Computational Models Describing Possible Mechanisms for Generation of Excessive Beta Oscillations in Parkinson’s Disease

In Parkinson’s disease, an increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with difficulty in movement initiation. An important role in the generation of these oscillations is thought to be played by the motor cortex and by a network composed of the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe). Several alternative models have been proposed to describe the mechanisms for generation of the Parkinsonian beta oscillations. However, a recent experimental study of Tachibana and colleagues yielded results which are challenging for all published computational models of beta generation. That study investigated how the presence of beta oscillations in a primate model of Parkinson’s disease is affected by blocking different connections of the STN-GPe circuit. Due to a large number of experimental conditions, the study provides strong constraints that any mechanistic model of beta generation should satisfy. In this paper we present two models consistent with the data of Tachibana et al. The first model assumes that Parkinsonian beta oscillation are generated in the cortex and the STN-GPe circuits resonates at this frequency. The second model additionally assumes that the feedback from STN-GPe circuit to cortex is important for maintaining the oscillations in the network. Predictions are made about experimental evidence that is required to differentiate between the two models, both of which are able to reproduce firing rates, oscillation frequency and effects of lesions carried out by Tachibana and colleagues. Furthermore, an analysis of the models reveals how the amplitude and frequency of the generated oscillations depend on parameters.Author Summary: The collective firing of neurons is an essential mechanism for communicating information in the brain. However, in Parkinson’s disease there is a disruption of healthy brain dynamics, which interrupts the processing of normal movement. In particular, the neurons become overly synchronized and produce abnormally large oscillations in their activity. The frequency band of the oscillations associated with the difficulty of movement initiation in primate Parkinson’s disease is in the range of 13–30Hz, which is called the beta band. Understanding the generation of beta oscillations is important to improve treatments for Parkinson’s disease. Competing theories exist for how these oscillations are generated in the affected brain circuits, which include the motor cortex and a set of subcortical nuclei called the basal ganglia. This paper suggests two hypotheses for the generation of beta oscillations. The first hypothesis is that beta oscillations are generated in the motor cortex, and the basal ganglia resonate to the cortical input. The second hypothesis additionally proposes that feedback from the basal ganglia to cortex is critically important for the presence of the oscillations. We show that the models can successfully account for a wide range of experimental data concerning the presence of beta oscillations in Parkinson’s disease.