Accelerated rTMS for Enhancing Intact Cognition: An Examination of Dose Effects on Electrocortical Indicators of Attention and Working Memory

BACKGROUND AND AIMS Improvements in cognition (e.g., attention, working memory) are common after repetitive trans-cranial magnetic stimulation (rTMS) treatment and have also been observed in non-clinical samples. This study investigated whether rTMS can enhance cognitive resilience in individuals who perform in high-stress environments using cognitive measures and electroencephalography (EEG) to explore potential neural mechanisms of rTMS-induced cognitive change. METHODS 40 college-educated adults not reporting cognitive or psychiatric concerns underwent a 5-day accelerated (10 sessions/ day) rTMS treatment and pre-post cognitive assessment. Participants were assigned to 1 of 10 doses defined as number of active vs. sham stimulation sessions/ day (total active pulses = 3,000-30,000). To assess cognitive effects, standard batteries (NIH Toolbox, Spaceflight Cognitive Assessment Tool for Windows WinSCAT) were administered-and a subset (n=21) also did an N-Back working memory task with EEG measurement-before, immediately after, and 1 month after rTMS. For all indices, linear and quadratic correlations of pre-to-post-rTMS change with dose were examined to test if an optimal dose was achieved. RESULTS From pre- to post-rTMS, participants improved in fluid cognition (working memory, processing speed) as measured by NIH toolbox, t(39)=8.4, p<.001, d=1.3, and WinSCAT, t(39)=4.1, p<.001, d=.65; and, improvement in the latter related linearly to rTMS dose, r(39)=.40, p=.01. Regarding EEG, subjects who received high (6+ active sessions/day) also showed increased amplitudes of an event-related marker of stimulus-directed attention (P300) whether it was elicited by simple task targets, t(10)=3.1, p=.01, d=.95, or task-unrelated noise stimuli played during the task as probes of peripheral attention, t(10)=3.6, p=.005, d=1.1. Additionally, there were linear relationships between change magnitude and rTMS dose for simple task target-related, r(20)=.45, p=.04, and peripheral noise-related, r(20)=.54, p=.009, P300s. CONCLUSIONS rTMS improved fluid reasoning abilities and also changed how dynamic attention is deployed during high-demand challenges as a potential mediator of fluid cognition improvements. While linear dose-response relationships support that changes were rTMS-elicited, absence of a response curve asymptote also suggests that still-higher doses could be warranted to achieve maximal effects in non-clinical samples.