Neural Correlates of Cognitive Alterations and Minor and Structured Hallucinations in Parkinson's Disease

Background: Hallucinations, ranging from minor (MH) to structured, are a common non-motor symptom in Parkinson's disease (PD). Structured hallucinations have been associated with altered functional connectivity (FC) between dorsal/ventral attention (DAN, VAN) and default mode (DMN) networks. As structured hallucinations are linked to rapid cognitive decline and MH are often viewed as their precursor, it is imperative to understand the neural basis of MH, and its relationship with cognitive alterations. Objectives: We aimed to identify a whole-brain FC pattern associated with MH and alterations in attention-executive functioning in PD, leveraging a robotic procedure inducing presence hallucinations (riPH) experimentally, to which patients with hallucinations previously showed increased sensitivity. Methods: Non-demented PD patients (N = 53) were categorized into three subgroups based on their hallucination symptoms: no hallucinations (nH; n = 19), MH (n = 18), and structured hallucinations, with or without MH (SMH; n = 16). We combined results from the riPH procedure and neuropsychological tests and applied multivariate methods capturing their shared variance in resting-state fMRI data across the three subgroups. Results: We identified a distributed FC pattern more strongly expressed in patients with hallucinations (MH, SMH), and equally so across both groups, significantly associated with alterations in attention-executive functions and differences in riPH sensitivity. The pattern was primarily driven by FC between subcortical areas and visual network, DAN and DMN, and within-cerebellar and within-subcortical FC. Conclusions: Our results highlight the role of subcortical-cortical connectivity in PD hallucinations, associated with cognitive alterations and already present in less advanced MH patients.