A closed-loop system for assessing target network engagement using concurrent TMS and functional MRI

The National Institute of Mental Health awarded Massachusetts General Hospital $453,750 under the Mental Health Research Grants program (CFDA 93.242) on September 1, 2026, to develop a closed-loop system for assessing target network engagement using concurrent transcranial magnetic stimulation and functional MRI.

The recipient is developing a flexible radiofrequency coil array (the RF Cap) that enables functional MRI acquisition simultaneously with transcranial magnetic stimulation in a clinically practical manner. The system integrates real-time functional MRI to identify optimal stimulation parameters, allowing clinicians to directly measure target engagement of brain networks during TMS intervention and verify cortical target activation at specified stimulation intensities. The approach addresses existing barriers to multimodal TMS/fMRI integration, including cumbersome mechanical setup, incomplete brain coverage, and patient discomfort, by providing improved sensitivity and neuronavigation capability for accurate targeting and dosing. Individual treatment protocols can be tuned to modulate dysfunctional networks efficiently.

Work is performed at Massachusetts General Hospital's Research Management Division in Charlestown, Massachusetts. The period of performance runs from September 1, 2026, through August 31, 2028. The award is a Project Grant, the assistance type for investigator-initiated research under the NIMH Mental Health Research Grants program.

Abstract

Functional MRI (fmri) is the most widely used non-invasive neuroimaging method in both human research studies and clinical applications. A key component behind state-of-the-art fmri is the multichannel radio frequency (RF) receive coil technology, which enables parallel imaging acceleration for improved spatial and temporal resolution. However, these RF coils are usually fabricated on a hard helmet-shaped plastic chassis. This constitutes a critical barrier for multimodal approaches combining fmri with non-invasive brain stimulation methods such as transcranial magnetic simulation (TMS). Concurrent TMS/fmri has the potential to directly assess target engagement of brain networks when stimulating cortical regions. This could offer clinicians a direct way to measure of the effects of a TMS intervention, such as verifying the cortical target activation at a given intensity. In general, this approach could be used to tune treatment protocol parameters for each individual to modulate dysfunctional networks in the most efficient way. Unfortunately, existing methods for full brain concurrent TMS/fmri are not well-suited for a translation into a clinical setting, mainly because of cumbersome mechanical setup, lack of whole brain coverage, and patient discomfort. We have built and tested a flexible RF coil array for multimodal imaging, the RF cap, that allows fmri acquisition concurrently with efficient TMS application in a highly practical manner. The RF cap significantly boosts the sensitivity of concurrent TMS/fmri acquisitions while allowing the use of a neuronavigation system to monitor the position of the TMS with respect to the subject's head and therefore enables accurate targeting and dosing. This proposal aims to first develop a closed loop system for concurrent TMS/fmri using the RF cap, by employing real-time fmri (rtfmri) to find the optimal stimulation intensity to produce clearly detectable activation changes in the targeted brain network (aim 1). Then, we propose to verify the operation of the developed system in the motor cortex with concurrent electromyographical recordings (EMG) in the scanner (aim 2). Finally, we will validate the system applying TMS at dorsolateral prefrontal cortex (dlpc) targeting either the location showing maximal negative functional connectivity to sgacc or the FDA-approved "5 CM anterior from motor cortex" target to quantify the differences in network-level engagement (aim 3). Our proposed novel hardware comprising of the RF cap used in conjunction with an MRI safe TMS coil and the closed loop system will enable recording and stimulating the brain to investigate directly the local and network-level effects of TMS. The developed system will provide highly- detailed millimeter-scale maps of TMS-induced brain activations for interactive assessment of therapeutic target engagement.