Intra-Subject Consistency and Reliability of Response Following 2 mA Transcranial Direct Current Stimulation

Highlights

• The intra-subject consistency and reliability of 2 mA anodal and cathodal tDCS were investigated.

• The effects of anodal and cathodal tDCS were found to show poor reliability at an individual level as the effects were not consistent across sessions.

• Sham stimulation is moderately reliable across sessions.

Abstract

Background

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed.

Objective/hypothesis

We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions.

Methods

Transcranial magnetic stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20 minutes of 2 mA stimulation or sham stimulation.

Results

Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra-subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC = 0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC = 0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC = .424).

Conclusions

Our findings indicate that although 2 mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2 mA cathodal tDCS does not significantly alter cortical excitability immediately following stimulation and that there is poor reliability of the effect within the same individual across different testing sessions.

Introduction

Transcranial direct current stimulation (tDCS) is an increasingly popular non-invasive brain stimulation technique, which is known to alter cortical excitability for periods that outlast the duration of stimulation. These effects have been reported to be polarity specific; specifically cortical areas beneath the anode are reported to increase in excitability whereas the reverse is true for locations below the cathode [1], [2]. Although this polarity specific pattern has beenfound in many studies, this is not always the case, and variability in the magnitude and direction of the effects are occasionally reported. Some variability between studies is likely caused by parameter selection; for example, 20 minutes of 2 mA cathodal stimulation has been found to increase cortical excitability rather than decrease it [3], and increasing the duration of 1 mA anodal stimulation to 26 minutes has led to findings of inhibition [4]. The measures used to quantify effects are also likely to influence findings [5], [6], as are factors such as the electrode montage used [1], [7]. These aspects are important sources of variability when comparing across studies; however, variability also occurs within studies in which the parameters are held constant. For example, Wiethoff et al. [8] found substantial inter subject variability in response to both 2 mA anodal and cathodal stimulation.

Variability in response to non-invasive brain stimulation is not unique to tDCS, and has also been reported in other techniques such as paired associative stimulation (PAS) and intermittent theta burst stimulation (iTBS) [9], [10], [11], [12]. Given individual differences in anatomy including skull shape, thickness and density; and additional factors such as baseline neuronal states, it is perhaps not surprising that these techniques do not yield identical results across individuals. However, developing an understanding of the factors that may predict this variability is a critical step in increasing the reliability and usefulness of such techniques for use within both research and therapeutic contexts.

To date, a number of inter-subject factors have been identified as influencing tDCS including anatomical structure [13], [14], age [15], [16], and potentially even genetic profile (for review see Li et al. [17]). Until recently, very little research has been conducted that systematically investigates the reliability of tDCS effects within individuals. A few notable studies have explored these issues for anodal stimulation at 1 mA [18], [19] and at 0.5 mA [20]. Interestingly, although 1 mA anodal tDCS was found to have a reasonable level of inter-subject reliability [19], the same was not true of 0.5 mA [20]. Furthermore, even when reliability has been explored using the same intensity the results are conflicting. Horvath et al. [18] found that reliability across sessions was poor, which contrasts with the findings of Lopez-Alonso et al. [19]. It is highly possible that the differences between the studies reflect the different methodologies used. A few notable and potentially influential differences include electrode size, duration between testing sessions, duration of stimulation, use of neural-navigation and the amount of session's tested. Less research exists exploring the reliability of cathodal stimulation although poor reliability across sessions has been reported when 1 mA intensity is used Horvath et al. [18].

To our knowledge, no studies have yet been conducted using 2 mA intensity. As these higher intensities are often used by researchers based upon the assumption that these higher intensities will be more effective [3], it is particularly important that these factors are explored.

The present study aimed to explore inter and intra subject variability using a repeated measures design in which participants experienced multiple sessions of 2 mA tDCS applied to the motor cortex for 20 minutes. Electrodes measuring 35 cm² each were attached in a standard electrode montage with the reference placed on the contralateral orbit and testing sessions were separated by a minimum of 3 days to allow for ‘wash out’. Changes in cortical excitability were assessed with reference to changes in transcranial magnetic stimulation (TMS) recruitment (Input Output, IO) curves and resting motor thresholds (RMT). TMS IO curves are thought to reflect the strength of corticospinal projections [21], and have previously been reported to increase following anodal and decrease following cathodal stimulation [2]; however, this is not always found to be significant [3]. Unlike IO curves RMT is thought to reflect the excitability of the main corticospinal projections to the target muscle with the lowest excitation threshold [22], and have not been found to alter following tDCS [2], [3]. By testing participants multiple times, we aimed to explore the reliability of 2 mA anodal and cathodal stimulation at both the group and individual levels.