Objective: The aim is to develop a novel implicit and quantitative marker for minor hallucinations (MH) in Parkinson’s disease (PD) for a better tracking of PD progression.

Background: Minor hallucinations are often the earliest hallucinations in PD [1], and have been associated with a more severe form of the disease, characterized by psychosis and cognitive decline [2,3]. However, the assessment of hallucinations is hampered by several methodological difficulties to detect and quantify them reliably [4]. That is, hallucinations are spontaneous and unpredictable phenomena, most often assessed using verbal interviews or scales [5]. These difficulties are even more prominent for monitoring hallucinations at the home of patients.

Method: We developed a paradigm (Numerosity Estimation of Humans – NEH ; Numerosity Estimation of Objects – NEO) to implicitly quantify a predominant MH: presence hallucinations (PH). We first conducted a study in healthy participants (n=28) using VR and a robotic platform that has recently been shown to experimentally induce PH in a controlled manner in healthy individuals and PD patients [6,7]. In a second study, we adapted both Numerosity Estimation tasks to a web-based digital test. 170 PD patients performed our online web-based digital test at home.

Results: Study 1: In healthy participants, numerosity estimation is significantly modulated by the robotic sensorimotor stimulation condition (PH-inducing vs control) and the type of stimuli (NEH vs. NEO). Critically, the robotic sensorimotor stimulation significantly modulates NEH, and the PH-inducing condition induces a stronger NEH overestimation bias than the control condition.

Study 2: In PD patients, online NEH is significantly modulated by the occurrence of disease-related PH (PD-PH vs PD-nH) and by the type of stimulus (online NEH vs. online NEO). Critically, PD patients who reported PH in daily life show stronger online NEH overestimation. This effect is absent for online NEO and cannot be explained by differences in task difficulty between groups, nor does it depend on clinical covariates.

Conclusion: Numerosity estimation is an implicit and quantitative marker for PH in PD that can be measured online at the patient’s home. This novel marker will allow continuous monitoring of patients’ hallucination proneness, potentially allowing treatment adaptations and monitoring of psychosis and related cognitive deficits.

References: [1] A. Lenka, J. Pagonabarraga, P. K. Pal, H. Bejr-Kasem, and J. Kulisvesky, “Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications,” Neurology, vol. 93, no. 6, pp. 259–266, Aug. 2019, doi: 10.1212/WNL.0000000000007913.
[2] F. Bernasconi, J. Pagonabarraga, H. Bejr-Kasem, S. Martinez-Horta, J. Kulisevsky, and O. Blanke, “Theta oscillations and minor hallucinations in Parkinson’s disease reveal decrease in frontal lobe functions and later cognitive decline.” bioRxiv, p. 2022.11.24.517668, Nov. 24, 2022. doi: 10.1101/2022.11.24.517668.
[3] H. Bejr-kasem, F. Sampedro, J. Marín-Lahoz, S. Martínez-Horta, J. Pagonabarraga, and J. Kulisevsky, “Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson’s disease,” European Journal of Neurology, vol. 28, no. 2, pp. 438–447, 2021, doi: 10.1111/ene.14576.
[4] G. Fénelon, T. Soulas, L. C. De Langavant, I. Trinkler, and A.-C. Bachoud-Lévi, “Feeling of presence in Parkinson’s disease,” J Neurol Neurosurg Psychiatry, vol. 82, no. 11, pp. 1219–1224, Nov. 2011, doi: 10.1136/jnnp.2010.234799.
[5] S. Rogers, R. Keogh, and J. Pearson, “Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 376, no. 1817, p. 20200233, Feb. 2021, doi: 10.1098/rstb.2020.0233.
[6] F. Bernasconi et al., “Neuroscience robotics for controlled induction and real-time assessment of hallucinations,” Nat Protoc, vol. 17, no. 12, Art. no. 12, Dec. 2022, doi: 10.1038/s41596-022-00737-z.
[7] F. Bernasconi et al., “Robot-induced hallucinations in Parkinson’s disease depend on altered sensorimotor processing in fronto-temporal network,” Science Translational Medicine, vol. 13, no. 591, p. eabc8362, Apr. 2021, doi: 10.1126/scitranslmed.abc8362.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-digital-marker-detects-minor-hallucinations-online-at-home-of-patients-with-parkinsons-disease/