Dopamine alters neural fingerprints and modulates hallucination-sensitivity in Parkinson’s disease
Poster No:
1434
Submission Type:
Abstract Submission
Authors:
Sara Stampacchia1, Fosco Bernasconi2, Killian Raude3, Lucas Burget4, Juan Carlos Farah3, Jevita Potheegadoo4, Marie Maradan5, Selim Habiby Alaoui12, Sabina Catalano6, Dimitri Van De Ville7, Vanessa Fleury6, Paul Krack5, Olaf Blanke4
Institutions:
1École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland, 2EPFL, Geneva, GE, 3Laboratory of Cognitive Neuroscience, Neuro-X institute & Brain Mind Institute, EPFL, Geneva, Switzerland, 4Ecole Polytechnique Federale de Lausanne, Geneva, Switzerland, 5Inselspital, Bern, Bern, 6HUG, Geneva, GE, 7École polytechnique fédérale de Lausanne (EPFL), Geneva, Geneva
First Author:
Co-Author(s):
Killian Raude
Laboratory of Cognitive Neuroscience, Neuro-X institute & Brain Mind Institute, EPFL
Geneva, Switzerland
Laboratory of Cognitive Neuroscience, Neuro-X institute & Brain Mind Institute, EPFL
Geneva, Switzerland
Juan Carlos Farah
Laboratory of Cognitive Neuroscience, Neuro-X institute & Brain Mind Institute, EPFL
Geneva, Switzerland
Laboratory of Cognitive Neuroscience, Neuro-X institute & Brain Mind Institute, EPFL
Geneva, Switzerland
Introduction:
Hallucinations in Parkinson's Disease (PD) are clinically significant and often linked to dopaminergic medication, but evidence remains inconclusive[1]. Our group developed a robotic-setup that allow to induce clinically relevant hallucinations (robot-induced presence hallucinations, riPH), allowing to empirically investigate hallucinations under controlled experimental settings[2,3]. Work also submitted to this conference demonstrated increased sensitivity to riPH in PD patients with hallucinations during dopaminergic treaement[4]. The present study complements that work by examining how dopaminergic medication impacts individual functional connectivity (FC) profiles, also known as FC fingerprints[5,6], and their relationship with sensitivity to riPH.
Methods:
20 PD patients underwent resting-state fMRI and the robot experiment in an ON- and an OFF-dopamine treatment session. riPH sensitivity was quantified for each individual as probability to report hallucinations as a function of sensorimotor delay dependency (slope of linear model response yes/no ~ delay)[3]. FC matrices were estimated using Pearson's correlations between 278 brain nodes[7]. Metrics for within- (ISelf) and between-subject (IOthers)[5,8] FC test-retest reliability were calculated within (ON and OFF) and across sessions (ON vs. OFF). The distance between ISelf and IOthers (IDiff) provided a group-level estimate of identifiability. Edgewise intra-class correlation (ICC) was used to assess spatial specificity of FC fingerprints. ICC measures how consistent the functional connectivity (FC) between two brain regions is across test and retest within subjects. A higher ICC indicates more stable connectivity patterns for that edge within subjects, and variability in connectivity patterns between subjects in the group[5,8]. ICC was estimated separately for ON- and OFF-medication states and the difference between the two was computed (delta-ICC = ICC ON – ICC OFF). Finally, linear mixed models tested whether individuals' FC edges with high ICC (≥ 0.1st percentile) was associated with riPH sensitivity, adjusting for medication state, age, sex, and disease duration and subjects as random effects to account for inter-individual variability (riPH ~ FC*Medication + Age + Sex + Disease Duration + (1|ID)).
Results:
Individual FC profiles were highly distinguishable within sessions regardless of medication status (IDiff ON=0.36; IDiff OFF=0.35; 100% identification success). Cross-medication comparisons (i.e., estimating identifiability across ON- vs. OFF-medication states) showed reduced identifiability (IDiff=0.17-0.21; mean success=97.9-99.2%) and decreased ISelf similarity (Fig.1). ON-medication increased ICC in visual, somatomotor, salience, subcortical, and cerebellar networks (FDR-corrected; Fig.2). Positive FC with high ICC (β=16.41, p=0.041) and medication state (β=67.52, p=0.017) significantly predicted riPH sensitivity. A significant interaction (β=-28.32, p=0.018) indicated FC effects were modified in the OFF-medication state, where a negative association was observed.
·Figure 1
·Figure 2
Conclusions:
Dopaminergic medication reconfigures FC fingerprints in PD, stabilizing networks linked to visual, somatomotor, salience, and subcortical-cerebellar functions. These findings align with roles of visual and salience networks in PD hallucinations[9,10] in PD hallucinations, and suggest sensorimotor alterations contribute to hallucinations[3]. Although individual FC profiles remained identifiable within sessions (ON- or OFF-dopamine treatment), cross-medication transitions (comparing ON- vs. OFF- dopamine states) reduced identifiability. High-ICC FC and medication state were significant predictors of riPH sensitivity, with altered effects during OFF-medication. These findings build on our previous work on FC fingerprinting[5,6] and group's research on riPH[2–4], advancing the understanding of how dopaminergic medication reconfigure individual functional connectomes and modulates hallucinations sensitivity in PD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Novel Imaging Acquisition Methods:
BOLD fMRI
Physiology, Metabolism and Neurotransmission:
Pharmacology and Neurotransmission
Keywords:
Computational Neuroscience
DISORDERS
Dopamine
Neurological
Other - Brain fingeprints
1|2Indicates the priority used for review
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