Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is not a treatment study.
In this study, the researchers are primarily interested in examining whether functional MRI (fMRI)-guided transcranial magnetic stimulation (TMS) may be more effective than traditional TMS methods at temporarily influencing neural circuit communication. The investigators test this by combining TMS and fMRI technologies to probe and modulate brain activity.
If the novel fMRI-guided TMS stimulation used in this study is more effective than traditional methods, future studies may utilize similar personalized TMS targeting methods to yield even better clinical outcomes.
This study will involve a baseline Magnetic Resonance Imaging (MRI) scan, Transcranial Magnetic Stimulation (TMS), and TMS interleaved with functional MRI (fMRI) scans.
After screening, eligible participants will undergo a 1-hour MRI scan, encompassing structural and functional scans to establish TMS stimulation targets for subsequent visits. During the baseline TMS/fMRI session or pre-intervention TMS/fMRI, single pulses of TMS and a short round of repetitive TMS (rTMS) will be administered to the participant's individualized target while functional MRI scans (fMRI) are collected. Following this, participants will commence a short TMS intervention regimen involving daily rTMS over 3 consecutive days. The day after the intervention, participants will undergo another TMS/fMRI session, or the post-intervention TMS/fMRI, to capture potential changes from the 3-day intervention.
Clinical assessments will be conducted at baseline before the first TMS/fMRI session and again after the final TMS/fMRI session to assess symptom changes.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Participants | Experimental | All participants follow the same procedures. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. Repetitive TMS (rTMS) is FDA-approved for depression treatment. TMS is administered over 5 study visits: an initial TMS/fMRI session, a 3-day TMS intervention regimen, and a post-intervention TMS/fMRI session. During TMS/fMRI sessions, participants receive single pulses of TMS pre/post a short round of Intermittent Theta Burst Stimulation (iTBS), a modified rTMS protocol. Throughout the 3-day intervention regimen, participants receive two full rounds of iTBS daily. All study participants receive active TMS. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Evoked Functional Brain Activity Pre/Post Short iTBS Stimulation Before and After the 3-Day TMS Intervention Regimen | Change in subgenual anterior cingulate evoked response (fMRI BOLD) at all four timepoints across the two TMS/fMRI scan sessions: pre-intervention and preceding a single round of iTBS in the scanner (pre-tx, pre-iTBS); pre-intervention, following single iTBS in the scanner (pre-tx, post-iTBS); post intervention, preceding iTBS in the scanner (post-tx, pre-iTBS); and post-intervention, post-iTBS in the scanner (post-tx, post-iTBS). Greater negative change is associated with more clinical improvement. | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Depression, Anxiety and Stress Scale (DASS-21) Score Pre/Post the 3-Day TMS Intervention Regimen | The Depression, Anxiety, and Stress Scale (DASS-21) is a self-report tool with 21 items, assessing depression, anxiety, and stress levels. The scale scores range from 0 to 63, with higher scores indicating more severe or frequent emotional symptoms. The change in DASS-21 score will be evaluated pre and post the 3-day TMS Intervention Regimen. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Evoked Functional Brain Activity Before and After the 3-Day TMS Intervention Regimen | Change in subgenual anterior cingulate evoked response (fMRI BOLD) Before and After the 3-Day TMS Intervention Regimen Greater negative change is associated with more clinical improvement. | Up to one week |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Desmond Oathes, PhD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41726164 | Derived | Oathes DJ, Duprat RJ, Reber J, Liang X, Scully M, Long H, Deluisi JA, Sheline YI, Linn KA. Non-Invasively Targeting, Probing, and Modulating a Deep Brain Circuit for Depression Alleviation. Nat Ment Health. 2023 Dec;1(12):1033-1042. doi: 10.1038/s44220-023-00165-2. Epub 2023 Nov 27. | |
| 41571696 | Derived | Bossus L, Dickson J, Blaine C, Khalilkhani H, Khan A, Oathes DJ. Causal connectivity maps derived from single-pulse interleaved TMS/fMRI. Sci Rep. 2026 Jan 22;16(1):3070. doi: 10.1038/s41598-025-23684-7. |
Not provided
Not provided
Of the 86 subjects screened for the study, 41 were enrolled and 45 did not start study procedures (32 screen failed, 9 withdrew from participation, and 4 lost to follow-up).
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All participants follow the same procedures. TMS/ fMRI Stimulation: The study uses a modified repetitive TMS stimulation protocol. Participants receive active TMS on five separate days: a baseline TMS/ fMRI scan, three "mini TMS" sessions, and a final TMS/ fMRI scan. Again, this level of stimulation is considered to be sub-threshold for that of a TMS treatment protocol. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline MRI and Assessments |
|
| ||||||||||||||||||
| Targeting TMS Scan |
| |||||||||||||||||||
| TMS + fMRI Scan #1 |
| |||||||||||||||||||
| Mini TMS Sessions (3 Visits) |
| |||||||||||||||||||
| TMS + fMRI Scan #2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants follow the same procedures. TMS/ fMRI Stimulation: The study uses a modified repetitive TMS stimulation protocol. Participants receive active TMS on five separate days: a baseline TMS/ fMRI scan, three "mini TMS" sessions, and a final TMS/ fMRI scan. Again, this level of stimulation is considered to be sub-threshold for that of a TMS treatment protocol. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Evoked Functional Brain Activity Pre/Post Short iTBS Stimulation Before and After the 3-Day TMS Intervention Regimen | Change in subgenual anterior cingulate evoked response (fMRI BOLD) at all four timepoints across the two TMS/fMRI scan sessions: pre-intervention and preceding a single round of iTBS in the scanner (pre-tx, pre-iTBS); pre-intervention, following single iTBS in the scanner (pre-tx, post-iTBS); post intervention, preceding iTBS in the scanner (post-tx, pre-iTBS); and post-intervention, post-iTBS in the scanner (post-tx, post-iTBS). Greater negative change is associated with more clinical improvement. | Of the 37 participants who completed all study procedures, the data from 36 participants was analyzed. Data one subject was not usable. | Posted | Mean | 95% Confidence Interval | % BOLD signal change | 5 days |
|
Adverse event (AE) data was collected from study enrollment until study completion (Up to 3 weeks).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All participants follow the same procedures. TMS/ fMRI Stimulation: The study uses a modified repetitive TMS stimulation protocol. Participants receive active TMS on five separate days: a baseline TMS/ fMRI scan, three "mini TMS" sessions, and a final TMS/ fMRI scan. Again, this level of stimulation is considered to be sub-threshold for that of a TMS treatment protocol. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting during TMS/fMRI scan | Gastrointestinal disorders | Systematic Assessment | Participant threw up during TMS/ fMRI scan and said it was due to not eaten all day; after they ate crackers they insisted on finishing rest of scan and had no further issues. Though rare, nausea is listed as a possible side effect of TMS. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Desmond Oathes, Principal Investigator | University of Pennsylvania | 215-573-9390 | oathes@pennmedicine.upenn.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 16, 2020 | May 18, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 16, 2020 | May 18, 2022 | ICF_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
All subjects receive active TMS to their individualized fMRI-guided target. Participants will first receive TMS in the MRI scanner, then over the course of 3-Day TMS Intervention Regimen, and lastly in a final MRI scan.
Not provided
Not provided
Not provided
Not provided
|
| Up to one week |
|
|
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Snaith-Hamilton Pleasure Scale | The SHAPS (Snaith et al, 1995) is a 14-item scale that measures anhedonia, the inability to experience pleasure. The items cover the domains of: social interaction, food and drink, sensory experience, and interest/pastimes. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. Either of the "disagree" responses score one point, and either of the "agree" responses score 0 points. Thus, the final score ranges from 0 to 14. | Only analyzed participants who completed all study procedures. | Mean | Standard Deviation | units on a scale |
|
|
|
|
| Secondary | Change in Depression, Anxiety and Stress Scale (DASS-21) Score Pre/Post the 3-Day TMS Intervention Regimen | The Depression, Anxiety, and Stress Scale (DASS-21) is a self-report tool with 21 items, assessing depression, anxiety, and stress levels. The scale scores range from 0 to 63, with higher scores indicating more severe or frequent emotional symptoms. The change in DASS-21 score will be evaluated pre and post the 3-day TMS Intervention Regimen. | Of the 37 participants who completed all study procedures, the data of one subject was unusable. Therefore, the data of 36 participants was used for analysis. | Posted | Mean | Standard Error | score on a scale | Up to one week |
|
|
|
| Other Pre-specified | Change in Evoked Functional Brain Activity Before and After the 3-Day TMS Intervention Regimen | Change in subgenual anterior cingulate evoked response (fMRI BOLD) Before and After the 3-Day TMS Intervention Regimen Greater negative change is associated with more clinical improvement. | Of the 37 participants who completed all study procedures, the data of one subject was unusable. Therefore, the data of 36 participants was used for analysis. | Posted | Mean | Standard Error | % BOLD signal change | Up to one week |
|
|
|
|
| 0 |
| 41 |
| 0 |
| 41 |
| 5 |
| 41 |
|
| Anxiety during TMS/fMRI scan | Psychiatric disorders | Systematic Assessment | Subject reported anxiety during TMS/ fMRI scan. Participant took a 15min break and then decided to finish scan. |
|
| Emotional Discomfort during assessment | Social circumstances | Non-systematic Assessment | Patient complained of emotional discomfort following the Columbia-Suicide Severity Rating Scale (C-SSRS). |
|
| Faint | General disorders | Systematic Assessment | Subject had a brief feeling of 'blacking out' and faint feeling during TMS stimulation. Subject was withdrawn from the study for safety. |
|
| Cutis verticis gyrata (CVG) | Musculoskeletal and connective tissue disorders | Systematic Assessment | After completing the structural scan (T1) staff noticed that subject had unsual folds in their scalp. They were referred to a radiologist who determined they had CVG. |
|
Not provided
Not provided
| D001519 |
| Behavior |