# Using RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related Dementias

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $405,000

## Abstract

The goal of this study is to determine the effects of degeneration of RDoC Negative and Positive Valence
Circuit Elements, and how these effects are associated with specific Neuropsychiatric Symptoms (NPS), in
persons with Alzheimer’s disease and related dementias (ADRD). Current pharmacological treatments for
NPS in ADRD were developed 50 years ago, are often inefficacious, and can have serious adverse effects
including increased mortality. Neuroanatomically-based treatments such as TMS, DBS, and tDCS for NPS are
promising, but their development has been hampered by our lack of knowledge about the mechanistic and
neuroanatomical bases of NPS in ADRD. The proposed project will leverage NIH-supported resources,
including the RDoC Project and a project in our laboratory (R01AG062268) to determine the factor structure of
NPS in ADRD, to better understand the connections between changes in the Negative (for example fear, pain,
and anxiety) and Positive (for example rewarding behaviors) Valence Systems and specific NPS across
different neurodegenerative disorders. The same NPS (e.g., apathy) occur across many ADRD diagnoses,
necessitating a trans-diagnostic approach to identify common neurobiologically-informed mechanisms of NPS
across diagnoses. We will study 40 participants with Alzheimer’s disease (AD), 20 with behavioral-variant
Frontotemporal dementia (bvFTD), 20 with Huntington’s disease (HD), and 20 with semantic-variant Primary
Progressive Aphasia (svPPA). We have chosen these disorders as they target specific RDoC Negative and
Positive Valence Circuit Elements including the prefrontal cortex (PFC), dorsal striatum, and anterior temporal
lobes. The first hypothesis is that the ventromedial (vm)PFC plays a central role in Negative Valence and
degeneration of the vmPFC will be associated with low Negative Valence on RDoC Paradigms, low
Internalizing psychiatric symptoms (including anxiety and depression), and the NPS of apathy. We also
hypothesize that degeneration of Negative Valence Circuit Elements that modulate the vmPFC, including the
dorsal PFC, dorsal striatum, and anterior temporal lobes, will be associated with high Negative Valence and
Internalizing psychiatric NPS. The ventral PFC and dorsal striatum are involved in goal-directed learning and
transferring learning from goal-directed to habit systems. We hypothesize that degeneration of the ventral PFC
will be associated with deficits in learning from feedback on RDoC Positive Valence Paradigms and with the
NPS of repetitive behaviors, and degeneration of the dorsal striatum with deficits in learning from punishment
vs. reward and habit learning and the NPS of repetitive thoughts. These investigations could, for the first time,
utilize RDoC Paradigms to better understand the development of NPS in humans from neurodegenerative
processes, to specific deficits in RDoC Valence Paradigms, to neuroanatomical findings, to NPS. These
investigations are clinically relevant as they will improve ...

## Key facts

- **NIH application ID:** 10166948
- **Project number:** 5R01MH120794-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Edward D Huey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166948

## Citation

> US National Institutes of Health, RePORTER application 10166948, Using RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related Dementias (5R01MH120794-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166948. Licensed CC0.

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