Decoding and Modulating Affective Brain States

August 26, 2025 updated by: Desmond Oathes, University of Pennsylvania
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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.
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Up to 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: Desmond Oathes, PhD, Associate Professor of Psychiatry

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

June 13, 2022

First Submitted That Met QC Criteria

June 23, 2022

First Posted (Actual)

June 29, 2022

Study Record Updates

Last Update Posted (Estimated)

September 3, 2025

Last Update Submitted That Met QC Criteria

August 26, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 850664

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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