The goal of this clinical trial is to determine the acceptability, feasibility, and validity of the bWell Cognitive Care Platform for Depression (bWell-D), a novel Virtual Reality (VR) cognitive assessment and remediation tool, in depressed populations. The main questions are:

• Do patients with Major Depressive Disorder (MDD) find the bWell-D cognitive assessment battery and protocol feasible, tolerable, and acceptable?
• Do patients with Major Depressive Disorder (MDD) find the 8 week bWell-D remediation protocol feasible, tolerable, and acceptable?

Following initial cognitive assessment, researchers will assess feasibility outcomes in the bWell remediation arm to a VR scenes experience arm to learn more about the feasibility of bWell for cognitive assessment and remediation.

Patients will:

• Complete an initial bWell cognitive assessment session
• Randomized to either receive bWell cognitive remediation or a VR scenes experience twice a week for eight weeks
• Complete cognitive/functional/clinical assessments and EEG at baseline, midpoint and endpoint of the remediation protocol, as well as two MRI scans and measures of tolerability, engagement, and enjoyment

Patients with a diagnosis of major depressive disorder, who are currently either euthymic or mildly depressed, will be recruited for this study. 40 participants (ages 19-55) will be recruited from the community from two outpatient sites. 20 patients will be recruited at University of British Columbia (UBC) and 20 patients will be recruited at Simon Fraser University (SFU). Patients will complete an initial virtual assessment to assess eligibility, after which patients will complete the bWell cognitive assessment session. This session will include rating scales for current symptoms of depression/anxiety, subjective cognitive functioning, global/occupational functioning and a validated computerized neuropsychological test battery to assess objective cognitive functioning. Participants will complete a brief VR training session with the VR equipment. Subsequently, the bWell cognitive assessment program will be administered, followed by scales assessing tolerability and enjoyability/engagement.

Patients will then be randomized in a 1:1 ratio to receive bWell cognitive remediation or to a control group in which they passively experience various VR scenes. Randomization will occur separately in inpatient and outpatient groups. Patients are told that either method is hypothesized to have effects on their cognition and are therefore blinded to whether they are in the 'active' treatment group. Assessors for outcomes that are not self-reported or self-administered will also be blinded to group assignment. Participants randomized to the bWell cognitive remediation program will complete 40-minute remediation sessions using bWell twice a week for 8 weeks; the other group will view VR scenes in bWell without any instructed cognitive tasks. EEG recordings will be administered at baseline, at midpoint, and after completing the 8 weeks. At the end of the 8 weeks, measures of subjective cognitive functioning, global/occupational functioning and the computerized objective cognitive testing battery will also be repeated. Patients will also undergo 2 MRI scans including a resting state fMRI and a structural MRI; these sessions will be scheduled once at baseline and once in the two following weeks after the last remediation/VR experience session. Patients will also complete tolerability and enjoyment/engagement scales during the remediation procedure. Patients will be debriefed at the end of their participation about their treatment groups. Patients randomized to bWell remediation group will also have the option of participating in a parallel study with the eBrain Lab at Simon Fraser University assessing neurophysiology of different brain regions using transcranial magnetic stimulation combined with electroencephalography (TMS-EEG).

In addition to MDD participants recruited and randomized, we will be recruiting 70 healthy individuals of the same age range (19-55) to complete the assessment session. Following phone screen, they will come in and complete the SCID, bWell-D assessment, session CNS vital signs, and rating scales for current symptoms of depression/anxiety, subjective cognitive functioning, global/occupational functioning and engagement and tolerability scales. This session will take approximately 3 hours, and participants will receive $60 for their participation.

Inclusion Criteria:

• 19-55 years old
• Meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD as assessed by a standardized psychiatric interview (SCID-5-RV) conducted by a trained clinician.
• Patients will be euthymic or mildly depressed (defined by a Montgomery-Asberg Depression Rating Scale [MADRS] score < 19)
• Patients will report subjective cognitive deficits at baseline, as indicated by a total Perceived Deficits Questionnaire - Depression 20 [PDQ-D-20] score > 20 at study enrollment.
• If using antidepressants, participants will be on stable antidepressant therapy for at least 4 weeks prior to randomization. All concomitant doctor-prescribed medications must be at a stable dose for 4 weeks prior to the randomization visit.
• If undergoing psychotherapy, participants will be on stable adjunct psychotherapy for at least 8 weeks prior to randomization
• If comorbid diagnosis of attention deficit hyperactivity disorder (ADHD), patients must be on stable dose of stimulants for at least 4 weeks prior to randomization.
• Participants will be able to follow written and verbal instructions in English

Exclusion Criteria:

• Moderate - severely depressed patients will be excluded at this point due to acceptability concerns (e.g. potential for cybersickness)
• Presence of significant neurological disorders, head trauma, or other unstable medical conditions. These conditions may adversely impact cognitive functioning and influence study results.
• Presence of other psychiatric disorder (e.g. anxiety, psychotic disorder) that may be considered primary.
• Meeting DSM-5 criteria for alcohol or other substance use disorder within three months prior to the randomization visit.*
• Use of benzodiazepine medications more than three times per week and/or within 24 hours of baseline or close out visit
• Use of cannabis or alcohol within 24 hours, or tobacco within 30 minutes of baseline or close out visit
• Suicidal ideation or self harm
• Completion of previous cognitive remediation

Additionally, patients will be excluded from the study if they meet any of the following criteria due to contraindications with MRI scanning:

• Retained wires from an electronic implant that has been removed (i.e. pacemaker wires not attached to a pacemaker)
• Cardiac pacemaker or defibrillator
• Metal in eye or orbit
• Ferromagnetic aneurysm clip
• Pregnancy
• Makeup tattoos that are not designed to fade over time
• Stainless steel intrauterine device (IUD)

Depending on the individual situation, they MAY NOT be able to participate if they have/had any of the following:

• Artificial Heart Valve
• Ear or eye implant
• Brain aneurysm clip
• Implanted electronic device (i.e. drug infusion pump, electrical stimulator)
• Coil, catheter, or filter in any blood vessel
• Orthopedic hardware (artificial joint, plate, screw, rod)
• Shrapnel, bullets, or other metal fragments
• Surgery, medical procedure or tattoos (including tattooed eyeliner) in the last six weeks
• Other metallic prostheses

If the participant has any of the above, or any safety issues arise during MRI screening process, the individual case will be reviewed by UBC Hospital MR Technologist and/or Radiologist and a case-by-case decision will be made regarding participation.

Additionally, for the healthy participant recruitment, the eligibility criteria is as follows:

Inclusion Criteria for healthy controls:

- 19-55 years old

Exclusion criteria for healthy controls:

• History of any psychiatric disorder, as assessed by a standardized psychiatric diagnostic interview
• Presence of significant neurological disorder, head trauma, or other unstable medical conditions which may adversely impact cognitive functioning
• Presence of any physical mobility issues that limit arm or neck movement

Patients are told that either arm is hypothesized to have effects on their cognition and are therefore blinded to whether they are in the 'active' treatment group.

Assessors for outcomes that are not self-reported or self-administered will also be blinded as to group allocation.