Dopaminergic therapy selectively amplifies hallucination susceptibility in patients with Parkinson's disease with cortico-striatal hyperconnectivity
- 1EPFL
Abstract
Dopamine replacement therapy (DRT) alleviates motor symptoms in Parkinsons disease (PD) but can trigger hallucinations in a subset of patients, yet the neural basis of this selective vulnerability is unknown. Hallucinations are among the most disabling non-motor symptoms of PD, linked to social isolation, dementia and institutionalization. Using a validated robotic paradigm to induce and quantify hallucinations in real-time, combined with resting-state fMRI in a crossover On/Off DRT design, we studied patients with PD with (PD-H) and without (PD-nH) hallucinations. DRT selectively amplified sensitivity to robot-induced hallucinations in patients with pre-existing hallucinatory phenotype (PD-H, but not PD-nH) and was accompanied by cortico-striatal and large-scale network hyperconnectivity. Rather than supporting a uniform hallucinogenic effect of dopamine in PD, these findings indicate that DRT interacts with an intrinsic neural vulnerability that varies in patients. Prospective studies will establish whether this pharmacological-behavioural signature identifies patients at risk before clinical hallucinations emerge.
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BibTeX
@misc{bernasconi2026dopaminergic,
title = {{Dopaminergic therapy selectively amplifies hallucination susceptibility in patients with Parkinson's disease with cortico-striatal hyperconnectivity}},
author = {F. Bernasconi and S. Stampacchia and L. Burget and J. Potheegadoo and M. Maradan and S. Habiby Alaoui and S. Catalano Chiuve and D. Van De Ville and P. Krack and V. Fleury and O. Blanke},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.26361921},
url = {https://www.medrxiv.org/content/10.64898/2026.09.01.26361921v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dopaminergic therapy selectively amplifies hallucination susceptibility in patients with Parkinson's disease with cortico-striatal hyperconnectivity
AU - F. Bernasconi
AU - S. Stampacchia
AU - L. Burget
AU - J. Potheegadoo
AU - M. Maradan
AU - S. Habiby Alaoui
AU - S. Catalano Chiuve
AU - D. Van De Ville
AU - P. Krack
AU - V. Fleury
AU - O. Blanke
PY - 2026
DA - 2026/09/01
PB - medRxiv
DO - 10.64898/2026.09.01.26361921
UR - https://www.medrxiv.org/content/10.64898/2026.09.01.26361921v1
AB - Dopamine replacement therapy (DRT) alleviates motor symptoms in Parkinsons disease (PD) but can trigger hallucinations in a subset of patients, yet the neural basis of this selective vulnerability is unknown. Hallucinations are among the most disabling non-motor symptoms of PD, linked to social isolation, dementia and institutionalization. Using a validated robotic paradigm to induce and quantify hallucinations in real-time, combined with resting-state fMRI in a crossover On/Off DRT design, we studied patients with PD with (PD-H) and without (PD-nH) hallucinations. DRT selectively amplified sensitivity to robot-induced hallucinations in patients with pre-existing hallucinatory phenotype (PD-H, but not PD-nH) and was accompanied by cortico-striatal and large-scale network hyperconnectivity. Rather than supporting a uniform hallucinogenic effect of dopamine in PD, these findings indicate that DRT interacts with an intrinsic neural vulnerability that varies in patients. Prospective studies will establish whether this pharmacological-behavioural signature identifies patients at risk before clinical hallucinations emerge.
ER -