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bioRxiv · 10.1101/2021.05.05.442704

Virtual deep brain stimulation: Multiscale co-simulation of a spiking basal ganglia model and a whole-brain mean-field model with The Virtual Brain

Meier, J.·Perdikis, D.·Blickensdörfer, A.·Stefanovski, L.·Liu, Q.·Maith, O.·Dinkelbach, H. U.·Baladron, J.·Hamker, F. H.·Ritter, P.
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Abstract

Deep brain stimulation (DBS) has been successfully applied in various neurodegenerative diseases as an effective symptomatic treatment. However, its mechanisms of action within the brain network are still poorly understood. Many virtual DBS models analyze a subnetwork around the basal ganglia and its dynamics as a spiking network with their details validated by experimental data. However, connectomic evidence shows widespread effects of DBS affecting many different cortical and subcortical areas. From a clinical perspective, various effects of DBS besides the motoric impact have been demonstrated. The neuroinformatics platform The Virtual Brain (TVB) offers a modeling framework allowing us to virtually perform stimulation, including DBS, and forecast the outcome from a dynamic systems perspective prior to invasive surgery with DBS lead placement. For an accurate prediction of the effects of DBS, we implement a detailed spiking model of the basal ganglia, which we combine with TVB via our previously developed co-simulation environment. This multiscale co-simulation approach builds on the extensive previous literature of spiking models of the basal ganglia while simultaneously offering a whole-brain perspective on widespread effects of the stimulation going beyond the motor circuit. In the first demonstration of our model, we show that virtual DBS can move the firing rates of a Parkinsons disease patients thalamus - basal ganglia network towards the healthy regime while, at the same time, altering the activity in distributed cortical regions with a pronounced effect in frontal regions. Thus, we provide proof of concept for virtual DBS in a co-simulation environment with TVB. The developed modeling approach has the potential to optimize DBS lead placement and configuration and forecast the success of DBS treatment for individual patients. Highlights- We implement and validate a co-simulation approach of a spiking network model for subcortical regions in and around the basal ganglia and interface it with mean-field network models for each cortical region. - Our simulations are based on a normative connectome including detailed tracts between the cortex and the basal ganglia regions combined with subject-specific optimized weights for a healthy control and a patient with Parkinsons disease. - We provide proof of concept by demonstrating that the implemented model shows biologically plausible dynamics during resting state including decreased thalamic activity in the virtual patient and during virtual deep brain stimulation including normalized thalamic activity and distributed altered cortical activity predominantly in frontal regions. - The presented co-simulation model can be used to tailor deep brain stimulation for individual patients.

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Meier, J., Perdikis, D., Blickensdörfer, A., Stefanovski, L., Liu, Q., Maith, O., Dinkelbach, H. U., Baladron, J., Hamker, F. H., Ritter, P.. 2021-05-05. Virtual deep brain stimulation: Multiscale co-simulation of a spiking basal ganglia model and a whole-brain mean-field model with The Virtual Brain. https://doi.org/10.1101/2021.05.05.442704

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