Dopamine induced cortico-striatal functional changes contribute to hallucinations in Parkinson's
Poster No:
104
Submission Type:
Abstract Submission
Authors:
Fosco Bernasconi1, Sara Stampacchia1, Lucas Burget1, Jevita Potheegadoo1, Marie Maradan2, Sabina Catalano3, Selim Habiby Alaoui11, Dimitri Van De Ville1, Vanessa Fleury3, Paul Krack2, Olaf Blanke1
Institutions:
1Ecole Polytechnique Federale de Lausanne (EPFL), Geneva, Switzerland, 2Inselspital, Bern, Switzerland, 3HUG - Hôpitaux universitaires de Genève, Geneva, Switzerland
First Author:
Co-Author(s):
Introduction:
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to various motor impairments. While dopaminergic treatments restore dopamine levels and alleviate motor symptoms, they may lead to hallucinations. While clinical wisdom and observations suggest that dopaminergic medication can trigger or exacerbate hallucinations, the mechanisms remain unclear. Furthermore, dopamine's role in hallucinations in PD has been widely debated, with some evidence suggesting an association between the two, while others show no (clear) link (Diederich et al., 2009; Fénelon et al., 2000; Ffytche et al., 2017). This divergent evidence might arise from the lack of methods and procedure allowing to investigate clinically relevant hallucinations in controlled lab-settings (Bernasconi et al., 2021, 2022). In this study, we aimed to explore whether dopaminergic medication influences the sensitivity to sensorimotor robot-induced presence hallucinations (riPH) in patients with PD.
Methods:
Based on a semi-structured interview twenty PD patients were divided into two subgroups: those with spontaneous hallucinations (PD-H; N=11) and those without hallucinations (PD-nH; N=9). The sensitivity to riPH was tested under i) On dopaminergic medication, ii) and Off dopaminergic medication (withdrawal of treatment). To induce sensorimotor hallucinations, we used a sensorimotor robotic paradigm in which patients performed repetitive movements to control a robot while receiving tactile feedback. The feedback was either synchronous or delayed (e.g. 500 ms), creating a sensorimotor conflict. riPH were assessed after each trial, with a "yes" or "no" response on whether the participant had riPH. Resting-state fMRI was also conducted to assess brain connectivity patterns during both On and Off medication states. Statistical analyses, including mixed models and Partial Least Squares correlation analysis, were performed to examine the effects of medication and hallucination status on riPH and brain connectivity.
Results:
Demographic and clinical characteristics did not differ between the PD-H and PD-nH (all p-values > 0.05). In the robotic paradigm, a significant interaction between medication state and group of patients was observed, where PD-H patients exhibited enhanced sensitivity to sensorimotor-induced hallucinations during the On medication state (p=0.008) (Figure 1, left panel). In contrast, PD-nH patients did not show significant changes in riPH with medication (p=0.92) (Figure 1, right panel). Through PLS analysis (Figure 2) we identified the neural correlates underlying those behavioral changes. In the On state, PD-H patients showed increased functional connectivity within a sensorimotor network involving the striatum and between the striatum and prefrontal-premotor cortical regions, which was associated with the increased sensitivity to riPH. Furthermore, there was also a reduced connectivity between the left inferior frontal gyrus and left posterior middle temporal gyrus, regions previously associated with hallucinations in PD.
Conclusions:
This study provides experimental evidence that dopaminergic medication increases the likelihood of experiencing sensorimotor-induced hallucinations in patients who already have a predisposition to hallucinations, and that dopaminergic medication induces changes in brain connectivity within a cortical and subcortical sensorimotor network. The relevance in hallucinations is PD also shown in a work from our lab presented at this conference, in which we show that dopamine alters neural fingerprints and modulates hallucination-sensitivity (Stampacchia et al.,). Collectively, these results extend previous findings on the relevance of sensorimotor regions in hallucinations in PD, and provide important insights into the neural mechanisms underlying dopaminergic-induced hallucinations in PD as well as the neural correlates of (aberrant) perception in humans.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
Perception, Attention and Motor Behavior:
Consciousness and Awareness 2
Keywords:
Cognition
Degenerative Disease
Dopamine
FUNCTIONAL MRI
Perception
Psychiatric
Somatosensory
1|2Indicates the priority used for review
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Bernasconi, F., Blondiaux, E., Rognini, G., Dhanis, H., Jenni, L., Potheegadoo, J., Hara, M., & Blanke, O. (2022). Neuroscience robotics for controlled induction and real-time assessment of hallucinations. Nature Protocols, 17(12), 2966–2989. https://doi.org/10.1038/s41596-022-00737-z
Diederich, N. J., Fénelon, G., Stebbins, G., & Goetz, C. G. (2009). Hallucinations in Parkinson disease. Nature Reviews. Neurology, 5(6), 331–342. https://doi.org/10.1038/nrneurol.2009.62
Fénelon, G., Mahieux, F., Huon, R., & Ziégler, M. (2000). Hallucinations in Parkinson’s disease: Prevalence, phenomenology and risk factors. Brain: A Journal of Neurology, 123 ( Pt 4), 733–745.
Ffytche, D. H., Creese, B., Politis, M., Chaudhuri, K. R., Weintraub, D., Ballard, C., & Aarsland, D. (2017). The psychosis spectrum in Parkinson disease. Nature Reviews Neurology, 13(2), 81–95. https://doi.org/10.1038/nrneurol.2016.200
Stampacchia, S., Bernasconi, F., Raude, K., Burget, L., Farah, J.C., Potheegadoo, J., Maradan, M., Habiby Alaoui, S., Catalano, S., Van De Ville, D., Fleury, D., Krack, P., Blanke, O. Dopamine alters neural fingerprints and modulates hallucination-sensitivity in Parkinson’s disease, in preparation