Long-term effects of cerebellar anodal transcranial direct current stimulation (tDCS) on the acquisition and extinction of conditioned eyeblink responses

Otilia Kimpel,Thomas Hulst,Michael A Nitsche,Giorgi Batsikadze,Thomas M Ernst,Marcus Gerwig,Dagmar Timmann

doi:10.1038/s41598-020-80023-8

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.

Highlights

Transcranial direct current stimulation can alter cortical excitability and enhance neuronal plasticity[1,2], an important physiological foundation of learning and memory formation. transcranial direct current stimulation (tDCS) of primary motor cortex (M1) has been shown to improve motor learning[3,4], and has become a promising option to enhance the beneficial effects of motor training in various neurological d isorders[5,6,7,8]
A more recent study in mice showed that the deletion of long-term potentiation (LTP) of Purkinje cells eliminates cerebellar tDCS effects on vestibulo-ocular reflex (VOR) h abituation[14], and delivers mechanistic information about the plasticity effects of cerebellar tDCS
We found that cerebellar tDCS of the cerebellum modulates delay eyeblink conditioning in healthy p articipants[24]

Summary

Introduction

Transcranial direct current stimulation (tDCS) can alter cortical excitability and enhance neuronal plasticity[1,2], an important physiological foundation of learning and memory formation. tDCS of primary motor cortex (M1) has been shown to improve motor learning[3,4], and has become a promising option to enhance the beneficial effects of motor training in various neurological d isorders[5,6,7,8]. We found that cerebellar tDCS of the cerebellum modulates delay eyeblink conditioning in healthy p articipants[24]. TDCS during pseudo-conditioning might have resulted in unforeseen learning during this stage, and interference in the acquisition stage, and the reduced reinforcement rate might have strengthened such an interference effect. The aim of the present study was to confirm our initial findings using the same experimental eyeblink conditioning set-up and paradigm, including the same reinforcement rate and onset of cerebellar tDCS. Because significant tDCS effects on CR acquisition were present within less than 10 min, decision was made to apply a more conventional stimulation time of 24.2 min. In addition to immediate effects, long-term effects of cerebellar tDCS on the acquisition and extinction of conditioned eyeblinks were evaluated across multiple days

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