Network-targeted, multi-site direct cortical stimulation enhances working memory by modulating phase lag of low frequency oscillations

Working memory, an important component of cognitive control, is supported by the coordinated activation of a network of cortical regions in the frontal and parietal cortices. Oscillations in theta and alpha frequency bands are thought to coordinate these network interactions. Thus, targeting multiple nodes of the network with brain stimulation at the frequency of interaction may be an effective means of modulating working memory. We tested this hypothesis by identifying regions that are functionally connected in theta and alpha frequency bands and intracranially stimulating both regions simultaneously in participants undergoing invasive monitoring. We found that in-phase stimulation resulted in improvement in performance compared to sham stimulation. In contrast, anti-phase stimulation did not affect performance. In-phase stimulation resulted in decreased phase lag between regions within working memory network while anti-phase stimulation resulted 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. More broadly, brain stimulation strategies that aim to improve cognition may be better served targeting multiple nodes of brain networks.