Aphasia is a common consequence of stroke and is caused by brain injury to the left cerebral hemisphere [1]. Although patients with aphasia tend to recover to a considerable extent after a stroke, most of the recovery occurs within the first 6 months and is incomplete [2]. Majority of aphasic patients continue to suffer from chronic deficits, for which conventional rehabilitative treatment is less effective [3,4]. Therefore, there is an increasing need to develop new interventions that enhance the recovery from chronic aphasia after a stroke.

Transcranial direct current stimulation (tDCS) is a non-invasive technique that has been found to modulate the excitability of neurons in the cerebral cortex [5,6]. The polarity of the current applied to the scalp determines the effect of tDCS on the underlying cortex. Anodal tDCS has been found to increase cortical excitability, whereas cathodal tDCS decreases it. Numerous reports have demonstrated the modulating effect of tDCS on various cortical functions, including motor learning, working memory, and language [7-9]. In recent studies, the application of anodal tDCS to the left frontal hemisphere was shown to increase the naming accuracy and response time in aphasic patients and healthy individuals [10-12]. These results suggest that stimulation of the perilesional area of the left hemisphere could result in improved recovery from aphasia.

In contrast, the role of the right hemisphere in the recovery from aphasia is still controversial. Previous studies hypothesized that the homologous language region in the right hemisphere has a capacity for language processing that is normally inhibited through transcallosal connections [13]. Although recruitment of the homologous language area in the right hemisphere is thought to be a crucial recovery pathway for relatively large stroke lesions in the left hemisphere, increased activity in the right hemisphere is not always beneficial for all patients. Increased activation of the right hemisphere may result in increased inter-hemispheric inhibition to the detriment of the left hemisphere and could interfere with the recovery of language function [14,15]. Consistent with the above hypothesis, some studies found that suppression of the right hemispheric homologous language region through the use of inhibitory techniques, such as repetitive transcranial magnetic stimulation (rTMS) or tDCS, resulted in an improvement in language [16,17]. Kang et al. [16] applied cathodal tDCS on the right Broca's homologue area for 5 consecutive days and reported improved picture naming in aphasic patients. Furthermore, You et al. [17] reported that cathodal tDCS to the right superior temporal gyrus produced a greater improvement in comprehension compared to the anodal tDCS to the left superior temporal gyrus or sham tDCS.

Dual-site stimulation using tDCS has received much attention for the purpose of developing more effective methods of stimulation. Vines et al. [18] applied a simultaneous dual-hemispheric tDCS to healthy subjects, using anodal tDCS over the non-dominant and cathodal tDCS over the dominant motor cortices. They confirmed an additive effect on motor function of the non-dominant hand compared with single-site stimulation. Furthermore, dual tDCS using a cathode over the right and an anode over the left parietal cortices produced a stronger neglect-like effect in healthy subjects compared with the single cathodal tDCS over the right parietal cortex [19].

To our knowledge, no study has reported the effect of simultaneous dual tDCS applied over the bihemispheric language-related regions in aphasic patients after suffering from a stroke. Therefore, in this study, we investigated the effects of dual tDCS on the language function of patients with aphasia and compared them with those of single tDCS in order to determine the most effective tDCS method for aphasic patients. We hypothesized that the simultaneous application of anodal tDCS over the left inferior frontal gyrus (IFG) and cathodal tDCS over the right IFG would have a greater effect than a single anodal tDCS over the left IFG.

None of the subjects reported severe adverse effects during or after the experiments, and they all tolerated the single and dual tDCS without interrupting the experiment.

We investigated the effect of the simultaneous application of anodal tDCS over the left IFG and cathodal tDCS over the right IFG on the language function of aphasic patients and compared the results with those of a single anodal tDCS on the left IFG. Our results demonstrated that the mean response time in the picture naming test was significantly shortened only after the dual tDCS, with an interaction between the two conditions, suggesting that dual tDCS may be more effective than single tDCS. In contrast, both single and dual tDCS were effective in enhancing the accuracy of picture naming, and the number of correct responses was significantly increased after both stimulation conditions.

The current consensus is that two important mechanisms are involved in the recovery from aphasia [25,26]. First, in patients with relatively small lesions in the left hemisphere, the recruitment of perilesional cortical neuronal elements plays an important role in the recovery from aphasia. A number of functional magnetic resonance imaging studies have demonstrated that greater activation in the left hemisphere is associated with a better outcome for language recovery [13,27,28]. Thus, the enhancement of the excitability of the left language-related cortical regions by non-invasive brain stimulation may improve recovery from aphasia [10,12].

Second, the recruitment of the homologous language area and speech-motor region in the right hemisphere may be a crucial pathway in patients with relatively large left hemispheric lesions. The right hemispheric perisylvian area is known to be involved to some extent in language recovery, but is less effective than the structural reorganization of the left hemispheric language areas [26]. The recruitment of the right hemispheric neuronal elements may be facilitated by a decrease in transcallosal inhibition resulting from the left hemispheric lesion. Although activation of the right hemisphere during the subacute phase of aphasia may be beneficial in severely affected patients, prolonged right hemispheric activity is considered to be deleterious as it may exert an increased inhibitory influence on the left perilesional activity [29,30]. Therefore, the inhibition of right hemispheric activity using cathodal tDCS may have a positive effect on language recovery, particularly in chronic aphasic patients [31].

Bihemispheric brain stimulation is based on the inter-hemispheric rivalry theory, which hypothesizes that unilateral lesions in the brain cause an imbalance between dominant and non-dominant hemispheres [32,33], and this may interfere with the natural recovery process [14]. Theoretically, increasing the excitability of the ipsilesional cortical region and decreasing the excitability of the contralesional, unaffected cortical region may help to restore the balance between both hemispheres and thus promote the appropriate recovery process [34]. For bihemispheric stimulation, tDCS has an advantage over rTMS because the dual stimulation can be applied over two hemispheres simultaneously using a single device. In addition, tDCS is cheaper, portable and less noisy compared to rTMS [35]. In the present study, both single and dual tDCS methods produced an improvement in accuracy in the picture naming test with no adverse effects, which suggests that both methods can be used as effective tools to enhance language function in patients with chronic aphasia after stroke. However, the dual tDCS additionally produced a greater improvement in response time in the picture naming test than the single tDCS. Therefore, it can be proposed that the dual tDCS contributed to an additive effect on the results obtained with the single tDCS in the improvement of the language function of chronic aphasic patients.

The patients included in our study varied greatly with respect to the subtypes of aphasia, lesion location, and the extent of brain damage. Regardless of the type of aphasia, the role of the left frontal cortex in its recovery has been demonstrated. A recent functional magnetic resonance imaging study revealed that the activation of the left frontal cortex was correlated with naming accuracy in stroke patients with aphasia [27]. Furthermore, increasing the excitability of the left frontal cortex using tDCS improved naming ability, irrespective of the subtype of the aphasia, and the extent of the stroke lesion [10]. The results from our study are consistent with previous reports and confirm that the activation of the left frontal cortex, particularly the IFG, improves naming ability in various types of aphasia.

However, the results did not demonstrate any significant change in the verbal fluency test after either type of tDCS. In the study by Cattaneo et al. [36], the application of tDCS to Broca's area improved the phonemic and semantic fluency of healthy individuals; however, their study design, outcome measurements and subjects differed from those in our study. Moreover, the Korean-language version of the verbal fluency test has not yet been validated as a quantitative method, especially in stroke patients and may need further investigation in order to define the different effects of tDCS on specific language functions.

The current study had several limitations. First, it did not examine the excitability of the stimulated cortical area directly. Therefore, the behavioral results may indirectly verify our hypothesis. Functional imaging techniques, such as functional magnetic resonance imaging, could be used to clarify this issue in future studies. Second, the total current intensities provided to the whole brain in the single and dual tDCS experiments differed (2.0 mA in the single vs. 4.0 mA in the dual tDCS, respectively). Therefore, a different modulatory effect due to a higher intensity of electric current cannot be ruled out as a cause of the differences in the results. Finally, the population in our study was relatively small and heterogeneous, and thus, we were unavailable to evaluate the effects relative to specific brain lesions or subtypes of aphasia.

Despite the above limitations, our study proposes that dual tDCS can be used as a safe and effective intervention method in addition to conventional speech-language therapy for the treatment of aphasic patients following a stroke.

The results of this study showed that simultaneous, bifrontal dual tDCS is a safe and effective method to improve language function in patients with chronic aphasia after a stroke. Further studies on the cumulative and long-term effects of dual tDCS are required for appropriate clinical application.