Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop

Abstract

BackgroundNeuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.ObjectiveThis report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment.MethodsThe National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs.ResultsAdvances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them.ConclusionsThese recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.

Blinding is compromised for transcranial direct current stimulation at 1 mA for 20 min in young healthy adults

“…Given the enormous popularity of this sham procedure (Bikson et al., ), we set out to investigate its blinding efficacy using data from our recent high‐powered, multi‐centre, pre‐registered study (Boayue et al., ). In this study, we collected data from 192 volunteers, who either received real tDCS (20 min) or FSF tDCS (40 s) at 1 mA over the left dorsolateral prefrontal cortex (DLPFC).…”

Integrating electric field modelling and neuroimaging to explain inter-individual variability of tACS effects

“…However, if and to which extent these differences explain variability of tES effects on behavioral or physiological outcome measures remains elusive. Individual differences in electric fields explain tES variability 4 In the current study, we investigated whether measures derived from individualized simulations of electric fields and source localization of the target brain activity can be used to explain variability of NIBS effects. Specifically, we tested whether the spatial correlation of the target brain activity (source of the α-oscillation) with the individually simulated electric field as well as the maximum field strength inside gray and white matter compartments can predict the variability of the power increase in the α-band after tACS.…”

Transcranial direct current stimulation (tDCS) for preventing major depressive disorder relapse: Results of a 6-month follow-up

“…Finally, the follow‐up was unblinded, which could have overestimated the results. In fact, a blinded protocol was not employed due to difficulties in maintaining nonpharmacological blinding for staff and patients over an extended period of time, particularly when a within‐study crossover (i.e., from sham to active tDCS) is performed (Bikson et al., ). Also, it would be important to keep the patients motivated and involved in their treatment regimens throughout the follow‐up period, which would be difficult to be achieved in a blinded fashion.…”

“…Nonetheless, negative findings were also reported in recent trials (Meron, Hedger, Garner, & Baldwin, ; Loo et al. 2018), possibly due to heterogeneity in clinical samples, inadequate sham methods, and low power (Bikson et al., ).…”