Exploring phase–amplitude coupling from primary motor cortex-basal ganglia–thalamus network model

Abstract

The purpose of this study is to develop a primary motor cortex (M1)-basal ganglia–thalamus model capable of reproducing the physiological phenomenon of exaggerated phase–amplitude coupling (PAC) in Parkinson’s disease and exploring the potential sources of PAC anomalies in M1. The subthalamic nucleus (STN) phase-STN amplitude coupling, STN phase–M1 amplitude coupling, and M1 phase–M1 amplitude coupling are reproduced, where the phase frequencies are distributed in the beta band and the amplitude frequencies are distributed in the broad gamma band. We mainly study the impacts of thalamus →M1 connections and STN↔M1 bidirectional synaptic connections. Abnormal beta oscillations generated within the basal ganglia are found to be transmitted to M1 through the STN or thalamus and could be one of the potential sources of PAC-related beta oscillations in M1, thereby interfering with high-frequency signals in the motor cortex. Furthermore, the weakening of M1→STN leads to a shift of the oscillations of the STN from the high beta band to the low beta band, which is more consistent with pathological experiments, thus supporting the experimental results that the hyper-direct path from M1 to STN drives the beta oscillations of STN. Finally, the suppression effect of STN deep brain stimulation on PAC is investigated. As the stimulation frequency increases, the PAC modulation index within different regions gradually decreases, in general agreement with the trend of synchronization level and beta oscillation energy, indirectly indicating that PAC can be used as a feedback indicator of parkinsonian state.