Vagus Nerve Stimulation: Integration of Behavior and Cardiac Modulation
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      This study characterized the impact of respiratory-gated transcutaneous vagus nerve
      stimulation (tVNS) on the modulation of the stress response circuitry, vagal tone and
      depressed mood in patients with major depressive disorder (MDD). Twenty premenopausal women
      with recurrent MDD in an active episode were recruited into a single-blind cross-over study
      that included two functional MRI visits within a one week period with simultaneous mood and
      physiological assessments. Randomization to exhalatory- or inhalatory-gated tVNS was
      performed to control for order effects. The study hypothesis was that exhalatory-gated tVNS
      would have a significantly greater impact on the regulation of brain activity in stress
      response circuitry, vagal tone and depressed mood in MDD patients compared to
      inhalation-gated tVNS.
    

Detailed description: 
      Major depressive disorder (MDD) has been associated with alterations of the stress response
      circuitry, including the hypothalamus, amygdala, hippocampus, anterior cingulate cortex,
      ventromedial, dorsolateral and orbital prefrontal cortices. Many of these regions are
      morphologically and functionally sexually dimorphic and associated with vulnerability for sex
      differences in MDD. A major role for the stress response circuitry is to assess potentially
      stressful stimuli and respond with a neuroendocrine signal that coordinates homeostatic
      responses throughout the body. Neuroimaging studies have suggested that alterations in this
      circuitry are implicated in mood dysregulation, increased activation of the
      hypothalamic-pituitary-adrenal (HPA) axis, and imbalance between the sympathetic and
      parasympathetic nervous system in depressed persons. Thus, the development of novel
      interventions that regulate this system may have a significant impact on the improvement of
      clinical and physiological alterations of MDD.

      Vagal nerve stimulation (VNS) is an FDA approved treatment for MDD that modulates circuitry
      implicated in mood regulation. Recently, a non-invasive variant of VNS, transcutaneous
      auricular vagus nerve stimulation (tVNS), which targets the auricular branch of the vagus
      nerve (ABVN) has been proposed. Moreover, previous studies have suggested that the dorsal
      medullary system receiving vagal afference inputs operates in tune with respiration and that
      tVNS may be optimized by gating ABVN stimulation to the exhalatory phase of the respiratory
      cycle. Thus, this study proposed to characterize the impact of respiratory-gated tVNS on the
      modulation of the stress response circuitry, vagal tone and depressed mood in patients with
      recurrent major depression (MDD).

      Twenty premenopausal women with recurrent MDD in an active episode were recruited into a
      single-blind cross-over study that included two functional MRI visits, within a one week
      period, with simultaneous mood and physiological assessments. Randomization to exhalatory- or
      inhalatory-gated tVNS was performed to control for order effects. Subjects were exposed to a
      mild visual stress challenge that preceded and followed 30 minutes of exhalatory- or
      inhalatory-gated tVNS. The study hypothesis was that exhalatory-gated tVNS would have a
      significantly greater impact on the regulation of brain activity in stress response
      circuitry, vagal tone and depressed mood in MDD patients compared to inhalation-gated tVNS
    

Intervention name(s): exhalatory-gated transcutaneous vagus nerve stimulation (e-RAVANS); Inhalatory-gated transcutaneous vagus nerve stimulation (i-RAVANS)
Intervention type(s): Device; Device
Intervention description(s): Non-painful exhalatory-gated electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session.; Non-painful inhalatory-gated electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session.
Other intervention name(s): e-RAVANS; i-RAVANS
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Transcutaneous vagus nerve stimulation; Stress response circuitry; functional magnetic resonance imaging; respiration; depression