Modulation of Cerebellar Oscillations with Subthalamic Stimulation in Patients with Parkinson's Disease

Abstract

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson's disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations.

Objective: To observe the effects of STN-DBS on cerebellar oscillations in patients with PD.

Methods: We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity.

Results: In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions.

Conclusions: While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Keywords: Parkinson’s disease; Subthalamic nucleus; cerebellar; deep brain stimulation; oscillations.

Fig. 1

Effects of HF STN-DBS on cerebellar theta and beta oscillations. A–C) Spectral power differences between OFF-DBS and HF-DBS at Cb1, Cbz, and Cb2. D–F) HF STN-DBS increases relative theta-band power across Cb1, Cbz, and Cb2 cerebellar electrode sites. G–I) HF STN-DBS increases relative beta-band power across Cb1, Cbz, and Cb2 cerebellar electrode sites. **p < 0.01, ***p < 0.001 vs. OFF-DBS. In violin plots, horizontal lines and white circles represent the mean and median values, respectively.

Fig. 2

Association between mid-cerebellar theta and beta and PD severity. No association between relative theta-band power and mUPDRS scores during A) OFF-DBS or B) HF-DBS. C) Relative beta-band power is positively associated with mUPDRS scores during OFF-DBS. D) No association between relative beta-band power and mUPDRS during HF-DBS. mUPDRS, motor portion of the Unified Parkinson’s Disease Rating Scale. *p < 0.05.