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Chapter 1. Introduction

6. Transcranial direct current stimulation (tDCS)

6.1 Effects of tDCS on working memory performance in young healthy adults

As it is mentioned previously, some critical cognitive abilities related to daily functioning depend on WM performance, which can be affected by the presence of distractions (Miyake et al., 1999). To assess WM performance, many studies use the n-back task, which requires monitoring a chain of visual or auditory information and comparing a new stimulus with a stimulus presented n trials before (Kane et al., 2007; Mackworth, 1959). Cognitive demands of the n-back task can be varied by asking participants to respond to the currently

presented stimuli (0-back) or one, two, or three stimuli presented before (1-back, 2-back or 3-back). The response times for stimulus detection and the rate of correct versus incorrect responses are used to evaluate performance on the n-back task (Jaeggi et al., 2010; Kane et al., 2007; Mackworth, 1959). In addition, WM depends on the activity of the frontoparietal network, mainly the DLPFC, which is associated with the encoding and updating of task-relevant information, and conflict resolution (André, 2016; D'Esposito et al., 2015; D'Esposito et al., 2000; Smith et al., 1997; Wager et al., 2003). Therefore, to assess the effect of tDCS on WM performance, several studies have hired the n-back task and have targeted the DLPFC region (André, 2016).

Regarding the effect of anodal tDCS over the left DLPFC on WM performance, Andrews and colleagues investigated the effect of applying tDCS over the left DLPFC (10 min at 1 mA) during the performance of a WM task on the performance of a subsequent WM task (Andrews et al., 2011b). Experimental conditions included either anodal tDCS during the performance of an n-back task, anodal tDCS during rest, or sham tDCS while performing an n-back task.

Participants performed the WM task (2-back), followed by a 3-back task, and finally a digit span task. The latter task consists of the repetition of a series of numbers after presentation either in the same order (digits forward) or in the opposite order (digits backward). The tasks were performed immediately before and after each stimulation condition. The findings showed that applying tDCS during the n-back task could improve the performance of digit span forward, compared with applying tDCS during rest and sham tDCS during the n-back task conditions. It suggested that using tDCS during a WM task improved performance on a following WM task (Andrews et al., 2011b). In addition, Martin and colleagues examined the effect of applying

anodal tDCS over the left DLPFC (30 min at 2 mA) immediately before (offline tDCS) and during (online tDCS) the performance of an n-back WM task (Martin et al., 2014; Martin et al., 2013). They found that WM performance was significantly improved in participants who received anodal tDCS during the n-back WM task compared to those who received anodal tDCS immediately before the task (Martin et al., 2014)(Martin et al., 2014). Similarly, Gill and colleagues tested the effect of tDCS on tasks with different WM loads. The results revealed that the effects of anodal tDCS over the left DLPFC (20 min at 2 mA) on a WM task depended on whether participants performed the 3-back or 1-back task, suggesting that the effect of tDCS on WM are dependent on the cognitive demands of the task (Gill et al., 2015). Another study revealed that anodal tDCS over the left DLPFC (10 min at 1 mA) significantly increased the number of correct responses on a 3-back task, while there was no significant effect of cathodal tDCS over the same area or anodal tDCS over the primary motor cortex (André, 2016; Fregni et al., 2005).

Another set of findings in the study showed that anodal tDCS over the left DLPFC (15 min at 1.5 mA) combined with ten WM training sessions improved WM in the verbal domain, compared to sham tDCS (Richmond et al., 2014). Likewise, Martin and colleagues not only studied the effect of ten sessions of WM training combined with anodal tDCS but also re-evaluated WM performance four weeks after the experiment (Martin et al., 2013). Their results showed that anodal tDCS improved performance on the WM training task, and at the follow-up evaluation four weeks later, participants who received anodal tDCS combined with training showed more significant improvements on attention and WM tasks (untrained tests) compared to participants who received only anodal tDCS. These results imply that repeated sessions of

WM training combined with anodal tDCS over the DLPFC (30 min at 2 mA), compared to either training or anodal tDCS alone, may bring particular advantages in WM performance (Martin et al., 2013). In line with other studies, Zaehle and colleagues found not only that anodal tDCS over the left DLPFC (15 min at 1 mA) could improve WM performance, but also that application of cathode tDCS over the same region could disturb WM performance (Zaehle et al., 2011).

Moreover, they used EEG to show possible neurophysiological alterations related to the effects of tDCS on WM. They found that applying anodal tDCS over the left DLPFC could increase activity in the theta band, which is related to memory encoding and retrieval (Jensen et al., 2002), as well as decrease activity in the alpha band, which is related to inhibition of irrelevant information and the maintenance of goal-relevant information (André, 2016; Zaehle et al., 2011).

Taken together, this evidence suggests that tDCS over the DLPFC (particularly left) can modify WM performance in healthy young adults. However, these findings are not entirely consistent. In order to reconcile inconsistent findings and optimize the beneficial effects of tDCS, two recent meta-analyses have suggested examining the effects of different stimulation parameters and study designs (Hill et al., 2016; Lefaucheur et al., 2017; Summers et al., 2016;

Woods et al., 2016b).

6.2 Effects of tDCS on working memory performance in healthy