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Dynasti: Patient-specific dynamical modelling and optimisation of Deep Brain Stimulation

Projectomschrijving

Diepe hersenstimulatie is een effectieve therapie voor mensen met de ziekte van Parkinson. Hoewel de therapie vaak succesvol is in het onderdrukken van bewegingssymptomen, komen bijwerkingen op het gebied van cognitie en gedrag relatief vaak voor. Het effect van de behandeling kan worden gestuurd door aanpassing van de instellingen van de stimulator. Gebrek aan kennis over hoe diepe hersenstimulatie precies werkt, maakt het echter moeilijk om te voorspellen wat de optimale instellingen voor een individuele patiënt zijn.

Doel en samenwerkingen

Het Dynasti consortium bestaat uit wetenschappers, neurologen, en hersenchirurgen uit Nederland, Duitsland, Zweden en Luxemburg. Samen willen zij diepe hersenstimulatie verbeteren door meer informatie te halen uit beeldvormende technieken en realistische computermodellen. Het doel is om neurologen en verpleegkundigen handvatten te bieden bij het instellen van de stimulator, zodat de behandeling efficiënter en met gunstiger resultaat kan plaatsvinden.

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Samenvatting van de aanvraag

The Dynasti consortium aims to enhance the outcome of Deep Brain Stimulation (DBS) in Parkinson’s disease (PD) through the individualization and optimization of stimulation settings. Our vision is to replace the current practice of selecting stimulation pulse width, amplitude, and frequency by trial and error with a model-based patient-specific calculation. This will be achieved by incorporating insights from novel clinical research studies into individualized mathematical models underpinning clinically relevant DBS programming tools. To reflect the cross-disciplinary nature of the DBS optimization problem, the consortium is composed of neurologists, electrical and control engineers, computer scientists, movement scientists, and neurosurgeons from four European countries. The partners have complementing research competences and contribute to the project in-house software tools for the automatization of DBS programming. Overall, DynaSti will acquire novel experimental data, extract new knowledge from it regarding the biologic mechanisms of DBS, and design open-source model-based algorithms to improve its effectiveness. These algorithms will then be tested in the participating clinics for improved convergence to clinically optimal DBS parameters in terms of patient benefit, i.e. improved motor control, minimized side effects, and battery consumption. The consortium partners in The Netherlands will focus on the following objectives: 1) The creation and coordination of a comprehensive DBS data repository to facilitate data exchange between the consortium partners and the wider research community. This will be done according to the FAIR principle: findable, accessible, interoperable and reusable. We aim to enter all data acquired within the scope of the DynaSti program into the repository. 2) To determine the utility of high-frequency oscillations (HFO) in local field potential (LFP) recordings from the subthalamic nucleus as a novel biomarker for optimizing the frequency of DBS stimulation in individual patients. LFP recordings will be obtained from ~30 patients implanted with the Medtronic Percept system. DBS stimulation frequency will be adjusted to the peak frequency of HFO and compared against conventional stimulation. UPDRS-III scores and additional measurements of motor functioning will serve as primary outcome measures. 3) To determine the source origin of STN-LFP oscillations as recorded with DBS electrodes. Pinpointing the exact anatomical origin of pathological neural oscillations is important for determining the exact target for DBS stimulation. Established source localization techniques in EEG/MEG will be made applicable to LFP recordings from DBS electrodes. 4) To establish the effects of DBS on functional connectivity between structures of the cortico-basal ganglia-thalamus network. For this, we aim to build a realistic model of the biophysical effects of stimulation on neural populations and networks. The spatiotemporal descriptions of DBS current spread developed by the consortium partners will be integrated in our neural mass model to infer how DBS-induced changes in LFP and EEG recordings arise within the cortico-basal ganglia-thalamus network. 5) To provide a clinical proof-of-principle and validation of DynaSti optimal stimulation settings. The combined efforts of the Dynasti consortium result in a prediction of patient-specific optimal DBS stimulation settings. The effect of these optimal DBS stimulation settings on clinical outcome will be compared against conventional programming strategies. Primary outcome measures include the UPDRS-III score and additional objective symptom quantification and rating of side effects via wearable sensors and experimental tasks. Expected outcomes of the Dynasti research program include higher therapeutic effects in individual treatments, reduced side effects, and improved treatment economy resulting from shorter DBS programming times. Higher degrees of automation in clinical processes will also advance consistency in care quality notwithstanding where it is provided. Further, our findings will result in improved understanding of the effects elicited by DBS through the development and validation of patient-specific dynamical models.

Kenmerken

Projectnummer:
733051122
Looptijd: 94%
Looptijd: 94 %
2021
2024
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. B.C.M. van Wijk
Verantwoordelijke organisatie:
Vrije Universiteit Amsterdam