Transcranial direct current stimulation (tDCS) is a technique that stimulates the cerebral cortex with a weak constant electric current in a non-invasive and painless manner . The current flows from an active to a reference electrode, a part being shunted through the scalp and the rest being delivered to the brain tissue , thereby inducing diminutions or enhancements of cortical excitability . The direction of the tDCS-induced effect depends on the current polarity: Anodal tDCS typically has an excitatory effect on the local cerebral cortex, while cathodal tDCS decreases the cortical excitability in the region under the electrode [3, 4]. The mechanisms underlying these neuromodulatory effects are not well understood . Animal studies suggest that anodal tDCS, via an extracellular negative sink, causes a depolarization of the resting-membrane potential and increases the firing rates of many perpendicularly oriented cortical neurons in the tissue under the electrode. Cathodal stimulation has the opposite effect, causing a hyperpolarisation of the resting-membrane potential and a decrease in firing rates [6, 7]. Thus, tDCS seems to modify spontaneous neural excitability by tonic de- or hyperpolarization of the resting-membrane potential . However, the effects of tDCS are not limited to modulations in cortical excitability during stimulation, and may outlast the stimulation period by several minutes or even hours [3, 4, 6, 8]. These after effects of tDCS are associated with a number of different mechanisms, including local changes in ionic concentrations (hydrogen, calcium) and levels of cyclic adenosine monophosphate (cAMP), alterations in protein synthesis, and modulation of N -methyl-D-aspartate (NMDA) receptor efficacy [5, 9–14].
The neuromodulatory changes induced by tDCS have been associated with modifications of a variety of behavioural brain functions. In animal studies, anodal tDCS of the cortical surface has been linked with facilitation of an unconditioned response [15, 16] and improved learning . In humans, the effects of tDCS have been demonstrated on various motor, visual, and somatosensory cortex functions (see  for a recent review). In particular, previous studies have reported enhancements in motor [19, 20] and visuo-motor learning  for anodal tDCS, while impairments in auditory learning have been observed for cathodal tDCS . Similarly, anodal tDCS improves language learning , picture-naming  as well as implicit grammar learning , whereas cathodal tDCS has been shown to impair verbal learning abilities [26, 27]. Analogous polarity-specific effects of tDCS have been reported for working memory (WM) functions, suggesting that anodal but not cathodal tDCS can improve WM performance [8, 28, 29]. However, the nature of the neurophysiological mechanisms underlying this cognitive enhancement is not yet well understood, because modifications of WM functions by tDCS have never been studied in combination with neurophysiological methods.
In general, WM refers to a set of basic mental operations that define the ability to hold an item of information transiently in mind, in order to recall, manipulate and associate this information to incoming new information . WM is crucial to many higher-order strategic functions and has been linked to frontal [31, 32] and parietal lobe functioning . A commonly used WM paradigm is the n-back task which activates a fronto-parietal network, including the dorsolateral prefrontal cortex (DLPFC) [34–37], and the posterior parietal cortex . While the DLPFC is involved in the processing of stimulus information during retention times , the parietal lobe participates in the storage of perceptual attributes . Furthermore, the prefrontal cortex seems to be functionally lateralized, with the right hemisphere being recruited in particular during spatial WM tasks, and the left hemisphere being crucial for the processing of non-spatial (i.e., verbal) WM tasks . The critical role for the left DLPFC in verbal WM performance has been confirmed by lesion studies and studies using TMS, showing that focal damage and temporary disruption of the left but not the right DLPFC is related to impairments in verbal WM task performance [42, 43].
The present study examined the impact of tDCS on WM performance and the underlying neural activity. In particular, we explored the effect of tDCS applied over the left DLPFC on oscillatory brain activity during a letter n-back WM task. Based on previous findings we hypothesized tDCS-dependent alteration of WM performance [8, 29]. Furthermore, we predicted tDCS-related modifications of the underlying rhythmic neural activity in the alpha and theta frequency range, given the view that alpha and theta oscillations play an important role in memory functions . To our knowledge this is the first study investigating the modulatory effects of tDCS on oscillatory brain activity in the context of a WM task. The better understanding of the neuromodulatory effects of tDCS is also of clinical interest, since electrical brain stimulation seems to have potential as a therapeutic tool applied for several neurological and psychiatric disorders [45–51], and particularly for the treatment of memory deficits in stroke patients , patients with Parkinson's disease , and patients suffering from Alzheimer's disease [53, 54].