Disrupted functional brain network associated with presence of hallucinations in Parkinson’s Disease

Abstract:

AbstractBackgroundHallucinations negatively impact quality of life in Parkinson’s 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 Parkinson’s Disease and to validate these findings across independent datasets.MethodsResting 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.ResultsNBS 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 (R² = 0.35, p = 0.01), and with baseline and future motor symptoms, cognition, and attention in hallucinators.ConclusionsThe identified functional subnetwork shows promise as a potential biomarker and therapeutic target for Parkinson’s disease psychosis, warranting further investigation and validation in future studies.