Effects of Transcranial Direct Current Stimulation (2 ma - 20min) in Patients with Non-Fluent Aphasia Disorder

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1 Effects of Transcranial Direct Current Stimulation (2 ma - 20min) in Patients with Non-Fluent Aphasia Disorder M. Saidmanesh, HR.Pouretemad, A. Amini, R. Nilipor, H. Ekhtiari Abstract we aimed to investigate the correlation between stimulation intensity, duration of session of transcranial direct current stimulation (ten 20- min anodal transcranial direct current stimulation (2mA) sessions and lesion location with the aphasia recovery and improvement of naming picture, Aphasia Quotient and working memory in Persian patients with non fluent aphasia disorder. To achieve this goal we evaluate the Efficacy of transcranial direct current stimulation on dorsolateral prefrontal cortex of the brain upon non fluent aphasia recovery, included 20 chronic and stroke-induced aphasia patients who each underwent 10 sessions of Anodal - transcranial direct current stimulation (2 mili- Ampere - 20min) and 10 sessions of sham- transcranial direct current stimulation (20-min) combined with a computerized anemia treatment. It was revealed that after ten 20-min anodal transcranial direct current stimulation (2mA), it significantly improves naming scores, working memory, Aphasia Quotient or severity and the Correlation Rate in non fluent aphasia patients as compared to sham- transcranial direct current stimulation. Additionally, our study demonstrated, there are significant differences between the results of our test According to the following variable, lesion location, but not genders variation. Treatment with10 sessions of Anodal - transcranial direct current stimulation (2 ma - 20min) enhance the non fluent aphasia recovery and improvement of naming picture, working memory and Aphasia Quotient or severity and lesion location but not gender factor play a main role in it. Key words Anodal transcranial direct current stimulation, non fluent aphasia, left dorsolateral prefrontal cortex (LDPC) INTRODUCTION One of the main impairment of language ability is aphasia or speechlessness disorders. It usually caused by head injury (left hemisphere, or stroke), but it can develop slowly from a brain tumor, dementia, infection and dysnomia (learning disability) [1]-[5]. According to last literatures, the main reason of the aphasia is stroke, approximately, 80,000 cases of adult aphasia is due to stroke, and more than 50 60% of them have chronic impairment[ 6],[7]. The aphasia disorders can be divided into: global, Broca s, trans-cortical motor, mixed transcortical, Wernicke s, trans- cortical sensory, conduction, and anomic types, moreover, the WAB demonstrate severities of aphasia as aphasia quotients (AQ), this kind of classification is according to the assessing profiles of language for repetition, fluency, comprehension, and naming[1]. During the acute phase of stroke, the global type of aphasia are more prevalence form and consist approximately 20-40% of aphasias, whereas the classic aphasia are found only in a 25 percent of patients, and 10-15% of patients are unclassifiable[8]. The ranges of language disorder are different and vary from naming picture, unable in speaking, writing, and reading to deficits in working memory (WM). Here working memory capacity has been identified as a unitary process of a single (resource) pool for attention, linguistic, and other plenary processing. The main reason of those kind disorders, is impairment in left hemisphere (LH) or in left dorsolateral part of prefrontal cortex (DLPFC)[1],[8].The critical function of left dorsolateral part of prefrontal cortex (DLPFC) in verbal working memory (WM) has been approved by Didit Span Test in pathological studies and in the study including effects of Trans Magnetic Stimulation (TMS) on left dorsolateral prefrontal cortex. This study showed that local damage and destruction of left DLPFC region, not right DLPFC region, Cause degradation in verbal working memory (WM) [1]. Previous studies also suggested that stimulation by transcranial direct current has a positive effect on the left dorsolateral part of prefrontal cortex, resulted in an improved ability to name pictures, working memory (WM) [9]-[12]. Today s, stimulation by transcranial direct current (tdcs) as a safe and non-invasive brain stimulation techniques and painless form of neuron stimulation methods have become increasingly important for the diagnosis and treatment of neuropsychiatric diseases [1]. These techniques are used to stimulate cortical neuronal assemblies. This methods works by sending the current from an active electrode to a 133

2 reference electrode, a part being diverted through the scalp and the remainder being delivered to tissue of the brain, thereby it leading to increase or decrease of cortical excitability [13].Here the current polarity determined the direction of the tdcs-induced effect. According to this, the stimulation of the brain can be classified as; Cathodal, Anodal and Sham stimulations. Stimulation by anodal is positive and it can increase the excitability of the neuron. In Contrary to this, the stimulation by the cathode decrease the excitability of the neurons in the stimulated area for reach to more constant level of activity Here the sham stimulation is one of the important stimulation, because it plays as a control groups. These types of stimulation help to prove the positive or negative effects of stimulation [1],[14]- [16]. It is important to remind, the ability of tdcs for creating cortical changes even after the end of stimulation is one of the important aspects of it. The stimulating effects and the continuity of this kind of change depend on the length stimulation as well as the intensity of stimulation and the session durations and location of the brain lesion. For example, in the several studies it was revealed that after five 20-min anodal tdcs (1 ma) sessions it has beneficial effect on aphasia recovery [19],[20]. And also, it was reported that stimulation by the same parameters enhanced working memory (WM) in healthy persons, as measured by three-back working memory method [21], and in patients with Parkinson s disease [22]. Review of the literatures shows that more sessions (> 5 sessions), longer sessions (> 20-min), and greater stimulation intensity (> 1 ma) may be able to elicited even greater success [13],[21]. Along to those, many treatments were designed to reveal the role of other stimulation intensity of tdcs and number of sessions in aphasia recovery. Therefore, for increasing the knowledge and helping to them, we decided to investigate the effect of ten 20-min anodal tdcs (2 ma) sessions on naming score and working memory according to the role of lesion location in the aphasia recovery, in the patient with non fluent aphasia disorder. Material and methods: Subjects: Twenty right hand Persian patients with chronicnon fluent aphasia disorders (range years; mean age, ± 2.4 years, at 60 month poststroke) participated in our present study. All of the subjects gave their written informed consent before participation (Table 1). In our study the patients were excluded if had been any speech therapy or had been used medication or psychotropic drugs during the 4 weeks prior to the study. And also, they were informed to avoid alcohol, cigarettes and drink of caffeinated things on the day of the test, and none reported fatigue due to inadequate sleep. The Persian aphasia test: This test includes the tests of continuous speech (content and fluency of speech), auditory perception, and continuous orders, naming and repeating. Each test had 10 scores that were in totally 60 scores. At the end of the test, the obtained number multiplied by 10 and then divided by 6. The obtained number is Aphasia Quotient [23],[24]. The Pictures naming aphasia test: This test consists 50 pictures witch patient should be tell the name of them. This kind of test according to the type and variety of category are classified to three groups, including the Name of animals (12 animals), 11 fruit and 27 categories of Construction. If the patient fails to express the desired word after 10 seconds, He or she was semantic guidance in initially and in the absence of response, he or she was phonetic guidance. Every patient's answer to the pictures recorded on the answer sheets and then the total number of correct answers, correct answers with no guidance, correct answers with semantic guidance, correct answers with phonetic guidance, wrong answers and not response answers were obtained[ 23]. The 2 back test: The 2 -back task has been used to evaluate the working memory ability in neurologically intact individuals as well as multiple clinical populations. It Includes 100 Number (1 to 9), that are randomly repeated. The 2-back needs contributors to process a stream of incoming data and respond when the current stimulus is the same as the stimulus 2 items ago. In this study, the number of correct answers has been considered as a test score [25]. The Computer program naming aphasia test: Program used in this study included 60 Image, Which com in three semantic categories including animals, fruits, and objects (20 images in each semantic category). During treatment with tdcs, Images and their name was presented using the computer. And none of these images wasn t seen in 134

3 the Pictures naming aphasia test [23],[ 24]. Electrodes and stimulation of the brain: In this study Direct current was induced by a pair of electrodes in a 5 5cm saline-soaked synthetic sponge and delivered by a battery steered constant current stimulator using (included of 20 min of 2 ma). According to Knoch et al. the device used, is particularly trustful for studies: a switch can be enabled to interrupt the electrical current while retaining the (ON) display and showing the stimulation parameters throughout the procedure to the participant [26]. In these conditions the interaction between the two hemispheres during task execution is also under control. So in present study for left DLPFC stimulation, the anodal electrode was located over the left DLPFC and the cathodal electrode over the right DLPFC. For the stimulation of sham group, the electrodes were located at the same positions as for stimulation in active manner, but the stimulator was turned on only for 30 s. Thus, these participants felt the primary itching sensation associated with trans direct current stimulating (tdcs), but received no active current for the remainder of the stimulation period [26]. Experimental Design: Twenty participants (8 women; and 12 man) were randomly assigned to receive cathodal electrode over the right predestinated DLPFC area (by using of the 10/20 EEG system) and anodal electrode as a active stimulation over the left predestinated DLPFC area ( n = 20) and sham stimulation or no stimulation group (n = 20) [27]. After selecting the participants, we consisted three ordered phases, separated by at least 3 days [19, 21 and 28]. In the first phase, the written informed consent was given to the participants prior to their inclusion in the study. Then the technique of MMSE test for Dementia and test for identify the type of aphasia was done in the same session [23],[ 24]. In the second phase (3 day after the first session), picture naming, Working Memory and Aphasia Quotient Were evaluated by The Pictures Naming Aphasia test, 2-back test and Persian aphasia test, respectively, and results were recorded in the patient questionnaire as a before tdcs treatment results. In the last phase (including treatment session), for stimulation of the left DLPFC and right DLPFC the anodal electrode and cathodal electrode were located over the left and right DLPFC respectively for 10 days. In this study, for active stimulation, the subjects received a steady current of 2 ma intensity for 20 min. the last studies have indicated that this kind of stimulation intensity is safe and can be more effective than 1 ma stimulation[ 19, 21and 28]. During the stimulation period, Patients Underwent the Computer program naming test for the naming performance. This test helps them to naming and tells pictures. At the end of treatment, picture naming, Working Memory and Aphasia Quotient Were evaluated by The Pictures Naming test, 2- back test and Persian aphasia test, respectively, and results were recorded in the patient questionnaire. For Statistical analysis, data was analyzed by SPSS 19 and Manova test and used Pearson correlation coefficient. It also describes the test score (before and after treatment). Results: All subjects without any complications ended the tree treatment phases. The ratings of Subject s selfreported of attention, perceived pain and fatigue were not statically significant during the treatment sessions, (F (2, 13) <1, p>0. 26). All of our measures completed within 20 minutes of the tdcs cessation. The results of statistical analysis of the naming Persian aphasia test without any guidance, with semantic guidance and with phonetic guidance are shown in the tables below (Table 2 and Fig.1). 135

4 According to the Multivariate analysis of variance (Hotelling,s Trace), the relationship between naming performance, before and following A-tDCS treatment were significant in The Pictures naming Persian aphasia test(fig1a). P و = 0/000 F = 208/551. And also, the relationship between naming performance before and following A-tDCS treatment among patients with different lesion location (anterior and posterior-anterior), were significant (P = 0/003 Fو = 7/873, (see table 3and Fig.1B) But there are no significant relationships between patients with different sex (Variable sex) in the same conditions (see table 4 and Fig. 1C) P = 1/038. = F و 0/406 Here, when the variables, gender and location of the lesion, considered together, no significant (P = Fو = 1/263) relationships were revealed 0/325 between the results of the naming aphasia test among patients before and following A-tDCS treatment (Table 5 and Fig.1D). 136

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6 The 2 Back Test: The results of statistical analysis of the 2 back test are shown in the tables above and below (see Table 2-4 and 6) and Fig 2). In the table 2 and figure 1A it was shown that, the results of statistical analysis the 2 back test before and following A-tDCS treatment was significant (P و = 0/000 F = 164/395), And also, the result of the 2 back test was significant among patients with different lesion location (anterior and posterior-anterior) (Table3, Fig. 2B). P = 0/010, F = 5/539, But not sex (Table 4 and Fig. 2C). P = 0/982, F = 0/056. Here, when the variables, gender and location of the lesion, considered together, no significant (P = Fو = 0/669) relationships were revealed 0/585 between the results of the 2 back test among patients before and following A-tDCS treatment (Table 6 and Fig. 1D). 138

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8 Aphasia Quotient test: The results of statistical analysis of The Aphasia Quotient test are shown in the tables above and below (Table 2-4 and 7) and Fig 3. From the table 2 and figure 3A it was concluded that, there are a significant difference between the results of The Aphasia Quotient test among the patients before and following A-tDCS treatment ( P = 0/000,F = 659/266 And also, the result of Aphasia Quotient test was significant difference among patients with different lesion locations(anterior and posterior-anterior)(table3, Fig3B). P = Fو = 15/312), But there are no significant relationships 0/000 between patients with different sex (Table4, Fig3C). P = 0/806 = 0/327 Fو Like other tests, the variables such as gender and location of the lesion, when considered together, there no significant (P Fو = 1/601 relationships were revealed between the = 0/234 results of Aphasia Quotient test among patients before and following A-tDCS treatment(table 7)and Fig3D. 140

9 The Correlation Rate of two-back test, total naming score and Aphasia Quotient: As shown in Table 8; The Pearson correlation between twoback test and the total naming score is significant. P =. /000,r = 0/763 The correlation between two-back test and Aphasia Quotient is significant. P =. /000,r = 0/801 The correlation between Aphasia Quotient and the total naming score is significant. P =. /000,r = 0/889 treatment of aphasia disorders, however, it seems insufficient. Discussion: One of the main and effective treatments is treatment with The aphasia disorders related to stroke is one of the main tanscranial direct current stimulation (tdcs). Treatment with impairment of language ability. It usually caused by head tanscranial direct current stimulation (tdcs) is a safe, painless injury or by impairment in left hemisphere (LH) or in left and relatively noninvasive method for modulating cortical dorsolateral part of prefrontal cortex. activity. It delivers a weak and brief polarizing electrical Deficits in working memory, unable to naming picture, current to the cortex through a pair of electrodes, and speaking, writing, and reading are the main symptom of it. according to the current flow polarity, the excitability of the Today, there have been proposed various methods for the brain can either be increased via anodal stimulation (A- tdcs) 141

10 or decreased via cathodal stimulation (C -tdcs)[14],[29]. Currently, transcranial direct current stimulation (tdcs) is used widely as a Clinical therapy for many diseases such as certain psychological disorders, post-stroke motor deficits such as aphasia disorders and fibromyalgia[ 30]. The our present study was designed to evaluate the effect of tdcs upon non fluent Persian aphasia recovery, included 20 patients with chronic, stroke- induced aphasia who each underwent 10 sessions of A-tDCS (2 ma and 20-min) and 10 sessions of Sham-Tdcs (20-min) combined with a computerized anemia treatment and also the role of lesion location in recovery of non fluent aphasia. Our results revealed that ten 20-min anodal tdcs (2 ma) sessions, significantly improves naming scores, Aphasia Quotient or severity, working memory and the Correlation Rate in non fluent aphasia patients as compared to sham-tdcs. Additionally, our study demonstrated, there was a significant difference in the results of our test before and following A- tdcs treatment between patients with different lesion locations (anterior and posterior-anterior),but not different gender (Variable sex). In our present study, the difference in treatment outcome between A-tDCS and S-tDCS wasn t related to the patients blood pressure and heart rate; because they recorded from preto post-tdcs administrations were found to be comparable across both tdcs conditions. Most early studies of tanscranial direct current stimulation (tdcs) performed in humans was on cortical regions of brain. Because monitoring of cortical excitability changes is easier than other parts of the brain. The brain has two hemispheres, right and left hemispheres. Every part of the hemispheres has different functions and damage to them can lead to diseases. Aphasia (non fluent aphasia) is a disease that occurs by lesion to the left hemisphere (LH). The study by Baker and his colleague revealed a positive and linear relationship between severity of activation of the LH, especially the left frontal cortex, and non fluent aphasia recovery. They concluded that, this region (LH) is exceedingly important for aphasia recovery. other studies showed that, tanscranial direct current stimulation over a region of the left cortex of frontal lob implicated in aphasia recovery and improved aphasia( non fluent aphasia)[11],[ 31] So according to important role of left hemisphere especially left dorsolateral prefrontal cortex in aphasia, we evaluated the effectiveness of tanscranial direct current stimulation on dorsolateral prefrontal cortex in aphasia disorders patients [14]. Recent studies have suggested that the patient with aphasia often exhibit deficits in working memory and naming picture. [14]. The study by Tino et al and Beeli et al revealed that stimulation of the DLPFC by trans direct current (tdcs) Can affect in the working memory, risk-taking behavior, making of adecision and in response to visual material emotions in healthy people. In addition, stimulation of the frontopolar cortex by tdcs was proven to affect in performance of a 142 probabilistic classification learning task. Therefore, it has been convincingly shown that tdcs can affect in functions of prefrontal cortex (working memory) [14],[33]. In the similar study by others it was revealed that tdcs modulated efficiency of working memory by hanging the brain activity in a polarityspecific way. They observed a growth in working memory performance and amplified oscillatory power in the anodal tdcs treatment not cathodal tdcs treatment as shown in current study. Marco Sandrini and his colleagues (2012) investigated the effects of transcranial direct current stimulation (tdcs) on working memory load performance, and they concluded that, verbal Working memory (tested by n-back task (2-back) and ANOVA before and after the application of bilateral tdcs over posterior parietal cortex (left anodal-right cathodal, left cathodal-right anodal or sham) was a significant interaction between tdcs and task [34]. These findings are in agreement with our results demonstrating that Anodal-tDCS over the left cortex improves language processing and working memory. In the study by Datte and his colleague, it was revealed that receiving anodal tdcs (1 ma for 20 minutes for about 5 days) by Ten patients with chronic and stroke- induced aphasia, resulted in significantly improvement of the naming accuracy in treated items compared with sham tdcs. Patients who showed the most progress were those with peri-lesional areas closest to the stimulation site [15],[35] and [36]. Alessia Monti and his colleagues measured The naming function before and immediately after tdcs treatment over the damaged left fronto-temporal areas by a computer-controlled task, and they concluded that, Cathodal tdcs over the damaged left fronto-temporal areas in patients with chronic non-fluent aphasia improves naming score[37]. It seems that A-tDCS increases cortical excitability, it presumably improved the patients ability to name pictures by focally stimulating function of the left frontal cortex Similar to the present research. Other studies have implicated the specific cortical location of left hemisphere in aphasia recovery, it is probable that improved speech and language functioning following aphasia treatment relies, at least partly, on spared left hemisphere regions [13],[23],[32]. We concluded that, after ten 20-min anodal tdcs (2 ma) sessions, the working memory and total naming score would be improved in the patient with non fluent aphasia and also the lesion location has a main role in aphasia recovery. Reference: [1] Julie Baker, Ph.D., Chris Rorden, et al.using transcranial direct current stimulation (tdcs) to treat stroke patients with aphasia Stroke June; 41(6): [2] Crosson B, McGregor K, Gopinath KS, et al. Functional MRI of language in aphasia: A review of

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12 Current Stimulation. J. Vis. Exp May (51), [28] Felipe Fregni a,, Fernanda Orsati, et al. Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods. Appetite [29] Nitsche MA, Cohen LG, Wassermann EM, et al: Transcranial direct current stimulation: State of the art Brain Stimulation 2008, 1: [30] Angela Valle, Suely Roizenblatt, Sueli Botte,et al. Efficacy of anodal transcranial direct current stimulation (tdcs) for the treatment of fibromyalgia: results of a randomized, shamcontrolled longitudinal clinical trialj Pain Manag ; 2(3): [31] Sarno M, Levita E. Recovery in treated aphasia in the first year post-stroke. Stroke 1979; 10:663. [32] Purpura DP, McMurtry JG: Intracellular activities and evoked potential changes during polarization of the motor cortex. J Neurophysiol 1965, 28: [33] Beeli G, Casutt G, Baumgartner T. Modulating presence and impulsiveness by external stimulation of the brain. Behavioral and Brain Functions 2008, 4:33. [34] Sandrini M, Fertonani A, Cohen LG. Double dissociation of working memory load effects induced by bilateral parietal modulation. Neuropsychologia Feb;50(3): [35] Datta, A., Baker, J.M., Bikson, M. Individualized model predicts brain current flow during transcranial direct current stimulation treatment in responsive stroke patient Brain Stimulation In Press (2011). [36] Nitsche MA, Liebetanz D, Lang N, et al. Safety criteria for transcranial direct current stimulation (tdcs) in humans. Clin Neurophysiol 2003; 114: [37] A Monti, F Cogiamanian,S Marceglia. Improved naming after transcranial direct current stimulation in aphasia J Neurol Neurosurg Psychiatry 2008;79: PO Box: Fax: Hamid Reza Pouretemad is Professor of clinical psychology and is currently working in Institute for Cognitive Science Studies (ICSS) Shahid Beheshti University of Medical Sciences, Tehran, Iran. P.O.Box: Abdollah Amini is currently a PhD student in Anatomical Sciences and Biology, in Cell and Molecular Biology Research Center, Medical Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran. D.amini2005@yahoo.com Reza Nilipour works as a teacher in speech therapy Department, University of Medical Sciences, and Tehran, Iran. Hamed Ekhtiari works as a Faculty Member in Institute of Cognitive Sciences, Tehran. Iran BIOGRAPHIES Mohsen saidmanesh has received BSc and MSc degree in speech therapy from the Tehran University, Iran, in 2007 and 2011 respectively. He is currently working as a PhD student in cognitive neuroscience and working in Institute for Cognitive Science Studies (ICSS), Tehran, Iran: d.amini2008@yahoo.com 144