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Neuroscience Letters 404 (2006) 232236

Enhancement of non-dominant hand motor function by anodaltranscranial direct current stimulation

Paulo S. Boggio b,c,, Letcia O. Castro c, Edna A. Savagim c, Renata Braite c, Viviane C. Cruz c,Renata R. Rocha c, Sergio P. Rigonatti b, Maria T.A. Silva b, Felipe Fregni a,b,

a Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, KS 452, Boston, MA 02215, USAb Department of Experimental Psychology and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil

cNucleo de Neurociencias, Psychology School, Mackenzie University, Sao Paulo, Brazil

Received 17 February 2006; received in revised form 18 April 2006; accepted 29 May 2006

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive powerful method to modulate brain activity. It can enhance motor learning and

working memory in healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the dominant and non-dominant primary motor

cortex (M1) on hand motor performancein healthy right-handed volunteers, healthy subjects underwent one session of both sham and active anodal

stimulation of the non-dominant or dominant primary motor cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand Function

Test. For the non-dominant hand, active tDCS was able to improve motor function significantlythere was a significant interaction between time

and condition of stimulation (p = 0.003). Post hoc tests showed a significant enhancement of JTT performance after 1 mA anodal tDCS of M1

(mean improvement of 9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84). For the dominant hand, however,

neither active nor sham tDCS resulted in a significant change in motor performance. Our findings show that anodal tDCS of the non-dominant

primary motor cortex results in motor function enhancement and thus confirm and extend the notion that tDCS can change behavior. We speculate

that the under-use of the non-dominant hand with its associated consequences in cortical plasticity might be one of the reasons to explain motor

performance enhancement in the non-dominant hand only.

2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Primary motor cortex; Transcranial direct current stimulation; Motor function performance; Brain polarization; tDCS

The development of non-invasive techniques of brain stimu-

lation, such as transcranial magnetic stimulation (TMS) and

transcranial direct current stimulation (tDCS), has opened new

windows of opportunities to modulate brain function in a pain-

less and non-invasive way, and thus behavioral changes are

possible depending on the parameters of stimulation, such as

intensity, duration and site of stimulation. For instance, it has

been demonstrated that rTMS can improve motor function in

healthy subjects [13] and stroke patients [16] as well as work-

Correspondence to: Department of Neurology, Beth Israel Deaconess Med-

ical Center, Harvard Medical School, 330 Brookline Ave, KS 452, Boston, MA

02215, USA. Corresponding author at: Department of Neurology, Beth Israel Deaconess

Medical Center, Harvard Medical School, 330 Brookline Ave, KS 452, Boston,

MA 02215, USA. Tel.: +1 617 667 5272; fax: +1 617 975 5322.

E-mail addresses: boggio@usp.br (P.S. Boggio),

ffregni@bidmc.harvard.edu (F. Fregni).

ing memory [11] in healthy subjects and in patients with major

depression [17]. Similarly, tDCS has been associated with an

improvement in motor learning and working memory in normal

subjects [6,12] and motor performance in stroke patients [5,7].

In tDCS, a weak electric current is applied continuouslybetween

two electrodes positioned on the scalp with the effects depend-

ing on the position and polarity of the electrodes, i.e., whereas

anodal stimulation increases cortical excitability, cathodal stim-

ulation decreases it [18].

Recently Hummel et al. [7] and our group [5] demonstrated

that anodaltDCS of thelesionedprimary motor cortex in patients

with chronic stroke results in an improvement in the distal motor

skill as measured by the Jebsen Taylor Hand Function Test. We

set out to investigate whether similar motor improvement could

be achieved in healthy right-handed subjects. We delivered stim-

ulation to both the dominant and non-dominant hemispheres.

The rationale of testing both hemispheres is that differences in

the use of the dominant hand and non-dominant hand could

0304-3940/$ see front matter 2006 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.neulet.2006.05.051

mailto:boggio@usp.brmailto:ffregni@bidmc.harvard.eduhttp://dx.doi.org/10.1016/j.neulet.2006.05.051http://dx.doi.org/10.1016/j.neulet.2006.05.051mailto:ffregni@bidmc.harvard.edumailto:boggio@usp.br

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P.S. Boggio et al. / Neuroscience Letters 404 (2006) 232236 233

mimic at some extent the differences between the paretic and

non-paretic hands in stroke patients. The asymmetric use of the

non-dominant compared to the dominant hand results in a rela-

tively decreaseddexterityof the non-dominant hand,extensively

demonstrated in the literature [2,24]. This asymmetric motor

skill can be explained not only by decreased use and training of

the hand muscles, but also by the relatively decreased cortical

excitability in the non-dominant motorcortex. Indeed TMS stud-

ies showed that the dominant, compared to the non-dominant,

motor cortex is characterized by having a lower motor thresh-

old, higher motor evoked potential [4] and shorter silent period

[25]. Therefore, tDCS could represent an effective means to

increase the excitability in the non-dominant motor cortex and

thus enhance the motor performance. An additional importance

of this study lies in the fact that tDCS may represent in the future

an important alternative therapy for motor recovery in stroke

patients and therefore this study provides additional evidence

regarding the behavioral motor effects of this technique.

Eight healthy subjects (all females) participated in this study.

The age range was 2226 years (mean of 22.8 years). Left-handed subjects were excluded as the laterality in the motor

hand function detected by neuropsychological tests might not

be present in these subjects [24]. The Edinburgh Handedness

Inventory was used to determine handedness. All subjects were

college students, thus all shared the same level of education.

Subjects gave informed consent and the local Human Subjects

Review Committee (Institute of Psychiatry, University of Sao

Paulo, Sao Paulo, Brazil) approved the study, which was con-

ducted in strict adherence to the Declaration of Helsinki.

Eight subjects participated in experiment 1. In this experi-

ment,each participant underwent two differenttreatments: sham

and active anodal tDCS of primary motor cortex of the non-dominant hand (right hemisphere). Theorder of these conditions

was counterbalancedand randomizedacross subjects.There was

an interval of at least 48 h between each session of tDCS to

minimize carryover effects and contamination of the sham stim-

ulation session by a preceding real tDCS session.

Initially, in order to familiarize subjects with the Jebsen Tay-

lor Hand Function Test, they performed this test 10 times. This

number of practice sessions was sufficient to reach a stable per-

formance as suggested by a previous study [7]. Subjects were

then randomized to receive sham or active tDCS treatment. For

each condition of stimulation, subjects performed the task three

times for the baseline (pre-treatment) evaluation and three times

after the stimulation.Five of the subjects who participated in experiment 1 also

participated in experiment 2. This experiment was similar to

experiment 1, however the left, dominant primary motor cor-

tex was targeted in this experiment. Importantly, there was an

interval period of 6 months between the two experiments, and

therefore subjects performed the same training session of the

Jebsen Taylor Hand Function Test.

Direct current was transferred by a saline-soaked pair of sur-

face sponge electrodes (35 cm2) and delivered by a specially

developed, battery-driven, constant current stimulator (Schnei-

der Electronic, Gleichen, Germany). To stimulate the primary

motor cortex (M1), the anodal electrode was placed over C3 or

C4 (international 10/20 EEG system). The other electrode was

placed over the contralateral supraorbital area. A constant cur-

rent of 1 mA intensity was applied for 20 minthis parameter

of stimulation is safe according to past human studies [8,19,20].

Subjects felt thecurrent as an itching sensation at both electrodes

at the beginning of the stimulation. For the sham stimulation, the

electrodes were placed in the same position; however, the stimu-

lator was turned off after 30 s [7]. In addition, for both conditions

(active and sham stimulation), current intensity was gradually

increased and decreased (ramp up and down) during the period

of 10 s. This procedure blinded subjects to the respective stim-

ulation conditions [18].

The Jebsen Taylor (JTT) Hand Function Test [10] was

designed as a broad measure of hand function and is widely

used by physical and occupational therapists in clinical practice

and clinical trials. Thedetails of this test are described elsewhere

[5,7]. As we were assessing the after-effects of tDCS, subjects

performedJTT immediately beforeand after tDCS. Both at base-

line and immediately after, subjects performed this test three

times (there was no interval between each test). Because thetotal performance time for these three tasks was not superior to

5 min, this was adequate to evaluate the after-effects of tDCS

as a previous study showed that the effects of 13 min of tDCS

on cortical excitability can last up to 90 minutes [21]. A rater

blinded to the experimental and treatment conditions evaluated

subjects performance.

The primary outcome for analysis was change in the total

time of JTT performance. Analyses were done with Statistica

for Windows (version 6.1, USA). The distribution of these data

was assessed using the ShapiroWilk test; homogeneity of vari-

ance was assessed by Levenes test. Because these tests showed

that these data were normally and homogeneously distributed,tests with the assumptions of normal distribution were used.

A repeated measures analysis of variance (ANOVA) was per-

formed to study the main effect of time (pre- and post-tDCS)

and condition (active tDCS and sham tDCS) and the interac-

tion term time condition on total JTT time. We performed

different models for experiments 1 and 2 as the number of sub-

jects was not the same in these two experiments. Finally, we

performed additional models in which the dependent variable

was the time to perform the JTT subtests (cards, small objects,

feeding, checkers, light and heavy cans). For the pre-stimulation

performance, we averaged the three baseline tests, and for the

post-stimulation performance, we averaged the three tests per-

formed post-treatment. We also performed an ANOVA to inves-tigate a possible treatment order effect by comparing subjects

performance between sham tDCS first and active tDCS first.

When appropriate, post hoc comparisons were carried out using

Tukeys HSD test. Furthermore, comparison between baseline

(mean of the three baseline tests) and the last three trials of the

training phase (mean of the last three tests of training period) was

performed using Students t-test. This analysis was performed

for both experiments. Data are reported as mean and standard

deviation if not stated otherwise. Statistical significance refers

to a two-tailed p-value

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234 P.S. Boggio et al. / Neuroscience Letters 404 (2006) 232236

Fig. 1. Motor performance (total execution timein seconds) before and after

sham and active tDCS of the primary motor cortex in the non-dominant hemi-

sphere (trainingphase, baselineand afterstimulation). For the trainingphase, we

show the result of each individual trial (note that there was no interval between

training trials). For baseline and after stimulation tests, results were averaged.

Eachpoint represents meanmotor functionperformance anderror barsrepresent

standard deviation.

underwent training and reached a performance plateau as shown

in Fig. 1. Furthermore, there was no significant difference in

motor performance between the last three sessions of training

and baseline.

A two-way ANOVA with repeated measures on time showed

that the main effect of group was not significant (F1,14 =0.9,

p = 0.36), but there was a significant effect of time (F1,14 = 22.3,

p = 0.0003) and significant interaction effect (F1,14 = 12.6,

p = 0.003). Post hoc comparisons demonstrated that motorperformance after anodal tDCS was significantly improved

(p = 0.0004, mean improvement of 9.41%) when compared to

baseline. There was no significant motor performance change

after sham stimulation (p = 0.84, mean performance change of

1.3%). Fig. 1 shows the results of motor performance during the

training phase and at baseline and post-treatment after sham and

active anodal tDCS (Fig. 2 shows details of the motor perfor-

mance at baseline and post-treatment for the active tDCS group).

Interestingly the results were consistent for four of the sub-

tests of the JTT test, i.e., individual ANOVAs for each subtest

found a significant interaction effect between time (pre- and

Fig. 2. Motor performance (total execution timein seconds) before and after

active tDCS of the primary motor cortex in the non-dominant and dominant

hemisphere (baseline and after stimulationnote that there was no interval

between trials at the baseline or after stimulation). Each point represents mean

motor function performance and error bars represent standard deviation.

post-stimulation) and condition of stimulation for the following

subtests: turning over cards (F=7.7,p = 0.015), picking up small

objects (F= 10.4,p = 0.0062), moving large empty cans (F=8.4,

p = 0.012) and moving large weighted cans (F= 8.7, p = 0.010).

Table 1 shows the performance of each group (anodal and sham

tDCS) in each JTT subtest.

Finally, we tested for an order effect. The motor perfor-

mance was evaluated considering the orderof stimulation(active

and sham tDCS). The result of the repeated measures ANOVA

showed that there was no significant effect of order of stimula-

tion on motor performance (F< 1 for the main term of order).We repeated the same analysis for experiment 2 (domi-

nant hand). Initially we performed a two-way repeated mea-

sures ANOVA in order to test whether the motor perfor-

mance was correlated with stimulation condition and time

(pre- and post-treatment). This analysis disclosed that there

was no significant group effect (F1,8 = 0.27, p = 0.61), time

effect (F1,8 = 0.81, p = 0.39) or interaction (time group) effect

(F1,8 = 0.37 p = 0.56). Indeed the absolute values showed the

lack of effects after active stimulation in this experiment: in the

active group there was a mean improvement in the motor func-

tion of 0.81% only (compared to 9.4% of the non-dominant hand

Table 1

JTT time (csec) for each subtask (experiment 1)

Anodal Sham ANOVA

Pre Post Pre Post F p

Cards* 314 59 277 66 315 65 347 75 7.7 0.015

Small objects* 535 41 500 59 517 39 557 59 10.4 0.006

Feeding 744 215 689 164 821 227 717 137 1.2 0.285

Checkers 318 50 294 49 324 26 340 20 3.8 0.072

Light cans* 383 36 329 48 378 45 374 48 8.4 0.012

Heavy cans* 424 54 373 49 423 57 407 54 8.8 0.010

*

Significant at p < 0.05. Values are meanS.D. for non-dominant hand performance.

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P.S. Boggio et al. / Neuroscience Letters 404 (2006) 232236 235

under the same experimental conditions). Because the results of

experiment 2 showed no significant effect of active tDCS on

motor function, we did not proceed with the post hoc tests and

additional analyses (see Fig. 2 for details).

The main finding of our study was a significant enhancement

of motor performance of the non-dominant hand as indexed by

the Jebsen Taylor Hand Function Test after active, but not sham,

tDCS of the contralateral primary motor cortex. In addition,

active and sham tDCS of the dominant primary motor cortex did

not result in a significant hand motor function improvement. The

motor function enhancement after anodal tDCS of M1 is in line

with other studies that showed an improvement in motor func-

tion and other aspects of cognition induced by tDCS. Nitsche et

al. [22] showed that anodal tDCS improves a serial reaction time

task performance when the primary motor, but not the premotor

or the prefrontal, cortex is stimulated [22]. In two other studies

from the same group, Antal et al. [1] showed that the perfor-

mance in a visuo-motor task is increasedsignificantly in theearly

learning phase during anodal stimulation of M1 and V5 (mid-

dle temporal cortex) and Kincses et al. [12] showed that anodalprefrontal stimulation improves implicit learning (as measured

by a probabilistic classification learning task). Finally, Fregni et

al. [6] showed that working memory enhancement occurs after

anodal tDCS of the dorsolateral prefrontal cortex. This evidence

suggests that anodal tDCS might improve cognitive function

focally, which might be explained by its effects on the neuronal

membrane, i.e., anodal tDCS is associated with a depolarization

of the neural tissue [26] that might facilitate the overall neu-

ral activity of the stimulated area. Indeed, animals studies have

shown that anodal tDCS increases the neural firing rate in the

stimulated area [3].

The results of this investigationshould be compared to similarstudies in stroke patients. Two studies, using the same methodol-

ogy, showedthat anodal stimulation of the affected M1 improves

motor function of theparetic hand [5,7]. Themagnitude of motor

improvement as indexed by the JTT was 6.7% in Fregnis study

and 8.9% in Hummels study, similar to the motor improvement

of 9.4% shown in this study. This finding raises an interesting

hypothesis: perhaps the motor improvement observed in stroke

patients after anodal tDCS is due to the reversal of the dele-

terious effects of the decreased use of the affected hand, as

this is similar to the improvement in the non-dominant hand

in healthy subjects. This hypothesis is also in line with the ther-

apeutic effects of constraint-induced therapy, which improves

motor function by forcing the use of the paretic hand, and inwhich successful treatment is associated with an increase in the

local cortical excitability [15] (mimicking the effects of anodal

tDCS).

The fact that the improvement of the motor function was

obtained in the non-dominant hand, rather than the dominant

hand, needs to be further discussed. Such results suggest that

under-use of one of the hands leads to functional changes in the

non-dominant motor cortex that can contribute to the decreased

dexterity of this hand and that can be reversed partially by facil-

itation of this area by anodal tDCS. In this case, the lack of

effects in the dominant hemisphere might be due to a ceiling

effect: given that this area is already optimally activated, an

additional increase in the excitability by anodal tDCS would not

result in additional behavioral benefits for these subjects. On the

other hand, the relative lack of use of the non-dominant hand

might result in an asymmetric cortical excitability between the

dominant and non-dominant hemisphere (i.e., the non-dominant

M1 showing a decreased excitability compared to the domi-

nant M1) and therefore a focal increase in the motor cortex

excitability of the non-dominant hemisphere might equal the

excitability between both hemispheres, accounting for the motor

enhancement. Interestingly, when the dominant hemisphere is

inhibited using 1-Hz rTMS, its performance decreases to the

level of the non-dominant hemisphere [9]; therefore, indicating

that the increased excitability in the dominant primary motor

cortex is indeed partially responsible for the superior motor per-

formance of the dominant hand. Analogously, a stroke leads to a

decrease of the activity in the lesioned hemisphere and therefore

this decreasedactivity mightrepresent the functionalcomponent

of the motor deficits that can be reversed partially by anodal

tDCS as shown by behavioral [5,7] and neurophysiological [7]

data.In our study, we aimed to explore the impact of the after-

effects of tDCS on motor function. It has been demonstrated

that the weak current delivered by tDCS causes a subthreshold

hyper- or depolarization that results in a prolonged change in

the cortical excitability that outlasts the period of stimulation

[21]. In two elegant studies from the same group, Liebetanz et

al. [14] and Nitsche et al. [23] showed that the after-effects of

tDCS might be associated with a changein thesynaptic strength-

ening due to a modulation of NMDA receptors. Liebetanz et al.

[14] showed that a NMDA-receptor antagonist, dextromethor-

phan, suppresses the after-effects of both anodal and cathodal

DC stimulation on motorcortical excitability, therefore,suggest-ing an association between NMDA receptors and DC-induced

neuroplasticity [14]. Another evidence suggesting that the motor

performance change in our study might have been associated

with changes in the synaptic strengthening comes from a recent

study showing that memantine, a NMDA-antagonist, can block

training-induced (as obtained by repetitive synchronized move-

ment of two limbs) cortex plasticity as indexed by motor output

map changes [27]. Therefore, in light of these previous studies,

further studies should explore whether the behavioral improve-

ment observed in our study can be blocked by NMDA antago-

nists, and thus shed light on the mechanisms of action of tDCS

on motor function modulation.

One can argue, based on our findings, that the differences inthe motor performance change after tDCS between the dominant

and non-dominant hand is due to the parameters of stimulation.

In other words, the current intensity and duration might not have

been strong enough to induce behavioral effects in the dominant

hand; however, we believe that this alternative explanation is

unlikely due to the reasons aforementioned.

Ourfindings show that anodaltDCS of theprimary motor cor-

tex canenhance motor performance of thenon-dominant hand in

healthy subjects. Future studies evaluating the effects of tDCS

coupled with motor training could indeed reveal an approach

of motor function enhancement that might be used in stroke

patients.

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236 P.S. Boggio et al. / Neuroscience Letters 404 (2006) 232236

Acknowledgements

F.F. was supported by a grant within the Harvard Medi-

cal School Scholars in Clinical Science Program (NIH K30

HL04095-03). The authors are thankful to Barbara Bonetti for

the invaluable administrative support and to Naomi Bass Pitskel

for the editorial suggestions.

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