#156 - Smell and Memory

0:02Hi everyone, it's Matt and welcome back to the podcast. Today, we'll look at how one particular sense reaches into your past in a way the others don't. We'll start with a glass jar without a label that sits on the back shelf of a spice rack. We'll open it, smell what's inside, and immediately recognize it. But then when you try to name it, that's when you'll likely struggle. That's because it's incredibly hard to identify familiar scent, even if your sense of smell is intact, and even if you can name objects you see without any trouble. And not only do you struggle with the name of a familiar scent, but often a memory comes to mind instead, frequently a long-forgotten one.

0:44In psychology, this effect is known as the Proust phenomenon. Researchers who set out to test it noted that support for the idea had mostly relied on anecdotal sources, and a later review of the field described scientific interest in it as sporadic. So let's ask our question, why does a scent go back further than a photo? The first clue is that one sensory system bypasses a stage in which all the others participate. Imagine the brain is a hotel, and all guests must pass through the lobby before entering the hallways. Sighted people walk through the lobby, as do those who hear and feel. Smell has a secret back entrance, with a staircase that leads to a hallway outside a storage room containing your memories.

1:34It may seem like a strange image, but the physical layout of the brain matches it surprisingly well. For the senses of sight, hearing, and touch, the lobby is the thalamus. It is the main source of sensory information for the brain's primary sensory cortices. Smell bypasses this lobby. The sensory neurons in the nose transmit signals to the olfactory bulb, which sends them directly to the primary olfactory cortex. This region includes the piriform cortex, part of the amygdala, and the lateral entorhinal cortex. Within one or two steps, the information arriving in your nose has reached regions involved in processing emotion, in processing reward and decision making, and in processing memories of the events in your life.

2:24When subjects are placed in an MRI scanner and instructed to simply lie still, we can examine which areas exhibit synchronized changes during rest. One study conducted this analysis for all four senses simultaneously within the same subjects. Smell, touch, vision, and hearing. In each case, the primary sensory area was contrasted with the hippocampus. This was a small sample of 25 healthy participants. During rest, the primary olfactory cortex showed greater connectivity with hippocampal circuits than the other sensory cortices did. The authors offer an evolutionary explanation, and suggest is their word for it.

3:07During the expansion of the primate brain, the hippocampus' functional networks shifted away from primary sensory areas and towards association areas, a shift observed in vision, hearing, and touch. The olfactory cortex appears to have remained largely unchanged across mammalian evolution, and the findings imply that this connection with the hippocampus may have persisted, while the other modalities underwent structural relocation. Back in the hotel, there was a remodeling in which every other department relocated to the upper floors, but the smell department retained its original workspace near the archives.

3:47When the olfactory cortex encounters a scent, it constructs an object from it. It extracts the physical and chemical properties of the molecules and converts them into an object, complete with associations and with a pleasantness or unpleasantness attached. If you scan people with FMRI as they sniff a range of odors, the pattern of activity in the posterior piriform cortex corresponds to the way they rate each odor. Two odors that generate similar patterns will be rated by people as similar. Two odors that generate dissimilar patterns will be rated as more different. The same relationship doesn't appear in the anterior piriform cortex, the amygdala, or the orbitofrontal cortex.

4:34It's in a specific region of the brain, in short, where a smell becomes a recognizable thing. This makes the blockage, when you can't name an object but remember it, we sometimes experience all the more mystifying. If we think of the pathway from odour to verbalization as a conveyor belt with three checkpoints, we can see why this happens. One checkpoint is for perceiving, one connects it to meaning and vocabulary, and one for the verbalization of the word itself. When you combine the behavioral data with the imaging results, the losses at each of the three checkpoints add up. And by the third checkpoint, the signal has thinned out.

5:15The scientists who designed this model titled their paper The Muted Sense. But losing the label doesn't just cost us the name of an object. A name is like a draw handle. Without it, the draw is still there, but you cannot draw it open when you need to. When you ask subjects to call up a smell in their imagination, the odors that are hardest to name are those they find hardest to imagine. When you train subjects to name a set of odors, then ask them to imagine these smells. Their ratings show that they find many of those odors easier to imagine than the subjects who simply smelled the odors or were only told the names of the odors or received no training at all.

5:58The authors are careful to point out that labeling might explain only some of the difficulty in recalling an odor. The drawer matters all the same. Which brings me to the one experiment I'd like you to keep in mind. Imagine that a memory is a room with two entrances. You can enter through the door marked word or the door marked smell. Does it matter which entrance you choose? Identify people who have a specific memory triggered by a specific smell, then scan their brains while cueing that same memory with the smell and separately with the name of that smell. Same people, same memory. Except through the doorway marked smell, there was greater activity in the medial temporal lobe regions, including the parahippocampal gyrus and regions associated with visual vividness.

6:54And there was significantly greater activity in the emotional centers of the brain, the limbic system and the temporal pole. With the word door, however, the brain activated a broader area spanning both hemispheres of the prefrontal cortex. Two additional findings worth mentioning at this junction. First, the activation in the hippocampus did not depend on the recency of the remembered event. Second, when a memory was triggered by the word alone. Without any odor being presented, the brain's olfactory regions lit up. The word alone stimulated the smell system. An extensive review of this entire field frames findings such as these within a broader context.

7:39Odors trigger memories in different ways than words, pictures, or sounds do. The same memory has two ways of getting in, and they aren't interchangeable.

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9:31So how does a smell end up having a specific meaning for our brains? The meaning of an odor is acquired and the learning of it leaves a mark in the cortex. One experiment used molecules that come in mirror image pairs. Imagine two radio stations broadcasting so close together on the dial that you can't distinguish between them. In the study, participants were given a pair of mirror image molecules they could not distinguish. Then one member of the pair was paired with something unpleasant. Subsequently, the same participants could tell the two apart, and the activity patterns in the piriform cortex produced by the two odors moved apart in parallel with that change.

10:15Learning had retuned the dial. Fear learning is usually described as teaching you how to respond to a cue. Here, it also changed how the cue itself was perceived. A later review builds this into a model in which the brain's smell cortex stores learned threat codes formed through unpleasant experience alongside the better known learning related changes in the amygdala. Experience, in other words, gets written into how things smell. People themselves have smells as well, and not just the kind that is emitted after a workout with no deodorant. Consider 75 mothers of babies up to 12 months of age.

10:5825 mothers were enrolled from a day hospital unit specializing in problems with mother-infant attachment, and 50 mothers were healthy controls of the same age. Each baby's body odor was sampled from a worn onesie under a standardized protocol, and each mother then evaluated her baby's sample and those of two other babies without being told which was which. The healthy mothers strongly preferred the scent of their own infant. The mothers with attachment problems did not. Moreover, within the sample, the greater the extent of the attachment problem a mother reported, the less her preference for her own baby's scent.

11:38Mothers with attachment problems also failed to identify their own baby's odor above chance, whereas the healthy mothers did. The authors offer an explanation. They assume that the reduced body contact and interaction time that come with bonding difficulties mean less exposure to the baby's odor and so less recognition of it. But the design cannot show that. the measures the authors report are odor ratings, smell tests, and a bonding questionnaire, not time spent in contact. So the link between contact and familiarity is an assumption, not a finding. More importantly, the two groups did not differ in their ability to detect odors in general.

12:22The difference was in the association of one particular odor to one particular individual. Something similar comes out of work on infants. This experiment starts from the idea that infant vision changes rapidly after birth and that an early maturing sense, smell, might stabilize this development. So 18 four-month-olds were shown a rapid stream of natural images with human faces appearing among animals, plants, and man-made objects as their brain activity was monitored. Each infant was tested under both conditions in the same session, alternating between a t-shirt carrying their mother's body odor resting on their chest and a clean, unworn t-shirt.

13:09When the infants could smell their mother, the brain response that singles out faces from the other images was enhanced compared to the control odor. The overall neural response to all images, faces, and objects didn't change between the two odors, ruling out a general increase in arousal or attention. By four months of age, infants use odor to process their visual environment. Odor also helps to cue episodic memories. In one study, participants were shown words one by one and asked to call out whatever words each one brought to mind. Without being told it mattered, they were simultaneously exposed to a particular smell.

13:50Five minutes later, they took a surprise memory test in which the original smell or a new smell was present. A wrinkle in this procedure is that a constant odor becomes less salient over time, much like the sound of your refrigerator. So the researchers introduced a fix, a brief exposure to a different odor at the start of the retention interval, after studying and before the test to reset the nose after this sensory adaptation. Bringing back the original smell at test helped free recall of the words. At the faster study pace, it did so even without the fix. At the slower pace, the effect appeared once the fix was in place.

14:34A common concern is that smell-induced memories may make everything feel familiar. For instance, if a participant studies a list of sleep-related words while a smell is in the room, bringing the smell back might make them remember the word sleep, even though it was never on the list. To investigate this, participants studied lists of semantically related words, like the kind just described, in the presence of a specific odor. At the memory test, the study odor was either brought back or not. When the study odor was present again at test, participants recalled more of the words they had actually seen, but they were no more likely to falsely recall the related words that had never been presented.

15:21These results suggest that odors specifically activate previously experienced memories. So how does smell trigger that memory from all those years ago. If you imagined your memories as photographs in an album, the pages would be at their thickest in adolescence and early adulthood, at least if words, pictures, or sounds were doing the prompting. This is called the reminiscence bump. But smell opens the album at a completely different point. In a study, researchers recruited 93 older adults and gave each of them one type of cue, a word, a picture, or a smell. They asked for an autobiographical memory that was evoked by the cue and to estimate its age.

16:07Memories evoked by words and pictures peaked in adolescence and early adulthood. Most of the memories evoked by smells came from the first decade of life, before the age of 10. Another lab, six years earlier, compared smells to word labels and found the same shift. When the researchers plotted the memories by age, the cued by words group produced the well-known hill shape rising and then falling. The smell cued memories made an entirely different shape, a peak between 6 and 10 and then a steady straight line decline. And at that earliest window, a significantly higher proportion of memories was recalled by smells than by words.

16:49There's a simple counter-argument. Maybe this pattern depends on the sensory life a person has lived. Early blindness is a powerful way to test this because it alters sensory experience. One study compared people who were blind from early in life with sighted people while cueing their memories using sounds and smells. Both groups showed similar age patterns with the sound-cued bump spanning the first two decades of life in both and the smell-cued bump landing in early childhood in both. Whatever causes smell memories to shift back toward childhood, it remains intact despite major differences in how people have experienced the world.

17:32These powerful smell-activated memories also seem different. In the study with 93 older adults, the smell-cued memories had a stronger sense of being transported back in time, and participants reported thinking about them less frequently. In another study by the same two authors using a different sample, 72 older adults were randomly assigned to be cued with a smell, its name, or both. Memories triggered by the smell elicited higher emotional arousal than memories triggered by the name, and the additional arousal could not be explained away by the physical sensations of the smell itself. This study also delivered the finding that brings us back to the jar.

18:19For participants who received both the smell and its name, the childhood peak was smaller. They reported their memories as being less positive and less likely to transport them back in time. The addition of a word shortened the journey. Notice what the research has measured, because these variables define the phenomenon, how recent or distant the memory is, its emotional charge, the frequency with which it has come to mind, and how strongly it takes you back. Another view of nostalgia describes the effect in almost identical terms, noting that nostalgic memories evoked by smell and taste tend to be self-relevant, emotionally arousing, highly familiar, and more positive than nostalgia triggered by other means.

19:05All of those factors have to do with how the memory is felt. None relate to whether the memory is reliable. The degree to which researchers have successfully accounted for all of this depends on which review you consult. The Nostalgia Review concludes that current studies have provided insight into the physiological, neurological, and psychological underpinnings of the phenomenon. The second review, however, which examines the studies in greater detail, views the current findings as preliminary, lists several existing and proposed theories, and suggests that researchers move on from identifying the effect to exploring its causes.

19:44That second view is more persuasive. The phenomenon has been observed over and over again, but what produces it remains unclear. And that is the part of the story I'd most like to learn.

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21:19So far, everything I've discussed is based on an intact olfactory system. The literature on smell loss introduces a different perspective. In a smell and taste outpatient clinic, 192 patients who had come in with smell loss of varying severity on testing completed a battery of tests, including two questionnaires, one assessing the impact of their condition on their quality of life and the other a short screen for the likelihood of clinical depression. There may be a higher risk of depressive symptoms with smell loss following COVID-19 compared to smell loss after other infections, although that link only held when the quality of life scores were left out of the analysis.

22:06And overall, the worse the smell loss affected their day-to-day lives, the higher the screening scores for depression. Longer term, the picture is more encouraging. An earlier paper from some of the same researchers followed up patients who had been treated at a smell and taste clinic before the pandemic. 65 of the original 325 agreed to reparticipate, at an average of 8.6 years later. About a third reported that their sense of smell had improved, rising to about 40 % among those whose loss followed an infection, and among the 19 who had smell identification scores from both visits. The later scores were higher.

22:50Quality of life was lowered for 4 in 10 of them, yet they showed minimal depressive symptoms, if any. Despite the real impact on cooking, recognizing spoiled food and personal hygiene, the authors concluded that people appear to adapt over the long term. This next study has the strongest design because the first brain scan happened before infection. Among UK Biobank participants who already had one brain scan, a second scan was done, and 785 of them, aged between 51 and 81 years old, make up this comparison. Of these, 401 had tested positive for COVID-19 between the two scans, on average 141 days before the second one, and 384 had not.

23:38Having that first scan makes it much less likely that existing differences could be mistaken for the effect of the illness. Compared with the control group, the infected group had greater reductions in gray matter thickness and tissue contrast in the orbitofrontal cortex and the parahippocampal gyrus. They had greater changes in markers of tissue damage in brain regions that are functionally connected to primary smell cortex, and they had a greater reduction in overall brain size. On average, they also had greater cognitive decline between the two scans. And even when we exclude the 15 people who were hospitalized, it was all still there.

24:18None of this is causative. The study does not claim to know why. The authors suggest three potential mechanisms. A degenerative process of the disease moving along the olfactory pathways, brain inflammation, or sensory deprivation due to the loss of smell, and leaves open the question of whether these changes might be at least partially reversible or whether they are permanent. The paper's own title says associated with, which is precisely the degree of certainty this design allows. A smaller scale study with an average age of 37 compared 23 people with long lasting smell loss following COVID-19 to 26 matched healthy controls.

25:04Volume reductions in the lateral orbital cortex, hippocampus and amygdala showed only a non-significant trend after corrections for multiple comparisons, and there were no significant structural differences between the groups. Now, let's summarize and recap some of the major talking points we have discussed. First, our olfactory system connects directly to the memory system via a much shorter path than other senses. Smells evoke older memories, and they are more strongly emotional. Why that is remains an open question. And so three takeaways emerge from this. A technique, a limitation, and something to try if you've lost your sense of smell.

25:49First, the technique. Study what you need to remember with a distinct odor in the room and bring the same odor back when you need to recall it. Across three experiments with 200 students, this increased the number of words recalled. and a second study found it did so without increasing false recall. However, the evidence is narrow. Word lists tested five minutes after study, so nothing is known about longer gaps. Second, the limitation, and it involves sleep. Think of sleep as a night shift worker filing the day's paperwork. Replay a study cue while the filing is happening, and that folder seems to get a bit more care.

26:30A meta-analysis of 91 experiments and over 2 ,000 people found that queuing during sleep boosts memory, with an effect that is small by conventional benchmarks, though the authors call the method effective. It works in light sleep and slow-wave sleep, but not in REM sleep or while awake, and smells work about as well as sounds. One of the two seminal studies used a scent replayed during slow-wave sleep. It improved memory for where objects had been, a hippocampus-dependent memory, but not a finger-tapping skill, and only when the smell had been present at study. Third, for anyone who has lost their sense of smell.

27:12The most recommended therapy is olfactory training, sniffing four scents, rose, eucalyptus, lemon and cloves, twice a day for 12 weeks. In a controlled study, which was not randomized, the 40 who trained with the four scents improved on a standard smell test, and the 16 who did not train did not change. However, the randomized evidence is less impressive. A meta-analysis of 10 trials and 628 patients with post-COVID smell loss found a small but significant improvement in smell scores and in quality of life. However, However, the authors of this warned against generalizing due to training protocols being so varied in the individual studies.

27:57None of this turns a spice jar into a medical treatment. Some of the brain findings rest on small samples, the sleep-queuing work lives in laboratories, and the trials in people with smell loss disagree. But it gives you something concrete to act on and something wonderful to think about. So back to the jar with no label. The missing name felt like a loss, as if the nose couldn't speak to the mouth, yet give people the label alongside the scent. And they recall fewer childhood memories with a weaker sense of being carried back. Without the label, the scent leads further. Thank you so much for listening.

28:38I really appreciate you giving me your time and your ears. Take good care of yourself and have a good night's sleep. Bye for now.

28:49Thank you.