Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation

Sheffield, James G.; Ramerpresad, Sumientra; Brem, Anna-Katharine; Mansfield, Karen; Orhan, Umut; Dillard, Michael; McKanna, James; Plessow, Franziska; Thompson, Todd; Santarnecchi, Emiliano; Pascual-Leone, Alvaro; Pavel, Misha; Mathan, Santosh; Kadosh, Roi Cohen (23 June 2022). Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation (In Press) (bioRxiv). Cold Spring Harbor Laboratory 10.1101/2022.03.04.482999

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As transcranial electrical stimulation (tES) protocols advance, assumptions underlying the technique need to be retested to ensure they still hold. Whilst the safety of stimulation has been demonstrated mainly for a small number of sessions, and small sample size, adverse events (AEs) following multiple sessions remain largely untested. Similarly, whilst blinding procedures are typically assumed to be effective, the effect of multiple stimulation sessions on the efficacy of blinding procedures also remains under question. This is especially relevant in multisite projects where small unintentional variations in protocol could lead to inter-site difference. We report AE and blinding data from 1,019 participants who received up to 11 semi-consecutive sessions of active or sham transcranial alternating current stimulation (tACS), direct current stimulation (tDCS), and random noise stimulation (tRNS), at 4 sites in the UK and US. We found that AEs were often best predicted by factors other than tES, such as testing site or session number. Results from the blinding analysis suggested that blinding was less effective for tDCS and tACS than tRNS. The occurrence of AEs did not appear to be linked to tES despite the use of smaller electrodes or repeated delivery. However, blinding efficacy was impacted in tES conditions with higher cutaneous sensation, highlighting a need for alternative stimulation blinding protocols. This may be increasingly necessary in studies wishing to deliver stimulation with higher intensities.

Item Type:

Working Paper


04 Faculty of Medicine > University Psychiatric Services > University Hospital of Geriatric Psychiatry and Psychotherapy

UniBE Contributor:

Brem, Anna- Katharine




Cold Spring Harbor Laboratory




Katharina Klink

Date Deposited:

22 Jun 2022 15:33

Last Modified:

05 Dec 2022 16:21

Publisher DOI:





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