The Virtual Parkinsonian patient

Abstract This study investigates the influence of the pharmacological nigrostriatal dopaminergic stimulation on the entire brain by analyzing EEG and deep electrodes, placed near the subthalamic nuclei, from 10 Parkinsonian patients before (OFF) and after (ON) L-Dopa administration. We characterize...

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Main Authors: Marianna Angiolelli, Damien Depannemaecker, Hasnae Agouram, Jean Régis, Romain Carron, Marmaduke Woodman, Letizia Chiodo, Paul Triebkorn, Abolfazl Ziaeemehr, Meysam Hashemi, Alexandre Eusebio, Viktor Jirsa, Pierpaolo Sorrentino
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-025-00516-y
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author Marianna Angiolelli
Damien Depannemaecker
Hasnae Agouram
Jean Régis
Romain Carron
Marmaduke Woodman
Letizia Chiodo
Paul Triebkorn
Abolfazl Ziaeemehr
Meysam Hashemi
Alexandre Eusebio
Viktor Jirsa
Pierpaolo Sorrentino
author_facet Marianna Angiolelli
Damien Depannemaecker
Hasnae Agouram
Jean Régis
Romain Carron
Marmaduke Woodman
Letizia Chiodo
Paul Triebkorn
Abolfazl Ziaeemehr
Meysam Hashemi
Alexandre Eusebio
Viktor Jirsa
Pierpaolo Sorrentino
author_sort Marianna Angiolelli
collection DOAJ
description Abstract This study investigates the influence of the pharmacological nigrostriatal dopaminergic stimulation on the entire brain by analyzing EEG and deep electrodes, placed near the subthalamic nuclei, from 10 Parkinsonian patients before (OFF) and after (ON) L-Dopa administration. We characterize large-scale brain dynamics as the spatio-temporal spreading of aperiodic bursts. We then simulate the effects of L-Dopa utilizing a novel neural-mass model that includes the local dopamine concentration. Whole-brain dynamics are simulated for different dopaminergic tones, generating predictions for the expected dynamics, to be compared with empirical EEG and deep electrode data. To this end, we invert the model and infer the most likely dopaminergic tone from empirical data, correctly identifying a higher Dopaminergic tone in the ON-state, and a lower dopaminergic tone in the OFF-state, for each patient. In conclusion, we successfully infer the dopaminergic tone by integrating anatomical and functional knowledge into physiological predictions, using solid ground truth to validate our findings.
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spelling doaj-art-47b185bbe9d946dcbaff9be8e76970942025-08-20T02:19:58ZengNature Portfolionpj Systems Biology and Applications2056-71892025-04-0111111210.1038/s41540-025-00516-yThe Virtual Parkinsonian patientMarianna Angiolelli0Damien Depannemaecker1Hasnae Agouram2Jean Régis3Romain Carron4Marmaduke Woodman5Letizia Chiodo6Paul Triebkorn7Abolfazl Ziaeemehr8Meysam Hashemi9Alexandre Eusebio10Viktor Jirsa11Pierpaolo Sorrentino12Aix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix Marseille Univ, CNRS, INT, Institut de Neurosciences de la TimoneAix Marseille Univ, UMR INSERM 1106, Dept of Functional NeurosurgeryAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesDepartment of Engineering, Universitá Campus Bio-Medico di RomaAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix Marseille Univ, CNRS, INT, Institut de Neurosciences de la TimoneAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAix-Marseille Univ, INSERM, INS, Institut de Neurosciences des SystémesAbstract This study investigates the influence of the pharmacological nigrostriatal dopaminergic stimulation on the entire brain by analyzing EEG and deep electrodes, placed near the subthalamic nuclei, from 10 Parkinsonian patients before (OFF) and after (ON) L-Dopa administration. We characterize large-scale brain dynamics as the spatio-temporal spreading of aperiodic bursts. We then simulate the effects of L-Dopa utilizing a novel neural-mass model that includes the local dopamine concentration. Whole-brain dynamics are simulated for different dopaminergic tones, generating predictions for the expected dynamics, to be compared with empirical EEG and deep electrode data. To this end, we invert the model and infer the most likely dopaminergic tone from empirical data, correctly identifying a higher Dopaminergic tone in the ON-state, and a lower dopaminergic tone in the OFF-state, for each patient. In conclusion, we successfully infer the dopaminergic tone by integrating anatomical and functional knowledge into physiological predictions, using solid ground truth to validate our findings.https://doi.org/10.1038/s41540-025-00516-y
spellingShingle Marianna Angiolelli
Damien Depannemaecker
Hasnae Agouram
Jean Régis
Romain Carron
Marmaduke Woodman
Letizia Chiodo
Paul Triebkorn
Abolfazl Ziaeemehr
Meysam Hashemi
Alexandre Eusebio
Viktor Jirsa
Pierpaolo Sorrentino
The Virtual Parkinsonian patient
npj Systems Biology and Applications
title The Virtual Parkinsonian patient
title_full The Virtual Parkinsonian patient
title_fullStr The Virtual Parkinsonian patient
title_full_unstemmed The Virtual Parkinsonian patient
title_short The Virtual Parkinsonian patient
title_sort virtual parkinsonian patient
url https://doi.org/10.1038/s41540-025-00516-y
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