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RecruitingNCT05437705Updated Sep 3, 2026

Decoding and Modulating Affective Brain States

An interventional study of Transcranial Magnetic Stimulation in Rumination, Major Depressive Disorder and Anxiety, sponsored by University of Pennsylvania. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-03.

Sponsored by University of Pennsylvania · Not applicable, Interventional, and Basic science

From the registry’s dates

  • Started Feb 2023; still recruiting 3 years 7 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The research study is being conducted to study brain patterns of negative emotion and develop personalized brain stimulation protocols to disrupt these patterns with transcranial magnetic stimulation (TMS). First, the investigators will use functional Magnetic Resonance Imaging (fMRI) data to generate a negative affect map for each participant. Then, the investigators will apply a variety of repetitive transcranial magnetic stimulation (rTMS) sequences while the participant is inside the MRI scanner to determine the optimal and least optimal rTMS frequencies at changing negative affect brain states. Finally, these two frequencies will be tested over two 3-day rTMS neuromodulation sessions to assess whether they can reduce negative emotions.

Read the detailed description

The study involves 11 visits over approximately 10 weeks, depending on scanner availability and scheduling. See below for the study schedule with a summary of the procedures:

  • Visit 1: Screening Procedures (\~3-4 hours). The first part of the screening will take place remotely (\~1 hour). The investigators will begin by reviewing the Informed Consent Form (ICF). Participants who agree to participate and sign the ICF will then complete several questionnaires. Those who meet preliminary eligibility criteria based on the remote procedures will be invited for an in-person visit. The in-person screening will include a brief TMS demonstration (\~20 minutes). If TMS is well tolerated, the visit will proceed to a comprehensive clinical interview (\~2-3 hours) to assess current and past mental health history.
  • Visit 2: Baseline MRI \& Assessments (\~2 hours). This visit will involve a 1-hour MRI scan, including both structural and functional sequences, and an assessment session with computerized tasks and questionnaires.
  • Visit 3: MRI Scan with TMS (\~2.5 hours). A second MRI scan will be conducted with concurrent TMS procedures. Participants will complete a mental task while interleaved rTMS is delivered at different frequencies. This scan will be used to determine the optimal stimulation frequency for each participant.
  • Visits 4-6: First Neuromodulation Session (\~1.5 hours each). Participants will receive rTMS using either the optimal or least optimal stimulation frequency. They will also complete two computerized tasks after rTMS, with questionnaires in between procedures.
  • Visit 7: MRI Scan with TMS (\~2 hours). This visit will be a shortened version of Visit 3, as some MRI scans and questionnaires will not need to be repeated.
  • Visits 8-10: Second Neuromodulation Session (\~1.5 hours each). These visits will mirror Visits 4-6. However, the TMS condition administered (optimal or suboptimal frequency) will be counterbalanced with the condition used during the first neuromodulation session. Visit 8 will be scheduled at least 2 weeks after Visit 7.
  • Visit 11: MRI Scan with TMS (\~2 hours). This visit will mirror Visit 7.

After completing all procedures, participants will receive the full study compensation. Payments may be issued earlier if participants request compensation after each visit or if they withdraw early.

02

Conditions studied

  • Rumination
  • Major Depressive Disorder
  • Anxiety

Keywords

  • TMS
  • rumination
  • depression
  • anxiety
03

In context

Rumination Syndrome

72 studies on the registry are indexed under Rumination Syndrome; 22 are open to participants now.

This study's planned enrollment of 40 is below the median of 62 across 63 interventional studies indexed under Rumination Syndrome.

Browse Rumination Syndrome studies →

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. 18-65 years old
  2. Patient Health Questionnaire (PHQ-9 score) = or > than 10
  3. Comprehension of instructions in the English language.
  4. Capacity to provide informed consent and follow study procedures.
  5. Availability for the duration of the study.

Exclusion criteria

Exclusion Criteria:

  1. Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder
  2. Recent use of psychoactive medications or substances as determined by investigators
  3. History of neurological disorder or traumatic brain injury (other than mild)
  4. Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
  5. Unable to receive or tolerate TMS
  6. Implanted devices, such as an aneurysm clip or cardiac pacemaker
  7. History of stroke, epilepsy, or brain scarring
  8. Pregnant, nursing, or trying to become pregnant (self-attestation alone)

During this study, participants are asked to:

  1. Refrain from substance use (including marijuana and illicit drugs) for duration of the study (self-attestation alone).
  2. Abstain from alcohol for 24 hours before the MRI scans (self-attestation alone).
  3. Abstain from increasing caffeine intake or begin taking any new medications (self-attestation alone).
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Participant)
Enrollment
40 participants (estimated)

Study arms

  • Experimental
    Neuromodulation using the optimal rTMS stimulation frequency

    Through manipulation of brain state with a negative-affect task and using fMRI as the feedback signal, the investigators aim to fine-tune repetitive Transcranial Magnetic Stimulation (rTMS) delivery to maximally impact the desired brain states in awake, behaving participants in a highly individualized manner (Visit 3). The optimal rTMS stimulation frequency will then be tested in a 3-day rTMS neuromodulation intervention.

    Device: Transcranial Magnetic Stimulation

  • Active comparator
    Neuromodulation using the least optimal rTMS stimulation frequency

    The investigators will compare the results of the optimal rTMS frequency neuromodulation with a separate 3-day neuromodulation session using the least optimal rTMS frequency, as determined by the results of Visit 3.

    Device: Transcranial Magnetic Stimulation

Interventions

  • DeviceTranscranial Magnetic Stimulation

    Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. The MagPro X100\* magnetic stimulator and Cool-B65 Butterfly Coil are FDA-approved for rTMS treatments of depression.

06

What researchers measure

Primary outcomes

  1. Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency

    By comparing the RRS score change pre/post rTMS of both neuromodulation sessions (Visits 4-6/7-9) the investigators will determine whether the optimal rTMS stimulation frequency is more effective at improving clinical outcomes.

    Time frame: Up to 4 weeks

07

Study locations

1 of 1 sites recruiting
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT05437705
Lead sponsor
University of Pennsylvania
Responsible party
Desmond Oathes (Assistant Professor of Psychiatry, University of Pennsylvania) — Principal investigator
First posted
Jun 29, 2022
Start date
Feb 21, 2023
Primary completion
Dec 1, 2028 (estimated)
Completion
Dec 1, 2029 (estimated)
Last update
Sep 3, 2026

Study contacts

Camille Blaine
Contact
camille.blaine@pennmedicine.upenn.edu
215-573-0828
Almaris Figueroa-Gonzalez
Contact
almaris.figueroa-gonzalez@pennmedicine.upenn.edu
215-746-6751
Desmond Oathes, PhD
principal investigator · Associate Professor of Psychiatry

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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