Preliminary Evidence That Excitatory Transcranial Direct Current Stimulation Extends Time to Task Failure of a Sustained, Submaximal Muscular Contraction in Older Adults

Abstract

Background:

Decreased cortical excitability has been proposed as a potential mechanism underlying task failure during sustained muscular contractions, and cortical excitability may decrease with old age. We tested the hypothesis that transcranial direct current stimulation, which has been reported to raise cortical excitability, would prolong the time to task failure during a sustained muscular contraction in older adults.

Methods:

Thirteen older adults (68.3±2.0 years; eight women and five men) performed isometric, elbow flexions to failure while receiving sham or anodal transcranial direct current stimulation. Order of stimulation was randomized, and the subjects and investigators were blinded to condition. Time to task failure was measured alongside selected psychological indices of perceived exertion and affect.

Results:

Anodal transcranial direct current stimulation prolonged mean time to task failure by approximately 15% (16.9±2.2 vs 14.7±1.8 minutes) and slowed the rate of increase in rating of perceived exertion (0.29±0.03 vs 0.31±0.03) relative to the sham condition.

Conclusions:

These preliminary findings suggest that anodal transcranial direct current stimulation enhances time to task failure of a sustained, submaximal contraction in older adults by potentially increasing cortical excitability and/or influencing the perception of exertion. These results raise the question of whether interventions that acutely increase cortical excitability could enhance physical function and/or exercise-induced adaptations in older adults.

Poor muscle endurance is linked to frailty (1) and “fatigue” and “exhaustion” are common complaints among the elderly people (2). Thus, enhancing muscular endurance may enhance physical function and performance. During sustained contractions, central (neural) and peripheral (muscle) mechanisms contribute to task failure (3,4). Anodal transcranial direct current stimulation (tDCS)—a painless, noninvasive brain stimulation that transiently increases motor cortex excitability (5)—enhances time to task failure (TTF) of a sustained, submaximal contraction by approximately 30% in a subset of young, healthy adults (6). Interestingly, prolonged TTF was associated with blunted ratings of perceived exertion (RPE) when compared to sham condition. In this study, we sought to determine whether anodal tDCS delivered during a sustained, submaximal elbow flexion task could lengthen TTF in older adults. We also sought to elucidate whether anodal tDCS altered RPE or affect during exercise.

Methods

Study Protocol

Thirteen older adults (68.3±2.0 years; 165±3cm; 74.5±3kg; eight women and five men) without history of major neurological disorders, myocardial infarction in the past year, musculoskeletal injury to the upper extremity, or participation in resistance exercise training in the prior 3 months completed the study. Subjects underwent two testing sessions (visits ≥ 4 days apart) where they performed a sustained elbow flexion (20% of maximal strength) to failure (6). Subjects received anodal tDCS to the motor cortex until task failure (maximum tDCS duration: 20 minutes) on one visit and received sham stimulation (30 seconds) on the other. Order was randomized, and subjects and investigators were blinded to condition. The biceps brachii “hot spot” was located using transcranial magnetic stimulation (70-mm diameter figure-of-8 coil, BiStim², The Magstim Co. Ltd., Whitland, UK). Sponge-wrapped electrodes (35cm²) were soaked in saline (0.9%), the anode was placed over the “hotspot,” and the cathode was placed on the left forehead just above the left eyebrow/orbit. A constant current stimulator delivered anodal or sham tDCS (1.5 mA; 0.043 mA/cm² current density; NeuroConn Eldith I Channel DC Stimulator Plus, Rogue Resolutions, Cardiff, UK).

Subjects provided affect ratings to indicate how they felt at baseline and how they expected to feel while performing the endurance task using a −5 (very bad) to +5 (very good) scale. This affect rating is a commonly used measure of one’s relatively positive or negative affect during exercise and is not designed to be specific to pain or any other sensation (7). Subjects were asked for RPE on a modified Borg scale of 0–10 – 10 being most difficult (8)—immediately after endurance task initiation and every 2 minutes thereafter. Upon task failure, the affect rating scale was re-administered to provide retrospective ratings of how subjects felt immediately after and during the task. Lastly, subjects rated treatment acceptability using a modified Treatment Evaluation Inventory Short Form (9). Nine statements, each rated on a scale of 1–5, were summed to create a total score with higher scores reflecting better treatment acceptance (example statements: I find it acceptable to perform exercise while receiving this treatment; Overall, I have a positive reaction to this treatment).

Statistical Analysis

Data are reported as mean ± SEM with Cohen’s d effect sizes when appropriate in the text and figures. For data with repeated observations, we used linear mixed-effects modeling (nlme package ver. 3.1 (10) in the R statistical language ver. 3.2 (11)). Strength was a covariate as it could influence TTF (12,13). Due to the nonlinear pattern of RPE change over time, we fitted a nonlinear logistic growth model to the data formulated as:

$$\text{RPE}=(asym\cdot \frac{1}{1+e^{\text{initial+rate}\times \text{time}}})$$

where initial represented the initial level of RPE, and rate represented the negative value of the growth rate. The asym was defined as $10/(1+e^{-A})$ to fix the asymptote at the empirical maximum of 10. Because RPE was measured repeatedly, we used nonlinear mixed-effects modeling to fit the logistic growth model to the data. To evaluate the model fit, we used the Akaike Information Criterion. A two-tailed p value less than .05 was required for statistical significance.

Results

Covaried for strength, anodal tDCS increased TTF by 15% when compared to sham (16.9±2.2 vs 14.7±1.8 minutes; p < .05; d = .31; Figure 1A). There was also a negative association between the degree of enhancement with anodal tDCS and baseline measures of muscle strength (Figure 1B; r = −.55; p = .05).

Figure 1.

(A) Anodal tDCS prolonged TTF by ~15% relative to sham (*anodal tDCS > sham; p < .05). (B) There was an association between the magnitude of treatment effect (difference in TTF between the anodal tDCS and sham conditions) and baseline level of muscle strength (r = −.55; p = .05), suggesting weaker seniors experienced the greatest treatment effect compared to stronger seniors. tDCS = transcranial direct current stimulation; TTF = time to task failure.

RPE values across conditions were similar at the beginning of the task and at the asymptote for TTF (for initial or asym: p values > .2). The rate of increase (slope) of the RPE curve was less in the anodal tDCS condition when compared to the sham condition (0.29±0.03 vs 0.31±0.03; p = .01; d = .35; Figure 2). Although participants in the anodal tDCS condition had marginally less positive affect ratings than the sham tDCS condition at baseline (p = .07; d = .55) and in anticipation of the exercise (p = .08; d = .54), there were no affect differences on the affect or post-exercise ratings. Although there was a modest tDCS effect on affect change (baseline subtracted from post-exercise rating), this difference was not significant compared to sham (Table 1).

Figure 2.

Logistic growth model was used to quantify the effects of tDCS on ratings of perceived exertion (RPE) in all subjects. Baseline RPE values across conditions did not differ at the beginning of the task (P _o) and at the asymptote for time of task failure (K) (p > .2). However, the rate of increase in the RPE (r) was blunted during tDCS (p < .05). The RPE lines between the two conditions represent the average responses. tDCS = transcranial direct current stimulation.

Table 1.

Means ± SEM Ratings of Affect Before and After Exercise

		Condition
		tDCS	Sham	Difference	p	d
Baseline affect	−5 to +5	3.8±0.3	4.3±0.2	−0.5±0.2	.07	.55
Predicted exercise affect	−5 to +5	2.4±0.5	3.0±0.4	−0.6±0.3	.08	.54
Exercise affect	−5 to +5	2.8±0.4	2.3±0.5	0.5±0.3	.19	.38
Post-exercise affect	−5 to +5	4.0±0.3	3.7±0.3	0.3±0.3	.36	.27

Note: tDCS = transcranial direct current stimulation.

Average treatment acceptability scores were high and did not differ between the tDCS versus sham conditions (32.5±1.3 vs 33.7±1.1; p = .51; d = .28), likely indicating that subjects were unable to discriminate between conditions with a relatively favorable perception of tDCS.

Discussion

The purpose of this study was to determine whether anodal tDCS applied to the motor cortex during a sustained, submaximal contraction prolongs TTF in older adults. The novel finding is that anodal tDCS increased TTF by approximately 15%, possibly by increasing cortical excitability and/or blunting the perception of exertion during the task. This enhancement in performance was most pronounced among the weakest older adults (Figure 1B).

Sustained task performance reduces spinal motor neuron excitability (4,14,15). Although task failure is inevitable (15–18), increased excitatory descending drive from supraspinal regions may compensate for reduced spinal excitation and prolong task performance. Studies have demonstrated that anodal tDCS acutely modulates the resting potential of the neurons under the electrodes and increases motor cortex excitability (19–21). Thus, the increase in TTF in response to anodal tDCS observed here is consistent with the notion that supraspinal mechanisms are involved in task failure of fatiguing contractions. As we have reported similar findings in young adults (6), this does not appear to be an age-related phenomenon. We did observe a large degree in the heterogeneity of response to anodal tDCS, with only approximately 45% of the subjects demonstrating a substantial positive response (61% in young subjects). One potential explanation relates to the weakest seniors exhibiting the most profound effect. Weaker older adults also exhibit lower cortical excitability and voluntary activation (22). It is possible that between-subject differences in baseline cortical excitability and/or voluntary activation contributed to this heterogeneity. Other potential explanations for the heterogeneity include between-subject differences in the degree to which central fatigue contributed to task failure (23) and/or anatomical factors (e.g., thicknesses of the cerebrospinal fluid and the skull, gyral depth) that alter the biophysics of tDCS (24).

Although the present data do not fully elucidate the mechanisms(s) underlying the increase in TTF, polarity-dependent neurotransmitter changes that occur during tDCS provide some insight. Anodal stimulation of the motor cortex increases motor cortex excitability by locally reducing GABAergic inhibition (25). The slowed rate of increase in RPE may reflect the amount of neural drive needed to perform the task (4,26,27), and it is plausible that anodal tDCS increases motor cortex excitability leading to enhanced descending drive to the motor neuron pool that ultimately increases TTF. Anodal tDCS may also induce an analgesic effect, blunting the perception of pain/discomfort associated with the fatiguing task. Our electrode configuration has been used in fibromyalgia patients with one longitudinal study indicating anodal tDCS decreases glutamate/glutamine levels in the pain-modulating anterior cingulate, resulting in larger declines in clinical pain scores compared to sham (28).

In summary, these preliminary findings suggest anodal tDCS enhances TTF of a sustained, submaximal contraction in older adults and likely alters the perception of exertion during the task. However, the overall mean effect of tDCS on TTF was driven by strong responses in less than 50% of the participants. This raises the question of whether interventions that acutely increase cortical excitability could enhance physical function and/or exercise-induced adaptations in healthy older adults, and to our knowledge, no investigation has examined the potential for anodal tDCS to do so. However, tDCS has been shown to contribute to improve motor recovery (29) and to transiently increase muscle strength in stroke patients (30,31). It seems reasonable to speculate that tDCS might be used to acutely increase cortical excitability and thereby enhance physical function and/or exercise performance in older adults.

We did not include a condition without electrodes. Although there are no data to suggest that electrodes on the head can affect TTF, it remains possible that such a setup might result in a longer TTF than either tDCS or sham. In the case of such an occurrence, the results of this study would have been interpreted differently. Further work is needed to address these issues and to examine the potential negative side effects.

Funding

This work was funded in part by a grant from the NIH’s National Institute on Aging (NIA) (R01AG044424 to B.C.C.).

Conflict of Interest

The authors report no declarations of interest