# Investigating neuroanatomical underpinnings of apathy in ADRD through neuroimaging and electrical manipulation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $620,678

## Abstract

With limited treatment options, apathetic symptoms often experienced by patients with Alzheimer's disease (AD),
related dementias (ADRD) and Parkinson's Disease (PD), significantly impact the quality of life of patients and
caregivers. Despite a well-grounded understanding of the essential roles played by frontal cortical and
subcortical structures on the apathy syndrome and on goal-directed behavior (GDB), lingering gaps remain on
the causal links from neurodegeneration to the development of apathy. Thus, the fragmented understanding of
the cognitive and neuroanatomical basis of apathy, stands on the way of developing neuro-biologically targeted
treatments for this debilitating neuropsychiatric issue across dementias. While our long-term goal is to develop
an effective treatment for apathy in ADRD and PD, the overall objectives of this application are to (i) test whether
the effects of focal neurodegeneration leading to apathy in ADRD and PD can be explained by differences in
reward and effort sensitivity - cognitive processes integral to GDB, and (ii) in PD participants referred to receive
deep-brain stimulation surgery (DBS), who are known to later develop high rates of apathy, directly test whether
stimulation of the subthalamic nucleus (STN) and connected frontal-subcortical circuits, would result in
immediate changes in GDB. The central hypothesis is that, regardless of the primary neuropathology or location
along the neural circuit, both atrophy, observed as structural and functional connectivity changes, and electrical
stimulation along the prefrontal-basal ganglia network, directly alter GDB and manifest as apathy. Two
independent aims are proposed: Aim 1. With all three study populations combined (PD n=100, FTD n=50, and
AD n=100), evaluate the independent effects of reward and effort sensitivity as a mechanistic link between
neurodegeneration of basal ganglia-to-frontal network and the development of specific dimensions of apathy, by
identifying the neuroanatomical underpinnings for (A) each of the three dimensions of apathy as measured by
Dimensional Apathy Scale (DAS), which provides subscores for three apathy dimensions, and (B) reward and
effort sensitivity from the Apple Gather task (AGt), and (C) evaluating reward and effort sensitivity as explanatory
mediators for neuroimaging metrics and apathy dimensions. The AGt is a 30-minute computer administered
effort-based decision-making paradigm in which rewards are weighed against effort. Consistent with the RDoC
framework, the AGt allows a mechanistic approach to apathy by dissociating components of GDB with distinct
neuroanatomical substrates. In Aim 2, for PD-DBS participants, determine whether electrical manipulation of the
STN directly alters reward and effort information processing and consequently GDB. To demonstrate a causal
effect of DBS on changes in motivated behavior in PD participants, while `on' dopaminergic medications, we will
assess their performance on AGt at three t...

## Key facts

- **NIH application ID:** 10438901
- **Project number:** 5R01MH127200-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Nora Vanegas-Arroyave
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $620,678
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438901

## Citation

> US National Institutes of Health, RePORTER application 10438901, Investigating neuroanatomical underpinnings of apathy in ADRD through neuroimaging and electrical manipulation (5R01MH127200-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438901. Licensed CC0.

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