Objective: Tremor and volitional rhythmic movement are frequency-specific motions. However, it remains unclear which area of the central nervous system can process frequency information. This study aims to provide an insight of frequency coding using electrophysiological recordings and manipulations.

Background: Cerebellar electroencephalography (EEG) has been used to detect cerebellar oscillations in essential tremor (ET) patients and parkinsonian patients. In our previous works, we have identified excessive cerebellar oscillations in ET patients. Cerebellar tACS also showed its amplitude modulatory effects in ET. However, the human evidence of cerebellar frequency-modulation remained to be explored.

Method: We record the kinematics of posture tremor with a 3-axis accelerometer in 15 ET patients and evaluate the dominant moving axis during tremor. tACS of 2 mA was applied to the cerebellar cortex at each patient’s tremor frequency. Each patient received 2 repeated trials in a single section. We extracted Hilbert-based instantaneous frequency and measured the frequency stability with or without tACS. In 6 healthy subjects, we applied the same protocol during figure tapping at 4 Hz and evaluate the frequency stability. Each subject received 3 repetitive trials. We also recorded cerebellar EEG of 10 healthy subjects during finger tapping at 4, 5, and 6 Hz.

Results: In ET patients, tACS showed a bidirectional effect of frequency modulation. 15 of the 30 trials showed reversible and increased frequency stability, while 13 of the 30 trials showed reversible and decreased frequency stability. Only one ET patient did not respond to tACS in his two trials. Similar bidirectional effects were also observed in 10 healthy subjects. In finger tapping with simultaneous cerebellar EEG recordings, induced cerebellar oscillations at the tapping frequency were reliably observed in all 10 subjects.

Conclusion: This study suggest that human cerebellum contributes to the frequency coding of motor rhythm in both tremor and volitional rhythmic movements. The frequency stability can be bidirectionally modulated by a in-phase or anti-phase tACS.

References: 1. 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
2. Ami Kumar, Chih-Chun Lin, Sheng-Han Kuo & Ming-Kai Pan*. Physiological recordings of the cerebellum in movement disorders. Cerebellum 2022 [Epub ahead of print].
3. Ming-Kai Pan* and Sheng-Han Kuo. Essential tremor: Clinical perspectives and pathophysiology. Journal of the Neurological Sciences 2022. Apr 15;435:120198
4. S-B Wong, Y-M Wang, C-C Lin, Scott Kun Geng, Nora Vanegas-Arroyave, Seth L. Pullman, S-H Kuo, M-K Pan*. Cerebellar Oscillations in Familial and Sporadic Essential Tremor. Cerebellum. 2021 Jun 21(3):425-431

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MDS Abstracts - https://www.mdsabstracts.org/abstract/human-cerebellum-contributes-to-the-motor-frequency-coding-for-essential-tremor-and-volitional-rhythmic-movements/