Concurrent TMS-fMRI

March 10, 2026 updated by: Jing Jiang

Neural Effects of Transcranial Magnetic Stimulation Using Concurrent Functional Magnetic Resonance Imaging

The goal of this clinical trial is to examine the neural mechanisms underlying transcranial magnetic stimulation (TMS) using concurrent functional magnetic resonance imaging (fMRI) in both healthy controls (HCs) and patients with high negative affect symptoms, such as depression. Approximately half male and half female participants aged 18-65 will be recruited.

The main questions it aims to answer are:

  1. Is the acute/transient effect induced by single-pulse TMS related to the long-term modulatory effect induced by repetitive TMS (rTMS)?
  2. Do any of these effects predict negative affect symptoms, such as depression?

Participants will:

  1. Complete several tests to assess their cognitive abilities and emotional states
  2. Undergo several brain scans, including resting-state fMRI, structural MRI, diffusion tensor imaging (DTI), and task fMRI
  3. Have two different types of TMS sequences, single-pulse and repetitive pulses, administered to specific brain regions while undergoing fMRI

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to examine the neural mechanisms underlying transcranial magnetic stimulation (TMS) using concurrent functional magnetic resonance imaging (fMRI). Research is conducted in both healthy controls (HCs) and patients with high negative affect symptoms, such as depression. Participants will undergo two visits, the first lasting about two hours and the second, scheduled within one week of the first, also lasting about two hours. Approximately half male and half female participants aged 18-65 will be recruited. The aims are to examine (1) whether the acute/transient effect induced by single-pulse TMS is related to the long-term modulatory effect induced by rTMS, and (2) whether any of these effects predict negative affect symptoms, such as depression.

In the first visit, participants will complete several tests to assess their cognitive abilities and emotional states, specifically measuring depression levels. These tests will help explore the relationship between their cognitive/emotional states and brain activity during TMS-fMRI. After the tests, participants will undergo several brain scans to determine the best locations for TMS during the second visit and to measure the strength of connections between different brain regions. During the second visit, participants will undergo three parts of TMS-fMRI scanning. The first part involves applying single-pulse TMS to the dorsolateral prefrontal cortex (DLPFC) and a control area (the vertex) while taking fMRI scans. This helps elucidate how TMS affects deep brain regions related to mood disorders. By comparing brain responses to TMS between healthy controls and patients, researchers can gain important knowledge of whether the neural pathways between stimulated region and these subcortical brain regions are disrupted in patients. The second part includes theta-burst stimulation (TBS) of TMS to the DLPFC, which is a stimulation protocol approved by Food and Drug Administration (FDA). Finally, in the third part, single-pulse TMS is administered again after TBS to see if the TBS has changed the brain's response. Comparing the after-TBS single-pulse TMS-evoked brain responses with before-TBS responses would allow the investigators to track whether the TBS could change the disrupted neural pathways in patients. Investigators will also examine how participants' cognitive/emotional test results and brain connectivity relate to the TMS-evoked brain responses and the effects of TBS. Any potential relationships found can provide insight into the underlying mechanisms of how individual differences in cognitive/emotional functioning and brain connectivity profile might influence or be influenced by brain stimulation, which could ultimately inform personalized approaches to neuromodulation therapies.

Study Type

Interventional

Enrollment (Estimated)

97

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

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Carver College of Medicine

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion for patients:

  • Diagnosis of major depressive disorder
  • Age greater than or equal to 18 years
  • Age less than or equal to 65 years
  • Able to understand and consent for research participation
  • English-speaking

Inclusion for healthy controls:

  • Report no lifetime psychiatric diagnosis and treatment
  • scores on Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Questionnaire (GAD-7) lower than 4
  • Age greater than or equal to 18 years
  • Age less than or equal to 65 years
  • Able to understand and consent for research participation
  • English-speaking

Exclusion for all subjects:

  • Age less than 18 years
  • Age greater than 65 years
  • With epilepsy or seizure disorder
  • With implanted ferromagnetic equipment in their face or skull near the stimulation target

MRI Exclusion criteria for all subjects:

  • Implanted device including pacemaker, coronary stent, defibrillator, or neurostimulation device that is not MRI-compatible
  • Metal in body including bullets, shrapnel, metal slivers
  • Claustrophobia
  • Uncontrolled high blood pressure
  • Blood circulation problems
  • Opiate medication, antihypertensive medication, or any medication that interferes with blood flow (interferes with fMRI recordings)
  • Significant heart disease, such as atrial fibrillation
  • Pregnancy in female participants
  • Prior exposure to deep brain stimulation, rTMS, or tDCS (transcranial direct current stimulation) therapies
  • History of neurological or cardiovascular disorders, brain surgery, radiation treatment, brain hemorrhage or tumor, stroke, or diabetes
  • Significant traumatic brain injury (loss of consciousness, post-injury amnesia, significant radiological/neurological findings, penetrating brain injury)
  • Refusal to abstain from illicit drug use for duration of the study
  • Refusal to abstain from alcohol within 24 hours of scans

If you would like to participate in the study, click this link to fill out the Screening Form: https://redcap.icts.uiowa.edu/redcap/surveys/?s=DEYHWF8TMCHHW4Y7. Kindly note that our research team will contact you directly only if you meet the eligibility criteria for the study. Due to the high volume of responses, we are unable to reply to individual inquiries or provide feedback about eligibility decisions.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: spTMS-TBS-spTMS
This is an open-label, single-arm study. The intervention will be delivered in spTMS-TBS-spTMS order to the dorsolateral prefrontal cortex (dlPFC) and vertex for each participant as described in the "Interventions" section. The order of the stimulation sites will be counterbalanced across participants.
Device: spTMS-TBS-spTMS
This study uses fMRI in combination with single-pulse TMS (spTMS) and theta-burst stimulation (TBS) to determine if the two effects coming from each are related to one another, and if there will be changes in brain activity when undergoing spTMS that are induced by TBS. Additionally, by stimulating the dlPFC in both patients and healthy controls with this paradigm, researchers are able to specifically compare the after-TBS single-pulse TMS-evoked brain responses with before-TBS responses to observe if TBS will change neural pathways disrupted in those who display high negative affect (e.g. depression).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pre and Post TBS Modulation Effect Comparison
Time Frame: Up To 10 Minutes
The primary outcome measure will be the modulation effect of TBS to the dlPFC, which is the difference between TMS-induced acute/transient effects before and after TBS. The acute/transient effects will be assessed through single-pulse TMS-induced fMRI blood oxygenation level-dependent (BOLD) responses. The difference in BOLD response before and after TBS (i.e., TBS modulation effect) will be assessed using paired t-tests reported with t and p values.
Up To 10 Minutes
Difference in TBS Modulation Effect Across Comparison Groups
Time Frame: Up to 10 Minutes
Another primary outcome measure is whether this TBS modulation effect is different between healthy controls and patients with high negative affect symptoms (e.g. depression). The difference will be assessed using independent t-tests reported with t and p values.
Up to 10 Minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TMS Effects with Neurocognitive and Emotion Functions
Time Frame: One Week

The secondary outcome measure is the relationship between the TBS modulation effect, TMS-induced acute/transient effects, intrinsic network properties, and participants' neurocognitive and emotion functions. This relationship will be assessed using the Pearson correlation reported using r and p values.

The intrinsic network properties will be assessed by participants' (1) resting-state fMRI-based functional connectivity reported with Pearson based r values between two brain regions, (2) DTI MRI-based structural connectivity reported by the number of white matter streamlines. The neurocognitive functions will be assessed with cognitive scales and questionnaires (e.g. Montreal Cognitive Assessment (MOCA)). The emotion functions will be assessed emotional scales and questionnaires (e.g. Montgomery-Åsberg Depression Rating Scale (MADRS)).
One Week

Collaborators and Investigators

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

Sponsor

Jing Jiang

Collaborators

National Institute of Mental Health (NIMH)
National Institutes of Health (NIH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 19, 2024

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

January 31, 2029

Study Registration Dates

First Submitted

September 30, 2024

First Submitted That Met QC Criteria

October 7, 2024

First Posted (Actual)

October 9, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202402416
  • R01MH136197 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data will be submitted to the NIMH Data Archive every 6 months.

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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