Parkinson’s disease progression and fronto-temporal disconnection relate to identity of minor hallucinations

Presence hallucinations (PH), a non-veridical perceptions of someone appearing around you, are frequent symptoms in Parkinson’s disease (PD). They belong to the group of minor hallucinations, predicting later appearance of structured visual hallucinations and PD psychosis. Despite their elevated frequency and negative clinical outcomes, differences in PH subtypes have not been examined.

Investigating PD patients with identified versus unidentified PH, this study aims to determine differences in disease progression, motor and cognitive performance, and brain mechanisms. From 77 PD patients, 27 reporting PH were grouped into those with identified PH versus unidentified PH (iPH-PD, n = 12; uPH-PD, n = 15). Disease progression (UPDRS, Hoehn Yahr), cognitive functions (PD-CRS) (with exploratory analysis of all clinical variables, uncorrected for multiple comparisons), sensitivity to robot-induced PH and resting-state functional connectivity were analysed. iPH reports mostly consisted of first-degree close others (e.g., partner). iPH-PD patients had a more advanced PD stage, reported more daily-life motor impairments and simple visual illusions than uPH-PD patients.

Both groups showed similar sensitivity to robot-induced PH. Resting-state functional connectivity showed that iPH-PD vs. uPH-PD patients had right IFG-pMTG functional disconnection within a previously defined PH network and the degree of this disconnection correlated with posterior cognitive impairment. Distinguishing iPH-PD from uPH-PD patients, we show that the former display worse daily motor functioning, more frequent visual illusions and stronger fronto-temporal disconnection, related to cognitive dysfunction.

Although the present findings need to be confirmed in larger samples, they suggest that iPH-PD have a more advanced form of PD, possibly representing an intermediate disease stage, between uPH-PD and PD patients with structured visual hallucinations. The authors would like to thank all Parkinson’s disease patients for their participation, as well as clinicians Dr. Benoît Wicki for help with recruitment of PD patients and Dimitri Van De Ville for his advice on fMRI analysis.

This research was supported by the Swiss National Science Foundation [grant n. 188798], CARIGEST SA (Fondazione Teofilo Rossi di Montelera e di Premuda and a second one wishing to remain anonymous) and Parkinson Suisse to O.B.; Empiris Foundation to OB; the Swiss National Science Foundation [grant n. 221182] and the Leenaards Foundation to F.B.; the Synapsis Foundation to O.B and F.B. Open access funding provided by EPFL Lausanne. Laboratory of Cognitive Neuroscience, Neuro X Institute, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Geneva, Switzerland Neza Vehar, Jevita Potheegadoo, Nathalie Heidi Meyer, Lada Kohoutová, Léa Florence Duong Phan Thanh, Cyrille Stucker, Herberto Dhanis, Lucas Burget, Sara Stampacchia, Fosco Bernasconi & Olaf Blanke Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland Graduate School for Health Sciences, University of Bern, Bern, Switzerland Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland O.B., F.B., and J.P. are inventors on patent EP4659254A1 held by the Swiss Federal Institute (EPFL) that covers a solution for measuring and quantifying an impairment in numerosity estimation in human subjects.

O.B. is inventor on patent US 10,286,555 B2 held by the Swiss Federal Institute (EPFL) that covers the robot-controlled induction of presence hallucination. O.B. is inventor on patent US 10,349,899 B2 held by the Swiss Federal Institute (EPFL) that covers a robotic system for the prediction of hallucinations for diagnostic and therapeutic purposes. O.B. is a member of the board and shareholder of Mindmaze Therapeutics.