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PLoS Comput Biol. 2015 Dec 18;11(12):e1004609. doi: 10.1371/journal.pcbi.1004609. eCollection 2015 Dec.

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

Author information

1
MRC Unit for Brain Network Dynamics, University of Oxford, Oxford, United Kingdom.
2
Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
3
Faculty of Engineering, University of Bristol, Bristol, United Kingdom.

Abstract

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.

PMID:
26683341
PMCID:
PMC4684204
DOI:
10.1371/journal.pcbi.1004609
[Indexed for MEDLINE]
Free PMC Article

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