Tuesday, June 28, 2022

Navigating the Information Gradient

Olfaction is so primitive in its function, that it's an ideal model for all kinds of things,  including navigation, but even moreso, information processing. The olfactory system might be the most effective information processing system we know of, and it's something we've barely begun to investigate. 

Chemotaxis doesn't make headlines often, but it should, because it's ultimately an information-processing problem (and the last time I checked, we were living in the Information Age).

Image credit: A smellmap of Amsterdam by Kate McLean circa 2017 at sensorymaps.com

Information processing constrains how E. coli bacteria navigate chemical gradients
Jan 2022, phys.org

Information that E. coli bacteria gather from their environment limits their performance at chemotaxis, the process by which they guide their movements in response to chemical signals.

And it's funny that they decided to use chemotaxis to test this, about using information efficiently, so in other words, chemosensation is a good model for testing and understanding how information is processed, biomimetically, if you will.

And why do we care? Because chemotaxis and olfaction are the same, at a primitive level. Not much has changed between the way E. coli navigates its environment and the way we do it.

"We wanted to test a broad biological hypothesis: that organisms make the best use of the information they acquire to perform behaviors and other functions. To investigate this, we needed a behavior simple enough that we could quantify how much information it needed and chemotaxis by the bacterium E. coli is a perfect example of such a behavior."

We realized we could measure the amount of information a bacterium was able to gather (in bits per second), while also understanding how much information they would need to navigate at the speeds observed."

To achieve this, they first set out to calculate the theoretical performance limit, which is the maximum speed at which a bacterium could navigate up a chemical gradient, based on a fixed rate at which it acquires information about chemical signals.

Finding the response strategy that maximized gradient-climbing speed with a fixed information cost resulted in the performance limit.

"We found that while climbing shallow gradients E. coli get very little information from their environment, about 0.01 bits/s.

via Yale: H. H. Mattingly et al, Escherichia coli chemotaxis is information limited, Nature Physics (2021). DOI: 10.1038/s41567-021-01380-3

Understanding how bacteria seek out and move towards food
Feb 2022, phys.org

Chemotaxis is the process of attraction in the direction of a chemical gradient. The primary way that organisms control their motion and progressively move toward a target is by inhibiting tumbling when sensing that the chemical concentration is increasing along their current direction.

The research team used stochastic optimal control theory (instead of linear control theory) to find the best possible fully nonlinear sensing and control strategy of run-and-tumble motion (of E. coli) in environments with noisy chemical gradients.

And it looks like chemotaxis, which is the progenitor of olfaction. It is not a stretch to say that olfaction is a form of chemotaxis, and we move through a room to locate a source by using the pattern of its vaporized chemical essence in the air in the room. We calculate its distribution pattern (by stochastic optimal control theory, apparently^), predict the source, and move towards it, updating as we go. The only difference here is that we use legs, and a pretty complex limbic system, whereas E. coli just tumbles and tumbles in the chemovoid. 

via University of Tokyo Institute of Industrial Science: Kento Nakamura et al, Optimal sensing and control of run-and-tumble chemotaxis, Physical Review Research (2022). DOI: 10.1103/PhysRevResearch.4.013120

Odour-Spatial Map - Diogo Matias - Champalimaud Foundation - 2021 [link]

Neurons in the olfactory cortex link smells to places
Feb 2022, phys.org

Sometimes it's good to have someone else say things like this, for a change: 

The researchers focused on the primary olfactory cortex. "The olfactory system is unique among the senses," said the study's senior author, Zachary Mainen, a principal investigator at the Champalimaud Centre for the Unknown in Portugal. "Only olfaction has direct reciprocal connections to the hippocampal system, which is involved in memory and navigation."

It looks like neurons in the posterior piriform cortex (part of the primary olfactory cortex) are encoding place information just like hippocampal cells, and especially behaviourally significant spots. So it's real -- smells are not just smells, they are places and smells at the same time; we can't extricate them from each other, at least not for some brain cells.  

via Champalimaud Centre for the Unknown: Cindy Poo, Spatial maps in piriform cortex during olfactory navigation, Nature (2021). DOI: 10.1038/s41586-021-04242-3

Post Script:
How the brain navigates cities: We seem to be wired to calculate not the shortest path but the 'pointiest' one
Oct 2021, phys.org

When people navigate through a city, they use not shortest path, but instead, pedestrians appear to choose paths that seem to point most directly toward their destination, even if those routes end up being longer, and this is called vector-based navigation.

via  Massachusetts Institute of Technology: Paolo Santi, Vector-based pedestrian navigation in cities, Nature Computational Science (2021). DOI: 10.1038/s43588-021-00130-y

Thursday, June 23, 2022

The Smell of Fear

Protecting gardens and crops from insects using the 'smell of fear'
Aug 2021, phys.org

They're using methoxypyrazines, such as isopropyl methoxypyrazine, isobutyl methoxypyrazine and sec-butyl methoxypyrazine. Methoxypyrazines smell like "green, herbaceous, vegetative, green peppers, freshly cut grass, and asparagus." 

But for aphids, methoxypyrazines smell like ladybugs. Aphids hate ladybugs. And farmers hate aphids. 

On a related note, the smell of cut grass is a defense mechanism for grass to tell other grass that it's being attacked, and to "brace yourselves." The next time you smell it, you can think of the sound of grass screaming.  

via American Chemical Society: Smell of fear: Harnessing predatory insect odor cues as a pest management tool for herbivorous insects, ACS Fall 2021.

Tuesday, June 21, 2022


This story keeps getting crazier the further you read. 

Woman with no left temporal lobe developed a language network in the right side of her brain
Apr 2022, phys.org

A woman without a left temporal lobe developed a language network in the right side of her brain that allowed her to communicate normally. She only came to realize she had an unusual brain by accident—her brain was scanned in 1987 for an unrelated reason. 

By all accounts she behaved normally, earning an advanced degree and excelling in languages—she speaks fluent Russian—which is all the more surprising considering the left temporal lobe is the part of the brain most often associated with language processing.

It was likely the woman had lost her left temporal lobe as a child, probably due to a stroke. The area where it had been had become filled with cerebrospinal fluid. To compensate, her brain had developed a language network in the right side of her brain that allowed her to communicate normally.

She also had a sister who was missing her right temporal lobe, and who also had no symptoms of brain dysfunction—an indication, the researchers suggest, that there is a genetic component to the stroke and recovery process in the two women.

via MIT, Carnegie Mellon University, UCLA and Harvard: Greta Tuckute et al, Frontal language areas do not emerge in the absence of temporal language areas: A case study of an individual born without a left temporal lobe, Neuropsychologia (2022). DOI: 10.1016/j.neuropsychologia.2022.108184

See this similar study on smell:
Left-handed women can have normal olfaction without apparent olfactory bulbs, and scientists are very confused.

via the Weizmann Institute: Human Olfaction without Apparent Olfactory Bulbs. Tali Weiss, Noam Sobel, et al. Neuron, volume 105,  issue 1, page 35-45.E5, Jan 2020. DOI:https://doi.org/10.1016/j.neuron.2019.10.006

Thursday, June 16, 2022

Word Avoidance

Did you just say what I think you said?

No, because this tree actually smells like semen, but nobody will ever say that out loud, or in print, so instead they call it rotting fish.

Tree that smells like rotting fish is so invasive states are offering bounties to kill it
Dec 2021, Bangor Daily News

And they're talking about the Bradford pear tree, which sucks as a tree, and is a great example of how good marketing can destroy the planet (or at least your charming downtown neighborhood).

Somebody was really successful circa the 1990's at selling these trees to urban planners looking to revitalize their downtowns with nice shade trees that have infrastructure-friendly root structures and "they even bloom pretty white flowers!" (that smell like a handful of hot semen for a couple weeks out of the year). The problem is that they only live about 30 years, they're brittle so their limbs break off easily, they're invasive so they make the soil inhospitable to other plants, and they multiply ferociously when you try to cut them down. Also their flowers smell like semen when they bloom, but nobody will tell you that, because nobody wants to say out loud that anything smells like semen. In fact, if you, for example, were anosmic to semen, you might go your entire life without knowing, because nobody ever talks about it. 

The Victorians would have called it "a man smell."

Post Script:
Also see the Tree of Heaven (Ailanthus altissima), which is another invasive and foul-smelling tree.

Monday, June 13, 2022

On Hedonic Consultation

AKA The Evolution of the Autobiographical Odor Encyclopedia 

This study copied below measures how fast we detect good smells vs bad smells (spoiler, bad smells are detected faster). 

But while reading through this, consider that bad smells can become good over a series of exposures matched with good feelings. Aged cheese, fermented cabbage, and burned cannabis are pretty well known examples of this. There's also people, who smell, each with our own odor fingerprint, although we may not realize it at times, as it might be below our limit of detection.

And then there's the reverse, where things (or people) that once smelled good, all of the sudden smell bad, such as with changes in birth control, or pregnancy, or after a viral infection like Covid (see the parosmia triggers study). In those cases, the whole olfactory system is rewritten, a kind of blank slate re-learning, where smells with strong odor components (like individually unique body odors, or coffee) are perceived as if for the first time, with the bad stuff up front. And all you can focus on is the bad, since you have to "re-learn" the smell, and how the good integrates with the bad to produce something that is neither good, nor bad, nor even identifiable by semantic description, but only by the name of the person. 

Nonetheless, there seem to be some good millisecond metrics here:

Seeing how odor is processed in the brain
Jun 2022, phys.org

  • Detection occurred before the odor was consciously perceived by the participant
  • Odor information in the brain is unrelated to perception during the early stages of being processed
  • Later, unpleasant odors were processed more quickly than pleasant odors

The participants wore an EEG cap while having smells shot at their face, and so that researchers could see when and where odors are processed in the brain.

"We were surprised that we could detect signals from presented odors from very early EEG responses, as quickly as 100 milliseconds after odor onset, suggesting that representation of odor information in the brain occurs rapidly"

Remember that the olfactory system has only a few synapse-steps, making it the most direct sensory system we have.

And then watch how they pretty much rehearse Proust's deep cookie immersion:

When unpleasant odors (such as rotten and rancid smells) were administered, participants' brains could differentiate them from neutral or pleasant odors as early as 300 milliseconds after onset. However, representation of pleasant odors (such as floral and fruity smells) in the brain didn't occur until 500 milliseconds onwards, around the same time as when the quality of the odor was also represented. From 600–850 milliseconds after odor onset, significant areas of the brain involved in emotional, semantic (language) and memory processing then became most involved.

via University of Tokyo: Mugihiko Kato et al, Spatiotemporal dynamics of odor representations in the human brain revealed by EEG decoding, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.211496611

Post Script:
Professor Robert Sapolsky Stanford Lecture - On Recognizing Relatives (with smell)

Learning to Smell: Olfactory Perception from Neurobiology to Behavior, by Donald Alan Wilson and Richard J. Stevenson, Johns Hopkins University Press (2006)

Thursday, June 9, 2022

Covid's Parosmia Uncovered

Covid has a smell. Not that you can smell sick people, although you can actually. Dogs have proven that it's possible; only that humans have never been trained, and for obvious reasons.

Instead, we mean that things "smell like Covid." That's because everyone who got pre-Omicron Covid also got hit with a neuroplastic time bomb where their olfactory neurons got attacked and then reconfigured. Half the people who got Covid, and its anosmic introduction, knew they had it, and the other half didn't. (This according to a May 2022 study, linked here, and repasted below.)

Lost of people would argue with that stat. And I would have to argue back. The absolute worst source of data for testing anosmia etc is the subjective reporting of the people themselves. We don't even know we have a sense of smell in the first place, nevermind detecting that it's been removed. There are congential anosmics (can't smell from birth) who don't realize they're anosmic until they're teenagers! How do you not realize that? Because we don't talk about smells. They're outright lingua-phobic. And so when we lose it, especially in the midst of a respiratory infection that messes with our breathing, we don't even notice. We also think it's our sense of taste, so when someone asks "have you experienced any change in your sense of smell," you say no, but I did lose my sense of taste. In that study, they used Sniffin' Sticks, so an objective measure, and so they got the 100% stat. 

Next, things "smell like Covid" because after a bout of anosmia, your olfactory system needs to reboot, retrain, pick your computer analogy, and in the process, there's some bugs in the code. Eggs smell like Covid, coffee smells like Covid. Shit? Smells like biscuits. Wait, what? Yes, the Faeces Paradox, see below, it's all been explained for us. Thanks, Flavor Center at University of Reading:

Researchers find cause of disordered smell
May 2022, phys.org

Among the 29 volunteers with post-viral parosmia, scientists found 15 commonly identified compounds that triggered parosmia. They also found reduced sensitivity in some people, via lower TDI scores from Sniffin’ Sticks, although some who were considered functionally anosmic could still detect some of the trigger smells...

Some of the most cited food and drinks that set off parosmia in sufferers include:
  • Coffee
  • Onions
  • Garlic
  • Chicken
  • Green peppers

The most common trigger molecules are grouped into four distinct categories based on structure: 
  • thiols
  • trisubstituted pyrazines
  • methoxypyrazines
  • disulfides
  • (and as always with smell-things: some less common triggers did not fall into any one of these categories)
  • (these molecules tend to be potent, have very low olfactory detection thresholds and, in isolation, are neither distorted nor unpleasant for nonparosmics)

Trigger Molecules and their Parosmic Descriptions:
  • 2-furanmethanethiol ("coffee") is the most frequently reported trigger. Whereas NONPAR (non-parasmics) used a range of food-related terms to describe it (coffee, roasty, popcorn, smoky), PAR (parosmics) often struggled to find suitable descriptors, as they were unable to relate it to anything they had smelled before. PAR typically used words describing its hedonic quality (disgusting, repulsive, and dirty) or new coffee (relating to the altered smell of coffee since onset of parosmia) as described previously. Four PAR described it in the same way as NONPAR (biscuit, toasty or roasty) indicating that it is not universally parosmic, but certainly an important and frequent molecular trigger of parosmia.
  • 2-methyl-3-furanthiol and its corresponding methyl disulfide  ("meaty") were detected but reported less frequently as distorted. 
  • 2-Ethyl-3,6-dimethylpyrazine (also "coffee") was the second most frequent trigger in coffee; described with a variety of food terms by NONPAR, but by “new coffee”, “unpleasant” and “distorted” by PAR.
  • 2,3-diethyl-5-methylpyrazine, 2-ethyl-3,5-dimethylpyrazine and trimethylpyrazine (found in roasted, fried and baked goods) were common triggers. These compounds also triggered a parosmic response to cocoa, grilled chicken, and peanut butter
  • 2-Ethyl-3-methoxypyrazine, 2-isobutyl-3-methoxypyrazine and 2-isopropyl-3-methoxyprazine (green peppers) were common triggers in coffee.
  • 3-methyl-2-butene-1-thiol (pungent and weedy) was reported as a trigger 9/29 times.
  • 3-mercapto-3-methylbutanol and its formyl ester are potent aroma compounds in coffee, and were detected in half the cases, but only reported as distorted 5 or 6 times.

  • The unknown compound has been tentatively identified as 4-methylthio-4-methyl-pentan-2-one, but this is yet unconfirmed. (What the heck is "the unknown compound?)
  • Although thiols and disulfides seem to effectively trigger a parosmic response, there are two notable exceptions.
  • Methanethiol, detected by some NONPAR, was not detected by any PAR. Likewise, dimethyl trisulfide is detected by 12/15 NONPAR but only by 4 PAR, and only reported once as a trigger.
  • A few compounds were detected but never reported as triggers.
  • 4-Ethylguaiacol was detected by 7 PAR and always described as spicy, sweet and smoky, but never parosmic.
  • Similarly, (E)-β-Damascenone, a key odour-active compounds in coffee, was detected by 6 PAR and always described as jammy and fruity.

The Faeces Paradox
  • Foods smell of faeces yet faeces smell of food (biscuity or pleasant)
  • Two parosmic researchers did not detect these compounds in a faecal slurry and were unaware of any foul smells.
  • However, they detected several other compounds, many of which they had also detected in coffee, and only some of which triggered parosmia.
  • In comparison, a normosmic scored the intensity of indole and skatole as close to the strongest imaginable. 
  • This provides a neat explanation as to why the changes in valence for faecal samples is reversed. 

How did they do it?
They GCMSd different sources, like coffee or onions, so that the individual molecules could be separated and presented one-at-a-time to the volunteers, so they could detect the specific molecules in the source that repulses them.

Why did they do it?
Prior to the global pandemic caused by COVID-19, parosmia was a rare condition known to occur after infections such as cold, flu or sinus infections, with very little awareness about the causes and treatments for the disease.

During the pandemic COVID-19 symptoms included loss of smell and taste in 50–60% of cases, of which about 10% developed parosmia. Since the omicron variant, loss of smell and taste has become a less common symptom (estimated to occur in about 10–20% of cases) and parosmia cases are likely to be fewer in number, parosmia is still estimated to affect 2 million people in Europe.
Not exactly. See below.

via the Flavor Center at University of Reading: Jane K. Parker et al, Insights into the molecular triggers of parosmia based on gas chromatography olfactometry, Communications Medicine (2022). DOI: 10.1038/s43856-022-00112-9

Study finds sensory loss in ~100% of active COVID infections, which is twice as high as self-reports
May 2022, phys.org

In participants with active infections during the delta surge, a majority (22 of 25) had been vaccinated. Objective screenings found that 100% were experiencing a diminished or lost sense of smell—but only 54.5% self-reported any problem with odor detection.

via Ohio State University: Kym Man et al, Chemosensory losses in past and active likely Delta variant break-through COVID-19 cases, Med (2022). DOI: 10.1016/j.medj.2022.05.004

Image credit: Free Photos at img freepic dot com [link]

Post Script:
Can 'smell' trigger tumors?
May 2022, phys.org
"Now that glioma preferentially emerges in the OB, will neuronal activity in the olfactory circuit affect the emergence of glioma?" the researchers wondered. This "mind-blowing" flash of inspiration became a turning point in this study. The research team attested to this hypothesis through a series of experiments.

In this study, they employed a cutting-edge chemogenetic technology to specifically manipulate the neuronal excitability of ORNs. They found that inhibiting the activity of ORNs reduced the size of the tumor significantly, whereas activating their activity increased the size of the tumor. It was therefore concluded that the neuronal excitability of ORNs was the root of gliomagenesis.

To further verify this conclusion, the researchers suppressed olfactory inputs through naris occlusion by using small plugs. They found that with naris occlusion, tumors were significantly hindered in the olfactory bulb, indicating that olfactory stimuli could regulate gliomagenesis.

via Zhejiang University: Pengxiang Chen et al, Olfactory sensory experience regulates gliomagenesis via neuronal IGF1, Nature (2022). DOI: 10.1038/s41586-022-04719-9

Post Post Script:
Clinical trial led by Thomas Jefferson University Hospital paves the way for innovative topical treatment
Mar 2022, Jefferson Hospital

Platelet-rich plasma (PRP) is a common restorative therapy used to regenerate cells, heal tissue, and address an array of medical conditions from healing injured muscles and tendons to increasing hair growth and reducing the appearance of scars. Animal studies have shown that PRP helps regenerate the olfactory epithelium, which may be the site affected in COVID-19 induced olfactory dysfunction (OD). As smell and taste are closely interrelated, improved sense of smell can help with sense of taste as well. Until now, PRP has been used as a nasal injectable in several small clinical trials for smell loss. Although the results were promising, nasal injections can be uncomfortable and invasive for patients.

A recent phase I clinical trial of eight patients who had at least six months of olfactory disturbance has shown preliminary success with 50 percent of participants (4 people) experiencing clinically significant improvements in smell and taste.

Autopsies suggest COVID’s smell loss is caused by inflammation, not virus
Apr 2022, Ars Technica

via Johns Hopkins: Ho C, Salimian M, Hegert J, et al. Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19. JAMA Neurol. Published online April 11, 2022. doi:10.1001/jamaneurol.2022.0154

Monday, June 6, 2022

Consistently Inconsistent

What's in your weed? You might be surprised
May 2022, phys.org

  • 90,000 samples across six states
  • Leafly database of chemical analyses compiled from cannabis testing centers
  • Largest analysis to date of the chemical composition of marijuana products
  • Commercial labels "do not consistently align with the observed chemical diversity"

"Our findings suggest that the prevailing labeling system is not an effective or safe way to provide information about these products," said co-author Brian Keegan, an assistant professor of Information Science at CU Boulder. "This is a real challenge for an industry that is trying to professionalize itself."

"A farmer can't just pick up an apple and decide to call it a Red Delicious. A beer manufacturer can't just arbitrarily label their product a Double IPA. There are standards. But that is not the case for the cannabis industry," said co-author Nick Jikomes, director of science and innovation for the e-commerce cannabis marketplace Leafly.com.

Products do tend to fall into three distinct categories:
  • high in the terpenes caryophyllene and limonene
  • high in myrcene and pinene
  • high in terpinolene and myrcene
  • (similar to Avery Gilbert's study; Citrus vs Earthy)
  • (but those categories do not neatly correspond to the indica, sativa and hybrid labeling scheme)

Some strains, such as one called White Tahoe Cookies, were surprisingly consistent from product to product, while others, such as one called Durbin Poison, were "consistently inconsistent," said Jikomes.

"There was actually more consistency among strains than I had expected," he said. "That tells me that the cultivators, at least in some cases, may not be getting enough credit."

via University of Colorado at Boulder: Christiana J. Smith et al, The phytochemical diversity of commercial Cannabis in the United States, PLOS ONE (2022). DOI: 10.1371/journal.pone.0267498

Thursday, June 2, 2022

Scientists Make Discovery

Olfactory neurons adapt to the surrounding environment
May 2022, phys.org

This title could have had way more clickbait. The news is that we have no idea what's going on with olfactory neurons. 

Not like it's ever been claimed; they just never seem to obey any sensical laws, and they're always doing things we can't understand, but now it seems that even basic assumptions about how they work are way off.

The scientists discovered an unsuspected variability in gene expression profiles depending on the expressed olfactory receptor and previous exposure to odors. 

And in a previous study, these scientists found that after stimulation of a receptor by an odorant molecule for less than an hour, the expression of the gene coding for this receptor decreased in the neuron, indicating a very rapid adaptation mechanism.

"While it was thought that the binding of an odorant molecule would only lead to the activation of the corresponding receptor, we discover that olfactory neurons drastically change their identity by modulating the expression of hundreds of genes after activation. And this new identity is again dependent on the expressed receptor. We are facing an unexpected, massive, rapid and reversible adaptation mechanism," explains Ivan Rodriguez, co-corresponding author of the study.

This work reveals that olfactory neurons are not to be considered as sensors simply passing from a resting state to a stimulated state, but that their identity is in permanent evolution, not only according to the expressed receptor but also according to past experiences. This discovery adds another level to the complexity and flexibility of the olfactory system. 

via Faculty of Science and the Faculty of Medicine of the University of Geneva: Luis Flores Horgue et al, Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity, Nature Communications (2022). DOI: 10.1038/s41467-022-30511-4

Image credit: Unexpected Outcome, by shironosov and Getty, 2022 - Three shocked scientists looking at the obtained substance expressing intense emotions [link]

Post Script:
Consider that the olfactory family of genes is evolving within us in real time. It's a huge group of genes, being the largest family there is, at 2% of the genome, and it's highly variable in the population, with a 30% variation from person to person. 

Do you remember that item we learned back when the Human Genome project came out, that we share over 90% of our genome with monkeys, and almost as much with bananas? Now consider that our individual olfactory apparatus is 30% different from that of other humans. There's a lot of action here in the olfactory system.

Just wait until we figure out that it's running our immune system, because that's when things will get really crazy.