# Positive valence systems engagement during social reward exposure psychotherapy for mid- and late-life depression

> **NIH NIH K23** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $191,063

## Abstract

PROJECT SUMMARY/ ABSTRACT
 The proposed K23 Patient-Oriented Research Career Development Award is designed to provide the
candidate with the conceptual knowledge and technical skills needed for a career of an independent
investigator focused on the engagement of behavioral and neural network targets during personalized
psychotherapies for mid- and late depression. The candidate will conduct her training and research activities at
the ALACRITY Center of the Weill Cornell Institute of Geriatric Psychiatry.
 The proposal is based on the premise that identifying specific behavioral and neural network targets
can guide development of streamlined interventions with potential for broad scalability and reach. “Engage”, a
streamlined therapy for late-life depression, whose principal intervention is “reward exposure”, may change
Positive Valence Systems (PVS) functions. Preliminary studies by the candidate show that early increase in
resting state functional connectivity (rsFC) of PVS structures during “Engage” predicts increased behavioral
activation. Additionally, compared to solitary pleasant activities, exposure to rewarding social interactions
during “Engage” leads to greater increase in behavioral activation and reduction of depression severity. Finally,
a machine learning analysis conducted by the candidate showed that low perceived social support is the
strongest predictor of poor response early in psychotherapy. These findings are in line with animal and human
studies demonstrating the protective role of social rewards. Based on these observations, the candidate
developed “Engage-S”, a social-reward based version of “Engage”, aimed to increase exposure to meaningful
social interactions with others.
 The training study proposes to examine whether social reward exposure in “Engage-S” enhances PVS
abnormalities and improves mid- and late-life depression. The participants will be 60 middle-aged and older
adults (age ≥ 50) with major depression who will be randomized to 9-weeks of “Engage-S” or to a Symptom
Review and Psychoeducation (SRP) comparison condition. During treatment, we will examine target
engagement of the PVS with rsFC, a behavioral activation scale (BADS), and performance on a novel social
reward paradigm at baseline, 5 weeks, and 9 weeks. We will use computational methods to identify
neuroimaging and behavioral profiles associated with treatment response.
 The training plan consists of formal courses, structured tutorials, and hands-on methodological training
that will offer the candidate knowledge and skills in: 1) Functional neuroanatomy of depression and aging; 2)
Use of fMRI to assess target engagement during psychotherapies for mid- and late-life depression; 3)
Computational modeling for the identification of clinical and neuroimaging predictors of treatment response that
can be used to personalize psychotherapy; and 4) Generate preliminary data for an R-series experimental
therapeutics target engagement application.

## Key facts

- **NIH application ID:** 10417136
- **Project number:** 5K23MH123864-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Nili Solomonov
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $191,063
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417136

## Citation

> US National Institutes of Health, RePORTER application 10417136, Positive valence systems engagement during social reward exposure psychotherapy for mid- and late-life depression (5K23MH123864-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10417136. Licensed CC0.

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