This study tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with MDD (60 in R61 phase and 80 in R33 Phase). This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task stimuli (in a closed loop) based on this state.

In both the R61and R33 phases we will compare cloud based real time fMRI feedback with placebo (sham feedback) in reducing negative attention bias and depressive symptoms. This study will be the first dose-finding test of real-time fMRI effect on negative attention bias. Measures include: Structured Clinical Interview for DSM-5 (SCID), Clinician-administered diagnostic exam, Montgomery Asberg Depression Rating Scale (MADRS), Clinician-administered scale used to assess the severity of depression, State-Trait Anxiety Inventory (STAI), Self-report questionnaire used to measure types of anxiety and mood symptoms, Mood and Anxiety Symptom Questionnaire (MASQ), Negative perseveration during a go/no-go task, Go/no-go task with overlaid face/scene stimuli; brain response triggers next stimulus, Negative gaze, Negative gaze collected in gaze data following each real time fMRI feedback session

Inclusion Criteria:

• gender, inclusive

  • adult aged 18 - 65 meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD according to the Clinician-Administered MDD Scale for DSM-5 (unipolar depression or bipolar II depressed)
  • scores at least a minimum score of 16 on Montgomery Asberg Depression Rating Scale (MADRS)
  • normal cognition
  • participants must be able to read and understand English
  • participants must be able to provide consent

Exclusion Criteria:

• pregnancy (female participants)

  • outside age range
  • MRI contraindications (medical implant, claustrophobia, etc.)
  • use of psychoactive medication (including antidepressants) or currently in therapy
  • neurological disorder or any condition that in the view of the PI could impact brain data, cause depression, require medication that could cause depressive symptoms, or otherwise result in participant being unfit for study (for example, co-morbid psychotic, neurological disorders, developmentally or cognitively disabled/impaired, active alcohol or drug abuse/dependence within the past 6 months).
  • non-English speaking
  • non-correctable vision loss
  • refusal to provide informed consent
  • representing an active suicide risk

Data will only be shared amongst the study sites.