# Resonant Frequency rTMS: A Novel Approach to Target Circuit Modulation in MDD > **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $738,063 ## Abstract ABSTRACT Repetitive Transcranial Magnetic Stimulation (rTMS) is effective for treatment of Major Depressive Disorder (MDD). Clinical improvement with rTMS is believed to reflect engagement of a target mood-regulating circuit. This innovative proposal aims to enhance target circuit engagement through stimulation at an individual’s optimal resonant frequency (RF). Circuit connectivity is maintained by oscillations at one or more RFs specific to that circuit for that individual. Personalizing stimulation frequency is an opportunity to optimize rTMS effectiveness, but there has been no method to identify optimal RF for rTMS treatment in a patient-specific way. We developed a novel TMS-electroencephalography (TMS-EEG) “interrogation” method that identifies RFs by examining the degree of resonance induced by stimulation frequencies from 5–18 Hz for a target circuit originating in left dorsolateral prefrontal cortex (DLPFC). Frequencies are then ranked based on resonance properties (degree to which they increase connectivity in the target circuit) and the highest-ranked frequency is identified. Our pilot data suggest that MDD treatment at maximum RF (rTMSRF-MAX) rapidly modifies connectivity and leads to early symptom improvement, providing preliminary support for a RF-based personalized approach to rTMS. This project will provide a mechanistic understanding and validation of the RF approach through three aims and hypotheses: 1. Establish reliability of a method for RF determination in a DLPFC-based target circuit. H1: An individual’s RF median values and rankings will be stable across repeated measurements; 2. Demonstrate superior neurophysiologic engagement of the target circuit with rTMSRF-MAX stimulation. H2: rTMSRF-MAX will be associated with greater increases in connectivity in a left DLPFC-based target circuit than rTMS at the lowest ranked resonant frequency (rTMSRF-MIN); 3. Contrast the neuroanatomic distribution and degree of target circuit engagement by rTMSRF-MAX and rTMSRF-MIN stimulation. H3: Whole-brain EEG source localization will display a distinct distribution and degree of regional brain activation following rTMSRF-MAX and rTMSRF-MIN, with rTMSRF-MAX better engaging circuits previously reported to be related to antidepressant response. 80 MDD subjects will undergo TMS-EEG interrogation at a neuroanatomically-defined left DLPFC region. We will measure the resonance profile across the 5-18 Hz frequency range on three occasions for each individual to evaluate the temporal stability of RF measurement. Subjects then will undergo separate stimulation sessions with rTMSRF-MAX and rTMSRF-MIN. We will compare the two frequency conditions with regard to the degree of stimulation-induced changes in EEG connectivity in the target circuit. Finally, we will utilize EEG source localization to determine the neuroanatomic distribution of the connectivity effects of rTMSRF-MAX vs. rTMSRF-MIN, and compare the distribution to determine if rTMSRF-MAX bett... ## Key facts - **NIH application ID:** 10781833 - **Project number:** 1R01MH135293-01 - **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES - **Principal Investigator:** LINDA L CARPENTER - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $738,063 - **Award type:** 1 - **Project period:** 2023-12-05 → 2028-10-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10781833 ## Citation > US National Institutes of Health, RePORTER application 10781833, Resonant Frequency rTMS: A Novel Approach to Target Circuit Modulation in MDD (1R01MH135293-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10781833. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*