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Anodal Transcranial Direct Current Stimulation Prolongs the Cross-education of Strength and Corticomotor Plasticity

Hendy, Ashlee M.1; Teo, Wei-Peng1; Kidgell, Dawson J.2

Medicine & Science in Sports & Exercise: September 2015 - Volume 47 - Issue 9 - p 1788–1797
doi: 10.1249/MSS.0000000000000600
CLINICAL SCIENCES
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Purpose This study aimed to assess the efficacy of applying anodal transcranial direct-current stimulation (a-tDCS) to the ipsilateral motor cortex (iM1) during unilateral strength training to enhance the neurophysiological and functional effects of cross-education.

Methods Twenty-four healthy volunteers were randomly allocated to perform either of the following: strength training during a-tDCS (ST + a-tDCS), strength training during sham tDCS (ST + sham), or a-tDCS during rest (a-tDCS) across 2 wk. Strength training of the right biceps brachii involved four sets of six repetitions at 80% of one-repetition maximum three times per week. Anodal tDCS was applied to the iM1 at 1.5 mA for 15 min during each strength training session. Outcome measures included one-repetition maximum strength of the untrained biceps brachii, corticomotoneuronal excitability, cross-activation, and short-interval intracortical inhibition (SICI) of the iM1 determined by transcranial magnetic stimulation.

Results Immediately after the final training session, there was an increase in strength for both the ST + a-tDCS (12.5%, P < 0.001) and the ST + sham group (9.4%, P = 0.007), which was accompanied by significant increases in corticomotoneuronal excitability and decreases in SICI for both groups. After a 48-h retention period, strength increase was maintained in the ST + a-tDCS (13.0%, P = 0.001) group, which was significantly greater than the ST + sham group (7.6%, P = 0.039). Similarly, increases in corticomotoneuronal excitability and decreases in SICI were maintained in the ST + a-tDCS group but not in the ST + sham group. No main effects were reported for the a-tDCS group (all P > 0.05).

Conclusions The addition of a-tDCS to the iM1 during unilateral strength training prolongs the benefits of cross-education, which may have significant implications to enhancement of rehabilitation outcomes after a single-limb injury or impairment.

1Centre for Physical Activity and Nutrition Research, Faculty of Health, Deakin University, Burwood, Victoria, AUSTRALIA; and 2School of Allied Health, Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, Victoria, AUSTRALIA

Address for correspondence: Dawson J. Kidgell, Ph.D., School of Allied Health, Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, Victoria, 3086 Australia; E-mail: d.kidgell@latrobe.edu.au.

Submitted for publication July 2014.

Accepted for publication November 2014.

It is well established that strength training of a single limb produces performance gains not only in the trained limb but also in the untrained contralateral limb (24). This phenomenon, termed cross-education, has been observed in a range of muscle groups after various types of motor training, including heavy-load strength training (14,23) and ballistic motor tasks (7,25). Because of the lack of hypertrophy (34), along with reports of increased corticospinal excitability (14,21) and voluntary activation (26) accompanying strength gain in the untrained limb, cross-education is believed to occur as a result of neural adaptations. Cross-education has recently gained scientific interest because of its potential to minimize strength loss and enhance recovery in patients who are unable to perform training because of a single-limb injury or impairment (37). Unilateral training of the unaffected limb has been found to maintain strength and function of the affected limb after periods of immobilization (10) and fracture (28). Given the clinical relevance of strength transfer, it seems logical to investigate the possibility of maximizing the magnitude of strength gain in the untrained limb to attain greater therapeutic benefits.

To further potentiate the cross-education of strength, the underpinning neurophysiological mechanisms, although somewhat unresolved at present, must be considered. Two theoretical models have been presented, as follows: the “cross-activation” hypothesis, characterized by the presence of neural activity in both the contralateral M1 (cM1) and the ipsilateral M1 (iM1) during effortful unilateral movement, and the “bilateral access” hypothesis, characterized by the development of motor engrams accessible by both the cM1 and iM1 (25,37). Both models suggest that the iM1 plays an important role in mediating cross-education of strength (37). Indeed, studies using functional magnetic resonance imaging (40) and transcranial magnetic stimulation (TMS) (17,33) have consistently demonstrated an acute increase in activity of the iM1 during unilateral muscle contractions, which seems to be accompanied by acute reductions in short-interval intracortical inhibition (SICI) (33) and interhemispheric inhibition (IHI) (16,18). Motor-evoked potentials (MEP) induced at the cervicomedullary junction are not affected by unilateral muscle contractions (17), suggesting that increases in corticospinal excitability are most likely to occur at the cortical, rather than the subcortical or spinal, levels. A number of studies examining corticospinal responses to repeated practice of ballistic motor tasks have reported an increase in MEP amplitude of the ipsilateral corticospinal pathway, together with performance improvements in the untrained limb (7,25), with one study reporting that training-related gains were abolished after the application of repetitive TMS to the iM1 (24). We have recently shown that the application of anodal transcranial direct current stimulation (a-tDCS) to the iM1 during unilateral contraction of the wrist extensors acutely facilitates plasticity and strength of the inactive contralateral limb (15). This provides strong evidence to suggest that plasticity of the iM1 plays a role in the cross-education of strength and may respond additionally to noninvasive brain stimulation; however, the effects of multiple sessions have not yet been investigated.

Importantly, longer-lasting adaptive changes in the ipsilateral corticospinal pathway have been reported after short-to moderate-term (3–12 wk) unilateral strength training studies (14,16,21,23,26). Increases in corticospinal excitability (14,16,21) and voluntary activation (26) of the untrained limb have been reported several days after the completion of strength training programs. One study found a strong relation between strength gain in the untrained limb and reduced IHI from the cM1 to the iM1, providing further evidence that adaptive changes occur at a cortical level possibly via transcallosal pathways (16). A release of SICI in the iM1 (14) and a reduction in silent period duration (23) after unilateral training of the lower limb have also been reported; however, this was not replicated in intrinsic hand muscles, indicating that neural responses may vary on the basis of muscle group and training task (16).

TDCS is a noninvasive brain stimulation technique that can be used to acutely modulate cortical plasticity in a polarity-specific manner (see (29) for review), and it may have the potential to facilitate cross-education (15). The procedure is safe, easy to administer, and is often imperceptible to the recipient, allowing for effective double-blinding during experiments (13,29). The application of a-tDCS is believed to increase the resting membrane potential of the underlying cortical tissue, which increases the likelihood of depolarization (30,35). Immediate increases in MEP amplitude have frequently been reported after a-tDCS in a range of muscle groups and current densities (29). These effects have also been shown to last for up to 90 min after stimulation, which is believed to be a result of short-term improvements in synaptic efficacy (11,27,30). Several studies have reported that modulation in cortical plasticity after single sessions of a-tDCS has also been accompanied by improvements in motor performance (3,19,20), force production (15,39), and muscular endurance (9). There is a trend in the current literature to investigate the role of tDCS in treating patients with motor impairments such as stroke (see (5) for review); however, healthy individuals also seem to attain functional benefits (3,20), especially when tDCS is combined with concurrent motor practice (15,38). There is also evidence that multiple sessions of tDCS produce a cumulative effect, with five consecutive days of tDCS alone improving motor performance in patients who experienced stroke (4) and repeated sessions of a-tDCS during motor practice producing benefits that lasted up to 3 months (36).

Given the recent report of acute increases in iM1 plasticity and strength of the untrained limb after a single session of a-tDCS during unilateral strength training (15), it is reasonable to speculate that the combination of these two procedures may produce compounding and longer-lasting benefits when applied repetitively. Therefore, the purpose of this study was to determine whether the application of a-tDCS to the iM1 during a 2-wk unilateral training program of the biceps brachii would facilitate strength transfer and induce neuroplastic changes in corticomotoneuronal excitability and SICI beyond that of strength training with sham-tDCS or a-tDCS alone. It was hypothesized that the combination of a-tDCS and strength training would result in greater magnitudes of strength transfer to the untrained limb than either strength training or a-tDCS applied independently. Furthermore, it was hypothesized that participants exposed to a-tDCS during training may exhibit larger reductions in SICI and greater increases in corticomotoneuronal excitability of the iM1, particularly when MEP are obtained during muscular contraction of the trained limb (cross-activation).

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METHODS

Participants

A total of 24 participants were selected on a voluntary basis (nine male and 15 female participants; average age, 25.8 ± 2.9 yr; height, 170.6 ± 5.9 cm; weight, 67.1 ± 6.5 kg). All participants were right hand dominant (determined by the Edinburgh Handedness Inventory) (32), free from any known history of peripheral or neurological impairment, and had not participated in strength training of the upper body for a minimum of 12 months. A written informed consent was obtained before participation in the study, which was approved by the Deakin University human research ethics committee. All experiments were conducted according to the standards established by the Declaration of Helsinki.

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Experimental design

The study was carried out as a double-blinded pseudorandomized controlled trial with three experimental groups. The ST + a-tDCS group performed strength training of the right biceps brachii with a-tDCS applied to the iM1, the ST + sham group performed strength training of the right biceps brachii with sham tDCS applied to the iM1, and the a-tDCS group received a-tDCS to the right M1 during seated rest. All participants attended a familiarization session before the commencement of the study to minimize the effect of learning. An external investigator then allocated participants to an experimental group on the basis of sex, age, and body weight. Outcome measures included the following: one-repetition maximum (1RM) strength of the left and right biceps brachii, MEP amplitude at 130% of active motor threshold (AMT) and 150% AMT, SICI, and cross-activation of the right M1 during unilateral maximal voluntary isometric contraction (MVIC) of the right biceps brachii. Pretesting took place no longer than 24 h before the first training session, and posttesting began 5 min after the final training session, with all outcome measures obtained within 30 min of tDCS cessation, and retention testing took place 48 h after the completion of the final training session. A total of six training sessions was performed over a 2-wk period, with no more than 48 h of rest between training sessions.

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Strength testing of the biceps brachii

Maximal voluntary dynamic strength of both the right and left biceps brachii was determined with a standard unilateral 1RM test to provide a functional measure of strength. Participants stood in the anatomical position while the researcher placed an adjustable weight dumbbell in the palm of the hand. Participants were then instructed to grasp the dumbbell and perform a single bicep curl (elbow flexion) without movement of the abdomen or altering of posture. A successful trial required the participant to lift the dumbbell throughout the full range of elbow flexion. The starting weight was estimated by the researcher and increased in increments of 0.25 kg (or greater, if appropriate) until the participant could no longer perform a successful trial. A 3-min recovery period separated each trial. A light warm-up was performed before testing, which allowed for accurate estimation of starting weight. Testing was performed unilaterally, with testing order randomized between limbs. Maximal isometric strength testing was performed on an isokinetic dynamometer (Biodex System 4 Pro; Biodex Medical Systems, Shirley, NY) with the elbow positioned at 90° flexion, forearm in horizontal orientation, and the hand supine. The torque was sampled at 1000 Hz. Participants were required to pull against the dynamometer handle and produce maximal flexion torque, maintained for 3 s. Maximal root mean squared EMG (rmsEMG) for the left bicep was calculated from a 500-ms segment occurring during the peak of the MVIC. This was used to ensure appropriate levels of background muscle activation during TMS testing. MVIC of the right bicep was recorded to ensure that maximal force production was reached during collection of cross-activation MEP, but it did not serve as an outcome measure.

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Strength training protocol

Strength training of the right biceps brachii was performed three times per week over the 2-wk intervention (six sessions in total). Participants were required to perform four sets of six standard bicep curls with a dumbbell weighted at 80% of their 1RM, with 3-min recovery between sets. Repetition timing was 3 s for concentric phase and 4 s for eccentric phase, guided by an electronic metronome. This method has been shown to enhance the demand on the nervous system and increase the magnitude of strength transfer (1). As strength increased, progressive overload was used by increasing the resistance by 5% to ensure optimal training gains. Maximal effort and correct technique were ensured with supervision and verbal encouragement for every session. Participants were instructed to relax the left (untrained) biceps brachii at all times, and surface EMG was recorded to ensure that no mirror activity was present.

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TDCS

a-tDCS was delivered with a direct current (DC) stimulator (NeuroConn, Ilmenau, Germany) for a period of 15 min at 1.5-mA intensity. The anode (stimulating electrode) was located over the right M1 in the area corresponding with the left biceps brachii, which was predetermined with TMS, and the cathode (reference electrode) was located over the left supraorbital area. Both electrodes were soaked in saline solution (0.9% NaCl) before being secured in place. The electrodes had an area of 25 cm2 and produced a current density of 0.06 mA·cm−2. The sham-tDCS condition followed the same initial protocol, with stimulation ceasing after 15 s. The pseudostimulation feature built in to the DC stimulator allowed both participants and researchers to be blinded to the sham stimulation and has been previously validated (13).

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TMS and EMG

Focal TMS was used to measure corticomotoneuronal excitability, SICI, and cross-activation of the left (untrained) biceps brachii before and after the training intervention. TMS was applied over the right M1 using a BiStim unit attached to two Magstim 2002 stimulators (Magstim Co., Dyfed, United Kingdom) to produce MEP recorded from the left biceps brachii. A figure-eight coil, with an external loop diameter of 9 cm, was held over the right M1 at the optimum scalp position to elicit MEP in the left biceps brachii. The induced current in the brain flowed in a posterior-to-anterior direction. Sites near the estimated center of the biceps brachii were explored to determine the “optimal site” at which the largest MEP amplitude was obtained, and this area was marked by a small “x” using a permanent marker. To ensure that all stimuli were delivered consistently throughout testing, participants wore a tight-fitted cap marked with a latitude–longitude matrix, positioned with reference to the nasion–inion and interaural lines. Care was taken by the researcher to ensure that the coil was held over the same position on the scalp so that the same area of the M1 was stimulated in each testing session. All stimuli were delivered during low-level isometric contraction of the biceps brachii, which were performed by supinating the hand and maintaining 90° elbow flexion. Joint angle was measured with an electromagnetic goniometer (ADInstruments, Bella Vista, New South Wales, Australia) with visual feedback provided on a screen visible to both the participant and the researcher. This joint position equated to 5% ± 2% of maximal rmsEMG, with consistent muscle activation confirmed by recording prestimulus rmsEMG for the 100-ms epoch before the delivery of each stimulus. AMT was determined as the minimum stimulus intensity that produced a small MEP (200 μV in five out of 10 consecutive trials) during isometric contraction of the biceps brachii at 5% ± 2% of maximal rmsEMG activity. The stimulus intensity started at 50% of maximal stimulator output (MSO) and was altered in increments of ±1% of MSO until the appropriate threshold level was achieved. Corticomotoneuronal excitability was determined by calculating the average peak-to-peak amplitude of 10 MEP delivered at a stimulus intensity of 130% and 150% AMT. To determine cross-activation, 10 stimuli were delivered to the right M1 at 130% AMT during MVIC of the right biceps brachii. To quantify SICI, 15 paired-pulse stimuli were delivered with a conditioning stimulus of 80% AMT and a test stimulus producing MEP amplitudes equal to 10% of M max, with an interstimulus interval of 3 ms (22). These MEP, along with 15 single-pulse MEP obtained by delivering matching test stimuli, were used to calculate the SICI ratio (see data analyses for more details).

Surface EMG activity was recorded from the left biceps brachii using bipolar Ag-AgCl electrodes. These electrodes were placed on the biceps brachii with an interelectrode distance (center to center) of 2 cm with a muscle belly–tendon montage. A grounding strap placed around the wrist was used as a common reference for all electrodes. All cables were fastened with tape to prevent movement artefact. The area of electrode placement was shaved to remove fine hair, rubbed with an abrasive skin rasp to remove dead skin, and then cleaned with 70% isopropyl alcohol. The exact sites were marked with a permanent marker by tracing around the electrode, and this was maintained for the entire 2-wk period to ensure consistency of electrode placement relative to the innervation zone. An impedance meter was used to ensure that impedance did not exceed 10 kΩ before testing. EMG signals were amplified (×1000), band pass-filtered (high pass at 13 Hz and low pass at 1000 Hz), digitized online at 2 kHz for 1000 ms, recorded, and analyzed using PowerLab 4/35 (ADInstruments, Bella Vista, New South Wales, Australia).

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Maximal compound muscle action potential

Direct muscle responses were obtained from the left biceps brachii by supramaximal electrical stimulation (pulse width, 200 μs) of the brachial plexus (DS7A; Digitimer, Hertfordshire, United Kingdom). The stimuli were delivered while the participant sat in an upright position, with the arm resting comfortably in the lap, producing no detectable background EMG. An increase in current strength was applied to Erbs point until there was no further increase observed in the amplitude of the EMG response (M max). To ensure maximal responses, the current was increased at an additional 20% and the average M max was obtained from five stimuli, with a period of 6–9 s separating each stimulus. The average current required to evoke M max across all testing sessions was 87.9 ± 19.4 mA. M max was recorded before TMS in all testing sessions (before, after, and retention), and used to normalize MEP responses.

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Data analysis

Prestimulus rmsEMG activity in the biceps brachii was determined 100 ms before each TMS stimulus during each testing session. Any prestimulus rmsEMG that exceeded 5% ± 2% maximal rmsEMG were discarded, and the trial, repeated. MEP amplitudes were analyzed using the LabChart 8 software (ADInstruments, Bella Vista, New South Wales, Australia) after each stimulus was automatically flagged with a cursor, providing peak-to-peak values in microvolts, which were then normalized to M max. Average MEP amplitudes were obtained for each trial for single, paired-pulse, and test TMS for each stimulation block separately. SICI was calculated by applying the following equation, which has recently been validated (22):

where SP represents the average MEP amplitude from the single-pulse stimuli and PP represents the average MEP amplitude from the paired-pulse stimuli.

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Statistical analysis

All data were screened with Shapiro–Wilk and Kolmogorov–Smirnov tests and were found to be normally distributed (all P > 0.05). Mixed factorial ANOVA appropriate for a three-group × three-time point design, comparing multiple outcome measures (1RM strength, prestimulus EMG, corticomotoneuronal excitability, SICI, and cross-activation) was used. The number of participants required was based on power calculations to detect a 19% difference (effect size, 0.3) in strength performance, assuming an SD of 10% between groups at P < 0.05 (two-tailed) (21). On the basis of the a priori power analysis, we recruited eight participants per group to provide at least 80% power. Univariate and post hoc (Fisher least significant difference) analysis for each dependent measure followed where significant multivariate effects were found. SPSS version 21 was used for all statistical analyses, with the level of significance used for all tests set at P < 0.05. All data are presented as mean ± SD.

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RESULTS

Strength

The 1RM strength of the left (untrained) biceps brachii is displayed in Figure 1. There was no significant difference in 1RM strength of the left biceps brachii between groups at baseline (P = 0.299). A main effect for time (F 2,23 = 46.807, P < 0.001) and group–time interaction (F 2,23 = 10.755, P < 0.001) was detected. Post hoc analysis revealed a significantly greater increase in mean 1RM strength for both the ST + a-tDCS group (P < 0.001) and the ST + sham group (P = 0.007) when compared with that for the a-tDCS only group immediately after the final training session. At retention, strength increase for the ST + a-tDCS group was maintained and was significantly greater than those for both the ST + sham group (P = 0.039) and the a-tDCS only group (P = 0.001).

FIGURE 1

FIGURE 1

The 1RM strength of the right (trained) biceps brachii is displayed in Table 1. A significant time effect was detected (F 2,23 = 10.717, P < 0.01). The mean 1RM for the ST + a-tDCS group increased by 12.99% (P < 0.01), and the ST + sham group increased by 10.18% (P = 0.01) after the training program (measured at retention). No group–time interactions were reported.

TABLE 1

TABLE 1

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Prestimulus EMG

Prestimulus EMG was recorded before each MEP, including the cross-activation protocol, to ensure consistent levels of muscle activation during TMS. Mean prestimulus EMG is reported in Table 1. No time effect (F 2,23 = 0.159, P = 0.854) or group–time interaction (F 2,23 = 1.680, P = 0.173) was detected.

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Corticomotoneuronal excitability

An example of MEP traces elicited at 130% AMT for a single participant is shown in Figure 2. Group averages for MEP amplitude at 130% AMT are displayed in Figure 3A. There was no significant difference in MEP amplitude at 130% or 150% AMT between groups at baseline (P = 0.771 and P = 0.319, respectively). A main effect for time (F 2,23 = 13.917, P < 0.001) and a group–time interaction (F 2,23 = 6.274, P = 0.007) was detected. Post hoc analysis revealed a significantly greater increase in mean MEP amplitude for the ST + a-tDCS group when compared with the a-tDCS group immediately after the intervention (P = 0.019), which was maintained at retention (P = 0.011).

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

MEP amplitude at 150% AMT is displayed in Figure 3B. A main effect for time (F 2,23 = 18.063, P < 0.001) was detected. There was a significant increase in MEP amplitude for both the ST + a-tDCS group and the ST + sham group immediately after training (P = 0.008 and P = 0.002, respectively) that was sustained at retention (P = 0.001 and P = 0.017, respectively). There was a nonsignificant trend for an increase in MEP amplitude for the a-tDCS group immediately after the final training session (P = 0.065). No group–time interactions were detected.

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SICI

SICI is displayed in Figure 4. There was no significant difference in SICI between groups at baseline (P = 0.451). A main effect for time (F 2,23 = 16.541, P < 0.01) and a group–time interaction (F 2,23 = 3.017, P = 0.02) were detected. Post hoc analysis revealed a significantly greater decrease in mean SICI for the ST + a-tDCS group (P = 0.025) when compared with that for the a-tDCS group immediately after the final training session. At retention, the reduction in SICI for the ST + a-tDCS group was maintained and was significantly lower than that for both the ST + sham group (P = 0.008) and the a-tDCS only group (P = 0.014).

FIGURE 4

FIGURE 4

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Cross-activation

MEP amplitude during cross-activation is displayed in Figure 5. There was no significant difference in cross-activation between groups at baseline (P = 0.240). A main effect for time (F 2,23 = 14.025, P < 0.01) was detected. There was a significant increase in cross-activation MEP amplitude for both the ST + a-tDCS group and the ST + sham group immediately after the final training session (P = 0.004 and P = 0.003, respectively) that was maintained at retention (P = 0.003 and P = 0.06, respectively). No group–time interactions were detected.

FIGURE 5

FIGURE 5

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DISCUSSION

This study has demonstrated that 2 wk of unilateral strength training combined with the application of a-tDCS to the iM1 produced a significant gain in strength of the untrained limb, accompanied by an increase in corticomotoneuronal excitability and a decrease in intracortical inhibition, with benefits remaining present for at least 48 h after the training protocol. An increase in strength of the untrained biceps brachii was also reported after strength training with sham-tDCS but not after a-tDCS alone. Importantly, the magnitude of strength gain in the untrained biceps brachii seems to be maintained for a longer duration when strength training and a-tDCS are combined, providing a significantly greater benefit in the days after training than that after strength training alone. These findings may have significant implications to enhancement of rehabilitation outcomes after a single-limb injury or impairment.

We observed a significant time effect for strength increase for both the trained and the untrained biceps brachii after strength training with a-tDCS and with sham-tDCS but not after a-tDCS without training. Immediately after the final training session, strength gain in the untrained biceps brachii was similar for both strength training groups regardless of the application of anodal or sham tDCS. The unique aspect of the current study was that the magnitude of strength gain in the untrained limb was maintained when strength training was combined with a-tDCS, providing a significantly greater benefit for the ST + a-tDCS group 48 h after the final training session. This indicates that the application of a-tDCS preferentially supports the retention of strength transfer, which may otherwise be reduced within 2 d of completing a short-term strength training program. Many previous studies investigating the potential for performance benefits after a-tDCS combined with motor practice focus primarily on the period directly after stimulation (typically 0–90 min) (11). However, our results demonstrate that greater benefits may be observed in the days after the intervention, particularly when repeated sessions of training and stimulation are performed. Interestingly our findings support previous evidence that a-tDCS may enhance skill acquisition over multiple days via an effect on consolidation (36). The authors examined the effects of five sessions of a-tDCS and fine motor skill practice on consecutive days and found that a-tDCS seemed to enhance “offline” motor learning in the period between the practice sessions rather than “online” motor learning during the practice sessions (36). Similarities between strength training and skill training have been frequently noted in previous literature (37), and despite differences in training tasks and study objectives, this could indicate that learning the skills required to perform a maximal bicep curl (i.e., effective activation of agonists and synergists and reduced antagonist coactivation) may have been enhanced in the group receiving a-tDCS. Because the within-session effects were not directly investigated in the present study, this observation remains speculative but certainly warrants consideration in future research. In addition, this evidence indicates that the application of a-tDCS in the period after training, during offline consolidation, may also be of merit.

When a-tDCS was applied to the right M1 independently (while the right limb rested), no significant strength gain was observed in the left biceps brachii. Although previous studies have shown increases in muscular force (39) and endurance (9) after single applications of a-tDCS, our results do not support the use of a-tDCS alone to improve muscular strength in gross motor tasks for healthy individuals. In contrast, our findings suggest that the application of a-tDCS may only produce functional benefits when the corticomotoneuronal pathway is concurrently targeted by multiple stimuli, particularly when tDCS-induced plasticity is accompanied by use-dependent plasticity from activating the motor pathway to the opposite limb. It is possible that the use of a-tDCS alone may have more favorable effects in participants experiencing motor impairments or the detrimental effects of aging, where a ceiling effect is less likely to occur, and may have a stronger effect on fine and dexterous skills, rather than gross motor tasks (19).

Overall, the mean strength gain of the untrained limb was reasonably well matched with increases in corticomotoneuronal excitability and decreases in SICI. When strength training was performed with sham tDCS, an increase in MEP amplitude and decrease in SICI of the untrained corticomotoneuronal pathway was present immediately after the final training session, with values returning to preintervention levels after the 48-h retention period. However, the addition of a-tDCS to the iM1 during training sessions seemed to prolong the neuroplastic effects of strength training, with the increase in MEP amplitude and decrease in SICI maintained for the 48-h retention period in the ST + a-tDCS group only. This further supports the concept that a-tDCS may play a role in the consolidation of skilled motor tasks and may contribute to the prolonged enhancement of strength that was observed for the untrained limb after the 2-wk training program.

Increases in corticomotoneuronal excitability of the unexercised motor pathway have previously been reported in the cross-education literature (14,16,21). Such changes are generally attributed to increased synaptic transmission within the neural pathways that contribute to force production in the unexercised muscle (14) and has been likened to the effects of long-term potentiation (24). A reduction in SICI of the iM1 (14) and decreased IHI from the cM1 to the iM1 (16) has also been reported, both of which are believed to contribute to greater net corticospinal output from the iM1 because of a reduction of inhibitory synapses onto corticospinal cells (14). Although our results support these findings, we have shown that when strength training is performed without a-tDCS, the duration of the effect may be limited. This may provide some explanation as to why some studies have failed to observe an increase in MEP amplitude of the untrained limb accompanying cross-education (23). Our findings demonstrate that the addition of a-tDCS to the iM1 during unilateral training prolongs the reduction in SICI and increases corticomotoneuronal excitability beyond the immediate posttraining effect. Previous studies have also suggested that increases in MEP amplitude and decreases in SICI in the period immediately after stimulation closely resemble increased synaptic efficacy seen with long-term potentiation, suggesting that similar underlying mechanisms are responsible (27,31). Therefore, on the basis of our findings, it seems reasonable to conclude that the combination of use-dependent plasticity induced by unilateral strength training and experimentally induced plasticity resulting from a-tDCS of the iM1 produces a complimentary effect on neuromodulation of the motor pathway controlling the inactive limb. We have shown that when these stimuli are applied concurrently, the duration of the observed neuromodulatory effects seems to be extended, which may possibly underpin the prolonged magnitude of strength gain that was reported in the untrained limb.

We have previously studied the immediate effects of a single session of strength training during a-tDCS of the iM1 (15). We reported increased strength, corticomotoneuronal excitability and cross-activation, as well as release of SICI after the combined intervention, whereas a-tDCS alone produced an increase in corticomotoneuronal excitability and strength training with sham-tDCS had no effect on outcome measures. When considering these findings together, it seems that the addition of a-tDCS during training acts to accelerate and prolong plasticity and performance gains in the untrained limb. The lack of any benefit for the ST + a-tDCS group immediately after the final training session in the present study suggests that multiple sessions of strength training with sham-tDCS may produce sufficient stimuli of the iM1 to reach a ceiling-like effect for plasticity and strength gain of the untrained limb, which is not further enhanced by a-tDCS. However, the benefits of applying a-tDCS seem to become evident when use-dependent plasticity from strength training alone is reduced, for example, when training is limited to a single session (15) or after the 48-h retention period in the present study. This also indicates that the benefits of applying a-tDCS to the iM1 may be less pronounced over longer training program durations or in higher-performing individuals.

Although we failed to report any significant changes in MEP amplitude or SICI for the a-tDCS alone group, we did observe nonsignificant trends consistent with typical responses to a-tDCS. Our results showed modest increases in corticomotoneuronal excitability at 130% AMT and 150% AMT (9.54% and 16.10%, respectively) and decreases in SICI (−9.30%). It is possible that by measuring MEP amplitude immediately after the a-tDCS protocol may have prevented the full neuromodulatory effects from being recorded. The intraeffects of a-tDCS are likely to have had greater influence on corticomotoneuronal excitability (12), and there is also evidence to suggest that the after-effects of a-tDCS may evolve over time, making it possible that optimal increases occurred outside the time window that we recorded (12). In addition, genetic factors such as polymorphism of brain-derived neurotropic factor have been shown to reduce the effectiveness of various forms of noninvasive brain stimulation techniques in some individuals (8). It is therefore possible that our inability to control for such genetic factors, along with our relatively small sample size, may have contributed to the lack of a main effect within the a-tDCS only group.

Consistent with previous findings, performing an MVIC with the right biceps brachii significantly increased the amplitude of the MEP recorded from the left biceps brachii despite comparable prestimulus rmsEMG (15,33). Strength training (regardless of anodal or sham tDCS) produced significant increase in cross-activation at both postintervention time points. Increases in cross-activation have previously been observed after fatiguing muscle contractions (2). Our results correspond well, with greatest increases in cross-activation occurring immediately after the final training session. It seems plausible that the increase in cross-activation was retained 48 h after the final training session is likely to be driven by residual fatigue of the trained muscle group. At retention, the strength gain in the trained limb was not substantially greater than the strength gain in the untrained limb. Because most cross-education studies report the magnitude of strength gain in the untrained limb to be approximately 25% of strength gain in the trained limb (6), it is likely that optimum strength gains in the trained limb were considerably masked by the effects of fatigue, especially given the high-intensity requirements of the training protocol and the untrained status of participants.

A significant limitation to the present study was the inability to quantify IHI after the intervention. Previous research has indicated that a reduction in IHI from the trained to the untrained M1 may play a significant role in mediating cross-education of strength during single sessions of muscle contractions (18) and after multiple training sessions (16). Without any direct measures, we are only able to speculate that IHI may have been reduced after training and we are unable to determine whether the application of a-tDCS to the iM1 during training may augment this effect. Another limitation in the current study was that active MEP, collected during 5% ± 2% of maximal rmsEMG, were normalized to M max values that were obtained from resting muscle. This variation in the contractile state of the muscle fibers may prevent the accurate determination of corticospinal excitability and should be considered in future studies.

The present findings have significant implications to enhancement of rehabilitation outcomes after a single-limb injury or impairment. When immobilization or fracture prevents strength training of a single limb, unilateral training of the healthy limb may be a viable option to assist with the maintenance of strength (10,28). Because the addition of a-tDCS to the iM1 during training sessions seems to prolong both functional and neurophysiological benefits in the untrained limb of healthy individuals, it is likely that similar benefits would be present in clinical populations. Furthermore, we have provided evidence for a-tDCS enhancing offline gains in strength and neural plasticity. It is therefore likely that longer training programs and more frequent sessions may provide greater compounding effect. Because most clinical manifestations of single-limb impairment are chronic, the application of a-tDCS during training could potentially provide greater outcomes for the impaired limb over time.

In conclusion, we have shown that the application of a-tDCSto the iM1 during short-term unilateral strength training prolongs strength gain in the untrained limb, which seems to be mediated by prolonged neural plasticity of the inactive corticomotoneuronal pathway. Unilateral strength training with sham-tDCS also produced significant gains in strength, corticomotoneuronal excitability, and decreased SICI of the untrained homologous muscle immediately after the final training session; however, these effects were considerably reduced within 48 h. These findings may have significant implications to improvement of rehabilitation outcomes after single-limb injury or impairment.

The authors report that no conflicts of interest associated with the current study have occurred.

The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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REFERENCES

1. Ackerley SJ, Stinear CM, Byblow WD. Promoting use-dependent plasticity with externally-paced training. Clin Neurophysiol. 2011; 122 (12): 2462–8.
2. Arányi Z, Rösler K. Effort-induced mirror movements. A study of transcallosal inhibition in humans. Exp Brain Res. 2002; 145 (1): 76–82.
3. Boggio PS, Castro LO, Savagim EA, et al. Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation. Neurosci Lett. 2006; 404 (1–2): 232–6.
4. Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci. 2007; 25 (2): 123–9.
5. Butler AJ, Shuster M, O’Hara E, Hurley K, Middlebrooks D, Guilkey K. A meta-analysis of the efficacy of anodal transcranial direct current stimulation for upper limb motor recovery in stroke survivors. J Hand Ther. 2013; 26 (2): 162–71.
6. Carroll TJ, Herbert RD, Munn J, Lee M, Gandevia SC. Contralateral effects of unilateral strength training: evidence and possible mechanisms. J Appl Physiol (1985). 2006; 101 (5): 1514–22.
7. Carroll TJ, Lee M, Hsu M, Sayde J. Unilateral practice of a ballistic movement causes bilateral increases in performance and corticospinal excitability. J Appl Physiol (1985). 2008; 104 (6): 1656–64.
8. Cheeran B, Talelli P, Mori F, et al. A common polymorphism in the brain derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J Physiol. 2008; 23 (6): 5717–25.
9. Cogiamanian F, Marceglia S, Ardolino G, Barbieri S, Priori A. Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas. Eur J Neurosci. 2007; 26 (1): 242–9.
10. Farthing JP, Krentz JR, Magnus CR. Strength training the free limb attenuates strength loss during unilateral immobilization. J Appl Physiol (1985). 2009; 106 (3): 830–6.
11. Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2011; 105 (3): 1141–9.
12. Furubayashi T, Terao Y, Arai N, et al. Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area. Exp Brain Res. 2008; 185 (2): 279–86.
13. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006; 117 (4): 845–50.
14. Goodwill AM, Pearce AJ, Kidgell DJ. Corticomotor plasticity following unilateral strength training. Muscle Nerve. 2012; 46 (3): 384–93.
15. Hendy AH, Kidgell DJ. Anodal-tDCS applied during unilateral strength training increases strength and corticospinal excitability in the untrained homologous muscle. Exp Brain Res. 2014; doi: 10.1007/s00221-014-4016-8.
16. Hortobágyi T, Richardson SP, Lomarev M, et al. Interhemispheric plasticity in humans. Med Sci Sports Exerc. 2011; 43 (7): 1188–99.
17. Hortobágyi T, Taylor JL, Petersen NT, Russell G, Gandevia SC. Changes in segmental and motor cortical output with contralateral muscle contractions and altered sensory inputs in humans. J Neurophysiol. 2003; 90 (4): 2451–9.
18. Howatson G, Taylor MB, Rider P, et al. Ipsilateral motor cortical responses to TMS during lengthening and shortening of the contralateral wrist flexors. Eur J Neurosci. 2011; 33 (5): 978–90.
19. Hummel FC, Heise K, Celnik P, Floel A, Gerloff C, Cohen LG. Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex. Neurobiol Aging. 2010; 31 (12): 2160–8.
20. Kidgell DJ, Goodwill AM, Frazer AK, Daly RM. Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex. BMC Neurosci. 2013; 14: 64.
21. Kidgell DJ, Stokes M, Pearce AJ. Strength training of one limb increases corticomotor excitability projecting to the contralateral homologous limb. Motor Control. 2011; 15 (2): 247–66.
22. Lackmy A, Marchand-Pauvert V. The estimation of short intra-cortical inhibition depends on the proportion of spinal motoneurones activated by corticospinal inputs. Clin Neurophysiol. 2010; 121 (4): 612–21.
23. Latella C, Kidgell DJ, Pearce AJ. Reduction in corticospinal inhibition in the trained and untrained limb following unilateral leg strength training. Eur J Appl Physiol. 2012; 112 (8): 3097–107.
24. Lee M, Carroll TJ. Cross education : possible mechanisms for the contralateral effects of unilateral resistance training. Sports Med. 2007; 37 (1): 1–14.
25. Lee M, Hinder MR, Gandevia SC, Carroll TJ. The ipsilateral motor cortex contributes to cross-limb transfer of performance gains after ballistic motor practice. J Physiol. 2010; 588 (1): 201–12.
26. Lee M, Gandevia SC, Carroll TJ. Unilateral strength training increases voluntary activation of the opposite untrained limb. Clin Neurophysiol. 2009; 120 (4): 802–8.
27. Liebetanz D, Nitsche MA, Tergau F, Paulus W. Pharmacological approach to the mechanisms of transcranial DC stimulation induced after effects of human motor cortex excitability. Brain. 2002; 125 (10): 2238.
28. Magnus CRA, Arnold CM, Johnston G, et al. Cross-education for improving strength and mobility after distal radius fractures: a randomized controlled trial. Arch Phys Med Rehabil. 2013; 94 (7): 1247–55.
29. Nitsche MA, Cohen LG, Wassermann EM, et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 2008; 1 (3): 206–23.
30. Nitsche MA, Fricke K, Henschke U, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003; 553 (1): 293–301.
31. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000; 527 (3): 633–9.
32. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971; 9 (1): 97–113.
33. Perez MA, Cohen LG. Mechanisms underlying functional changes in the primary motor cortex ipsilateral to an active hand. J Neurosci. 2008; 28 (22): 5631–40.
34. Ploutz LL, Tesch PA, Biro RL, Dudley GA. Effect of resistance training on muscle use during exercise. J Appl Physiol (1985). 1994; 76 (4): 1675–81.
35. Purpura DP, McMurtry JG. Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol. 1965; 28 (1): 166–85.
36. Reis J, Schambra HM, Cohen LG, et al. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc Natl Acad Sci U S A. 2009; 106 (5): 1590–5.
37. Ruddy KL, Carson RG. Neural pathways mediating cross education of motor function. Front Hum Neurosci. 2013; 7 (397): 1–22.
38. Stagg CJ, Jayaram G, Pastor D, Kincses ZT, Matthews PM, Johansen-Berg H. Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning. Neuropsychologia. 2011; 49 (5): 800–4.
39. Tanaka S, Hanakawa T, Honda M, Watanabe K. Enhancement of pinch force in the lower leg by anodal transcranial direct current stimulation. Exp Brain Res. 2009; 196 (3): 459–65.
40. van Duinen H, Renken R, Maurits NM, Zijdewind I. Relation between muscle and brain activity during isometric contractions of the first dorsal interosseus muscle. Hum Brain Mapp. 2008; 29 (3): 281–99.
Keywords:

BICEPS BRACHII; CROSS-TRANSFER; EXCITABILITY; MOTOR CORTEX; INHIBITION; TRANSCRANIAL MAGNETIC STIMULATION

© 2015 American College of Sports Medicine