Decoding and Modulating Affective Brain States

NCT05437705 | Recruiting FDA Device

• 1 other identifier: 850664
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

TMS; rumination; depression; anxiety

Outcome Measures

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.

  Up to 4 weeks

Study Arms (2)

Neuromodulation using the optimal rTMS stimulation frequency

EXPERIMENTAL

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

Neuromodulation using the least optimal rTMS stimulation frequency

ACTIVE COMPARATOR

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

Transcranial Magnetic Stimulation DEVICE

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.

Neuromodulation using the least optimal rTMS stimulation frequency; Neuromodulation using the optimal rTMS stimulation frequency

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder
• Recent use of psychoactive medications or substances as determined by investigators
• History of neurological disorder or traumatic brain injury (other than mild)
• Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
• Unable to receive or tolerate TMS
• Implanted devices, such as an aneurysm clip or cardiac pacemaker
• History of stroke, epilepsy, or brain scarring
• Pregnant, nursing, or trying to become pregnant (self-attestation alone)
• During this study, participants are asked to:
• Refrain from substance use (including marijuana and illicit drugs) for duration of the study (self-attestation alone).
• Abstain from alcohol for 24 hours before the MRI scans (self-attestation alone).
• Abstain from increasing caffeine intake or begin taking any new medications (self-attestation alone).

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Rumination Syndrome; Depressive Disorder, Major; Anxiety Disorders; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Feeding and Eating Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Desmond Oathes, PhD

  Associate Professor of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Camille Blaine

CONTACT

215-573-0828; camille.blaine@pennmedicine.upenn.edu

Almaris Figueroa-Gonzalez

CONTACT

215-746-6751; almaris.figueroa-gonzalez@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The study will use a single-blind design.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: All subjects will receive TMS using the optimized and least optimized frequencies, but the order is randomized and counterbalanced.

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 29, 2022
• Study Start: February 21, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-08

Locations

US (1)