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

Abstract

Background: Neuropsychiatric 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.

Objective: This 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.

Methods: The 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.

Results: Advances 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.

Conclusions: These 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.

Keywords: Neuromodulation; Reproducibility; Transcranial alternating current stimulation (tACS); Transcranial direct current stimulation (tDCS); Transcranial electrical stimulation (tES).

Fig. 1. Common tDCS/tACS montages and corresponding simulated electric field distribution

A. M1-SO configuration: Sponge electrodes, one over left primary motor cortex, one over the contralateral supraorbital ridge. B. Bilateral dorsolateral prefrontal cortex configuration: Sponge electrodes over the F3 and F4 EEG sites. C. 4 × 1 HD-tDCS M1 configuration: High-definition electrodes, one over M1, four return electrodes surrounding the center electrode. The electric field was simulated with a current amplitude of 1 mA. Electric field simulation was performed using SimNIBS 2.0.1 [191].