Articles in PresS. J Neurophysiol (January 28, 2015). doi:10.1152/jn.00832.2014
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Improving motor performance without training: The effect of
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combining mirror visual feedback with transcranial direct current
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stimulation
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Erik von Rein1, Maike Hoff1, Elisabeth Kaminski1, Bernhard Sehm1, Christopher J.
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Steele1, Arno Villringer1,2 and Patrick Ragert1*
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Neurology, D-04103 Leipzig, Germany, 2Mind and Brain Institute, Charité and Humboldt
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Max Planck Institute for Human Cognitive and Brain Sciences, Department of
University, D-10117 Berlin, Germany
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corresponding author
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Patrick Ragert, PhD, Max Planck Institute for Human Cognitive and Brain
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Sciences, Department of Neurology, Stephanstrasse 1a, D-04103 Leipzig, E-
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mail:
[email protected]
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Copyright © 2015 by the American Physiological Society.
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Abstract
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Mirror visual feedback (MVF) during motor training has been shown to improve motor
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performance of the untrained hand. Here we thought to determine if MVF-induced
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performance improvements of the left hand can be augmented by up-regulating
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plasticity in right M1 by means of anodal transcranial direct current stimulation (a-tDCS)
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while subjects trained with the right hand. Participants performed a ball-rotation task
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with either their left (untrained) or right (trained) hand on two consecutive days (d1-d2).
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During training with the right hand, MVF was provided concurrent with two tDCS
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conditions: Group 1 received a-tDCS over right M1 (n=10) while group 2 received sham
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tDCS (s-tDCS, n=10). On d2, performance was re-evaluated under the same
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experimental conditions as compared to d1 but without tDCS. While baseline
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performance of the left hand (d1) was not different between groups, a-tDCS exhibited
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stronger MVF-induced performance improvements as compared to s-tDCS. Similar
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results were observed for d2 (without tDCS application). A control experiment (n=8) with
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a-tDCS over right M1 as outlined above but without MVF revealed that left hand
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improvement was significantly less pronounced than that induced by combined a-tDCS
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and MVF. Based on these results, we provide novel evidence that up-regulating activity
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in the untrained M1 by means of a-tDCS is capable of augmenting MVF-induced
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performance improvements in young normal volunteers. Our findings suggest that
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concurrent MVF and tDCS might have synergistic and additive effects on motor
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performance of the untrained hand, a result of relevance for clinical approaches in
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neurorehabilitation and/ or exercise science.
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Key words: transcranial direct current stimulation (tDCS), motor learning, mirror visual
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feedback (MVF), primary motor cortex (M1)
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Introduction
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Mirror visual feedback (MVF) during practice of a novel motor skill has been shown to
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improve performance not only of the trained but also of the untrained hand (Nojima et
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al. 2012). The fact MVF leads to behavioral gains in the untrained body part suggests
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that it might be an interesting adjuvant approach for neurorehabilitation. Indeed, the
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concept of MVF was originally used to reduce phantom-limb pain after upper limb
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amputation (Ramachandran and Rogers-Ramachandran 1996). Since then, the
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technique has been successfully applied to improve upper limb function in specific
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neurological diseases such as in patients suffering from stroke (Hamzei et al. 2012) or
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complex regional pain syndrome (Moseley 2004). Similarly, specific non-invasive brain
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stimulation (NIBS) protocols have also been shown to improve training outcomes (Reis
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et al. 2008), an effect which could be used to complement MVF.
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While the underlying neural mechanisms of MVF-induced behavioral gains still remain
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elusive, there is ample evidence that plasticity within primary motor cortex (M1)
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ipsilateral to the trained hand might play an important role in mediating performance
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improvements of the stationary (untrained) hand (Garry et al. 2005; Giraux and Sirigu
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2003; Nojima et al. 2012; Waters-Metenier et al. 2014). For example, Nojima and
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colleagues found that MVF is associated with an increase in corticospinal excitability
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within M1 representing the untrained hand and that such M1 plasticity is directly
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correlated with behavioral improvements in a ball-rotation task. Furthermore, disrupting
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activity within ipsilateral M1 by means of continuous theta burst stimulation (cTBS), a
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specific form of non-invasive brain stimulation (NIBS), blocked MVF-induced
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performance improvements of the untrained hand (Nojima et al. 2012). Apart from local 4
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alterations in M1, a recent neuroimaging study in stroke patients revealed MVF-induced
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functional alterations in other motor-related brain areas such as dorsal and ventral
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premotor cortex (Hamzei et al. 2012).
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Based on the afore-mentioned findings, the present study was designed to further
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investigate the role of M1 in MVF-induced performance improvements in the untrained
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hand by assessing the interaction with NIBS. We hypothesized that up-regulating
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excitability within M1 by means of a single session of anodal transcranial direct current
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stimulation (a-tDCS) will augment MVF-induced behavioral gains in a ball-rotation task
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as compared to sham stimulation (s-tDCS). Since unilateral tDCS might have the
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potential to modulate performance of both hands (Vines et al. 2008; Vines et al. 2006),
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we also tested the effect of a-tDCS without MVF. We hypothesized here that a-tDCS
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without MVF will also improve performance in the untrained hand but to a smaller
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degree as compared to a-tDCS with MVF. To investigate the stability of the potential
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tDCS-mediated MVF effects, performance of the trained and untrained hand was re-
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evaluated 24 hours initial training of the groups that received combined a-tDCS or s-
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tDCS and MVF.
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Material and Methods
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A total number of 29 right-handed healthy young participants (mean age: 26.64 ± 3.58
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years; range: 20-37 years; 11 female) were enrolled in the study and gave written
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informed consent. 21 participants (mean age: 25.40 ± 2.80 years; range: 20-30 years; 9
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female) participated in a randomized double-blind, sham controlled study design (main 5
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experiment). Eight additional participants were tested in a post-hoc control experiment
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(mean age: 29.75 ± 3.57 years; range: 25-37 years; 2 female, see below).
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The study was performed in accordance with the Declaration of Helsinki and was
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approved by the local ethics committee of the University of Leipzig. All participants were
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right handed, as assessed by the Edinburgh Handedness Questionnaire (mean score
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90.93; range 63-100) (Oldfield 1971) and underwent a detailed neurological
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examination to exclude any evidence for neurological disease and/ or contraindications
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relevant for the study procedures outlined below. None of the participants were taking
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any central acting drugs during the time of the experiment. All participants were task
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naïve. We did not include highly skilled musicians, typists or sportsmen even though
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some of the participants were experienced in playing a musical instrument or were
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currently doing sports as a regular leisure activity. One participant was excluded from
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the final analysis (main experiment) since performance in the ball-rotation task (see
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below) could not be analyzed due to technical problems while video taping. Hence, a
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total of 28 participants (17 male, 11 female) were included in the final analyses.
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For the main experiment (n=20), participants were invited to take part in the study over
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two consecutive days (d1 and d2). Detailed study procedures have been described
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previously (Nojima et al. 2012). In brief, participants performed a complex ball rotation
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task where they were asked to rotate two cork balls with their left and right hand in
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separate sessions and specific rotations. On the first day (d1), participants first
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performed the task with their left (untrained) hand (L pre) and had to rotate the cork
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balls in counter-clockwise orientation for a single trial as quickly as possible (1 min trial
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length). This trial served as baseline performance. Subsequently, the ball-rotation task 6
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was performed with the right (trained) hand in clockwise orientation for 20 minutes (10
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trials with a trial length of 1 min with, 1 min rest periods in between) while participants
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received mirror visual feedback (MVF). Here, subjects were instructed to observe the
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movement of the hand in a mirror; the performing hand was covered by a wooden box.
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During the right hand training period, participants were instructed to relax the left
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(untrained) hand as much as possible. The experimenter monitored the left hand by
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visual inspection to ensure that the left hand was not moving throughout the training
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period. After this training period, performance of the left (untrained) hand was re-tested
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(L post). During MVF, 20 minutes of anodal tDCS (a-tDCS+MVF group, n=10, 4 female)
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or sham stimulation (s-tDCS+MVF group, n=10, 5 female) was applied over the right
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(untrained) M1. In order to investigate the stability and/or reversibility of the potential
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tDCS-induced behavioral effects, the ball-rotation task was performed again on the
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second day (d2, 24 hrs. later) under the same experimental conditions as described
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above but without tDCS application (Fig. 1).
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In a post-hoc control experiment, a total number of eight participants performed the ball-
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rotation task (d1 only) as outlined above but without MVF during 20 min of a-tDCS over
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right M1 (a-tDCS w/o MVF group, n=8). During training of the right hand, participants
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were instructed to watch the stationary left hand, the right hand was covered with a box
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(see also Fig. 1 for experimental setup and design). This control experiment was
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performed in order to investigate the sole effect of a-tDCS on performance of the left
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(untrained) hand.
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In summary, the common feature of all experimental groups was the training of the ball-
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rotation task with the right hand and the pre and post investigation of motor 7
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performance of the left (untrained) hand. The difference between groups was either the
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type of tDCS stimulation (a-tDCS vs. s-tDCS) and/ or the feedback provided during
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training of the right hand (with or w/o MVF, see also Fig. 1). Motor performance in the
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ball-rotation task was videotaped throughout the experiment and analyzed (number of
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ball-rotations/min) offline by an experimenter who was blinded to the study procedures.
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Transcranial direct current stimulation (tDCS) was delivered via saline-soaked sponge
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electrodes using a weak direct current of 1mA generated from a battery driven
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stimulator (NeurConn GmbH, Ilmenau, Germany). Anodal tDCS (a-tDCS) or sham (s-
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tDCS) stimulation was applied over the right (untrained) M1, during training of the right
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hand concurrent with MVF. The target electrode (anode; 35 cm2) was placed over the
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following MNI coordinates: 40, -20, 54 (x, y, z), which corresponds to the right M1
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(Mayka et al. 2006). In order to minimize stimulation effects of the “reference” electrode
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(cathode), a 100 cm2 electrode was placed over the frontal orbit. Flexible elastic straps
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were used to fixate the electrodes on the head. Electrode positioning was guided by a
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3D neuronavigation device (Brainsight Version 2, Rogue Research Inc., Montreal,
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Canada). In brief, for localization of right M1 in MNI coordinates, participants were first
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registered to an individual MR scan using predefined landmarks (nasion, left and right
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tragus). Subsequently, anatomical images were transformed into 3D-MNI normalized
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space. Target coordinates were then individually localized on the head of the participant
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with a 3D motion tracked pointer stick to guide electrode placement.
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Impedance during tDCS was always kept below 10 kΩ. During a-tDCS, the current was
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increased at the start and decreased at the end of tDCS for 30s in a ramp-like fashion.
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Current density under the anode (right M1) was 0.028 mA/cm2 (total charge 0.033 8
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C/cm2) and 0.01 mA/cm2 (total charge 0.012 C/cm2) under the cathode (frontal orbit).
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During s-tDCS, the current was increased, maintained and then decreased for 30 s
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each.
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Statistical Analyses
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Statistical analyses were performed using the Statistical Software Package for Social
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Sciences (IBM SPSS Version 22). Initially, baseline performance of the left (untrained)
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hand was compared between groups (a-tDCS+MVF vs. s-tDCS+MVF, main
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experiment) using an independent samples T-Test. Differences in performance of the
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untrained hand after MVF were evaluated by repeated measures ANOVA (ANOVA-RM)
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with factor TRIAL (L pre vs. L post) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). To
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investigate the stability of tDCS-induced behavioral effects, performance of L post (d1)
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was compared with L pre (d2) for both groups separately using paired T-Tests. In this
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and all subsequent analyses, post-hoc T-Tests were Bonferroni-corrected for multiple
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comparisons.
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Right (trained) hand performance was evaluated using another ANOVA-RM with factor
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TRIAL (R 1-10) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). The same comparisons
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were performed for day 1 (d1) and day 2 (d2) for both hands. Performance differences
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between the trained (R 10) and untrained hand (L post) were investigated using paired
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T-Tests in order to evaluate if concurrent MVF and a-tDCS improved performance of the
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untrained hand to a similar amount as the trained hand.
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Performance of the left (untrained) hand in the control experiment (a-tDCS w/o MVF)
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was evaluated using an ANOVA-RM with factor TRIAL (L pre vs. L post). Subsequently,
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absolute performance changes (L post – L pre) of the untrained hand across groups (a-
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tDCS+MVF, s-tDCS+MVF, a-tDCS w/o MVF) were compared using an univariate
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ANOVA with factor GROUP.
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Levene’s tests were performed to check for differences in variance and (if necessary) p-
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values were corrected accordingly. Behavioral data is presented as mean ± SEM
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values. Behavioral data is presented as mean ± SEM values.
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Results
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Performance of the left (untrained) hand
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At the beginning of the experiment (d1), baseline performance of the untrained hand (L
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pre) did not differ between groups (a-tDCS+MVF: 43.80 ± 2.30; s-tDCS+MVF: 43.20 ±
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4.38 ball-rotations/min, t(18)=0.121; p=0.905, Fig.2, Table 1). However, 20 min of
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concurrent a-tDCS and MVF resulted in superior performance gains of the untrained
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hand as compared to s-tDCS (ANOVA-RM with factor TRIAL (L pre vs. L post) X
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GROUP (a-tDCS+MVF vs. s-tDCS+MVF): F(1,18)=10.778; p=0.004). Manual dexterity
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improved significantly in both groups by 10.80 ± 1.11 ball-rotations/min in the a-
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tDCS+MVF group (t(9)=-9,699; p0.05 for
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all comparisons). These results indicate that performing the ball-rotation task for 1 min
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does not lead to performance changes within each trial.
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Performance of the right (trained) hand
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Performing the ball-rotation task on d1 during MVF resulted in significant performance
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improvements of the trained hand in both groups (ANOVA-RM with factor TRIAL (R1-
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10): F(9,161)=38.373; p
