Beta-Band Resonance and Intrinsic Oscillations in a Biophysically Detailed Model of the Subthalamic Nucleus-Globus Pallidus Network

Abstract

Increased beta-band oscillatory activity in the basal ganglia network is associated with Parkinsonian motor symptoms and is suppressed with medication and deep brain stimulation (DBS). The origins of the beta-band oscillations, however, remains unclear with both intrinsic oscillations arising within the subthalamic nucleus (STN)—external globus pallidus (GPe) network and exogenous beta-activity, originating outside the network, proposed as potential sources of the pathological activity. The aim of this study was to explore the relative contribution of autonomous oscillations and exogenous oscillatory inputs in the generation of pathological oscillatory activity in a biophysically detailed model of the parkinsonian STN-GPe network. The network model accounts for the integration of synaptic currents and their interaction with intrinsic membrane currents in dendritic structures within the STN and GPe. The model was used to investigate the development of beta-band synchrony and bursting within the STN-GPe network by changing the balance of excitation and inhibition in both nuclei, and by adding exogenous oscillatory inputs with varying phase relationships through the hyperdirect cortico-subthalamic and indirect striato-pallidal pathways. The model showed an intrinsic susceptibility to beta-band oscillations that was manifest in weak autonomously generated oscillations within the STN-GPe network and in selective amplification of exogenous beta-band synaptic inputs near the network's endogenous oscillation frequency. The frequency at which this resonance peak occurred was determined by the net level of excitatory drive to the network. Intrinsic or endogenously generated oscillations were too weak to support a pacemaker role for the STN-GPe network, however, they were considerably amplified by sparse cortical beta inputs and were further amplified by striatal beta inputs that promoted anti-phase firing of the cortex and GPe, resulting in maximum transient inhibition of STN neurons. The model elucidates a mechanism of cortical patterning of the STN-GPe network through feedback inhibition whereby intrinsic susceptibility to beta-band oscillations can lead to phase locked spiking under parkinsonian conditions. These results point to resonance of endogenous oscillations with exogenous patterning of the STN-GPe network as a mechanism of pathological synchronization, and a role for the pallido-striatal feedback loop in amplifying beta oscillations.

Self-Tuning Deep Brain Stimulation Controller for Suppression of Beta Oscillations: Analytical Derivation and Numerical Validation

“…Increasing the strength of the hyperdirect pathway led to increased resonance in the model and also to a widening of the frequency bands where resonance was observed ( Figure 3B). This observed resonance is consistent with other modeling investigations of the STN-GPe network, where firing-rate models (Nevado-Holgado et al, 2014;Detorakis and Chaillet, 2017;Liu et al, 2017Liu et al, , 2020 and conductancebased neuron models (Ahn et al, 2016;Shouno et al, 2017;Koelman and Lowery, 2019) were used to investigate the behavior of STN-GPe network in response to external drives. Although those studies have illustrated the resonant capabilities of the STN-GPe network of both firing-rate and conductance-based models separately, this study is the first to demonstrate that both modeling approaches lead to comparable results (Figure 3).…”

Simulation of Closed-Loop Deep Brain Stimulation Control Schemes for Suppression of Pathological Beta Oscillations in Parkinson’s Disease

“…As the primary focus of this study, however, was not the role of the striatum in the generation of network pathological oscillations, its contribution to the network was simplified. A recent study investigating the role of exogenous cortical and striatal beta inputs to the STN-GPe network using detailed multi-compartment models of STN and GPe showed that resonant beta-band oscillatory activity within the STN-GPe loop becomes phase-locked to exogenous cortical beta inputs and that this behavior can be further promoted by striatal input to the loop with the correct phase (Koelman and Lowery, 2019). The network presented here captures the exogenous cortical patterning of the STN-GPe loop but omits possible further amplification of the beta-band oscillatory activity due to the striatum.…”

A novel low-cost electrode for recording the local field potential of freely moving rat’s brain

“…Currently, increasing amounts of LFP data are obtained from patients with various brain disorders and in related animal models, such as AD and PD. Among these diseases, LFP recording and analysis play a key role in decoding PD, and levodopa and DBS have been widely used to modulate beta oscillations in PD patients and to treat PD symptoms [7][8][9][10]. However, commercial implantable recording electrodes are expensive and one-off in recording LFPs in freely moving animals, forcing more and more neuroscientists to prepare an implantable electrode by themselves.…”

“…Among these brain disorders, numerous LFP data were recorded from the PD patient and animal model to decode its brain circuit. It has been found that the beta-band oscillations are consistently strengthened with dopamine loss both in PD patients and parkinsonian animal models, while levodopa and deep brain stimulation (DBS) have been witnessed to improve PD symptoms and decrease the beta oscillations [7][8][9][10]. Thus, a good recording electrode will be a powerful tool to investigate LFPs and reveal the mechanisms underlying brain disorders.…”