ABSTRACT: Transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) is a promising tool to enhance working memory (WM) in clinical as well as healthy populations. Yet, tDCS does not affect everyone similarly: whereas tDCS improves WM in most individuals, some individuals do not, or actually show detriments in WM performance after stimulation. One hypothesis that has been put forward to account for individual differences in tDCS response is that baseline cortical excitability levels in the stimulated cortex may determine the strength and the direction of the effects of tDCS. Specifically, by locally affecting neuronal excitability, tDCS may interact with baseline cortical excitability levels, thereby pushing or pulling individuals toward or away from an optimal level of cortical functioning. In the current study, we put this hypothesis to the test with regard to prefrontal cortex stimulation and WM. In 20 healthy male participants, using magnetic resonance spectroscopy (MRS) at 3T, we measured concentrations of Glutamate and GABA in the lDLPFC and calculated individual Glutamate/GABA ratios as a measure for cortical excitability. Subsequently, in two stimulation sessions, we once applied anodal and once cathodal tDCS over the lDLPFC (20 min, 1 mA). Stimulation was always applied in the second block of three blocks of a WM updating task. Surprisingly, at the group-level, we found no effects of anodal or cathodal stimulation on WM performance. Yet, in line with previous studies, large individual variability was observed in the strength and direction of tDCS effects; whereas about half of the participants improved, the other half showed lower accuracy after stimulation. This was true for both anodal and cathodal tDCS. Nevertheless, contrary to our expectations, individual baseline prefrontal cortical excitability did not predict these individual differences in the effect of anodal or cathodal stimulation on WM accuracy. Future studies with larger sample sizes, which use higher magnetic field strengths (e.g., 7T) to measure cortical excitability and/or apply individualized stimulation protocols, are necessary to shed more light on the influence of baseline cortical excitability on effects of anodal and cathodal tDCS over lDLPFC on WM performance.
