Transcranial Direct Current Stimulation in Major Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation
      technique of minimal risk that has been used as an experimental procedure for reducing
      depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal
      brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD),
      the extent of antidepressant response often differs. Methods that map current flow directly
      in the brain while a person is receiving tDCS and that determine how functional neuroimaging
      signal changes after a series of tDCS sessions may help us understand how tDCS works, how it
      can be optimized, and if it can be used as an effective intervention for reducing depressive
      symptoms. We will investigate these questions in a two-part randomized double blind
      exploratory clinical trial. The first part of the trial will compare how current flow and
      functional imaging signal differs in the brain when using tDCS with more focal stimulation,
      called high definition (HD) tDCS, compared to conventional tDCS (C-tDCS) or sham (non-active)
      tDCS in patients with MDD.

      Sixty people with depression (20 in each group) will be randomized to receive either HD-tDCS,
      C-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on
      consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of
      active or sham tDCS in the MRI scanner, which will allow us to map tDCS currents, and track
      changes in regional cerebral blood flow (rCBF) pre-to- post treatment using completely
      non-invasive methods. At the first and last session and mid-way through the trial,
      participants will also complete a series of clinical ratings and neurocognitive tests
    

Detailed description: 
      Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique,
      applied to the left dorsolateral prefrontal cortex (DLPFC) can reduce depressive symptoms and
      improve cognitive control in major depressive disorder (MDD). Such findings suggest
      modulation of top down prefrontal-limbic circuits, which are functionally distinct from
      ventro-limbic networks and include reciprocally connected DLPFC and dorsomedial anterior
      cingulate cortex (dACC). However, substantial variation in tDCS response is observed in MDD.
      This may be due to imprecise stimulation protocols and suboptimal engagement of the neural
      circuits mediating antidepressant response. Methods that optimize electrode placement and
      account for individual variation in anatomy and that map current flow directly in the brain
      may inform the mechanisms and potential clinical utility of tDCS. A new tDCS technique, high
      definition (HD) tDCS, offers more focal stimulation than conventional tDCS (C-tDCS). The
      degree to which C-tDCS or HD-tDCS engage dorsal prefrontal-limbic neural circuits is unknown,
      yet is vital for understanding, confirming and subsequently improving possible therapeutic
      effects. Innovative MRI techniques that are able to map tDCS currents in vivo and that track
      changes in regional cerebral blood flow occurring with tDCS over time can provide direct
      evidence of neural effects. Based on a) theoretical modeling of tDCS current flow, b) studies
      showing hypo-metabolism, decreased CBF or activity in dorsal prefrontal-limbic networks, c)
      modulation of these regions with treatment, and, c) our prior results showing significant
      relationships in between change in dACC rCBF and clinical response to electroconvulsive
      therapy (ECT), an established brain stimulation treatment, we will test for the tDCS
      engagement and modulation of the DLPFC and dACC using tDCS current mapping performed in vivo
      and perfusion MRI. MRI-guided neuronavigation will be used to optimize and standardize
      electrode placement for DLPFC stimulation.

      In this trial we will test for the target engagement of the DLPFC and dACC by comparing
      C-tDCS, HD-tDCS and sham tDCS applied to the left DLPFC in patients with moderate to severe
      MDD before and after they complete 12 daily 20-minute sessions of C-tDCS, HD-tDCS or Sham
      tDCS (n=20 randomized to each group). In-vivo electric current mapping performed at different
      current intensities (0-2 mA) for 20-30 minutes, and change in regional cerebral blood flow
      (rCBF) measured before and after a 12-day tDCS trial will determine acute and longer-term
      modulation of DLPFC and dACC circuitry for each tDCS modality respectively.
    

Intervention name(s): Active - HD tDCS; Sham - HD tDCS; Active - Conventional tDCS; Sham - Conventional tDCS
Intervention type(s): Device; Device; Device; Device
Intervention description(s): Non-invasive neuromodulation using HD electrodes placed on the scalp to deliver a constant, low current at 2 mA.; Sham neuromodulation using HD electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec.; Non-invasive neuromodulation using standard 7 cm x 5 cm electrodes placed on the scalp to deliver a constant, low current at 2 mA.; Sham neuromodulation using standard 7 cm x 5 cm electrodes electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Active and Sham controlled
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Transcranial direct current stimulation; major depression; MRI