Resonant Frequency rTMS: A Novel Approach to Target Circuit Modulation in Major Depressive Disorder
NCT Number: NCT06572683
Acronym: R01RF
Status: ENROLLING_BY_INVITATION
Study Type: INTERVENTIONAL
Phases: NA
Conditions: MDD|Depression
Interventions: DEVICE: Transcranial Magnetic Stimulation
Sponsor: University of California, Los Angeles
Collaborators: National Institute of Mental Health (NIMH)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 84
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-02-12
Completion Date: 2028-10-31
Locations: University of California, Los Angeles, California, 90024, United States

Summary:
The purpose of the study is to develop a more personalized brain stimulation using repetitive transcranial magnetic stimulation or rTMS approach to treat major depressive disorder (MDD). The investigators had previously developed a personalized rTMS treatment by examining the effectiveness of different rTMS frequency from 5 to 18 Hertz (Hz). The optimal treatment frequency is termed resonance frequency and varies across individuals. There has not been a systematic method to identify the best stimulation frequency in an individual-specific way. In this project, the investigators will identify and compare 3 rTMS frequencies, all targeting the brain region called left dorsolateral prefrontal cortex (DLPFC): 1 that engages brain circuit connectivity the most- the investigators call this resonant frequency (RF)-max (RF-max), 1 that is the lowest ranked resonance frequency called RF-min and 1 that is standard of care treatment - rTMS of 10 Hz as a point of comparison.

This study is a multi-sites project that will be conducted at UCLA and Butler hospital. This study will enroll 84 participants with MDD over the course of 4.5 years.

Participants will undergo a brain imaging scan or magnetic resonance imaging (MRI), 3 electroencephalograms (or EEG, a measurement of electrical activity of the brain), to identify rTMS resonance frequencies (RFs), 3 sessions of different resonant frequencies of rTMS in combination with EEG, totaling up to 7 in person visits. Participation will take up to 4 weeks.

Primary Outcome Measures: Repeatability of the Resonant Frequency measure, Resonant Frequency (RF) of brain oscillations will be measured three times for each participant. Each time, all unique frequencies will be assigned a ranking corresponding to the degree of elicited network activity. We will then compute pairwise Spearman's correlation coefficients (R) between individual rankings obtained at time 1 (T1) vs time 2 (T2), T1 vs Time 3 (T3), and T2 vs T3. We expect that all R-values will be above R = 0.4.

This will be single-subject level analysis., 1 week per subject (Three RF measurements will happen within 1 week)|Changes in Electroencephalograms (EEG) functional connectivity, Electroencephalograms functional connectivity (EEG-FC) will be measured after rTMS stimulation 1) at the maximal and 2) at the minimal RF (RFmax, RFmin, respectively), as derived from the ranking using Outcome Measure 1.

We will compare changes in EEG-FC after RFmax to changes in EEG-FC after RFmin. This will be a group-level analysis., Ten days for each subject (2 sessions (RFmax/RFmin) separated by one week).|Spatial maps of source-localized EEG connectivity, We will quantitatively compare the spatial extend of source-localized connectivity elicited by RFmax vs. RFmix stimulation. Binary statistical connectivity maps will be compared for size and percentage of overlap between the two conditions., Ten days for each subject (2 sessions (RFmax/RFmin) separated by one week)|Percent overlap between spatial maps of source-localized EEG connectivity and fMRI-based MDD-rTMS responsive network, Similar to Outcome measure 3, but instead of comparing the spatial extend of EEG connectivity between RFmax vs. RFmin, this analysis will quantify the similarity to an MDD-rTMS responsive network derived from functional MRI data (Siddiqi et al. 2020)., 1 week per subject.