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

> **NIH NIH K23** · ADVENTHEALTH ORLANDO · 2024 · $192,534

## Abstract

PROJECT SUMMARY/ABSTRACT
 This K23 Career Development Award is designed to provide the conceptual knowledge and technical
skills necessary for the PI to pursue a career as an independent investigator evaluating brain network targets
to optimize non-pharmacologic interventions for difficult-to-treat mood and cognitive disturbances in aging.
 Apathy is a persistent and disabling disorder of motivation that afflicts 30-50% of patients with late-life
depression (LLD). Apathy worsens clinical outcomes in LLD, as apathetic depressed patients have poor
response to existing treatments and higher rates of hospitalization, functional decline, and increased caregiver
burden. Functional network abnormalities in a core set of brain circuits that interact to support motivated
behavior (salience, executive control, and reward networks) may underlie apathy of LLD. Options for the
efficacious treatment of apathy of LLD are limited, and novel interventions are urgently needed.
 This proposal is based on the premise that customizing interventions based on theorized brain
mechanisms of apathy may increase the potency and scalability of promising therapies. This K23 proposes to
conduct a randomized controlled trial evaluating the potential of a customized digital cognitive training (DCT)
intervention to target brain network abnormalities in apathy of LLD and reduce symptoms of apathy and related
cognitive and behavioral deficits. Eighty-four older adults with major depressive disorder and clinically
significant apathy will be randomized to four weeks of a home-based DCT intervention or an active
expectancy-matched control. The DCT will involve a suite of exercises designed to engage brain networks
disrupted in apathy by targeting cognitive processes (i.e., salience processing, sustained attention, cognitive
control) supported by these networks. Aligned with NIMH’s experimental therapeutics approach, we will
examine the extent to which a targeted DCT program modulates functional network disturbances in apathy of
LLD and improves apathy and associated cognitive deficits. The proposed study will generate preliminary data
regarding network targets of a customized digital therapeutic that may translate to mood and cognitive benefits,
and may guide future personalization of treatments for motivational disturbances in older adulthood.
 The training provided through this K23 will advance my knowledge and skillsets in: 1) the design and
delivery of a neuroscience-informed, virtually-delivered intervention targeting a distinct subtype of depressed
older adults; 2) use of functional MRI to probe mechanisms of action of the proposed DCT; 3) advanced
longitudinal modeling of clinical trial data to assess trajectories of change and identify predictors of response
and; 4) generating an R-series experimental therapeutics target engagement application. This training will
prepare me for an independent research career developing and refining neuroscience-based interventions
targeting t...

## Key facts

- **NIH application ID:** 11022758
- **Project number:** 7K23MH129882-02
- **Recipient organization:** ADVENTHEALTH ORLANDO
- **Principal Investigator:** Lauren Elizabeth Oberlin
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,534
- **Award type:** 7
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11022758

## Citation

> US National Institutes of Health, RePORTER application 11022758, Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics (7K23MH129882-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11022758. Licensed CC0.

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