A population level computational model of the basal ganglia that generates parkinsonian local field potential activity

Abstract

Recordings from the basal ganglia's subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality-effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD.

A biologically constrained model of the whole basal ganglia addressing the paradoxes of connections and selection

“…Alike in these works, θ MSN has the highest value while both θ GPe and θ GPi are set to low values. The comparison of θ STN is hard to make, as it is set heterogeneously in previous models: at a middle value for Tsirogiannis et al (2010), and at a low value for Van Albada and Robinson (2009). Overall, these superficial comparisons show that our optimized θ parameters are, as far as any parallel can be drawn, globally consistent with previous works, which is remarkable given that there was no direct pressure to set them at any preferred value inside their permitted range.…”

“…leaky integrators in Berns and Sejnowski (1994); Gurney et al (2001) or lPDS in Girard et al (2008)), more recent ones have been using more plausible models (e.g. fine-tuned spiking neurons in Humphries et al (2006) or mean fields in Van Albada and Robinson (2009); Tsirogiannis et al (2010)).…”

Fitting local field potentials generating model of the basal ganglia to actual recorded signals

“…Recently, Wendling et al [12], [13] have also used that methodology to generate depth-EEG signals in epileptic states. In our previous work, we have adapted the methodology to model the basal ganglia's LFP generating mechanisms, incorporating all major nuclei and an extensive set of pathways [6]. A block diagram of the model is presented in Fig.…”

“…This is described in a recent work [6], where the authors present a biologically plausible population level model of the basal ganglia that generates LFPs of the STN. The model has provided indications concerning the role of the duration and the amplitude of the post-synaptic potentials (PSPs) in the pathophysiology of Parkinson's disease.…”

System identification of Local Field Potentials under Deep Brain Stimulation in a healthy primate

“…1 for a schematic of the pallidal-subthalamic circuit. Whereas LFPs have been proposed as a useful tool to investigate the behavior before and after stimulation [6,7,8], we reproduce them from single Spike Unit Recordings (SURs) from 20 neurons in GPi and GPe. A least squares approach is then used to define an input-output autoregressive model of BG.…”