| Abstract | The low-dopamine state as is seen in Parkinson’s disease (PD) is marked by an increase of oscillatory and synchronous activity in the beta frequency band. While casual relationship between oscillatory synchronized activity in the beta band and motor symptoms of PD is not completely certain, multiple recent experimental results suggest that this activity is closely related to the pathologies of motor behavior. Understanding the dynamical nature of this synchronization is essential for the understanding of its function as well as for determining potentially efficient therapeutic ways to suppress this synchrony in PD. The present study explores this dynamical nature of synchronous oscillations in PD as well as its potential mechanisms. We simultaneously record spikes and LFP from subthalamic nucleus of PD patients, analyze the phase synchronization between these signals as it develops in time and use mathematical modeling to study the network mechanisms of the observed dynamics. To explore synchrony patterns on a fine time scale we analyzed the first-return plots of the phase differences between recorded signals. Observed synchronized dynamics is interrupted by desynchronization events. These events are irregular, although not completely random – there is a predominance of short desynchronization events. The signals go out of phase for just one cycle of oscillations more often than for two or a larger number of cycles. The chances of longer desynchronization events decrease with the duration of these events. An alternative scenario (longer but less frequent desynchronization events) would produce the same degree of average synchronization, however, it is not supported by the data analysis. Numerical simulation of conductance-based models of subthalamo-pallidal circuits allowed us to identify the parameter domains, where the model without any external input or plasticity effects reproduces imperfect synchronization with the same characteristic fine temporal structure. This dynamics is robust to the small noise perturbations and persists in simplified model of two synaptically coupled neurons. The parameter values correspond to the relatively strong synaptic strengths in the model, which is realistic for PD (in a healthy state these synaptic connections would be inhibited by dopaminergic action). The computational results indicate that this variability can be generated intrinsically in pallido-subthalamic circuits without any external inputs due to moderately large strength of synaptic coupling. The dominance of the short desynchronization events indicates that even though the synchronization in parkinsonian basal ganglia is fragile enough to be frequently destabilized, it has the ability to reestablish itself very quickly, which may be important for the development of the therapeutically relevant methods to suppress this synchrony. |
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