Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation
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.
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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.
References (35)
- et al.
Transcranial magnetic stimulation: neurophysiological applications and safety
Brain Cogn
(2002) - et al.
Pain assessment in cognitively impaired and unimpaired older adults: a comparison of four scales
Pain
(2001) - et al.
The effect of short-duration bursts of high-frequency, low-intensity transcranial magnetic stimulation on the human motor cortex
Clin Neurophysiol
(2004) - et al.
Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials
Biol Psychiatry
(2001) - et al.
Modulation of cortical excitability by weak direct current stimulation—technical, safety and functional aspects
Suppl Clin Neurophysiol
(2003) - et al.
Safety criteria for transcranial direct current stimulation (tDCS) in humans
Clin Neurophysiol
(2003) - et al.
Level of action of cathodal DC polarisation induced inhibition of the human motor cortex
Clin Neurophysiol
(2003) - et al.
Transcranial magnetic stimulation in cognitive neuroscience—virtual lesion, chronometry, and functional connectivity
Curr Opin Neurobiol
(2000) Transcranial direct current stimulation (tDCS)
Suppl Clin Neurophysiol
(2003)Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5–7, 1996
Electroencephalogr Clin Neurophysiol
(1998)
Therapeutic application of repetitive transcranial magnetic stimulation: a review
Clin Neurophysiol
Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans
J Cogn Neurosci
Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain
J Physiol
Studies of human motor physiology with transcranial magnetic stimulation
Muscle Nerve Suppl
Studies of neuroplasticity with transcranial magnetic stimulation
J Clin Neurophysiol
Statistics notes: blinding in clinical trials and other studies
Br Med J
Influence of somatosensory input on motor function in patients with chronic stroke
Ann Neurol
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Both authors contributed equally.