Investigation of Brain Network Dynamics in Depression

NCT01931995 | Completed Results

• 1 other identifier: 2012p001784
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being done to gain a better understanding about brain networks that may be involved in depression. The investigators plan to examine how these networks change after the brain is stimulated with "Transcranial Magnetic Stimulation" (TMS). TMS is a way of stimulating the brain in order to mildly activate or mildly suppress different brain areas, and is used to treat some forms of depression. It is hoped that this study will facilitate learning more about the structure and function of different brain areas and the ways that they are interconnected to form networks, both in depressed people and in people without depression. In this research study, the effects of TMS will be measured by obtaining "pictures" of the brain with "Magnetic Resonance Imaging" (MRI) and with "Positron Emission Tomography" (PET). More specifically, this will be accomplished with a combined MRI and PET scanner, which is capable of simultaneously obtaining both MRI and PET images of the brain. This scanning paradigm will allow the assessment of local metabolic changes resulting from TMS (with PET images) and brain network changes resulting from TMS (with fMRI). Changes resulting from TMS between 20 subjects with depression and 20 healthy volunteers will be calculated and will form the main outcome measure.

Conditions

Major Depressive Disorder, Recurrent

Outcome Measures

Primary Outcomes (1)

• Relative Changes in Corticolimbic Functional Connectivity as a Result of TMS

  The primary outcome measure is the relative change in functional connectivity in prefrontal corticolimbic brain networks resulting from TMS stimulation of two nodes in the dorsolateral prefrontal cortex: one which is positively correlated to the subgenual cingulate and one which is negatively correlated to this area. Functional connectivity is a measure of correlation strength which biologically reflects correlations between low-frequency oscillations in the fMRI blood oxygenation level dependent signal. As a correlation, this ranges from -1 to 1. This is then Fisher transformed from an r value to a z value (range -2 to -2).

  Assessed immediately following each intervention

Secondary Outcomes (1)

• Changes in Local Glucose Metabolism at Corticolimbic Network Nodes

  Assessed immediately following each intervention.

Study Arms (2)

TMS to positively correlated DLPFC

ACTIVE COMPARATOR

High frequency TMS to a target region of dorsolateral prefrontal cortex which is positively correlated with the subgenual cingulate cortex

Device: TMS positively correlated DLPFC

TMS to negatively correlated DLPFC

ACTIVE COMPARATOR

High frequency TMS to a target region of dorsolateral prefrontal cortex which is positively correlated with the subgenual cingulate cortex

Procedure: TMS to negatively correlated DLPFC

Interventions

TMS positively correlated DLPFC DEVICE

TMS, or transcranial magnetic stimulation, is a technique that is employed to non-invasively activate or suppress targeted regions of the cerebral cortex. One TMS system has been FDA approved to treat certain medically refractory forms of depression.

Also known as: This study will employ a TMS system that includes a stimulator, TMS coil and neuronavigation system

TMS to positively correlated DLPFC

TMS to negatively correlated DLPFC PROCEDURE

TMS, or transcranial magnetic stimulation, is a way of non-invasively activating or suppressing targeted regions of the cerebral cortex. One TMS system has been FDA approved to treat certain medically refractory forms of depression.

Also known as: This study will employ a TMS system that includes a stimulator, TMS coil and neuronavigation system

TMS to negatively correlated DLPFC

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 18-50
• Patients with Major Depressive Disorder, as confirmed by a referring provider, DSM-IVR criteria, and/or a Structured Clinical Interview (SCID)
• Score of ≥18 on the 24 item version of the Hamilton Depression Rating Scale (HDRS)
• Meeting criteria to safely receive fMRI scanning, PET scanning and rTMS.

You may not qualify if:

• Any subject who is pregnant or lactating
• Patients with bipolar disorder, schizoaffective disorder, suicidal ideation, or any history of psychosis. Concurrent anxiety disorders will be allowed.
• Any serious concurrent medical or neurological illness
• Any contraindication to receiving TMS, fMRI or PET scans including, but not limited to having: a pacemaker, metallic implants, implanted pumps, surgical aneurysm clips, history of severe head trauma, history of seizures or a first degree relative with epilepsy, been involved in a nuclear medicine study in the past 12 months, diabetes

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Martinos Center for Biomedical Imaging/Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (1)

• Sun W, Billot A, McMains S, Rodrigues K, Braga RM, Izquierdo-Garcia D, Eldaief MC. Relationships between local metabolic activity and distributed functional connectivity in major depressive disorder. Transl Psychiatry. 2025 Dec 1. doi: 10.1038/s41398-025-03766-w. Online ahead of print.

  PMID: 41326377 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Recurrence

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Mark Eldaief
• Organization: Massachusetts General Hospital

MELDAIEF@PARTNERS.ORG

6177261728

Study Officials

• Mark C Eldaief, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mark Eldaief, MD, Associate Neurologist

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 30, 2013
• Study Start: February 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: July 1, 2018
• Last Updated: July 7, 2021
• Results First Posted: July 7, 2021

Record last verified: 2021-06

Locations

US (1)