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

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 Parkinson’s disease patient’s 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 Parkinson’s 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.

BOLD Monitoring in the Neural Simulator ANNarchy

“…Especially for the study of neuronal diseases in humans, model-based analysis offers new opportunities. Network models customized to patients can be compared with network models customized to healthy controls, or the customized network models can be used as a virtual test bed for specific treatments (Cabral et al, 2013 ; Van Hartevelt et al, 2014 ; Jirsa et al, 2017 ; Meier et al, 2021 ). Since this approach has been mainly performed with macroscopic network models, ANNarchy can extend this approach by being used mainly in the study of processes at the mesoscopic level of detail.…”

“…Since this approach has been mainly performed with macroscopic network models, ANNarchy can extend this approach by being used mainly in the study of processes at the mesoscopic level of detail. A possible application would be the study of deep brain stimulation (DBS) in, e.g., Parkinson's disease patients, the mechanisms of which may be more extensively and realistically implemented in ANNarchy (similar to other mesoscopic network models, e.g., Rubin and Terman, 2004 ; Hahn and McIntyre, 2010 ) than in macroscopic network models (e.g., Meier et al, 2021 ). Similar to the recently proposed approach to predict DBS-induced clinical improvements using MRI data from Parkinson's disease patients (Horn et al, 2017 , 2019 ), predictors for clinical improvements could also be obtained from model-based analysis of the MRI data.…”

“…In TVB, network models are usually implemented as a combination of neural mass models, sets of equations that describe the average dynamics of large neuron populations (macroscopic models), but neglect processes at the single-neuron level. Therefore, a TVB – multi-scale co-simulation toolbox that links TVB and neural simulators which model the lower scale processes such as ANNarchy and NEST (Gewaltig and Diesmann, 2007 ), has been recently introduced (Meier et al, 2021 ; Schirner et al, 2022 ). BOLD simulation in TVB is mainly used to validate large-scale network models on experimental MRI data.…”

“…The ANNarchy neural simulator (Vitay et al, 2015 ) provides a user-friendly equation-based interface which can be used to create large-scale rate-coded and spiking network models at different levels of biological realism. Recently, the ANNarchy neural simulator has been combined with the whole-brain neural simulator The Virtual Brain (TVB) (Ritter et al, 2013 ; Sanz Leon et al, 2013 ; Meier et al, 2021 ) to allow the creation of multi-scale network models. This allows to study how processes in detailed spiking network models of specific brain regions such as the basal ganglia created in ANNarchy affect the dynamics of the whole cortex simulated in TVB (Meier et al, 2021 ).…”

“…Recently, the ANNarchy neural simulator has been combined with the whole-brain neural simulator The Virtual Brain (TVB) (Ritter et al, 2013 ; Sanz Leon et al, 2013 ; Meier et al, 2021 ) to allow the creation of multi-scale network models. This allows to study how processes in detailed spiking network models of specific brain regions such as the basal ganglia created in ANNarchy affect the dynamics of the whole cortex simulated in TVB (Meier et al, 2021 ). To further improve the usability of ANNarchy, we introduce a BOLD signal monitoring module (called BOLD monitor in ANNarchy) that allows obtaining simulated BOLD signals from spiking and rate-coded network models in an on-line manner.…”