Targeting Large-scale Networks in Depression With Real-time Functional Magnetic Resonance Imaging (fMRI) Neurofeedback

Part 3/Phase 3 study hypothesis are:

• Rest Focus Task (RFT) will activate brain networks at the individual subject level to provide a viable signal for Neurofeedback (NF)
• At the group level, RFT in the Active>Passive contrast will activate canonically defined salience network
• Neurofeedback-reinforced practice over the session will increase RFT activation over the course of the training session, comparing RFT activation, without NF, before and after NF runs.
• Valid Neurofeedback will increase RFT activation more compared to sham NF (assessed during the no-NF session).

Inclusion criteria

• Meets The Diagnostic and Statistical Manual of Mental Disorders five (DSM5) criteria for Major Depressive Disorder, single or recurrent, active or in partial remission
• Patient Health Questionnaire (PHQ9) greater or equal (≥)6, and approximately (~) 50% with PHQ9≥10
• If participants are taking antidepressant medications, on stable dosage for 4 weeks
• No history of active substance use disorder in the past 6 months
• Absence of suicidal thoughts with plans or intentions, as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
• If a woman of child-bearing age, not pregnant or trying to become pregnant
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (for example metal workers with exposures, protocol has more details), etc.
• Size compatible with scanner gantry (per protocol)
• Ability and willingness to give informed consent to participate.

Exclusion criteria

• Size not compatible with scanner
• Not meeting diagnostic criteria for bipolar disorder, schizophrenia, other psychosis, obsessive-compulsive disorder, active eating disorder or Post-traumatic stress disorder (PTSD)
• No history of serious neurological illness (including, but not limited to, seizures/epilepsy) or current medical condition that could compromise brain function, such as liver failure
• No history of closed head injury, e. g. loss of consciousness > ~5 min, hospitalization, neurological sequela