title: Coordinated reset stimulation in a large-scale model of the STN-GPe circuit.
abstract: Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR) stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g., for the treatment of Parkinson's disease (PD), is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incorporated a detailed numerical representation of 2 · 10(4) simulated neurons. We simulated the subthalamic nucleus (STN) and the globus pallidus externus (GPe). Connections within the STN were governed by spike-timing dependent plasticity (STDP). In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological) activity to strongly desynchronized (healthy) activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward toward a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.
authors.affiliation: Institute of Neuroscience and Medicine - Neuromodulation, Juelich Research Center GmbH Juelich, Germany ; Department of Physics, Institute of Nuclear Physics, University of Cologne Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebert
authors.affiliation: Institute of Neuroscience and Medicine - Neuromodulation, Juelich Research Center GmbH Juelich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hauptmann
authors.affiliation: Institute of Neuroscience and Medicine - Neuromodulation, Juelich Research Center GmbH Juelich, Germany ; Department of Neurosurgery, Stanford University Stanford, CA, USA ; Department of Neuromodulation, University of Cologne Cologne, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Tass
keywords: coordinated reset stimulation; deep brain stimulation; electrode design; high-performance computing