Recruiting

Affective Brain

Sponsor:

University of Pennsylvania

Code:

NCT05437705

Conditions

Rumination

Major Depressive Disorder

Anxiety

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Transcranial Magnetic Stimulation

Study Details

Brief 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.

Conditions

Rumination

Major Depressive Disorder

Anxiety

Study ID

NCT05437705

Start date

Feb 21, 2023

Status verified date

Sep, 2026

Completion date

Dec 1, 2029

Anticipated

Primary completion date

Dec 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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:

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).

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

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.

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.

Interventions

Transcranial 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.

Primary outcome measure

  • Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency [ Time Frame: Up to 4 weeks ]

Central Contacts and Locations

Locations

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Principal Investigator:

Desmond J Oathes, PhD

More Information

Sponsor

University of Pennsylvania

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Keywords

  • TMS
  • rumination
  • depression
  • anxiety

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by University of Pennsylvania on 2026-09-03.