# Efficacy and target engagement of a digital intervention to improve the depression-executive dysfunction syndrome after stroke

> **NIH NIH K23** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $195,480

## Abstract

Project Summary/Abstract
The goal of the proposed K23 Career Development Award is to provide the PI with the mentorship, knowledge,
and skillset to develop into an independent investigator studying neuroscience-inspired, targeted therapeutics
for comorbid mood and cognitive dysfunction after stroke. The PI's mentoring team will provide him with
training in the brain-based mechanisms of mood disorders, use of functional MRI to examine target
engagement, and clinical trial design and data analytic approaches. The training will incorporate individualized
tutorials, formal coursework, national and international workshops and conferences, research collaboration,
manuscript preparation, and grant writing. The training is integrated in a research proposal that evaluates the
efficacy and target engagement of a digital intervention for the depression-executive dysfunction syndrome
(DED) after stroke. Stroke is a leading cause of disability worldwide. Post-stroke DED is associated with more
persistent depressive symptoms and executive dysfunction, worse social functioning, and greater loss of
independence than post-stroke depression or executive dysfunction alone. Existing interventions have limited
evidence of efficacy, side effects, and can be difficult for stroke patients to access. Novel and scalable
approaches that target the mechanisms underlying post-stroke DED may yield more efficacious treatment. To
address these barriers, the PI proposes to study a remote intervention for post-stroke DED that combines an
iPad-based digital therapy called AKL-T01 that intensively trains rapid multitasking skills, together with virtual
metacognitive coaching. AKL-T01 is designed to target a common mechanism underlying post-stroke
depressive symptoms and executive dysfunction, which is reduced intrinsic functional connectivity in the
executive control network (ECN). Virtual metacognitive coaching is included to address patient unawareness of
deficits to enhance transfer of training gains to daily functioning. In this pilot clinical trial, N=70 patients with a
first-time stroke and DED will be randomized to receive the intervention, or to a control condition with general
and non-targeted cognitive stimulation together with metacognitive coaching. Participants will complete
measures of executive dysfunction, depressive symptoms, and disability at baseline, week 3 (mid treatment),
and week 6 (end treatment). Participants will complete resting state fMRI scans at baseline and week 6. Linear
mixed-effects models will test the hypotheses that the intervention will be associated with greater
improvements in executive function, depressive symptoms, and disability relative to the control group. Also
tested is the hypothesis that the intervention group will have greater change in intrinsic functional connectivity
in the ECN from baseline to week 6, relative to the control group. This project has the potential to address, in a
scalable manner, a highly debilitating consequence...

## Key facts

- **NIH application ID:** 10873174
- **Project number:** 5K23MH129849-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Abhishek Jaywant
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,480
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873174

## Citation

> US National Institutes of Health, RePORTER application 10873174, Efficacy and target engagement of a digital intervention to improve the depression-executive dysfunction syndrome after stroke (5K23MH129849-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873174. Licensed CC0.

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