# Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $394,830

## Abstract

ABSTRACT
Research in our laboratory focuses on understanding how the human brain encodes and interprets information
about odor stimuli. Often regarded as the trivial “fifth” sense, the human sense of smell is in fact remarkably
robust. The human nose can discriminate odors with subtle differences in molecular structure, distinguish
thousands of unique smells, and transport us back in time to reactivate distant memories and emotional states.
Additionally, the olfactory system (in human and non-human animals) is an increasingly attractive and powerful
model for studying brain function under normal and pathological conditions.
Studies investigating the human olfactory system have traditionally relied on two types of methods: functional
magnetic resonance imaging (fMRI) and scalp-based EEG. While these non-invasive approaches have yielded
important insights about odor processing, the scope of testable questions is limited due to temporal (MRI) and
spatial (EEG) constraints. In particular, there is a critical knowledge gap in understanding the physiological
basis of the human sense of smell. Over the last few years, we have had the opportunity to obtain intracranial
EEG (iEEG) recordings from epilepsy patients with medically resistant seizures. As part of a standard surgical
pre-clinical evaluation, patients undergo surgery during which invasive depth electrodes are implanted into the
brain to localize epileptogenic foci. This approach provides an invaluable opportunity to characterize human
olfactory cortical processing with high spatiotemporal resolution. Our recent studies have established that odor
stimuli evoke rhythmic oscillations of 3-7 Hz (“theta” frequency) in human piriform cortex (PC), and that distinct
odors evoke distinct theta activity as soon as 100 ms after the onset of a sniff. We have also shown that theta
phase coupling between PC and hippocampus increases in the presence of odor but not air.
These novel findings provide a platform for experiments outlined here. By leveraging our expertise in olfactory
cognitive neuroscience with state-of-the-art iEEG signal analysis tools, we will establish a physiological
foundation of human olfactory processing at the level of population dynamics and network interactions. Our
proposed studies, informed by data from animal models, are designed to test forward-based, hypothesis-driven
questions about the mechanistic underpinnings of odor perception. Aim 1 will address how changes in
fundamental features of odor stimuli alter PC neural dynamics as assessed by changes in theta oscillatory
features. Aim 2 will test the role of PC-hippocampal coupling in odor discrimination. Aim 3 will examine whether
PC theta plays a causal role in odor perception, and will identify potential mechanisms by which theta can
shape odor processing. The conceptual approaches developed here should help guide future basic and clinical
research strategies for assessing the biological relevance of olfactory oscillations in th...

## Key facts

- **NIH application ID:** 10376359
- **Project number:** 5R01DC018075-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jay A Gottfried
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,830
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376359

## Citation

> US National Institutes of Health, RePORTER application 10376359, Spatiotemporal Mechanisms of Olfactory Processing in the Human Brain (5R01DC018075-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376359. Licensed CC0.

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