# Validate a Shared Neural Circuit Underlying Multiple Neuropsychiatric Symptoms

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

Abstract Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI),
especially those worsening over time, are associated with more rapid cognitive and functional decline and a
greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS
simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this
proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared
neural circuit we previously discovered and various NPS. We will modify a key region within the NPS-shared
neural circuit [i.e. left precentral gyrus (LPG), critical for regulating visual attention] with anodal transcranial direct
current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-
shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial
design we will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which
is considered the most detrimental type of NPS in MCI. We will assign participants to 4-week active anodal vs.
sham LPG online tDCS group. We will assess resting-state and visual attention task-related functional MRI and
informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two
primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship
between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine
the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared
neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship
between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research
is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS.
Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing
NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.

## Key facts

- **NIH application ID:** 9971583
- **Project number:** 5R21MH120734-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** KATHI L HEFFNER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-07-03 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971583

## Citation

> US National Institutes of Health, RePORTER application 9971583, Validate a Shared Neural Circuit Underlying Multiple Neuropsychiatric Symptoms (5R21MH120734-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971583. Licensed CC0.

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