Combined Dysfunction of the Amygdala and Nucleus Basalis Underlies Visual Hallucinations in Parkinson's Disease.

Abstract

BACKGROUND Visual hallucinations (VHs) are a common feature of Parkinson's disease (PD) believed to arise from disruptions to the functional architecture supporting sensory integration and attentional control. Across synucleinopathies, increased pathological burden in the amygdala and deficits in cholinergic modulation have been linked to VHs. However, the interaction of these changes and their combined contribution to the neurobiological mechanisms underlying hallucinatory phenomena remain poorly understood. OBJECTIVES To investigate the convergent impact of amygdala and cholinergic dysfunction on VHs in PD. METHODS Seventy patients with PD, including 30 with and 40 without VHs, underwent structural and resting-state functional magnetic resonance imaging. Seed-based analyses were performed to examine whether altered functional connectivity between the bilateral amygdala and the cholinergic nucleus basalis of Meynert (NBM) with cortical networks involved in attention and visual processing is related to the presence of VHs. RESULTS Patients with VHs exhibited reduced amygdala connectivity with the visual network and reduced left amygdala connectivity with both dorsal and ventral attentional networks compared with those without VHs. Furthermore, mediation analyses indicated that the association between amygdala-attentional network dysconnectivity and VHs was at least partially explained by functional interactions between the left NBM and the ventral attention network. These functional alterations were not associated with amygdala or NBM volumes, suggesting they may occur independently of measurable gray matter atrophy. CONCLUSIONS Our findings demonstrate that VHs are associated with a network signature of impaired functional connectivity linking the amygdala, cholinergic dysfunction, and cortical networks associated with attention and perception. These results highlight the interplay between distinct but related neural circuitries and provide new insights into the pathophysiological mechanisms of VHs in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.