The Effect of Single Pulse TMS on Working Memory Performance: An Online TMS And fNIRS Study

Transcranial magnetic stimulation (TMS) is widely used in both clinical and research settings to study and treat neurological and neuropsychiatric disorders, yet its underlying neural mechanisms remain unclear; particularly how stimulation influences both local and distant regional activity in relation to behavior. In this study, we combined single-pulse TMS with concurrent whole-head functional near-infrared spectroscopy (fNIRS) to examine hemodynamic and behavioral responses during a working memory task, with a focus on behavioral variability. Single TMS pulses were delivered to the left dorsolateral prefrontal cortex (DLPFC) while healthy participants rested; additionally, single pulses were delivered online to the left DLPFC while participants performed the working memory task. Across all participants, we observed a reliable load-dependent increase in hemodynamic activity associated with task. However, behavioral responses to TMS varied during the task. When participants were stratified into subgroups based on performance, a distinct topographic pattern emerged. During the task, TMS systematically modulated hemodynamic responses in regions including DLPFC, superior medial gyrus, precuneus, and parietal lobule, which are areas belonging to the default mode network. Moreover, the hemodynamic response during the single pulse alone sessions without any task was also found to be associated with the behavioral responses in a coherent pattern involving DLPFC, precuneus and parietal lobules. These findings suggest that variable behavioral outcomes during online TMS task are linked to distinct hemodynamic responses in a topographic pattern of local and distant regional areas.