Neural effects of TMS trains on the human prefrontal cortex.

Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, a lack of understanding of its neural effects limits our ability to monitor, personalize, and adapt treatments. Here we address the methodological limitations in capturing the neural response to a single TMS train, the fundamental building block of treatment. We developed methods to measure these effects noninvasively and evaluated the acute neural response to single and sequential TMS trains. In 16 healthy adults, we applied 10 Hz trains to the dorsolateral prefrontal cortex (dlPFC) in a randomized, sham-controlled, event-related design and assessed changes to the TMS-evoked potential (TEP), a measure of local cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude that would accumulate across trains, but we found no evidence in support of this hypothesis. However, exploratory analyses demonstrated modulations non-locally and in phase and source space. Single and sequential TMS trains may not be sufficient to modulate the local TEP amplitude, but induce acute neural changes measured in alternative ways. This work should be contextualized as methods development for the monitoring of transient neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS.