Effect of Amygdala Neurofeedback on Depressive Symptoms and Processing Biases
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether upregulating the left amygdala during
      positive autobiographical memory recall via real time functional magnetic resonance imaging
      neurofeedback will lead to an improvement in clinician administered ratings of depressive
      symptoms. The investigators predict that patients with major depressive disorder receiving
      left amygdala neurofeedback will increase their amygdala response during positive
      autobiographical memory recall compared to those receiving control feedback from a region not
      involved in emotional processing and that this ability will be associated with clinically
      significant improvement.
    

Detailed description: 
      Major depressive disorder (MDD) is the leading cause of years lived with disability
      worldwide. Traditional pharmacological and/or psychological interventions are ineffective in
      up to one-half of patients, and treatments (such as electroconvulsive therapy, vagus nerve
      stimulation, and deep brain stimulation) available for severely ill patients who do not
      respond to standard interventions are invasive, and associated with potentially significant
      side effects. Therefore, there is a need to explore and develop novel non-invasive
      treatments.

      One such non-invasive method is real-time functional magnetic resonance imaging neurofeedback
      (rtfMRI-nf), which allows a person to see and regulate the fMRI signal from his or her own
      brain. Emerging evidence suggests rtfMRI-nf has clinical utility in reducing symptoms of
      chronic pain, tinnitus, and Parkinson's disease. The goal of the current study is to leverage
      recent advances in rtfMRI-nf to determine whether this procedure can be adapted as treatment
      for MDD. While amygdala activity is exaggerated in response to negative stimuli in MDD,
      evidence further suggests that the amygdala response to positive stimuli is attenuated in MDD
      and normalizes with remission. Therefore, the target for our rtfMRI-nf procedure is the left
      amygdala. Participants will be randomly assigned to receive rtfMRI-nf from either the left
      amygdala or the left horizontal segment of the intraparietal sulcus (HIPS; a region not
      involved in emotional processing) and to increase the activity within that region to a target
      level by thinking of positive autobiographical memories. This neurofeedback condition will
      alternate with periods of rest and counting backwards in order to allow participants to
      disengage from memory contemplation. A final run without neurofeedback information will be
      included to determine whether participants can maintain the learned amygdala elevation during
      positive memory recall in the absence of neurofeedback. Participants will complete two
      sessions within a one-week period. Clinical ratings will be taken at the time of each scan to
      determine whether the amygdala rtfMRI-nf procedure results in improvement of depression
      symptoms, and changes within the emotional regulation network that occur with successful
      amygdala regulation will be examined. Furthermore, the investigators aim to determine whether
      the rtfMRI-nf procedure will alter assessments of emotional processing conducted within three
      days prior to, and following completion of, the rtfMRI-nf procedure.

      Specific Aim 1: In individuals with MDD, determine the degree to which rtfMRI-nf enhances
      voluntary control over neural activity in the amygdala, co-modulates other brain regions
      within the emotion regulation circuitry, and alters depressive symptom severity ratings.

        -  Hypothesis 1.1: MDD participants receiving rtfMRI-nf regarding blood oxygen-level
           dependent (BOLD) activity within their amygdala can learn to voluntarily regulate this
           activity in response to positive stimuli. MDD participants receiving rtfMRI-nf regarding
           left amygdala activity will demonstrate greater activity in this region while
           contemplating positive autobiographical memories (AMs) than MDD participants receiving
           rtfMRI-nf regarding BOLD activity in the left HIPS, a region not involved in emotion.

        -  Hypothesis 1.2: The investigators hypothesize enhancing control over the amygdala via
           rtfMRI-nf will increase connectivity strengths between the amygdala and prefrontal
           regions involved in modulating emotional behavior including the pregenual anterior
           cingulate cortex and ventromedial prefrontal cortex.

        -  Hypothesis 1.3: The investigators hypothesize participants showing the greatest
           enhancement of amygdala activity in response to rtfMRI-nf also will show the greatest
           improvement in depressive symptom severity ratings at the end of the study.

      Specific Aim 2: In MDD patients, determine the degree to which rtfMRI-nf from the amygdala
      restores a normative mood-congruent processing bias during the processing of emotionally
      valenced stimuli.

        -  Hypothesis 2.1: During the performance of a backward masking task in which emotional
           faces are presented below conscious awareness, the investigators hypothesize MDD
           participants will initially show a processing bias toward negative stimuli in the
           amygdala that will reverse to a processing bias toward positive stimuli in participants
           receiving active vs HIPS rtfMRI-nf

        -  Hypothesis 2.2: The investigators hypothesize that MDD patients will initially show a
           mood-congruent processing bias toward negative stimuli on the P1Vital Emotional Test
           Battery that will reverse to a bias toward positive stimuli following amygdala (vs HIPS)
           rtfMRI-nf.

      Results from this project will lead to new insights into the plastic neurobiological
      mechanisms that govern recovery from MDD and promote novel, non-invasive approaches to MDD
      treatment.
    

Intervention name(s): real-time fMRI neurofeedback: Amygdala; real-time fMRI neurofeedback: HIPS
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories.; Participants are shown activity from their left horizontal segment of the intraparietal sulcus in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Depression; Neurofeedback; Amygdala