Long-term Effects of Cerebellar Anodal Transcranial Direct Current Stimulation (tDCS) on the Acquisition and Extinction of Conditioned Eyeblink Responses

Overview

Journal Sci Rep

Specialty Science

Date 2021 Jan 1

PMID 33384434

Citations 3

Authors

Otilia Kimpel

Thomas Hulst

Giorgi Batsikadze

Thomas M Ernst

Michael A Nitsche

Dagmar Timmann

Marcus Gerwig

Affiliations

Soon will be listed here.

Abstract

Cerebellar transcranial direct current stimulation (tDCS) has been reported to enhance the acquisition of conditioned eyeblink responses (CR), a form of associative motor learning. The aim of the present study was to determine possible long-term effects of cerebellar tDCS on the acquisition and extinction of CRs. Delay eyeblink conditioning was performed in 40 young and healthy human participants. On day 1, 100 paired CS (conditioned stimulus)-US (unconditioned stimulus) trials were applied. During the first 50 paired CS-US trials, 20 participants received anodal cerebellar tDCS, and 20 participants received sham stimulation. On days 2, 8 and 29, 50 paired CS-US trials were applied, followed by 30 CS-only extinction trials on day 29. CR acquisition was not significantly different between anodal and sham groups. During extinction, CR incidences were significantly reduced in the anodal group compared to sham, indicating reduced retention. In the anodal group, learning related increase of CR magnitude tended to be reduced, and timing of CRs tended to be delayed. The present data do not confirm previous findings of enhanced acquisition of CRs induced by anodal cerebellar tDCS. Rather, the present findings suggest a detrimental effect of anodal cerebellar tDCS on CR retention and possibly CR performance.

Citing Articles

Acute aerobic exercise enhances associative learning in regular exercisers but not in non-regular exercisers.

Gultig K, Boele C, Roggeveen L, Soong T, Koekkoek S, De Zeeuw C Front Behav Neurosci. 2025; 18():1515682.

PMID: 39839536 PMC: 11747211. DOI: 10.3389/fnbeh.2024.1515682.

The cerebellum and fear extinction: evidence from rodent and human studies.

Doubliez A, Nio E, Senovilla-Sanz F, Spatharioti V, Apps R, Timmann D Front Syst Neurosci. 2023; 17:1166166.

PMID: 37152612 PMC: 10160380. DOI: 10.3389/fnsys.2023.1166166.

Portable Neuroimaging-Guided Noninvasive Brain Stimulation of the Cortico-Cerebello-Thalamo-Cortical Loop-Hypothesis and Theory in Cannabis Use Disorder.

Walia P, Ghosh A, Singh S, Dutta A Brain Sci. 2022; 12(4).

PMID: 35447977 PMC: 9027826. DOI: 10.3390/brainsci12040445.

Transcranial Direct Current Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis.

Liu X, Liu H, Liu Z, Rao J, Wang J, Wang P Front Aging Neurosci. 2021; 13:746797.

PMID: 34776931 PMC: 8584149. DOI: 10.3389/fnagi.2021.746797.

References

Bracha V, Zhao L, Irwin K, Bloedel J . The human cerebellum and associative learning: dissociation between the acquisition, retention and extinction of conditioned eyeblinks. Brain Res. 2000; 860(1-2):87-94. DOI: 10.1016/s0006-8993(00)01995-8. View

Garcia K, Mauk M . Pharmacological analysis of cerebellar contributions to the timing and expression of conditioned eyelid responses. Neuropharmacology. 1998; 37(4-5):471-80. DOI: 10.1016/s0028-3908(98)00055-0. View

Schmitz-Hubsch T, Tezenas Du Montcel S, Baliko L, Berciano J, Boesch S, Depondt C . Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006; 66(11):1717-20. DOI: 10.1212/01.wnl.0000219042.60538.92. View

Messerschmidt A, Brugger P, Boltshauser E, Zoder G, Sterniste W, Birnbacher R . Disruption of cerebellar development: potential complication of extreme prematurity. AJNR Am J Neuroradiol. 2005; 26(7):1659-67. PMC: 7975176. View

Prokasy W, EBEL H, Thompson D . Response shaping at long interstimulus intervals in classical eyelid conditioning. J Exp Psychol. 1963; 66:138-41. DOI: 10.1037/h0049246. View

Perrett S, Ruiz B, Mauk M . Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci. 1993; 13(4):1708-18. PMC: 6576722. View

Mauk M, Li W, Khilkevich A, Halverson H . Cerebellar mechanisms of learning and plasticity revealed by delay eyelid conditioning. Int Rev Neurobiol. 2014; 117:21-37. DOI: 10.1016/B978-0-12-420247-4.00002-6. View

Jimenez-Diaz L, Navarro-Lopez J, Gruart A, Delgado-Garcia J . Role of cerebellar interpositus nucleus in the genesis and control of reflex and conditioned eyelid responses. J Neurosci. 2004; 24(41):9138-45. PMC: 6730068. DOI: 10.1523/JNEUROSCI.2025-04.2004. View

Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb F, Frings M . Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci. 2005; 25(15):3919-31. PMC: 6724917. DOI: 10.1523/JNEUROSCI.0266-05.2005. View

10.

Zuchowski M, Timmann D, Gerwig M . Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS. Brain Stimul. 2014; 7(4):525-31. DOI: 10.1016/j.brs.2014.03.010. View

11.

Lipp J, Draganova R, Batsikadze G, Ernst T, Uengoer M, Timmann D . Prefrontal but not cerebellar tDCS attenuates renewal of extinguished conditioned eyeblink responses. Neurobiol Learn Mem. 2019; 170:107137. DOI: 10.1016/j.nlm.2019.107137. View

12.

Rahman A, Reato D, Arlotti M, Gasca F, Datta A, Parra L . Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects. J Physiol. 2013; 591(10):2563-78. PMC: 3678043. DOI: 10.1113/jphysiol.2012.247171. View

13.

Delgado-Garcia J, Gruart A . The role of interpositus nucleus in eyelid conditioned responses. Cerebellum. 2003; 1(4):289-308. DOI: 10.1080/147342202320883597. View

14.

Benussi A, DellEra V, Cotelli M, Turla M, Casali C, Padovani A . Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia. Brain Stimul. 2016; 10(2):242-250. DOI: 10.1016/j.brs.2016.11.001. View

15.

Galea J, Vazquez A, Pasricha N, Orban de Xivry J, Celnik P . Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. Cereb Cortex. 2010; 21(8):1761-70. PMC: 3138512. DOI: 10.1093/cercor/bhq246. View

16.

Miterko L, Baker K, Beckinghausen J, Bradnam L, Cheng M, Cooperrider J . Consensus Paper: Experimental Neurostimulation of the Cerebellum. Cerebellum. 2019; 18(6):1064-1097. PMC: 6867990. DOI: 10.1007/s12311-019-01041-5. View

17.

Molchan S, Sunderland T, McIntosh A, Herscovitch P, Schreurs B . A functional anatomical study of associative learning in humans. Proc Natl Acad Sci U S A. 1994; 91(17):8122-6. PMC: 44557. DOI: 10.1073/pnas.91.17.8122. View

18.

Ferrucci R, Cortese F, Priori A . Cerebellar tDCS: how to do it. Cerebellum. 2014; 14(1):27-30. PMC: 4318979. DOI: 10.1007/s12311-014-0599-7. View

19.

Labruna L, Jamil A, Fresnoza S, Batsikadze G, Kuo M, Vanderschelden B . Efficacy of Anodal Transcranial Direct Current Stimulation is Related to Sensitivity to Transcranial Magnetic Stimulation. Brain Stimul. 2015; 9(1):8-15. PMC: 4724228. DOI: 10.1016/j.brs.2015.08.014. View

20.

Herzfeld D, Hall N, Tringides M, Lisberger S . Principles of operation of a cerebellar learning circuit. Elife. 2020; 9. PMC: 7255800. DOI: 10.7554/eLife.55217. View