Brain Polarization Enhances the Formation and Retention of Motor Memories

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J Neurophysiol. 2009 July; 102(1): 294301.

Published online 2009 April 22. doi: 10.1152/jn.00184.2009

PMCID: PMC2712265

Brain Polarization Enhances the Formation and Retention of Motor Memories

Joseph M. Galea and Pablo Celnik

Department of Physical Medicine and Rehabilitation, Johns Hopkins Medical Institution, Baltimore, Maryland

Address for reprint requests and other correspondence: P. Celnik, Department of Physical Medicine and Rehabilitation, Johns Hopkins

Medical Institution, 98 North Broadway, Baltimore, MD 21231 (E-mail: [email protected])

Received March 2, 2009; Accepted April 13, 2009.

Copyright 2009, American Physiological Society

AbstractOne of the first steps in the acquisition of a new motor skill is the formation of motor memories. Here

we tested the capacity of transcranial DC stimulation (tDCS) applied over the motor cortex during motor

practice to increase motor memory formation and retention. Nine healthy individuals underwent a

crossover transcranial magnetic stimulation (TMS) study designed to test motor memory formation

resulting from training. Anodal tDCS elicited an increase in the magnitude and duration of motor

memories in a polarity-specific manner, as reflected by changes in the kinematic characteristics of TMS-

evoked movements after anodal, but not cathodal or sham stimulation. This effect was present only

when training and stimulation were associated and mediated by a differential modulation of

corticomotor excitability of the involved muscles. These results indicate that anodal brain polarization

can enhance the initial formation and retention of a new motor memory resulting from training. Theseprocesses may be the underlying mechanisms by which tDCS enhances motor learning.

INTRODUCTION

The ability to learn an unlimited repertoire of motor skills is one of the main characteristics of human

beings. Recent studies have suggested that the primary motor cortex (M1) is crucially involved in this

ability by forming and retaining short-term memory representations of recently practiced movements

(Classen et al. 1998; Hadipour-Niktarash et al. 2007; Molina-Luna et al. 2008; Muellbacher et al. 2002).

In particular, it has been shown that although disruption of M1 activity can interfere with retention of

practiced motor tasks (Hadipour-Niktarash et al. 2007; Muellbacher et al. 2002), enhancing M1

excitability with transcranial DC stimulation can improve it (Reis et al. 2009). However, it is not clearwhether this beneficial effect on retention is mediated by a larger amount of motor memory formation

or changes in retention mechanisms.

One of the initial steps in the acquisition of new complex motor skills is the formation of motor

memories (Classen et al. 1998; Muellbacher et al. 2002). Classen et al. (1998) used transcranial

magnetic stimulation (TMS) over M1 to ascertain how simple motor memories are formed. In this

paradigm, the preferred direction of TMS-evoked thumb movements is measured before and after

performance of motor training. In this manner, it is possible to observe that training results in changes

in the direction of TMS-evoked movements, indicative of formation of new motor memories containing

the kinematic details of the practiced motions retrieved by the magnetic stimulation. This phenomenon

is mediated byN-methyl-D-aspartate (NMDA), muscarinic, adrenergic and GABAergic

neurotransmission (Butefisch et al. 2000; Sawaki et al. 2002b, 2003) and can be enhanced by
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RECORDINGS AND STIMULATION PROCEDURES.

TRANSCRANIAL MAGNETIC STIMULATION.

dopaminergic (Floel et al. 2005a,b) and adrenergic agents (Butefisch et al. 2002; Sawaki et al. 2002a),

D-amphetamine, congruent action observation (Celnik et al. 2006; Stefan et al. 2008), and hebbian-type

noninvasive stimulation (Butefisch et al. 2004).

Transcranial DC stimulation (tDCS) is a noninvasive, painless cortical stimulation technique (Nitsche

and Paulus 2000, 2001; Nitsche et al. 2003a,b, 2005). Whereas anodal tDCS results in increased

cortical excitability without direct neuronal depolarization, cathodal tDCS decreases excitability

(Nitsche and Paulus 2000; Nitsche et al. 2003; Purpura and McMurtry 1965). Interestingly, anodaltDCS appears to have a facilitatory effect on different forms of learning in healthy individuals (Antal et

al. 2004; Floel et al. 2008; Kincses et al. 2004; Nitsche et al. 2003c; Reis et al. 2009) and in stroke

(Hummel et al. 2005) and Parkinson patients (Boggio et al. 2006; for a review see Wu et al. 2007).

However, it is not clearly understood what specific process mediates the enhanced learning when tDCS

is applied during training. For instance, it is possible that the performance improvement described after

learning a motor task under the influence of tDCS is mediated by increased memory formation, stronger

retention of the formed memories, or better recall.Antal et al. (2004) and Nitsche et al. (2003c)

previously showed performance improvements during early learning, which suggests that tDCS may

influence memory formation. In this study, we used a well-established paradigm that assesses the

formation and retention of a motor memory without engaging voluntary recall to test the hypothesis that

anodal tDCS over M1 enhances these processes relative to sham stimulation. In addition, in three

separate controls we determine 1) the polarity specificity of the effects by testing cathodal stimulation, 2)

the longevity of the effects by periodically reassessing the effects of stimulation and training, and3) the

association between motor practice and stimulation by testing the effects of anodal tDCS without

training.

METHODS

Subjects

Nine right-handed (self-assessed) healthy individuals with no history of neurological or psychiatric

conditions (mean SD: 30 9 yr old, six females) participated in the study. All subjects denied the use

of acute or chronic CNS-acting medication, drinking alcohol in the previous 24 h, and reported to have

had 5 h of sleep the previous night. All subjects signed informed consent approved by Johns Hopkins

Medical Institution Institutional Review Board and in accordance with the Declaration of Helsinki.

Experimental design

All subjects participated in two randomly ordered sessions separated by5 days and designed to

evaluate the effect of anodal tDCS on the encoding of motor memories (Fig. 1) (Classen et al. 1998).

Subjects sat comfortably in a chair while the right

forearm was restrained in a semipronated position with a molded cast with the four fingers in a slightlyextended position and the thumb left entirely free. Using a two-dimensional accelerometer (Kistler

Instruments, Amherst, NY) placed on the proximal phalanx of the thumb, movement directions were

determined and calculated from the first peak acceleration vector in both the vertical axis

(extension/flexion) and the horizontal axis (adduction/adduction) (Fig. 1) (Classen et al. 1998).

Electromyographic (EMG) activity was recorded through pairs of disposable electrodes placed over the

right extensor pollicis brevis and right flexor pollicis brevis muscles. EMG signals were recorded,

amplified, and filtered (bandwidth 5 Hz to 1 kHz) with a Viking IVP (Nicolet, Viasys Healthcare). All

signals were sampled at 2 kHz, visually displayed on-line, and stored for off-line analysis using a custom

LabVIEW program (National Instruments, Austin, TX).

Transcranial magnetic stimulation (TMS) was delivered using a

70-mm loop-diameter figure-of-eight coil (Magstim BiStim2, Whitland, South West Wales, UK) placed
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TRANSCRANIAL DC STIMULATION.

EXPERIMENTAL PROCEDURE.

DURATION OF MOTOR MEMORIES.

SPECIFICITY OF POLARITY EFFECTS ON MOTOR TRAINING.

over the left M1 to optimally activate the corticospinal tract and elicit focal isolated and directionally

consistent thumb movements. Using a frameless neuronavigation system (BrainSight, Rogue Research,

Montreal, Quebec, Canada) we coregistered the subjects' heads to a standard magnetic resonance image

and marked this hot spot. We decided to use BrainSight because this is an accurate way to ensure the

TMS coil remains in the same position within the X, Y, and Z directions during and between each

session. Resting motor threshold for the muscle agonist to the training (see following text) was

determined at this position and defined as the minimum TMS intensity that evoked motor-evoked

potentials (MEPs) of 50 V in 5 of 10 trials (Rossini et al. 1994). Muscle relaxation was monitored by

visual feedback of the EMG recording.

Transcranial DC stimulation (tDCS) was delivered through two sponge

electrodes (surface area: 25 cm ) embedded in a saline-soaked solution. Depending on the session, the

anode or cathode was positioned on the marked motor hot spot and the other electrode on the skin

overlying the contralateral supraorbital region. During training, 1-mA anodal tDCS was delivered for

about 30 min in the corresponding session and 30 s in the sham session using a Phoresor Auto

(Model PM850; IOMED, Salt Lake City, UT). At the onset and offset of tDCS, the current was increased

or decreased in a ramplike fashion, a method shown to achieve good blinding level (Gandiga 2006).

The formation of a motor memory was assessed using a previouslydescribed protocol (Butefisch et al. 2000; Celnik et al. 2006; Classen et al. 1998; Stefan et al. 2008). At

the beginning of each session, 65 TMS stimuli were delivered at 0.1 Hz over the hot spot to determine

the baseline TMS-evoked thumb movement direction (Pre; Fig. 1). Subjects subsequently performed

motor training, consisting of voluntary thumb brisk movements paced by an audio metronome at 1 Hz

for 30 min in a direction opposite to the baseline TMS-evoked direction. For example, if the principal

baseline direction was extension and abduction, then subjects were instructed to perform repetitive

flexion and adduction movements (Figs. 1 and 2). The participants were instructed to relax and let the

thumb return to its original position after each motion. This was ensured by monitoring on-line EMG

and acceleration signals and providing verbal feedback when needed. Consistency and accuracy of

training movements were quantified off-line by calculating the angular variance and compoundacceleration of the first peak acceleration vector (Table 1) (Stefan et al. 2008).

In the main experiment, while subjects performed the motor training, one of two interventions were

delivered in separate sessions: 1) anodal tDCSapplied over the active M1 for a total of 30 min and 2)

sham tDCSapplied in an identical manner to the anodal session except that stimulation lasted for only

30 s at the beginning of training.

At the end of each intervention, 65 TMS-evoked thumb movement directions were determined again as

done at baseline for about 11 min [post 1 (p1)]. Then, subjects rested for 10 min and another 65 TMS

pulses were applied [post 2 (p2); Fig. 1].

At the end of each session, subjects reported their alertness, attention, and perceived pain of tDCS using

a self-scored visual analog scale (VAS), where 1 represents poorest attention, maximal fatigue, and

maximal pain and 7 represents maximal attention, least fatigue, and least pain (Table 1) (Stefan et al.

2005).

Controls

To assess the longevity of the effects observed with anodal tDCS, three

subjects that took part in the main experiment were exposed to an additional block of TMS 50 min after

the cessation of anodal tDCS and training (p3).

To determine whether tDCS effects werepolarity specific, three subjects who completed the main experiment underwent a third session where

training was performed under the influence of cathodal tDCS applied over the active M1 as done in the

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COMBINATION OF TRAINING AND TDCS.

TRAINING TARGET ZONE.

TMS-EVOKED MOVEMENT DIRECTION DISTANCE RELATIVE TO TRAINING DIRECTION.

COMPOUND ACCELERATION VECTOR.

CORTICOMOTOR EXCITABILITY.

anodal session.

To test whether stimulation alone could elicit changes in TMS-

evoked movement directions, three additional subjects (two females, mean age 24 3 yr) were tested

using a similar experimental protocol, although they received anodal tDCS for 30 min without

performance of motor training.

Data analysis

We defined a training target zone (TTZ) as a window of 20 centered on the

mean direction of the performed training movements (Butefisch et al. 2000; Celnik et al. 2006; Stefan et

al. 2008). The percentage of TMS-evoked thumb movements falling within the TTZ, the primary

outcome measure, was calculated for pre, p1, and p2.

For each session we

calculated the mean angular direction of the training movements. Then, the angular direction of each

individual TMS-evoked movement was subtracted from this mean value (Classen et al. 1998). For

example, if the mean training direction was 320 and a movement in pre had an angular direction of

150 then the deviation from training would be 170 (Fig. 1). These values were averaged for each

subject for pre, p1, and p2.

The mean magnitude of the first-peak acceleration in the

extension/flexion direction during pre, p1, and p2 was calculated (Stefan et al. 2008). Since the

principal training direction differed across subjects, we inverted the values so that all subjects had an

extension movement within the pre block (Stefan et al. 2008).

We calculated the MEP amplitudes in muscles acting as either agonist or

antagonist of the trained movement direction for each subject. Amplitudes were measured as peak-to-

peak for each individual MEP and then averaged for pre, p1, and p2. Ratios between post and pre

amplitudes for the agonist and antagonist muscles were calculated.

Statistical analysis

Separate repeated-measures ANOVAs (ANOVA ) were used for the percentage of movements falling

in TTZ, deviation from the training direction, and compound acceleration with factors block (pre, p1, p2)

and session (sham, anodal). ANOVA was also used for the MEP ratio with factors muscle (agonist,

antagonist), block (p1, p2), and session (sham, anodal). Measures of baseline corticomotor excitability

(motor threshold, TMS stimulus intensity, and MEPagonist and MEPantagonist amplitudes), attention,

fatigue, pain of tDCS, and training movement kinematics (angular variance and compound acceleration)

were analyzed with separate paired t-tests. When significant differences were found, post hoc analysis

was performed using paired t-test. Data are expressed as means SE and effects were considered

significant ifP 0.05.

RESULTS

Summary

At baseline, TMS-evoked movements were consistent across sessions. Subjects were then trained in the

opposite direction for 30 min (Fig. 2). Both, anodal and sham sessions showed training-induced effects

where the proportion of TMS-evoked movements reflected the practiced movement direction. However,

this effect was more prominent in the anodal session immediately after the training (p1) and lasted

longer (p2) relative to sham (Fig. 2).

Training parameters

Subjects' ratings of attention, fatigue, and pain were comparable across sessions [separate paired t-tests:

RM

RM
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t 0.9,P 0.38; Table 1]. For the sham session five of nine subjects believed they had received real

stimulation and seven of nine subjects felt that way in the anodal session. Motor training kinematics

measured as compound acceleration and angular variance did not differ across sessions [separate paired

t-test: t 1.2,P 0.13; Table 1]. Preceding interventions, motor thresholds, and both MEPantagonist

and MEPagonist amplitudes were comparable across sessions [separate paired t-test: t 1.6,P 0.13;

Table 1].

Effects of tDCS on motor memory formation

ANOVA revealed a significant main effect for block [F = 21.7,P< 0.001], session [F = 16,P

= 0.004], and block session interaction [F = 3.6,P= 0.05] for the percentage of movements

falling within TTZ, the primary outcome measure. Paired t-tests showed that in both sham and anodal

sessions there was a significant increase in the percentage of movements falling in the TTZ from pre to

p1 [from 2 1 to 12 4% in sham, t = 2.9,P= 0.02; and from 2 1 to 17 4% in anodal, t = 7.4,P

< 0.001; Fig. 3A]. However, only in the anodal session was this effect significantly maintained at p2 [11

4%, t = 2.9,P= 0.002; Fig. 3A]. In addition, compared with the sham the anodal session had

significantly more movements falling in the TTZ within p1 [t = 2.6,P= 0.015] and p2 [t = 3.6,P=

0.004].

TMS-evoked movement direction distance relative to training direction

ANOVA revealed a significant main effect for block [F = 23.6,P< 0.001], session [F = 16.8,

P= 0.003], and block session interaction [F = 5.4,P= 0.016]. Post hoc paired t-tests showed that

both sham and anodal sessions had a significant decrease in the relative angular distance from pre to p1

and p2 [sham: pre (146 4) to p1 (112 9) and p2 (128 10), t = 4,P= 0.002, t = 2.3,P= 0.03;

and anodal: pre (150 4) to p1 (83 10) and p2 (98 14), t = 8.4,P< 0.001, t = 4.6,P= 0.001;

Fig. 4A]. However, the TMS-evoked movement directions in the anodal intervention were significantly

closer to the training direction than sham during p1 [t = 3.4,P= 0.005] and p2 [t = 2.7,P= 0.02;

Fig. 4A].

Compound acceleration vector

ANOVA revealed a significant main effect for block [F = 10,P= 0.001], session [F = 5.4,P=

0.05], and block session interaction [F = 6,P= 0.01]. Paired t-tests revealed that in both sham

and anodal sessions there was a significant change in direction of compound acceleration from pre to p1

[from pre (0.36 0.14 m/s ) to p1 (0.06 0.05 m/s ) in sham, t = 2.5,P= 0.02; and from pre (0.42

0.11 m/s ) to p1 (0.19 0.1 m/s ) in anodal, t = 3.6,P= 0.003; Fig. 4B]. However, only in the

anodal session was this effect significantly maintained at p2 [0.12 0.08 m/s , t = 3,P= 0.009;

Fig. 4B]. In addition, there was a significantly greater change in compound acceleration vector in the

anodal session for p1 and p2 relative to sham [t = 2.4,P= 0.02, t = 2.7,P= 0.02, respectively;

Fig. 4B].

Corticomuscular excitability

ANOVA revealed a significant main effect of session [F = 7.1,P= 0.03], block [F = 20,P=

0.002], and muscle [F = 41,P< 0.001] in assessment of MEP amplitudes. In addition, there were

significant interactions between session and muscle [F = 10.2,P= 0.01] and block and muscle

[F = 7,P= 0.03]. Paired t-tests showed that within the sham session there was a significant

difference between the increase of the MEPagonist ratio (post/pre) (1.4 0.15) compared with the

MEPantagonist ratio (1.18 0.07) for p1 only [t = 2.4,P= 0.02; Fig. 5B], whereas in the anodal

session there was a significant difference at p1 [MEPagonist (1.8 0.2), MEPantagonist (1.14 0.16),

t = 5.5,P= 0.002] and p2 measures] MEPagonist (1.38 0.17), MEPantagonist (0.93 0.11), t =

2.8,P= 0.04; Fig. 5B]. In addition, relative to sham the anodal session showed a significantly greater

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increase in the MEPagonist ratio for p1 [t = 2,P= 0.05] and p2 [t = 2,P= 0.05].

Control results

Only the anodal group showed a clear training effect during p2, suggesting that the motor memory had

been retained for a longer period (~30 min). To test whether this effect was still present 50 min after the

cessation of training, three subjects were given an additional block of TMS (p3, Fig. 3B). The percentage

of movements falling in the TTZ were not significantly different between pre and p3 [2.2 2 and 3 1%,

respectively; paired t-test: t = 0.6,P= 0.6]. Similarly, at p3 there were no significant differences in

MEPagonist and MEPantagonist ratios [1.1 0.03 and 0.9 0.08 mV, respectively; paired t-test: t =

2.1,P= 0.16], indicating a return to similar excitability to the pre measure.

To determine whether the previously described anodal tDCS effects were polarity specific, three subjects

participated in a third session in which cathodal stimulation was applied over M1 during training. Here,

the percentage of movements falling in the TTZ were not significantly different from sham stimulation

in either p1 or p2 [cathodal: 10.4 0.6 and 2.1 0.6%, respectively, ANOVA session:F = 0.3,P

= 0.3; block:F = 53,P= 0.001; session blockF = 0.6P= 0.6; Fig. 3C]. MEP ratios were also

statistically similar across sham and cathodal sessions for p1 [MEPagonist (1.39 0.03), MEPantagonist

(1.1 0.09)] and p2 measures [MEPagonist (1.0 0.04), MEPantagonist (1.0 0.1); ANOVA :session:F = 0.3,P= 0.66; block:F = 23,P= 0.04; muscle:F = 50,P= 0.019; all

interactions:F 5.6,P 0.14].

Finally, to determine whether anodal tDCS without training could elicit changes in TMS-evoked

movement directions we studied an additional group of three subjects. In this group there was no

significant difference in the percentage of movements falling in the TTZ between pre (1 0.7%) and p1

[1 0.5%, paired t-test: t = 0.5,P= 0.7; Fig. 3D]. Similarly, there was no significant difference

between MEPagonist and MEPantagonist muscle ratios [1.09 0.02 and 1.1 0.07, respectively; paired

t-test: t = 0.3,P= 0.8].

DISCUSSION

The main finding of the present study was that anodal transcranial DC stimulation (tDCS) over the

primary motor cortex, engaged in generating the training movements, enhanced the encoding and

retention of motor memories. This effect was reflected by1) changes in all kinematic measures

(movements falling in the training zone, angular differences, and compound muscle accelerations), 2)

longer-lasting effects relative to training alone,3) the required association of training and stimulation,

and 4) the polarity specificity.

Previous studies have shown that performing simple motor training results in the formation of motor

memories containing kinematic details of the practiced motions (Butefisch et al. 2002, 2004; Celnik et

al. 2006; Classen et al. 1998; Floel et al. 2005a,b; Stefan et al. 2008). Consistent with these, we foundthat motor training with sham tDCS increased the probability of TMS-evoked movements falling in the

TTZ, decreased the net TMS-evoked movement direction distance relative to the training direction, and

changed toward the direction of the practiced movements the net acceleration of all TMS-evoked thumb

movements. However, when the same group of participants performed the motor training under the

influence of anodal tDCS they experienced larger gains in all measures in p1 and maintained the effects

into p2. These findings appear to be polarity specific, since training during cathodal tDCS resulted in

effects similar to those during training with sham and required the association of physical practice with

anodal stimulation because tDCS alone did not result in any kinematic change.

Since subjects performing the training combined with anodal tDCS have persistence of the effects 30

min after the completion of training (p2)longer motor memory retentionwe decided to investigatethe longevity of the motor memory formed. With this aim, we retested a subgroup of participants 50 min

(8) (8)

(2)

(2)

RM: (1,2)

(1,2) (2,4)

RM(1,2) (1,2) (1,2)

(1,2)

(2)

(2)
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after the cessation of training and stimulation (p3). Across all measures, performance returned to

pretraining values, indicating that any changes within the motor cortex representation had reverted to

baseline. This type of motor memory encoding enhancement has been previously observed with D-

amphetamine (Butefisch et al. 2001; Sawaki et al. 2002a), hebbian-type TMS stimulation during

training (Butefisch et al. 2004), and congruent action observation (Celnik et al. 2006; Stefan et al.

2008). Of note, because ratings of attention, fatigue, and pain of the tDCS were similar across sessions,

it is unlikely that these results could directly be explained by unspecific psychological differences across

sessions.

Similar to previous studies, we found that training resulted in a specific increase in the excitability of the

training muscles (Butefisch et al. 2004; Celnik et al. 2006; Classen et al. 1998). Interestingly, anodal

tDCS increased the excitability of the muscle agonist to the training without a similar change in the

antagonist muscle, suggesting that tDCS had a training-specific effect rather than a global increase in

corticomotor excitability. These results, together with the findings that the no-training plus tDCS

control group had minimal changes in the excitability of either muscle, suggest that the effect of tDCS on

cortical excitability is more prominent on neuronal populations engaged in motor actions.

Cathodal tDCS, although known to reduce the excitability of the motor cortex at rest (Nitsche et al.

2003a; Purpura and McMurtry 1965), in the present study did not influence corticomotor excitabilityrelative to sham. It is possible that this lack of effect was due to the performance of motor training,

which elicits increased excitability (Butefisch et al. 2002, 2004; Celnik et al. 2006; Classen et al. 1998;

Floel et al. 2005a,b; Stefan et al. 2008), thus overiding or masking the effect of cathodal tDCS.

The mechanism behind the current enhancement of motor memory encoding through anodal tDCS is

unknown. However, this form of motor memory encoding is influenced by NMDA-receptor function

(Butefisch et al. 2000) and it has been indirectly shown that within humans the mechanisms underlying

the effect of tDCS involves the modulation of NMDA receptors (Nitsche et al. 2003d). Therefore it is

plausible that the observed results are due to anodal tDCS increasing the efficacy of NMDA-receptor

function, possibly through an increase in intracellular calcium concentration (Bennett 2000).

A previous study by Rosenkranz et al. (2000) explored the effect of tDCS during a paradigm identical to

that of the present study by applying tDCS only during the last 10 min of training. The authors found

that both anodal and cathodal tDCS had a negative effect on the formation and retention of a motor

memory. We believe that the stark difference in results may be due to the differing tDCS protocols.

Work byIezzi et al. (2008) and Siebner et al. (2004) have shown that a TMS protocol can be either

facilitatory or inhibitory, depending on the prior state of the system. It is possible that applying tDCS

after 20 min of training has an effect different from that of tDCS at the onset of training due to the

preconditioning of the motor cortex resulting from training. Alternatively, it is possible that the lack of

findings in the Rosenkranz investigation was due to a shorter stimulation period.

Noninvasive cortical stimulation with tDCS elicits behavioral gains during implicit motor learning

(Nitsche et al. 2003d), visuomotor processing (Antal et al. 2004; Reis et al. 2009), and probabilistic

learning (Kincses et al. 2004) in healthy volunteers. In addition, it has been shown to improve motor

performance in stroke (Hummel et al. 2005) and Parkinson disease patients (Boggio et al. 2006). More

recently, Reis et al. (2009) reported that tDCS in association with training enhances learning of a novel

skill by modulation of short-term retention. The present study supports these observations and suggests

that anodal tDCS enhances both the process of encoding and retention of simple motor memories. In

addition, we can rule out changes in memory-recall mechanisms since the behavioral measures obtained

with the TMS paradigm used here do not require voluntary engagement of recall processes.

One of the initial steps in the development of more complex skills is the encoding of motor memories

(Classen et al. 1998; Molina-Luna et al. 2008). It has been suggested that the motor cortex may encode

the memory trace of a skill (Monfils et al. 2005) because changes in corticomotor organization occur
http://www.ncbi.nlm.nih.gov/pubmed/16151047http://www.ncbi.nlm.nih.gov/pubmed/18329289http://www.ncbi.nlm.nih.gov/pubmed/9463469http://www.ncbi.nlm.nih.gov/pubmed/19164589http://www.ncbi.nlm.nih.gov/pubmed/17079967http://www.ncbi.nlm.nih.gov/pubmed/15634731http://www.ncbi.nlm.nih.gov/pubmed/14615081http://www.ncbi.nlm.nih.gov/pubmed/19164589http://www.ncbi.nlm.nih.gov/pubmed/15147322http://www.ncbi.nlm.nih.gov/pubmed/12803972http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712265/?report=printable#r40http://www.ncbi.nlm.nih.gov/pubmed/18753328http://www.ncbi.nlm.nih.gov/pubmed/12803972http://www.ncbi.nlm.nih.gov/pubmed/10716702http://www.ncbi.nlm.nih.gov/pubmed/18279325http://www.ncbi.nlm.nih.gov/pubmed/16087920http://www.ncbi.nlm.nih.gov/pubmed/15984008http://www.ncbi.nlm.nih.gov/pubmed/9463469http://www.ncbi.nlm.nih.gov/pubmed/16125417http://www.ncbi.nlm.nih.gov/pubmed/14711974http://www.ncbi.nlm.nih.gov/pubmed/11782985http://www.ncbi.nlm.nih.gov/pubmed/14244793http://www.ncbi.nlm.nih.gov/pubmed/12949224http://www.ncbi.nlm.nih.gov/pubmed/9463469http://www.ncbi.nlm.nih.gov/pubmed/16125417http://www.ncbi.nlm.nih.gov/pubmed/14711974http://www.ncbi.nlm.nih.gov/pubmed/18279325http://www.ncbi.nlm.nih.gov/pubmed/16125417http://www.ncbi.nlm.nih.gov/pubmed/14711974http://www.ncbi.nlm.nih.gov/pubmed/11784739


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during training (Karni et al. 1995; Kleim et al. 2004; Nudo et al. 1996a,b,c) and skill learning is

associated with an enlargement of representations of trained body parts (Pascual-Leone et al. 1995).

Therefore this study, showing that anodal tDCS over M1 enhances the motor memory formed after

simple repetitive practice, may provide evidence as to how this form of stimulation results in the

behavioral gains observed in previous studies (Antal et al. 2004; Kincses et al. 2004; Nitsche et al.

2003d; Reis et al. 2009).

In summary, we showed that anodal tDCS enhances the effects of simple repetitive training on theformation and retention of motor memories. This effect was polarity specific, relied on the interaction

between motor training and tDCS, and lasted longer than performance of training without stimulation.

The observed changes in the motor cortex representation may play an important role in the acquisition

of more complex skills. The current results provide a rationale for the possible mechanism that may

underlie the behavioral gains observed with the application of tDCS in previous studies. It also supports

the view that such noninvasive cortical stimulation can be a useful tool in the rehabilitation of patients

with brain damage.

GRANTS

This work was supported by National Institute of Child Health and Human Development Grants R01HD-053793 and R21 HD-060169.

REFERENCES

Antal A, Nitsche MA, Kincses TZ, Kruse W, Hoffmann KP, Paulus W. Facilitation of visuo-motor

learning by transcranial direct current stimulation of the motor and extrastriate visual areas in

humans. Eur J Neurosci 19: 28882892, 2004. [PubMed: 15147322]

Boggio PS, Alonso-Alonso M, Mansur CG, Rigonatti SP, Schlaug G, Pascual-Leone A, Fregni F. Hand

function improvement with low-frequency repetitive transcranial magnetic stimulation of the

unaffected hemisphere in a severe case of stroke. Am J Phys Med Rehabil 85: 927930, 2006.

[PubMed: 17079967]Butefisch CM, Davis BC, Sawaki L, Waldvogel D, Classen J, Kopylev L, Cohen LG. Modulation of use-

dependent plasticity by d-amphetamine. Ann Neurol 51: 5968, 2002. [PubMed: 11782985]

Butefisch CM, Davis BC, Wise SP, Sawaki L, Kopylev L, Classen J, Cohen LG. Mechanisms of use-

dependent plasticity in the human motor cortex. Proc Natl Acad Sci USA 97: 36613665, 2000.

[PMCID: PMC16296] [PubMed: 10716702]

Butefisch CM, Khurana V, Kopylev L, Cohen LG. Enhancing encoding of a motor memory in the

primary motor cortex by cortical stimulation. J Neurophysiol 91: 21102116, 2004.

[PubMed: 14711974]

Celnik P, Stefan K, Hummel F, Duque J, Classen J, Cohen LG. Encoding a motor memory in the

older adult by action observation. Neuroimage 29: 677684, 2006. [PubMed: 16125417]Classen J, Liepert J, Wise SP, Hallett M, Cohen LG. Rapid plasticity of human cortical movement

representation induced by practice. J Neurophysiol 79: 11171123, 1998. [PubMed: 9463469]

Floel A, Breitenstein C, Hummel F, Celnik P, Gingert C, Sawaki L, Knecht S, Cohen LG.

Dopaminergic influences on formation of a motor memory. Ann Neurol 58: 121130, 2005a.

[PubMed: 15984008]

Floel A, Hummel F, Breitenstein C, Knecht S, Cohen LG. Dopaminergic effects on encoding of a

motor memory in chronic stroke. Neurology 65: 472474, 2005b. [PubMed: 16087920]

Floel A, Rosser N, Michka O, Knecht S, Breitenstein C. Noninvasive brain stimulation improves

language learning. J Cogn Neurosci 20: 14151422, 2008. [PubMed: 18303984]

Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blindsham-controlled clinical studies in brain stimulation. Clin Neurophysiol 117: 845850, 2006.

[PubMed: 16427357]
http://www.ncbi.nlm.nih.gov/pubmed/19164589http://www.ncbi.nlm.nih.gov/pubmed/12803972http://www.ncbi.nlm.nih.gov/pubmed/14615081http://www.ncbi.nlm.nih.gov/pubmed/15147322http://www.ncbi.nlm.nih.gov/pubmed/7500130http://www.ncbi.nlm.nih.gov/pubmed/8650578http://www.ncbi.nlm.nih.gov/pubmed/8551360http://www.ncbi.nlm.nih.gov/pubmed/14736848http://www.ncbi.nlm.nih.gov/pubmed/7675082


9/15



Hadipour-Niktarash A, Lee CK, Desmond JE, Shadmehr R. Impairment of retention but not

acquisition of a visuomotor skill through time-dependent disruption of primary motor cortex. J

Neurosci 27: 1341313419, 2007. [PubMed: 18057199]

Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical

stimulation on skilled motor function in chronic stroke. Brain 128: 490499, 2005.

[PubMed: 15634731]

Iezzi E, Conte A, Suppa A, Agostino R, Dinapoli L, Scontrini A, Berardelli A. Phasic voluntary

movements reverse the aftereffects of subsequent theta-burst stimulation in humans. J

Neurophysiol 100: 20702076, 2008. [PubMed: 18753328]

Karni A, Meyer G, Jezzard P, Adams MM, Turner R, Ungerleider LG. Functional MRI evidence for

adult motor cortex plasticity during motor skill learning. Nature 377: 155158, 1995.

[PubMed: 7675082]

Kincses TZ, Antal A, Nitsche MA, Bartfai O, Paulus W. Facilitation of probabilistic classification

learning by transcranial direct current stimulation of the prefrontal cortex in the human.

Neuropsychologia 42: 113117, 2004. [PubMed: 14615081]

Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, Remple M. Cortical synaptogenesis

and motor map reorganization occur during late, but not early, phase of motor skill learning. J

Neurosci 24: 628633, 2004. [PubMed: 14736848]Molina-Luna K, Hertler B, Buitrago MM, Luft AR. Motor learning transiently changes cortical

somatotopy. Neuroimage 40: 17481754, 2008. [PubMed: 18329289]

Monfils MH, Plautz EJ, Kleim JA. In search of the motor engram: motor map plasticity as a

mechanism for encoding motor experience. Neuroscientist 11: 471483, 2005.

[PubMed: 16151047]

Muellbacher W, Ziemann U, Wissel J, Dang N, Kofler M, Facchini S, Boroojerdi B, Poewe W, Hallett

M. Early consolidation in human primary motor cortex. Nature 415: 640644, 2002.

[PubMed: 11807497]

Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, Henning S, Tergau F, Paulus

W. Pharmacological modulation of cortical excitability shifts induced by transcranial directcurrent stimulation in humans. J Physiol 553: 293301, 2003a. [PMCID: PMC2343495]

[PubMed: 12949224]

Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by

weak direct current stimulation: technical, safety and functional aspects. Suppl Clin Neurophysiol

56: 255276, 2003b. [PubMed: 14677403]

Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct

current stimulation (tDCS) in humans. Clin Neurophysiol 114: 22202222; author reply 2222

2223, 2003c. [PubMed: 14580622]

Nitsche MA, Niehaus L, Hoffmann KT, Hengst S, Liebetanz D, Paulus W, Meyer BU. MRI study of

human brain exposed to weak direct current stimulation of the frontal cortex. Clin Neurophysiol115: 24192423, 2004. [PubMed: 15351385]

Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial

direct current stimulation. J Physiol 527: 633639, 2000. [PMCID: PMC2270099]

[PubMed: 10990547]

Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex

stimulation in humans. Neurology 57: 18991901, 2001. [PubMed: 11723286]

Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F. Facilitation of

implicit motor learning by weak transcranial direct current stimulation of the primary motor

cortex in the human. J Cogn Neurosci 15: 619626, 2003d. [PubMed: 12803972]

Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, Nitsche MS, Fricke K, Liebetanz D, LangN, Antal A, Paulus W, Tergau F. Modulating parameters of excitability during and after

transcranial direct current stimulation of the human motor cortex. J Physiol 568: 291303, 2005.


10/15



[PMCID: PMC1474757] [PubMed: 16002441]

Nudo RJ, Milliken GW. Reorganization of movement representations in primary motor cortex

following focal ischemic infarcts in adult squirrel monkeys. J Neurophysiol 75: 21442149, 1996.

[PubMed: 8734610]

Nudo RJ, Milliken GW, Jenkins WM, Merzenich MM. Use-dependent alterations of movement

representations in primary motor cortex of adult squirrel monkeys. J Neurosci 16: 785807,

1996a. [PubMed: 8551360]

Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative

training on motor recovery after ischemic infarct. Science 272: 17911794, 1996b.

[PubMed: 8650578]

Pascual-Leone A, Nguyet D, Cohen LG, Brasil-Neto JP, Cammarota A, Hallett M. Modulation of

muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine

motor skills. J Neurophysiol 74: 10371045, 1995. [PubMed: 7500130]

Purpura DP, McMurtry JG. Intracellular activities and evoked potential changes during polarization

of motor cortex. J Neurophysiol 28: 166185, 1965. [PubMed: 14244793]

Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW.

Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an

effect on consolidation. Proc Natl Acad Sci USA 106: 15901595, 2009. [PMCID: PMC2635787][PubMed: 19164589]

Rosenkranz K, Nitsche MA, Tergau F, Paulus W. Diminution of training-induced transient motor

cortex plasticity by weak transcranial direct current stimulation in the human. Neurosci Lett 15:

6163, 2009.

Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M,

Katayama Y, Lucking CH, Maertens de Noordhout AL, Marsden CD, Murray NMF, Rothwell JC,

Swash M, Tomberg C. Non-invasive electrical and magnetic stimulation of the brain, spinal cord

and roots: basic principles and procedures for routine clinical application. Report of an IFCN

committee. Electroencephalogr Clin Neurophysiol 91: 7992, 1994. [PubMed: 7519144]

Sawaki L, Boroojerdi B, Kaelin-Lang A, Burstein AH, Butefisch CM, Kopylev L, Davis B, Cohen LG.Cholinergic influences on use-dependent plasticity. J Neurophysiol 87: 166171, 2002a.

[PubMed: 11784739]

Sawaki L, Cohen LG, Classen J, Davis BC, Butefisch CM. Enhancement of use-dependent plasticity

by D-amphetamine. Neurology 59: 12621264, 2002b. [PubMed: 12391362]

Sawaki L, Werhahn KJ, Barco R, Kopylev L, Cohen LG. Effect of an alpha(1)-adrenergic blocker on

plasticity elicited by motor training. Exp Brain Res 148: 504508, 2003. [PubMed: 12582834]

Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC. Preconditioning of

low-frequency repetitive transcranial magnetic stimulation with transcranial direct current

stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci 31: 3379

3385, 2004.Stefan K, Classen J, Celnik P, Cohen LG. Concurrent action observation modulates practice-induced

motor memory formation. Eur J Neurosci 27: 730738, 2008. [PubMed: 18279325]

Wu AD Functional neuroimaging and repetitive transcranial magnetic stimulation in Parkinson's

disease. Rev Neurol Dis 4: 19, 2007. [PubMed: 17514152]

Figures and Tables

FIG. 1.


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Schematic representation of the main experiment setup.A: pre. Transcranial magnetic stimulation

(TMS)evoked movement directions were derived from the first-peak acceleration in the 2 major axes ofthe movement (extension/flexion and abduction/adduction) measured by an accelerometer mounted on

the proximal phalanx of the thumb. Black arrows indicate the direction of individual TMS-evoked

thumb movements (in this case extension and abduction).B: motor training. Pre was followed in 2

separate sessions randomly ordered by 30 min of motor training with either sham or anodal transcranial

DC stimulation (tDCS) being applied over the left primary motor cortex (M1). Voluntary thumb

movements were performed in a direction opposite to the baseline TMS-evoked movement direction (in

this case: flexion and adduction). C: post 1 (p1). The direction of TMS-evoked thumb movements was

determined as previously measured in pre.D: post 2 (p2). The subjects rested for 10 min and the

direction of TMS-evoked thumb movements was again determined.

FIG. 2.

Intervention-dependent changes in TMS-evoked thumb movement directions in a representative

subject. Each line represents the first-peak acceleration direction vector of a single thumb movement.The pre block is characterized by predominantly extension/adduction movement directions in both

sessions.A: after motor training with anodal tDCS the direction of TMS-evoked thumb movements (p1)


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changed to a direction similar to training (flexion/abduction). This was partially maintained in p2.B:

after training with sham tDCS the direction of TMS-evoked thumb movements within p1 did not have

such a dramatic change with only a small proportion of movements moving in a direction similar to

motor training. For p2 all movements were in a direction similar to the pre block.

FIG. 3.

Percentage of movements falling in the training target zone (pTTZ).A: with anodal tDCS applied during

training there was a significant increase in movements falling within the TTZ during p1 and p2.

Asterisks denoteP 0.02.B: 50 min after the cessation of anodal tDCS (p3) TMS-evoked movement

directions returned to premotor training values (n = 3). C: TMS-evoked movement directions were

similar between sham and cathodal sessions at p1 and p2 times (n = 3).D: application of anodal tDCS

for 30 min without motor training did not elicit changes in pTTZ. Data are means SE.

FIG. 4.


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Angular distance and compound acceleration of TMS-evoked movements.A: angular distance of TMS-

evoked movements relative to training during pre, p1, and p2. In comparison to sham, anodal tDCS led

to a greater reduction in the angular distance between training movements and those evoked by TMS at

p1 and p2 times. Please note that at pre, both sessions have similar angular difference from the trained

direction.B: average compound acceleration during pre, p1, and p2. Anodal tDCS led to a greater change

in direction of compound acceleration during p1 and p2 relative to sham. Asterisks,P

0.03. Data aremeans SE.

FIG. 5.


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Corticomotor excitability, measured by the motor-evoked potential (MEP) amplitude for the agonist and

antagonist muscles involved in motor training.A: changes in the MEP amplitude recorded from the

training antagonist (closed squares) and agonist (open diamonds) muscles. MEP amplitudes increasedwith both sham and anodal tDCS.B: MEP amplitude ratio (post/pre) significantly increased in the

MEPagonist muscle compared with the MEPantagonist during p1 for both sham and anodal tDCS. For

anodal tDCS this difference was maintained during p2. For both p1 and p2, anodal tDCS resulted in a

greater increase in the MEPagonist ratio. Asterisks,P 0.05. Data are means SE.

TABLE 1.

Baseline measures

Parameter Sham Anodal Paired t-Test: Sham Anodal

A. Psychological measures

Attention, VAS 4.7 0.4 4.6 0.4 P= 0.5, t= 0.7

Fatigue, VAS 2.3 0.6 2.8 0.7 P= 0.5, t= 0.6

Pain, VAS 1.4 0.2 2.0 0.6 P= 0.38, t= 0.9

B. Motor training kinematics

Compound acceleration, m/s 1.07 0.13 1.06 0.23 P= 0.6, t= 0.5

Angular variance, deg 17.2 2.0 21.0 3.0 P= 0.26, t= 1.2

C. Measures of corticomotor excitability preceding interventions

Motor threshold (agonist muscle), % 45.0 2.0 43.0 2.0 P= 0.13, t= 1.6

MEPantagonist, mV 2.9 0.7 3.1 0.6 P= 0.9, t= 0.14

MEPagonist, mV 1.3 0.4 1.4 0.4 P= 0.9, t= 0.05

2


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Psychological measures. Values (meansSE) depict subject's choice in a visual analog scale (VAS),

where 1 represents poorest attention, maximal fatigue and pain, and 7 represents maximal attention,

least fatigue, and least pain.Motor training kinematics. Units (meansSE) are in meters per second

squared for compound acceleration and degrees for angular variance.Measures of corticomotor

excitability preceding interventions. Units (meansSE) are the percentage of stimulator's output for

motor threshold and millivolts for MEP amplitudes elicited in muscles acting as antagonist and agonist

to the trained thumb movements.Pand tvalues originate from paired t-tests performed on the sham

and anodal sessions.

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Brain Polarization Enhances the Formation and Retention of Motor Memories