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. Author manuscript; available in PMC: 2022 Mar 16.
Published in final edited form as: Restor Neurol Neurosci. 2021;39(5):379–391. doi: 10.3233/RNN-211210

Effect of Conventional Transcranial Direct Current Stimulation Devices and Electrode Sizes on Motor Cortical Excitability of the Quadriceps Muscle

Adam Z GARDI a, Amanda K VOGEL a, Aastha K DHARIA a, Chandramouli KRISHNAN a,b,c,d,✉
PMCID: PMC8926458  NIHMSID: NIHMS1783830  PMID: 34657855

Abstract

Background:

There is a growing concern among the scientific community that the effects of transcranial direct current stimulation (tDCS) are highly variable across studies. The use of different tDCS devices and electrode sizes may contribute to this variability; however, this issue has not been verified experimentally.

Objective:

To evaluate the effects of tDCS device and electrode size on quadriceps motor cortical excitability.

Methods:

The effect of tDCS device and electrode size on quadriceps motor cortical excitability was quantified across a range of TMS intensities using a novel evoked torque approach that has been previously shown to be highly reliable. In experiment 1, anodal tDCS-induced excitability changes were measured in twenty individuals using two devices (Empi and Soterix) on two separate days. In experiment 2, anodal tDCS-induced excitability changes were measured in thirty individuals divided into three groups based on the electrode size. A novel Bayesian approach was used in addition to the classical hypothesis testing during data analyses.

Results:

There were no significant main or interaction effects, indicating that cortical excitability did not differ between different tDCS devices or electrode sizes. The lack of pre-post time effect in both experiments indicated that cortical excitability was minimally affected by anodal tDCS. Bayesian analyses indicated that the null model was more favored than the main or the interaction effects model.

Conclusions:

Motor cortical excitability was not altered by anodal tDCS and did not differ by devices or electrode sizes used in the study. Future studies should examine if behavioral outcomes are different based on tDCS device or electrode size.

Keywords: corticospinal excitability, MEP, knee, evoked torque, bayes factor, rehabilitation

INTRODUCTION

The central nervous system (CNS) is an intricate mapping network of electrical connections, composed of neurons and synapses in the brain that deliver vital information to the rest of the body via the spinal cord. Appropriate levels of neural excitation and inhibition in the CNS are crucial for growth and development of behavioral responses, including involuntary reflex responses, voluntary motor control, deep thought, learning, memory, and emotion (Deco et al., 2014; Wood et al., 1999). Brain plasticity (i.e., neuroplasticity), which is defined as the ability of the brain to adapt to experiences through the formation of new neural pathways, is primarily mediated by electrical and chemical excitation and inhibition (de Oliveira, 2020). An abnormal excitatory and inhibitory balance of neural pathways can lead to neurological disorders such as Alzheimer’s and Parkinson’s disease, epilepsy, and multiple sclerosis (Bonansco & Fuenzalida, 2016; Busche & Konnerth, 2016; Lindenbach & Bishop, 2013; Zhong et al., 2016). Therefore, a CNS capable of efficiently transmitting information and balancing neuronal excitation and inhibition is vital to everyday human life.

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that is commonly used to induce neuroplasticity by altering motor cortical excitability (Fritsch et al., 2010; Liebetanz et al., 2002; Podda et al., 2016). Current commercial tDCS devices have been known to artificially alter the intracellular ionic concentrations in the cortical tissue such that it mimics the naturally occurring excitation process (M. A. Nitsche et al., 2003). Previous research has illustrated that anodal tDCS tends to enhance the neuronal excitability of the area being stimulated, while cathodal tDCS inhibits the neuronal excitability of the stimulated area (Galea et al., 2009; M. A. Nitsche & Paulus, 2000). Typically, the effects of tDCS intervention on motor cortical excitability can be objectively measured by quantifying motor evoked potentials (MEPs) or twitch responses induced by transcranial magnetic stimulation (TMS). Thus, altered motor evoked responses offer an indirect means of investigating changes in motor cortical excitability.

While many initial studies have demonstrated that anodal tDCS intervention increases motor cortical excitability (A. Bastani & Jaberzadeh, 2012; Horvath et al., 2015; M. A. Nitsche & Paulus, 2000), recent studies have shown variability in the motor cortical excitability elicited after anodal tDCS intervention with some showing no effect (Jonker et al., 2021; Kristiansen et al., 2021; López-Alonso et al., 2014; Wiethoff et al., 2014). The variability in the effects of tDCS are not limited to motor cortical excitability but has also been reported in behavioral outcomes. For example, some studies have shown that anodal tDCS when combined with behavioral interventions can improve motor function and pain (Gunduz et al., 2021; Llorens et al., 2021; Subramanian & Prasanna, 2018), whereas other studies have shown that the addition of anodal tDCS to behavioral training paradigms elicited no further improvements (Edwards et al., 2019; Horvath et al., 2016; Madhavan et al., 2020).

Prior research suggests that the effects of tDCS are influenced by the size of the electrodes used in the study (Andisheh Bastani & Jaberzadeh, 2013; Foerster et al., 2018; Ho et al., 2016; M. A. Nitsche et al., 2007). However, there appears to be no consensus how these variables affect motor cortical excitability, as the results are not consistent among studies. For example, some studies have shown that small active electrodes induce the biggest increase in motor cortical excitability compared with bigger electrode sizes (A. Bastani & Jaberzadeh, 2013; M. A. Nitsche et al., 2007), whereas other studies have shown that larger electrodes induce the greatest increase in motor cortical excitability compared with smaller electrodes (Ho et al., 2016). As a result, the effects of tDCS are still under debate and more research is needed to determine how these variables affect tDCS outcomes, and whether or not their effects are practically meaningful. Another issue that could contribute to the observed variability in the effects of tDCS on motor cortical excitability is the use of different tDCS devices. A quick review of literature suggests that there are at least six tDCS devices currently available on the market (Wexler, 2016), but to our knowledge, differential effects across devices have not been studied to date. Therefore, the purpose of our investigation was to determine whether two commonly used anodal tDCS devices and different tDCS electrode size configurations have any differential effects on the changes in motor cortical excitability. We hypothesized that the type of tDCS device and the size of electrodes used would significantly affect the extent of tDCS-induced changes in motor cortical excitability.

METHODS

Experimental Design

We conducted two experiments to study the effect of tDCS devices and electrode sizes on motor cortical excitability. In Experiment 1, we tested the effect of two tDCS devices (1×1 tDCS System [Soterix Medical, NY] and Dupel Iontophoresis System [Empi, DJO, LLC, TX]) on motor cortical excitability of the quadriceps muscle, using a crossover design, in 20 healthy participants. In Experiment 2, we tested the effect of three tDCS electrode sizes (large active-large reference, small active-small reference, and small active-large reference) on motor cortical excitability of the quadriceps muscle in 30 healthy subjects that were equally divided into three groups.

Participants

A convenience sample of twenty participants (18 right foot dominant and 2 left foot dominant, age: 21.5 ± 4.7 years, height: 172.0 ± 10.0 cm, and body mass: 71.2 ± 12.2 kg) were included in Experiment 1 and thirty participants (27 right foot dominant and 3 left foot dominant, age: 21.5 ± 4.4 years, height: 171.7 ± 10.3 cm, and body mass: 70.5 ± 12.6 kg) were included in Experiment 2. All participants were free of neurological or orthopedic disorders and musculoskeletal injuries. Participants were excluded if they: (1) were pregnant, (2) were taking medications that are likely to alter motor cortical excitability, (3) had metal implants in the skull, (4) had a cardiac pacemaker, (5) had a history of unexplained headaches, seizures, head injury, significant adverse reactions to TMS or tDCS, or a major medical or heart condition that would likely affect the outcomes of the study. Participants reviewed a thorough description of the study prior to providing verbal and written informed consent approved by the University of Michigan Institutional Review Board. Participants and experimenters also completed a safety questionnaire, proposed by Brunoni et al. and Krishnan et al, after each experimental session to note any side effects of tDCS and TMS (Brunoni et al., 2011; Krishnan et al., 2015).

Experimental Approach

After obtaining written consent, participants were comfortably seated on an isokinetic dynamometer (Biodex Medical Systems, Inc., Shirley, NY, USA). The knee of their dominant leg was aligned to the dynamometer’s axis of rotation and was positioned at 60° of flexion. The dominant leg was determined by having participants respond to a self-reported questionnaire indicating their preferred leg to kick a ball (Dharia et al., 2021; Krishnan, 2019b; Krishnan, Dharia, et al., 2019; Washabaugh et al., 2016). The knee angle, along with participant-specific dynamometer chair settings, was held constant between sessions to ensure that the lower limb position was replicated reliably across sessions. After a brief warm-up with submaximal contractions (2 trials at 50% and 2 trials at 75% of perceived maximum contraction), participants performed two trials of maximum voluntary isometric contraction (MVIC) of the knee extensor muscles. The participants received strong verbal encouragement from the experimenters along with visual feedback of their torque outputs to ensure that they provided their best effort during maximal contractions. The participants were tested on two separate days, set at least 48 hours apart.

Transcranial Magnetic Stimulation Protocol

TMS pulses (single monophasic) were delivered at random intervals over the quadriceps hotspot using a standard double cone coil (110 mm – diameter) that was attached to a Magstim 2002 stimulator (Magstim Inc., Morrisville, NC, USA). The TMS coil was oriented to induce a posterior-anterior current flow in the primary motor cortex. To find the hotspot, a linen cap was first tightly secured over the participant’s head. The vertex was then identified by finding the midpoint intersection of the lines connecting the right and left tragus and the nasion and inion. After accounting for the offset of the TMS coil dimensions, an initial mark that was 2 cm posterior and 2 cm lateral to the vertex was made on the linen cap to identify an approximate location of the quadriceps hotspot (Dharia et al., 2021; Groppa et al., 2012). From this marked location, the coil was systematically moved to determine the location (i.e., hotspot) that produced the largest and most consistent knee extensor twitch torque at the lowest TMS intensity while the participant performed a small background contraction of their quadriceps muscle at 5% of their MVIC (Dharia et al., 2021; Krishnan, 2019a; Krishnan, Washabaugh, et al., 2019). The participant received visual feedback of their torque curves while performing the background contraction at 5% MVIC so that they exerted consistent torque throughout the experiment. The location of the quadriceps hotspot was registered digitally using a custom-developed frameless stereotaxic camera system (NeuRRoNav) (Rodseth et al., 2017). The coil was then maintained at this location using an adjustable TMS coil holder. The feedback from the NeuRRoNav system was used to maintain the position and orientation of the coil over the hotspot during all experimental sessions.

The Active Motor Threshold (AMT) was then established by determining the minimum stimulus intensity at which a motor evoked twitch response was produced in at least 50% of trials while the participant maintained knee extensor torque at 5% of their MVIC. An adaptive threshold-hunting method based on maximum-likelihood parameter estimation by sequential testing (TMS Motor Threshold Assessment Tool, MTAT 2.0, http://www.clinicalresearcher.org/software.htm) was used to determine the AMT (Borckardt et al., 2006). TMS recruitment curves were then recorded before and after tDCS at eight different intensities (70%–140% AMT) with 5 trials at each intensity (Dharia et al., 2021; Madhavan et al., 2020).

Transcranial direct current stimulation

Anodal tDCS was applied at a current intensity of 2 mA for 15 minutes. For experiment 1, two tDCS devices (Soterix and Empi) were used on separate occasions to deliver anodal tDCS to the quadriceps motor cortical region. For experiment 2, only the Soterix device was used to deliver anodal tDCS. The active (anode) and the reference (cathode) carbon electrodes of the Soterix device were covered with saline-soaked sponges (0.9% NaCl) during stimulation. An EASYstrap™ positioning system secured the active and the reference electrodes of the Soterix device during stimulation. The saline (0.9% NaCl) soaked active electrode and a self-adhesive reference electrode of the Empi device was secured using Coban wraps. All experiments utilized the same electrode positioning (Fig. 1) with current densities that were well within reported safety limits for tDCS (Michael A. Nitsche & Paulus, 2001). The most common adverse effects were mild tingling, itching and burning sensations, and redness on the stimulation site. A few participants reported headache, sleepiness, trouble concentrating, scalp pain, and neck pain.

Fig. 1 -.

Fig. 1 -

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A schematic of the (A) experimental set-up for collecting motor evoked torque responses elicited by transcranial magnetic stimulation (TMS) and (B) electrode placements for anodal transcranial direct current stimulation (tDCS) in a right-leg dominant individual. Note that the anode (active electrode) was placed over the primary motor cortical area of the quadriceps muscle and the cathode (reference electrode) was placed over the contralateral supraorbital region.

Experiment 1 - protocol

This was a within-subjects crossover design (Fig. 2). The order of tDCS devices (Soterix and Empi) was randomly assigned such that half the participants received stimulation using the Soterix device on Day 1 and the other half received stimulation using the Empi device on Day 1. On day 2, the same tDCS intervention was repeated with the other device. Ten of the twenty participants received anodal tDCS using large active-large reference electrode configuration and the remaining participants received small active-small reference electrode configuration (see Experiment 2 for more details). Testing began by having participants perform MVICs of their quadriceps muscle. Following this, the AMT was determined and a pre-tDCS intervention TMS input-output recruitment curve was recorded. This was followed by 15 minutes of anodal tDCS with the assigned tDCS device. Thereafter, a post-intervention recruitment curve was performed to complete the experiment for that session. The participant was then rescheduled for their second visit during which all procedures were repeated identically with the other device.

Fig. 2 -.

Fig. 2 -

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Schematics of the experimental protocols for Experiment 1 and Experiment 2. In Experiment 1, the effect of two different transcranial direct current stimulation (tDCS) devices (Soterix and Empi) on motor cortical excitability of the quadriceps muscle was evaluated before and after anodal tDCS. In Experiment 2, the effect of three different tDCS electrode sizes (large active-large reference, small active-small reference, small active-large reference) on motor cortical excitability of the quadriceps muscle was evaluated before and after anodal tDCS.

Experiment 2 - Protocol

This was a between-subjects, pre-post experimental design (Fig. 2). In addition to the 20 participants from Experiment 1, data from 10 participants were collected. Participants were assigned to one of the three different tDCS electrode size montage groups (large active-large reference, small active-small reference, and small active-large reference). The dimensions of the large and small electrodes were 35.0 cm2 (5 cm × 7 cm) and 15.0 cm2 (3 cm × 5 cm), respectively. Testing began by having participants perform MVICs of the quadriceps muscle. Following this, the AMT was determined and a pre-tDCS intervention TMS input-output recruitment curve was recorded. This was followed by 15 minutes of anodal tDCS with the Soterix tDCS device. Thereafter, a post-intervention recruitment curve was performed to complete the experiment.

Data Analysis

Data collection and signal processing were performed using a custom program written in LabVIEW (Version 11.0, National Instruments Corp., Austin, TX, USA). The analog outputs from the torque signals along with the TMS synchronization pulses were low pass filtered at 500 Hz using an 8th order analog Butterworth filter (SCXI 1143, National Instruments Corp.) and sampled at 1000 Hz using a Windows desktop computer with an 18-bit high-accuracy M-series data acquisition module (USB 6281, National Instruments). The size of the motor evoked torque response was determined by computing the average peak twitch torque elicited by the TMS at each testing intensity after removing the torque offset associated with the background contraction. Motor evoked torque data were then normalized to the MVIC values obtained from maximal contractions—a method that has been previously shown to be highly reliable (Dharia et al., 2021). The total area under the recruitment curve was computed using the trapezoidal integration method to provide a summary measure of motor cortical excitability across all stimulation intensities (Brown et al., 2020; Carson et al., 2013; Mason et al., 2017; Talelli et al., 2008).

Statistical Analysis

All statistical analyses were performed using the JASP version 0.9.2.0. Descriptive statistics was computed for each variable and raincloud plots were generated for robust data visualization (Allen et al., 2019). Shapiro-Wilk test was used to test normality and Levene’s test for equality of variances was used to test homogeneity of variances across groups. We adopted an inclusive statistical approach where both classical and Bayesian analyses were included (Krishnan, 2019a; Ruiz-Ruano Garcia & López Puga, 2018; E.-J. Wagenmakers et al., 2016; E. J. Wagenmakers et al., 2018). A 2 × 2 repeated measures ANOVA, with device (Soterix and Empi) and time (pre and post tDCS intervention) as within-subjects factors, was used to evaluate whether TMS-induced motor evoked responses differed between the two different tDCS devices. A 3 × 2 repeated measures ANOVA with electrode size (large active-large reference, small active-small reference, and small active-large reference) as a between-subjects factor and time (pre and post tDCS intervention) as a within-subjects factor was used to evaluate whether TMS-induced motor evoked responses differed between the three electrode size montages. We also performed Bayesian analyses (Bayesian Repeated Measures ANOVA) using the default prior in JASP to obtain Bayesian inference. The Volk-Selke Maximum p-Ratio (VS-MPR) was also computed to estimate the maximum possible odds in favor of the alternative hypothesis (H1) over the null hypothesis (H0), based on a two-sided p-value. This was computed using the following equation:

MPR=1(−e×p×ln(p))forp≤0.37

(Sellke et al., 2001)(Vovk, 1993). A significance level of α=0.05 was used for all analyses.

RESULTS

Experiment 1

Raincloud plots showing the distributions of quadriceps motor evoked torque before and after anodal tDCS using different tDCS devices (Soterix and Empi) and electrode sizes (large active-large reference [L-L], small active-small reference [S-S], and small active-large reference [S-L]) are shown in Fig. 3 and Fig. 4, respectively. Shapiro-Wilk test and Levene’s test indicated no violations of normality or homogeneity of variances (all p > 0.05). When evaluating the changes in motor cortical excitability induced with two different anodal tDCS devices (Soterix and Empi), we found no significant main effect of tDCS device on motor cortical excitability (F(1, 19) = 0.402, p = 0.533, VS-MPR = 1.000 (Fig. 3 and Fig. 5A)). There was also no significant main effect of time (pre- to post-tDCS intervention) (F(1, 19) = 3.311, p = 0.085, VS-MPR = 1.761) or time × device interaction effect on motor cortical excitability (F(1, 19) = 0.592, p = 0.451, VS-MPR = 1.000). Bayesian statistical analysis favored the null effect model and indicated that the null hypothesis (no differences between tDCS devices) was much more likely than the alternative hypothesis (see supplementary data).

Fig. 3 -.

Fig. 3 -

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Raincloud plots showing distributions (Allen et al., 2019) of quadriceps motor evoked torque before and after 15 minutes of anodal transcranial direct current stimulation of the quadriceps motor area using Soterix and Empi devices. The circles on the plot indicate individual data points for all TMS intensities between 100% to 140% of active motor threshold (AMT). Rainclouds and notched box plots show the distribution of the data and the horizontal line on the box plot indicates the mean of the distribution. Note that the changes in motor cortical excitability were minimal after anodal tDCS and this effect was similar between both devices.

Fig. 4 -.

Fig. 4 -

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Raincloud plots showing distributions (Allen et al., 2019) of quadriceps motor evoked torque before and after 15 minutes of anodal transcranial direct current stimulation of the quadriceps motor area using three different electrode sizes (large active-large reference [L-L], small active-small reference[S-S], and small active-large reference [S-L]). The circles on the plot indicate individual data points for all TMS intensities between 100% to 140% of active motor threshold (AMT). Rainclouds and notched box plots show the distribution of the data and the horizontal line on the box plot indicates the mean of the distribution. Note that the changes in motor cortical excitability were minimal after anodal tDCS and this effect was similar between all three combinations of electrode size.

Fig. 5 -.

Fig. 5 -

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Scatterplots showing the mean transcranial magnetic stimulation (TMS)-induced motor evoked torque responses of the quadriceps muscle elicited across 8 TMS intensities (70% to 140% of active motor threshold [AMT]) before (pre) and after 15 minutes (post) of anodal tDCS using (A) two different devices (Soterix and Empi) and (B) three different electrode sizes (L-L: large active-large reference; S-S: small active-small reference; S-L: small active-large reference).

Experiment 2

When evaluating the changes in motor cortical excitability with three different electrode size montages (large active-large reference, small active-small reference, small active-large reference), we found no significant main effect of electrode size on motor cortical excitability (F(2, 27) = 0.755, p = 0.480, VS-MPR = 1.000) (Fig. 4 and Fig. 5B). There was also no significant main effect of time (pre- to post-tDCS intervention) (F(1, 27) = 3.185, p = 0.086, VS-MPR = 1.749) or time × electrode size interaction effect on motor cortical excitability (F(2, 27) = 1.155, p = 0.330, VS-MPR = 1.005). Bayesian statistical analysis favored the null effect model and indicated that the null hypothesis (no differences between tDCS electrode sizes) was much more likely than the alternative hypothesis (see supplementary data).

DISCUSSION

The present investigation evaluated the effect of tDCS device and electrode size on motor cortical excitability of the quadriceps muscle. Unlike most prior studies, we evaluated the changes in motor cortical excitability comprehensively by assessing TMS-induced motor evoked torque responses over a range of TMS intensities before and after anodal tDCS intervention. When evaluating TMS-induced motor evoked responses of the quadriceps muscle between the two tDCS devices (Soterix and Empi), the area underneath the recruitment curve (70% to 140% of AMT) was similar between the two devices, indicating that there was no difference in motor cortical excitability between the two tDCS devices. This same result was also seen when evaluating the different electrode sizes (large active-large reference, small active-small reference, and small active-large reference), indicating that the effect of tDCS on motor cortical excitability is not altered by the size of the electrodes used during the stimulation period. More importantly, we did not find a significant time, time × device, or time × electrode size effect, indicating that there were no significant changes in motor cortical excitability pre- to post-tDCS intervention. To our knowledge, these results show for the first time that the variability in responses to the anodal tDCS intervention in the lower-extremity muscles is not likely caused by the differences in tDCS device or electrode size used in prior studies. These results also support the growing body of literature that points to the lack of anodal tDCS effects on motor cortical excitability (Jonker et al., 2021; Kristiansen et al., 2021).

Past studies have used a wide range of tDCS devices; however, there are virtually no studies that have evaluated whether or not the effects are consistent across different tDCS devices. This information is particularly important, considering the current literature demonstrates a high degree of variability in the responses to anodal tDCS (López-Alonso et al., 2014; Wiethoff et al., 2014). We hypothesized that the differences in tDCS devices could help explain some of the variability in motor cortical excitability changes due to tDCS; however, the results of our study did not support our hypothesis. While there are several tDCS devices, we chose to compare Soterix and Empi because these devices have been widely used in the literature, and the costs of these devices vary significantly (Empi is a low-cost device whereas Soterix is a relatively expensive device). The finding that there were no differential effects in motor cortical excitability between the two tDCS devices suggests that the type of device utilized for the study may have little to no effect on experimental applications and/or therapeutic uses. Thus, if monetary value is a limiting factor, a less expensive device, such as the Empi (rebranded as Chattanooga), may prove to be sufficient for standard tDCS intervention. As an added advantage, this device can provide up to 4mA of current. However, for more nuanced applications (e.g., controlled laboratory research studies) that may benefit from additional features like SMARTscan™ (provides early warning of poor contact conditions), true current (visually represents the actual current administered at the moment), tickle (supplies a very weak current prior to tDCS to help condition the skin), and auto sham (which automatically calculates and produces a sham waveform based on the indicated “real” waveform), it may remain necessary to utilize Soterix for the additional features included. Further, the Soterix 1×1 device is compatible with High Definition-tDCS (HD-tDCS), which enables users to focalize and target cortical and deep brain structures (Minhas et al., 2010; Sasia & Cacciamani, 2021; Turski et al., 2017). However, further studies are required to evaluate if other devices with equivalent features could be more beneficial than Soterix.

The current evidence regarding the effect of electrode size on tDCS efficacy is conflicting. Because the size of the electrode has the potential to change the current density (which is a function of current and area) and focality of stimulation, it was necessary to consider the impact of different electrode sizes on the efficacy and consistency of treatment. While some studies have reported that small electrodes produce greater increases in motor cortical excitability compared with large electrodes (Andisheh Bastani & Jaberzadeh, 2013; M. A. Nitsche et al., 2007), other studies have reported the opposite effect (Ho et al., 2016). However, with common application variables controlled for (including tDCS montage, stimulation dosage, stimulation site, and stimulation duration), we were unable to find a significant difference in motor cortical excitability changes across multiple electrode size montages. Our results are also consistent with the recent finding that higher current density may not correlate with greater changes in excitability (Andisheh Bastani & Jaberzadeh, 2013) since our data suggest that changes in current density had no significant effects on excitability. Moreover, improving the focality of stimulation using a smaller active electrode did not facilitate the outcomes of anodal tDCS. This is not surprising, considering that prior studies that have compared the effects of HD-tDCS (a type of stimulation that is regarded to improve focality of stimulation) with conventional tDCS on motor cortical excitability have not shown any added benefits of HD-tDCS when compared with conventional tDCS (Kuo et al., 2013; Pellegrini et al., 2020). Interestingly, the use of a smaller active and a smaller reference electrode produced the biggest effect among the three combinations, albeit these differences were minimal and not statistically significant. It is currently unclear whether the shape of the electrodes relative to the motor cortex, as opposed to the size of the electrodes, may have a differential effect on lower-extremity motor cortical excitability. A recent study demonstrated that electrodes tailored to participant’s cortical geometry produced greater changes in excitability than traditional electrodes that were untailored (Cancelli et al., 2015). Hence, it may be worth investigating whether the geometry of the electrodes is more important than the size of the electrodes.

The results of this study not only demonstrated that there were no significant differences in motor cortical excitability changes between the two devices and the three electrode size configurations, but also no significant excitability changes from pre- to post-tDCS intervention for any of the electrode sizes or tDCS devices. Although this finding could be attributed to a lack of statistical power issue, it is to be noted that the effect sizes were generally small and Bayesian analysis indicated that the null model (and hypothesis) was more favorable, suggesting that cortical excitability was minimally affected by anodal tDCS. This is an interesting and important finding because there has been a growing body of evidence that suggests that tDCS has minimal effect on motor cortical excitability (Horvath et al., 2016; Jonker et al., 2021; Kristiansen et al., 2021). Prior studies have attributed this finding to the “shunting phenomenon,” where a majority of the applied current intended for the target brain region is redirected by the skin covering the skull (Vöröslakos et al., 2018). Another potential reason for the observed lack of excitability changes pre- to post-tDCS intervention may be due to the location of the lower-extremity primary motor cortex (M1) homunculus. Compared to the representations of the upper extremity muscles, the M1 representation for the lower-extremity (LE) muscles including vastus medialis and rectus femoris are located at a greater depth in the interhemispheric fissure (Kesar et al., 2018; Smith et al., 2017; Y. Terao et al., 1994; Yasuo Terao et al., 2000). As a result, it is possible that the stimulation may not have penetrated deep enough to induce changes in the excitability of the quadriceps muscle; however, recent results from hand muscles suggest that this is more of a global phenomenon and not something specific to the lower-extremity muscles (Horvath et al., 2016; Jonker et al., 2021). It is to be noted that the lack of excitability change seen pre- to post-tDCS intervention does not demonstrate that the therapeutic effects of tDCS are also minimal. Previous studies have demonstrated that changes in excitability are not necessarily critical for positive behavioral effects to occur (Carson et al., 2016). While the intent of the study was not to measure behavioral responses, a lack of excitability change demonstrated from pre- to post-tDCS intervention does not rule out the potential therapeutic effects that these devices and their accompanying electrode sizes can administer. Thus, if future studies aim to evaluate the behavioral or therapeutic effects of tDCS, it may be beneficial to utilize additional outcome metrics in conjunction with excitability measures.

There are some potential limitations to this study. Only two different tDCS devices were evaluated in this experiment; however, there are many different devices currently on the market. While we intentionally chose these devices for their popularity and differences in cost, several other devices could be tested to further solidify conclusions regarding inter-device consistency. With all data collected through anodal stimulation, it is also unclear whether the same results regarding electrode size and device type are applicable when using cathodal stimulation. Although previous studies have demonstrated cathodal stimulation will most often produce an opposing excitability effect when compared with its anodal counterpart (M. A. Nitsche & Paulus, 2000), it is worth validating the same principle when studying the effect of tDCS device and electrode size. Additionally, we only used two of the several available electrode sizes in this study. As a result, it is unclear whether using different electrode sizes (e.g., 5 cm × 5 cm) would have yielded different results. However, considering that there were only minimal differences between the S-S (3 cm × 5 cm active and reference electrodes) and L-L (5 cm × 7 cm active and reference electrodes) electrode sizes, it is unlikely that the results would differ for any electrodes sizes that fall between the two sizes used in this study. Similarly, we did not test the effect of intensity or duration of stimulation on motor cortical excitability. It is possible that higher intensity (e.g., 4 mA) or longer duration of tDCS (e.g., 20 mins) could result in greater excitability changes. However, there is currently no evidence to strongly support that greater intensity or duration of stimulation boosts the efficacy of tDCS (Agboada et al., 2019; Esmaeilpour et al., 2018; Ho et al., 2016; Tremblay et al., 2016). Finally, because the current study evaluated excitability changes in healthy participants, the excitability response seen pre- to post-tDCS intervention may differ in participants impacted by neurological disorders (e.g., cerebral palsy, stroke, etc.). Further studies should evaluate how the current study’s results may differ in patient populations.

CONCLUSION

In conclusion, the findings from this study indicate that the tDCS-mediated changes in motor cortical excitability did not differ between devices (Soterix and Empi) or electrode sizes (large active-large reference, small active-small reference, small active-large reference). The similarity of results between Soterix and Empi suggest that the type of device utilized for the study may have little to no effect on experimental applications and/or therapeutic uses. If cost is a limiting factor, a less expensive device such as the Empi may be sufficient for eliciting the same motor cortical excitability changes as seen with the Soterix device. However, the observed lack of motor cortical excitability changes before and after the tDCS intervention questions the basic scientific premise upon which tDCS-supplemented motor behavioral interventions are based. Hence, future studies should aim to evaluate whether or not behavioral outcomes are different based on tDCS device or electrode size and study these outcomes in patient populations (e.g., stroke) using a broader range of tDCS devices and electrode configurations.

Supplementary Material

1

Acknowledgments

This study was funded in part by the undergraduate research opportunity program at the University of Michigan and the National Institutes of Health (Pilot Grant [Grant # P2CHD086844] from the National Center of Neuromodulation for Rehabilitation [NM4R]). The authors would like to thank the members of the Neuromuscular and Rehabilitation Robotics Laboratory (NeuRRo Lab) for their assistance with data collection, processing, and critically reviewing an earlier version of the manuscript.

Footnotes

Conflicts of interest

The authors declare no conflicts of interest.

References

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