Objective: Investigate how the cerebellum computes and regulates motor precision during daily movements

Background: Motor coordination, ensuring movement precision and reliability, is governed by the cerebellum. However, how it encodes coordination remains unclear. Cerebellar disorders like tremors and ataxias exhibit excessive or diminished motor rhythm. While most daily movements are non-rhythmic, they can be mathematically represented as dynamic instantaneous frequencies. We hypothesize the cerebellum encodes these frequencies to regulate movement.

Method: We conducted electrophysiological investigations in mice and humans. In mice, single-unit activities and local field potentials (LFPs) were recorded during movements with changing frequencies and natural licking behaviors. Optogenetics manipulated cerebellar neuron firing. In humans, cerebellar electroencephalography (cEEG) assessed rhythmic dynamics during volitional movements. Transcranial alternating current stimulation (tACS) modulated cerebellar oscillatory frequencies.

Results: In mice, cerebellar LFPs dynamically matched motor frequencies. Individual neuron firing rates correlated weakly with motor frequencies, but collective neuronal activity converged to match instantaneous motor frequency. Optogenetic cerebellar stimulation generated complex movements following designed frequency dynamics. In humans, cEEG confirmed cerebellar oscillatory frequencies aligned with volitional movement frequencies. tACS modulated movement frequency stability, reinforcing or disrupting motor rhythm depending on parameters.

Conclusion: The cerebellum ensures precise motor coordination through frequency coding. Rhythmic movements rely on stable frequencies, while non-rhythmic movements involve dynamically varying frequencies. Our findings show movements can be engineered via cerebellar frequency manipulation in mice and modulated using tACS in humans, offering therapeutic insights for movement disorders.

References: 1. Chih-Chun Lin, Ke-Chu Fang, Ilaria Balbo, Ting-Yu Liang, Chia-Wei Liu, Wen-Chuan Liu, Yi-Mei Wang, Yen-Ling Hung, Kai-Chien Yang, Scott Kun Geng, Chun-Lun Ni, Christopher P. Driscoll, David S. Ruff, Ami Kumar, Nadia Amokrane, Natasha Desai, Phyllis L. Faust, Elan D. Louis, Sheng-Han Kuo*, Ming-Kai Pan*. Reduced cerebellar rhythm by climbing fiber denervation is linked to motor rhythm deficits in mice and ataxia severity in patients. Science Translational Medicine. 2025 Feb 26;17(787):eadk3922.
2. Ming-Kai Pan*. Targeting the fundamentals for tremors: the frequency and amplitude coding in essential tremor. Journal of Biomedical Science. 2025 Feb 10;32(1):18.
3. Yi-Mei Wang, Chia-Wei Liu, Shun-Ying Chen, Liang-Yin Lu, Wen-Chuan Liu, Jia-Huei Wang, Chun-Lun Ni, Shi-Bing Wong, Ami Kumar, Jye-Chang Lee, Sheng-Han Kuo, Shun-Chi Wu, Ming-Kai Pan*. Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients. Science Translational Medicine. 2024 May 15;16(747):eadl1408.
4. Yin-Tzu Hsieh, Kai-Chun Jhan, Jye-Chang Lee, Guan-Jie Huang, Chang-Ling Chung, Wun-Ci Chen, Ting-Chen Chang, Bi-Chang Chen, Ming-Kai Pan*, Shun-Chi Wu*, Shi-Wei Chu* TAG-SPARK: Empowering High-Speed Volumetric Imaging with Deep Learning and Spatial Redundancy. Advanced Science 2024 Nov; 11(41):e2405293.
5. Pan M-K*, Li Y-S, Wang S-B, Ni C-L, Wang Y-M, Liu W-C, Lu L-Y, Lee J-C, Cortes EP, Vonsattel J-P, Sun Q, Louis E, Faust P, Kuo S-H*. Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology. Science Translational Medicine. 2020 Jan 15;12(526):eeey1769.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-cerebellum-encodes-dynamic-motor-frequencies-for-volitional-movements/