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Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task
Clinical Neurophysiology xxx (2014) xxx–xxx
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Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task q Shuhei Fujimoto a,1, Tomofumi Yamaguchi a,b, Yohei Otaka a,b, Kunitsugu Kondo a, Satoshi Tanaka c,⇑,1 a
Tokyo Bay Rehabilitation Hospital, Chiba, Japan Keio University School of Medicine, Tokyo, Japan c Nagoya Institute of Technology, Aichi, Japan b
a r t i c l e
i n f o
Article history: Accepted 12 December 2013 Available online xxxx Keywords: Cortical plasticity Inter-hemispheric inhibition (IHI) Somatosensory cortex Tactile Transcranial direct current stimulation (tDCS) Transcranial magnetic stimulation (TMS)
h i g h l i g h t s Dual-hemisphere transcranial direct stimulation (tDCS) is a novel and powerful strategy to improve
human cognitive and motor function, but its effect on somatosensory function remains unknown. We demonstrated that dual-hemisphere tDCS over the primary somatosensory cortex facilitates
greater improvements for performance in a tactile discrimination task in healthy adults compared with uni-hemisphere and sham tDCS. Dual-hemisphere tDCS might be useful to improve sensory function in patients with sensory dysfunctions.
a b s t r a c t Objective: The aim of this study was to test the hypothesis that dual-hemisphere transcranial direct current stimulation (tDCS) over the primary somatosensory cortex (S1) could improve performance in a tactile spatial discriminative task, compared with uni-hemisphere or sham tDCS. Methods: Nine healthy adults participated in this double-blind, sham-controlled, and cross-over design study. The performance in a grating orientation task (GOT) in the right index finger was evaluated before, during, immediately after and 30 min after the dual-hemisphere, uni-hemisphere (1 mA, 20 min), or sham tDCS (1 mA, 30 s) over S1. In the dual-hemisphere and sham conditions, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the right S1. In the uni-hemisphere condition, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the contralateral supraorbital front. Results: The percentage of correct responses on the GOT during dual-hemisphere tDCS was significantly higher than that in the uni-hemisphere or sham tDCS conditions when the grating width was set to 0.75 mm (all p < 0.05). Conclusions: Dual-hemisphere tDCS over S1 improved performance in a tactile spatial discrimination task in healthy volunteers. Significance: Dual-hemisphere tDCS may be a useful strategy to improve sensory function in patients with sensory dysfunctions. Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Transcranial direct current stimulation (tDCS) is a non-invasive technique that stimulates brain regions by delivering weak direct
q
This study was conducted in Tokyo Bay Rehabilitation Hospital, Chiba, Japan.
⇑ Corresponding authors. Address: Center for Fostering Young and Innovative Researchers, Nagoya Institute of Technology, Gokiso-cho Showa-Ku, Nagoya 4668555, Japan. Tel./fax: +81 52 735 7150. E-mail addresses: [email protected], [email protected] (S. Tanaka). 1 These authors contributed equally to this work.
currents through the skull (Priori et al., 1998; Nitsche and Paulus, 2000). Depending on the polarity of stimulation, tDCS can increase or decrease the excitability of a stimulated cortical region. The excitability of the primary motor cortex (M1), for example, is transiently increased by anodal tDCS and decreased by cathodal tDCS (Nitsche and Paulus, 2000, 2001; Furubayashi et al., 2008; Tatemoto et al., 2013). Furthermore, tDCS-induced excitability changes are associated with changes in the performance of motor tasks (Fregni et al., 2005; Hummel et al., 2005; Hummel and Cohen, 2006; Tanaka et al., 2009, 2011a,b). Since a tDCS device is relatively small and elicits no acoustic noise and muscle twitching compared with other brain stimulation techniques, it is suitable for
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.12.100
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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double-blind sham-controlled studies and clinical applications (Gandiga et al., 2006; Fregni and Pascual-Leone, 2007; Hummel et al., 2008; Tanaka and Watanabe, 2009). Previous studies have shown that tDCS can modulate somatosensory evoked potentials (SEP) and somatosensory processing (Song et al., 2011). For example, anodal tDCS over the M1 increased SEPs (Matsunaga et al., 2004), whereas cathodal tDCS over the primary somatosensory cortex (S1) decreased SEPs (Dieckhofer et al., 2006). Behaviorally, cathodal tDCS over S1 decreased the performance of a tactile frequency discrimination task (Rogalewski et al., 2004), while anodal tDCS over S1 improved the performance of a tactile spatial discrimination task (Ragert et al., 2008). A recent study also showed that repeated application of tDCS over S1 improved spatial tactile sensation in multiple sclerosis (MS) patients (Mori et al., 2012). These findings imply that tDCS may be a useful tool for modulating somatosensory function, and may promote functional recovery in patients with somatosensory dysfunction (Song et al., 2011). Recently, a dual-hemisphere tDCS protocol was proposed as a new powerful strategy to modulate brain function (Vines et al., 2008a). In dual-hemisphere tDCS, both hemispheres are simultaneously stimulated in order to excite one hemisphere by anodal tDCS and inhibit the other by cathodal tDCS. The dual-hemisphere tDCS technique is based on the phenomenon of inter-hemispheric inhibition (Curtis, 1940), whereby one hemisphere of the brain inhibits the contralateral hemisphere, and has been demonstrated using transcranial magnetic stimulation (Theoret et al., 2003; Kobayashi et al., 2004, 2009; Takeuchi et al., 2005) and tDCS (Fregni et al., 2005; Boggio et al., 2006; Vines et al., 2006, 2008b). Recent studies have shown that dual-hemisphere tDCS improved motor and cognitive function in both healthy volunteers and stroke patients (Vines et al., 2008a; Cohen Kadosh et al., 2010; Lindenberg et al., 2010; Williams et al., 2010; Lefebvre et al., 2012, 2013; Kasahara et al., 2013; Vandermeeren et al., 2013). However, effect of dual-hemisphere tDCS on somatosensory function remains unknown. The purpose of the present study was to investigate the effect of dual-hemisphere tDCS over S1 on somatosensory function in healthy volunteers. A dual-hemisphere tDCS protocol that excites the left S1 and inhibits the right S1 would increase the excitability of the left S1 and simultaneously decrease the excitability of the right S1. There is some evidence of inter-hemispheric inhibition between S1 in human subjects (Werhahn et al., 2002; Hlushchuk and Hari, 2006; Ragert et al., 2011). Thus, a decrease in excitability of the right S1 might further increase the excitability of the left S1 through a reduction in inter-hemispheric inhibition, and improve somatosensory performance in the right hand. Thus, we hypothesized that the performance of a tactile spatial discrimination task in the right index finger would be enhanced by dual-hemisphere tDCS (anodal stimulation over the right S1 and cathodal over left S1) relative to anodal application over the left S1 or sham stimulation (Ragert et al., 2008).
2. Methods 2.1. Participants Nine healthy volunteers (7 males and 2 females; mean age ± SD = 24.3 ± 0.71 years) participated in the study. All participants were right hand dominant, as assessed with the Edinburgh handedness inventory (Oldfield, 1971), and no participants had a history of psychiatric or neurological illness. All participants gave written, informed consent before the experiments, which were approved by the local ethics committee of Tokyo Bay Rehabilitation Hospital.
2.2. Experimental procedure The study employed a double-blind, crossover, sham-controlled experimental design (Hummel et al., 2005; Gandiga et al., 2006). We compared the effect of dual-, uni-hemisphere, and sham tDCS over S1 on performance of the grating orientation task (GOT) using the right index finger in healthy participants (Johnson and Phillips, 1981; Van Boven and Johnson, 1994; Ragert et al., 2008). All participants underwent 3 conditions (dual-, uni-hemisphere, and sham stimulation) separated by at least 3 days. In the dual-hemisphere tDCS condition, 20 min of anodal tDCS was applied over the left S1 and cathodal tDCS was applied over the right S1. In the unihemisphere condition, anodal tDCS was applied over the left S1 and cathodal tDCS was applied over the forehead above the contralateral orbit. In the sham condition, tDCS over bilateral S1 was applied only for first 30 s. The condition order was counterbalanced among the participants using a Latin square. The experimenter who measured performance of the GOT and participants did not know which session was real and which a sham stimulation. Before starting the first session the participants were familiarized with the tasks. Each session consisted of 4 task blocks (before, during, 0 and 30 min after each intervention). For all conditions, a block of the GOT with stimulation began 5 min after the stimulation current was ramped up. It took roughly 10 min for participants to complete a block of the GOT. Questionnaires’ scores of participants’ attention, fatigue, pain and discomfort levels were obtained after each intervention. 2.3. Grating orientation task Performance of spatial tactile discrimination was evaluated using the GOT (Van Boven and Johnson, 1994). The GOT is a widely accepted measure of tactile spatial acuity (Johnson and Phillips, 1981; Van Boven and Johnson, 1994). A facilitative effect of anodal tDCS over S1 on the GOT performance was previously reported (Ragert et al., 2008; Mori et al., 2012). During the task, participants sat on a chair in a comfortable position and their eyes were masked. The tactile stimuli were applied using six hemispherical plastic domes with grooves of a different width cut (0.5, 0.75, 1.0, 1.2, 1.5 and 2.0 mm) into their surfaces (Tactile Acuity Grating, MedCore). The domes were applied with moderate force onto the palmar side of right index finger for 2 s. In each trial, the Grooves of the dome were randomly oriented in one of two directions: parallel or orthogonal to the axis of the index finger. Immediately after touching the domes, participants answered verbally whether the orientation of the grating of the presented dome was parallel or orthogonal in a two-alternative force-choice paradigm. Each dome was presented 20 times in one block (10 trials for parallel and 10 trials for orthogonal directions). In each block, the trial started with the largest grating (2.0 mm) and ended with the smallest grating (0.5 mm). To standardize these procedures, a custom-made device that helped the investigator to control the up-down movements of the domes was used. Only one skill investigator tested all participants in order to minimize possible performance variance. Instead of using a grating discrimination threshold (width of grating below 75% correct response), we used the percentage of the correct response at each width as a primary outcome measurement. This is because dual-hemisphere tDCS is a powerful method of intervention, and it is possible that dualhemisphere tDCS could improve the GOT performance with a small width of grating at which participants’ correct response are far below 75%. If we tested only the width of grating around the grating discrimination threshold, such an improvement would be overlooked. The grating discrimination threshold was used as a secondary outcome measure. The grating discrimination
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
S. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
threshold was defined as the level at which 75% of the responses were correct. For details about our grating discrimination threshold calculations, see Ragert et al. (2008).
2.4. Transcranial direct current stimulation tDCS was delivered using a DC Stimulator Plus (NeuroConn, Germany) with a direct current through two sponge surface electrodes (each with a surface area of 25 cm2). The intensity of stimulation was 1 mA. In the dual and uni-hemisphere tDCS conditions, the direct current was applied for 20 min (including the initial 15 s during which the current was gradually increased from 0 and the last 15 s during which it was gradually decreased to 0). The current density at the stimulation electrodes was 0.025 mA/cm2. These parameters are in accordance with a safety criterion and far below the threshold for tissue damage (Nitsche et al., 2003; Poreisz et al., 2007). For the sham condition, the same procedure was used but the current was applied for only 30 s (Gandiga et al., 2006). In all conditions the electrodes were placed over the bilateral S1 and contralateral orbit. However, active electrodes always accounted for two out of the three electrodes according to the type of condition. This procedure enabled us to blind the investigator to the experimental condition. To identify the region of S1, T1 anatomical images in all participants were obtained using magnetic resonance imaging (Intera 1.5T; Philips, Netherlands) before the tDCS experiment. For each participant, the centers of the stimulation electrodes were placed over the area of S1 that was identified in the individual T1 anatomical image. This area was localized using a frameless stereotaxic navigation system (Brainsight2; Rogue Research Inc., Montreal, Canada).
2.5. Questionnaires As it was possible that the subjective state of the participants during each intervention might influence their performance, they completed questionnaires to rate their level of attention (1 = no distraction of attention, 4 = highest distraction of attention), fatigue (1 = no fatigue, 4 = highest level of fatigue), pain (1 = no pain, 4 = strongest pain) and discomfort (1 = no discomfort, 4 = strongest discomfort) using a four-point scale at the end of each intervention (Poreisz et al., 2007).
2.6. Statistical analysis For each participant, mean percentage of the correct response at each width of grating was calculated for each block, and then averaged across the participants. The mean percentage of the correct response was subjected to a three-way repeated measures analysis of variance (ANOVA) with INTERVENTION (dual-, uni-hemisphere, and sham tDCS), WIDTH (width of grating; 0.5, 0.75, 1.0, 1.2 1.5 and 2.0 mm) and TIME (pre, during, 0 and 30 min after the interventions) as within-subject factors. Dunnett’s test (one-tailed; compared with the dual-hemisphere tDCS condition) was adopted for multiple-planned comparisons (Dunnett, 1955; Hsu 1996) based on the hypothesis that the percentage of the correct response of the GOT in the dual-hemisphere tDCS condition was significantly higher than that in the uni-hemisphere and sham conditions. The questionnaires’ scales were analyzed using Fisher’s exact test. In all statistics in the present study, the level of significance was defined as p < 0.05.
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3. Results 3.1. The grating orientation task Three-way repeated measures ANOVA adjusted by HuynhFeldt’s e revealed significant main effects of TIME [F(2.8, 22.6) = 18.48, p < 0.05] and WIDTH [F(4.5, 36.2) = 139.66, p < 0.05], and no significant main effect of INTERVENTION [F(2.0, 16.0) = 3.04, p = 0.076]. The three-way interaction among TIME, WIDTH and INTERVENTION was significant [F(28.7, 230.0) = 1.80, p < 0.05], suggesting that the effect of these interventions on the performance of the GOT was different among the different time points. To further explore this interaction, two-way repeated measures of ANOVA were performed for each time point. 3.1.1. Performance before the interventions Percentages of correct responses before the interventions were not significantly different among the three interventions [WIDTH: F(5, 40) = 81.02, p < 0.05; INTERVENTION: F(2, 16) = 2.03, p = 0.16; interaction: F(10,80) = 1.37, p = 0.21] (Fig. 1A). 3.1.2. Performance during the interventions Two-way repeated ANOVA revealed significant main effects of INTERVENTION [F(2, 16) = 9.83, p < 0.05], WIDTH [F(2.4, 19.2) = 138.85, p < 0.05], and their interaction [F(4.3, 34.1) = 4.15, p < 0.05] (Fig. 1B). Post hoc analysis revealed that the percentage of correct responses during the dual-hemisphere tDCS condition was significantly higher relative to the sham condition when the width of grating was 0.75, 1.0 and 1.2 mm (all p < 0.05). The percentage of correct responses at the width of 1.2 mm during the sham condition was 76.7%, which was closest to the participants’ discrimination threshold (75%). More importantly, the percentage of correct responses during the dual-hemisphere tDCS condition (70.6%) was higher relative to the uni-hemisphere tDCS condition (58.9%) at the width of 0.75 mm (p < 0.05). Previous findings have suggested that uni-hemisphere tDCS improved GOT performance compared with a sham condition (Ragert et al., 2008). We replicated this finding by showing that the percentage of correct responses in the uni-hemisphere tDCS condition was significantly higher than that in the sham condition when the grating width was set at 0.75 mm and 1.2 mm (one tail, p < 0.05). As a secondary outcome measurement, we analyzed the effect of tDCS on the grating discrimination threshold (Table 1). We found that the discrimination threshold in the dual(0.90 + 0.08 mm) and uni-tDCS conditions (1.02 + 0.05 mm) was significantly lower than that in the sham condition (1.27 + 0.08 mm) (p < 0.01 for dual vs. sham; p < 0.05 for uni vs. sham). However, the grating discrimination threshold was not significantly different between the dual and uni- tDCS conditions (p = 0.39). 3.1.3. Performance immediately after the end of interventions There were significant main effects of INTERVENTION [F(2, 16) = 3.75, p < 0.05] and WIDTH [F(2.6, 20.7) = 88.33, p < 0.05], while their interaction was not significant [F(4.32, 34.6) = 1.88, p = 0.13] (Fig. 1C). However, planed comparison revealed that the percentage of correct responses during the dual-hemisphere tDCS condition (63.9%) was significantly higher relative to the uni-hemisphere tDCS (54.4%) and the sham (53.9%) conditions when the width of grating was 0.75 mm (both p < 0.05). 3.1.4. Performance 30 min after the end of interventions The percentage of correct responses at 30 min after the interventions was not significantly different among the three interventions [main effect of WITDH: F(5, 40) = 97.65, p < 0.05;
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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S. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
A
B
Correct Response (%)
100
C
100
Pre
90
During 90
80
80
70
70
60
60
50
50
40
40 2.0
1.5
1.2
1.0
0.75
0.5
* * 2.0
D
100
#
1.5
1.2
1.0
Correct Response (%)
0 min after
0.5
30 min after 90
80
80
#
0.75
100
90
70
*
70
60
60
50
50
*
40
40 2.0
1.5
1.2
1.0
0.75
0.5
2.0
Widths of gratings (mm)
1.5
1.2
1.0
0.75
0.5
Widths of gratings (mm)
Dual
Uni
Sham
Fig. 1. Group results of grating orientation task. Mean percentage of correct response (%) is plotted as a function of width of grating relative to the intervention, with bars indicating standard error. Dual-hemisphere tDCS (white circle) significantly improved the percentage of correct responses compared with the uni-hemisphere (black circle) and sham tDCS (black triangle) conditions during and immediately after the stimulation (B and C). On the other hand, no significant improvement was observed before and 30 min after the stimulation (A and D). #significant difference in the performance between dual- and uni-hemisphere conditions (p < 0.05). *significant difference in the performance between dual-hemisphere and sham conditions (p < 0.05).
Table 1 Grating discrimination threshold (mm). Data represent the group mean ± SE before, during and after each intervention. (mm)
Pre
During
Post
Post 30 min
Dual Uni Sham
1.31 ± 0.06 1.20 ± 0.05 1.26 ± 0.11
0.90 ± 0.08 1.02 ± 0.05 1.27 ± 0.08
1.05 ± 0.12 1.08 ± 0.04 1.28 ± 0.10
1.23 ± 0.11 1.17 ± 0.05 1.32 ± 0.09
INTERVENTION: F(2, 16) = 2.12, p = 0.15; interaction: F(4.2,33.3) = 0.71, p = 0.60] (Fig. 1D).
Table 2 Questionnaires’ scores after each intervention. Data represent the group mean ± SD. Attention was scored on a scale of 1 to 4 (1 = no distraction of attention; 4 = highest distraction of attention). Fatigue was scored on a scale of 1 to 4 (1 = no fatigue; 4 = highest level of fatigue). Pain was scored on a scale of 1 to 4 (1 = no pain; 4 = strongest pain). Discomfort was scored on a scale of 1 to 4 (1 = no discomfort; 4 = strongest discomfort).
Attention Fatigue Pain Discomfort
Dual
Uni
Sham
Statistics (Fisher’s exact test)
1.2 ± 0.4 1.6 ± 0.5 1.1 ± 0.3 1.1 ± 0.3
1.1 ± 0.3 1.3 ± 0.5 1.7 ± 0.9 1.6 ± 0.9
1.4 ± 0.7 1.4 ± 0.7 1.1 ± 0.3 1.3 ± 1.0
Non Non Non Non
significant significant significant significant
3.2. Questionnaires’ scores None of the participants reported side effects. The questionnaires’ scores recorded after each intervention revealed that the tDCS (dual-, uni-hemisphere, or sham) did not significantly influence the participants’ attention, fatigue, pain or discomfort (Table 2). 4. Discussion Using a double-blind, sham-controlled and cross-over design, the present results demonstrated for the first time that dual-hemisphere
tDCS over S1 temporarily facilitated performance of the tactile spatial discrimination task compared with uni-hemisphere and sham stimulation. The significant performance improvement was mostly observed during the stimulation period, and was diminished 30 min after the end of stimulation. The absence of significant difference in the questionnaires’ scores among the stimulation conditions indicated that the results were not caused by differences in general effects among the conditions such as changes in attention, fatigue or pain/discomfort. Improvement of spatial tactile acuity by uni-hemisphere anodal tDCS has been observed in previous tDCS studies (Ragert et al.,
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
S. Fujimoto et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
2008; Mori et al., 2012). For example, 20 min of anodal tDCS applied over S1 enhanced the GOT performance in the contralateral hand relative to sham stimulation (Ragert et al., 2008). In that study, the performance improvement lasted for 40 min after the end of the stimulation. The present study replicated these findings by showing that uni-hemisphere tDCS improved performance of the GOT more than the sham condition. One difference between our results and those reported by Ragert et al. (2008) lies in the duration of the after-effects of tDCS. In their study, uni-hemisphere tDCS affected performance for at least 40 min after the intervention (Ragert et al., 2008). In contrast, we observed the effects of tDCS to be relatively short-lasting. The reason for this discrepancy is unclear. One possibility might be differences in the study populations, because there are known to be individual differences in the response to tDCS (Furubayashi et al., 2008). Our small sample size may have emphasized this individual difference. Another possibility is that the contrasting results are due to differences in equipment and/or experimental conditions between the two studies. More importantly, we found that dual hemispheric tDCS over S1 improved the GOT performance more strongly than the uni-hemisphere stimulation protocol. A significant improvement was observed during the intervention at a 0.75 mm width of grating. The percentage of correct responses in the uni-hemisphere tDCS (58.9%) and sham condition (54.4%) was at the chance level, while the performance during dual-hemisphere tDCS (70.6%) was significantly greater than the chance level (binominal test, p < 0.05). This result implies that dual-hemispheric tDCS might be effective in relatively difficult tactile discrimination tasks. Functional improvement by dual-hemisphere tDCS was previously reported in motor and cognitive domains (Vines et al., 2008a; Cohen Kadosh et al., 2010; Lindenberg et al., 2010; Lefebvre et al., 2012, 2013; Kasahara et al., 2013; Vandermeeren et al., 2013). The present study showed that the dual-hemisphere tDCS protocol was also effective for the somatosensory domain. This may be due to a combined effect of increased excitability in the left S1 by anodal tDCS, and decreased inter-hemispheric inhibition from the right to the left S1, probably via inter-hemispheric connections. In turn, the decrease in excitability of the right S1 has add-on effects to the excitability of S1 through a reduction in inter-hemispheric inhibition. Recent concurrent studies of dual tDCS and functional MRI have indicated that dual tDCS over the sensorimotor cortex may transiently modulate functional connectivity. This effect may occur not only locally, within the stimulated cortical regions, but also in remote interconnected brain regions, such as the prefrontal cortex (Sehm et al., 2012, 2013; Lindenberg et al., 2013). The behavioral impact of such physiological changes, activated by dual tDCS in remote brain regions, is unclear, warranting further investigation. It is possible that network level global changes may underlie the behavioral gains induced by dual tDCS. In the present study, the stimulation electrode was placed centered over S1. However, due to low spatial focality of tDCS, it is possible that the present protocol stimulated both S1 and M1. To our knowledge, there is no evidence that M1 involves tactile spatial discrimination. By contrast, there is strong evidence that S1 is involved with tactile spatial discriminative function (Burton et al., 1997; Hodzic et al., 2004; Zhang et al., 2005; Kitada et al., 2006; Ragert et al., 2008). Therefore, we consider that improvement of the GOT performance observed in the present study was due to S1 stimulation. The after-effect of dual-hemisphere tDCS on the GOT performance in our study was short-lasting, and diminished 30 min after the end of stimulation period. Therefore, a single session of dualhemispheric tDCS itself might not be powerful enough to be utilized in the clinical setting. Recently, repeated applications of daily tDCS were reported to have long-lasting beneficial effects on cognitive and motor function (Reis et al., 2008, 2009; Cohen Kadosh
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et al., 2010; Lindenberg et al., 2010; Tanaka et al., 2011a). Further, a recent study has shown that daily uni-hemisphere anodal tDCS over S1 ameliorated tactile sensory loss with long-lasting beneficial effects in MS patients (Mori et al., 2012). These findings raise the possibility that repeated applications of dual-hemisphere tDCS over S1 might have a long-term beneficial effect on somatosensory function, although multiple treatment sessions in stroke patients may not necessarily lead to a linear pattern of functional improvement (Lindenberg et al., 2012). In summary, we found that the performance of tactile spatial discrimination task in healthy participants was transiently enhanced by dual-hemisphere hemispheric tDCS over S1. This is the first evidence that dual-hemisphere tDCS is effective for both motor function and somatosensory function in the hand, although the small participant group and unbalanced ratio of male/female participants may limit the strength of our conclusions. Therefore, dual-hemisphere tDCS over S1 might be useful in the neuro-rehabilitation of patients with somatosensory deficits. 5. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgements This work was supported by grants from the Grants-in-Aid for Scientific Research (KAKENHI 24680061) and Funds for the Development of Human Resources in Science and Technology to Satoshi Tanaka. We thank Dr. Rieko Osu and Dr. Norihiro Sadato for technical help in this study. References Boggio PS, Castro LO, Savagim EA, Braite R, Cruz VC, Rocha RR, et al. Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation. Neurosci Lett 2006;404:232–6. Burton H, MacLeod AM, Videen TO, Raichle ME. Multiple foci in parietal and frontal cortex activated by rubbing embossed grating patterns across fingerpads: a positron emission tomography study in humans. Cereb Cortex 1997;7:3–17. Cohen Kadosh R, Soskic S, Iuculano T, Kanai R, Walsh V. Modulating neuronal activity produces specific and long-lasting changes in numerical competence. Curr Biol 2010;20:2016–20. Curtis HJ. Intercortical connections of corpus callosum as indicated by evoked potentials. J Neurophysiol 1940;3:407–13. Dieckhofer A, Waberski TD, Nitsche M, Paulus W, Buchner H, Gobbele R. Transcranial direct current stimulation applied over the somatosensory cortex – differential effect on low and high frequency SEPs. Clin Neurophysiol 2006;117:2221–7. Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955;50:1096–121. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport 2005;16:1551–5. Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol 2007;3:383–93. Furubayashi T, Terao Y, Arai N, Okabe S, Mochizuki H, Hanajima R, et al. Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area. Exp Brain Res 2008;185:279–86. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol 2006;117:845–50. Hlushchuk Y, Hari R. Transient suppression of ipsilateral primary somatosensory cortex during tactile finger stimulation. J Neurosci 2006;26:5819–24. Hodzic A, Veit R, Karim AA, Erb M, Godde B. Improvement and decline in tactile discrimination behavior after cortical plasticity induced by passive tactile coactivation. J Neurosci 2004;24:442–6. Hsu JC. Multiple comparison: theory and methods. New York: Chapman & Hall; . Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. Effects of noninvasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005;128:490–9.
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Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task q Shuhei Fujimoto a,1, Tomofumi Yamaguchi a,b, Yohei Otaka a,b, Kunitsugu Kondo a, Satoshi Tanaka c,⇑,1 a
Tokyo Bay Rehabilitation Hospital, Chiba, Japan Keio University School of Medicine, Tokyo, Japan c Nagoya Institute of Technology, Aichi, Japan b
a r t i c l e
i n f o
Article history: Accepted 12 December 2013 Available online xxxx Keywords: Cortical plasticity Inter-hemispheric inhibition (IHI) Somatosensory cortex Tactile Transcranial direct current stimulation (tDCS) Transcranial magnetic stimulation (TMS)
h i g h l i g h t s Dual-hemisphere transcranial direct stimulation (tDCS) is a novel and powerful strategy to improve
human cognitive and motor function, but its effect on somatosensory function remains unknown. We demonstrated that dual-hemisphere tDCS over the primary somatosensory cortex facilitates
greater improvements for performance in a tactile discrimination task in healthy adults compared with uni-hemisphere and sham tDCS. Dual-hemisphere tDCS might be useful to improve sensory function in patients with sensory dysfunctions.
a b s t r a c t Objective: The aim of this study was to test the hypothesis that dual-hemisphere transcranial direct current stimulation (tDCS) over the primary somatosensory cortex (S1) could improve performance in a tactile spatial discriminative task, compared with uni-hemisphere or sham tDCS. Methods: Nine healthy adults participated in this double-blind, sham-controlled, and cross-over design study. The performance in a grating orientation task (GOT) in the right index finger was evaluated before, during, immediately after and 30 min after the dual-hemisphere, uni-hemisphere (1 mA, 20 min), or sham tDCS (1 mA, 30 s) over S1. In the dual-hemisphere and sham conditions, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the right S1. In the uni-hemisphere condition, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the contralateral supraorbital front. Results: The percentage of correct responses on the GOT during dual-hemisphere tDCS was significantly higher than that in the uni-hemisphere or sham tDCS conditions when the grating width was set to 0.75 mm (all p < 0.05). Conclusions: Dual-hemisphere tDCS over S1 improved performance in a tactile spatial discrimination task in healthy volunteers. Significance: Dual-hemisphere tDCS may be a useful strategy to improve sensory function in patients with sensory dysfunctions. Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Transcranial direct current stimulation (tDCS) is a non-invasive technique that stimulates brain regions by delivering weak direct
q
This study was conducted in Tokyo Bay Rehabilitation Hospital, Chiba, Japan.
⇑ Corresponding authors. Address: Center for Fostering Young and Innovative Researchers, Nagoya Institute of Technology, Gokiso-cho Showa-Ku, Nagoya 4668555, Japan. Tel./fax: +81 52 735 7150. E-mail addresses: [email protected], [email protected] (S. Tanaka). 1 These authors contributed equally to this work.
currents through the skull (Priori et al., 1998; Nitsche and Paulus, 2000). Depending on the polarity of stimulation, tDCS can increase or decrease the excitability of a stimulated cortical region. The excitability of the primary motor cortex (M1), for example, is transiently increased by anodal tDCS and decreased by cathodal tDCS (Nitsche and Paulus, 2000, 2001; Furubayashi et al., 2008; Tatemoto et al., 2013). Furthermore, tDCS-induced excitability changes are associated with changes in the performance of motor tasks (Fregni et al., 2005; Hummel et al., 2005; Hummel and Cohen, 2006; Tanaka et al., 2009, 2011a,b). Since a tDCS device is relatively small and elicits no acoustic noise and muscle twitching compared with other brain stimulation techniques, it is suitable for
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.12.100
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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double-blind sham-controlled studies and clinical applications (Gandiga et al., 2006; Fregni and Pascual-Leone, 2007; Hummel et al., 2008; Tanaka and Watanabe, 2009). Previous studies have shown that tDCS can modulate somatosensory evoked potentials (SEP) and somatosensory processing (Song et al., 2011). For example, anodal tDCS over the M1 increased SEPs (Matsunaga et al., 2004), whereas cathodal tDCS over the primary somatosensory cortex (S1) decreased SEPs (Dieckhofer et al., 2006). Behaviorally, cathodal tDCS over S1 decreased the performance of a tactile frequency discrimination task (Rogalewski et al., 2004), while anodal tDCS over S1 improved the performance of a tactile spatial discrimination task (Ragert et al., 2008). A recent study also showed that repeated application of tDCS over S1 improved spatial tactile sensation in multiple sclerosis (MS) patients (Mori et al., 2012). These findings imply that tDCS may be a useful tool for modulating somatosensory function, and may promote functional recovery in patients with somatosensory dysfunction (Song et al., 2011). Recently, a dual-hemisphere tDCS protocol was proposed as a new powerful strategy to modulate brain function (Vines et al., 2008a). In dual-hemisphere tDCS, both hemispheres are simultaneously stimulated in order to excite one hemisphere by anodal tDCS and inhibit the other by cathodal tDCS. The dual-hemisphere tDCS technique is based on the phenomenon of inter-hemispheric inhibition (Curtis, 1940), whereby one hemisphere of the brain inhibits the contralateral hemisphere, and has been demonstrated using transcranial magnetic stimulation (Theoret et al., 2003; Kobayashi et al., 2004, 2009; Takeuchi et al., 2005) and tDCS (Fregni et al., 2005; Boggio et al., 2006; Vines et al., 2006, 2008b). Recent studies have shown that dual-hemisphere tDCS improved motor and cognitive function in both healthy volunteers and stroke patients (Vines et al., 2008a; Cohen Kadosh et al., 2010; Lindenberg et al., 2010; Williams et al., 2010; Lefebvre et al., 2012, 2013; Kasahara et al., 2013; Vandermeeren et al., 2013). However, effect of dual-hemisphere tDCS on somatosensory function remains unknown. The purpose of the present study was to investigate the effect of dual-hemisphere tDCS over S1 on somatosensory function in healthy volunteers. A dual-hemisphere tDCS protocol that excites the left S1 and inhibits the right S1 would increase the excitability of the left S1 and simultaneously decrease the excitability of the right S1. There is some evidence of inter-hemispheric inhibition between S1 in human subjects (Werhahn et al., 2002; Hlushchuk and Hari, 2006; Ragert et al., 2011). Thus, a decrease in excitability of the right S1 might further increase the excitability of the left S1 through a reduction in inter-hemispheric inhibition, and improve somatosensory performance in the right hand. Thus, we hypothesized that the performance of a tactile spatial discrimination task in the right index finger would be enhanced by dual-hemisphere tDCS (anodal stimulation over the right S1 and cathodal over left S1) relative to anodal application over the left S1 or sham stimulation (Ragert et al., 2008).
2. Methods 2.1. Participants Nine healthy volunteers (7 males and 2 females; mean age ± SD = 24.3 ± 0.71 years) participated in the study. All participants were right hand dominant, as assessed with the Edinburgh handedness inventory (Oldfield, 1971), and no participants had a history of psychiatric or neurological illness. All participants gave written, informed consent before the experiments, which were approved by the local ethics committee of Tokyo Bay Rehabilitation Hospital.
2.2. Experimental procedure The study employed a double-blind, crossover, sham-controlled experimental design (Hummel et al., 2005; Gandiga et al., 2006). We compared the effect of dual-, uni-hemisphere, and sham tDCS over S1 on performance of the grating orientation task (GOT) using the right index finger in healthy participants (Johnson and Phillips, 1981; Van Boven and Johnson, 1994; Ragert et al., 2008). All participants underwent 3 conditions (dual-, uni-hemisphere, and sham stimulation) separated by at least 3 days. In the dual-hemisphere tDCS condition, 20 min of anodal tDCS was applied over the left S1 and cathodal tDCS was applied over the right S1. In the unihemisphere condition, anodal tDCS was applied over the left S1 and cathodal tDCS was applied over the forehead above the contralateral orbit. In the sham condition, tDCS over bilateral S1 was applied only for first 30 s. The condition order was counterbalanced among the participants using a Latin square. The experimenter who measured performance of the GOT and participants did not know which session was real and which a sham stimulation. Before starting the first session the participants were familiarized with the tasks. Each session consisted of 4 task blocks (before, during, 0 and 30 min after each intervention). For all conditions, a block of the GOT with stimulation began 5 min after the stimulation current was ramped up. It took roughly 10 min for participants to complete a block of the GOT. Questionnaires’ scores of participants’ attention, fatigue, pain and discomfort levels were obtained after each intervention. 2.3. Grating orientation task Performance of spatial tactile discrimination was evaluated using the GOT (Van Boven and Johnson, 1994). The GOT is a widely accepted measure of tactile spatial acuity (Johnson and Phillips, 1981; Van Boven and Johnson, 1994). A facilitative effect of anodal tDCS over S1 on the GOT performance was previously reported (Ragert et al., 2008; Mori et al., 2012). During the task, participants sat on a chair in a comfortable position and their eyes were masked. The tactile stimuli were applied using six hemispherical plastic domes with grooves of a different width cut (0.5, 0.75, 1.0, 1.2, 1.5 and 2.0 mm) into their surfaces (Tactile Acuity Grating, MedCore). The domes were applied with moderate force onto the palmar side of right index finger for 2 s. In each trial, the Grooves of the dome were randomly oriented in one of two directions: parallel or orthogonal to the axis of the index finger. Immediately after touching the domes, participants answered verbally whether the orientation of the grating of the presented dome was parallel or orthogonal in a two-alternative force-choice paradigm. Each dome was presented 20 times in one block (10 trials for parallel and 10 trials for orthogonal directions). In each block, the trial started with the largest grating (2.0 mm) and ended with the smallest grating (0.5 mm). To standardize these procedures, a custom-made device that helped the investigator to control the up-down movements of the domes was used. Only one skill investigator tested all participants in order to minimize possible performance variance. Instead of using a grating discrimination threshold (width of grating below 75% correct response), we used the percentage of the correct response at each width as a primary outcome measurement. This is because dual-hemisphere tDCS is a powerful method of intervention, and it is possible that dualhemisphere tDCS could improve the GOT performance with a small width of grating at which participants’ correct response are far below 75%. If we tested only the width of grating around the grating discrimination threshold, such an improvement would be overlooked. The grating discrimination threshold was used as a secondary outcome measure. The grating discrimination
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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threshold was defined as the level at which 75% of the responses were correct. For details about our grating discrimination threshold calculations, see Ragert et al. (2008).
2.4. Transcranial direct current stimulation tDCS was delivered using a DC Stimulator Plus (NeuroConn, Germany) with a direct current through two sponge surface electrodes (each with a surface area of 25 cm2). The intensity of stimulation was 1 mA. In the dual and uni-hemisphere tDCS conditions, the direct current was applied for 20 min (including the initial 15 s during which the current was gradually increased from 0 and the last 15 s during which it was gradually decreased to 0). The current density at the stimulation electrodes was 0.025 mA/cm2. These parameters are in accordance with a safety criterion and far below the threshold for tissue damage (Nitsche et al., 2003; Poreisz et al., 2007). For the sham condition, the same procedure was used but the current was applied for only 30 s (Gandiga et al., 2006). In all conditions the electrodes were placed over the bilateral S1 and contralateral orbit. However, active electrodes always accounted for two out of the three electrodes according to the type of condition. This procedure enabled us to blind the investigator to the experimental condition. To identify the region of S1, T1 anatomical images in all participants were obtained using magnetic resonance imaging (Intera 1.5T; Philips, Netherlands) before the tDCS experiment. For each participant, the centers of the stimulation electrodes were placed over the area of S1 that was identified in the individual T1 anatomical image. This area was localized using a frameless stereotaxic navigation system (Brainsight2; Rogue Research Inc., Montreal, Canada).
2.5. Questionnaires As it was possible that the subjective state of the participants during each intervention might influence their performance, they completed questionnaires to rate their level of attention (1 = no distraction of attention, 4 = highest distraction of attention), fatigue (1 = no fatigue, 4 = highest level of fatigue), pain (1 = no pain, 4 = strongest pain) and discomfort (1 = no discomfort, 4 = strongest discomfort) using a four-point scale at the end of each intervention (Poreisz et al., 2007).
2.6. Statistical analysis For each participant, mean percentage of the correct response at each width of grating was calculated for each block, and then averaged across the participants. The mean percentage of the correct response was subjected to a three-way repeated measures analysis of variance (ANOVA) with INTERVENTION (dual-, uni-hemisphere, and sham tDCS), WIDTH (width of grating; 0.5, 0.75, 1.0, 1.2 1.5 and 2.0 mm) and TIME (pre, during, 0 and 30 min after the interventions) as within-subject factors. Dunnett’s test (one-tailed; compared with the dual-hemisphere tDCS condition) was adopted for multiple-planned comparisons (Dunnett, 1955; Hsu 1996) based on the hypothesis that the percentage of the correct response of the GOT in the dual-hemisphere tDCS condition was significantly higher than that in the uni-hemisphere and sham conditions. The questionnaires’ scales were analyzed using Fisher’s exact test. In all statistics in the present study, the level of significance was defined as p < 0.05.
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3. Results 3.1. The grating orientation task Three-way repeated measures ANOVA adjusted by HuynhFeldt’s e revealed significant main effects of TIME [F(2.8, 22.6) = 18.48, p < 0.05] and WIDTH [F(4.5, 36.2) = 139.66, p < 0.05], and no significant main effect of INTERVENTION [F(2.0, 16.0) = 3.04, p = 0.076]. The three-way interaction among TIME, WIDTH and INTERVENTION was significant [F(28.7, 230.0) = 1.80, p < 0.05], suggesting that the effect of these interventions on the performance of the GOT was different among the different time points. To further explore this interaction, two-way repeated measures of ANOVA were performed for each time point. 3.1.1. Performance before the interventions Percentages of correct responses before the interventions were not significantly different among the three interventions [WIDTH: F(5, 40) = 81.02, p < 0.05; INTERVENTION: F(2, 16) = 2.03, p = 0.16; interaction: F(10,80) = 1.37, p = 0.21] (Fig. 1A). 3.1.2. Performance during the interventions Two-way repeated ANOVA revealed significant main effects of INTERVENTION [F(2, 16) = 9.83, p < 0.05], WIDTH [F(2.4, 19.2) = 138.85, p < 0.05], and their interaction [F(4.3, 34.1) = 4.15, p < 0.05] (Fig. 1B). Post hoc analysis revealed that the percentage of correct responses during the dual-hemisphere tDCS condition was significantly higher relative to the sham condition when the width of grating was 0.75, 1.0 and 1.2 mm (all p < 0.05). The percentage of correct responses at the width of 1.2 mm during the sham condition was 76.7%, which was closest to the participants’ discrimination threshold (75%). More importantly, the percentage of correct responses during the dual-hemisphere tDCS condition (70.6%) was higher relative to the uni-hemisphere tDCS condition (58.9%) at the width of 0.75 mm (p < 0.05). Previous findings have suggested that uni-hemisphere tDCS improved GOT performance compared with a sham condition (Ragert et al., 2008). We replicated this finding by showing that the percentage of correct responses in the uni-hemisphere tDCS condition was significantly higher than that in the sham condition when the grating width was set at 0.75 mm and 1.2 mm (one tail, p < 0.05). As a secondary outcome measurement, we analyzed the effect of tDCS on the grating discrimination threshold (Table 1). We found that the discrimination threshold in the dual(0.90 + 0.08 mm) and uni-tDCS conditions (1.02 + 0.05 mm) was significantly lower than that in the sham condition (1.27 + 0.08 mm) (p < 0.01 for dual vs. sham; p < 0.05 for uni vs. sham). However, the grating discrimination threshold was not significantly different between the dual and uni- tDCS conditions (p = 0.39). 3.1.3. Performance immediately after the end of interventions There were significant main effects of INTERVENTION [F(2, 16) = 3.75, p < 0.05] and WIDTH [F(2.6, 20.7) = 88.33, p < 0.05], while their interaction was not significant [F(4.32, 34.6) = 1.88, p = 0.13] (Fig. 1C). However, planed comparison revealed that the percentage of correct responses during the dual-hemisphere tDCS condition (63.9%) was significantly higher relative to the uni-hemisphere tDCS (54.4%) and the sham (53.9%) conditions when the width of grating was 0.75 mm (both p < 0.05). 3.1.4. Performance 30 min after the end of interventions The percentage of correct responses at 30 min after the interventions was not significantly different among the three interventions [main effect of WITDH: F(5, 40) = 97.65, p < 0.05;
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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A
B
Correct Response (%)
100
C
100
Pre
90
During 90
80
80
70
70
60
60
50
50
40
40 2.0
1.5
1.2
1.0
0.75
0.5
* * 2.0
D
100
#
1.5
1.2
1.0
Correct Response (%)
0 min after
0.5
30 min after 90
80
80
#
0.75
100
90
70
*
70
60
60
50
50
*
40
40 2.0
1.5
1.2
1.0
0.75
0.5
2.0
Widths of gratings (mm)
1.5
1.2
1.0
0.75
0.5
Widths of gratings (mm)
Dual
Uni
Sham
Fig. 1. Group results of grating orientation task. Mean percentage of correct response (%) is plotted as a function of width of grating relative to the intervention, with bars indicating standard error. Dual-hemisphere tDCS (white circle) significantly improved the percentage of correct responses compared with the uni-hemisphere (black circle) and sham tDCS (black triangle) conditions during and immediately after the stimulation (B and C). On the other hand, no significant improvement was observed before and 30 min after the stimulation (A and D). #significant difference in the performance between dual- and uni-hemisphere conditions (p < 0.05). *significant difference in the performance between dual-hemisphere and sham conditions (p < 0.05).
Table 1 Grating discrimination threshold (mm). Data represent the group mean ± SE before, during and after each intervention. (mm)
Pre
During
Post
Post 30 min
Dual Uni Sham
1.31 ± 0.06 1.20 ± 0.05 1.26 ± 0.11
0.90 ± 0.08 1.02 ± 0.05 1.27 ± 0.08
1.05 ± 0.12 1.08 ± 0.04 1.28 ± 0.10
1.23 ± 0.11 1.17 ± 0.05 1.32 ± 0.09
INTERVENTION: F(2, 16) = 2.12, p = 0.15; interaction: F(4.2,33.3) = 0.71, p = 0.60] (Fig. 1D).
Table 2 Questionnaires’ scores after each intervention. Data represent the group mean ± SD. Attention was scored on a scale of 1 to 4 (1 = no distraction of attention; 4 = highest distraction of attention). Fatigue was scored on a scale of 1 to 4 (1 = no fatigue; 4 = highest level of fatigue). Pain was scored on a scale of 1 to 4 (1 = no pain; 4 = strongest pain). Discomfort was scored on a scale of 1 to 4 (1 = no discomfort; 4 = strongest discomfort).
Attention Fatigue Pain Discomfort
Dual
Uni
Sham
Statistics (Fisher’s exact test)
1.2 ± 0.4 1.6 ± 0.5 1.1 ± 0.3 1.1 ± 0.3
1.1 ± 0.3 1.3 ± 0.5 1.7 ± 0.9 1.6 ± 0.9
1.4 ± 0.7 1.4 ± 0.7 1.1 ± 0.3 1.3 ± 1.0
Non Non Non Non
significant significant significant significant
3.2. Questionnaires’ scores None of the participants reported side effects. The questionnaires’ scores recorded after each intervention revealed that the tDCS (dual-, uni-hemisphere, or sham) did not significantly influence the participants’ attention, fatigue, pain or discomfort (Table 2). 4. Discussion Using a double-blind, sham-controlled and cross-over design, the present results demonstrated for the first time that dual-hemisphere
tDCS over S1 temporarily facilitated performance of the tactile spatial discrimination task compared with uni-hemisphere and sham stimulation. The significant performance improvement was mostly observed during the stimulation period, and was diminished 30 min after the end of stimulation. The absence of significant difference in the questionnaires’ scores among the stimulation conditions indicated that the results were not caused by differences in general effects among the conditions such as changes in attention, fatigue or pain/discomfort. Improvement of spatial tactile acuity by uni-hemisphere anodal tDCS has been observed in previous tDCS studies (Ragert et al.,
Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100
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2008; Mori et al., 2012). For example, 20 min of anodal tDCS applied over S1 enhanced the GOT performance in the contralateral hand relative to sham stimulation (Ragert et al., 2008). In that study, the performance improvement lasted for 40 min after the end of the stimulation. The present study replicated these findings by showing that uni-hemisphere tDCS improved performance of the GOT more than the sham condition. One difference between our results and those reported by Ragert et al. (2008) lies in the duration of the after-effects of tDCS. In their study, uni-hemisphere tDCS affected performance for at least 40 min after the intervention (Ragert et al., 2008). In contrast, we observed the effects of tDCS to be relatively short-lasting. The reason for this discrepancy is unclear. One possibility might be differences in the study populations, because there are known to be individual differences in the response to tDCS (Furubayashi et al., 2008). Our small sample size may have emphasized this individual difference. Another possibility is that the contrasting results are due to differences in equipment and/or experimental conditions between the two studies. More importantly, we found that dual hemispheric tDCS over S1 improved the GOT performance more strongly than the uni-hemisphere stimulation protocol. A significant improvement was observed during the intervention at a 0.75 mm width of grating. The percentage of correct responses in the uni-hemisphere tDCS (58.9%) and sham condition (54.4%) was at the chance level, while the performance during dual-hemisphere tDCS (70.6%) was significantly greater than the chance level (binominal test, p < 0.05). This result implies that dual-hemispheric tDCS might be effective in relatively difficult tactile discrimination tasks. Functional improvement by dual-hemisphere tDCS was previously reported in motor and cognitive domains (Vines et al., 2008a; Cohen Kadosh et al., 2010; Lindenberg et al., 2010; Lefebvre et al., 2012, 2013; Kasahara et al., 2013; Vandermeeren et al., 2013). The present study showed that the dual-hemisphere tDCS protocol was also effective for the somatosensory domain. This may be due to a combined effect of increased excitability in the left S1 by anodal tDCS, and decreased inter-hemispheric inhibition from the right to the left S1, probably via inter-hemispheric connections. In turn, the decrease in excitability of the right S1 has add-on effects to the excitability of S1 through a reduction in inter-hemispheric inhibition. Recent concurrent studies of dual tDCS and functional MRI have indicated that dual tDCS over the sensorimotor cortex may transiently modulate functional connectivity. This effect may occur not only locally, within the stimulated cortical regions, but also in remote interconnected brain regions, such as the prefrontal cortex (Sehm et al., 2012, 2013; Lindenberg et al., 2013). The behavioral impact of such physiological changes, activated by dual tDCS in remote brain regions, is unclear, warranting further investigation. It is possible that network level global changes may underlie the behavioral gains induced by dual tDCS. In the present study, the stimulation electrode was placed centered over S1. However, due to low spatial focality of tDCS, it is possible that the present protocol stimulated both S1 and M1. To our knowledge, there is no evidence that M1 involves tactile spatial discrimination. By contrast, there is strong evidence that S1 is involved with tactile spatial discriminative function (Burton et al., 1997; Hodzic et al., 2004; Zhang et al., 2005; Kitada et al., 2006; Ragert et al., 2008). Therefore, we consider that improvement of the GOT performance observed in the present study was due to S1 stimulation. The after-effect of dual-hemisphere tDCS on the GOT performance in our study was short-lasting, and diminished 30 min after the end of stimulation period. Therefore, a single session of dualhemispheric tDCS itself might not be powerful enough to be utilized in the clinical setting. Recently, repeated applications of daily tDCS were reported to have long-lasting beneficial effects on cognitive and motor function (Reis et al., 2008, 2009; Cohen Kadosh
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et al., 2010; Lindenberg et al., 2010; Tanaka et al., 2011a). Further, a recent study has shown that daily uni-hemisphere anodal tDCS over S1 ameliorated tactile sensory loss with long-lasting beneficial effects in MS patients (Mori et al., 2012). These findings raise the possibility that repeated applications of dual-hemisphere tDCS over S1 might have a long-term beneficial effect on somatosensory function, although multiple treatment sessions in stroke patients may not necessarily lead to a linear pattern of functional improvement (Lindenberg et al., 2012). In summary, we found that the performance of tactile spatial discrimination task in healthy participants was transiently enhanced by dual-hemisphere hemispheric tDCS over S1. This is the first evidence that dual-hemisphere tDCS is effective for both motor function and somatosensory function in the hand, although the small participant group and unbalanced ratio of male/female participants may limit the strength of our conclusions. Therefore, dual-hemisphere tDCS over S1 might be useful in the neuro-rehabilitation of patients with somatosensory deficits. 5. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgements This work was supported by grants from the Grants-in-Aid for Scientific Research (KAKENHI 24680061) and Funds for the Development of Human Resources in Science and Technology to Satoshi Tanaka. We thank Dr. Rieko Osu and Dr. Norihiro Sadato for technical help in this study. References Boggio PS, Castro LO, Savagim EA, Braite R, Cruz VC, Rocha RR, et al. Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation. Neurosci Lett 2006;404:232–6. Burton H, MacLeod AM, Videen TO, Raichle ME. Multiple foci in parietal and frontal cortex activated by rubbing embossed grating patterns across fingerpads: a positron emission tomography study in humans. Cereb Cortex 1997;7:3–17. Cohen Kadosh R, Soskic S, Iuculano T, Kanai R, Walsh V. Modulating neuronal activity produces specific and long-lasting changes in numerical competence. Curr Biol 2010;20:2016–20. Curtis HJ. Intercortical connections of corpus callosum as indicated by evoked potentials. J Neurophysiol 1940;3:407–13. Dieckhofer A, Waberski TD, Nitsche M, Paulus W, Buchner H, Gobbele R. Transcranial direct current stimulation applied over the somatosensory cortex – differential effect on low and high frequency SEPs. Clin Neurophysiol 2006;117:2221–7. Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955;50:1096–121. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport 2005;16:1551–5. Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol 2007;3:383–93. Furubayashi T, Terao Y, Arai N, Okabe S, Mochizuki H, Hanajima R, et al. Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area. Exp Brain Res 2008;185:279–86. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol 2006;117:845–50. Hlushchuk Y, Hari R. Transient suppression of ipsilateral primary somatosensory cortex during tactile finger stimulation. J Neurosci 2006;26:5819–24. Hodzic A, Veit R, Karim AA, Erb M, Godde B. Improvement and decline in tactile discrimination behavior after cortical plasticity induced by passive tactile coactivation. J Neurosci 2004;24:442–6. Hsu JC. Multiple comparison: theory and methods. New York: Chapman & Hall; . Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. Effects of noninvasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005;128:490–9.
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Please cite this article in press as: Fujimoto S et al. Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.100