Transcranial magnetic stimulation (TMS) treats neuropsychiatric disorders, but effects of stimulation are highly state-dependent and in most therapeutic applications, mental state is not controlled. This exploratory proposal will test the broad hypothesis that when TMS, specifically intermittent theta burst stimulation (iTBS), is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto-parietal network (FPN), which subserves cognitive control, an important neural and behavioral target of therapeutic TMS. After a baseline functional magnetic resonance imaging (fMRI) session, iTBS will be administered to 40 healthy subjects in three sessions over three days in a within-subjects, cross-over design: (1) dlPFC stimulation by iTBS alone, (2) dlPFC stimulation by iTBS while simultaneously performing a cognitive task, and (3) vertex (control) iTBS stimulation. Immediately after each iTBS session, we will measure blood oxygenation level-dependent (BOLD) activation during a cognitive control task (“n-back” task) and during the resting state, using BOLD connectivity and arterial spin labeling (ASL). We will test hypotheses that persisting neural changes and performance enhancement induced by iTBS to the dlPFC, compared to iTBS to the vertex, will affect the FPN, and these effects will be modulated by whether or not subjects receive iTBS when they are engaged in a cognitive control task. Demonstrating this interaction between iTBS and mental state will lay critical groundwork for future studies to show how controlling mental state during TMS can improve therapeutic effects. Trial Registration: Clinicaltrials.gov NCT04010461.
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