Odor for Smell Perception

Overseen By Naelly Arriaga, MPH

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Smell or taste problems

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the brain perceives different strengths of smells. Researchers aim to understand how the brain processes odor intensity, independent of the smell's strength in the air. Participants will experience various odors to help identify patterns in the brain's response. This trial suits English-speaking individuals aged 12 to 65 who are undergoing brain surgery for medication-resistant epilepsy. As an unphased study, it offers a unique opportunity to contribute to groundbreaking research on brain function and sensory perception.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this method is safe for investigating odor intensity in humans?

Research shows that odors, the focus of this study, are generally safe for humans. While odors can vary in strength, they are usually harmless at detectable levels. Some substances might be harmful if inhaled in extremely high amounts, but everyday smells don't reach these levels.

In this study, participants will smell different odors to learn how the brain perceives their strength. Participants will experience various smells at different intensities. Specific data about negative effects from these odors is not available, but since the trial is in a "Not Applicable" phase, it focuses on basic research rather than testing a new drug. This suggests a lower risk of harmful effects.

Overall, because the study uses common odors and aims to understand perception, it appears safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different concentrations of odors are perceived by the human brain, specifically in the piriform cortex. Unlike traditional studies that might focus on altering smell perception through medications or therapies, this approach directly examines the brain's response to varying odor intensities. Understanding these neural representations could lead to breakthroughs in treating smell-related disorders, offering a more precise and tailored approach than current standard care options. This research could pave the way for new diagnostic tools or interventions that are directly informed by how our brains process smells.

What evidence suggests that this method is effective for studying odor perception?

Research has shown that the piriform cortex, a part of the brain, is crucial for sensing the strength of smells. This area processes smell information from both nostrils and combines it to assess odor intensity. Individual brain cells in the piriform cortex respond to different smells, aiding in rating their intensity. Additionally, activity in both the olfactory bulb and piriform cortex reflects not only the actual amount of odor but also how strong the smell feels to a person. These findings suggest that the piriform cortex plays a key role in perceiving and distinguishing the strength of different smells.

In this trial, researchers will present odors at various concentrations to investigate how the human piriform cortex represents odor intensity. ^{6 7 8 9 10}

Who Is on the Research Team?

christina zelano

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This study is for individuals who can perceive body odor. It aims to understand how the brain processes different intensities of odors, regardless of their concentration. Specific details about inclusion and exclusion criteria are not provided.

Exclusion Criteria

Screening for history of smell or taste problems

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experiment 1A

Matching perceived intensities across odors of different concentrations to identify a neural representation of intensity independent of stimulus identity and concentration

15 minutes per session

Multiple sessions

Experiment 1B

Creating conditions of different perceived intensity over constant odor stimuli using adaptation

15 minutes per session

Multiple sessions

Follow-up

Participants are monitored for safety and effectiveness after experiments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Odor

Trial Overview The trial is exploring how the human piriform cortex represents odor intensity by conducting two experiments: one matches perceived intensities across various concentrations, and another manipulates perceived intensity with constant stimuli using adaptation.

How Is the Trial Designed?

Group I: Investigating representations of odor intensity in human piriform cortex. Experimental Treatment 1 Intervention

Odors will be presented at different concentrations.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

A study involving 613 subjects found that identifying just one odor can effectively diagnose normal olfactory function (normosmia), simplifying clinical testing procedures.

Using a screening test with three specific odors (cinnamon, fish, and banana) achieved a sensitivity of 80.4% and specificity of 84.3%, allowing for reliable identification of normosmia and reducing the need for extensive olfactory assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Many and Which Odor Identification Items Are Needed to Establish Normal Olfactory Function? Lötsch, J., Ultsch, A., Hummel, T.[2022]

The paper provides a comprehensive review of odor thresholds for 214 potentially hazardous chemical vapors and gases, offering quantitative data crucial for industrial health and safety specialists.

It includes calculated safe dilution factors and odor safety factors for each compound, along with calibration charts to help estimate the detectability and warning potential of these chemicals, enhancing safety measures in environments where these substances are present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odor as an aid to chemical safety: odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Amoore, JE., Hautala, E.[2019]

The study utilized a quantitative structure-activity relationship (QSAR) approach to analyze how different volatile organic compounds (VOCs) affect the senses of smell and nasal irritation, using data from 64 VOCs across various chemical series.

It was found that nasal pungency thresholds (NPTs) can effectively distinguish between selective and specific chemosensory effects in odor detection thresholds (ODTs), allowing for the prediction of ODTs based on NPTs for VOCs primarily influenced by selective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quantitative structure activity analysis on the relative sensitivity of the olfactory and the nasal trigeminal chemosensory systems. Abraham, MH., Sánchez-Moreno, R., Cometto-Muñiz, JE., et al.[2016]

In a study of 445 patients with olfactory testing, 76% had some level of olfactory impairment, with 30% experiencing complete anosmia, indicating a significant prevalence of smell disorders.

Patients with olfactory impairment were 37% more likely to encounter hazardous events related to their inability to smell, such as cooking incidents and undetected gas leaks, compared to only 19% of those with normal olfactory function, highlighting the safety risks associated with impaired smell.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hazardous events associated with impaired olfactory function. Santos, DV., Reiter, ER., DiNardo, LJ., et al.[2022]

In a study with 76 participants evaluating 24 everyday odors, it was found that knowing the source of an odor significantly increased ratings of its intensity, pleasantness, and familiarity.

Participants rated odors highest when the names provided matched their own perceptions, indicating that cognitive understanding of odors influences how we perceive them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Judgement of odor intensity is influenced by subjects' knowledge of the odor source. Distel, H., Hudson, R.[2019]

About 40% of non-expert consumers in Pennsylvania cannot detect rotundone, a compound that gives a peppery flavor to some wines, indicating a specific anosmia for this compound in a North American population.

Detection thresholds for rotundone were similar whether assessed through orthonasal or retronasal methods, suggesting that future studies can focus on orthonasal assessments; however, added rotundone was generally disliked by participants, highlighting the need for winemakers to consider consumer preferences when producing peppery wines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual Differences in Thresholds and Consumer Preferences for Rotundone Added to Red Wine. Gaby, JM., Bakke, AJ., Baker, AN., et al.[2021]

The study successfully cloned and characterized the first human olfactory receptor (OR 17-40), which is crucial for understanding how humans perceive different smells.

Testing revealed that the receptor specifically responds to the odorant helional and one closely related compound, heliotropyl acetone, highlighting the receptor's selectivity and providing insights into the molecular mechanisms of olfactory perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cloning, functional expression and characterization of a human olfactory receptor. Hatt, H., Gisselmann, G., Wetzel, CH.[2016]

In a study of 272 participants, including healthy individuals and those with varying degrees of smell dysfunction, significant differences in chemical sensory functions were observed, particularly in patients with functional anosmia, who exhibited prolonged latency and reduced amplitude in olfactory and trigeminal event-related potentials (oERPs and tERPs).

The findings suggest that patients with functional anosmia also experience hypogeusia (reduced taste sensitivity), indicating a potential dysfunction of both olfactory and trigeminal nerves, which could be useful for clinical diagnosis and treatment strategies in affected populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of chemosensory functions in patients with dysosmia. Yang, L., Wei, Y., Zhang, W., et al.[2021]

The Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) is a newly developed and validated quality-of-life measure specifically for patients experiencing parosmia, demonstrating strong reliability and validity in a study involving 134 patients and 20 healthy controls.

DisODOR effectively distinguishes between patients with parosmia and healthy individuals, with a significant mean score difference of 45.0, and is sensitive to changes in patients' conditions, making it a useful tool for evaluating treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR). Ioerger, P., Kallogjeri, D., Roland, L., et al.[2023]

The Affordable Rapid Olfaction Measurement Array (AROMA) is a novel, essential oil-based smell test that shows strong reliability and correlation with the established University of Pennsylvania Smell Identification Test (UPSIT), making it a promising tool for assessing olfactory function.

AROMA not only correlates well with UPSIT but also with sinonasal outcomes and perceived loss of smell, suggesting it could be particularly useful for evaluating olfactory dysfunction in patients with sinonasal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Affordable Rapid Olfaction Measurement Array: A Novel, Essential Oil-Based Test Strongly Correlated with UPSIT and Subjective Outcome Measures. Villwock, JA., Li, J., Moore, C., et al.[2022]

A review of 28 studies on odor perception revealed that the outcomes of these studies are heavily influenced by factors such as individual differences in perception, the characteristics of the odors tested, data collection methods, and analysis techniques.

Despite over 50 years of research, a universally accepted classification system for odor qualities remains elusive, indicating that current methodologies may need significant improvement to achieve unbiased results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odor classification: a review of factors influencing perception-based odor arrangements. Kaeppler, K., Mueller, F.[2016]

Patients with persistent olfactory impairment reported significantly more difficulties in daily activities, with an average of 4.70 activities affected compared to only 0.61 in those who felt their sense of smell had improved.

Quality of life was notably lower in patients with ongoing smell issues, as only 50% reported overall life satisfaction compared to 87% in those who perceived their olfactory function as normal, highlighting the impact of smell on safety and eating habits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of olfactory impairment on quality of life and disability. Miwa, T., Furukawa, M., Tsukatani, T., et al.[2019]

Our sense of smell can detect an incredibly wide range of chemical compounds at very low levels, making it a crucial chemical sense that helps us interact with our environment.

Olfaction serves as a protective mechanism by alerting us to potentially harmful substances, while also being deeply connected to our emotions and memories, influencing our instinctive reactions to different odors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The power of odors--pathogenic or unpleasant]. Glück, U.[2016]

In a study involving 20 human subjects, it was found that people could distinguish between certain aromatic compounds better than others, particularly those containing methyl benzoate or phenyl methyl ketone, indicating that the type of functional group significantly affects odor discrimination.

The results suggest that functional oxygen-containing groups play a crucial role in how odorants interact with olfactory receptors, and that the structure of the alkyl group attached to these functional groups also influences odor quality, leading to poorer discrimination of aromatic compounds compared to aliphatic ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory discrimination ability for aromatic odorants as a function of oxygen moiety. Laska, M.[2019]

In a study involving 32 participants, researchers identified four distinct groups based on their sensitivity to 11 different musk odorants, revealing a range of olfactory detection thresholds.

Two specific groups of individuals exhibited heightened sensitivity to certain musk compounds, suggesting the existence of unique odor perception phenotypes (MSHM1 and MSHM2) that could have implications for understanding human olfactory diversity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odor perception phenotypes: multiple, specific hyperosmias to musks. Gilbert, AN., Kemp, SE.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2834563/

Odor quality coding and categorization in human posterior ... We show that spatially distributed ensemble activity in human posterior piriform cortex (PPC) coincides with perceptual ratings of odor quality.

2. nature.com nature.com/articles/s41586-024-08016-5

Single-neuron representations of odours in the human brain Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960982223015373

Olfactory cortex: Temporal segregation of inputs from the ... Piriform cortex processes odor information coming from two nostrils to give rise to unified perception of odorant identity and intensity.

4. biorxiv.org biorxiv.org/content/10.1101/2025.05.26.656087v1.full-text

Olfactory bulb and cortex activity reflects subjective odor ... We investigated how the human olfactory bulb (OB) and piriform cortex (PC) process odor concentration versus subjective perceived intensity.

5. elifesciences.org elifesciences.org/articles/13732

The role of piriform associative connections in odor ... Pharmacological fMRI reveals that associative connections contribute to odor categorization by supporting discrimination and generalization ...

6. tools.niehs.nih.gov tools.niehs.nih.gov/wetp/Public/DOE_Trainers/13_HANDOUT_SENSE_OF_SMELL.pdf

Sense of Smell Unit Some materials can be detected with your nose while they are below a life- threatening threshold; others cannot be detected until a life-threatening.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0160412025003472

Advancements in understanding emission characteristics ... Analytical data reveal that odor concentrations vary over three to four orders of magnitude across different emission sources. These discrepancies are ...

8. science.org science.org/doi/10.1126/sciadv.adn3028

Nature and human well-being: The olfactory pathway Vearrier, The perception of odor is not a surrogate marker for chemical exposure: A review of factors influencing human odor perception.

9. jneurosci.org jneurosci.org/content/45/14/e1159242024

Smell the Label: Odors Influence Label Perception and ... This study explored the neural processing of the interplay between odors and nutrition labels using fMRI in 63 participants of either sex.

10. nature.com nature.com/articles/s41598-021-96334-3

Odours count: human olfactory ecology appears to be ... The aim of our study was to quantify olfactory perception and preliminarily identify factors affecting the frequency of odorous experiences.