ESTIA: Computerized Intervention Targeting Cognitive Control Deficits in Depressed Adults

Project: EVO (or "EVO") is a mobile 3D video game that has been shown to reduce older adults'
susceptibility to interference by augmenting sustained attention and working memory abilities
(e.g. cognitive control) through targeted adaptive algorithms. The combination of
peer-reviewed validity, adaptivity, and fun video game mechanics elevates the EVO platform
beyond other at-home training tools while reducing burden associated with tedious task
replication. We propose to study EVO as a potential intervention for the treatment of
depression, a disorder that worsens medical outcomes, promotes disability, increases expense,
and complicates medical care by clouding the clinical picture and undermining treatment
adherence.

R61 Phase (COMPLETE):

In this first phase, we conducted a 2-year proof of concept study to determine if EVO could
engage the cognitive control network (CCN) in 30 middle-aged and older adults with major
depression. Primary aims for this phase of the proposed project were to determine if EVO will
result in greater CCN engagement using three levels of analysis (circuitry, performance,
self-report). At the circuitry level, we measured CCN engagement by probing the system using
task-based fMRI. We hypothesized that activation and functional connectivity (FC) of anterior
aspects of the CCN will increase from baseline to 4-weeks after treatment initiation. Our
decision to move to the next phase of the planned study was that 66% of our sample showed
significant increases in CCN functions at the circuitry level of analysis (CCN activation and
FC) and at either the performance level or self-report level of analysis.

R33 Phase (CURRENT):

Successful proof of concept has initiated the second phase of the ESTIA study. In this phase,
we plan to conduct a 3-year pilot study to compare "Band Together" (an EVO analog) to an
expectancy-matched control game in terms of CCN target engagement at the circuitry
(task-based fMRI) and behavioral levels (task performance, self-report) in 60 middle-aged and
older adults with major depression. In addition, we well determine if changes in target
engagement are associated with changes in mood and mood-induced disability. The decision to
move onto development of a proposal to study the clinical efficacy of Band Together in a
larger randomized clinical trial will be based on whether we find (1) that Band Together
out-performs our control condition in terms of the engagement of CCN at the circuitry and
behavioral levels (2) significant associations between changes in engagement of the CCN and
changes in mood and (3) that the study methods are feasible to complete (sampling rate,
retention, intervention adherence, intervention acceptability and expectancy-match for our
control condition).

Inclusion Criteria:

- (1) Age 45 to 75; (2) unipolar, nonpsychotic major depression (by SCID, DSM-V), (3)
Hamilton Depression Rating Scale > 20; (4) off antidepressants or have been on a
stable dose for 12 weeks and do not intend to change dose in the next 5 weeks, (5)
capacity to consent; (6) ability to participate in MRI.

Exclusion Criteria:

- 1) Intent or plan to attempt suicide in the near future; 2) history or presence of
psychiatric diagnoses other than unipolar, non-psychotic major depression or
generalized anxiety disorder; 3) use of psychotropic drugs or cholinesterase
inhibitors other than mild doses of benzodiazepines 4) dementia or MCI (please see
Human Subjects). Participants with an MMSE score falling 1 SD below the mean score for
their age and education will be excluded as well.