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- Title
Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.
- Authors
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; Pan, Ming-Kai
- 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 Grid2dupE3 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. Editor's summary: Understanding how essential tremor (ET) is encoded within the cerebello-thalamo-cortical network could help to optimize brain stimulation for ET treatment. Here, Wang et al. show that tremor frequency is encoded by coherent population activity in the cerebellum. This activity occurred spontaneously in a mouse model of essential tremor and could be elicited by optogenetic stimulation to induce tremor in wild-type mice. Cerebellar oscillations in patients with ET occurred independently of thalamic activity and could be modulated by transcranial alternating current stimulation (tACS) to disrupt tremors. These findings indicate that disrupting cerebellar oscillations by noninvasive tACS could be a viable strategy for ET therapy, warranting further validation and optimization. —Daniela Neuhofer
- Subjects
ESSENTIAL tremor; TRANSCRANIAL alternating current stimulation; CEREBELLAR nuclei; DEEP brain stimulation; ACTION potentials; NEURAL codes
- Publication
Science Translational Medicine, 2024, Vol 16, Issue 747, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.adl1408