Investigation of Brain Network Dynamics in Depression
Condition: Major Depressive Disorder, Recurrent
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional

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.
    

Intervention name(s): TMS positively correlated DLPFC; TMS to negatively correlated DLPFC
Intervention type(s): Device; Procedure
Intervention description(s): 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, 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.
Other intervention name(s): 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
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other