Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.
Journal
Science translational medicine
Journal Volume
16
Journal Issue
747
Start Page
adl1408
ISSN
1946-6234
Date Issued
2024-05-15
Author(s)
Wang, Yi-Mei
Liu, Chia-Wei
Chen, Shun-Ying
Lu, Liang-Yin
Liu, Wen-Chuan
Wang, Jia-Huei
Ni, Chun-Lun
Wong, Shi-Bing
Kumar, Ami
Lee, Jye-Chang
Kuo, Sheng-Han
Wu, Shun-Chi
Abstract
Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.
Type
journal article