Investigation of Brain Network Dynamics in Depression

NCT ID: NCT01931995

Last Updated: 2021-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2018-07-31

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.

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS), when delivered to the dorsolateral prefrontal cortex (DLPFC) is a clinically effective treatment for major depressive disorder (MDD). Network models of MDD are increasingly gaining acceptance, and functional connectivity MRI (fcMRI) has revealed topographically specific aberrations in functional network architecture in MDD. And yet, despite hints that the therapeutic effects of rTMS are actuated through distributed impacts upon cortical and subcortical limbic centers, the network effects of rTMS remain mysterious. This study seeks to investigate the way rTMS to DLPFC modulates network functional connectivity between the site of stimulation and a critical limbic region, the subgenual cingulate (sgACC), and between the sgACC and other limbic regions. In this study, high frequency rTMS will be used to stimulate the left DLPFC (recapitulating the therapeutic methodology), specifically, regions of the DLPFC that are functionally correlated and anti-correlated with the sgACC. This will be accomplished in a group of patients with MDD, and in a group of carefully matched controls. These subjects will be scanned before and after rTMS is delivered, as a way of gauging its effects. The feasibility of this design was recently demonstrated by our group (Eldaief et al. PNAS 2011). Changes induced by the stimulation will be charted with a novel combined MRI-PET (Positron Emission Tomography) scanner at the MGH Martinos Center, which is capable of simultaneously recording fcMRI BOLD (Blood oxygenation level-dependent) and 18Flurodeoxyglucose (FDG) PET data. This will permit cortico-limbic networks to be characterized dynamically through (1) examination of the differential effects of stimulating two networks in the DLPFC, and (2) by tracking the dynamic interplay between rTMS induced changes in local glucose metabolism at DLPFC and sgACC on the one hand, and changes in distributed connectivity between these regions on the other. In an exploratory aim, MDD patients will return three months later (after they have undergone a non-specific treatment intervention with their psychiatric provider) for the identical rTMS/fcMRI/FDG-PET procedures. This aim will establish, as proof of principle, that treatment of MDD is associated with changes in cortico-limbic functional network architecture, and in cortico-limbic dynamics. Eventually, it is hoped that this work will lead to the emergence of aberrant cortical dynamics as a biomarker for MDD. In addition, this work might pollinate future studies which use aberrant cortical dynamics as a novel therapeutic target upon which neuromodulatory interventions might intervene.

Conditions

Major Depressive Disorder, Recurrent

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

TMS to positively correlated DLPFC

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

Group Type: ACTIVE_COMPARATOR

TMS positively correlated DLPFC

Intervention Type: 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.

TMS to negatively correlated DLPFC

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

Group Type: ACTIVE_COMPARATOR

TMS to negatively correlated DLPFC

Intervention Type: 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.

Interventions

TMS positively correlated DLPFC

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.

Intervention Type: DEVICE

TMS to negatively correlated DLPFC

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.

Intervention Type: PROCEDURE

Other Intervention Names

This study will employ a TMS system that includes a stimulator, TMS coil and neuronavigation system; This study will employ a TMS system that includes a stimulator, TMS coil and neuronavigation system

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mark C. Eldaief, MD

Mark Eldaief, MD, Associate Neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark C Eldaief, M.D.

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Martinos Center for Biomedical Imaging/Massachusetts General Hospital

Charlestown, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012p001784

Identifier Type: -

Identifier Source: org_study_id