By The Biomedical Observer
Quick question: when was the last time a smell made you do something? Maybe you walked into a bakery because fresh bread was calling your name. Maybe you avoided the gym bathroom because, well, you know. Perhaps a whiff of perfume triggered a memory so vivid you could practically see your grandmother's kitchen.
Smells run our lives more than we realize, and scientists have known for decades that the olfactory system has a VIP pass straight to the brain's emotion and memory centers. But here's the problem: they've never been able to prove exactly HOW it works in humans. Until now.
A new clinical trial (NCT07099092) at the NIH is using focused ultrasound to literally poke the smell-processing parts of your brain and see what happens. Science is weird and wonderful.
The Mystery of the Smell Superhighway
Your nose is not like your other senses. When you see something, visual information travels through multiple relay stations and processing centers before reaching conscious awareness - it's like a letter going through the postal system. When you hear something, similar story.
But smell? Smell takes the express lane. Olfactory information goes from your nose to the olfactory bulb (a structure that looks like two tiny onions sitting at the base of your brain) and from there it has almost direct connections to the hippocampus (memory) and amygdala (emotion).
This is why a smell can transport you back to childhood in a way that looking at a photograph simply can't. The signal through the olfactory system is, as researchers describe it, "simply less filtered and processed." Your nose is whispering directly to the parts of your brain that feel things.
As Courtiol and Wilson noted in their review for the Oxford Research Encyclopedia of Neuroscience, the olfactory system plays a fundamental role in guiding behaviors ranging from food selection to social interaction to danger avoidance. But most of what we know about the neural mechanisms comes from animal studies - and humans, as it turns out, are quite different from mice when it comes to smelling things.
The Problem with Brain Research
Understanding how brain regions cause behavior is tricky. You can't just remove parts of someone's brain to see what happens - ethics committees frown on that sort of thing. You can study people who had strokes or injuries in specific regions, but those cases are rare and the damage is never neat and tidy.
Brain imaging techniques like fMRI can show you which areas activate when someone smells something, but correlation isn't causation. Just because a brain region lights up during a task doesn't mean that region is necessary for the task.
What you really want is a way to temporarily turn brain regions on or off in healthy people and see what changes. For cortical areas near the skull, transcranial magnetic stimulation (TMS) can do this - it uses magnetic pulses to activate or inhibit neurons. But the primary olfactory cortex is buried deep in the brain, where TMS can't reach effectively.
Enter: transcranial focused ultrasound stimulation (TUS).
Ultrasound: Not Just for Babies Anymore
You probably think of ultrasound as the technology that lets expectant parents see their babies or helps doctors look at your gallbladder. But at different intensities and frequencies, ultrasound can actually modulate neural activity. It can make neurons more or less excitable without surgery, without permanent effects, and - this is the key part - it can reach deep brain structures.
The physics is pretty wild. Focused ultrasound uses multiple transducers (think of them as tiny speakers for sound waves) aimed to converge at a single point. Most of the ultrasound passes harmlessly through tissue, but at the focal point, all those waves add up and create effects. It's like how sunlight through a magnifying glass is harmless except at the tiny spot where the light focuses - except instead of starting a fire, you're gently nudging neurons.
Recent work has successfully used TUS to modulate activity in the thalamus, amygdala, hippocampus, and various cortical regions. One research group even used it to stimulate the olfactory bulb itself - inducing artificial smells in human subjects. As their team described it, they "induced distinct artificial smells like campfire and fresh air using focused ultrasound." That's right - they made people smell things that weren't there by beaming ultrasound at their brains.
The Clinical Trial: Poking Your Smell Brain
Clinical trial NCT07099092, titled "Causal Mechanisms of Odor-Guided Behavior in Humans," is using TUS to directly test whether primary olfactory cortex regions actually cause specific olfactory functions.
According to the trial description, "Primary olfactory cortex has been implicated in a variety of odor-guided behaviors in both animal models and humans. However, direct causal evidence for the functional role of different primary olfactory regions in humans is currently missing."
The study will recruit healthy, right-handed adults aged 18-45. Participants can volunteer for up to two different experiments, each requiring five visits spaced about a week apart. At each visit, researchers will assess participants' sense of smell and potentially have them perform computer tasks while smelling different odors, looking at pictures, and listening to sounds.
The TUS will be applied to temporarily modulate activity in specific olfactory regions while participants perform these tasks. By comparing performance with and without stimulation, researchers can determine which brain areas are actually necessary for which olfactory functions.
What Does "Odor-Guided Behavior" Even Mean?
We tend to think of smell as passive - odors float by, we notice them, end of story. But humans engage in all sorts of behaviors that are influenced or directed by smell:
Food selection: You smell milk before drinking it to check if it's spoiled. You sniff wine before sipping it. The aroma of food affects your appetite and eating behavior.
Social behavior: Humans can detect fear and stress in others' body odor. Mothers recognize their babies by smell, and vice versa. There's evidence that romantic attraction is influenced by how someone smells to us (thanks, major histocompatibility complex).
Safety: The smell of smoke triggers immediate alertness. Natural gas companies add mercaptans to their product specifically because we're so responsive to that sulfur smell.
Memory and emotion: Odor-triggered memories (known as Proust phenomena) are often more emotional and vivid than memories triggered by other senses.
Understanding how the olfactory cortex supports all these behaviors isn't just academically interesting - it could have real clinical applications.
Why This Matters
About 12% of adults have some form of olfactory dysfunction - reduced or lost sense of smell. After COVID-19, that number has likely increased substantially. For these individuals, the world loses a dimension that most of us take for granted. Food becomes boring, safety becomes compromised, and that visceral connection to memory and emotion is damaged.
If we understand exactly how different olfactory brain regions contribute to smell function, we might be able to develop better treatments. Perhaps targeted stimulation could help restore function in people with specific types of smell loss. Perhaps we could develop rehabilitation approaches that specifically target the underlying neural circuitry.
There are also implications for mental health. The olfactory system's direct connections to emotion-processing regions mean it may be involved in depression, anxiety, and PTSD. Understanding these connections could open new therapeutic avenues.
The Future Smells Interesting
The trial is expected to start around August 2025 and will be conducted at the NIH Clinical Center in Bethesda, Maryland. It's part of a broader movement toward using focused ultrasound as a precise, non-invasive tool for brain research.
What makes this study particularly exciting is that it's asking fundamental questions about human neuroscience using methods that simply weren't possible until recently. For decades, researchers have had to extrapolate from animal studies or correlational human data. Now they can directly test causal hypotheses in healthy human brains.
The olfactory system has always been the neglected stepchild of sensory neuroscience - vision and hearing get all the attention. But smell was the first sense to evolve, it's arguably the most emotionally powerful, and we're only just beginning to understand how it works in humans.
So the next time a smell stops you in your tracks or triggers an unexpected memory, remember: scientists are working on figuring out exactly how that happens. They're literally using sound waves to probe the deepest parts of your brain.
The nose knows. And soon, so will we.
References:
- Courtiol, E., & Wilson, D.A. (2017). "Neural Mechanisms for Odor-Guided Behavior." Oxford Research Encyclopedia of Neuroscience. DOI: 10.1093/acrefore/9780190264086.013.359
- Legon, W., et al. (2014). "Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans." Nature Neuroscience, 17(2), 322-329. DOI: 10.1038/nn.3620
- Deffieux, T., et al. (2013). "Low-intensity focused ultrasound modulates monkey visuomotor behavior." Current Biology, 23(23), 2430-2433.
- ClinicalTrials.gov Identifier: NCT07099092 - "Causal Mechanisms of Odor-Guided Behavior in Humans"
Disclaimer: This blog post is for informational purposes only and does not constitute medical advice. Clinical trials are ongoing research and results are not yet confirmed. The described interventions are experimental and not available outside of research settings. Always consult with qualified healthcare professionals regarding any medical conditions or treatments. Images and graphics are for illustrative purposes only and do not depict actual medical devices, procedures, mechanisms, or research findings from the referenced studies.
No comments:
Post a Comment