Patterns of Subthalamic Synchronized Oscillatory Activity Associated with Subtypes of Parkinson's Disease

Abstract

Background: The pathophysiology underlying subtypes of Parkinson’s disease (PD) remain unclear. The study was to explore whether synchronized subthalamic oscillatory neurons can be a biomarker for parkinsonian subtypes. 

Methods: Thirty patients undergoing subthalamic nucleus (STN) deep brain stimulation were included and classified as postural instability and gait disorder (PIGD), tremor dominant (TD), or intermediate (IT) subtypes. Microelectrode recordings in STN and EMG were simultaneously recorded. Neuronal background was extracted. Spectral and coherence analysis was performed, Correlation test was used. The locations of the oscillatory neurons were noted. 

Results: Of 116 oscillatory neurons, 95.0% β frequency and 83.3% tremor frequency oscillatory neurons were coherent with their background activity. Of 76 synchronized β frequency oscillatory neurons, 13.2% were coherent with limb rigidity in PIGD group whereas of 30 synchronized tremor frequency oscillatory neurons, 20% were coherent with tremor in TD group. Tremor and β frequency oscillatory neurons were correlated with tremor and rigidity/bradykinesia subscores, respectively. Particularly, β frequency oscillatory neurons in subbands of 8-13 Hz, 13-20 Hz and 20-35 Hz correlated with rigidity/bradykinesia subscores; the 13-20 Hz had the strongest correlation. The majority of synchronized oscillatory neurons located in dorsal-STN. 

Conclusion: Different patterns of oscillatory neurons are involved in producing subtypes of TD and PIGD. Tremor and β frequency oscillatory neurons can serve as biomarkers for parkinsonian tremor and rigidity/bradykinesia. The low β frequency subband of 13 ̶ 20 Hz is more implicated for rigidity/bradykinesia. Synchronized oscillatory neurons in the dorsal-STN suggest that the neurons can be used to guide electrode placement.

Note:
Funding Declaration: This work was supported by the National Natural Science Foundation of China (81371256, 81171061, and 81361128012) and the National Key Research and Development Program of China, No.2021YFC2501200. Dr Hallett is supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA.

Conflict of Interests: None.

Ethical Approval: This study was approved by the local Ethics Committee of Xuanwu Hospital, Capital Medical University. All patients signed written informed consents for STN DBS surgery.

Keywords: Parkinson's Disease, tremor, Rigidity/bradykinesia, subthalamic nucleus, Neuronal activity, Microelectrode recordings