Articles in PresS. J Neurophysiol (January 28, 2015). doi:10.1152/jn.00832.2014
1
Improving motor performance without training: The effect of
2
combining mirror visual feedback with transcranial direct current
3
stimulation
4
5
Erik von Rein1, Maike Hoff1, Elisabeth Kaminski1, Bernhard Sehm1, Christopher J.
6
Steele1, Arno Villringer1,2 and Patrick Ragert1*
7 8
1
9
Neurology, D-04103 Leipzig, Germany, 2Mind and Brain Institute, Charité and Humboldt
10
Max Planck Institute for Human Cognitive and Brain Sciences, Department of
University, D-10117 Berlin, Germany
11 12 13
*
corresponding author
14 15
Patrick Ragert, PhD, Max Planck Institute for Human Cognitive and Brain
16
Sciences, Department of Neurology, Stephanstrasse 1a, D-04103 Leipzig, E-
17
mail: [email protected]
18 19
1
Copyright © 2015 by the American Physiological Society.
20
Abstract
21
Mirror visual feedback (MVF) during motor training has been shown to improve motor
22
performance of the untrained hand. Here we thought to determine if MVF-induced
23
performance improvements of the left hand can be augmented by up-regulating
24
plasticity in right M1 by means of anodal transcranial direct current stimulation (a-tDCS)
25
while subjects trained with the right hand. Participants performed a ball-rotation task
26
with either their left (untrained) or right (trained) hand on two consecutive days (d1-d2).
27
During training with the right hand, MVF was provided concurrent with two tDCS
28
conditions: Group 1 received a-tDCS over right M1 (n=10) while group 2 received sham
29
tDCS (s-tDCS, n=10). On d2, performance was re-evaluated under the same
30
experimental conditions as compared to d1 but without tDCS. While baseline
31
performance of the left hand (d1) was not different between groups, a-tDCS exhibited
32
stronger MVF-induced performance improvements as compared to s-tDCS. Similar
33
results were observed for d2 (without tDCS application). A control experiment (n=8) with
34
a-tDCS over right M1 as outlined above but without MVF revealed that left hand
35
improvement was significantly less pronounced than that induced by combined a-tDCS
36
and MVF. Based on these results, we provide novel evidence that up-regulating activity
37
in the untrained M1 by means of a-tDCS is capable of augmenting MVF-induced
38
performance improvements in young normal volunteers. Our findings suggest that
39
concurrent MVF and tDCS might have synergistic and additive effects on motor
40
performance of the untrained hand, a result of relevance for clinical approaches in
41
neurorehabilitation and/ or exercise science.
42 2
43
Key words: transcranial direct current stimulation (tDCS), motor learning, mirror visual
44
feedback (MVF), primary motor cortex (M1)
45 46
3
47
Introduction
48
Mirror visual feedback (MVF) during practice of a novel motor skill has been shown to
49
improve performance not only of the trained but also of the untrained hand (Nojima et
50
al. 2012). The fact MVF leads to behavioral gains in the untrained body part suggests
51
that it might be an interesting adjuvant approach for neurorehabilitation. Indeed, the
52
concept of MVF was originally used to reduce phantom-limb pain after upper limb
53
amputation (Ramachandran and Rogers-Ramachandran 1996). Since then, the
54
technique has been successfully applied to improve upper limb function in specific
55
neurological diseases such as in patients suffering from stroke (Hamzei et al. 2012) or
56
complex regional pain syndrome (Moseley 2004). Similarly, specific non-invasive brain
57
stimulation (NIBS) protocols have also been shown to improve training outcomes (Reis
58
et al. 2008), an effect which could be used to complement MVF.
59
While the underlying neural mechanisms of MVF-induced behavioral gains still remain
60
elusive, there is ample evidence that plasticity within primary motor cortex (M1)
61
ipsilateral to the trained hand might play an important role in mediating performance
62
improvements of the stationary (untrained) hand (Garry et al. 2005; Giraux and Sirigu
63
2003; Nojima et al. 2012; Waters-Metenier et al. 2014). For example, Nojima and
64
colleagues found that MVF is associated with an increase in corticospinal excitability
65
within M1 representing the untrained hand and that such M1 plasticity is directly
66
correlated with behavioral improvements in a ball-rotation task. Furthermore, disrupting
67
activity within ipsilateral M1 by means of continuous theta burst stimulation (cTBS), a
68
specific form of non-invasive brain stimulation (NIBS), blocked MVF-induced
69
performance improvements of the untrained hand (Nojima et al. 2012). Apart from local 4
70
alterations in M1, a recent neuroimaging study in stroke patients revealed MVF-induced
71
functional alterations in other motor-related brain areas such as dorsal and ventral
72
premotor cortex (Hamzei et al. 2012).
73
Based on the afore-mentioned findings, the present study was designed to further
74
investigate the role of M1 in MVF-induced performance improvements in the untrained
75
hand by assessing the interaction with NIBS. We hypothesized that up-regulating
76
excitability within M1 by means of a single session of anodal transcranial direct current
77
stimulation (a-tDCS) will augment MVF-induced behavioral gains in a ball-rotation task
78
as compared to sham stimulation (s-tDCS). Since unilateral tDCS might have the
79
potential to modulate performance of both hands (Vines et al. 2008; Vines et al. 2006),
80
we also tested the effect of a-tDCS without MVF. We hypothesized here that a-tDCS
81
without MVF will also improve performance in the untrained hand but to a smaller
82
degree as compared to a-tDCS with MVF. To investigate the stability of the potential
83
tDCS-mediated MVF effects, performance of the trained and untrained hand was re-
84
evaluated 24 hours initial training of the groups that received combined a-tDCS or s-
85
tDCS and MVF.
86 87
Material and Methods
88
A total number of 29 right-handed healthy young participants (mean age: 26.64 ± 3.58
89
years; range: 20-37 years; 11 female) were enrolled in the study and gave written
90
informed consent. 21 participants (mean age: 25.40 ± 2.80 years; range: 20-30 years; 9
91
female) participated in a randomized double-blind, sham controlled study design (main 5
92
experiment). Eight additional participants were tested in a post-hoc control experiment
93
(mean age: 29.75 ± 3.57 years; range: 25-37 years; 2 female, see below).
94
The study was performed in accordance with the Declaration of Helsinki and was
95
approved by the local ethics committee of the University of Leipzig. All participants were
96
right handed, as assessed by the Edinburgh Handedness Questionnaire (mean score
97
90.93; range 63-100) (Oldfield 1971) and underwent a detailed neurological
98
examination to exclude any evidence for neurological disease and/ or contraindications
99
relevant for the study procedures outlined below. None of the participants were taking
100
any central acting drugs during the time of the experiment. All participants were task
101
naïve. We did not include highly skilled musicians, typists or sportsmen even though
102
some of the participants were experienced in playing a musical instrument or were
103
currently doing sports as a regular leisure activity. One participant was excluded from
104
the final analysis (main experiment) since performance in the ball-rotation task (see
105
below) could not be analyzed due to technical problems while video taping. Hence, a
106
total of 28 participants (17 male, 11 female) were included in the final analyses.
107
For the main experiment (n=20), participants were invited to take part in the study over
108
two consecutive days (d1 and d2). Detailed study procedures have been described
109
previously (Nojima et al. 2012). In brief, participants performed a complex ball rotation
110
task where they were asked to rotate two cork balls with their left and right hand in
111
separate sessions and specific rotations. On the first day (d1), participants first
112
performed the task with their left (untrained) hand (L pre) and had to rotate the cork
113
balls in counter-clockwise orientation for a single trial as quickly as possible (1 min trial
114
length). This trial served as baseline performance. Subsequently, the ball-rotation task 6
115
was performed with the right (trained) hand in clockwise orientation for 20 minutes (10
116
trials with a trial length of 1 min with, 1 min rest periods in between) while participants
117
received mirror visual feedback (MVF). Here, subjects were instructed to observe the
118
movement of the hand in a mirror; the performing hand was covered by a wooden box.
119
During the right hand training period, participants were instructed to relax the left
120
(untrained) hand as much as possible. The experimenter monitored the left hand by
121
visual inspection to ensure that the left hand was not moving throughout the training
122
period. After this training period, performance of the left (untrained) hand was re-tested
123
(L post). During MVF, 20 minutes of anodal tDCS (a-tDCS+MVF group, n=10, 4 female)
124
or sham stimulation (s-tDCS+MVF group, n=10, 5 female) was applied over the right
125
(untrained) M1. In order to investigate the stability and/or reversibility of the potential
126
tDCS-induced behavioral effects, the ball-rotation task was performed again on the
127
second day (d2, 24 hrs. later) under the same experimental conditions as described
128
above but without tDCS application (Fig. 1).
129
In a post-hoc control experiment, a total number of eight participants performed the ball-
130
rotation task (d1 only) as outlined above but without MVF during 20 min of a-tDCS over
131
right M1 (a-tDCS w/o MVF group, n=8). During training of the right hand, participants
132
were instructed to watch the stationary left hand, the right hand was covered with a box
133
(see also Fig. 1 for experimental setup and design). This control experiment was
134
performed in order to investigate the sole effect of a-tDCS on performance of the left
135
(untrained) hand.
136
In summary, the common feature of all experimental groups was the training of the ball-
137
rotation task with the right hand and the pre and post investigation of motor 7
138
performance of the left (untrained) hand. The difference between groups was either the
139
type of tDCS stimulation (a-tDCS vs. s-tDCS) and/ or the feedback provided during
140
training of the right hand (with or w/o MVF, see also Fig. 1). Motor performance in the
141
ball-rotation task was videotaped throughout the experiment and analyzed (number of
142
ball-rotations/min) offline by an experimenter who was blinded to the study procedures.
143
Transcranial direct current stimulation (tDCS) was delivered via saline-soaked sponge
144
electrodes using a weak direct current of 1mA generated from a battery driven
145
stimulator (NeurConn GmbH, Ilmenau, Germany). Anodal tDCS (a-tDCS) or sham (s-
146
tDCS) stimulation was applied over the right (untrained) M1, during training of the right
147
hand concurrent with MVF. The target electrode (anode; 35 cm2) was placed over the
148
following MNI coordinates: 40, -20, 54 (x, y, z), which corresponds to the right M1
149
(Mayka et al. 2006). In order to minimize stimulation effects of the “reference” electrode
150
(cathode), a 100 cm2 electrode was placed over the frontal orbit. Flexible elastic straps
151
were used to fixate the electrodes on the head. Electrode positioning was guided by a
152
3D neuronavigation device (Brainsight Version 2, Rogue Research Inc., Montreal,
153
Canada). In brief, for localization of right M1 in MNI coordinates, participants were first
154
registered to an individual MR scan using predefined landmarks (nasion, left and right
155
tragus). Subsequently, anatomical images were transformed into 3D-MNI normalized
156
space. Target coordinates were then individually localized on the head of the participant
157
with a 3D motion tracked pointer stick to guide electrode placement.
158
Impedance during tDCS was always kept below 10 kΩ. During a-tDCS, the current was
159
increased at the start and decreased at the end of tDCS for 30s in a ramp-like fashion.
160
Current density under the anode (right M1) was 0.028 mA/cm2 (total charge 0.033 8
161
C/cm2) and 0.01 mA/cm2 (total charge 0.012 C/cm2) under the cathode (frontal orbit).
162
During s-tDCS, the current was increased, maintained and then decreased for 30 s
163
each.
164 165
Statistical Analyses
166
Statistical analyses were performed using the Statistical Software Package for Social
167
Sciences (IBM SPSS Version 22). Initially, baseline performance of the left (untrained)
168
hand was compared between groups (a-tDCS+MVF vs. s-tDCS+MVF, main
169
experiment) using an independent samples T-Test. Differences in performance of the
170
untrained hand after MVF were evaluated by repeated measures ANOVA (ANOVA-RM)
171
with factor TRIAL (L pre vs. L post) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). To
172
investigate the stability of tDCS-induced behavioral effects, performance of L post (d1)
173
was compared with L pre (d2) for both groups separately using paired T-Tests. In this
174
and all subsequent analyses, post-hoc T-Tests were Bonferroni-corrected for multiple
175
comparisons.
176
Right (trained) hand performance was evaluated using another ANOVA-RM with factor
177
TRIAL (R 1-10) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). The same comparisons
178
were performed for day 1 (d1) and day 2 (d2) for both hands. Performance differences
179
between the trained (R 10) and untrained hand (L post) were investigated using paired
180
T-Tests in order to evaluate if concurrent MVF and a-tDCS improved performance of the
181
untrained hand to a similar amount as the trained hand.
9
182
Performance of the left (untrained) hand in the control experiment (a-tDCS w/o MVF)
183
was evaluated using an ANOVA-RM with factor TRIAL (L pre vs. L post). Subsequently,
184
absolute performance changes (L post – L pre) of the untrained hand across groups (a-
185
tDCS+MVF, s-tDCS+MVF, a-tDCS w/o MVF) were compared using an univariate
186
ANOVA with factor GROUP.
187
Levene’s tests were performed to check for differences in variance and (if necessary) p-
188
values were corrected accordingly. Behavioral data is presented as mean ± SEM
189
values. Behavioral data is presented as mean ± SEM values.
190 191
Results
192
Performance of the left (untrained) hand
193
At the beginning of the experiment (d1), baseline performance of the untrained hand (L
194
pre) did not differ between groups (a-tDCS+MVF: 43.80 ± 2.30; s-tDCS+MVF: 43.20 ±
195
4.38 ball-rotations/min, t(18)=0.121; p=0.905, Fig.2, Table 1). However, 20 min of
196
concurrent a-tDCS and MVF resulted in superior performance gains of the untrained
197
hand as compared to s-tDCS (ANOVA-RM with factor TRIAL (L pre vs. L post) X
198
GROUP (a-tDCS+MVF vs. s-tDCS+MVF): F(1,18)=10.778; p=0.004). Manual dexterity
199
improved significantly in both groups by 10.80 ± 1.11 ball-rotations/min in the a-
200
tDCS+MVF group (t(9)=-9,699; p0.05 for
222
all comparisons). These results indicate that performing the ball-rotation task for 1 min
223
does not lead to performance changes within each trial.
11
224
Performance of the right (trained) hand
225
Performing the ball-rotation task on d1 during MVF resulted in significant performance
226
improvements of the trained hand in both groups (ANOVA-RM with factor TRIAL (R1-
227
10): F(9,161)=38.373; p
1
Improving motor performance without training: The effect of
2
combining mirror visual feedback with transcranial direct current
3
stimulation
4
5
Erik von Rein1, Maike Hoff1, Elisabeth Kaminski1, Bernhard Sehm1, Christopher J.
6
Steele1, Arno Villringer1,2 and Patrick Ragert1*
7 8
1
9
Neurology, D-04103 Leipzig, Germany, 2Mind and Brain Institute, Charité and Humboldt
10
Max Planck Institute for Human Cognitive and Brain Sciences, Department of
University, D-10117 Berlin, Germany
11 12 13
*
corresponding author
14 15
Patrick Ragert, PhD, Max Planck Institute for Human Cognitive and Brain
16
Sciences, Department of Neurology, Stephanstrasse 1a, D-04103 Leipzig, E-
17
mail: [email protected]
18 19
1
Copyright © 2015 by the American Physiological Society.
20
Abstract
21
Mirror visual feedback (MVF) during motor training has been shown to improve motor
22
performance of the untrained hand. Here we thought to determine if MVF-induced
23
performance improvements of the left hand can be augmented by up-regulating
24
plasticity in right M1 by means of anodal transcranial direct current stimulation (a-tDCS)
25
while subjects trained with the right hand. Participants performed a ball-rotation task
26
with either their left (untrained) or right (trained) hand on two consecutive days (d1-d2).
27
During training with the right hand, MVF was provided concurrent with two tDCS
28
conditions: Group 1 received a-tDCS over right M1 (n=10) while group 2 received sham
29
tDCS (s-tDCS, n=10). On d2, performance was re-evaluated under the same
30
experimental conditions as compared to d1 but without tDCS. While baseline
31
performance of the left hand (d1) was not different between groups, a-tDCS exhibited
32
stronger MVF-induced performance improvements as compared to s-tDCS. Similar
33
results were observed for d2 (without tDCS application). A control experiment (n=8) with
34
a-tDCS over right M1 as outlined above but without MVF revealed that left hand
35
improvement was significantly less pronounced than that induced by combined a-tDCS
36
and MVF. Based on these results, we provide novel evidence that up-regulating activity
37
in the untrained M1 by means of a-tDCS is capable of augmenting MVF-induced
38
performance improvements in young normal volunteers. Our findings suggest that
39
concurrent MVF and tDCS might have synergistic and additive effects on motor
40
performance of the untrained hand, a result of relevance for clinical approaches in
41
neurorehabilitation and/ or exercise science.
42 2
43
Key words: transcranial direct current stimulation (tDCS), motor learning, mirror visual
44
feedback (MVF), primary motor cortex (M1)
45 46
3
47
Introduction
48
Mirror visual feedback (MVF) during practice of a novel motor skill has been shown to
49
improve performance not only of the trained but also of the untrained hand (Nojima et
50
al. 2012). The fact MVF leads to behavioral gains in the untrained body part suggests
51
that it might be an interesting adjuvant approach for neurorehabilitation. Indeed, the
52
concept of MVF was originally used to reduce phantom-limb pain after upper limb
53
amputation (Ramachandran and Rogers-Ramachandran 1996). Since then, the
54
technique has been successfully applied to improve upper limb function in specific
55
neurological diseases such as in patients suffering from stroke (Hamzei et al. 2012) or
56
complex regional pain syndrome (Moseley 2004). Similarly, specific non-invasive brain
57
stimulation (NIBS) protocols have also been shown to improve training outcomes (Reis
58
et al. 2008), an effect which could be used to complement MVF.
59
While the underlying neural mechanisms of MVF-induced behavioral gains still remain
60
elusive, there is ample evidence that plasticity within primary motor cortex (M1)
61
ipsilateral to the trained hand might play an important role in mediating performance
62
improvements of the stationary (untrained) hand (Garry et al. 2005; Giraux and Sirigu
63
2003; Nojima et al. 2012; Waters-Metenier et al. 2014). For example, Nojima and
64
colleagues found that MVF is associated with an increase in corticospinal excitability
65
within M1 representing the untrained hand and that such M1 plasticity is directly
66
correlated with behavioral improvements in a ball-rotation task. Furthermore, disrupting
67
activity within ipsilateral M1 by means of continuous theta burst stimulation (cTBS), a
68
specific form of non-invasive brain stimulation (NIBS), blocked MVF-induced
69
performance improvements of the untrained hand (Nojima et al. 2012). Apart from local 4
70
alterations in M1, a recent neuroimaging study in stroke patients revealed MVF-induced
71
functional alterations in other motor-related brain areas such as dorsal and ventral
72
premotor cortex (Hamzei et al. 2012).
73
Based on the afore-mentioned findings, the present study was designed to further
74
investigate the role of M1 in MVF-induced performance improvements in the untrained
75
hand by assessing the interaction with NIBS. We hypothesized that up-regulating
76
excitability within M1 by means of a single session of anodal transcranial direct current
77
stimulation (a-tDCS) will augment MVF-induced behavioral gains in a ball-rotation task
78
as compared to sham stimulation (s-tDCS). Since unilateral tDCS might have the
79
potential to modulate performance of both hands (Vines et al. 2008; Vines et al. 2006),
80
we also tested the effect of a-tDCS without MVF. We hypothesized here that a-tDCS
81
without MVF will also improve performance in the untrained hand but to a smaller
82
degree as compared to a-tDCS with MVF. To investigate the stability of the potential
83
tDCS-mediated MVF effects, performance of the trained and untrained hand was re-
84
evaluated 24 hours initial training of the groups that received combined a-tDCS or s-
85
tDCS and MVF.
86 87
Material and Methods
88
A total number of 29 right-handed healthy young participants (mean age: 26.64 ± 3.58
89
years; range: 20-37 years; 11 female) were enrolled in the study and gave written
90
informed consent. 21 participants (mean age: 25.40 ± 2.80 years; range: 20-30 years; 9
91
female) participated in a randomized double-blind, sham controlled study design (main 5
92
experiment). Eight additional participants were tested in a post-hoc control experiment
93
(mean age: 29.75 ± 3.57 years; range: 25-37 years; 2 female, see below).
94
The study was performed in accordance with the Declaration of Helsinki and was
95
approved by the local ethics committee of the University of Leipzig. All participants were
96
right handed, as assessed by the Edinburgh Handedness Questionnaire (mean score
97
90.93; range 63-100) (Oldfield 1971) and underwent a detailed neurological
98
examination to exclude any evidence for neurological disease and/ or contraindications
99
relevant for the study procedures outlined below. None of the participants were taking
100
any central acting drugs during the time of the experiment. All participants were task
101
naïve. We did not include highly skilled musicians, typists or sportsmen even though
102
some of the participants were experienced in playing a musical instrument or were
103
currently doing sports as a regular leisure activity. One participant was excluded from
104
the final analysis (main experiment) since performance in the ball-rotation task (see
105
below) could not be analyzed due to technical problems while video taping. Hence, a
106
total of 28 participants (17 male, 11 female) were included in the final analyses.
107
For the main experiment (n=20), participants were invited to take part in the study over
108
two consecutive days (d1 and d2). Detailed study procedures have been described
109
previously (Nojima et al. 2012). In brief, participants performed a complex ball rotation
110
task where they were asked to rotate two cork balls with their left and right hand in
111
separate sessions and specific rotations. On the first day (d1), participants first
112
performed the task with their left (untrained) hand (L pre) and had to rotate the cork
113
balls in counter-clockwise orientation for a single trial as quickly as possible (1 min trial
114
length). This trial served as baseline performance. Subsequently, the ball-rotation task 6
115
was performed with the right (trained) hand in clockwise orientation for 20 minutes (10
116
trials with a trial length of 1 min with, 1 min rest periods in between) while participants
117
received mirror visual feedback (MVF). Here, subjects were instructed to observe the
118
movement of the hand in a mirror; the performing hand was covered by a wooden box.
119
During the right hand training period, participants were instructed to relax the left
120
(untrained) hand as much as possible. The experimenter monitored the left hand by
121
visual inspection to ensure that the left hand was not moving throughout the training
122
period. After this training period, performance of the left (untrained) hand was re-tested
123
(L post). During MVF, 20 minutes of anodal tDCS (a-tDCS+MVF group, n=10, 4 female)
124
or sham stimulation (s-tDCS+MVF group, n=10, 5 female) was applied over the right
125
(untrained) M1. In order to investigate the stability and/or reversibility of the potential
126
tDCS-induced behavioral effects, the ball-rotation task was performed again on the
127
second day (d2, 24 hrs. later) under the same experimental conditions as described
128
above but without tDCS application (Fig. 1).
129
In a post-hoc control experiment, a total number of eight participants performed the ball-
130
rotation task (d1 only) as outlined above but without MVF during 20 min of a-tDCS over
131
right M1 (a-tDCS w/o MVF group, n=8). During training of the right hand, participants
132
were instructed to watch the stationary left hand, the right hand was covered with a box
133
(see also Fig. 1 for experimental setup and design). This control experiment was
134
performed in order to investigate the sole effect of a-tDCS on performance of the left
135
(untrained) hand.
136
In summary, the common feature of all experimental groups was the training of the ball-
137
rotation task with the right hand and the pre and post investigation of motor 7
138
performance of the left (untrained) hand. The difference between groups was either the
139
type of tDCS stimulation (a-tDCS vs. s-tDCS) and/ or the feedback provided during
140
training of the right hand (with or w/o MVF, see also Fig. 1). Motor performance in the
141
ball-rotation task was videotaped throughout the experiment and analyzed (number of
142
ball-rotations/min) offline by an experimenter who was blinded to the study procedures.
143
Transcranial direct current stimulation (tDCS) was delivered via saline-soaked sponge
144
electrodes using a weak direct current of 1mA generated from a battery driven
145
stimulator (NeurConn GmbH, Ilmenau, Germany). Anodal tDCS (a-tDCS) or sham (s-
146
tDCS) stimulation was applied over the right (untrained) M1, during training of the right
147
hand concurrent with MVF. The target electrode (anode; 35 cm2) was placed over the
148
following MNI coordinates: 40, -20, 54 (x, y, z), which corresponds to the right M1
149
(Mayka et al. 2006). In order to minimize stimulation effects of the “reference” electrode
150
(cathode), a 100 cm2 electrode was placed over the frontal orbit. Flexible elastic straps
151
were used to fixate the electrodes on the head. Electrode positioning was guided by a
152
3D neuronavigation device (Brainsight Version 2, Rogue Research Inc., Montreal,
153
Canada). In brief, for localization of right M1 in MNI coordinates, participants were first
154
registered to an individual MR scan using predefined landmarks (nasion, left and right
155
tragus). Subsequently, anatomical images were transformed into 3D-MNI normalized
156
space. Target coordinates were then individually localized on the head of the participant
157
with a 3D motion tracked pointer stick to guide electrode placement.
158
Impedance during tDCS was always kept below 10 kΩ. During a-tDCS, the current was
159
increased at the start and decreased at the end of tDCS for 30s in a ramp-like fashion.
160
Current density under the anode (right M1) was 0.028 mA/cm2 (total charge 0.033 8
161
C/cm2) and 0.01 mA/cm2 (total charge 0.012 C/cm2) under the cathode (frontal orbit).
162
During s-tDCS, the current was increased, maintained and then decreased for 30 s
163
each.
164 165
Statistical Analyses
166
Statistical analyses were performed using the Statistical Software Package for Social
167
Sciences (IBM SPSS Version 22). Initially, baseline performance of the left (untrained)
168
hand was compared between groups (a-tDCS+MVF vs. s-tDCS+MVF, main
169
experiment) using an independent samples T-Test. Differences in performance of the
170
untrained hand after MVF were evaluated by repeated measures ANOVA (ANOVA-RM)
171
with factor TRIAL (L pre vs. L post) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). To
172
investigate the stability of tDCS-induced behavioral effects, performance of L post (d1)
173
was compared with L pre (d2) for both groups separately using paired T-Tests. In this
174
and all subsequent analyses, post-hoc T-Tests were Bonferroni-corrected for multiple
175
comparisons.
176
Right (trained) hand performance was evaluated using another ANOVA-RM with factor
177
TRIAL (R 1-10) and GROUP (a-tDCS+MVF vs. s-tDCS+MVF). The same comparisons
178
were performed for day 1 (d1) and day 2 (d2) for both hands. Performance differences
179
between the trained (R 10) and untrained hand (L post) were investigated using paired
180
T-Tests in order to evaluate if concurrent MVF and a-tDCS improved performance of the
181
untrained hand to a similar amount as the trained hand.
9
182
Performance of the left (untrained) hand in the control experiment (a-tDCS w/o MVF)
183
was evaluated using an ANOVA-RM with factor TRIAL (L pre vs. L post). Subsequently,
184
absolute performance changes (L post – L pre) of the untrained hand across groups (a-
185
tDCS+MVF, s-tDCS+MVF, a-tDCS w/o MVF) were compared using an univariate
186
ANOVA with factor GROUP.
187
Levene’s tests were performed to check for differences in variance and (if necessary) p-
188
values were corrected accordingly. Behavioral data is presented as mean ± SEM
189
values. Behavioral data is presented as mean ± SEM values.
190 191
Results
192
Performance of the left (untrained) hand
193
At the beginning of the experiment (d1), baseline performance of the untrained hand (L
194
pre) did not differ between groups (a-tDCS+MVF: 43.80 ± 2.30; s-tDCS+MVF: 43.20 ±
195
4.38 ball-rotations/min, t(18)=0.121; p=0.905, Fig.2, Table 1). However, 20 min of
196
concurrent a-tDCS and MVF resulted in superior performance gains of the untrained
197
hand as compared to s-tDCS (ANOVA-RM with factor TRIAL (L pre vs. L post) X
198
GROUP (a-tDCS+MVF vs. s-tDCS+MVF): F(1,18)=10.778; p=0.004). Manual dexterity
199
improved significantly in both groups by 10.80 ± 1.11 ball-rotations/min in the a-
200
tDCS+MVF group (t(9)=-9,699; p0.05 for
222
all comparisons). These results indicate that performing the ball-rotation task for 1 min
223
does not lead to performance changes within each trial.
11
224
Performance of the right (trained) hand
225
Performing the ball-rotation task on d1 during MVF resulted in significant performance
226
improvements of the trained hand in both groups (ANOVA-RM with factor TRIAL (R1-
227
10): F(9,161)=38.373; p
