Brain Connectivity in Depression

NCT03276793 | Recruiting DMC

• 2 other identifiers: 2021P000335R01MH113929
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 4

Brief Summary

This study originally included 140 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham \& Women's Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data was utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. This was the only study group until August 30, 2022, and the primary outcome was analyzed for the 10Hz-TMS group. Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed intermittent theta burst (iTBS), in September 2022 a second group was added to include patients receiving this new form of TMS. This second group included another 100 patients with medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data will be utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. Due to a higher dropout rate than anticipated, in March of 2025 an amendment was added to include an additional 20 subjects in the second group's enrollment goal to increase the likelihood of achieving 80 completers.

Conditions

Depression

Outcome Measures

Primary Outcomes (2)

• Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response

  Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).

  1 year after study completion

• Prediction of intermittent theta burst stimulation (iTBS) clinical response

  Normative connectivity of each patient's stimulation site to a previously-published "depression network" (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.

  1 year after study completion

Study Arms (1)

MRI and behavioral assessment for patients receiving TMS

EXPERIMENTAL

Subjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course.

Other: MRI scan; Behavioral: Behavioral testing

Interventions

MRI scan OTHER

Patients will undergo an MRI scan

MRI and behavioral assessment for patients receiving TMS

Behavioral testing BEHAVIORAL

Patients will complete a series of cognitive tasks

MRI and behavioral assessment for patients receiving TMS

Eligibility Criteria

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

You may qualify if:

• Male or female
• Aged 18 or older
• Have previously received or will once daily TMS treatment to the left dorsolateral prefrontal cortex at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for treatment of medication resistant depression

You may not qualify if:

• Lack of response to an adequate trial of electroconvulsive therapy (ECT) or any ECT in the preceding 3 months
• Prior adequate trial of TMS treatment in the last 12 months
• Positive MRI screen that would preclude the subject from undergoing magnetic resonance imaging. These include, but are not limited to any of the following:
• Known metal in the head (such as a surgical aneurysm clip), or a history of prior neurosurgical procedures
• Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means such as: cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts
• Subjects who have or might have bullet fragments or other metal fragments (veterans or workers exposed to metal in their work environment)
• Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)
• Subjects expressing significant anxiety or claustrophobia about being in the magnet.
• Subjects that cannot adhere to the experimental protocol for any reason.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Butler Hospital: collaborator
• Massachusetts General Hospital: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (4)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

COMPLETED

Butler Hospital

Providence, Rhode Island, 02906, United States

ACTIVE NOT RECRUITING

Related Publications (1)

• Khosravani S, Palm ST, Drew W, Frandsen SB, Lin C, Tirrell E, Hindley L, Schineller M, Garimella A, Chiulli N, Lawson D, Jones E, Press DZ, Stern AP, Brown JC, Barbour TA, Taylor JJ, Carpenter LL, Siddiqi SH, Fox MD. Predictive value of subgenual cingulate normative connectivity to TMS treatment site for antidepressant response in routine clinical practice: a prospective, multisite cohort study. Mol Psychiatry. 2025 Aug 22. doi: 10.1038/s41380-025-03153-3. Online ahead of print.

  PMID: 40847007 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

David Lawson, BA

CONTACT

617-732-6658; bwh_fdctrial@mgb.org

Emma Jones, BS

CONTACT

bwh_fdctrial@mgb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 8, 2017
• Study Start: April 3, 2018
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 21, 2025

Record last verified: 2025-04

Locations

US (4)