implicate the cholinergic system as a mechanistic and therapeutic target for depressive and anxiety disorders.