Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials

Fonteneau, Clara; Mondino, Marine; Arns, Martijn; Baeken, Chris; Bikson, Marom; Brunoni, André R.; Burke, Matthew J.; Neuvonen, Tuomas; Padberg, Frank; Pascual‐Leone, Álvaro; Poulet, Emmanuel; Ruffini, Giulio; Santarnecchi, Emiliano; Sauvaget, Anne; Schellhorn, Klaus; Suaud-Chagny, Marie-Françoise; Palm, Ulrich

doi:10.1016/j.encep.2019.04.033

Cited by 24 publications

(33 citation statements)

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“…Furthermore, differently from previous studies, we compared the efficacy of one versus two daily sessions of tDCS showing that two daily sessions have a greater impact on depression severity but not on cognitive functioning. Prior studies have reported significant neuromodulatory effects at the lower end of stimulation intensities [64e67], however in many recent studies low current intensities have been used for the length of the whole stimulation to mimic the sensations of a real stimulation [64,65] whereas, to avoid the biological effect due to low current stimulations, we used a protocol characterized by 0 mA and just two short 30-s current ramps up to 2 mA.…”

Section: Discussionmentioning

confidence: 99%

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression

et al. 2020

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Background: Despite the impact of depression in terms of personal suffering and socioeconomic burden, most currently available treatment options are often ineffective. A particularly difficult-to-treat depressive disorder characteristic of the elderly is vascular depression, a late-life depressive syndrome related to a variety of potential vascular mechanisms. Transcranial Direct Current Stimulation (tDCS), a non-invasive and effective somatic approach to depression, also showed positive effects on cognitive deficits. Aim: We performed a double-blind randomized study to investigate the efficacy of tDCS as augmentation strategy to sertraline in the treatment of vascular depression, hypothesizing a positive effect in both depressive symptoms and cognitive functions. Methods: We enrolled 93 inpatients over 60 years of age with a diagnosis of vascular depression. Depressive symptoms were weekly assessed (T0, T1, T2) with the 21-items Hamilton depression rating scale (HDRS). Cognitive functioning was evaluated with the Milan Overall Dementia Assessment (MODA) at baseline and after the treatment protocol. All patients were randomly assigned into three groups, Group I: one tDCS stimulation per day, Group II: two tDCS stimulations per day, Sham group: one sham tDCS stimulation per day. Stimulation was performed for 10 consecutive working days. Results: A significant interaction time*treatment was observed on HDRS scores (F ¼ 14, p < 0.001). All groups improved at T1 but whereas Group II significantly differed from the Sham group (p < 0.001) we observed no difference between Sham and Group I. At T2 all groups improved but Group II showed the greater improvement (vs. Sham p < 0.001; vs. Group I p < 0.001) and the Sham group the smallest (vs. Group I p ¼ 0.005). A significant interaction time*treatment was also observed on MODA scores (F ¼ 3.31, p ¼ 0.04). Only subjects treated with tDCS improved at T2 (Group I: p < 0.001; Group II: p ¼ 0.007). However, no difference between Group I and II was shown. Conclusion: tDCS as augmentation treatment of an adequate pharmacotherapy is a potential strategy in the management of vascular depression, a disease known to be often unresponsive to antidepressants only. Non-invasiveness, the absence of severe side effects and the possibility of administering it to outpatients at an affordable price make tDCS an important tool in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression

et al. 2020

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“…According to the study mode of the DC-Stimulator (neuroConn GmbH, Ilmenau, Germany), a short stimulation of 2 mA was applied for 20s between the fade-in and fade-out periods, which were identical to the anodal stimulation and lasted 6 s each. This procedure prevented any effective modulation of cortical excitability by tDCS [ 17 ] and ensured blinding of the patients, since any putative sensations associated with anodal tDCS (e.g., itching, tingling) would also occur for sham tDCS [ 19 ]. The investigator, who applied tDCS (JMA), was blinded for the type of tDCS (anodal or sham) with the help of the NeuroConn study mode, in which an individual code triggered either anodal or sham stimulation of a given patient by the pre-programmed tDCS study device.…”

Section: Methodsmentioning

confidence: 99%

“…However, the participants of the current pilot study were LH stroke patients suffering from cognitive (e.g., apraxic, aphasic) deficits of different severity, which most likely have reduced their ability to distinguish real from sham tDCS, as has previously shown in clinical populations [ 19 ]. Nevertheless, future clinical tDCS studies should include a systematic assessment of blinding efficacy (e.g., by using questionnaires as in [ 4 ]) and employ optimized sham tDCS protocols [ 17 ].…”

Section: Limitationsmentioning

confidence: 99%

Anodal tDCS over left parietal cortex expedites recovery from stroke-induced apraxic imitation deficits: a pilot study

Ant

Niessen

Achilles

et al. 2019

Neurol. Res. Pract.

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Background: To date, specific therapeutic approaches to expedite recovery from apraxic deficits after left hemisphere (LH) stroke remain sparse. Thus, in this pilot study we evaluated the effect of anodal transcranial direct current stimulation (tDCS) in addition to a standardized motor training on apraxic imitation deficits. Methods: In a rehabilitation hospital, we assessed apraxic, aphasic, and motor deficits in 30 LH stroke patients before and after a five-day standard programme of motor training combined with either anodal (10 min, 2 mA; n = 14) or sham (10 min, 0 mA, n = 16) tDCS applied in a double-blind fashion over left posterior parietal cortex (PPC). Where appropriate, data were analyzed with either t-test, Fisher's exact test, or univariate/ repeated measures ANOVA. Results: Compared to sham tDCS, five sessions of anodal tDCS expedited recovery from apraxic imitation deficits (p < 0.05): Already after 5 days, the anodal tDCS group showed levels of imitation performance that were achieved in the sham tDCS group after 3 months. However, the primary outcome of the study (i.e., anodal tDCS induced improvement of the total apraxia score) failed significance, and there was no significant tDCS effect on apraxia after 3 months. Anodal tDCS improved grip force (of the contra-lesional, i.e., right hand), but had no effect on aphasia. Conclusions: Data from this pilot study show that repetitive, anodal tDCS over left PPC combined with a standardized motor training expedites recovery from imitation deficits in LH stroke patients with apraxia (relative to sham stimulation). Results suggest that in patients suffering from apraxic imitation deficits a randomized controlled trial (RCT) is warranted that investigates the effects of tDCS applied over PPC in addition to a standardized motor training.

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“…Control condition (sham and/or active control) : The usual approach for blinding a study is to use a sham stimulation (no stimulation during the session but inducing sensations at the beginning and/or end of the session via ramp up/ ramp down of current). However, inconsistency in sham‐controlled studies in tDCS literature resulted in debates on whether different sham protocols are equivalent (Fonteneau et al, ). Another approach in blinding a study is active control, which refers to a condition where the stimulation is performed over an area irrelevant for the purpose of study. 4.…”

Section: Tdcs‐mr Imaging: Trial Design Parameter Spacementioning

confidence: 99%

Methodology for tDCS integration with fMRI

Esmaeilpour

Shereen

Ghobadi‐Azbari

et al. 2019

Human Brain Mapping

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Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state‐level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS‐fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS‐fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS‐fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.

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Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials

Cited by 24 publications

References 1 publication

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression

Anodal tDCS over left parietal cortex expedites recovery from stroke-induced apraxic imitation deficits: a pilot study

Methodology for tDCS integration with fMRI

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