Validation of Closed-Loop Prefrontal Transcranial Magnetic Stimulation in a Non-Human Primate Model

Abstract This project aims to advance transcranial magnetic stimulation (TMS) technologies for psychiatric disorders. TMS outcomes vary among participants, likely due to a lack of adaptation to individual brain states. We thus propose a closed-loop approach where real-time electroencephalographic (EEG) recordings of brain

oscillations can inform the timing of TMS at the prefrontal cortex. However, closed-loop TMS applications are currently not implemented in clinical practice due to a lack of validated methods for targeting prefrontal brain oscillations and identifying markers of TMS target engagement. Invasive electrophysiological recordings in

nonhuman primates (NHPs) offer a high signal-to-noise ratio and improved localization of brain responses. Simultaneous scalp EEG recordings will inform translational efforts in humans. We aim to identify markers of TMS engagement in the prefrontal cortex from invasive electrophysiological recordings in NHPs and

differentiate direct neural responses from indirect stimulation effects. We will further characterize the effects of closed-loop TMS on invasive electrophysiological responses and determine optimal stimulation parameters. By delivering TMS at different phases and power states, we will measure TMS evoked potentials (TEPs) to

identify the most effective stimulation parameters for prefrontal closed-loop TMS. Finally, we will evaluate the effects of closed-loop theta burst stimulation (TBS) on neural plasticity. By tracking prefrontal theta rhythms in real-time, we will deliver TMS pulse bursts at specific phases to enhance the effectiveness of TBS protocols.

We will assess induced neural plasticity through the measurement of TEPs and local functional connectivity. Successful completion of this research could lead to the development of improved closed-loop TMS protocols for the prefrontal cortex, with direct implications for the treatment of psychiatric disorders in humans.