# Principles of olfactory reward processing in the human brain

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $316,610

## Abstract

ABSTRACT
Dementia or mild cognitive impairment due to Alzheimer’s disease affect millions of Americans. Clinically, it is
characterized by general cognitive decline and prominent memory impairments. However, one of the first
functions to be affected in Alzheimer’s disease is the sense of smell. In fact, olfactory dysfunction often precedes
the onset of other cognitive and memory impairments. In the brain, olfactory information is processed along the
lateral olfactory tract (LOT), a white-matter bundle that connects the olfactory bulb to cortical areas including the
piriform cortex and entorhinal cortex. Paralleling olfactory perceptual deficits in Alzheimer’s disease, post-
mortem studies show that neurodegeneration is first observable in olfactory brain regions such as the olfactory
bulb and entorhinal cortex. Based on this evidence, we hypothesize that olfactory impairments and cognitive
decline in early-stage Alzheimer’s disease are both related to neurodegeneration in the LOT. The integrity of
white-matter pathways in the human brain can be measured in vivo using diffusion-weighted magnetic resonance
imaging (dMRI). However, dMRI in olfactory structures is technically challenging because of prominent signal
dropout and image deformations in these areas. To overcome these challenges, a major goal of the parent
project (R01DC015426) is to develop a novel dMRI protocol and analysis pipeline to image the human LOT. Our
preliminary results of aim 3 of the parent project demonstrate that we are now able to image the human LOT
with unprecedented quality. The goal of this application for administrative supplement is to use our new imaging
technologies to directly test our hypothesis regarding LOT neurodegeneration in Alzheimer’s disease. We
propose to measure the integrity of the LOT in participants with early-stage Alzheimer’s disease and age-
matched cognitively normal control participants. We will compare LOT integrity between groups, and test whether
these measures correlate with olfactory perceptual deficits and cognitive decline. The proposed work will
characterize LOT neurodegeneration in Alzheimer’s disease using in vivo imaging techniques, and build the
basis for novel biomarkers for Alzheimer’s disease that are sensitive to cognitive decline. Such biomarkers will
be non-invasive and thus can be used to identify at-risk populations before cognitive decline occurs. In addition,
the results from this project may inform mechanistic models of Alzheimer’s disease and aid the development of
new treatments that target neurodegeneration in specific brain areas.

## Key facts

- **NIH application ID:** 10097477
- **Project number:** 3R01DC015426-04S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Thorsten Kahnt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $316,610
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10097477

## Citation

> US National Institutes of Health, RePORTER application 10097477, Principles of olfactory reward processing in the human brain (3R01DC015426-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10097477. Licensed CC0.

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