Neuroimaging in Patients Undergoing TMS for Depression
Condition: Treatment Resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      The goal of this project is to guide rTMS using functional magnetic resonance imaging (fMRI)
      in individuals with depression who did not respond to standard TMS treatment to evaluate
      whether targeted TMS using individualized functional MRI scans produce outcome superior to
      that of conventional approaches. The study team also plans to scan patients with Major
      Depression Disorder (MDD) patients prescribed to receive standard TMS for the first time
      before and after which they will have resting-state Functional Magnetic Resonance Imaging
      (rs-FMRI) scan in order to see if we can predict their responsiveness based on the functional
      connectivity maps.
    

Detailed description: 
      Significance: There are few therapeutic options for individuals with treatment resistant
      depression (TRD). One recently developed approach is rTMS over left dorsolateral prefrontal
      cortex. Recent studies have demonstrated overall antidepressant benefit of rTMS in patients
      who fail to respond to a trial of antidepressant medication (1, 2, 3). Nevertheless, for many
      patients the response is incomplete, suggesting the need for further optimization. One
      potential cause of heterogeneous response might relate to individual differences in brain
      anatomy and connectivity patterns. At present, the rTMS stimulation site across subjects is
      based upon fixed location relative to motor cortex. Potentially, however, the approach could
      be optimized by stimulating based upon individual brain functional connectivity pattern. The
      present project will collect pre- and post-treatment brain functional connectivity measures
      in a group of patients who will be receiving independent clinical rTMS for resistant
      depression, a connectivity-based targeting approach will be applied at the single-subject
      level to individualize therapy in those patients who do not respond to standard approaches.

      Patients will be divided in 2 groups. Group 1 (N=30) will be depressed patients undergoing
      standard TMS for the first time. Group 2 (N=30) constitutes those who have previously
      demonstrated that they do not respond to standard TMS. MDD patients prescribed to receive
      standard TMS for the first time (group 1) will have resting-state FMRI in order to see if
      their responsiveness based on the functional connectivity maps can be predicted.
      Non-responders to standard TMS approaches (Group 2) will be randomized (3:2) to either
      receive targeted (N=18) or standard (N=12) repetitive TMS (rTMS) treatments. A
      connectivity-based targeting strategy will be used on patients undergoing targeted rTMS to
      optimize target for focal brain stimulation. Raters and patients in group 2 will be kept
      blinded to the treatment assignment. All patients referred from the ongoing treatment study
      will be assessed by 3 tesla brain MRI, Magnetic Resonance Spectroscopy (MRS) and Cerebral
      Blood Flow/Volume (CBF/CBV) procedures at baseline and immediately following the final
      treatment.
    

Intervention name(s): transcranial magnetic stimulation
Intervention type(s): Device
Intervention description(s): non invasive brain stimulation approach
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment