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Polarity- and Intensity-Independent Modulation of Timing During Delay Eyeblink Conditioning Using Cerebellar Transcranial Direct Current Stimulation

Abstract

Delay eyeblink conditioning (dEBC) is widely used to assess cerebellar-dependent associative motor learning, including precise timing processes. Transcranial direct current stimulation (tDCS), noninvasive brain stimulation used to indirectly excite and inhibit select brain regions, may be a promising tool for understanding how functional integrity of the cerebellum influences dEBC behavior. The aim of this study was to assess whether tDCS-induced inhibition (cathodal) and excitation (anodal) of the cerebellum differentially impact timing of dEBC. A standard 10-block dEBC paradigm was administered to 102 healthy participants. Participants were randomized to stimulation conditions in a double-blind, between-subjects sham-controlled design. Participants received 20-min active (anodal or cathodal) stimulation at 1.5 mA (n = 20 anodal, n = 22 cathodal) or 2 mA (n = 19 anodal, n = 21 cathodal) or sham stimulation (n = 20) concurrently with dEBC training. Stimulation intensity and polarity effects on percent conditioned responses (CRs) and CR peak and onset latency were examined using repeated-measures analyses of variance. Acquisition of CRs increased over time at a similar rate across sham and all active stimulation groups. CR peak and onset latencies were later, i.e., closer to air puff onset, in all active stimulation groups compared to the sham group. Thus, tDCS facilitated cerebellar-dependent timing of dEBC, irrespective of stimulation intensity and polarity. These findings highlight the feasibility of using tDCS to modify cerebellar-dependent functions and provide further support for cerebellar contributions to human eyeblink conditioning and for exploring therapeutic tDCS interventions for cerebellar dysfunction.

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Acknowledgments

We wish to thank Karen Lorite-Gomez for her assistance with the data collection.

Funding

This work was supported by the National Institutes of Health (grant number T32 MH103213 to WPH, ABM, and NBL; R01 MH074983 to WPH; R21 MH091774 to BFO; Indiana Clinical and Translational Sciences Institute award TL1 TR001107 and UL1 TR001108 to ABM), the National Science Foundation (Graduate Research Fellowship Program Award 1342962 to NBL), and the Brain and Behavior Research Foundation (NARSAD Young Investigator Award to ARB).

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Correspondence to William P. Hetrick.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Indiana University Institutional Review Board protocol no. 1508694422) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Mitroi, J., Burroughs, L.P., Moussa-Tooks, A.B. et al. Polarity- and Intensity-Independent Modulation of Timing During Delay Eyeblink Conditioning Using Cerebellar Transcranial Direct Current Stimulation. Cerebellum (2020). https://doi.org/10.1007/s12311-020-01114-w

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Keywords

  • Cerebellum
  • Transcranial direct current stimulation
  • Associative learning
  • Eyeblink conditioning
  • Polarity
  • Intensity