Generation mechanisms and species-specific properties of parkinsonian beta oscillations in the basal ganglia

Abstract

The basal ganglia (BG), thalamus and cortex form the BG–thalamo–cortical (BGTC) network, which is essential for voluntary movement and centrally involved in Parkinson’s disease (PD). In both patients and animal models, BG neuronal activity exhibits exaggerated oscillatory synchronization in the beta frequencies (13–30 Hz). Theoretical studies have proposed multiple network mechanisms for the generation of these abnormal beta oscillations. However, key properties, such as frequency and power distribution across BG nuclei, vary substantially among patients and between animal models (rodents vs. non-human primates). This variability complicates direct comparisons between theoretical models and experimental data, and questions whether distinct neuronal mechanisms may underlie beta oscillations across species. In an experimentally constrained BGTC network model with species-specific parameters (synaptic, neuronal, and network properties), we evaluate the features of abnormal beta oscillatory activity generated by different mechanisms. The network’s negative feedback loops serve as potential sources of spontaneous oscillations. Using rodent- or primate-constrained models, we compare the spectral properties of oscillatory activity across network populations for each loop and derive the expected phase relationships between populations to align predictions with existing rodent data and propose testable hypotheses for primates. We also demonstrate how oscillation frequency can be modulated when multiple generation mechanisms interact as coupled oscillators in the full network. Our results, combined with observed cross-species beta oscillations characteristics, suggest that abnormal beta oscillations likely arise from distinct mechanisms in rodents and primates. Significance statement A hallmark of Parkinson’s disease is exaggerated beta-frequency (13–30 Hz) oscillatory synchronization in the basal ganglia–thalamo–cortical network. Yet beta oscillation properties vary greatly between patients and animal models, and whether they arise from a common mechanism across species remains unknown. Using an experimentally constrained computational model with species-specific parameters, we identify which circuit may generate beta oscillations, predicting their frequency, power distribution, and phase signatures. Our results suggest that abnormal beta oscillations likely arise from distinct mechanisms in rodents and primates, and yield testable hypotheses for primates. Moreover, we show that interacting mechanisms can jointly modulate oscillation frequency. These findings offer experimentally verifiable predictions to guide future research and refine how preclinical findings translate to patients.