Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation

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Abstract

Objective

Brain polarization in the form of transcranial direct current stimulation (tDCS), which influences motor function and learning processes, has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind sham-controlled study designs. Here, we evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and stroke patients' self-report measures of attention, fatigue, duration of elicited sensations and discomfort.

Methods

tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue, and discomfort were self rated by study participants using visual analog scales. Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined. Investigators questioning the patients were blind to the intervention type.

Results

tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue, and could not be distinguished from SHAM by study participants nor investigators.

Conclusions

Successful blinding of subjects and investigators and ease of application simultaneously with training protocols supports the feasibility of using tDCS in double-blind, sham-controlled randomized trials in clinical Neurorehabilitation.

Significance

tDCS could evolve into a useful tool, in addition to TMS, to modulate cortical activity in Neurorehabilitation.

Introduction

Non-invasive brain polarization through transcranial direct current stimulation (tDCS) influences cognitive functions in healthy volunteers (Antal et al., 2004, Fregni et al., 2005a, Iyer et al., 2005, Nitsche et al., 2003a) and transiently enhances motor performance in patients with chronic stroke (Hummel et al., 2005a, Hummel and Cohen, 2005, Fregni et al., 2005b). tDCS can be applied continuously and safely for up to 30 min (Hummel et al., 2005a, Iyer et al., 2005, Nitsche et al., 2005), close to the typical duration of a session of rehabilitative treatment, and can be administered in synchrony with motor training protocols (Hummel et al., 2005a). However, it remains to be determined if tDCS is amenable for use in strict randomized control trial designs in clinical Neurorehabilitation. Failure of blinding could compromise objective evaluations, resulting in biased assessment of intervention effects (Day and Altman, 2000, Schulz et al., 1995). Here, we evaluated perceived sensations, discomfort, ratings of attention and fatigue, and the ability to retrospectively identify each intervention during both tDCS and SHAM in chronic stroke patients and healthy volunteers and the ability of investigators questioning the subjects to identify the tDCS and SHAM sessions, to determine the quality and effectiveness of this technique for double-blind sham-controlled experimental designs. Data was pooled from several studies performed over the last 3 years spanning over 170 sessions in our laboratory at the NINDS.

Section snippets

Subjects

We studied healthy volunteers (HV) and chronic stroke patients (CSP) who participated in protocols examining the effects of anodal (HV: n=8, 4 of them women, age 60.7±6.5 yo; CSP: n=14, 7 of them women, age 57.6±3.8 yo) or cathodal tDCS (HV: n=16, 8 of them women, age 46.3±5.6 yo; CSP: n=9, 4 of them women, age 62.3±4.9 yo) on motor function. MMSE was >28 in all subjects, some of whom participated in both experiments for a total of 170 sessions. Some of the subjects did not take part in all

Results

Subjects (CSP and elder HV) described no sensations (tDCS: 19.6% and SHAM: 22.2% of the group), slight tingling (tDCS: 46.4% and SHAM: 51.9%), or a transient mild burning (tDCS: 33.9% and SHAM: 25.9%) associated with the onset of stimulation. Ratings of discomfort and duration of sensations were comparable with tDCS and SHAM in both groups (Table 1A, Table 1B) as were attention and fatigue across time (before [Pre-Stim] and after stimulation [Post-Stim]) and intervention (tDCS and SHAM). Elder

Discussion

The findings of minimal discomfort (1–2 out of 10), absence of overt effects on subjective ratings of attention or fatigue, and easiness of blinding investigators, healthy volunteers and stroke patients indicate that tDCS can be used in the setting of strict double-blind sham-controlled randomized trials in Neurorehabilitation and cognitive neuroscience.

Differences in perceptual cues as well as presence of side effects often blur double-blind, sham-controlled experimental designs (Day and

Acknowledgements

The authors thank S. Ravindran, for patient recruitment, N. Dang and M. Lomarev for technical assistance, J. Samuels for data acquisition and M. Harris-Love and N.-J. Paik for application of tDCS/SHAM in the double blind design. This research was supported by the intramural research program of NINDS, NIH, a grant from the Alexander von Humboldt Foundation (Feodor-Lynen) to F. Hummel and by the Clinical Research Training Program (Pfizer Pharmaceuticals Group) to P. Gandiga.

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    Both authors contributed equally.

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