Accelerated TMS to a Novel Brain Target in MDD and PTSD
Condition: Post Traumatic Stress Disorder; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      This is a Clinical Trial designed to evaluate novel transcranial magnetic stimulation (TMS)
      methods for treating depression/PTSD. TMS is an FDA-approved procedure for
      treatment-resistant depression. The use of the stimulation in this current study is
      considered experimental. The purpose of this research study is to compare the effects of TMS
      at two different brain regions. This information will help the investigators to determine
      which treatment strategies provide the greatest clinical benefit to patients. Results of the
      study will provide brain and behavior measures for future work, which may be critical to
      developing effective disease markers and novel treatments for psychiatric conditions.
    

Detailed description: 
      Non-invasive transcranial magnetic stimulation (TMS) is now FDA-approved for the treatment of
      major depressive disorder (MDD). However, there is growing evidence that the targeting
      strategy for delivering TMS treatment would yield superior clinical outcomes if it were more
      tailored to individual neuroanatomy. The current study take this idea one step further and
      suggest that functional MRI guided TMS might yield an even greater leap forward in promoting
      optimal clinical outcomes.

      The sgACC has been well established as a brain area sensitive to negative mood inductions and
      implicated in neural abnormalities associated with affective and stress disorders. It is
      therefore one of the primary targets for deep brain stimulation (DBS) treatment of MDD using
      surgically implanted DBS devices. Recent posthoc imaging studies of patients who have
      undergone TMS treatment for depression suggest that treatment outcomes tended to be better
      when patients were by chance stimulated in an area of lateral prefrontal cortex that had high
      levels of functional connectivity with sgACC. Based on this finding and on interleaved
      TMS/fMRI probe data, the investigators contend that targeting delivery of TMS to the brain
      surface non-invasively as indicated by sgACC resting functional connectivity may be
      especially effective in downregulating sgACC and thereby producing superior clinical
      outcomes.

      Researchers have used TMS/fMRI to better understand causal communication among circuits
      typically examined with resting fMRI alone. Recent work suggests that there are specific
      sites that, when stimulated, influence subcortical brain areas implicated in affective
      disorders such as the sgACC. Previously, TMS targets were based on brain atlases mapped onto
      individual brain surfaces. This proposal will utilize more individualized targeting from
      participants' own resting connectivity data to guide stimulation that we show is especially
      effective in influencing downstream brain areas of interest. The investigators will focus on
      a target region of the lateral prefrontal cortex (LPFC) that data suggest is particularly
      effective at influencing the sgACC. As an alternative brain target, we will also test the
      efficacy of the dorsolateral prefrontal cortex as a target given its precedence in the
      literature as an effective stimulation site for remediating depressive symptoms. The target
      will be chosen based on an atlas and will adjust the target coordinates based on the inverse
      of a nonlinear normalization of each participant's brain to standard brain space. Thus,
      individual anatomical differences will be taken account with this target though without
      guidance from individual functional imaging data.

      To increase generalizability to other disorders and to patients with comorbid anxiety and
      depression (the typical clinical profile), the investigators will recruit patients who are
      diagnosed PTSD and have symptoms of depression or those who experience trauma-induced MDD.
      Participants will be scanned in an MRI to get anatomical and resting fMRI data to guide TMS,
      then participants will be invited to participate in two rounds of two week TMS treatment to
      each site (order counterbalanced) with one month between treatments. Participants will be
      monitored to assess PTSD symptoms, depressive symptoms,and quality of life before, acutely
      after, and one month following TMS treatments to evaluate the effectiveness of each site in
      mitigating symptoms or improving functioning.
    

Intervention name(s): Transcranial Magnetic Stimulation (TMS); Task; fMRI-guided TMS target
Intervention type(s): Device; Behavioral; Procedure
Intervention description(s): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. In this study, we used administered theta burst TMS stimulation.; Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.; Administration of TMS to individualized targeting from the participant's fMRI scans. Our preliminary data suggest this target region is particularly effective at influencing the sgACC.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a randomized study. All subjects will receive active TMS, so there is no placebo or sham condition. However, the patients will be blinded as to whether or not their site of stimulation is based on the standard targeting method or our novel fMRI-guided targeting method. TMS is administered over to one of these two sites over a two week period, and then TMS will be administered to the other site over a subsequent two-week period. All subjects will receive TMS to both sites as a part of the study, but the order is randomized and counterbalanced.
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: post-traumatic stress; depression; ptsd; tms