Concurrent TMS-fMRI

Not Applicable

Recruiting

• Conditions: Healthy Control; Depression; Anxiety

• Registration Number: NCT06633913
• Lead Sponsor: Jing Jiang

Brief Summary

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 and anxiety. 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 and anxiety?

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

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 and anxiety. Participants will undergo two visits, the first lasting about two hours and the second, scheduled within one week of the first, lasting about one hour. 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 and anxiety.

In the first visit, participants will complete several tests to assess their cognitive abilities and emotional states, specifically measuring depression and anxiety 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 Timeline

• Study Start: 2024-04-19
• Study First Submitted: 2024-09-30
• Study First Submitted QC: 2024-10-07
• Study First Posted: 2024-10-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Primary Completion: 2028-03-01
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Pre and Post TBS Modulation Effect Comparison	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.
Difference in TBS Modulation Effect Across Comparison Groups	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, anxiety). The difference will be assessed using independent t-tests reported with t and p values.

Secondary Outcome Measures

Name	Time	Method
TMS Effects with Neurocognitive and Emotion Functions	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)).

Trial Locations

Locations (1)

University of Iowa Carver College of Medicine; 🇺🇸 Iowa City, Iowa, United States