Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up

Highlights

• We tested safety, tolerability and blinding efficacy of a novel high-definition tDCS set-up.

• We also assessed behavioural effects and compatibility with functional MRI.

• Effects were compared to those of conventional-tDCS.

• Only HD-tDCS modulated performance and was better tolerated than conventional-tDCS.

• The novel set-up is safe for use during MRI.

Abstract

Background

High-definition transcranial direct current stimulation (HD-tDCS) may allow more specific neural modulation than conventional-tDCS.

Objective

We compared safety, tolerability, blinding efficacy and cognitive effects of a novel HD-tDCS set-up to that of conventional-tDCS and established compatibility with simultaneous functional magnetic resonance imaging (fMRI).

Methods

Two groups of healthy participants completed a visual flanker task either with conventional (N = 30) or HD-tDCS (N = 30) administered to the right dorsolateral prefrontal cortex (1 mA) in a double-blind, sham-tDCS-controlled, cross-over design. HD-tDCS was administered with a one-channel DC-stimulator using a small conductive rubber “centre” electrode and a circular return electrode, mimicking the frequently used 4 × 1 HD-tDCS set-up. Tolerability, adverse effects, impact on performance and blinding efficacy were compared within and between the two montages. In a separate experiment, potential heating and impact on image quality of the novel HD-tDCS set-up were assessed during simultaneous fMRI.

Results

Both montages elicited only mild adverse effects and those were less pronounced for the novel HD-tDCS set-up. Participant and investigator blinding was achieved with both montages. Only HD-tDCS resulted in significant modulation of the conflict adaptation effect during the flanker task; however, no differences were found for the direct comparison of the two montages. No significant heating occurred during fMRI and only minor effects on image quality were observed during HD-tDCS.

Conclusions

This study confirmed safety, tolerability and blinding efficacy of a novel, re-usable and MRI-compatible HD-tDCS set-up. It also highlights its potential to exert beneficial effects on behavioural performance. Use of this novel set-up during simultaneous fMRI in future studies will help clarify the neural mechanisms by which this HD-tDCS impacts on behavioural and neural function.

Introduction

Transcranial direct current stimulation (tDCS) can improve cognition, motor function and learning in health and disease [1], [2], [3], [4]. Conventional-tDCS set-ups typically employ two rubber electrodes (e.g., 5 × 5 or 5 × 7 cm²) and the ingoing current is projected from one electrode that is attached over a cortical target region to a return electrode that is attached over a different cortical area or an extracranial region [5]. This set-up may result in relatively non-focal stimulation due to the size of the electrodes, and regions between the two electrodes may also be affected as demonstrated by recent current modelling studies [6], [7].

More recently, “high-definition” tDCS (HD-tDCS) has been introduced to address these issues [6], [7], [8], [9], [10], [11], [12]. HD-tDCS typically employs more than two smaller electrodes and electrode positioning is frequently guided by advanced computational modelling approaches to optimize stimulation of the target region [8], [12]. To date, one of the most frequently used HD-tDCS montages is the so-called “4 × 1 ring set-up” which employs a centre electrode that is surrounded by four return electrodes. The latter are arranged in a circle around the centre electrode and thought to constrain the current flow to the region between the centre and ring electrodes [6]. This set-up may result in more focal stimulation and potentially more effective modulation of behaviour and neurophysiological parameters than conventional-tDCS. For example, HD-tDCS has been shown to enhance motor cortex excitability with comparable [13] or longer lasting effects [7] compared to conventional-tDCS. HD-tDCS also resulted in significantly improved verbal learning and working memory in healthy individuals [14], facilitated naming in patients with post-stroke language impairment [15], and has been shown to be safe and well tolerated while blinding of participants was maintained [7], [10], [15], [16], [17].

However, previous HD-tDCS studies employed silver chloride electrodes that are susceptible to electrochemical changes requiring costly replacement sets after only a few stimulation sessions [6], [18]. HD-tDCS also requires expensive multi-channel stimulators [7] or additional soft- and hardware [6] compared to conventional-tDCS. Moreover, while conductive rubber electrodes used during conventional-tDCS can be used during simultaneous functional magnetic resonance imaging (fMRI) to explore the impact of the stimulation on brain function (e.g., References [19], [20], [21], [22]), electrodes employed in previous HD-tDCS studies are incompatible with fMRI.

Thus, the present study employed a novel HD-tDCS set-up that utilizes conductive rubber electrodes (i.e., a small centre electrode and a ring-shaped circular electrode) mimicking the standard 4 × 1 ring set-up. Importantly, the electrodes used in the present study were developed to be re-usable over longer time periods and are fMRI compatible (NeuroConn, Illmenau). We assessed safety, tolerability, blinding effectiveness and the impact on mood and performance during a cognitive task using this novel set-up and also aimed to compare effects to those of fMRI compatible conventional-tDCS. In addition, MRI-compatibility of the new HD-tDCS set-up was established. Based on previous studies that compared the 4 × 1 set-up with conventional-tDCS [7], [23], we hypothesized that the novel HD-tDCS set-up would be safe and well tolerated, allows for effective blinding of participants and researchers, and improves cognitive performance compared to sham HD-tDCS, with comparable or superior effects compared to conventional-tDCS. Further, as in previous studies that employed conventional-tDCS during simultaneous fMRI [19], [20], [24], no heating underneath the electrodes and only minor imaging artefacts were expected.