Tremor-correlated spike activity in Parkinson's disease detected in a distributed subthalamic network

Introduction: There is clinical and neurophysiological evidence for the involvement of the basal ganglia in the pathogenesis of Parkinsonian tremor. The aim of this study was to investigate the relation between tremor and spike activity in the subthalamic nucleus (STN) of patients with Parkinson's disease. Methods: Data was obtained during stereotactic surgery on patients with tremor-dominant Parkinson's disease. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. Wavelet-based spike-sorting was performed to enable coherence analysis between spike activity of spatially distributed neurons and tremor activity. Results: Significant coherence at the tremor frequency was detected between the tremor EMG and spike activity of several simultaneously recorded neurons in the STN. Tremor-correlated spike activity of multiple neurons was observed both locally within the reach of one microelectrode and spatially distributed at different microelectrodes up to 5mm apart. We observed also interneuronal coherence between local and distant subthalamic neurons at the tremor frequency as well as in the beta frequency range. These findings were detected in different depths of the STN. Conclusion: Our results support the hypothesis that synchronous neuronal activity in the STN contributes to the pathogenesis of Parkinsonian tremor. This synchronous activity was not restricted to local portions of the STN. The wide-spread spatial distribution of coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.