Sensorimotor Processing in the Basal Ganglia Leads to Transient Beta Oscillations during Behavior

Abstract

Brief epochs of beta oscillations have been implicated in sensorimotor control in the basal ganglia of task-performing healthy animals. However, which neural processes underlie their generation and how they are affected by sensorimotor processing remains unclear. To determine the mechanisms underlying transient beta oscillations in the LFP, we combined computational modeling of the subthalamo-pallidal network for the generation of beta oscillations with realistic stimulation patterns derived from single-unit data recorded from different basal ganglia subregions in rats performing a cued choice task. In the recordings, we found distinct firing patterns in the striatum, globus pallidus, and subthalamic nucleus related to sensory and motor events during the behavioral task. Using these firing patterns to generate realistic inputs to our network model led to transient beta oscillations with the same time course as the rat LFP data. In addition, our model can account for further nonintuitive aspects of beta modulation, including beta phase resets after sensory cues and correlations with reaction time. Overall, our model can explain how the combination of temporally regulated sensory responses of the subthalamic nucleus, ramping activity of the subthalamic nucleus, and movement-related activity of the globus pallidus leads to transient beta oscillations during behavior. Transient beta oscillations emerge in the normal functioning cortico-basal ganglia loop during behavior. Here, we used a unique approach connecting a computational model closely with experimental data. In this way, we achieved a simulation environment for our model that mimics natural input patterns in awake, behaving animals. We demonstrate that a computational model for beta oscillations in Parkinson's disease (PD) can also account for complex patterns of transient beta oscillations in healthy animals. Therefore, we propose that transient beta oscillations in healthy animals share the same mechanism with pathological beta oscillations in PD. This important result connects functional and pathological roles of beta oscillations in the basal ganglia.

Uncoupling the roles of firing rates and spike bursts in shaping the STN-GPe beta band oscillations

“…All the neurons in the STN and GPe were modelled as SSBNs. The neuron parameters used are consistent with the STN-GPe network used in a recent work by [28] and are listed in Table. 1. We used the same neuron parameters for STN and GPe neurons, however the two neuron types received different amount of external inputs as we explored network state space for different external inputs to the GPe and STN.…”

“…All neurons in the STN and GPe received external excitatory input which was modelled as uncorrelated Poisson spike trains. This input was tuned to match the range of firing rates of the STN and GPe observed in in vivo data during healthy and Parkinsonian conditions [12,28,36].…”

“…PD patients suffer from a host of cognitive and motor impairments, the behavioral symptoms of which are accompanied by various changes in the neuronal activity in Basal Ganglia (BG): e.g, increased firing rate of D2 type dopamine receptors expressing striatal neurons [1][2][3]; increased bursting in striatum, globus pallidus externa (GPe), globus pallidus interna (GPi) and subthalamic nuclei (STN) [2] and increased synchrony in all BG nuclei [4] including striatum [5], GPe [6,7], STN [3,8,9] and GPi/SNr [6,10,11]. Besides these changes in neuronal activity, at the population level, there is an increase in the power and duration of β band oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in local field potential (LFP) recorded from the basal ganglia of PD patients [8,[11][12][13]. The β band oscillations are mainly correlated with motor deficits such as rest tremor and akinesia [3,8,14,15] and, suppression of these oscillations, for example, by deep brain stimulation (DBS) ameliorates motor symptoms of PD.…”

“…Therefore, there is a great interest in understanding the mechanisms underlying the origin of β band oscillations which are still not well understood [16]. For instance, it is unclear whether the oscillations are imposed by cortical inputs [17][18][19] or they are generated within the BG, either in striatum [20], in pallidostriatal circuit [21] or the GPe-STN circuit [2,16,[22][23][24][25][26][27][28]. Several experimental results indicate that GPe-STN network plays an integral role in generating and modulating these oscillations [8,11,12,29] and their stimulation have been shown to affect (disrupt/modulate) oscillations [2,30,31].…”

“…In both firing rate-based and spiking neuronal network models, an increase in the coupling between STN and GPe is sufficient to induce strong persistent oscillations [23,26,27]. However, the oscillations may also be created if effective excitatory input to STN neurons (from the cortex) or effective inhibitory input to GPe neurons (from the striatum) is increased [24,28]. Besides, the GPe-STN network,the imbalance of the direct (effectively excitatory) and hyper-direct (effectivey inhibitory) pathways of the BG can also cause oscillations [33].…”