Kobi Snitz

Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white

In vision, two mixtures, each containing an independent set of many different wavelengths, may produce a common color percept termed “white.” In audition, two mixtures, each containing an independent set of many different frequencies, may produce a common perceptual hum termed “white noise.” Visual and auditory whites emerge upon two conditions: when the mixture components span stimulus space, and when they are of equal intensity. We hypothesized that if we apply these same conditions to odorant mixtures, “whiteness” may emerge in olfaction as well. We selected 86 molecules that span olfactory stimulus space and individually diluted them to a point of about equal intensity. We then prepared various odorant mixtures, each containing various numbers of molecular components, and asked human participants to rate the perceptual similarity of such mixture pairs. We found that as we increased the number of nonoverlapping, equal-intensity components in odorant mixtures, the mixtures became more similar to each other, despite not having a single component in common. With ∼30 components, most mixtures smelled alike. After participants were acquainted with a novel, arbitrarily named mixture of ∼30 equal-intensity components, they later applied this name more readily to other novel mixtures of ∼30 equal-intensity components spanning stimulus space, but not to mixtures containing fewer components or to mixtures that did not span stimulus space. We conclude that a common olfactory percept, “olfactory white,” is associated with mixtures of ∼30 or more equal-intensity components that span stimulus space, implying that olfactory representations are of features of molecules rather than of molecular identity.

Predicting Odor Perceptual Similarity from Odor Structure

To understand the brain mechanisms of olfaction we must understand the rules that govern the link between odorant structure and odorant perception. Natural odors are in fact mixtures made of many molecules, and there is currently no method to look at the molecular structure of such odorant-mixtures and predict their smell. In three separate experiments, we asked 139 subjects to rate the pairwise perceptual similarity of 64 odorant-mixtures ranging in size from 4 to 43 mono-molecular components. We then tested alternative models to link odorant-mixture structure to odorant-mixture perceptual similarity. Whereas a model that considered each mono-molecular component of a mixture separately provided a poor prediction of mixture similarity, a model that represented the mixture as a single structural vector provided consistent correlations between predicted and actual perceptual similarity (r≥0.49, p<0.001). An optimized version of this model yielded a correlation of r = 0.85 (p<0.001) between predicted and actual mixture similarity. In other words, we developed an algorithm that can look at the molecular structure of two novel odorant-mixtures, and predict their ensuing perceptual similarity. That this goal was attained using a model that considers the mixtures as a single vector is consistent with a synthetic rather than analytical brain processing mechanism in olfaction.

A Mechanistic Link between Olfaction and Autism Spectrum Disorder

Summary Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors [1]. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD) [2–4]. However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication [5], remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence [6–12]. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children—18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = −0.75, p < 0.001), specifically with social (r = −0.72, p < 0.001), but not motor (r < −0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities.

The perceptual logic of smell.

Mammals have ∼1000 different olfactory receptor subtypes, each responding to a number of different odorants, and each odorant activating a number of different receptor subtypes. These molecular and anatomical underpinnings of olfaction imply a perceptual structure of very high dimensionality that relies on combinatorial coding. In contrast to this expectation, the study of olfactory perception reveals a structure of much lower dimensionality. Moreover, a low-dimensionality approach to olfaction enabled derivation of perception-based structural metrics for smell. These metrics provided meaningful predictions of odorant-induced neural activity and perception from odorant structure alone. Based on this low functional dimensionality, we speculate that olfaction likely does not functionally rely on 1000 different receptor subtypes, and their persistence in evolution may imply that they have additional roles in non-olfactory functions such as in guidance of embryogenesis and development.

Individual olfactory perception reveals meaningful nonolfactory genetic information

Significance Cyrano de Bergerac observed that “a large nose is the mark of a witty, courteous, affable, generous and liberal man.” Here we report that individual noses, not how they look but rather how they function, indeed say a lot about a person. Each person expresses a nearly unique set of different olfactory receptor genes, and therefore may have unique olfactory perception. We developed a highly sensitive perceptual test we call the “olfactory fingerprint” that captures this variability. Individual olfactory fingerprints are therefore mirrors of individual olfactory genomes. We demonstrate that such fingerprints predict genetic features linked to the olfactory system, such as aspects of immune regulation. Thus, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information. Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

A Cross Modal Performance-Based Measure of Sensory Stimuli Intricacy

We define a new measure of sensory stimuli which has the following properties: It is cross modal, performance based, robust, and well defined. We interpret this measure as the intricacy or complexity of the stimuli, yet its validity is independent of its interpretation. We tested the validity and cross modality of our measure using three olfactory and one visual experiment. In order to test the link between our measure and cognitive performance we also conducted an additional visual experiment. We found that our measure is correlated with the results of the well-established Rapid Serial Visual Presentation masking experiment. Specifically, ranking stimuli according to our measure was correlated at r = 0.75 (p < 0.002) with masking effectiveness. Thus, our novel measure of sensory stimuli provides a new quantitative tool for the study of sensory processing.

Predicting odor perceptual similarity from odor structure

not submitted for publication. Published: 16 April 2014 doi:10.1186/2044-7248-3-S1-O2 Cite this article as: Snitz et al.: Predicting odor perceptual similarity from odor structure. Flavour 2014 3(Suppl 1):O2. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel Snitz et al. Flavour 2014, 3(Suppl 1):O2 http://www.flavourjournal.com/content/3/S1/O2

Individual olfactory fingerprints: from mapping odors in people-space to mapping people in odor-space

not submitted for publication. Published: 16 April 2014 doi:10.1186/2044-7248-3-S1-P17 Cite this article as: Secundo et al.: Individual olfactory fingerprints: from mapping odors in people-space to mapping people in odor-space. Flavour 2014 3(Suppl 1):P17. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel Secundo et al. Flavour 2014, 3(Suppl 1):P17 http://www.flavourjournal.com/content/3/S1/P17