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Cathodal HD-tDCS on the right V5 improves motion perception in humans

Cathodal HD-tDCS on the right V5 improves motion perception in humans ORIGINAL RESEARCH published: 23 September 2015 doi: 10.3389/fnbeh.2015.00257 Cathodal HD-tDCS on the right V5 improves motion perception in humans 1 1 1 1,2 1,3 Giuseppe A. Zito , Theresa Senti , Dario Cazzoli , René M. Müri , Urs P. Mosimann , 4 1,5 Thomas Nyffeler and Tobias Nef * 1 2 Gerontechnology and Rehabilitation Group, University of Bern, Bern, Switzerland, Division of Cognitive and Restorative Neurology, Department of Neurology, University Hospital Inselspital, University of Bern, Bern, Switzerland, University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland, Center of Neurology and Neurorehabilitation, Luzerner Kantonsspital, Luzern, Switzerland, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy Edited by: Agnes Gruart, volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right University Pablo de Olavide, Spain V5 and their performance on a visual test was recorded. The results showed significant Reviewed by: improvement in motion perception in the left hemifield after cathodal HD-tDCS, but Jason Moser, Michigan State University, USA not in shape perception. Sham and anodal HD-tDCS did not affect performance. The Andrés Molero-Chamizo, specific effect of influencing performance of visual tasks by modulating the excitability University of Huelva, Spain of the neurons in the visual cortex might be explained by the complexity of perceptual *Correspondence: information needed for the tasks. This provokes a “noisy” activation state of the encoding Tobias Nef, Gerontechnology and Rehabilitation neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the Group and ARTORG Center for correct perception by decreasing global excitation and thus diminishing the “noise” Biomedical Engineering Research, University of Bern, Murtenstrasse 50, below threshold. CH-3010 Bern, Switzerland [email protected] Keywords: HD-tDCS, motion perception, shape perception, unilateral brain stimulation, visual test Received: 18 May 2015 Introduction Accepted: 07 September 2015 Published: 23 September 2015 The visual cortex is the region of the brain responsible for visual perception. It is Citation: divided into the primary visual cortex V1, anatomically equivalent to Brodmann Zito GA, Senti T, Cazzoli D, Müri RM, Area (BA) 17, and the extrastriate visual cortical areas V2, V3, V4, and V5, Mosimann UP, Nyffeler T and Nef T corresponding to BA 18 and 19 (Engel et al., 1997; Van den Stock et al., 2014). (2015) Cathodal HD-tDCS on the right V5 improves motion perception in humans. Abbreviations:HD-tDCS, High Definition transcranial direct current stimulation; BA, Brodmann Area; MT, Middle Front. Behav. Neurosci. 9:257. temporal area; MST, Medial superior temporal area; VA, Visual angle; VH, Visual hemifield; TAP, Test of Attentional doi: 10.3389/fnbeh.2015.00257 Performance. Frontiers in Behavioral Neuroscience | www.frontiersin.org 1 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception These visual areas are organized into two hierarchically and In the present paper, we investigated the influence of functionally specialized processing pathways: a ventral ‘‘what’’ HD-tDCS on motion and shape perception. HD-tDCS was stream, including V1, V2, V4 and the inferior temporal areas applied over the right V5 of healthy volunteers, and the TEO and TE, for object vision; and a dorsal ‘‘where’’ stream, performance on visual tests was recorded. The aim of the including V1, V2, V3, the middle temporal area (V5-MT), the study was to investigate the focality of HD-tDCS using medial superior temporal area (MST), and further stations in the known properties of distinct areas of the visual cortex (i.e., inferior parietal and superior temporal sulcal cortex, for spatial the visual motion processing area located in V5), and to vision and motion perception (Ungerleider and Haxby, 1994; examine polarity-dependent inhibitory and excitatory effects Huberle et al., 2012). of HD-tDCS on behavioral performance. Two hypotheses Visual perception can be influenced by non-invasive brain were tested: first, if HD-tDCS focuses the stimulation on V5 stimulation. Transcranial direct current stimulation (tDCS), only, a behavioral effect in only motion perception should for instance, is a technique widely used to influence the be observed. Other properties of objects, such as shape, are neuronal excitability (Antal et al., 2001). tDCS is performed processed in distinct, although near V5, areas, and should by applying a constant low current, delivered to the brain therefore not be influenced by HD-tDCS. Second, anodal area of interest via external electrodes. Typical stimulation and cathodal HD-tDCS on the visual cortex do not provoke parameters are 1–2 mA for a duration of up to 20 min (Nitsche excitatory and inhibitory effects, respectively, on behavioral et al., 2008). High Definition tDCS (HD-tDCS) is a recently performance. developed method (Villamar et al., 2013), in which small HD- electrodes are used instead of the two large sponge electrodes Material and Methods in the conventional approach. Compared to the conventional approach, HD-tDCS has the advantage to give much higher Participants and Ethical Approval focality over the target region (Bikson et al., 2012). A typical Twenty one healthy volunteers (11 men and 10 women, montage for HD-tDCS is the 4  1 ring configuration, in 12 right handed, mean age = 30.5, SD = 5.1 years) were which a central electrode is placed over the target region, and recruited to participate in the study. All subjects had at least a four return electrodes are placed around it in a ring-shape Bachelor Diploma and were experienced computer users. The configuration (Datta et al., 2009). Many studies have investigated inclusion criterion was a visual acuity of > 0.8, corrected with the effects of tDCS on the visual cortex. For instance, Antal lenses if needed. Exclusion criteria were: serious head injuries, et al. reported reduced phosphene thresholds after 10 min of seizures, frequent or severe headaches, metal pieces in the 1 mA anodal tDCS and increased phosphene threshold after body, and implanted medical devices (Villamar et al., 2013). cathodal tDCS over Oz in the occipital pole (Antal et al., None of the subjects was taking any medication at the time 2003). Using a similar protocol, Accornero et al. studied the of the study. tDCS-induced modifications in visual evoked potentials (VEP- The study was carried out in accordance with the latest version P100) in humans, and found that anodal polarization reduced of the Declaration of Helsinki, and ethical approval was provided VEP-P100 amplitude whereas cathodal polarization significantly by the Ethics Committee of the Canton of Bern, Switzerland. increased amplitude (Accornero et al., 2007). This suggests that, according to the polarity of the stimulation, anodal and Experimental Design cathodal tDCS elicits different effects. Anodal tDCS is known The study was designed as a single blind, within-subject, sham to cause a depolarization of the resting membrane potential in controlled, randomized, cross-over trial. Prior to the study, the neurons, which increases excitability; whereas cathodal tDCS all subjects gave written informed consent. Subjects performed causes a hyperpolarization of the resting membrane potential, a practice session of the visual tests, followed by the actual with a decrease of the neuronal excitability (Nitsche et al., 2008). testing session. As a control task, subjects also performed an However, some studies have found contradictory behavioral alertness task, preceded by a corresponding practice session effects and different theories have been proposed to justify (Zimmermann and Fimm, 2002). The stimulation (anodal, such results (Antal et al., 2004; Batsikadze et al., 2013). Antal cathodal, or sham) was then administered. Right after the et al., for instance, showed that conventional cathodal tDCS stimulation, the subjects then repeated the visual tests and the over the left V5 affected a visuomotor task by modifying only alertness task, this time without practice sessions. Performance visual perception, and controlled it by stimulating different during the stimulation was not measured. In this way, areas of the visual and motor cortex; anodal tDCS did not participants could make a break between the two sessions and affect behavior. The effects depended also on task difficulty. an attention decrease due to tiredness was avoided. Finally, they But, to our knowledge, no studies with HD-tDCS over the were asked about potential adverse effects, such as headache, right V5 have been conducted up to date. Given the task- and nausea, pain, or trouble concentrating (Villamar et al., 2013). location-dependent effects of tDCS (Nitsche et al., 2008), the Moreover, they were asked to state whether they believed to have theory about the depolarization and hyperpolarization of the received sham or real stimulation. The experimental design is neurons is somewhat too ingenuous to explain the complexity depicted in Figure 1. of the problem. Behavioral performance on a visual motion The duration of the experiment was about 1 h, roughly task after stimulation of the right V5 needs to be further divided in the following way: 5 min for general assessment, explored. 15 min for first measurement, 5 min to prepare the subjects Frontiers in Behavioral Neuroscience | www.frontiersin.org 2 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 1 | Experimental design of the single blind within-subject, sham controlled randomized cross-over trial. for the stimulation, 20 min stimulation, and 15 min for the 1.07 VA/s, 1.80 VA/s, and 2.52 VA/s. In the second subtask, second measurement. The second and the third sessions took called the Shape Task, two ellipses with different ratios between place at least 1 week after the previous session, respectively, the vertical and the horizontal axes, were presented. The subjects and at the same time of the day. The order of the stimulation were asked to consider the ellipse on the right VH as reference, conditions in the respective sessions was counterbalanced across and to change the ratio of the ellipse on the left VH until it was subjects. perceived as identical as the one on the right VH (Figure 2C). Reference ratios were 0.3, 0.6, 1.5 and 1.8. The visual tests were performed under central fixation, which Test Setup was controlled using an eye tracking system integrated in the For the visual tests, subjects were seated with their head resting hemispherical screen. If the subjects moved their gaze outside an on a chin- and forehead rest at the center of a hemispherical allowed region of 5 VA from the central fixation marker, the screen (cupola, Figure 2A), where visual stimuli were projected, visual stimuli disappeared, and they only reappeared when the and held an input device with three buttons in their dominant central marker was fixated again. The technical setup is described hand; two buttons to manipulate the images and one to confirm in detail elsewhere (Zito et al., 2014). the choice. The tests followed a balance paradigm, in which Alertness was measured with the Test of Attentional subjects had to compare two images presented on the left and Performance (TAP; Zimmermann and Fimm, 2002). In this test, the right half of the cupola, respectively, at an eccentricity of 7.6 a cross appeared on a computer flat screen at randomly varying visual angles (VA) from its center, while fixating a central marker time intervals, and the subjects were asked to respond to it as point (0 VA eccentricity). In this setup, the two halves of the quickly as possible by pressing a key. hemispherical screen corresponded to the two visual hemifields Both the visual tests and the TAP were run on an Intel (VH). Two different subtasks, with 12 repetitions per task, were TM Core i5 (3.10 GHz) with Windows 7 operating system administered in a pseudo-random order. In the first one, called (Microsoft Inc.). The monitor of the computer for the TAP test the Speed Task, two patterns of dots moving in random direction was a 24 screen with a resolution of 1920 1080 pixels. at two different speeds were presented. The subjects were asked to consider the speed of the dots on the right VH as reference, and to use the two buttons of the input device to change (increase or HD-tDCS Stimulation decrease) the speed of the dots on the left VH until they matched The selected target region for the stimulation was V5. HD-tDCS the reference (Figure 2B). Reference speeds were 0.36 VA/s, was administered using a battery-driven, constant-current FIGURE 2 | Visual tests setup, as it appeared to the subjects. (A) hemispherical screen used to perform the tests. (B) Speed Task. The arrows represent the speed of the dots, which, in this example, are faster in the left hemisphere. Here subjects are asked to decrease the speed of the dots on the left in order to make them as fast as the dots on the right. (C) Shape Task with two ellipses, the axes ratio of the ellipse in the left hemisphere is higher than the one in the right. Here subjects are asked to decrease the axes ratio of the ellipse on the left in order to make it identical to the ellipse on the right. Frontiers in Behavioral Neuroscience | www.frontiersin.org 3 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception generator (DC-Stimulator MC, neuroConn GmbH, Germany), participants a few seconds to adapt to the tickling sensation of connected to a passive HD-tDCS distributor (Soterix Medical, the current. NY, USA). The optimal electrodes montage was selected by means of a bioelectromagnetic simulator of the current flow Data Analysis into the brain (Soterix HD-Explore, Soterix Medical, NY, USA). The distribution of the electrical field into the brain was This software uses a finite element method to compute the graphically analysed with the bioelectromagnetic simulator distribution of the electrical field into a standard adult male head (Soterix HD-Explore, Soterix Medical, NY, USA). model, once the location of the electrodes and the stimulation For the visual tests, the performance per subject was the parameters are given. Optimization criteria for the software mean value, out of the 12 repetitions, of the ratio between were high focality and high field intensity in the target area. the two images at the very time when the confirmation According to the solution of the optimization problem, the button was pressed. In particular, for the Shape Task it following montage was selected: the HD-tDCS cathode casing was the ratio between the eccentricity of the ellipse under (Minhas et al., 2010) was placed in PO and four anode manipulation and the eccentricity of the reference ellipse. casings were placed at a distance of about 5 cm from the For the Speed Task it was the ratio between the speed cathode, their location corresponding to P , OZ, TP , and of the dots under manipulation and the speed of the 4 8 PO according to the 10–10 standard EEG system (Figure 3). reference dots. The performance on the TAP—Alertness With this montage, the central electrode is right above V5 Task was expressed in terms of mean reaction time (Dumoulin et al., 2000). In order to increase conductivity, following target stimulus presentation. Tukey Test with the hair under the casings was separated to expose the scalp scaling factor 1.5 was used to identify potential outliers skin, and about 3 ml of Signa Gel (Parker Laboratories, NJ, (Richmond, 2000). USA) were injected into the electrode casings. The electrodes The influence of HD-tDCS on the performance was assessed were then placed into the gel solution inside the casings, and with Repeated Measures Analysis of Variance (rmANOVA) held in place with the casing cap (Easycap GmbH, Germany) with time (pre, post)  condition (sham, cathodal, anodal) (Borckardt et al., 2012). Impedance values were examined for  task (Speed Task, Shape Task) as within-subjects factors, each of the 5 electrodes and were all verified to be < 6 k2 gender (male, female) and handedness (right, left) as between- for the duration of the entire session. For real HD-tDCS, the subjects factors. Alertness was tested with a rmANOVA with current was ramped up to 2 mA (ramp duration of 30 s and time (pre, post) condition (sham, cathodal, anodal) as within- maintained for 20 min. For sham HD-tDCS, the current was subjects factors, gender (male, female) and handedness (right, ramped up to 2 mA (ramp duration of 30 s and, after 1 left) as between-subjects factors. Tukey’s HSD tests were used for min of full stimulation, it was ramped down to 0 mA (ramp post hoc comparisons. duration of 30 s, and stayed off until the end of the session. Chi-square tests were used to evaluate the number of subjects This helped to mask sham and real conditions and gave to the correctly guessing whether they received real or sham HD-tDCS FIGURE 3 | Electrodes montage for the High Definition transcranial direct current stimulation (HD-tDCS) experiment. (A) the gray point represents the central electrode, placed over PO8; the black points represent the other four (return) electrodes, placed over P4, OZ, TP8 and PO10. (B) Easycap, with electrodes placed according to the selected montage. Frontiers in Behavioral Neuroscience | www.frontiersin.org 4 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception (Borckardt et al., 2012). Data were analyzed using STATISTICA performance on the Alertness Task (F = 1.03, p = 0.37). .2,19/ 8.0 (StatSoft Inc.). No main effects of Gender and Handedness were observed in the performance on the visual tests (F = 0.38, p = 0.54) for .1,20/ Gender, (F = 0.01, p = 0.92) for Handedness, nor in the .1,20/ Results Alertness (F = 0.89, p = 0.36) for Gender, (F = 1.92, p = .1,20/ .1,20/ 0.18) for Handedness. HD-tDCS Stimulation The simulated distribution of the electrical field in the brain with the selected montage is shown in Figure 4. Discussion The maximal intensity of 0.4 V/m is located in the right visual cortex, on the Brodmann Area (BA) 18 and 19. The The aims of the present paper were to investigate focality of HD- surrounding BA 17, 37, 39, and 7 are only partially stimulated, tDCS and to find evidence of the effects of tDCS on behavioral performance. The tested hypotheses were: first, HD-tDCS over and the maximal field intensity in those regions is about 0.2 V/m, reaching a depth of a few centimeters. These results are in line the right V5 affects motion perception, but not shape perception; second, cathodal and anodal HD-tDCS do not induce decreased with previous studies using HD-tDCS in the 4 1 ring electrodes configuration (Borckardt et al., 2012; Villamar et al., 2013). and increased performance, respectively, on behavioral tasks. Performance on the Visual Tests Performance on the Visual Tests All subjects tolerated well HD-tDCS, without any side effects The results of the visual tests showed a significant effect of (such as headache, pain, nausea, or trouble concentrating). cathodal HD-tDCS on the motion perception task. Performance For both sham and real conditions, the subjects frequently during stimulation was not measured. However, in other studies reported perceiving a tickling sensation, but only at the very on the visual cortex with during- and immediately after- beginning of the stimulation session, and then they rapidly stimulation protocols, the results did not show differences adapted to this sensation. None of the subjects was aware between the two time points measures (for a review, see of the expected effects of HD-tDCS. The results of the Chi- Antal et al., 2006) and the conclusions were not affected square tests with respect to the blinding of the study showed by this additional information. According to the organization that subjects were not able to correctly guess above chance of visual processing into a ‘‘what’’ and a ‘‘where’’ stream whether they received real or sham stimulation (X = 2.85, (Ungerleider and Haxby, 1994), a visual test involving motion T1U p > 0.05 for the first session, X = 2.74, p > 0.05 for perception, like the Speed Task, would critically rely on T1U the second session; X = 2.76, p > 0.05 for the third areas of the ‘‘where’’ stream, such as V5. Conversely, a test T1U session). involving perception of shapes, like the Shape Task, would The results of the visual tests and the alertness test are shown critically rely on areas of the ‘‘what’’ stream. Our montage was in Figure 5. selected to specifically target area V5, and this localization was RmANOVA on the performance revealed a significant effect supported by the simulated distribution of the electrical field of interaction time  condition  task (F = 7.76, p = (Figure 4). .2,19/ 0.002). Post hoc tests revealed a significant improvement in the While the individual distribution of the field in the brain performance for the Speed Task after cathodal HD-tDCS (p < of single subjects is not known, the pattern of our results 0.05). No significant effects of interaction were found in the supports the focality of stimulation over V5 only, as behavioral FIGURE 4 | Simulated distribution of the electrical field in the brain with the selected montage. The white circle represents the presumed V5 in the head model. (A) coronal view. (B) sagittal view. (C) axial view. Frontiers in Behavioral Neuroscience | www.frontiersin.org 5 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 5 | Line charts of the results of the Speed Task, the Shape Task, and the Alertness Task. In the graphs, the performance represents the ratio between the two compared images. Values close to 1 depict high performance. Error bars represent the standard error of the mean. (A) results of the Speed Task, the asterisks depicts a significant difference at p < 0.05 as assessed by Tukey’s HSD post hoc tests. (B) results of the Shape Task. (C) results of the Alertness Task. performance was affected only in the motion perception task activation state, where optimal and suboptimal patterns are (Speed Task). Stimulation in other areas, namely the ‘‘what’’ both present at the same time (Figure 6A). Hypothesizing stream, may thus not be strong enough to elicit behavioral a threshold in the neuronal activation, above which a effects in the shape perception task (Shape Task). Furthermore, behavioral change can be observed, Antal et al. speculated it has been shown in studies on the motor cortex that a that cathodal stimulation may focus the correct perception maximum field intensity of 0.4 V/m elicits behavioral changes of these parameters by decreasing global activation level. (Borckardt et al., 2012). No studies with lower field intensities As a consequence of this, the amount of activation of have been reported, suggesting that such intensities have no concurrent patterns is diminished below threshold (Figure 6B; effects. According to Figure 4, brain areas around V5 also Antal et al., 2006). Similar argumentations can be made involved in motion processing, like the posterior parietal cortex for the results of the present study. In our Speed Task, (Koch et al., 2008) or V1, were stimulated with a field intensity for instance, speeds of dots moving in several random < 0.2 V/m, and this may not be sufficient to provoke behavioral directions are compared. The random directions of the changes. dots might tune different groups of neurons, and this The results of the Alertness Task showed no difference might result in the ‘‘noisy’’ activation state addressed by between stimulation conditions. This indicates that the Antal et al. Here the optimal neuronal patterns represent improvement of behavioral performance in the Speed Task the target speeds, and the suboptimal patterns represent is not due to unspecific stimulation effects, such as changes in the different motion directions of the dots. It is plausible the alertness level. that, after cathodal HD-tDCS, the neuronal activation This effect of enhancing behavioral performance by inhibiting state looks like the one shown in Figure 6B, where cortical activity was highly specific and, apparently, paradoxical. only the optimal pattern is still above threshold. Anodal However, such effects have already been reported in a previous stimulation would, on the other hand, increase the neuronal tDCS study: Batsikadze et al. found that cathodal tDCS might activation even more but, since the mentioned concurrent induce qualitatively different effects, depending on current patterns are already above threshold, no effect on the intensities (Batsikadze et al., 2013); Antal et al. showed performance is observed (Figure 6C). This explanation is that, in a visuo-motor coordination task similar to our supported by studies in macaque monkeys, where it has paradigm, cathodal tDCS over V5 ameliorated behavioral been demonstrated that different neurons in V5 show a performance, whereas anodal stimulation had no effect high selectivity for different motion speeds and directions (Antal et al., 2004). (Maunsell and Van Essen, 1983; Albright, 1984; Duijnhouwer A speculative explanation of such effects was found in et al., 2013). the complexity of perceptual information needed for the tasks. When high resolution, temporo-spatial analysis, HD-tDCS Stimulation and comparison of motion speeds and directions are When conducting HD-tDCS experiments, it is important to involved, different encoding neuronal patterns in response optimize the stimulation parameters, in order to achieve high to the different speeds and motion directions may activate focus and high field intensity over a given target region. The simultaneously. This probably results in a globally ‘‘noisy’’ manipulated parameters to investigate this optimization problem Frontiers in Behavioral Neuroscience | www.frontiersin.org 6 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 6 | Figure adapted from Antal et al. (2004). Example of the mechanism of interaction between tDCS and the cortical excitability. (A) in the Sham condition, many concurrent neuronal patterns, together with the optimal one, are simultaneously activated producing a “noisy” activation state. (B) in the Cathodal condition, the cortical excitability is globally decreased and the optimal pattern is the only one still above threshold, thus a focus effect is present. (C) in the Anodal condition, the global excitation of the concurrent patterns does not produce any change in the behavior because the “noise” is not filtered. are usually the shape and the size of the electrodes, and only computes field distribution in a standard head, which could the inter-electrodes distance. It has been shown that ring-like be different from the individual heads. In future studies, subject- electrodes decrease tickling sensation when compared with other specific head models derived from MRI, could be helpful. shapes, such as pellets, rectangles, and disks (Minhas et al., Future research in the field should also conduct an in- 2010, 2011). The electrodes size is positively correlated with the depth study of the exact molecular mechanism of interaction current density in the brain (Miranda et al., 2009). Therefore, in between tDCS and the brain, because the question of how order to achieve a strong field, bigger electrodes are desirable. tDCS affects brain functioning, explored in recent publications Unfortunately, it is more difficult to reach high focality with (Stagg et al., 2013; Pirulli et al., 2014; Bikson, 2015), is still large electrodes, as the electrical field propagates from a larger unanswered. In addition, other human factors which have surface. For this reason, ring-shape HD-electrodes (Borckardt been shown to play a role in visual perception, like anxiety et al., 2012), which fulfill the above mentioned criteria, were and stress (Tyler and Tucker, 1982), or the presence of the selected. menstrual cycle during the experiment (Ward et al., 1978), The results of the Chi-square test supported indeed that should be considered in the analysis, but this would require a the tickling sensation due to the stimulation did not affect the much higher sample size, and was not the main goal of the effectiveness of the blinding procedure, because subjects could current study. Task difficulty might also be manipulated, in not guess above chance whether they were receiving real or sham order to see behavioral effects of tDCS only in demanding tasks stimulation. It might be possible, however, that with slightly (Antal et al., 2004). different protocols the difference in correct guessing would have been significant (Borckardt et al., 2012). Author Contributions Regarding the distance among the electrodes, it has been shown that the higher the distance, the higher the field intensity GAZ carried out the technical implementation of the test and the (Faria et al., 2011), but, conversely, the lower the focus over the stimulation setup. TS studied the feasibility of the test battery and target region (Dmochowski et al., 2011). A good compromise was collected the data from the subjects. DC helped in the statistical found with the montage proposed in the present study, in which analysis of the results and in the discussion of the findings. RM the target electrode was placed over the visual area V5 (PO in helped in the conception of the test battery. UPM carried out the the EEG standard 10–10 system), and the four return electrodes clinical evaluation of the experimental procedure. TN provided at the edge of the desired stimulation region (P , OZ, TP and 4 8 important feedbacks regarding the data analyses. TNef helped in PO ). the conceptual framework of the study design and coordinated the work. All authors contributed in designing the entire study, Strengths, Limitations and Outlook of the reading, correcting and approving the final manuscript. Present Study The strengths of this study are the use of HD-tDCS instead of Acknowledgments conventional tDCS to increase the focality of the stimulation, and the use of a bioelectromagnetic simulator to compute the This project was partially financed by Haag-Streit Foundation. It was then extended in order to be able to present the study distribution of the current into the brain, essential for HD-tDCS experiments. However, this method has limitations, because it described in this paper. Frontiers in Behavioral Neuroscience | www.frontiersin.org 7 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception Maunsell, J. H., and Van Essen, D. C. (1983). 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A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution Conflict of Interest Statement: The authors declare that the research was of the current density in tDCS. J. Neural Eng. 8:066017. doi: 10.1088/1741- conducted in the absence of any commercial or financial relationships that could 2560/8/6/066017 be construed as a potential conflict of interest. Huberle, E., Rupek, P., Lappe, M., and Karnath, H.-O. (2012). Perception of biological motion in visual agnosia. Front. Behav. Neurosci. 6:56. doi: 10. Copyright © 2015 Zito, Senti, Cazzoli, Müri, Mosimann, Nyffeler and Nef. This 3389/fnbeh.2012.00056 is an open-access article distributed under the terms of the Creative Commons Koch, G., Fernandez Del Olmo, M., Cheeran, B., Schippling, S., Caltagirone, C., Attribution License (CC BY). The use, distribution and reproduction in other forums Driver, J., et al. (2008). Functional interplay between posterior parietal and is permitted, provided the original author(s) or licensor are credited and that the ipsilateral motor cortex revealed by twin-coil transcranial magnetic stimulation original publication in this journal is cited, in accordance with accepted academic during reach planning toward contralateral space. J. Neurosci. 28, 5944–5953. practice. No use, distribution or reproduction is permitted which does not comply doi: 10.1523/jneurosci.0957-08.2008 with these terms. Frontiers in Behavioral Neuroscience | www.frontiersin.org 8 September 2015 | Volume 9 | Article 257 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Frontiers in Behavioral Neuroscience Unpaywall

Cathodal HD-tDCS on the right V5 improves motion perception in humans

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ORIGINAL RESEARCH published: 23 September 2015 doi: 10.3389/fnbeh.2015.00257 Cathodal HD-tDCS on the right V5 improves motion perception in humans 1 1 1 1,2 1,3 Giuseppe A. Zito , Theresa Senti , Dario Cazzoli , René M. Müri , Urs P. Mosimann , 4 1,5 Thomas Nyffeler and Tobias Nef * 1 2 Gerontechnology and Rehabilitation Group, University of Bern, Bern, Switzerland, Division of Cognitive and Restorative Neurology, Department of Neurology, University Hospital Inselspital, University of Bern, Bern, Switzerland, University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland, Center of Neurology and Neurorehabilitation, Luzerner Kantonsspital, Luzern, Switzerland, ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy Edited by: Agnes Gruart, volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right University Pablo de Olavide, Spain V5 and their performance on a visual test was recorded. The results showed significant Reviewed by: improvement in motion perception in the left hemifield after cathodal HD-tDCS, but Jason Moser, Michigan State University, USA not in shape perception. Sham and anodal HD-tDCS did not affect performance. The Andrés Molero-Chamizo, specific effect of influencing performance of visual tasks by modulating the excitability University of Huelva, Spain of the neurons in the visual cortex might be explained by the complexity of perceptual *Correspondence: information needed for the tasks. This provokes a “noisy” activation state of the encoding Tobias Nef, Gerontechnology and Rehabilitation neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the Group and ARTORG Center for correct perception by decreasing global excitation and thus diminishing the “noise” Biomedical Engineering Research, University of Bern, Murtenstrasse 50, below threshold. CH-3010 Bern, Switzerland [email protected] Keywords: HD-tDCS, motion perception, shape perception, unilateral brain stimulation, visual test Received: 18 May 2015 Introduction Accepted: 07 September 2015 Published: 23 September 2015 The visual cortex is the region of the brain responsible for visual perception. It is Citation: divided into the primary visual cortex V1, anatomically equivalent to Brodmann Zito GA, Senti T, Cazzoli D, Müri RM, Area (BA) 17, and the extrastriate visual cortical areas V2, V3, V4, and V5, Mosimann UP, Nyffeler T and Nef T corresponding to BA 18 and 19 (Engel et al., 1997; Van den Stock et al., 2014). (2015) Cathodal HD-tDCS on the right V5 improves motion perception in humans. Abbreviations:HD-tDCS, High Definition transcranial direct current stimulation; BA, Brodmann Area; MT, Middle Front. Behav. Neurosci. 9:257. temporal area; MST, Medial superior temporal area; VA, Visual angle; VH, Visual hemifield; TAP, Test of Attentional doi: 10.3389/fnbeh.2015.00257 Performance. Frontiers in Behavioral Neuroscience | www.frontiersin.org 1 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception These visual areas are organized into two hierarchically and In the present paper, we investigated the influence of functionally specialized processing pathways: a ventral ‘‘what’’ HD-tDCS on motion and shape perception. HD-tDCS was stream, including V1, V2, V4 and the inferior temporal areas applied over the right V5 of healthy volunteers, and the TEO and TE, for object vision; and a dorsal ‘‘where’’ stream, performance on visual tests was recorded. The aim of the including V1, V2, V3, the middle temporal area (V5-MT), the study was to investigate the focality of HD-tDCS using medial superior temporal area (MST), and further stations in the known properties of distinct areas of the visual cortex (i.e., inferior parietal and superior temporal sulcal cortex, for spatial the visual motion processing area located in V5), and to vision and motion perception (Ungerleider and Haxby, 1994; examine polarity-dependent inhibitory and excitatory effects Huberle et al., 2012). of HD-tDCS on behavioral performance. Two hypotheses Visual perception can be influenced by non-invasive brain were tested: first, if HD-tDCS focuses the stimulation on V5 stimulation. Transcranial direct current stimulation (tDCS), only, a behavioral effect in only motion perception should for instance, is a technique widely used to influence the be observed. Other properties of objects, such as shape, are neuronal excitability (Antal et al., 2001). tDCS is performed processed in distinct, although near V5, areas, and should by applying a constant low current, delivered to the brain therefore not be influenced by HD-tDCS. Second, anodal area of interest via external electrodes. Typical stimulation and cathodal HD-tDCS on the visual cortex do not provoke parameters are 1–2 mA for a duration of up to 20 min (Nitsche excitatory and inhibitory effects, respectively, on behavioral et al., 2008). High Definition tDCS (HD-tDCS) is a recently performance. developed method (Villamar et al., 2013), in which small HD- electrodes are used instead of the two large sponge electrodes Material and Methods in the conventional approach. Compared to the conventional approach, HD-tDCS has the advantage to give much higher Participants and Ethical Approval focality over the target region (Bikson et al., 2012). A typical Twenty one healthy volunteers (11 men and 10 women, montage for HD-tDCS is the 4  1 ring configuration, in 12 right handed, mean age = 30.5, SD = 5.1 years) were which a central electrode is placed over the target region, and recruited to participate in the study. All subjects had at least a four return electrodes are placed around it in a ring-shape Bachelor Diploma and were experienced computer users. The configuration (Datta et al., 2009). Many studies have investigated inclusion criterion was a visual acuity of > 0.8, corrected with the effects of tDCS on the visual cortex. For instance, Antal lenses if needed. Exclusion criteria were: serious head injuries, et al. reported reduced phosphene thresholds after 10 min of seizures, frequent or severe headaches, metal pieces in the 1 mA anodal tDCS and increased phosphene threshold after body, and implanted medical devices (Villamar et al., 2013). cathodal tDCS over Oz in the occipital pole (Antal et al., None of the subjects was taking any medication at the time 2003). Using a similar protocol, Accornero et al. studied the of the study. tDCS-induced modifications in visual evoked potentials (VEP- The study was carried out in accordance with the latest version P100) in humans, and found that anodal polarization reduced of the Declaration of Helsinki, and ethical approval was provided VEP-P100 amplitude whereas cathodal polarization significantly by the Ethics Committee of the Canton of Bern, Switzerland. increased amplitude (Accornero et al., 2007). This suggests that, according to the polarity of the stimulation, anodal and Experimental Design cathodal tDCS elicits different effects. Anodal tDCS is known The study was designed as a single blind, within-subject, sham to cause a depolarization of the resting membrane potential in controlled, randomized, cross-over trial. Prior to the study, the neurons, which increases excitability; whereas cathodal tDCS all subjects gave written informed consent. Subjects performed causes a hyperpolarization of the resting membrane potential, a practice session of the visual tests, followed by the actual with a decrease of the neuronal excitability (Nitsche et al., 2008). testing session. As a control task, subjects also performed an However, some studies have found contradictory behavioral alertness task, preceded by a corresponding practice session effects and different theories have been proposed to justify (Zimmermann and Fimm, 2002). The stimulation (anodal, such results (Antal et al., 2004; Batsikadze et al., 2013). Antal cathodal, or sham) was then administered. Right after the et al., for instance, showed that conventional cathodal tDCS stimulation, the subjects then repeated the visual tests and the over the left V5 affected a visuomotor task by modifying only alertness task, this time without practice sessions. Performance visual perception, and controlled it by stimulating different during the stimulation was not measured. In this way, areas of the visual and motor cortex; anodal tDCS did not participants could make a break between the two sessions and affect behavior. The effects depended also on task difficulty. an attention decrease due to tiredness was avoided. Finally, they But, to our knowledge, no studies with HD-tDCS over the were asked about potential adverse effects, such as headache, right V5 have been conducted up to date. Given the task- and nausea, pain, or trouble concentrating (Villamar et al., 2013). location-dependent effects of tDCS (Nitsche et al., 2008), the Moreover, they were asked to state whether they believed to have theory about the depolarization and hyperpolarization of the received sham or real stimulation. The experimental design is neurons is somewhat too ingenuous to explain the complexity depicted in Figure 1. of the problem. Behavioral performance on a visual motion The duration of the experiment was about 1 h, roughly task after stimulation of the right V5 needs to be further divided in the following way: 5 min for general assessment, explored. 15 min for first measurement, 5 min to prepare the subjects Frontiers in Behavioral Neuroscience | www.frontiersin.org 2 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 1 | Experimental design of the single blind within-subject, sham controlled randomized cross-over trial. for the stimulation, 20 min stimulation, and 15 min for the 1.07 VA/s, 1.80 VA/s, and 2.52 VA/s. In the second subtask, second measurement. The second and the third sessions took called the Shape Task, two ellipses with different ratios between place at least 1 week after the previous session, respectively, the vertical and the horizontal axes, were presented. The subjects and at the same time of the day. The order of the stimulation were asked to consider the ellipse on the right VH as reference, conditions in the respective sessions was counterbalanced across and to change the ratio of the ellipse on the left VH until it was subjects. perceived as identical as the one on the right VH (Figure 2C). Reference ratios were 0.3, 0.6, 1.5 and 1.8. The visual tests were performed under central fixation, which Test Setup was controlled using an eye tracking system integrated in the For the visual tests, subjects were seated with their head resting hemispherical screen. If the subjects moved their gaze outside an on a chin- and forehead rest at the center of a hemispherical allowed region of 5 VA from the central fixation marker, the screen (cupola, Figure 2A), where visual stimuli were projected, visual stimuli disappeared, and they only reappeared when the and held an input device with three buttons in their dominant central marker was fixated again. The technical setup is described hand; two buttons to manipulate the images and one to confirm in detail elsewhere (Zito et al., 2014). the choice. The tests followed a balance paradigm, in which Alertness was measured with the Test of Attentional subjects had to compare two images presented on the left and Performance (TAP; Zimmermann and Fimm, 2002). In this test, the right half of the cupola, respectively, at an eccentricity of 7.6 a cross appeared on a computer flat screen at randomly varying visual angles (VA) from its center, while fixating a central marker time intervals, and the subjects were asked to respond to it as point (0 VA eccentricity). In this setup, the two halves of the quickly as possible by pressing a key. hemispherical screen corresponded to the two visual hemifields Both the visual tests and the TAP were run on an Intel (VH). Two different subtasks, with 12 repetitions per task, were TM Core i5 (3.10 GHz) with Windows 7 operating system administered in a pseudo-random order. In the first one, called (Microsoft Inc.). The monitor of the computer for the TAP test the Speed Task, two patterns of dots moving in random direction was a 24 screen with a resolution of 1920 1080 pixels. at two different speeds were presented. The subjects were asked to consider the speed of the dots on the right VH as reference, and to use the two buttons of the input device to change (increase or HD-tDCS Stimulation decrease) the speed of the dots on the left VH until they matched The selected target region for the stimulation was V5. HD-tDCS the reference (Figure 2B). Reference speeds were 0.36 VA/s, was administered using a battery-driven, constant-current FIGURE 2 | Visual tests setup, as it appeared to the subjects. (A) hemispherical screen used to perform the tests. (B) Speed Task. The arrows represent the speed of the dots, which, in this example, are faster in the left hemisphere. Here subjects are asked to decrease the speed of the dots on the left in order to make them as fast as the dots on the right. (C) Shape Task with two ellipses, the axes ratio of the ellipse in the left hemisphere is higher than the one in the right. Here subjects are asked to decrease the axes ratio of the ellipse on the left in order to make it identical to the ellipse on the right. Frontiers in Behavioral Neuroscience | www.frontiersin.org 3 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception generator (DC-Stimulator MC, neuroConn GmbH, Germany), participants a few seconds to adapt to the tickling sensation of connected to a passive HD-tDCS distributor (Soterix Medical, the current. NY, USA). The optimal electrodes montage was selected by means of a bioelectromagnetic simulator of the current flow Data Analysis into the brain (Soterix HD-Explore, Soterix Medical, NY, USA). The distribution of the electrical field into the brain was This software uses a finite element method to compute the graphically analysed with the bioelectromagnetic simulator distribution of the electrical field into a standard adult male head (Soterix HD-Explore, Soterix Medical, NY, USA). model, once the location of the electrodes and the stimulation For the visual tests, the performance per subject was the parameters are given. Optimization criteria for the software mean value, out of the 12 repetitions, of the ratio between were high focality and high field intensity in the target area. the two images at the very time when the confirmation According to the solution of the optimization problem, the button was pressed. In particular, for the Shape Task it following montage was selected: the HD-tDCS cathode casing was the ratio between the eccentricity of the ellipse under (Minhas et al., 2010) was placed in PO and four anode manipulation and the eccentricity of the reference ellipse. casings were placed at a distance of about 5 cm from the For the Speed Task it was the ratio between the speed cathode, their location corresponding to P , OZ, TP , and of the dots under manipulation and the speed of the 4 8 PO according to the 10–10 standard EEG system (Figure 3). reference dots. The performance on the TAP—Alertness With this montage, the central electrode is right above V5 Task was expressed in terms of mean reaction time (Dumoulin et al., 2000). In order to increase conductivity, following target stimulus presentation. Tukey Test with the hair under the casings was separated to expose the scalp scaling factor 1.5 was used to identify potential outliers skin, and about 3 ml of Signa Gel (Parker Laboratories, NJ, (Richmond, 2000). USA) were injected into the electrode casings. The electrodes The influence of HD-tDCS on the performance was assessed were then placed into the gel solution inside the casings, and with Repeated Measures Analysis of Variance (rmANOVA) held in place with the casing cap (Easycap GmbH, Germany) with time (pre, post)  condition (sham, cathodal, anodal) (Borckardt et al., 2012). Impedance values were examined for  task (Speed Task, Shape Task) as within-subjects factors, each of the 5 electrodes and were all verified to be < 6 k2 gender (male, female) and handedness (right, left) as between- for the duration of the entire session. For real HD-tDCS, the subjects factors. Alertness was tested with a rmANOVA with current was ramped up to 2 mA (ramp duration of 30 s and time (pre, post) condition (sham, cathodal, anodal) as within- maintained for 20 min. For sham HD-tDCS, the current was subjects factors, gender (male, female) and handedness (right, ramped up to 2 mA (ramp duration of 30 s and, after 1 left) as between-subjects factors. Tukey’s HSD tests were used for min of full stimulation, it was ramped down to 0 mA (ramp post hoc comparisons. duration of 30 s, and stayed off until the end of the session. Chi-square tests were used to evaluate the number of subjects This helped to mask sham and real conditions and gave to the correctly guessing whether they received real or sham HD-tDCS FIGURE 3 | Electrodes montage for the High Definition transcranial direct current stimulation (HD-tDCS) experiment. (A) the gray point represents the central electrode, placed over PO8; the black points represent the other four (return) electrodes, placed over P4, OZ, TP8 and PO10. (B) Easycap, with electrodes placed according to the selected montage. Frontiers in Behavioral Neuroscience | www.frontiersin.org 4 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception (Borckardt et al., 2012). Data were analyzed using STATISTICA performance on the Alertness Task (F = 1.03, p = 0.37). .2,19/ 8.0 (StatSoft Inc.). No main effects of Gender and Handedness were observed in the performance on the visual tests (F = 0.38, p = 0.54) for .1,20/ Gender, (F = 0.01, p = 0.92) for Handedness, nor in the .1,20/ Results Alertness (F = 0.89, p = 0.36) for Gender, (F = 1.92, p = .1,20/ .1,20/ 0.18) for Handedness. HD-tDCS Stimulation The simulated distribution of the electrical field in the brain with the selected montage is shown in Figure 4. Discussion The maximal intensity of 0.4 V/m is located in the right visual cortex, on the Brodmann Area (BA) 18 and 19. The The aims of the present paper were to investigate focality of HD- surrounding BA 17, 37, 39, and 7 are only partially stimulated, tDCS and to find evidence of the effects of tDCS on behavioral performance. The tested hypotheses were: first, HD-tDCS over and the maximal field intensity in those regions is about 0.2 V/m, reaching a depth of a few centimeters. These results are in line the right V5 affects motion perception, but not shape perception; second, cathodal and anodal HD-tDCS do not induce decreased with previous studies using HD-tDCS in the 4 1 ring electrodes configuration (Borckardt et al., 2012; Villamar et al., 2013). and increased performance, respectively, on behavioral tasks. Performance on the Visual Tests Performance on the Visual Tests All subjects tolerated well HD-tDCS, without any side effects The results of the visual tests showed a significant effect of (such as headache, pain, nausea, or trouble concentrating). cathodal HD-tDCS on the motion perception task. Performance For both sham and real conditions, the subjects frequently during stimulation was not measured. However, in other studies reported perceiving a tickling sensation, but only at the very on the visual cortex with during- and immediately after- beginning of the stimulation session, and then they rapidly stimulation protocols, the results did not show differences adapted to this sensation. None of the subjects was aware between the two time points measures (for a review, see of the expected effects of HD-tDCS. The results of the Chi- Antal et al., 2006) and the conclusions were not affected square tests with respect to the blinding of the study showed by this additional information. According to the organization that subjects were not able to correctly guess above chance of visual processing into a ‘‘what’’ and a ‘‘where’’ stream whether they received real or sham stimulation (X = 2.85, (Ungerleider and Haxby, 1994), a visual test involving motion T1U p > 0.05 for the first session, X = 2.74, p > 0.05 for perception, like the Speed Task, would critically rely on T1U the second session; X = 2.76, p > 0.05 for the third areas of the ‘‘where’’ stream, such as V5. Conversely, a test T1U session). involving perception of shapes, like the Shape Task, would The results of the visual tests and the alertness test are shown critically rely on areas of the ‘‘what’’ stream. Our montage was in Figure 5. selected to specifically target area V5, and this localization was RmANOVA on the performance revealed a significant effect supported by the simulated distribution of the electrical field of interaction time  condition  task (F = 7.76, p = (Figure 4). .2,19/ 0.002). Post hoc tests revealed a significant improvement in the While the individual distribution of the field in the brain performance for the Speed Task after cathodal HD-tDCS (p < of single subjects is not known, the pattern of our results 0.05). No significant effects of interaction were found in the supports the focality of stimulation over V5 only, as behavioral FIGURE 4 | Simulated distribution of the electrical field in the brain with the selected montage. The white circle represents the presumed V5 in the head model. (A) coronal view. (B) sagittal view. (C) axial view. Frontiers in Behavioral Neuroscience | www.frontiersin.org 5 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 5 | Line charts of the results of the Speed Task, the Shape Task, and the Alertness Task. In the graphs, the performance represents the ratio between the two compared images. Values close to 1 depict high performance. Error bars represent the standard error of the mean. (A) results of the Speed Task, the asterisks depicts a significant difference at p < 0.05 as assessed by Tukey’s HSD post hoc tests. (B) results of the Shape Task. (C) results of the Alertness Task. performance was affected only in the motion perception task activation state, where optimal and suboptimal patterns are (Speed Task). Stimulation in other areas, namely the ‘‘what’’ both present at the same time (Figure 6A). Hypothesizing stream, may thus not be strong enough to elicit behavioral a threshold in the neuronal activation, above which a effects in the shape perception task (Shape Task). Furthermore, behavioral change can be observed, Antal et al. speculated it has been shown in studies on the motor cortex that a that cathodal stimulation may focus the correct perception maximum field intensity of 0.4 V/m elicits behavioral changes of these parameters by decreasing global activation level. (Borckardt et al., 2012). No studies with lower field intensities As a consequence of this, the amount of activation of have been reported, suggesting that such intensities have no concurrent patterns is diminished below threshold (Figure 6B; effects. According to Figure 4, brain areas around V5 also Antal et al., 2006). Similar argumentations can be made involved in motion processing, like the posterior parietal cortex for the results of the present study. In our Speed Task, (Koch et al., 2008) or V1, were stimulated with a field intensity for instance, speeds of dots moving in several random < 0.2 V/m, and this may not be sufficient to provoke behavioral directions are compared. The random directions of the changes. dots might tune different groups of neurons, and this The results of the Alertness Task showed no difference might result in the ‘‘noisy’’ activation state addressed by between stimulation conditions. This indicates that the Antal et al. Here the optimal neuronal patterns represent improvement of behavioral performance in the Speed Task the target speeds, and the suboptimal patterns represent is not due to unspecific stimulation effects, such as changes in the different motion directions of the dots. It is plausible the alertness level. that, after cathodal HD-tDCS, the neuronal activation This effect of enhancing behavioral performance by inhibiting state looks like the one shown in Figure 6B, where cortical activity was highly specific and, apparently, paradoxical. only the optimal pattern is still above threshold. Anodal However, such effects have already been reported in a previous stimulation would, on the other hand, increase the neuronal tDCS study: Batsikadze et al. found that cathodal tDCS might activation even more but, since the mentioned concurrent induce qualitatively different effects, depending on current patterns are already above threshold, no effect on the intensities (Batsikadze et al., 2013); Antal et al. showed performance is observed (Figure 6C). This explanation is that, in a visuo-motor coordination task similar to our supported by studies in macaque monkeys, where it has paradigm, cathodal tDCS over V5 ameliorated behavioral been demonstrated that different neurons in V5 show a performance, whereas anodal stimulation had no effect high selectivity for different motion speeds and directions (Antal et al., 2004). (Maunsell and Van Essen, 1983; Albright, 1984; Duijnhouwer A speculative explanation of such effects was found in et al., 2013). the complexity of perceptual information needed for the tasks. When high resolution, temporo-spatial analysis, HD-tDCS Stimulation and comparison of motion speeds and directions are When conducting HD-tDCS experiments, it is important to involved, different encoding neuronal patterns in response optimize the stimulation parameters, in order to achieve high to the different speeds and motion directions may activate focus and high field intensity over a given target region. The simultaneously. This probably results in a globally ‘‘noisy’’ manipulated parameters to investigate this optimization problem Frontiers in Behavioral Neuroscience | www.frontiersin.org 6 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception FIGURE 6 | Figure adapted from Antal et al. (2004). Example of the mechanism of interaction between tDCS and the cortical excitability. (A) in the Sham condition, many concurrent neuronal patterns, together with the optimal one, are simultaneously activated producing a “noisy” activation state. (B) in the Cathodal condition, the cortical excitability is globally decreased and the optimal pattern is the only one still above threshold, thus a focus effect is present. (C) in the Anodal condition, the global excitation of the concurrent patterns does not produce any change in the behavior because the “noise” is not filtered. are usually the shape and the size of the electrodes, and only computes field distribution in a standard head, which could the inter-electrodes distance. It has been shown that ring-like be different from the individual heads. In future studies, subject- electrodes decrease tickling sensation when compared with other specific head models derived from MRI, could be helpful. shapes, such as pellets, rectangles, and disks (Minhas et al., Future research in the field should also conduct an in- 2010, 2011). The electrodes size is positively correlated with the depth study of the exact molecular mechanism of interaction current density in the brain (Miranda et al., 2009). Therefore, in between tDCS and the brain, because the question of how order to achieve a strong field, bigger electrodes are desirable. tDCS affects brain functioning, explored in recent publications Unfortunately, it is more difficult to reach high focality with (Stagg et al., 2013; Pirulli et al., 2014; Bikson, 2015), is still large electrodes, as the electrical field propagates from a larger unanswered. In addition, other human factors which have surface. For this reason, ring-shape HD-electrodes (Borckardt been shown to play a role in visual perception, like anxiety et al., 2012), which fulfill the above mentioned criteria, were and stress (Tyler and Tucker, 1982), or the presence of the selected. menstrual cycle during the experiment (Ward et al., 1978), The results of the Chi-square test supported indeed that should be considered in the analysis, but this would require a the tickling sensation due to the stimulation did not affect the much higher sample size, and was not the main goal of the effectiveness of the blinding procedure, because subjects could current study. Task difficulty might also be manipulated, in not guess above chance whether they were receiving real or sham order to see behavioral effects of tDCS only in demanding tasks stimulation. It might be possible, however, that with slightly (Antal et al., 2004). different protocols the difference in correct guessing would have been significant (Borckardt et al., 2012). Author Contributions Regarding the distance among the electrodes, it has been shown that the higher the distance, the higher the field intensity GAZ carried out the technical implementation of the test and the (Faria et al., 2011), but, conversely, the lower the focus over the stimulation setup. TS studied the feasibility of the test battery and target region (Dmochowski et al., 2011). A good compromise was collected the data from the subjects. DC helped in the statistical found with the montage proposed in the present study, in which analysis of the results and in the discussion of the findings. RM the target electrode was placed over the visual area V5 (PO in helped in the conception of the test battery. UPM carried out the the EEG standard 10–10 system), and the four return electrodes clinical evaluation of the experimental procedure. TN provided at the edge of the desired stimulation region (P , OZ, TP and 4 8 important feedbacks regarding the data analyses. TNef helped in PO ). the conceptual framework of the study design and coordinated the work. All authors contributed in designing the entire study, Strengths, Limitations and Outlook of the reading, correcting and approving the final manuscript. Present Study The strengths of this study are the use of HD-tDCS instead of Acknowledgments conventional tDCS to increase the focality of the stimulation, and the use of a bioelectromagnetic simulator to compute the This project was partially financed by Haag-Streit Foundation. It was then extended in order to be able to present the study distribution of the current into the brain, essential for HD-tDCS experiments. However, this method has limitations, because it described in this paper. Frontiers in Behavioral Neuroscience | www.frontiersin.org 7 September 2015 | Volume 9 | Article 257 Zito et al. HD-tDCS and visual motion perception Maunsell, J. H., and Van Essen, D. C. (1983). 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A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution Conflict of Interest Statement: The authors declare that the research was of the current density in tDCS. J. Neural Eng. 8:066017. doi: 10.1088/1741- conducted in the absence of any commercial or financial relationships that could 2560/8/6/066017 be construed as a potential conflict of interest. Huberle, E., Rupek, P., Lappe, M., and Karnath, H.-O. (2012). Perception of biological motion in visual agnosia. Front. Behav. Neurosci. 6:56. doi: 10. Copyright © 2015 Zito, Senti, Cazzoli, Müri, Mosimann, Nyffeler and Nef. This 3389/fnbeh.2012.00056 is an open-access article distributed under the terms of the Creative Commons Koch, G., Fernandez Del Olmo, M., Cheeran, B., Schippling, S., Caltagirone, C., Attribution License (CC BY). The use, distribution and reproduction in other forums Driver, J., et al. (2008). Functional interplay between posterior parietal and is permitted, provided the original author(s) or licensor are credited and that the ipsilateral motor cortex revealed by twin-coil transcranial magnetic stimulation original publication in this journal is cited, in accordance with accepted academic during reach planning toward contralateral space. J. Neurosci. 28, 5944–5953. practice. No use, distribution or reproduction is permitted which does not comply doi: 10.1523/jneurosci.0957-08.2008 with these terms. Frontiers in Behavioral Neuroscience | www.frontiersin.org 8 September 2015 | Volume 9 | Article 257

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