# Neuroplasticity-Based Computerized Cognitive Remediation (nCCR) for Treatment Resistant Late-Life Depression

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $1,469,147

## Abstract

Abstract
 This proposal is submitted in response to RFA-MH-18-707 and NOT-MH-20-027, and aims to conduct a
randomized, double-blind, controlled confirmatory efficacy trial of a novel, neuroplasticity-based computerized
cognitive remediation (nCCR) intervention for treatment resistant late-life major depressive disorder (LLD). We
developed nCCR to target cognitive control deficits (CCD), a behavioral expression of altered function of the
Research Domain Criteria (RDoC)-defined, cognitive control network (CCN). This novel intervention is
consistent with NIMH priorities to advance interventions informed by cognitive and affective neuroscience
(strategy 3.1) that can be disseminated to the community (strategy 3.3). In LLD, deficits in cognitive control
functions (CCD) are common, and disabling. We and others have documented that specific CCD, and their
underlying brain network abnormalities, are associated with poor response to antidepressants, relapse, and
increased risk for suicide. These deficits are mediated by the CCN, a frontoparietal circuit that comprises the
dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and posterior parietal cortex, as well as
projections to the ventromedial prefrontal cortex and subcortical structures, including the striatum.
 The theory guiding neuroplasticity-based cognitive interventions is that network abnormalities associated
with negative disease-specific clinical outcomes can be altered through the induction of neuroplasticity (even in
the aging brain), resulting in enhanced functioning of the target network, and symptomatic improvements. The
methodology we employed is founded in basic animal science of induction of plasticity in the aging brain, and
it is translated into computer algorithms that deliver (1) increasingly challenging; (2) dynamic difficulty adjusted;
(3) attention demanding; and (4) immediately rewarding cognitive training designed to activate CCD associated
with poor clinical outcomes. We recently tested nCCR in three preliminary clinical trials.
 Our preliminary data indicate that nCCR will likely engage our proposed target, CCD. Further, nCCR
appears to have more robust mood effects in participants who have pronounced CCD, while SSRI/SNRI-
treated patients are two times less likely to benefit. We designed nCCR to be: short (4-week dose), efficacious,
mobile (available via web), cost-effective (does not require an MD/PhD), with the potential for wide distribution,
easy adoptability, and extensibility to address this urgent, unmet therapeutic need in LLD. For these patients
there is currently no treatment that adequately addresses both mood and cognitive impairment. The data
produced by this proposal will allow us to study the relationship between CCD and changes in mood, and
compare these effects to a control condition in LLD participants who have failed first-line treatments. Further,
we propose a two-site, sufficiently powered trial to study our technology-facilitated paramete...

## Key facts

- **NIH application ID:** 10795921
- **Project number:** 5R01MH126051-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Sarah Shizuko Morimoto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,469,147
- **Award type:** 5
- **Project period:** 2021-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795921

## Citation

> US National Institutes of Health, RePORTER application 10795921, Neuroplasticity-Based Computerized Cognitive Remediation (nCCR) for Treatment Resistant Late-Life Depression (5R01MH126051-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10795921. Licensed CC0.

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