Network-Targeted, Multi-site Direct Cortical Stimulation Enhances Working Memory by Modulating Phase Lag of Low-Frequency Oscillations.

Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory nodes that are functionally connected in theta and alpha frequency bands and intracranially stimulate both nodes simultaneously in participants performing working memory tasks. We find that in-phase stimulation results in improvements in performance compared to sham stimulation. In addition, in-phase stimulation results in decreased phase lag between regions within working memory network, while anti-phase stimulation results in increased phase lag, suggesting that shorter phase lag in oscillatory connectivity may lead to better performance. The results support the idea that phase lag may play a key role in information transmission across brain regions. Thus, brain stimulation strategies to improve cognition may require targeting multiple nodes of brain networks.