Saturday, January 9, 2021


AKA Regeneration of Olfactory Neurons and Combinatorial Perception in People Recovering from the Novel Coronavirus of 2019

This comes from a post-scripted entry to another post about the Tree of Heaven, to which I am pseudo-anosmic.

After some traumatic disturbance to your olfactory neurons, like from being attacked by a virus, you may experience changes in smell or taste. This is also called anosmia, partial anosmia, paraosmia, or phantosmia, the last referring to not a loss of smell but a change in the way things smell.

Phantosmia, like all phenomena in olfactory science, is not understood enough to say much from an evidenced-based point of view. I'm making a broad speculation here, not to explain, but to make someone interested enough that they will investigate further for themselves, and maybe even initiate more research into the topic.

The change in smell that comes from phantosmia is common, but its origins are often overlooked. It likely signals a change in the structure of neurons used to smell. These are the only part of your brain that pass the blood-brain barrier and rest outside your skull, in the mucous atop the epithelium skin way up in the top of your nostril canal (right where they swab that sample for your PCR test by the way, and not a coincidence). These neurons are thus both very vulnerable to damage, and able to regenerate indefinitely.

Combine this with another fact about olfaction -- it is combinatorial. That means when you smell "apple," there are a bunch of different receptors all lighting up in a pattern that means "apple." There is no Apple receptor, and no gene that codes our nose for Apple. For some there are, but for the most part, no. Olfaction is all gestalt. Take one piece out, and the entire picture gets weird as hell. Something's wrong but you can't tell what. So your brain misfires, it says "cigarette smoke" when it's really something else entirely. 

But after damage to your system, it is re-learning how to smell. Your nose-brain is a deep learning neural network that requires countless iterations to "learn" what a smell is. And while it's relearning after an infection, it gets confused.

In a very mild manner, and for reasons I will attribute to having been infected myself, my Tom Ford Italian Cypress lost its depth and presented as cinnamon and bubblegum, for about three days. If you've ever smelled Italian Cypress (and if not good luck it's discontinued since 2014), you would know that it does NOT smell like cinnamon and bubble gum. That's happened to me once before, and I will now assume it was because I was then also mildly infected with a virus. (Twice before actually, because the first time I ever smelled it, this is what I got, and why I didn't buy it; after almost a week the blotter revealed its powerful basenote, so I eventually gave it another try, and eventually I could smell the "whole thing," and then went and bought a bottle). 

And another thing -- when faced with new smells, we tend to call them bad. After repeated exposure, we can start to see them as good, but it's more likely we call new smells bad at first. Or at least "weird." So if your system is relearning how to smell, then lots of typical odor exposures will present as "bad" to you, simply by their being new, that is, new to your newly developing system. And all of the sudden, anything that doesn't compute properly on your new system could become "cigarette smoke," for example. Rotten meat is another good one for this, but it could be anything really (and it could also be really debilitating, just imagine.)

We also really suck at naming and describing bad smells. What does the Tree of Heaven smell like? How about a stink bug? Or go ask the folks at the South Coast Air Quality Management District about this. There's a direct correlation then, about the mental propensity for linguistically encoding sensory data, and combinatorially processing that raw data in the first place. Not only is it hard to "find the name" of a bad smell, it's actually hard to even "smell" it in the first place. 

Eventually, the system will recalibrate and relearn how to smell, and you'll be back to normal. But that doesn't always happen. Blunt trauma can kill those neurons forever. Really bad infections too. Sometimes it doesn't come back because you're not using it; like therapy after a stroke, it only comes back if you try really hard to use it.

And some of us, well, we're just getting older. Things don't work like they used to. And not only that, changes in smell can predict all kinds of neurological diseases decades in advance (Parkinson's, Alzheimer's, etc.).

But don't lose hope, I have apparently learned how to smell something new at 40 years old -- something I never had smelled before -- the Tree of Heaven. This may sound outrageous (it still does to me), but this massive revelation in olfactory research puts a lot of the details into that story. It comes from two different studies, one from Hebrew University and one from the Harvard Medical School, both of which are saying that there's two layers to olfactory perception, with the first layer of coding based on physicochemical properties of the odorant, and a second layer coded by your previous interactions with it. 

I'll repaste their description:
The general profile of excitatory vs. inhibitory responses by mitral cells changed with learning and task demands. In naive animals, most responsive cells (71%) responded by excitation to the odours. Following the learning of the 5-decision boundary task, the ratio of excitatory/inhibitory responses reversed. After learning, the majority (71.4%) of neurons now responded by inhibitory calcium transients to the odours (Fig. 6C,E). The ratio of inhibitory vs. excitatory responses reverted back to normal after retraining the mice on the 1-decision boundary task. Specifically, 73.3% of responsive neurons were again excitatory on day 18.

Hebrew University - Flexible Representations of Odour Categories in the Mouse Olfactory Bulb. Elena Kudryavitskaya, Eran Marom, David Pash, Adi Mizrahi. Hebrew University of Jerusalem. Mar 24 2020. BioRxiv. doi:

Harvard Medical School - Stan L. Pashkovski et al, Structure and flexibility in cortical representations of odor space, Nature (2020). DOI: 10.1038/s41586-020-2451-1

If you lost your sense of smell, or can't get it back, check out some of these links to get more info about it and what you can do:

How Covid-19 can damage the brain
June 2020, BBC Future

How COVID-19 causes smell loss
July 25,

Suggested mechanism for COVID-induced smell loss - David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia, Science Advances (2020). DOI: 10.1126/sciadv.abc5801

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

What Makes a Better Smeller?
Asifa Majid, Laura Speed, Ilja Croijmans, et al. Sage Pub., Jan 2017, volume 46 issue pp 406-430

This paper covers olfactory deficiencies and factors that make someone a better smeller, is based on neurodiversity and odor environment, and reviews how ambient odor or culinary traditions can influence odor perception.

There are at least three factors to consider as foundations of variation: our biological infrastructure, the experiences we navigate during our lifetime, and our physical and social environment (biology, experience, environment). Note the Japanese masters of koh-doóan, the ancient Japanese tradition of incense appreciation.

A few more recent sources of info on this topic:
Eric Song et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain, Journal of Experimental Medicine (2021). DOI: 10.1084/jem.20202135

David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia, Science Advances (2020). DOI: 10.1126/sciadv.abc5801

Trying to Make Sense of Long COVID Syndrome, Dr. Francis Collins. NIH Director's Blog, January 19th, 2021.
image source: Neural cells in a live mouse - Richard Roth and Richard Huganir