Modulation of Cerebellar Nuclear Activity by Transcranial AC Stimulation in Awake Rats

Overview

Journal Annu Int Conf IEEE Eng Med Biol Soc

Specialty Biomedical Engineering

Date 2025 Mar 5

PMID 40039851

Authors

Nuran Kavakli

Sofyan Hammad

Mesut Sahin

Affiliations

Soon will be listed here.

Abstract

Transcranial alternating current stimulation of the cerebellum (ctACS) is an emerging neuromodulation technique that can potentially be leveraged to treat neurological disorders and improve learning in healthy individuals. Yet, the effects of ctACS on the neuronal circuits of the cerebellum is elusive. We implanted carbon fiber bundle electrodes in the interpositus nucleus of the cerebellum and an array electrode on the posterior surface of the skull for stimulation in chronic rats. Multi-unit activities (MUA) were recorded from three unanesthetized and quietly resting animals during transcranial application of the current stimuli at various frequencies (10 Hz-300 Hz) and amplitudes as well as after harmaline induced tremors. A frequency-spectrum based method for assessing the modulation strength from the MUA was developed. The results show that the interpositus MUA can be modulated transcranially in a range of frequencies with a peak modulation around 50 Hz. This agrees with an earlier report in general [1] although the peak frequency is lower. This study demonstrates the feasibility of entraining the activity of the cerebellar nuclear cells in awake animals by transcranial application of AC stimulation, as well as the detection of harmaline induced tremor from the MUAs. Future research will be directed towards testing the ctACS effects on this animal model of essential tremor.

References

Guerra A, Paparella G, Passaretti M, Costa D, Birreci D, De Biase A . Theta-tACS modulates cerebellar-related motor functions and cerebellar-cortical connectivity. Clin Neurophysiol. 2024; 158:159-169. DOI: 10.1016/j.clinph.2023.12.129. View

Stanford J, Fowler S . At low doses, harmaline increases forelimb tremor in the rat. Neurosci Lett. 1998; 241(1):41-4. DOI: 10.1016/s0304-3940(97)00974-9. View

Middleton F, Strick P . Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev. 2000; 31(2-3):236-50. DOI: 10.1016/s0165-0173(99)00040-5. View

Mehta A, Brittain J, Brown P . The selective influence of rhythmic cortical versus cerebellar transcranial stimulation on human physiological tremor. J Neurosci. 2014; 34(22):7501-8. PMC: 4035515. DOI: 10.1523/JNEUROSCI.0510-14.2014. View

Hurtado J, Rubchinsky L, Sigvardt K . Statistical method for detection of phase-locking episodes in neural oscillations. J Neurophysiol. 2004; 91(4):1883-98. DOI: 10.1152/jn.00853.2003. View

Stoodley C, Schmahmann J . Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2008; 44(2):489-501. DOI: 10.1016/j.neuroimage.2008.08.039. View

Naro A, Leo A, Russo M, Cannavo A, Milardi D, Bramanti P . Does Transcranial Alternating Current Stimulation Induce Cerebellum Plasticity? Feasibility, Safety and Efficacy of a Novel Electrophysiological Approach. Brain Stimul. 2016; 9(3):388-395. DOI: 10.1016/j.brs.2016.02.005. View

Bello 2nd E, Blumenfeld M, Dao J, Krieg J, Wilmerding L, Johnson M . Considerations Using Harmaline for a Primate Model of Tremor. Tremor Other Hyperkinet Mov (N Y). 2021; 11:35. PMC: 8447964. DOI: 10.5334/tohm.634. View

Scherer M, Wang T, Guggenberger R, Milosevic L, Gharabaghi A . Direct modulation index: A measure of phase amplitude coupling for neurophysiology data. Hum Brain Mapp. 2022; 44(5):1862-1867. PMC: 9980882. DOI: 10.1002/hbm.26190. View

10.

Kang Q, Lang E, Sahin M . Transsynaptic entrainment of cerebellar nuclear cells by alternating currents in a frequency dependent manner. Front Neurosci. 2023; 17:1282322. PMC: 10667418. DOI: 10.3389/fnins.2023.1282322. View

11.

Chan C, Nicholson C . Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. J Physiol. 1986; 371:89-114. PMC: 1192712. DOI: 10.1113/jphysiol.1986.sp015963. View

12.

Naro A, Bramanti A, Leo A, Manuli A, Sciarrone F, Russo M . Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function. Brain Struct Funct. 2017; 222(6):2891-2906. DOI: 10.1007/s00429-016-1355-1. View

13.

Wessel M, Draaisma L, de Boer A, Park C, Maceira-Elvira P, Durand-Ruel M . Cerebellar transcranial alternating current stimulation in the gamma range applied during the acquisition of a novel motor skill. Sci Rep. 2020; 10(1):11217. PMC: 7343806. DOI: 10.1038/s41598-020-68028-9. View

14.

Grimaldi G, Manto M . Topography of cerebellar deficits in humans. Cerebellum. 2011; 11(2):336-51. DOI: 10.1007/s12311-011-0247-4. View

15.

Aydore S, Pantazis D, Leahy R . A note on the phase locking value and its properties. Neuroimage. 2013; 74:231-44. PMC: 3674231. DOI: 10.1016/j.neuroimage.2013.02.008. View

16.

Feng T, Zhang L, Wu Y, Tang L, Chen X, Li Y . Exploring the Therapeutic Effects and Mechanisms of Transcranial Alternating Current Stimulation on Improving Walking Ability in Stroke Patients via Modulating Cerebellar Gamma Frequency Band-a Narrative Review. Cerebellum. 2023; 23(4):1593-1603. PMC: 11269344. DOI: 10.1007/s12311-023-01632-3. View

17.

Wessel M, Draaisma L, Hummel F . Mini-review: Transcranial Alternating Current Stimulation and the Cerebellum. Cerebellum. 2022; 22(1):120-128. DOI: 10.1007/s12311-021-01362-4. View

18.

Strick P, Dum R, Fiez J . Cerebellum and nonmotor function. Annu Rev Neurosci. 2009; 32:413-34. DOI: 10.1146/annurev.neuro.31.060407.125606. View