Authors: Stephanie S.Y. Au-Yeung, PhD Juliana Wang, MSc Ye Chen, MSc Eldrich Chua, MSc
Stroke
Affiliations: From the Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.
Correspondence: All correspondence and requests for reprints should be addressed to: Stephanie S.Y. Au-Yeung, PhD, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
ORIGINAL RESEARCH ARTICLE
Transcranial Direct Current Stimulation to Primary Motor Area Improves Hand Dexterity and Selective Attention in Chronic Stroke
Disclosures: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
0894-9115/14/9312-1057 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000127
ABSTRACT Au-Yeung SSY, Wang J, Chen Y, Chua E: Transcranial direct current stimulation to primary motor area improves hand dexterity and selective attention in chronic stroke. Am J Phys Med Rehabil 2014;93:1057Y1064.
Objective: The aim of this study was to determine whether transcranial direct current stimulation (tDCS) applied to the primary motor hand area modulates hand dexterity and selective attention after stroke. Design: This study was a double-blind, placebo-controlled, randomized crossover trial involving subjects with chronic stroke. Ten stroke survivors with some pinch strength in the paretic hand received three different tDCS interventions assigned in random order in separate sessionsVanodal tDCS targeting the primary motor area of the lesioned hemisphere (M1lesioned), cathodal tDCS applied to the contralateral hemisphere (M1nonlesioned), and sham tDCSVeach for 20 mins. The primary outcome measures were Purdue pegboard test scores for hand dexterity and response time in the color-word Stroop test for selective attention. Pinch strength of the paretic hand was the secondary outcome.
Results: Cathodal tDCS to M1nonlesioned significantly improved affected hand dexterity (by 1.1 points on the Purdue pegboard unimanual test, P = 0.014) and selective attention (0.6 secs faster response time on the level 3 Stroop interference test for response inhibition, P = 0.017), but not pinch strength. The outcomes were not improved with anodal tDCS to M1lesioned or sham tDCS.
Conclusions: Twenty minutes of cathodal tDCS to M1nonlesioned can promote both paretic hand dexterity and selective attention in people with chronic stroke. Key Words:
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Transcranial Direct Current Stimulation, Stroke, Dexterity, Selective Attention
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any stroke survivors experience one or more movement-related impairments and activity limitations. Cognitive decline is also associated with stroke but receives little attention during standard stroke rehabilitation. The cognitive domains most commonly involved after stroke are attention, orientation, language, and memory.1 The prevalence of dementia within the first year after stroke is estimated to be 10% after a first stroke and 30% after a recurrent stroke.2 It has been noted that stroke survivors without dementia also demonstrate poorer attention and executive function compared with healthy elderly controls.1 Transcranial direct current stimulation (tDCS) has been reported as a promising treatment for promoting motor recovery after stroke.3 tDCS is a form of noninvasive brain stimulation that delivers weak direct current via electrodes on the scalp to the underlying brain tissue to alter membrane excitability.4 The anode and cathode are placed on the scalp directly over the target brain region.4 The direct current enhances the conductance of voltage-gated sodium and calcium channels to induce subthreshold membrane depolarization of neuronal structures near the anode.5 The depolarization improves N-methyl-D-aspartate (NMDA) receptor efficacy and increases postsynaptic calcium levels.5 The increased membrane excitability also leads to a reduction in the level of an enzyme responsible for the production of gamma-aminobutyric acid (GABA), thereby reducing GABA-ergic synaptic activity.6 Both NMDA and GABA mediate long-term potentiation, a process involved in synaptic plasticity.7 The increase in membrane excitability and long-term potentiation explains how anodal tDCS (a-tDCS) may promote brain function in the target region. Near the cathode, in contrast, sodium and calcium channel conductance is reduced, resulting in membrane hyperpolarization and decreased NMDA receptor activity.5 In addition, reduced glutamine activity leads to less synthesis of the excitatory neurotransmitter glutamate,6 and the reduction can contribute to long-term depression.8 tDCS as a therapy for motor function after stroke involves applying the active electrode on the scalp over the target primary motor cortex (M1) with the reference electrode over the contralateral supraorbital region.4 This arrangement delivers a weak direct current through M1, but because the reference electrode is not completely inert,4 the current also passes through the prefrontal region, a brain region associated with cognitive functioning.9 It has been reported that a-tDCS applied over the dorsolateral prefrontal cortex can improve attention
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deficit in patients with stroke,10 but it is not currently known whether tDCS targeting M1 can also modulate cognitive functioning, particularly attention, along with its expected motor effects. tDCS studies on motor functions after stroke commonly adopted anodal or cathodal stimulation targeting, respectively, M1 of the hemisphere with stroke lesion and the contralateral nonlesioned hemisphere.11 The outcomes evaluated have focused on movements in the paretic limbs.12Y14 With the proximity of the frontal cortex to M1 and the current flow between the two electrodes during tDCS, it is plausible that tDCS targeting M1 might modulate cognitive as well as motor functions. This study was therefore designed to investigate the effects of anodal and cathodal tDCS (c-tDCS) on hand dexterity and selective attention in stroke survivors.
METHODS Design This study was a double-blind, three-arm crossover, randomized, controlled trial conducted in a university laboratory from February to April 2013. The university’s human subjects ethics subcommittee approved the study protocols.
Subjects Ten community-dwelling stroke survivors were recruited using convenience sampling from two patient self-help groups for stroke. The candidates were screened using telephone interviews. Those included were younger than 80 yrs, had experienced a single stroke more than a year previously, demonstrated weakness in the hand contralateral to the cerebral hemisphere with stroke, and could perform a pincer grip with the index finger. Those excluded were either illiterate in Chinese, had a history of neurologic disorders other than stroke (particularly epilepsy or depression), had metal implant in the brain, had musculoskeletal pathology affecting movements in the upper limbs, had aphasia, or scored less than 18 on the Mini-Mental State Examination, which indicated moderate-to-severe cognitive impairment.15 All subjects gave their informed consent in writing in accordance with the Declaration of Helsinki before the experiments.
Procedure Each subject attended three treatment sessions with a washout period of at least 5 days between sessions. All of the subjects received a-tDCS, c-tDCS, and sham tDCS (sham), one in each of the three sessions they attended. The sequence was determined
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in advance for each subject by drawing lots from an envelope. The distribution of subjects to the three stimulation conditions in each session is presented in Table 1. Two other investigators (J.W. and E.C.) who were blinded to the allocated tDCS conditions then assessed the baseline motor status of the subjects’ paretic upper limb using the Composite Spasticity Scale16 for muscle tone, Fugl-Meyer Assessment for sensorimotor impairment,17 and the Action Research Arm Test18 for functional ability. tDCS was delivered using a dual-channel iontophoresis system (Ionto; Chattanooga Medical Supply, Chattanooga, TN) whose carbon electrodes (size, 35 cm2) were covered with saline-soaked sponges. To target M1, which controls finger movements, the anode was positioned on the scalp over C3/C4 (International 10/20 Electroencephalogram System) of the hemisphere affected by the stroke. This will be designated as M1lesioned. The cathode was placed over the contralateral supraorbital area at the forehead. The leads were connected to channel 1 of the tDCS machine. On the M1 of the nonlesioned hemisphere (M1nonlesioned), the cathode was placed over the C3/C4 location; and the anode, over the contralateral supraorbital area. The leads of this pair of electrodes were connected to channel 2 of the machine. All four electrodes were secured using straps to ensure maximal skin contact. It was the third investigator (C.Y.) who set the tDCS parameters for both channels and operated the machine behind the subject throughout the experimental procedure. This ensured that the subject was blinded to the designated tDCS condition for the session. For all conditions, both channels of the
TABLE 1 Results of randomization of subjects to the three tDCS protocols in each session tDCS Protocol Subject
Session 1
Session 2
Session 3
1 Cathodal Sham Anodal 2 Cathodal Anodal Sham 3 Sham Anodal Cathodal 4 Anodal Cathodal Sham 5 Sham Cathodal Anodal 6 Cathodal Sham Anodal 7 Anodal Sham Cathodal 8 Cathodal Sham Anodal 9 Anodal Cathodal Sham 10 Cathodal Anodal Sham Summary Three a-tDCS Three a-tDCS Four a-tDCS Five c-tDCS Three c-tDCS Two c-tDCS Two sham Four sham Four sham
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machine were initially switched on, and the current was set to ramp up to an intensity of 1 mA. The subjects would usually feel a mild tingling sensation on the scalp under the electrodes. This sensation would disappear after the initial few seconds even if the current was maintained for the rest of the stimulation period. For the a-tDCS runs, channel 2 was switched off after 10 secs, but channel 1 remained on with a constant current output of 1 mA. For c-tDCS, only channel 2 remained switched on with a current intensity of 1 mA, and channel 1 was switched off after the initial 10 secs. For sham stimulation, both channels were switched off after the initial 10 secs. Stimulation then lasted 20 mins in all three conditions. The subjects remained seated throughout the experimental procedure.
Outcome Measures The primary outcome measurements were dexterity of the paretic hand and selective attention. They were evaluated before and immediately after the tDCS intervention in each session, again by J.W. and E.C., who were blinded to the type of treatment the subjects had received. The Purdue pegboard19 was used to assess hand dexterity. The seated subjects rested both hands and forearms on the table on each side of the pegboard. They were instructed to perform three tasks in the following sequence: (1) a unimanual task for the nonparetic hand (hand ipsilateral to the side of stroke lesion), (2) a unimanual task for the paretic hand (hand contralateral to the side of stroke lesion), and then, (3) an assembly task. During the unimanual task, subjects were first required to use the hand ipsilateral to the side of their stroke lesion to pick up one pin at a time from the upper corner cup of the pegboard ipsilateral to that hand and insert as many pins as possible into the pegboard’s ipsilateral column of holes starting from the uppermost hole. The score was the number of pins inserted in the holes in 30 secs. For the assembly task, subjects were required to construct fourcomponent assemblies along the column ipsilateral to the nonparetic hand, constructing as many as possible in 60 secs. To construct one assembly, the subjects had to pick up a pin from a cup on the pegboard using the nonparetic hand and insert it into the uppermost hole ipsilateral to the hand. The paretic hand then picked up a washer from another cup and placed it over the pin. When the paretic hand was placing the washer over the pin, the nonparetic hand picked up a collar and then placed it over the washer. Finally, the paretic hand picked tDCS Improves Dexterity and Attention
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up another washer and placed it over the collar to complete the assembly. This task therefore demanded bilateral coordination of dexterous hand and finger movements in designated sequence for constructing the assemblies. On each visit, the subjects were allowed to practice all three tasks and construct three or four assemblies before the actual test. The Purdue pegboard test has been shown to give excellent testretest reliability with healthy subjects, with intraclass correlation greater than 0.80.20 A color-word Stroop test21 (Stroop) was used to evaluate selective attention. Selective attention refers to the ability to suppress extraneous information so that one can pay attention to the stimuli currently most relevant.21 The Stroop test had three levels. Level 1 involved naming colors, level 2 involved identifying the color corresponding to that name, and level 3 required naming the color in which a word was printed when the word in question was the name of a different color. Previous studies have shown that word reading is an automatic response, but color naming requires conscious effort.22,23 The level 3 task therefore requires additional time to suppress the habitual response and name only the color in which the word is presented, ignoring its semantic meaning. This is known as the Stroop interference effect.22 Impaired cognition is associated with a longer time delay for level 3.22 In this study, the Stroop test was administered using a customized computer program written with LabVIEW version 8.6 (National Instruments, Texas) and presented on the screen of a laptop computer. A series of ten frames were presented in each level of the test. In the center of each frame was the test item, with two choices for the answer shown at the bottom of the frame, one choice on each side. In Stroop level 1, the frame’s center presented a blue, white, yellow, red, purple, orange, or green square. Two color names were presented below in Chinese characters, and the subject was required to select the correct one as quickly as possible by pressing a designated key on either side of the keyboard. In the level 2 test, a Chinese color word was presented in white font in the center of the frame with two colored squares below on either side of the frame, and the subject had to indicate the correct square. Level 3 was like level 2 except that the Chinese character at the center of the frame was presented in color, but the color in which it was written did not correspond with its semantic meaning. In the ten tests at each level, the colors or the words used and the order of presentation were randomized by the computer program. The program recorded the response
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times in milliseconds from the time the frame was presented to the time the subject pressed an answer key with the paretic hand. A subject’s response time for a particular level was the mean time of the correct key presses. Pinch grip strength of the paretic hand was assessed using a handheld digital dynamometer (Sammons Preston, Illinois). Each subject was tested while sitting with the forearm positioned in the midrange of supination and pronation and the elbow in 90 degrees of flexion. They were instructed to pinch the gauge with the thumb and index finger of the paretic hand as hard as possible. The pinch strength was the mean of three trials in one assessment. To address the possibility of fatigue confounding attention test performance, the subjects were asked to rate their perception of fatigue using a numerical rating scale marked 0 to 10 before and after tDCS in each session.
Data Analysis Statistical analyses were conducted using version 20.0 of the Statistical Package for the Social Sciences software (SPSS Inc, Chicago, IL). Normality of the data was examined using the ShapiroWilk test, revealing that four of the seven dependent variables did not have data in normal distribution. A Wilcoxon’s signed-rank test was used to examine changes in the outcomes within each tDCS condition. To compare the outcomes across the three stimulation conditions, repeated-measures analysis of variance was conducted, with stimulation and time as the within-subject factors to determine the effect of time by stimulation. A P = 0.05 was set as the acceptable level of confidence.
RESULTS Ten subjects, all men, with a mean age of 62.6 yrs (SD, 5.7 yrs) and a mean time since stroke of 8.3 yrs (SD, 3.2 yrs), were recruited and completed this study. All subjects were right-handed as defined by their preferred hand for writing and picking up chopsticks before their stroke. Their baseline demographic and clinical characteristics are listed in Table 2. Table 3 shows the results of comparison within each session and across sessions for the primary and secondary outcome measures. The baseline measurements of all outcome variables were not different across the three sessions. The subjects’ rating of perceived fatigue was similar before and after the tDCS interventions. The pegboard task performed by the paretic hand was significantly improved by 1.1 points (23.4% more
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16 46 45 57 45 57 56 52 53 46 47.3 (12.1) Composite spasticity score, maximum score of 12; score of greater than 6 indicates spasticity, and score of less than 6 indicates hypotonicity. L, left; M, male; R, right.
42 51 53 66 58 65 64 63 60 61 58.3 (7.6) 10 8 7 4 3 4 9 8 7 4 6.4 (2.5) 30 30 30 30 30 30 30 30 29 23 29.2 (2.2) 23.0 23.8 23.2 21.7 24.5 26.8 22.7 26.1 29.5 23.4 24.5 (2.3) 7 14 12 10 4 9 8 8 4.5 6 8.3 (3.2) L R R L R R L L R L Hemorrhage Infarct Infarct Infarct Infarct Infarct Infarct Infarct Infarct Hemorrhage 57 70 66 53 61 60 67 64 58 70 62.6 (5.7) 1 2 3 4 5 6 7 8 9 10 Mean (SD)
M M M M M M M M M M
Duration Since Body Mass MMSE Score, Composite Fugl-Meyer Assessment, Action Research Arm Test Stroke, Yrs Index 0Y30 Spasticity Score, 0Y12 Upper Limb Score, 0Y66 Score, 0Y57 Lesion Side Type of Stroke Sex Age, Yrs Subject
TABLE 2 Baseline demographic and clinical characteristics of the ten subjects
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pins) after c-tDCS (P = 0.014), but after a-tDCS or sham stimulation, there was no significant improvement. The change in dexterity performance of the paretic hand after intervention was not significant across the three tDCS conditions (repeatedmeasures analysis of variance, time-by-stimulation interaction effect, P = 0.318). Neither the performance of the nonparetic hand nor the assembly performance was significantly changed after any of the three tDCS interventions. The Stroop test levels 1 and 2 did not show any significant change with the three tDCS interventions. On level 3, however, response time was significantly shortened by 0.6 secs (20% faster than baseline performance) after c-tDCS (P = 0.017), although not after a-tDCS or sham stimulation (see Table 3). The improvement in Stroop level 3 was significantly different across the three tDCS sessions (P = 0.041). Pinch strength was not changed significantly with any of the three tDCS conditions.
DISCUSSION These results show that a single session of c-tDCS applied to M1nonlesioned for 20 mins can enhance dexterity in the paretic hand and improve selective attention in patients with chronic impairment after stroke. No such effects were found with a-tDCS. During the unimanual pegboard task, the action of repetitively picking up small pins and inserting them in small holes should be mediated by neural networks that relay visual and tactile information to M1 contralateral to the hand executing the fine finger movements.24 Compared with the assembly task, this unimanual task requires less planning of the movement sequences. Performance in this unimanual test could be attributed to the integrity of sensorimotor and cognitive networks for movement coordination. The results show that a dose of 20 mA-minutes of c-tDCS over M1nonlesioned significantly improved paretic hand dexterity in men after stroke. The performance of the nonparetic hand was not altered in any of the tDCS conditions. It has been found that movement attempts with the paretic hand are associated with inhibition of M1 of the lesioned hemisphere from the homologous M1 of the nonlesioned hemisphere.25 The resultant imbalance in neural activity between the two hemispheres further reduces corticomotor excitability of the lesioned hemisphere during voluntary limb movements.26 Persistent reduction in corticomotor excitability of the lesioned hemisphere may then impede the recovery of motor function in tDCS Improves Dexterity and Attention
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All ratings are expressed as mean (SD). P denotes the level of significance of comparison within a stimulation condition using Wilcoxon’s signed-rank test. a Statistical significance of e0.017 after Bonferroni adjustment for the three pairwise comparisons within tDCS conditions. b Statistical significance at 5% for the repeated-measures analysis of variance. Purdue-assembly, Purdue pegboard bilateral assembly task performance; Purdue-nonparetic, Purdue pegboard unimanual task performed with the nonparetic arm (ipsilateral to the side of stroke lesion); Purdue-paretic, Purdue pegboard unimanual task performed with the paretic arm (contralateral to the side of stroke lesion).
0.545 0.318 0.492 0.066 0.714 0.041b 0.594 0.201 0.776 0.546 0.573 0.285 0.139 0.575 0.475 0.121 12.8 (1.9) 5.8 (4.2) 15.9 (6.8) 1.5 (0.4) 1.5 (0.7) 2.0 (0.5) 5.2 (1.8) 2.8 (2.5) 12.6 (2.8) 5.4 (4.1) 15.4 (6.5) 1.4 (0.3) 1.3 (0.3) 2.2 (0.9) 5.3 (1.7) 1.6 (1.8) 0.773 12.5 (2.2) 12.0 (1.8) 0.260 0.589 4.7 (4.2) 5.8 (4.0) 0.014a 0.473 14.6 (5.1) 13.6 (5.2) 0.235 0.093 1.7 (0.4) 1.6 (0.5) 0.093 0.575 1.6 (0.6) 1.6 (0.7) 0.953 0.445 3.0 (1.4) 2.4 (0.9) 0.017a 0.373 5.5 (1.6) 5.4 (1.6) 0.944 0.655 2.5 (2.0) 2.7 (2.5) 0.577 12.2 (1.9) 5.3 (3.6) 15.7 (7.1) 1.6 (0.5) 1.6 (0.7) 2.5 (0.9) 5.4 (1.8) 2.8 (3.1) 12.1 (2.4) 5.1 (4.0) 15.0 (6.3) 1.8 (0.5) 1.5 (0.8) 2.3 (0.6) 5.3 (1.5) 3.2 (2.9) Purdue-nonparetic Purdue-paretic Purdue-assembly Stroop test level 1, sec Stroop test level 2, sec Stroop test level 3, sec Pinch grip, kg Fatigue score
Repeated-Measures Analysis of Variance, Time Stimulation Effect, P P Post Pre
Post
P
Pre
Post
P
Pre
Comparison of Change Across All tDCS Conditions Sham tDCS (n = 10) c-tDCS (n = 10) a-tDCS (n = 10)
TABLE 3 Test performance and perceived fatigue before (pre) and after (post) stimulation
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the paretic limb after stroke. The finding of the present study suggests that c-tDCS might help correct the overriding influence of M1nonlesioned over the lesioned hemisphere.26 The inhibitory influence of M1nonlesioned might have been dampened so as to allow activation of the corticomotor pathways in the lesioned hemisphere for the control of movement in the paretic hand. In contrast to the findings of two other research teams,12,13 a-tDCS to M1lesioned did not yield improvements in hand dexterity. One reason might be differences in the current density applied. This study used 35-cm2 electrodes, whereas those used by Hummel et al.12 were 25 cm2. The group of Boggio et al.13 used 35-cm2 electrodes, but larger saline-soaked sponges (8 cm 9 cm) were used in this study to cover the electrodes, which could possibly have resulted in lower current density. The weaker current density in the present study might not have been sufficient to depolarize the neurons in M1lesioned to overcome the inhibitory influence of the nonlesioned hemisphere in a-tDCS. At the same time, the favorable effect on upper limb function after a-tDCS observed by Hummel and his colleagues12 could have resulted from the combined effects of training in the motor tasks used in the hand dexterity test and tDCS. The authors suggested that the mechanism underlying improvement in function could be that a-tDCS lowered the motor thresholds for coactivation of synaptic inputs to augment motor learning.12 This present study did not involve dexterity training for either hand, which might explain why dexterity of the paretic hand was not improved after a-tDCS to M1lesioned. The pegboard test involves small objects that demand relatively intricate, fine motor control of the fingers compared with the Jebsen-Taylor hand function test used to quantify hand dexterity in previous studies.12,13 The assembly task requires working memory for the correct sequence, coordination between the two hands, eye-hand coordination, attention, error detection, and motor planning. Such a complex activity requires the activation of several brain regions and vast neural networks integrating prefrontal,27 corpus callosum,28 and cerebellar29 inputs, among others. Applying tDCS to one primary motor area alone may not have been sufficient to induce changes in the assembly scores. On the other hand, Mahmoudi and co-workers30 applied the anode to M1lesioned and the cathode to M1nonlesioned and observed significant improvement in JebsenTaylor hand function test scores after one tDCS session for subjects with stroke. Using similar dual-hemisphere tDCS, Lefebvre and colleagues31
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also found significant gains in pegboard scores of the paretic hand in their randomized shamcontrolled trial (n = 19), with an effect size of 0.3 compared with sham stimulation evaluated 20 mins after the cessation of tDCS.31 The effect size was less than 0.2 immediately after tDCS.31 The present study used the same stimulation parameters as in the two reports above (35-cm2 electrodes, 1-mA current for 20 mins),30,31 but the immediate gain in pegboard scores after c-tDCS on M1nonlesioned vs. sham tDCS showed an effect size of 0.48 evaluated with Cohen d.32 Such a magnitude of effect on hand dexterity may be comparable with that of dualhemisphere tDCS applied to people with chronic stroke. Indeed, Mahmoudi’s team30 found that the functional improvement in the paretic arm after dualhemisphere tDCS was not different from that with a-tDCS or c-tDCS. Whether c-tDCS to M1nonlesioned would lead to lasting hand dexterity improvement as that found with dual-hemisphere tDCS 31 is worthy of further exploration. Neither a-tDCS applied to M1lesioned nor c-tDCS applied to M1nonlesioned improved pinch force. Hummel et al.33 have reported similar results when they applied a-tDCS to M1lesioned with subjects with chronic stroke. No report of the effects of c-tDCS over M1nonlesined on the pinch force of stroke survivors has previously been published. Whether tDCS combined with motor training might improve pinch strength requires further study. For cognitive function, studies have shown that working memory and attention during task performance improved after a session of a-tDCS targeting the left dorsolateral prefrontal cortex in patients with Parkinsonism or stroke.10,34,35 The present study has been the first to examine the effects on selective attention with tDCS targeting M1 after stroke. Selective attention involves higherorder cognitive processes that contribute to decision making, attention switching, and selection of response strategies for purposeful movements.36,37 This attention domain is a component of executive function, which is fundamental to learning.38 Selective attention evaluated with the Stroop test is known to reflect activity in the dorsolateral prefrontal cortex and the anterior cingulate cortex.39 In this study, selective attention was quantified using reaction time after the color-word stimulus was presented. The Stroop 3 score should reflect the aggregate effect of tDCS on both the sensorimotor pathways controlling movements of the paretic upper limb and the cognitive neural circuitry for response inhibition. During c-tDCS, the cathode was positioned over M1 of the nonlesioned hemiwww.ajpmr.com
sphere, and the anode was placed over the supraorbital frontal lobe ipsilateral to the lesioned hemisphere. The direct current could have depolarized the neural circuitry in the frontal lobe, which might have modulated both the cognitive and motor pathways involved in the Stroop test performance. Conversely, positioning the anode over M1lesioned and the cathode over the contralateral supraorbital region might have enhanced the motor but not the cognitive pathways involved in pressing the key for the correct answer. This could explain why c-tDCS enhanced selective attention and a-tDCS did not. It may have been the motor effects of c-tDCS that induced better Stroop 3 performance. However, it is noteworthy that none of the tDCS sessions changed Stroop performance on level 1 or 2, both of which involved more sensorimotor than cognitive processing. Interpretation of results in this study is somewhat limited by the small sample of stroke survivors with mild disability for finger manipulation tasks (the mean Action Research Arm Test score was 47.3/57). The observed effects of c-tDCS may not be so apparent among more disabled patients or earlier after stroke. Moreover, it is not known whether cortical and/or subcortical stroke lesions influence the effect of tDCS on hand dexterity and selective attention to different extents. Clearly, a larger scale study is needed to validate the effects of c-tDCS to M1nonlesioned as a treatment for promoting motor and cognitive functions after stroke.
CONCLUSIONS Applying c-tDCS to M1nonlesioned for 20 mins can improve selective attention and hand dexterity in people with mildly to moderately affected hand function after stroke. REFERENCES 1. Tatemichi TK, Desmond DW, Stern Y, et al: Cognitive impairment after stroke: Frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatr 1994;57:202Y7 2. Pendlebury ST, Rothwell PM: Prevalence, incidence, and factors associated with pre-stroke and poststroke dementia: A systematic review and metaanalysis. Lancet Neurol 2009;8:1006Y18 3. Bastani A, Jaberzadeh S: Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: A systematic review and metaanalysis. Clin Neurophysiol 2012;123:644Y57 4. Nitsche MA, Paulus W: Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 2000;527:633Y9
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9. Liddle PF, Kiehl KA, Smith AM: Event-related fMRI study of response inhibition. Hum Brain Mapp 2001; 12:100Y9
27. D’Esposito M, Postle BR, Rypma B: Prefrontal cortical contributions to working memory: Evidence from eventrelated fMRI studies. Exp Brain Res 2000;133:3Y11
10. Kang EK, Baek MJ, Kim S, et al: Non-invasive cortical stimulation improves post-stroke attention decline. Restor Neurol Neurosci 2009;27:645Y50 11. Nitsche MA, Cohen LG, Wassermann EM, et al: Transcranial direct current stimulation: State of the art 2008. Brain Stim 2008;1:206Y23 12. Hummel F, Celnik P, Giraux P, et al: Effects of noninvasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005;128:490Y9 13. Boggio PS, Nunes A, Rigonatti SP, et al: Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci 2007;25:123Y9 14. Fregni F, Boggio PS, Mansur CG, et al: Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. NeuroReport 2005;16:1551Y5 15. Chiu HFK, Lee HC, Chung WS, et al: Reliability and validity of the Cantonese version of mini-mental state examination: A preliminary study. Hong Kong J Psychiatr 1994;4:25Y8 16. Levin MF, Hui-Chan C: Are H and stretch reflexes in hemiparesis reproducible and correlated with spasticity? J Neurol 1993;240:63Y71 17. Fugl-Meyer AR, Jaasko L, Leyman I, et al: The poststroke hemiplegic patient: 1. A method for evaluation of physical performance. Scand J Rehabil Med 1975;7:13Y31 18. Lyle R: A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res 1981;4:483Y92 19. Tiffin J, Asher EJ: The Purdue pegboard: Norms and studies of reliability and validity. J Appl Psychol 1948;32:234Y47
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28. Hanakawa T, Dimyan MA, Hallett M: Motor planning, imagery, and execution in the distributed motor network: A time-course study with functional MRI. Cereb Cortex 2008;18:2775Y88 29. Miall RC, Reckess GZ, Imamizu H: The cerebellum coordinates eye and hand tracking movements. Nat Neurosci 2001;4:638Y44 30. Mahmoudi H, Borhani Haghighi A, Petramfar P, et al: Transcranial direct current stimulation: Electrode montage in stroke. Disab Rehabil 2011;33:1383Y8 31. Lefebvre S, Thonnard J, Laloux P, et al: Single session of dual-tDCS transiently improves precision grip and dexterity of the paretic hand after stroke. Neurorehabil Neural Repair 2014;28:100Y10 32. Cohen J: Statistical Power Analysis for the Behavioral Sciences. ed 2. Hillsdale, NJ, Lawrence Erlbaum, 1988 33. Hummel FC, Voller B, Celnik P, et al: Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neurosci 2006;7:73 34. Boggio PS, Ferrucci R, Rigonatti SP, et al: Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease. J Neurol Sci 2006;249:31Y8 35. Jo JM, Kim YH, Ko MH, et al: Enhancing the working memory of stroke patients using tDCS. Am J Phys Med Rehabil 2009;88:404Y9 36. Fan J, McCandliss BD, Fossella J, et al: The activation of attentional networks. NeuroImage 2005; 26:471Y9
20. Buddenberg LA, Davis C: Test-retest reliability of the Purdue pegboard test. Am J Occup Ther 1999;54:555Y8
37. Mitchell RLC: Linear increases in BOLD response associated with increasing proportion of incongruent trials across time in a colour Stroop task. Exp Brain Res 2010;203:193Y204
21. Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643Y62
38. Dayan P, Kakade S, Montague PR: Learning and selective attention. Nat Neurosci 2000;3:S1218Y23
22. Davidson DJ, Zacks RT, Williams CC: Stroop interference, practice, and aging. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2003;10:85Y98
39. Zoccatelli G, Beltramello A, Alessandrini F, et al: Word and position interference in Stroop tasks: A behavioral and fMRI study. Exp Brain Res 2010;207:139Y47
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Am. J. Phys. Med. Rehabil. & Vol. 93, No. 12, December 2014
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Stroke
Affiliations: From the Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.
Correspondence: All correspondence and requests for reprints should be addressed to: Stephanie S.Y. Au-Yeung, PhD, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
ORIGINAL RESEARCH ARTICLE
Transcranial Direct Current Stimulation to Primary Motor Area Improves Hand Dexterity and Selective Attention in Chronic Stroke
Disclosures: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
0894-9115/14/9312-1057 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000127
ABSTRACT Au-Yeung SSY, Wang J, Chen Y, Chua E: Transcranial direct current stimulation to primary motor area improves hand dexterity and selective attention in chronic stroke. Am J Phys Med Rehabil 2014;93:1057Y1064.
Objective: The aim of this study was to determine whether transcranial direct current stimulation (tDCS) applied to the primary motor hand area modulates hand dexterity and selective attention after stroke. Design: This study was a double-blind, placebo-controlled, randomized crossover trial involving subjects with chronic stroke. Ten stroke survivors with some pinch strength in the paretic hand received three different tDCS interventions assigned in random order in separate sessionsVanodal tDCS targeting the primary motor area of the lesioned hemisphere (M1lesioned), cathodal tDCS applied to the contralateral hemisphere (M1nonlesioned), and sham tDCSVeach for 20 mins. The primary outcome measures were Purdue pegboard test scores for hand dexterity and response time in the color-word Stroop test for selective attention. Pinch strength of the paretic hand was the secondary outcome.
Results: Cathodal tDCS to M1nonlesioned significantly improved affected hand dexterity (by 1.1 points on the Purdue pegboard unimanual test, P = 0.014) and selective attention (0.6 secs faster response time on the level 3 Stroop interference test for response inhibition, P = 0.017), but not pinch strength. The outcomes were not improved with anodal tDCS to M1lesioned or sham tDCS.
Conclusions: Twenty minutes of cathodal tDCS to M1nonlesioned can promote both paretic hand dexterity and selective attention in people with chronic stroke. Key Words:
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Transcranial Direct Current Stimulation, Stroke, Dexterity, Selective Attention
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any stroke survivors experience one or more movement-related impairments and activity limitations. Cognitive decline is also associated with stroke but receives little attention during standard stroke rehabilitation. The cognitive domains most commonly involved after stroke are attention, orientation, language, and memory.1 The prevalence of dementia within the first year after stroke is estimated to be 10% after a first stroke and 30% after a recurrent stroke.2 It has been noted that stroke survivors without dementia also demonstrate poorer attention and executive function compared with healthy elderly controls.1 Transcranial direct current stimulation (tDCS) has been reported as a promising treatment for promoting motor recovery after stroke.3 tDCS is a form of noninvasive brain stimulation that delivers weak direct current via electrodes on the scalp to the underlying brain tissue to alter membrane excitability.4 The anode and cathode are placed on the scalp directly over the target brain region.4 The direct current enhances the conductance of voltage-gated sodium and calcium channels to induce subthreshold membrane depolarization of neuronal structures near the anode.5 The depolarization improves N-methyl-D-aspartate (NMDA) receptor efficacy and increases postsynaptic calcium levels.5 The increased membrane excitability also leads to a reduction in the level of an enzyme responsible for the production of gamma-aminobutyric acid (GABA), thereby reducing GABA-ergic synaptic activity.6 Both NMDA and GABA mediate long-term potentiation, a process involved in synaptic plasticity.7 The increase in membrane excitability and long-term potentiation explains how anodal tDCS (a-tDCS) may promote brain function in the target region. Near the cathode, in contrast, sodium and calcium channel conductance is reduced, resulting in membrane hyperpolarization and decreased NMDA receptor activity.5 In addition, reduced glutamine activity leads to less synthesis of the excitatory neurotransmitter glutamate,6 and the reduction can contribute to long-term depression.8 tDCS as a therapy for motor function after stroke involves applying the active electrode on the scalp over the target primary motor cortex (M1) with the reference electrode over the contralateral supraorbital region.4 This arrangement delivers a weak direct current through M1, but because the reference electrode is not completely inert,4 the current also passes through the prefrontal region, a brain region associated with cognitive functioning.9 It has been reported that a-tDCS applied over the dorsolateral prefrontal cortex can improve attention
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deficit in patients with stroke,10 but it is not currently known whether tDCS targeting M1 can also modulate cognitive functioning, particularly attention, along with its expected motor effects. tDCS studies on motor functions after stroke commonly adopted anodal or cathodal stimulation targeting, respectively, M1 of the hemisphere with stroke lesion and the contralateral nonlesioned hemisphere.11 The outcomes evaluated have focused on movements in the paretic limbs.12Y14 With the proximity of the frontal cortex to M1 and the current flow between the two electrodes during tDCS, it is plausible that tDCS targeting M1 might modulate cognitive as well as motor functions. This study was therefore designed to investigate the effects of anodal and cathodal tDCS (c-tDCS) on hand dexterity and selective attention in stroke survivors.
METHODS Design This study was a double-blind, three-arm crossover, randomized, controlled trial conducted in a university laboratory from February to April 2013. The university’s human subjects ethics subcommittee approved the study protocols.
Subjects Ten community-dwelling stroke survivors were recruited using convenience sampling from two patient self-help groups for stroke. The candidates were screened using telephone interviews. Those included were younger than 80 yrs, had experienced a single stroke more than a year previously, demonstrated weakness in the hand contralateral to the cerebral hemisphere with stroke, and could perform a pincer grip with the index finger. Those excluded were either illiterate in Chinese, had a history of neurologic disorders other than stroke (particularly epilepsy or depression), had metal implant in the brain, had musculoskeletal pathology affecting movements in the upper limbs, had aphasia, or scored less than 18 on the Mini-Mental State Examination, which indicated moderate-to-severe cognitive impairment.15 All subjects gave their informed consent in writing in accordance with the Declaration of Helsinki before the experiments.
Procedure Each subject attended three treatment sessions with a washout period of at least 5 days between sessions. All of the subjects received a-tDCS, c-tDCS, and sham tDCS (sham), one in each of the three sessions they attended. The sequence was determined
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in advance for each subject by drawing lots from an envelope. The distribution of subjects to the three stimulation conditions in each session is presented in Table 1. Two other investigators (J.W. and E.C.) who were blinded to the allocated tDCS conditions then assessed the baseline motor status of the subjects’ paretic upper limb using the Composite Spasticity Scale16 for muscle tone, Fugl-Meyer Assessment for sensorimotor impairment,17 and the Action Research Arm Test18 for functional ability. tDCS was delivered using a dual-channel iontophoresis system (Ionto; Chattanooga Medical Supply, Chattanooga, TN) whose carbon electrodes (size, 35 cm2) were covered with saline-soaked sponges. To target M1, which controls finger movements, the anode was positioned on the scalp over C3/C4 (International 10/20 Electroencephalogram System) of the hemisphere affected by the stroke. This will be designated as M1lesioned. The cathode was placed over the contralateral supraorbital area at the forehead. The leads were connected to channel 1 of the tDCS machine. On the M1 of the nonlesioned hemisphere (M1nonlesioned), the cathode was placed over the C3/C4 location; and the anode, over the contralateral supraorbital area. The leads of this pair of electrodes were connected to channel 2 of the machine. All four electrodes were secured using straps to ensure maximal skin contact. It was the third investigator (C.Y.) who set the tDCS parameters for both channels and operated the machine behind the subject throughout the experimental procedure. This ensured that the subject was blinded to the designated tDCS condition for the session. For all conditions, both channels of the
TABLE 1 Results of randomization of subjects to the three tDCS protocols in each session tDCS Protocol Subject
Session 1
Session 2
Session 3
1 Cathodal Sham Anodal 2 Cathodal Anodal Sham 3 Sham Anodal Cathodal 4 Anodal Cathodal Sham 5 Sham Cathodal Anodal 6 Cathodal Sham Anodal 7 Anodal Sham Cathodal 8 Cathodal Sham Anodal 9 Anodal Cathodal Sham 10 Cathodal Anodal Sham Summary Three a-tDCS Three a-tDCS Four a-tDCS Five c-tDCS Three c-tDCS Two c-tDCS Two sham Four sham Four sham
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machine were initially switched on, and the current was set to ramp up to an intensity of 1 mA. The subjects would usually feel a mild tingling sensation on the scalp under the electrodes. This sensation would disappear after the initial few seconds even if the current was maintained for the rest of the stimulation period. For the a-tDCS runs, channel 2 was switched off after 10 secs, but channel 1 remained on with a constant current output of 1 mA. For c-tDCS, only channel 2 remained switched on with a current intensity of 1 mA, and channel 1 was switched off after the initial 10 secs. For sham stimulation, both channels were switched off after the initial 10 secs. Stimulation then lasted 20 mins in all three conditions. The subjects remained seated throughout the experimental procedure.
Outcome Measures The primary outcome measurements were dexterity of the paretic hand and selective attention. They were evaluated before and immediately after the tDCS intervention in each session, again by J.W. and E.C., who were blinded to the type of treatment the subjects had received. The Purdue pegboard19 was used to assess hand dexterity. The seated subjects rested both hands and forearms on the table on each side of the pegboard. They were instructed to perform three tasks in the following sequence: (1) a unimanual task for the nonparetic hand (hand ipsilateral to the side of stroke lesion), (2) a unimanual task for the paretic hand (hand contralateral to the side of stroke lesion), and then, (3) an assembly task. During the unimanual task, subjects were first required to use the hand ipsilateral to the side of their stroke lesion to pick up one pin at a time from the upper corner cup of the pegboard ipsilateral to that hand and insert as many pins as possible into the pegboard’s ipsilateral column of holes starting from the uppermost hole. The score was the number of pins inserted in the holes in 30 secs. For the assembly task, subjects were required to construct fourcomponent assemblies along the column ipsilateral to the nonparetic hand, constructing as many as possible in 60 secs. To construct one assembly, the subjects had to pick up a pin from a cup on the pegboard using the nonparetic hand and insert it into the uppermost hole ipsilateral to the hand. The paretic hand then picked up a washer from another cup and placed it over the pin. When the paretic hand was placing the washer over the pin, the nonparetic hand picked up a collar and then placed it over the washer. Finally, the paretic hand picked tDCS Improves Dexterity and Attention
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up another washer and placed it over the collar to complete the assembly. This task therefore demanded bilateral coordination of dexterous hand and finger movements in designated sequence for constructing the assemblies. On each visit, the subjects were allowed to practice all three tasks and construct three or four assemblies before the actual test. The Purdue pegboard test has been shown to give excellent testretest reliability with healthy subjects, with intraclass correlation greater than 0.80.20 A color-word Stroop test21 (Stroop) was used to evaluate selective attention. Selective attention refers to the ability to suppress extraneous information so that one can pay attention to the stimuli currently most relevant.21 The Stroop test had three levels. Level 1 involved naming colors, level 2 involved identifying the color corresponding to that name, and level 3 required naming the color in which a word was printed when the word in question was the name of a different color. Previous studies have shown that word reading is an automatic response, but color naming requires conscious effort.22,23 The level 3 task therefore requires additional time to suppress the habitual response and name only the color in which the word is presented, ignoring its semantic meaning. This is known as the Stroop interference effect.22 Impaired cognition is associated with a longer time delay for level 3.22 In this study, the Stroop test was administered using a customized computer program written with LabVIEW version 8.6 (National Instruments, Texas) and presented on the screen of a laptop computer. A series of ten frames were presented in each level of the test. In the center of each frame was the test item, with two choices for the answer shown at the bottom of the frame, one choice on each side. In Stroop level 1, the frame’s center presented a blue, white, yellow, red, purple, orange, or green square. Two color names were presented below in Chinese characters, and the subject was required to select the correct one as quickly as possible by pressing a designated key on either side of the keyboard. In the level 2 test, a Chinese color word was presented in white font in the center of the frame with two colored squares below on either side of the frame, and the subject had to indicate the correct square. Level 3 was like level 2 except that the Chinese character at the center of the frame was presented in color, but the color in which it was written did not correspond with its semantic meaning. In the ten tests at each level, the colors or the words used and the order of presentation were randomized by the computer program. The program recorded the response
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times in milliseconds from the time the frame was presented to the time the subject pressed an answer key with the paretic hand. A subject’s response time for a particular level was the mean time of the correct key presses. Pinch grip strength of the paretic hand was assessed using a handheld digital dynamometer (Sammons Preston, Illinois). Each subject was tested while sitting with the forearm positioned in the midrange of supination and pronation and the elbow in 90 degrees of flexion. They were instructed to pinch the gauge with the thumb and index finger of the paretic hand as hard as possible. The pinch strength was the mean of three trials in one assessment. To address the possibility of fatigue confounding attention test performance, the subjects were asked to rate their perception of fatigue using a numerical rating scale marked 0 to 10 before and after tDCS in each session.
Data Analysis Statistical analyses were conducted using version 20.0 of the Statistical Package for the Social Sciences software (SPSS Inc, Chicago, IL). Normality of the data was examined using the ShapiroWilk test, revealing that four of the seven dependent variables did not have data in normal distribution. A Wilcoxon’s signed-rank test was used to examine changes in the outcomes within each tDCS condition. To compare the outcomes across the three stimulation conditions, repeated-measures analysis of variance was conducted, with stimulation and time as the within-subject factors to determine the effect of time by stimulation. A P = 0.05 was set as the acceptable level of confidence.
RESULTS Ten subjects, all men, with a mean age of 62.6 yrs (SD, 5.7 yrs) and a mean time since stroke of 8.3 yrs (SD, 3.2 yrs), were recruited and completed this study. All subjects were right-handed as defined by their preferred hand for writing and picking up chopsticks before their stroke. Their baseline demographic and clinical characteristics are listed in Table 2. Table 3 shows the results of comparison within each session and across sessions for the primary and secondary outcome measures. The baseline measurements of all outcome variables were not different across the three sessions. The subjects’ rating of perceived fatigue was similar before and after the tDCS interventions. The pegboard task performed by the paretic hand was significantly improved by 1.1 points (23.4% more
Am. J. Phys. Med. Rehabil. & Vol. 93, No. 12, December 2014
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16 46 45 57 45 57 56 52 53 46 47.3 (12.1) Composite spasticity score, maximum score of 12; score of greater than 6 indicates spasticity, and score of less than 6 indicates hypotonicity. L, left; M, male; R, right.
42 51 53 66 58 65 64 63 60 61 58.3 (7.6) 10 8 7 4 3 4 9 8 7 4 6.4 (2.5) 30 30 30 30 30 30 30 30 29 23 29.2 (2.2) 23.0 23.8 23.2 21.7 24.5 26.8 22.7 26.1 29.5 23.4 24.5 (2.3) 7 14 12 10 4 9 8 8 4.5 6 8.3 (3.2) L R R L R R L L R L Hemorrhage Infarct Infarct Infarct Infarct Infarct Infarct Infarct Infarct Hemorrhage 57 70 66 53 61 60 67 64 58 70 62.6 (5.7) 1 2 3 4 5 6 7 8 9 10 Mean (SD)
M M M M M M M M M M
Duration Since Body Mass MMSE Score, Composite Fugl-Meyer Assessment, Action Research Arm Test Stroke, Yrs Index 0Y30 Spasticity Score, 0Y12 Upper Limb Score, 0Y66 Score, 0Y57 Lesion Side Type of Stroke Sex Age, Yrs Subject
TABLE 2 Baseline demographic and clinical characteristics of the ten subjects
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pins) after c-tDCS (P = 0.014), but after a-tDCS or sham stimulation, there was no significant improvement. The change in dexterity performance of the paretic hand after intervention was not significant across the three tDCS conditions (repeatedmeasures analysis of variance, time-by-stimulation interaction effect, P = 0.318). Neither the performance of the nonparetic hand nor the assembly performance was significantly changed after any of the three tDCS interventions. The Stroop test levels 1 and 2 did not show any significant change with the three tDCS interventions. On level 3, however, response time was significantly shortened by 0.6 secs (20% faster than baseline performance) after c-tDCS (P = 0.017), although not after a-tDCS or sham stimulation (see Table 3). The improvement in Stroop level 3 was significantly different across the three tDCS sessions (P = 0.041). Pinch strength was not changed significantly with any of the three tDCS conditions.
DISCUSSION These results show that a single session of c-tDCS applied to M1nonlesioned for 20 mins can enhance dexterity in the paretic hand and improve selective attention in patients with chronic impairment after stroke. No such effects were found with a-tDCS. During the unimanual pegboard task, the action of repetitively picking up small pins and inserting them in small holes should be mediated by neural networks that relay visual and tactile information to M1 contralateral to the hand executing the fine finger movements.24 Compared with the assembly task, this unimanual task requires less planning of the movement sequences. Performance in this unimanual test could be attributed to the integrity of sensorimotor and cognitive networks for movement coordination. The results show that a dose of 20 mA-minutes of c-tDCS over M1nonlesioned significantly improved paretic hand dexterity in men after stroke. The performance of the nonparetic hand was not altered in any of the tDCS conditions. It has been found that movement attempts with the paretic hand are associated with inhibition of M1 of the lesioned hemisphere from the homologous M1 of the nonlesioned hemisphere.25 The resultant imbalance in neural activity between the two hemispheres further reduces corticomotor excitability of the lesioned hemisphere during voluntary limb movements.26 Persistent reduction in corticomotor excitability of the lesioned hemisphere may then impede the recovery of motor function in tDCS Improves Dexterity and Attention
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All ratings are expressed as mean (SD). P denotes the level of significance of comparison within a stimulation condition using Wilcoxon’s signed-rank test. a Statistical significance of e0.017 after Bonferroni adjustment for the three pairwise comparisons within tDCS conditions. b Statistical significance at 5% for the repeated-measures analysis of variance. Purdue-assembly, Purdue pegboard bilateral assembly task performance; Purdue-nonparetic, Purdue pegboard unimanual task performed with the nonparetic arm (ipsilateral to the side of stroke lesion); Purdue-paretic, Purdue pegboard unimanual task performed with the paretic arm (contralateral to the side of stroke lesion).
0.545 0.318 0.492 0.066 0.714 0.041b 0.594 0.201 0.776 0.546 0.573 0.285 0.139 0.575 0.475 0.121 12.8 (1.9) 5.8 (4.2) 15.9 (6.8) 1.5 (0.4) 1.5 (0.7) 2.0 (0.5) 5.2 (1.8) 2.8 (2.5) 12.6 (2.8) 5.4 (4.1) 15.4 (6.5) 1.4 (0.3) 1.3 (0.3) 2.2 (0.9) 5.3 (1.7) 1.6 (1.8) 0.773 12.5 (2.2) 12.0 (1.8) 0.260 0.589 4.7 (4.2) 5.8 (4.0) 0.014a 0.473 14.6 (5.1) 13.6 (5.2) 0.235 0.093 1.7 (0.4) 1.6 (0.5) 0.093 0.575 1.6 (0.6) 1.6 (0.7) 0.953 0.445 3.0 (1.4) 2.4 (0.9) 0.017a 0.373 5.5 (1.6) 5.4 (1.6) 0.944 0.655 2.5 (2.0) 2.7 (2.5) 0.577 12.2 (1.9) 5.3 (3.6) 15.7 (7.1) 1.6 (0.5) 1.6 (0.7) 2.5 (0.9) 5.4 (1.8) 2.8 (3.1) 12.1 (2.4) 5.1 (4.0) 15.0 (6.3) 1.8 (0.5) 1.5 (0.8) 2.3 (0.6) 5.3 (1.5) 3.2 (2.9) Purdue-nonparetic Purdue-paretic Purdue-assembly Stroop test level 1, sec Stroop test level 2, sec Stroop test level 3, sec Pinch grip, kg Fatigue score
Repeated-Measures Analysis of Variance, Time Stimulation Effect, P P Post Pre
Post
P
Pre
Post
P
Pre
Comparison of Change Across All tDCS Conditions Sham tDCS (n = 10) c-tDCS (n = 10) a-tDCS (n = 10)
TABLE 3 Test performance and perceived fatigue before (pre) and after (post) stimulation
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the paretic limb after stroke. The finding of the present study suggests that c-tDCS might help correct the overriding influence of M1nonlesioned over the lesioned hemisphere.26 The inhibitory influence of M1nonlesioned might have been dampened so as to allow activation of the corticomotor pathways in the lesioned hemisphere for the control of movement in the paretic hand. In contrast to the findings of two other research teams,12,13 a-tDCS to M1lesioned did not yield improvements in hand dexterity. One reason might be differences in the current density applied. This study used 35-cm2 electrodes, whereas those used by Hummel et al.12 were 25 cm2. The group of Boggio et al.13 used 35-cm2 electrodes, but larger saline-soaked sponges (8 cm 9 cm) were used in this study to cover the electrodes, which could possibly have resulted in lower current density. The weaker current density in the present study might not have been sufficient to depolarize the neurons in M1lesioned to overcome the inhibitory influence of the nonlesioned hemisphere in a-tDCS. At the same time, the favorable effect on upper limb function after a-tDCS observed by Hummel and his colleagues12 could have resulted from the combined effects of training in the motor tasks used in the hand dexterity test and tDCS. The authors suggested that the mechanism underlying improvement in function could be that a-tDCS lowered the motor thresholds for coactivation of synaptic inputs to augment motor learning.12 This present study did not involve dexterity training for either hand, which might explain why dexterity of the paretic hand was not improved after a-tDCS to M1lesioned. The pegboard test involves small objects that demand relatively intricate, fine motor control of the fingers compared with the Jebsen-Taylor hand function test used to quantify hand dexterity in previous studies.12,13 The assembly task requires working memory for the correct sequence, coordination between the two hands, eye-hand coordination, attention, error detection, and motor planning. Such a complex activity requires the activation of several brain regions and vast neural networks integrating prefrontal,27 corpus callosum,28 and cerebellar29 inputs, among others. Applying tDCS to one primary motor area alone may not have been sufficient to induce changes in the assembly scores. On the other hand, Mahmoudi and co-workers30 applied the anode to M1lesioned and the cathode to M1nonlesioned and observed significant improvement in JebsenTaylor hand function test scores after one tDCS session for subjects with stroke. Using similar dual-hemisphere tDCS, Lefebvre and colleagues31
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also found significant gains in pegboard scores of the paretic hand in their randomized shamcontrolled trial (n = 19), with an effect size of 0.3 compared with sham stimulation evaluated 20 mins after the cessation of tDCS.31 The effect size was less than 0.2 immediately after tDCS.31 The present study used the same stimulation parameters as in the two reports above (35-cm2 electrodes, 1-mA current for 20 mins),30,31 but the immediate gain in pegboard scores after c-tDCS on M1nonlesioned vs. sham tDCS showed an effect size of 0.48 evaluated with Cohen d.32 Such a magnitude of effect on hand dexterity may be comparable with that of dualhemisphere tDCS applied to people with chronic stroke. Indeed, Mahmoudi’s team30 found that the functional improvement in the paretic arm after dualhemisphere tDCS was not different from that with a-tDCS or c-tDCS. Whether c-tDCS to M1nonlesioned would lead to lasting hand dexterity improvement as that found with dual-hemisphere tDCS 31 is worthy of further exploration. Neither a-tDCS applied to M1lesioned nor c-tDCS applied to M1nonlesioned improved pinch force. Hummel et al.33 have reported similar results when they applied a-tDCS to M1lesioned with subjects with chronic stroke. No report of the effects of c-tDCS over M1nonlesined on the pinch force of stroke survivors has previously been published. Whether tDCS combined with motor training might improve pinch strength requires further study. For cognitive function, studies have shown that working memory and attention during task performance improved after a session of a-tDCS targeting the left dorsolateral prefrontal cortex in patients with Parkinsonism or stroke.10,34,35 The present study has been the first to examine the effects on selective attention with tDCS targeting M1 after stroke. Selective attention involves higherorder cognitive processes that contribute to decision making, attention switching, and selection of response strategies for purposeful movements.36,37 This attention domain is a component of executive function, which is fundamental to learning.38 Selective attention evaluated with the Stroop test is known to reflect activity in the dorsolateral prefrontal cortex and the anterior cingulate cortex.39 In this study, selective attention was quantified using reaction time after the color-word stimulus was presented. The Stroop 3 score should reflect the aggregate effect of tDCS on both the sensorimotor pathways controlling movements of the paretic upper limb and the cognitive neural circuitry for response inhibition. During c-tDCS, the cathode was positioned over M1 of the nonlesioned hemiwww.ajpmr.com
sphere, and the anode was placed over the supraorbital frontal lobe ipsilateral to the lesioned hemisphere. The direct current could have depolarized the neural circuitry in the frontal lobe, which might have modulated both the cognitive and motor pathways involved in the Stroop test performance. Conversely, positioning the anode over M1lesioned and the cathode over the contralateral supraorbital region might have enhanced the motor but not the cognitive pathways involved in pressing the key for the correct answer. This could explain why c-tDCS enhanced selective attention and a-tDCS did not. It may have been the motor effects of c-tDCS that induced better Stroop 3 performance. However, it is noteworthy that none of the tDCS sessions changed Stroop performance on level 1 or 2, both of which involved more sensorimotor than cognitive processing. Interpretation of results in this study is somewhat limited by the small sample of stroke survivors with mild disability for finger manipulation tasks (the mean Action Research Arm Test score was 47.3/57). The observed effects of c-tDCS may not be so apparent among more disabled patients or earlier after stroke. Moreover, it is not known whether cortical and/or subcortical stroke lesions influence the effect of tDCS on hand dexterity and selective attention to different extents. Clearly, a larger scale study is needed to validate the effects of c-tDCS to M1nonlesioned as a treatment for promoting motor and cognitive functions after stroke.
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