Friday, May 13, 2022


The world of smell goes unnoticed to most of us. There are more books in the Library of Congress on perfume bottles than there are about smell itself. The year 2020 will mean lots of things to lots of people, but most of us will not remember it as the year that changed the literary world of smell forever.  

Image credit: Camillo Golgi's image of a dog’s olfactory bulb from his Sulla fina anatomia degli organi centrali del sistema nervoso, 1885. [link]

Together, Smellosophy by Ann Sophie Barwich and Nose Dive by Harold McGee have advanced the written record of our sense of smell by 40 years. Trygg Engen wrote The Perception of Odors in 1982, and we haven't seen a real update since. Obviously there have been scores of researchers writing journal articles since then, but an article is not a book. Also, there have been books written about smell, by well-regarded scientists and writers like Avery Gilbert, Rachel Herz, Synnott, Classen and Howes, Wilson and Stevenson, Alain Corbin, to name a few that come to mind.

But these books, both of them, are something else. They are dense, they are exhaustive, and they offer the most detailed explanation of how your sense of smell works, and what things smell like, than any other book you could read about the topic. 

*For third place in the most important smell-books of the past 40 years, maybe we should add The Essence: Discovering the World of Scent, Perfume and Fragrance by artbook publisher Gestalten, also in the year 2020/2021, and runner-up to Nose-Dive for The Perfumed Plume's best fragrance book of 2021

I'll save Harold McGee for another day, since I'm still parsing his almost 700 page codex. I thought it more important to finish Barwich's book first; it's the more scientifically hardcore of the two, and I was afraid my attention might wane the other way around. And this is not a book you want to breeze through. Again, it's probably the most comprehensive book on smell ever written. I took notes, some of which I'll paste here:

Notes on the author: Sophie Ann Barwich is a a cognitive scientist and empirical philosopher with a doctorate in odor classification and a background in philosophy and history, and spent time in Stuart Firestein's Columbia lab, and also interviewed a ton of perfumers, fragrance industry professionals, and just about anyone else who's important in the olfactory world that's still alive (except Asifa Majid, although she is cited in the book). She's an Assistant Professor at Indiana University Bloomington, between the Department of History & Philosophy of Science and the Cognitive Science Program.

Your nose is tailored to measure the world as calibrated by your mental life and physiological conditions. (p12)

Important terms for the olfactory enthusiast: Combinatorial and combinatorics refers to the combination of massive datapoints into a single datapoint, like how the olfactory bulb takes thousands of chemicals and pulses out a single signal in response; Foregrounding like from this sentence, "Smell is frequently embedded in the conscious experience of the world without being foregrounded as an olfactory experience" (p91); juxtaglomerular cells means next-to-glomerulus cells, juxta-anything sounds interesting, so...

Referencing Asifa Majid: Odor language is strongly contingent upon the rules of conventionalization (p102)

  • The Lingua Anosmia is Perishable: Leslie Vosshall - One central problem with these new computational studies were the data; "Most of the theoretical work has been based on a single 30 yr old dataset. Why has no one done an update?" (p173)
  • Andrew Dravnieks Atlas of Odor Character Profiles: "a great list in the early 80's, for use in the Northeast of the United States, for people who are baby boomers." (p173)
  • But so many of the words on that list have no frame of reference for the people who come to our studies. Any of these lists...they are perishable, highly culturally biased lists, that will work for some specific period in history, for a specific target audience. (p173)
  • The Odor Atlas didn't map odor quality space, "they mapped the odor quality space of Dravnieks." (p173)
  • The DREAM Project did provide a strong case for data mining, but only had a 0.3 correlation. (p175)

Polar surface area is a key metric for olfactory receptors (p185) -Poivet et al. "Functional Odor Classification through a Medical Chemistry Approach", Science Advances 4 n2 (2018)

Terry Acree's potato chips, only 3 odorants do the trick: methanethiol (rotten cabbage), methionol (potato), 2-ethyl-3,5-dimethylpyrazine (toast) -Computing Odor Images. Rochelle MM, Prévost GJ, Acree TE. J Agric Food Chem. 2018 Mar 14;66(10):2219-2225. doi: 10.1021/acs.jafc.6b05573.

Stimulus Representation Beyond the Map: Gordon Shephard and Thomas Cleland: Olfactory perception is more like the feature coding of face recognition in the visual system. The olfactory bulb does not represent chemical classes but the chemical environment; it tracks the statistics of a changing odor environment (Shephard and Cleland, p233) [And I would say that society and culture are part of that environment, and that given enough data, the language of smell can be a map of our changing social environment.]

"The brain evolved from the body and not the other way around" -Terry Acree (p237)

Predictive powers of the nose, Walter Freeman studying neural networks at Berkeley in the 1980's:
How brains make chaos in order to make sense of the world. Skarda, C. A., & Freeman, W. J. (1987).  Behavioral and Brain Sciences, 10(2), 161–195.
Simulation of chaotic EEG patterns with a dynamic model of the olfactory system, Walter J. Freeman, Biological Cybernetics (2004) v56 p139-150.
Model of biological pattern recognition with spatially chaotic dynamics, Yong Yao and Walter J. Freeman, Neural Networks (1990), v3 p153-170.
Neural networks and chaos. Freeman WJ, J Theor Biol. 1994 Nov 7;171(1):13-8. doi: 10.1006/jtbi.1994.1207.
Characterization of state transitions in spatially distributed, chaotic, nonlinear, dynamical systems in cerebral cortex. Freeman, W.J. Integrative Physiological and Behavioral Science 29, 294–306 (1994).

Unknown Odors (Covid) - based on Walter Freeman's work: "known odors elicit an established spatiotemporal signature of activity. Unknown odors first evoke chaotic activity before acquiring their own spatiotemporal signature for future recall. Chaos here was a condition for learners so that the brain would not confuse a novel odor with the signature of an already known one." (p238-239)

"The spatiotemporal activity in the bulb should thus be seen as an expression of the dynamic coding space -- not a fixed representation of odors, since odorants can be assigned various meanings, and, in turn, patterns." (p242)

The wide distribution of decorrelated signals in the olfactory cortex "allows olfactory signals to be integrated and synchronized with parallel processes in neighboring cortical domains..." Sparse coding is less detailed but faster in processing and recognition. Temporal patterns is where it's at, not topographical patterns, so it's about measurement, not mapping. "dynamically encoded signatures" (p242-243)

"Rather than molecules, your brain depicts transient information patterns, extracted and weighed in a given context, without a superimposed matrix of chemical classes to accommodate for countless permutations." (p246)

"Olfaction becomes an ideal model for higher-order processing other modalities.

Higher-brain integration is notoriously tricky to understand; it's signaling is not topographic, seemingly random, and autoassociate, just like in the olfactory system." (p247)

Relearning to Smell, Post-Covid: Mark Stopfer: "The first time you present an odor, there are no oscillations, you have to present an odor two or three times before the oscillation begins to build up. That's because there's this activity-dependent plasticity that takes place within the antennal lobe [we're talking insects here]. The local neurons that are activated become more effective over repeated activations. The inhibitory local neurons become more and more effective at synchronizing the projecting neurons over the course of repeated odor presentations. We think that's enabling the system to become more specific as the odor remains present." (p257)

"You go from a very general response to a more specific response. At the very beginning, you get this big burst that tells you there's something novel in the environment. Then right after that, you start to categorize it: it smells floral versus savory, for example. If the odor is still present, the system becomes more and more specific as this process builds up, the response downstream becomes more specific, and then you can identify exactly what it is. The same circuit at first will give you this generalization: it's something [fruity] -- and then the same circuit over time will say: oh well, it's cherry, not strawberry. It only happens if the odor is there long enough to perhaps be of interest to the organism." [this is why we can't name bad smells]

Beautiful description: The olfactory brain measures "odor situations" to evaluate how cues are related to each other (temporally, combinatorially, causally) and to attribute these perceptions a specific value (pleasant, putrid) and behavioral response." (p260)

Odor images are not encoded in the stimulus; they constitute mental impressions that arise from the categorization of sensory information. (p268)

One of a Kind: "When we manufactured a standard solution of an odorant, all we have to do is make another one, and it will smell different every time." -Terry Acree (p269)

  • Christophe Laudamiel's description of what a perfumer does - refinement of observation through cognitive engagement: "We don't have a super nose, but we notice things; it's our job to recognize a lot of smells, we pay attention, we recognize what we smell. We know how to describe things, and we know how to compose." (p272)
  • Christophe again: Perfumery is more than the sum of its parts: "What about black olive? when you want black olive, it's burnt rubber with wood." (p286)
  • Christophe again: Odorants convey more than one qualitative note: "I don't know a single molecule. You say cut grass? Cut grass is a whole world. In cut grass is wet dirt. There is a pear note. There is a green note, which you would say is a green, leafy note. But then how do you define a green, leafy note? That's the one that smells like cut grass. So it's a catch 22." (p297)

Visuocentric theories often follow the idea that perception is all about the stable representation fo objects [but odors are constantly changing.] (p303)

The brain is dynamic; it measures the world rather than mapping it. (p304)

Individual variation is not at odds with the notion of objectivity in perception; rather it is an expression of the core mechanisms of sensory systems ... The traditional dualism between objectivity and subjectivity in sensory perception presents itself as an artifact of older philosophical framing. It is time to change... (p311)

Smellosophy: What the Nose Tells the Mind
Ann Sophie Barwich, Harvard University Press, 2020

Nose Dive: A Field Guide to the World's Smells
Harold McGee, Penguin, 2020

Personal criticisms:
If you're not already familiar with the science of olfaction, this book is not an easy read. That's mostly understandable, because it is so comprehensive, airtight in fact. Less excusable is another pattern I noticed, which is that it's hard to follow the quotations and remember who is saying what, and that's because people are referred to by their first names; this is a multidisciplinary crowd, from philosophers to chemists to perfumers to neuroscientists; it's very unlikely that the reader would be on a first name basis with all these people. Using their full names would give the reader a little bit more to hang onto in their working memory. For example, in another, completely unrelated book Chimpanzee Culture Wars, author Nicolas Langlitz continues to write linguist Michael Tommasello's full title after already having mentioned him like 300 times throughout the book.

Next, although less severe of a criticism, is that at one point the book changes in tone quite dramatically, almost as if it were two different books (circa p210). And last thing, which isn't a criticism but a simple note: She opens her chapter 9 with Parmesan Vomit (p264), which I called "Quantum Hedonics" in Hidden Scents in 2015.

Monday, May 9, 2022

Ant Ink and Infotaxis

The ant secretion methyl-4-methyl-pyrrole-2-carboxylate - "innocuous, faintly grassy, sulphurous, or fruitlike with a hint of naphtha", "an ichor of extraordinary power for the ants.

"They sweep their antennae back and forth in advance of the head to catch the odorant molecules. When a forager takes a long turn to the left and starts to run away from the track, its left antenna break out of the odor space first and is no longer stimulated by the guiding substance. In a few thousandths of a second, the any perceives the change and pulls back to the right." (p30-31) 

Biophilia: The Human Bond with Other Species 
E. O. Wilson, Harvard University Press, 1984

Tuesday, May 3, 2022

Downwind Odor

It's called the Rolling Unmasking Effect: "The source is a complex mixture of odorants, yet it is simplified to a single impactful odorant at the receptor downwind. The odor frontal boundary represents the farthest downwind reach of a single compound, while the internal colored ovals represent the boundaries of sequential odor unmasking as the secondary-impact odorants are diluted below their detection/masking concentration levels."

Qualitative Exploration of the ‘Rolling Unmasking Effect’ for Downwind Odor Dispersion from a Model Animal Source. Donald W. Wright et al. International Journal of Environmental Research and Public Health, 2021,18,13085. DOI: 10.3390/ijerph182413085

It's already hard enough to identify odors by their source, but these researchers show us that matching an odor "in the field" to one you think is the source, needs to account for the differentiated dispersal of odorants as the odor plume moves through space.

Just because one odorant scores high on the sniff test --at the source--, doesn't mean that odorant won't be the first to disappear at 10 yards. And just because you smell rotten eggs, doesn't mean that odorant is found in more abundance relative to others at the source, it could be that the rotten egg parts of the smell are better at avoiding dispersal, riding the edge of the odor plume as it emanates from its source. 

Some good terms:
  • rolling unmasking effect
  • downwind odor frontal boundary
  • odorant prioritization 
  • downwind odor impact
  • dynamic dilution olfactormetry

From the paper:

We propose solving environmental odor issues by utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries.

While the composition of environmental odors, as detected by human receptors, carries the potential for extreme complexity, the reality is that there is a high degree of compositional simplification, which typically develops with increasing distance separation from the odor source.

We refer to these two effects as the Rolling Unmasking Effect (i.e., RUE). 

Odors generated from rural and agricultural sources are lowered by "downwind diultion" dispersion strategies, and monitored by dynamic dilution olfactormetry.

There is also broad recognition of a challenge to link specific compounds to resulting downwind odor [10,11]. In one notable example from an odorant prioritization study to the rendering industry [12], just two odorants (trimethylamine (TMA) and dimethylsulfide (DMS)) were identified as the impact-priority odorants downwind of a fish meal processing plant. 

In a more recent study [14,15], these authors were able to identify the specific chemical odorant that is believed primarily responsible for the reported ‘skunky’ odor downwind of dense cannabis-growing operations. ... The compound 3-methyl-2-butene- 1-thiol (i.e., 321 MBT), was the primary source of this ‘skunky’ odor of cannabis [14,15].

This has been shown for p-cresol as a 'sognature' [signature?] downwind odor from confined animal feeding operations (CAFOs), recognizable at a great distance from the source. 

Odors from a large colony of Mexican fee-tailed bats: ammonia, "rat nest",  and "bat cave" or "taco shell", which was dominated by 2-aminoacetophenone, upon approach to the outer ‘odor frontal boundary’; enabled by the decline of odor masking by the quinazoline odorant.

Figure 3. P.T. porcupine encounter in Moody Gardens. (1) Wind direction; (2) odor frontal boundary; (3) approximate secondary (near-source) boundary; (4) investigator's approximate location upon initial encounter and (5) location of outdoor enclosure of the odor source.

PT Porcupine Urine Sampling:

Unfortunately, the panelist (D.W.W.) was unable to confirm the chemical identities of the two character-defining ‘grilled onion’ odorants from the P.T. porcupine environments. Therefore, in a further attempt to identify these unknowns, collaborations with experts in the food flavor/aroma field were engaged.

The near-source smell was perceived as ‘phenolic,’ ‘industrial,’ and ‘foul.’ The dramatic difference in character was particularly surprising considering that only a few paces separated the pleasant 'gilled onion' at the odor frontal boundary and the 'foul' odor deeper into the plume. 

Although the PT porcupine and swine barn sources generate distinctly different odor characteristics at their respective odor boundaries, despite sharing much in common through their VOC emission profiles at the source. 

Focusing on all compounds present at the source often expands the study to include background noise, an unnecessary expenditure if the goal is to reduce downwind environmental odor impact.

One team member did not characterize the odor as 'onion' specifically; instead, it had reminded her of a favorite sauce that her grandmother frequently made. The second team member called the odor character ‘stale onion’.

Post Script:
Here's an odor network for all the odor complaints in southern California circa 2012, via the South Coast Air Quality Management District (SCAQMD)and UCLA post-grad Jane Curren:
Local Odor Vocab

Post Post Script:
Odor wheel for drinking water:
Torrice, M. (adapted from Suffet, M.). The scientists who sniff water. Chem. Eng. News 2017, 95, 16–19.
Suffet, I.H., and P.E. Rosenfeld (2007). The Anatomy of Odour Wheels for Odors of Drinking Water, Wastewater, Compost and the Urban Environment, Water Science and Technology 55(5), 335-344.

Monday, May 2, 2022

Consumer Engineering


Here's an old study I came across while reading this very interesting and disturbing book on electronic drugs: Addiction By Design: Machine Gambling in Las Vegas, Natasha Dow Schüll, Princeton University Press, 2012. [link

Effects of Ambient Odors on Slot-Machine Usage in a Las Vegas Casino.
Alan R. Hirsch. Smell & Taste Treatment and Research Foundation, Ltd. Psychology & Marketing Vol. 12(7):585-594 (October 1995). John Wiley & Sons, Inc. [link]

Our data show that the amount of money gambled in the slot machines surrounding Odorant No. 1 during the experimental weekend was greater than the amount gambled in the same area during the weekends before and after the experiment by an average of 45%.

  • The odor was noticeable (suprathreshold levels)
  • It showed a dose-response relationship because they emitted less on Sundays, and people spent less on Sundays (yet still more than the other days)
  • I don't see any description of how they ensured the emitted smell actually accumulated in the targeted area instead of getting blown away by ventilation or occupant circulation, but that's a minor criticism
  • Although both odorants were described as pleasant by a panel, I don't see  any other information about them, although it should be pointed out that only one of the odorants had an effect;
  • On multi-modal stimulation and hijacking your hindbrain, he reminds us, "In casinos it is common to incite patrons to gamble by directly appealing to their senses: the exciting sounds of coins jingling, sirens screaming when someone hits the jackpot, intense lighting, plush carpets, luxurious surroundings, and controlled temperature."

*Wordplay, not to be taken seriously; hindbrain refers to the cerebellum and below, whereas the limbic system, which is where smell happens, is located above, in the midbrain

Note on the Author: Alan R. Hirsch was the Neurological Director of the Smell & Taste Research and Treatment Foundation in Chicago.

Wednesday, April 20, 2022

Odor Radar and Situational Awareness

Smell significantly enhances sense of realism in virtual reality, researchers find
Apr 2022,

While fighting zombies in survival mode, smell is likely the last thing on your mind. But our research has shown that the sense least associated with virtual reality actually holds the key to a more immersive experience. Participants in our study felt that smell gave them a greater sense of really "being there" in the virtual environment.

Surely a sweet-smelling game like Animal Crossing would be a better candidate for testing this theory? Well, as it turns out, bad smells may enhance the VR experience much more than good smells. 

Yes, and in fact, bad smells are about to do a lot more than good smells. Whether it's monitoring isoprene in the workplace to enforce occupational mental health regulations (science fiction I know, but it has to start somewhere), or using an odor alert system at work that gets more intense as your inbox gets too full, so you don't have to look or listen to it, we will be using odors in new ways in our everyday lives. It's the last sense to be digitized, to enter the interconnected datasphere, but universal odor machines and the coming chemosensor revolution are just two examples of why the time is coming for us to recognize the untapped potential of this new channel for communication. 

via The Commonwealth Scientific and Industrial Research Organisation CSIRO, Australia: Nicholas S. Archer et al, Odour enhances the sense of presence in a virtual reality environment, PLOS ONE (2022). DOI: 10.1371/journal.pone.0265039

Post Script:
Little Signals: A Google multi-object system to deliver notifications in a gentler manner
Apr 2022,

Only a few days after this post was published, I'm updating it with a news article from engineers at Google tells us there are other people thinking about how to communicate to users in new ways. 

Designed to deliver notifications to users in a gentler manner than current systems.

One such device is called simply Air, and it sends notifications via puffs of air, similar, Google says, to the slight movement of leaves on a plant as they rustle in response to a slight breeze. Another is called Button—it grows as it fills with information, such as messages piling up in an email folder. Twisting it one way reveals more details, while twisting the other way reveals fewer details. There is also a device called Movement—it has seven pegs that are lined up and which rise and fall. It is meant to convey timer or calendar notifications.

Putting a nose in the visual field acts as a point of reference thereby lessening motion sickness and disorientation in virtual reality:
Simulated Oversight, 2022

Smells aren't just good for video games, but for old-fashioned role playing games as well:
Adventure Scents - Try our scent special effects to enhance your favorite games, books, movies, costumes, and more. Alchemist's Lab, Ancient Library, Bombed-Out Ruins; there's 60 in all.

Monday, April 11, 2022

Another Step Towards Artificial Olfaction

Artificial recreation of smells using a multicomponent olfactory display
Apr 2022,

Twenty odor components were extracted using the mass spectra of 185 essential oils. The sensory test for seven typical essential oils revealed that their scents could be successfully replicated. The researchers mimicked a variety of smells simply by adjusting the mixture composition of various odor components. The odor components ejected from microdispensers were blended at the surface of the surface acoustic wave device. 

The 7 odors are lemon, palmaloza, carrot seed, elmi, lavender, chypre, and mentha arvensis. (And note these are essential oils, not individual molecules.)

There is still no formula for primary smells in the same way that we have the 3 primary colors of red, blue, and yellow/green. This is an advance nonetheless - 7 molecules are used to create 185 odors.

For reference, the Davnieks set has 146 descriptors; although it was made in 1985, it still represents a fair sampling of all the smells you might encounter in a day (see here for a more sophisticated description of this set and its shortcomings). 

via Tokyo Institute of Technology: Masaaki Iseki et al, A Study of Odor Reproduction Using Multi-component Olfactory Display, IEEJ Transactions on Sensors and Micromachines (2022). DOI: 10.1541/ieejsmas.142.63

Image credit: Dimensionality reduction: Each dot represents a point in the original space that corresponds to a point (shown by a dot) in the lower-dimensional reduced space. Deep learning approach based on dimensionality reduction for designing electromagnetic nanostructures, npj Computational Materials, 2020. [link]

Dravnieks A. Atlas of odor character profiles. Philadelphia: ASTM; 1985.
Arctander S. Perfume and flavor chemicals (aroma chemicals). Montclair, NJ: Author; 1969.
Keller A, Vosshall LB. Olfactory perception of chemically diverse molecules. BMC Neurosci. 2016 Aug 8; 17(1):55.

Thursday, April 7, 2022

Smells Like News

Too many headlines, too little time.
Image credit: Smell Test, Win McNamee Getty Images, 2010

Smelling Disease
Monell Updates, Feb 2022

Led by Monell chemical ecologist Bruce A. Kimball, PhD, the research team is taking the innovative approach of classifying fever-inducing diseases based on their distinctive signatures of volatile compounds in urine and saliva.

via the Monell Chemical Senses Center: Millet P., Martin, T., Opiekun, M., Beauchamp, G.K., and Kimball, B.A. (2021). Differing Alterations of Odor Volatiles among Pathogenic Stimuli. Chem. Senses. 46: bjab030.

'E-nose' could someday diagnose Parkinson's disease by 'smelling' skin
Feb 2022,
Three odor compounds (octanal, hexyl acetate and perillic aldehyde) were significantly different between the two groups, which they used to build a model for PD diagnosis.

Next, the researchers analyzed sebum from an additional 12 PD patients and 12 healthy controls, finding that the model had an accuracy of 70.8% in predicting PD. The model was 91.7% sensitive in identifying true PD patients, but its specificity was only 50%, indicating a high rate of false positives.

Sorry to say but those might not be false positives...we've seen this before (they haven't been diagnosed yet).

via Department of Biomedical Engineering, Zhejiang University, Hangzhou: Wei Fu et al, Artificial Intelligent Olfactory System for the Diagnosis of Parkinson's Disease, ACS Omega (2022). DOI: 10.1021/acsomega.1c05060

Study identifies brain areas that support social semantic accumulation
Feb 2021,

Olfaction is a social sense, and more reasons why we're bad at naming smells, because as somewhat social words, we think of them in sentences not in words...

via CAS Key Laboratory of Behavioral Science in China and University of Trento in Italy: The brain network in support of social semantic accumulation. Social Cognitive and Affective Neuroscience(2021). DOI: 10.1093/scan/nsab003.

Odd smell: Flies sniff ammonia in a way new to science
Jun 2021,

They probed all three types of scent neurons in the flies' sensilla, but they didn't respond to ammonia. But the fly was obviously smelling it, based on its behavior. So the researchers realized there had to be a fourth scent neuron they hadn't known was there. And they found it—but it didn't seem to have the usual odor receptors on it. It was covered in ammonia transporter (Amt), a molecule that is known to allow ammonia in and out of cells.

No one had ever known a transporter molecule to also act as an odor receptor. But there it was. When they selectively killed off only that type of neuron, the flies did not respond to ammonia at all. And when the team forced scent neurons that don't normally respond to ammonia to express Amt on their surfaces, those neurons began responding to ammonia, too.

via University of Connecticut: Alina Vulpe et al, An ammonium transporter is a non-canonical olfactory receptor for ammonia, Current Biology (2021). DOI: 10.1016/j.cub.2021.05.025

Scientists on the scent of flavor enhancement
Jul 2021,

On smelling -- The less they knew about the reference aroma, the higher their chances of correctly identifying a match—a finding that suggests aroma detection involves learning, memory and cognitive strategy.

via The Ohio State University: Mackenzie E. Hannum et al, Non-food odors and the duality of smell: Impact of odorant delivery pathway and labeling convention on olfactory perception, Physiology & Behavior (2021). DOI: 10.1016/j.physbeh.2021.113480

Image credit: Zebrafish Brains - Stephanie Fore - 2021

Smells and emotions tug on the brain's habenula, or 'little rein'
Aug 2021,

Situational awareness:
Kavli Institute researchers showed that the habenula relays information from the outside world, such as smell and sight, along with internal states associated with emotions and learning, to the brain regions that control adaptive behaviors.

"It turns out that the habenula is an information hub," said Emre Yaksi, a professor at NTNU's Kavli Institute for Systems Neuroscience and head of the research group that did the study. "It integrates information about odors from the environment with the information from the limbic system, which is involved in emotional behaviors and learning."

"We argue that the habenula helps the brain to stop certain actions and communications across brain regions, in order to shift it to another mode that is better suited to the situation that the scent warns of," he said. 

via Norwegian University of Science and Technology: Ewelina Magdalena Bartoszek et al, Ongoing habenular activity is driven by forebrain networks and modulated by olfactory stimuli, Current Biology (2021). DOI: 10.1016/j.cub.2021.08.021

Your sense of smell may be the key to a balanced diet
Aug 2021,

Long story short -- if you just ate a cinnamon bun, you're less likely to want a cinnamon bun, because something about your olfactory acclimation, adaptation, attenuation... 

via Northwestern University: Laura K. Shanahan et al, Olfactory perceptual decision-making is biased by motivational state, PLOS Biology (2021). DOI: 10.1371/journal.pbio.3001374

New research 'sniffs out' how associative memories are formed
Sep 2021,

Neuroscientists at the University of California, Irvine have discovered specific types of neurons within the memory center of the brain that are responsible for acquiring new associative memories. Additionally, they have discovered how these associative memory neurons are controlled. 

Specific cells in the lateral entorhinal cortex of the medial temporal lobe, called fan cells, are required for the acquisition of new associative memories and these cells are controlled by dopamine, a brain chemical known to be involved in our experience of pleasure or reward.

In the study, researchers used electrophysiological recordings and optogenetics to record and control activity from fan cells in mice as they learn to associate specific odors with rewards. This approach led researchers to discover that fan cells compute and represent the association of the two new unrelated items (odor and reward). Without these cells, pre-learned associations can be retrieved, but the new associations cannot be acquired. Additionally acquiring new associations also requires dopamine.

"We never expected that dopamine is involved in the memory circuit. However, when the evidence accumulated, it gradually became clear that dopamine is involved," said Igarashi. "These experiments were like a detective story for us, and we are excited about the results."

via University of California, Irvine: Lee, J.Y. et al. Dopamine facilitates associative memory encoding in the entorhinal cortex. Nature (2021).

A universal law of physiology emerges from a professor's research
Oct 2021,

"Imagine you walk into a room someone has just painted. You'll likely think, 'This smells bad.' But the sensation decreases as you stay in there. The molecules don't disappear, not within that time frame. You've just gotten used to it."
-University of Toronto Engineering professor Willy Wong 

From an initial state, the organism's response activity rises to a peak response, then falls to a new final steady state. Wong has discovered that those three fixed points on the adaptation curve form a mathematical relationship that is obeyed across all sensory modalities and organisms.

"I compared 250 measurements of adaptation from different branches of sensory physiology and found that they are all compatible with a single, simple equation," says Wong.

via University of Toronto: Willy Wong, Consilience in the Peripheral Sensory Adaptation Response, Frontiers in Human Neuroscience (2021). DOI: 10.3389/fnhum.2021.727551

Scent of newborn infants blocks aggression in men, stimulates aggression in women
Nov 2021,

Dr. Eva Mishor from Prof. Noam Sobel's research group at Weizmann's Brain Sciences Department and the Azrieli Institute for Human Brain Imaging and Research have found that a molecule that can likely be sensed by all mammals, and that is found in abundance on the scalps of newborns, sparks brain and behavioral changes in adults who are exposed to it, affecting women one way, and having the opposite effect on men.

The finding is among the first to provide a direct link between human behavior and a single molecule picked up through the sense of smell. Furthermore, the diametrically opposed change it effected in women and men sheds new and surprising light on the mediating role sex plays in olfactory perception and its resulting neurological processes.

They're talking about pheromones, which as far as we know, do not work in humans. Apparently that has changed now?

The odor is hexadecanal, or HEX, and although you can't smell it, if you sniff it, it will affect your behavior. We already know it affects mice, but humans not so much. Not until now that is. We also know, through less-scientific means, that the only universally-liked smell for all people everywhere is the baby's head. 

via Weizmann Institute of Science: Eva Mishor et al, Sniffing the human body volatile hexadecanal blocks aggression in men but triggers aggression in women, Science Advances (2021). DOI: 10.1126/sciadv.abg1530

Thursday, March 31, 2022

Skunk Notes

Why cannabis smells skunky
Dec 2021,

Finally, move over terpenes, the real smell of cannabis is here -- a new family of prenylated volatile sulfur compounds (VSCs), aka "skunk" is found in dank buds. 

Of the VSC varieties, 3-methyl-2-butene-1-thiol (VSC3) was the skunkiest. And of the 13 strains of cannabis tested, Bacio Gelato was the skunkiest.

via American Chemical Society: Iain W. H. Oswald et al, Identification of a New Family of Prenylated Volatile Sulfur Compounds in Cannabis Revealed by Comprehensive Two-Dimensional Gas Chromatography, ACS Omega (2021). DOI: 10.1021/acsomega.1c04196

Post Script:
Don't forget that dank smells does not mean potent pot, yet people associate citrusy-sweet-sour aroma with more THC:
Gilbert AN, DiVerdi JA (2018) Consumer perceptions of strain differences in Cannabis aroma. PLoS ONE 13(2): e0192247.

And, from a separate study, it was noticed that the genetic, terpinoid and cannabinoid profiles of selected strains didn't match their descriptions as either Sativa or Indica. Instead, it looks like people just name them whatever they smell like, sweet for Sativa and earthy for Indica:
S. Watts et al, Cannabis labelling is associated with genetic variation in terpene synthase genes, Nature Plants (2021) DOI: 10.1038/s41477-021-01003-y

Can't leave without this; why does natural gas smell somewhat skunky? It's been odorized on purpose since a big explosion that killed almost 300 people in the 1930's:
49 CFR, Part 192:Transportation of Natural and Other Gas by Pipeline: Minimum Federal Safety Standard, Subpart L: Operations, 192.625 - "Odorization of Gas"

Are Terpenes the New Antioxidants, 2018

Monday, March 28, 2022

Simulated Oversight

'Virtual nose' may reduce simulator sickness in video games
Purdue University News, Mar 2015  

Yes, you can relieve motion sickness in virtual reality by coding a nose overlay into the frame as a visual guide.

I sure didn't realize it until I read this, but you're looking at your nose all day; you're looking at it right now. Well, maybe you're not looking at it, but it's there. Maybe now you're looking at it, since we're talking about it. Anyway, it's there all day. If your eyes are open, your nose is in your field of vision. And when it's not, you're disoriented.

I'm pretty sure this is not what they mean when they say "right under your nose" or "right in front of your face," but it sure works in this case. Throw that onto the heaping pile of other things we don't notice about our nose or what it does for us. And add that to the other pile of things that we could improve if we looked to the nose and olfaction in general as a source of biomimetic supremacy.

via Purdue University: Whittinghill, D.M. et al. Nasum virtualis: A simple technique for reducing simulator sickness. In Proceedings of the Games Developers Conference (GDC), San Francisco, CA, USA, 2–6 March 2015; p. 74.

via University of Wuerzburg: A Virtual Nose as a Rest-Frame - The Impact on Simulator Sickness and Game Experience. Carolin Wienrich et al, 10th International Conference on Virtual Worlds and Games for Serious Applications, Sep 2018. DOI:10.1109/VS-Games.2018.8493408

via the BioComputing Lab at Korea University of Technology and Education: A Study on Visually Induced VR Reduction Method for Virtual Reality Sickness. Ju-hye Won and Yoon Sang Kim. Appl. Sci. 2021, 11(14), 6339;

Thursday, March 17, 2022

Flipping the Switch

The 'surprisingly simple' arithmetic of smell
Jan 2022,

The age of artificial olfaction is upon us.

This is now the second report in the last few months that presents a computational model for the olfactory bulb, which is the biological supercomputer on your face that crushes gigtons of databytes per attosecond (slight exaggeration).

The last paper came from a physicist working on information theory (Tavoni et al at Penn State). Another paper the month prior, which came from none other than the lab that discovered olfactory receptors, found, again, a computational model, discovered via machine learning, that compresses the n-dimensionality of odorant sensory data. 

But again, this new paper comes primarily from a department of electrical and systems engineering, in collaboration with the biomedical engineering department. I don't know everything that's going on, I only read the papers on the weekends, but that's a lot of papers about computing in olfaction, and from people who do not study olfaction exclusively.

And this is at the level of the bulb. We're not talking about the DREAM project, where big-data's worth of words and molecules are processed by GPT-3 to predict the names of smells. This is about looking at the hardware. How in the world does that bulb, which compresses thousands of receptors, themselves receiving information from un-countable stimuli, into dozens of signals that go on to control the entire enormity of a mammalian body via its limbic system. The bulb is the choke point for this system, and it's using magic that we are only now beginning to understand to the point of copying it. 

I doubt this is the earliest example, but as far back as 1991, scientists were talking about olfaction as a model system for computational neuroscience. These were neuroscientists and psychologists writing about this. But they could see the significance -- it's literally wired like the deep learning neural networks you hear about in the news (you know, powering the AI in your toaster, your tissue box and your alarm clock). 

It really looks like we're getting the hang of this. They started with a simple question -- how come things smell the same to us, even in different contexts or environments? Like how a plaid shirt looks okay in your sunlit bedroom, but later looks like a shit sandwich in the fluorescent lights of your office (or remember the black-and-gold dress? maybe you're trying to forget). 

If smells come from evaporating molecules, which are literally volatile, changing all the time based on environmental conditions, how come they always smell the same to us? Maybe olfaction would be a good model to investigate. 

So they did, by pairing locusts with a training smell, under all kinds of different conditions, hungry, full, hot, cold, humid, dry. Every time, the locust recognized the training smell (with the locust equivalent of a salivating dog). Yet, "The neural responses were highly variable," one of the researchers said. Same molecule, same response, but completely different receptor patterns, every time. It just doesn't make sense.

Deep learning to the rescue (obviously). The algorithm found that it's the interaction of activating and inhibiting neurons; I'll copy the copy directly:

Finding the features you want is similar to the information conveyed by the ON neurons. Absence of deal breakers is similar to silencing of the OFF neurons. As long as enough ON neurons that are typically activated by an odorant have fired—and most OFF neurons have not—it would be a safe bet to predict that the locust will open its palps in anticipation of a grassy treat.

via the Department of Electrical and Systems Engineering and the Department of Biomedical Engineering, Washington University in St. Louis: Srinath Nizampatnam et al, Invariant odor recognition with ON–OFF neural ensembles, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2023340118

And further reading:
via University of Pennsylvania: Gaia Tavoni et al, Cortical feedback and gating in odor discrimination and generalization, PLOS Computational Biology (2021). DOI: 10.1371/journal.pcbi.1009479

via Massachusetts Institute of Technology's McGovern Institute for Brain Research: Peter Y. Wang et al, Evolving the olfactory system with machine learning, Neuron (2021). DOI: 10.1016/j.neuron.2021.09.010.

via MIT: Davis J L & Eichenbaum H, eds. (1991). Olfaction: A Model System for Computational Neuroscience. Boston: Bradford Books/MIT Press.

Deep Nose, 2022
Signal to Noise for the Win, 2021
Olfatory Overload, 2021

Image credit: Inhibitory Synapse - TAO Changlu, LIU Yuntao, and BI Guoqiang; Image design: WANG Guoyan, MA Yanbing - 2021

Friday, March 11, 2022

Somatic Semantics

The above image was illustrated by Joe Scordo for Hidden Scents circa 2014, and based on the 1950's illustrations credited to Penfield and Rasmussen, which is need of an update, no?

Brain computer interface turns mental handwriting into text on screen
May 2021,

My rudimentary understanding of the brain says that the patterns coming from you head when you use any form of motor control would be much easier to see that patterns from simply visualizing letterforms. Something about the somatosensory cortex anatomical map.

For the first time, researchers have deciphered the brain activity associated with trying to write letters by hand. Working with a participant with paralysis who has sensors implanted in his brain, the team used an algorithm to identify letters as he attempted to write them. Then, the system displayed the text on a screen—in real time.

via Howard Hughes Medical Institute: High-performance brain-to-text communication via handwriting, Nature (2021). DOI: 10.1038/s41586-021-03506-2

Post Script:

'Rough' words feature a trill sound in languages around the globe
Jan 2022,

"They demonstrate a deep-rooted and widespread association between the sounds of speech and our sense of touch."" -Mark Dingemanse, Co-author and Associate Professor in Language and Communication at Radboud University

Also, kiki bouba.

via Radboud University, home of the Limbic Signal patron saint Asifa Majid: Bodo Winter et al, Trilled /r/ is associated with roughness, linking sound and touch across spoken languages, Scientific Reports (2022). DOI: 10.1038/s41598-021-04311-7

Why writing by hand makes kids smarter
Oct 2020,

"The use of pen and paper gives the brain more 'hooks' to hang your memories on. Writing by hand creates much more activity in the sensorimotor parts of the brain. A lot of senses are activated by pressing the pen on paper, seeing the letters you write and hearing the sound you make while writing. These sense experiences create contact between different parts of the brain and open the brain up for learning. We both learn better and remember better," says Van der Meer.

via Norwegian University of Science and Technology: Eva Ose Askvik et al. The Importance of Cursive Handwriting Over Typewriting for Learning in the Classroom: A High-Density EEG Study of 12-Year-Old Children and Young Adults, Frontiers in Psychology (2020). DOI: 10.3389/fpsyg.2020.01810


Mechanism behind loss of smell with COVID-19 revealed
Feb 2022,

  • For more than 12 percent of COVID-19 patients, olfactory dysfunction persists 
  • SARS-CoV-2, indirectly dials down the action of olfactory receptors
  • The new study may also shed light on the effects of COVID-19 on other types of brain cells, and on other lingering neurological effects of COVID-19 like "brain fog," headaches, and depression
  • Presence of the virus near nerve cells in olfactory tissue brought an inrushing of immune cells, microglia, T cells, and cytokines that changed the genetic activity of olfactory nerve cells
  • They used infected golden hamsters and olfactory tissue from 23 human autopsies [hamsters are more susceptible to nasal cavity infections]

Reminder of why it's such a big deal when you start messing with smell:
"Other work posted by these authors suggests that olfactory neurons are wired into sensitive brain regions, and that ongoing immune cell reactions in the nasal cavity could influence emotions, and the ability to think clearly (cognition), consistent with long COVID."

The talk on gene behavior and downregulation of receptor building is lost on me (not a geneticist, not a neurologist), but one of the main points I am reminded of when reading this is -- for those who experienced a change in taste or smell, for any reason, but especially after a COVID infection, long-term brain damage is possibly ongoing, but it's the kind to go undetected for another 20-30 years, depending on how old you are, of course. 

They also seem to suggest that this is an explanation for why people experience brain fog, and even emotional disturbance, all of which makes a lot of sense, because your sense of smell is connected to the all those brain areas -- the hippocampus for memory and the amygdala for emotion, both integral parts of the limbic system. 

via NYU Langone Health Department of Microbiology, NYU Grossman School of Medicine and Columbia University: Marianna Zazhytska et al, Non-cell autonomous disruption of nuclear architecture as a potential cause of COVID-19 induced anosmia, Cell (2022). DOI: 10.1016/j.cell.2022.01.024


Monell Anosmia Project - US Organization studying smell and taste

AbScent - UK Organization raising public awareness of smell loss

National Institute on Deafness and Other Communicable Disorders (NIDC) - Smell Disorders

ENT UK - Loss of Smell as Marker of Covid-19 Infection

Post Script:

Thursday, March 3, 2022

Organoids of the Nasal Persuasion

Model of the human nose reveals first steps of SARS-CoV-2 and RSV infection
Feb 2022,

I used to think it was a big deal that we knew how to grow diamonds in a laboratory. But then we started to grow organs. Intestines, kidneys, lungs,  brains (pictured above) and now noses.

They made a nose from scratch, using nose epithelial cells swabbed from somebody's nose, and placed on a substrate designed to enable them to interact as they normally would with the environment. (For this study, they were adding to that environment SARS-CoV-2 and RSV virions.) We could then call this an artificial nose, although that might be misleading. It's not full-blown olfaction, but it's a step. 

via Baylor College of Medicine: Anubama Rajan et al, The Human Nose Organoid Respiratory Virus Model: an Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics, mBio (2022). DOI: 10.1128/mbio.03511-21

Image credit: This is a human brain organoid, from the National Institutes of Health, circa 2021.

Wednesday, February 16, 2022

Deep Nose

Artificial networks learn to smell like the brain
Oct 2021,

We now have an artificial neural network that works like the nose. It's not an electronic nose; that's not the big deal part. 

What's important here is that, first of all, this is from the lab that brought us olfactory receptors. Next, these scientists didn't even model the network on evolution. They made an algorithm to solve an odor categorization task, and let the network run with it. Some might call that artificial evolution, but scientists will call it machine learning. After several iterations, the network found an optimized structure for solving this task -- the network ended up looking just like our olfactory system. Go figure.

The "brains" of a neural network lies in its ability to reduce the dimensionality of the information thereby optimizing computation. This is done using compression layers that learn to accept information from some neurons and not from others. After enough iterations, a pattern emerges between the layers of neurons.

Talking about this pattern, and the number of neurons connected to by each neuron on the compression layer:
"It could have been one, it could have been 50. It could have been anywhere in between," Yang says. "Biology finds six, and our network finds about six as well."

The first part of our nose where the hundreds of olfactory receptors collapse into far less neural nodes, one layer up the network, is very similar to the type of artificial neural network used in this study. It is, apparently now supported by these findings, a very effective way to condense a multi-dimensional information-space of chemical signals. Would it work for other information-spaces? What other Big Data can this deep nose model compute?

The side story: Evolution found this organization through random mutation and natural selection over eons; the artificial network found it through standard machine learning algorithms, in under one minute. 

via  Massachusetts Institute of Technology: Peter Y. Wang et al, Evolving the olfactory system with machine learning, Neuron (2021). DOI: 10.1016/j.neuron.2021.09.010

Image credit: Google's quantum computer, totally unrelated, just for looks

Post Script:
Neural network reveals new insights into how the brain functions
Dec 2021,

"The neural network model approach we have developed in this work presents an 'instruction manual' for other researchers to use to study other areas of the brain or other organs"
-co-author Dr. James Martin, co-author and professor of molecular physiology and biophysics at Baylor College
Their model is called Spatial Transcriptomics cell-types Assignment using Neural Networks (STANN).

via Baylor College of Medicine: Francisco Jose Grisanti Canozo et al, Cell-type modeling in spatial transcriptomics data elucidates spatially variable colocalization and communication between cell-types in mouse brain, Cell Systems (2021). DOI: 10.1016/j.cels.2021.09.004

I'm not certain about this, but I think the reason they chose the olfactory system is because they were looking at the interaction of transcription genes and brain cell types, and the olfactory receptor brain cells are the only one's that each get their own gene. So that would make the olfactory bulb an ideal nexus for investigation of this kind. See studies below for further reference:

Marei H.E.S. et. al. Gene expression profile of adult human olfactory bulb and embryonic neural stem cell suggests distinct signaling pathways and epigenetic control. PLoS One. 2012; 7: e33542.

Nagayama S. et. al.  Neuronal organization of olfactory bulb circuits. Front. Neural Circuits. 2014; 8: 98.

Social Deodorization

AKA Life Without Body Odor, Coming Soon

Life in the pits - Scientists identify the key enzyme behind body odor
Aug 2020,

We already knew the bacterium Staphylococcus hominis was the culprit, but these researchers have identified the specific enzyme (C-T lyase) in the bacteria that turns our odorless sweat into body odor, or what scientists call thiolalcohol. So now we can create a model of that enzyme, and figure out how to deactivate it. 

There's not enough science fiction out there looking at a society without body odor. Just kidding, this is already reality. And what happens is, the people who don't smell still use deodorant, because the people who do smell have just enough spending power to sustain a global corporate personal hygiene complex so powerful it can influence you to deodorize yourself even if you have no odor in the first place. 

If you're interested in this sort of thing, soft paywall to the New York Times about Unilever's attempts to sell deodorant in China, "a market with 2.6 billion armpits" (2018).

via University of York and Unilever: The molecular basis of thioalcohol production in human body odour, Scientific Reports (2020). DOI: 10.1038/s41598-020-68860-z

Post Script:
The smell of your breath is a subset of body odor. 
Research reveals details of how salivary glands collectively produce constellation of proteins found in saliva
Nov 2020,

What's in your saliva? Here you go. They don't tell you what it smells like, but with this info you'll be halfway there. Also, "oral biofluid" is science for saliva.

Also, in case you were wondering, "cysteine-rich secretory protein 3 (CRISP3) ... is expressed by human labial glands."

via University at Buffalo: Marie Saitou et al. Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Cell Reports Volume 33 Issue 7, 108402, Nov 17, 2020. DOI: 10.1016/j.celrep.2020.108402

Tuesday, February 1, 2022

You Don't Know What You're Missing

Attention and memory deficits persist for months after recovery from mild Covid
University of Oxford News, Jan 2022

"Although our Covid-19 survivors did not feel any more symptomatic at the time of testing, they showed degraded attention and memory."
-Dr Sijia Zhao of the Department of Experimental Psychology, University of Oxford
Repasted from above article:
All the participants had previously suffered from Covid-19 but were not significantly different from a control group at the time of testing on factors such as fatigue, forgetfulness, sleep patterns or anxiety.

But, they displayed significantly worse episodic memory and a greater decline in the ability to sustain attention over time than uninfected individuals for 6-9 months.

Note, the COVID-19 survivors in this study were young, mean age around 28, n=136.

How bad was it? Here is a measurements for context: Over the course of the 9-minute experiment, control participants’ accuracy dropped from 78.5% to 75.4%, whilst COVID survivors started with a similar baseline at 75.5%, reducing to 67.8% ... For a 30-minute memory test, COVID-19 survivors showed a significant memory decrement which was larger than in controls by 9.2%.

And to be specific: The larger episodic memory decrement amongst COVID-19 survivors was driven by errors in which the wrong orientation was chosen for a correct item. This difference suggests that the deficit in episodic memory in the COVID group might be associated with a deficit in binding information in memory. 

Interesting: word-memory tasks showed no change. 

How it might happen, if you're interested: One investigation of COVID-19 survivors demonstrated that the most severely cognitively affected patients demonstrated a degree of cognitive impairment accompanied by hypometabolism in the frontoparietal regions. These brain regions are implicated in sustained attention as well as in episodic memory. Reassuringly, the follow-up study of Hosp et al. showed slow but evident improvement after 6 months.

Last thing: The good news is that COVID-19 survivors performed well in most cognitive abilities tested, including working memory, executive function, planning and mental rotation. 

via University of Oxford: Rapid vigilance and episodic memory decrements in COVID-19 survivors. Zhao et al. Brain Communications. Jan 2022.

How Is This Related to Smell?
We already know that changes in our ability to smell were the primary symptom of the initial varieties of covid. Some of us still deal with these changes. But something we also know, regardless of any pandemic, is that smell is tightly linked to episodic memory -- "grandma's attic" or "first boyfriend's cologne" -- and a subset called autobiographical memory. These type of memories tie together people, places, feelings and smells into the olfactory cluster. Chemosensation enabled the first navigation, as primordial protists sniffed their way through the soup of early Earth. Chemosensation enabled the first social experience, when you detected your mother's immunity profile via her amniotic fluid. And chemosensation enabled your primate ancestors to remember where that really ripe fruit tree was. 

So it does seem appropriate that a virus attacking your olfactory neurons would also affect your episodic memory.

Image credit: Just astrocytes, upsplash

Post Script:
For those who haven't heard about this enough already, here's a good reminder of what Long Covid is: People who survive COVID-19 infection present a significantly higher risk of major neurological and psychiatric conditions, particularly if they were hospitalized. These include acute cerebrovascular events such as ischaemic stroke and intracerebral haemorrhage. In addition to severe neurological conditions, there can also be more chronic, longer-term consequences such as fatigue, low motivation, disturbed mood and poor sleep—all commonly reported symptoms amongst survivors, the so-called long-COVID (see recent review). -source