Objective: REM sleep behavior disorder (RBD) is a prodromal state for alpha-synucleinopathy. Here, we present a behavioral marker for hallucination propensity that distinguishes Dementia with Lewy Bodies (DLB) from Parkinson’s Disease (PD) and may predict the trajectory of disease progression in RBD. Additionally, we seek to investigate the neural mechanisms underlying this hallucination propensity.
Background: RBD predicts the development of alpha-synucleinopathy in over 90% of patients at 14 years, with approximately 44% converting to DLB and 51% to PD [1]. Unlike PD, DLB is marked by early, prominent non-motor symptoms, including vivid visual hallucinations and cognitive fluctuations, with milder motor deficits. Currently, there are no reliable methods for predicting the clinical course in individuals with prodromal RBD. Identifying behavioral markers and neural mechanisms of hallucination propensity in RBD and DLB could enable earlier diagnosis and targeted interventions.
Method: We acquired structural and functional MRI in n=20 participants (DLB: 5, PD: 7, RBD: 7, HC: 1), including a visual conditioned hallucinations (VCH) task. The VCH task began by consistently pairing a tone with a visual stimulus. The target visual stimulus was increasingly presented at sub-threshold intensities and gradually omitted over the course of the experiment. VCH rate was measured as the proportion of trials where participants reported seeing the visual stimulus despite its absence. Whole-brain functional activation was measured during the task, along with its association with VCH rate.
Results: DLB participants exhibited higher mean VCH rates than PD (Cohen’s d = 1.82). RBD participants displayed intermediate rates, with a subset showing scores near zero, resembling PD, and others demonstrating elevated scores similar to DLB [figure1]. Regression analyses linked higher VCH rates to increased occipital and pulvinar activity during VCH events [figure2].
Conclusion: The VCH task may distinguish DLB from PD and identify clinically relevant subgroups within prodromal RBD. Future longitudinal work will determine whether this serves as a biomarker that accurately predicts the phenotypic trajectory of patients. Moreover, these results enhance our understanding of the neural mechanisms underlying VH propensity in DLB and RBD, offering potential for early detection and guiding future therapies.
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References: 1. Postuma, R. B., Iranzo, A., Hu, M., Högl, B., Boeve, B. F., Manni, R., … & Pelletier, A. (2019). Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain, 142(3), 744-759.
To cite this abstract in AMA style:
R. Vin, S. Moret, HY. Yi, M. Lawrence, V. Santini, J. Cedarbaum, A. Powers, C. Fredericks. Neural Signatures of Hallucination Emergence in Dementia with Lewy Bodies [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/neural-signatures-of-hallucination-emergence-in-dementia-with-lewy-bodies/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/neural-signatures-of-hallucination-emergence-in-dementia-with-lewy-bodies/