Decoding and Modulating Affective Brain States

Not Applicable

Recruiting

• Conditions: Rumination; Major Depressive Disorder; Anxiety
• Interventions: Device: Transcranial Magnetic Stimulation

• Registration Number: NCT05437705
• Lead Sponsor: University of Pennsylvania

Brief Summary

Generating personalized brain signatures of negative emotion along with personalized brain stimulation protocols to disrupt these patterns. We plan to use fMRI and muscle activity data to determine negative affect maps for each participant. We will then try a variety of patterned repetitive transcranial magnetic stimulation sequences while recording fMRI which will be the basis of two sessions of 3-day individualized brain stimulation designed to reduce negative affect.

Detailed Description

The study involves 9 visits and 4 optional visits. Visit 1 will consist of a consenting and extended screening visit. Visit 2 will involve a 1hour MRI scan and an assessment session. The MRI scan will include both structural and functional scans, facial electromyography (EMG) recordings, cognitive tasks, and multiple questionnaires.Visit 3 will be a 2-hour TMS/fMRI session, where the participant will engage in behavioral tasks while interleaved rTMS rounds are delivered at different excitatory frequencies. This scan will be used to determine the optimal stimulation frequency for the participant. During the Visits 4-6, participants will receive rTMS using either the optimal or least optimal rTMS stimulation frequency. They will also complete a worry induction or relaxation task before and after rTMS, with assessments in between. We will counterbalance whether do worry or relax first. After these visits there will be two optional MRI scans, one similar to Visit 2, and another similar to TMS/fMRI visit. After two weeks, the study Visits 7-9 will mirror the Visits 4-6 study visits, however the rTMS stimulation frequency used would be counterbalanced. The order of optimized and least-optimized frequencies will be counterbalanced across participants between Visit 4-6 and Visit 7-9 (i.e. half of the participants will receive stimulations of the two frequencies in one order, and the other half will receive stimulations of the two frequencies in the reverse order). After this second round of neuromodulation, the same optional visits will be repeated. These optional visits will examine brain and behavioral changes after each round of neuromodulation. After completing all procedures, participants will receive the study compensation. Payment procedures completed may be given earlier if participants withdraw from the study.

Study Timeline

• Study First Submitted: 2022-06-13
• Study First Submitted QC: 2022-06-23
• Study First Posted: 2022-06-29
• Study Start: 2023-02-21
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22
• Primary Completion: 2027-12-01
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

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)
9. Otherwise determined by investigator to be unfit for study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency	Up to 4 weeks	By comparing the RRS score change pre/post rTMS of both neuromodulation sessions (Visits 4-6/7-9) we will see if our optimal rTMS stimulation frequency is more effective at improving clinical outcomes.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States