No Evidence That Baseline Prefrontal Cortical Excitability (3T-MRS) Predicts the Effects of Prefrontal tDCS on WM Performance.

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.

Boosting Cognition: Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory.

Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may be an effective method to enhance domain-independent WM functioning in some individuals, but not others, or can even impair WM. They thus call for a thorough investigation into individual differences in tDCS respondence as well as further research into the design of multisession tDCS protocols that may be optimal for boosting cognition across a wide range of individuals.

Cognitive enhancement: it's about time.

Voelker et al. (2016) discuss the intriguing possibility that faster response times after training result from changes in white matter pathways, and propose that frontal theta activity is important for inducing these changes. We argue that, depending on the specific cognitive processes and brain networks targeted by training, oscillatory activity in other frequency bands could produce similar changes in white matter. Such changes can have a profound effect on brain function and performance if they optimize the timing of information transmission through neural networks. It is not about frequency or speed per se; it is about time.

Biasing neural network dynamics using non-invasive brain stimulation.

Recently, non-invasive brain stimulation (NBS) has been discovered as a tool to improve human performance on a wide variety of tasks. Although these observations are highly intriguing, the underlying mechanisms of such enhancements are still poorly understood. Here, we argue that in order to advance our understanding of these mechanisms it is necessary to focus on intrinsic network dynamics in the brain. Taking into account well-known network dynamics, increased excitation in one particular network or brain region may necessarily lead to inhibition of an opposing network (and vice versa). As a consequence, observed behavioral improvements due to NBS may emerge from a shift in the balance between (competing) neural networks in the brain, implicating that behavioral enhancement due to stimulation most likely comes with a cost or side effect. We conclude that more elaborate experimental designs are essential for a better understanding of the relationship between network interactions and the behavioral effects of NBS.