Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics

Inclusion criteria

• Age 60+ years
• Diagnosis of unipolar major depressive disorder without psychotic features, as assessed by the Mini International Neuropsychiatric Interview
• Montgomery-Åsberg Depression Rating Scale (MADRS) score > or = 16.
• Clinically significant apathy, determined by the Clinician-rated Apathy Evaluation Scale (C-AES > or = to 37)
• Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 5 weeks.
• On a stable dose of other psychotropic medications, deemed by the investigator to be associated with brain networks of interest, for at least 8 weeks.
• Capacity to provide written consent for research assessment and treatment
• Ability to follow written and verbal instructions (English) as assessed by the PI and/or study staff.
• Total score of > 29 on the Telephone Interview for Cognitive Status (TICS)
• Eligible to undergo MRI
• Access to a computer or tablet with Wifi capabilities
• Able to comply with all testing and study requirements and willingness to participate in the full study duration.

Exclusion criteria

• History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, persistent depressive disorder, generalized anxiety disorder, social anxiety disorder, or specific phobia
• Use of cholinesterase inhibitors or psychoactive drugs other than antidepressants or benzodiazepines, including antipsychotics, that in the opinion of the Investigator may confound study data/assessments.
• Presence or history of significant neurologic or neurodegenerative disorder (e.g., Alzheimer's disease and other dementias, amnestic Mild Cognitive Impairment, history of stroke, Multiple Sclerosis, Parkinson's disease, epilepsy).
• Any other acute medical condition (e.g., cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses) that may influence brain systems of interest or interfere with participation or interpretation of the study results.
• Participant is currently considered at risk for attempting suicide by the Investigator, has made a suicide attempt within the past year, or is currently demonstrating active suicidal ideation or self-injurious behavior.
• Electroconvulsive therapy within the past 12 months
• Recent history (within 6 months prior to screening/baseline) of Substance Use Disorder.
• Participant is currently enrolled in ongoing concurrent cognitive rehabilitation (note that if a subject is enrolled in psychotherapy, this will not be grounds for exclusion)
• Claustrophobia
• Color Blindness
• Sensory or physical impairment that would preclude cognitive testing or participation in the intervention (e.g., upper limb paralysis) as reported by the participant or observed by the Investigator.
• Travelling consecutively for 2+ weeks during the study period to a location that will preclude timely collection of post-treatment MRI data.
• Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, cochlear implant, any other metallic biomedical implant contraindicating to MRI.