# CRCNS: Scale-invariant navigation and its degradation in Alzheimer's disease

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $339,043

## Abstract

This project seeks to advance what is known about the neural mechanisms of navigation. Our approach is
through the development and empirical testing of a computational framework for how neural circuits encode
and decode information to form scale invariant memories. This framework is referred to as SIPI, short for
Scale Invariant Path Integration framework. Applying the SIPI framework to navigation provides a
mechanistic model for how neurons obtain spatial tuning by encoding an animals’ movements and for how
neural degeneration affects path integration ability. This project will generate new tools to facilitate broader
application and testing of SIPI and test strong predictions of the SIPI framework through empirical studies
of rodent and human behavior and brain activity. The new tools include a simulation environment for
analyzing SIPI function across parameterizations and variants of SIPI that 1) use visual input to guide
navigation, 2) address how positional coding interacts with noisy self-motion cues, and 3) perform memory
guided navigation. High-density single unit electrophysiology in rodents will test strong predictions of SIPI
regarding whether head direction and boundary tuned neurons encode a multiscale history of movements
and whether the history encoded by those neurons accounts for navigation ability in healthy and transgenic
models of Alzheimer’s disease (AD). Behavioral and ultra-high resolution functional imaging in humans will
test predictions from SIPI that 1) path-integration performance has diagnostic value for identifying
preclinical AD, 2) that reduced velocity coding and path integration ability in elderly patients are addressed
by approved AD treatments, 3) that AD is associated with increased dependence on environmental
boundaries for orienting, and 4) that, in healthy volunteers, the proximity of environmental boundaries are
encoded in a multiscale fashion in the entorhinal cortex. That is, this project will perform strong tests of the
SIPI framework, will advance our understanding of spatial coding in the brain, and test new avenues for
insight into the behavioral deficits that accompany Alzheimer’s disease.
RELEVANCE (See instructions):
Navigation is a core competency that depends upon intact functioning of circuits impacted first in
Alzheimer’s disease. This project aims to determine the neurophysiological mechanisms that contribute to
path integration and boundary coding impairments in human preclinical Alzheimer’s disease individuals and
develop translatable outcome measures for assessing animal models of Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10495226
- **Project number:** 5R01AG076198-02
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Ehren L. Newman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $339,043
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495226

## Citation

> US National Institutes of Health, RePORTER application 10495226, CRCNS: Scale-invariant navigation and its degradation in Alzheimer's disease (5R01AG076198-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10495226. Licensed CC0.

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