Disrupted functional brain network associated with presence of hallucinations in Parkinsons Disease

Background Hallucinations negatively impact quality of life in Parkinsons disease, yet their neural mechanisms remain poorly understood, particularly in early disease stages. This study aimed to identify functional connectivity differences associated with visual hallucinations in early Parkinsons Disease and to validate these findings across independent datasets. Methods Resting state fMRI data from two prior independent studies was used (total N=185; N=84 hallucinators and N=101 non-hallucinators). Group differences in functional connectivity were assessed within predefined cytoarchitectonic cortical classes and functional networks, followed by whole-brain analysis using Network-Based Statistics (NBS). Associations with clinical measures, including hallucination severity, motor symptoms, cognition, and attention, were also evaluated. Results NBS identified a subnetwork of reduced functional connectivity in hallucinators, connecting regions involved in the default mode, somatomotor and attentional networks. This subnetwork was replicated in a matched sample from our independent cohort (N=50; p<0.01). Functional connectivity within the identified network was significantly associated with hallucination severity (Rsquare = 0.35, p = 0.01), and with baseline and future motor symptoms, cognition, and attention in hallucinators. Conclusions The identified functional subnetwork shows promise as a potential biomarker and therapeutic target for Parkinsons disease psychosis, warranting further investigation and validation in future studies.