Ultrasound Neuromodulation
We can now turn on or off any brain region, without surgery
In 1958, neurologist F.J. Fry discovered that low-intensity ultrasound could affect the brain.1
Through a hole in a cat’s skull, he directed 20 seconds of focused ultrasound to the lateral geniculate nucleus (LGN), deep inside the hindbrain. The ultrasound administration temporarily blocked the cat’s neural response to a flash of bright light, as measured by electrodes on the visual cortex. 30 minutes after ultrasound administration, the cat’s response to light returned to normal.
In other words, Fry was able to use ultrasound to temporarily turn off the normal function of neurons in a specific part of the brain, without any long-term damage.
Since then, as ultrasound devices have become smaller and cheaper in the past two decades, transcranial focused ultrasound (tFUS) has been tested on many animals including humans, where it has been found to sometimes increase and sometimes decrease the neural excitability of any targeted brain region, depending on the settings of the ultrasound signal.
Ultrasound, at the relevant intensities, appears to be harmless to brain tissue. And modern devices can focus energy to few-millimeter-sized regions of the brain, at any depth, from noninvasive stimulation outside the head (i.e. no surgery needed.)
Turning up and down arbitrary brain regions noninvasively is a huge deal.
First of all, it means a safer approach to the disorders we already treat through invasive neuromodulation. Certain kinds of epilepsy or severe motor disorders can only be treated by implanting electrodes inside the brain or destroying the brain regions responsible for uncontrollable seizures or involuntary motions. If an ultrasound device could “turn down” or “turn up” the volume of neuron firing in those brain regions, the risk of surgical complications or brain damage would be far lower.
Second of all, it’s a huge opportunity for research. If you can “turn up” or “turn down” any brain region at will, safely enough to mess around with it on healthy human subjects, you can develop a functional atlas of the brain, where you find out exactly what each part is doing.
To date, we have only been able to do this by:
observing case studies of humans who happen to have brain damage in different regions
but of course you can’t ethically give people brain lesions
operating on animals to damage or stimulate parts of the brain
but of course animals can’t talk or reveal the effects of brain modifications on “higher” cognitive functions
observing patterns of blood flow activity in different brain regions (fMRI)
but this is observational rather than interventional — you’ll never know what would have happened counterfactually if those brain regions were activated or inactivated
inducing temporary “virtual lesions” through noninvasive brain stimulation via applying magnetic (rTMS) or electrical (tDCS) stimulation to the outside of the head.
but these methods can’t penetrate deep within the brain, so they are only usable for experimenting on the cerebral cortex and not the deeper structures that affect emotion, motivation, and memory.
Also, rTMS is a bulky fixed device, while tDCS electrode stimulation can be noisy and sensitive to head movements and hair interference.
Compared to these existing methods, neuromodulatory ultrasound (newly miniaturized and affordable thanks to MEMS innovations), if used to explore the brains of healthy humans, could vastly expand the range of our knowledge.
Ideally, a wearable ultrasound device would allow exploration of what happens when you experiment with different brain stimulation patterns during a variety of activities. Not just sitting in a chair in a lab or clinic with your head in a heavy device, but sleeping, exercising, having social interactions, and so on.
A wearable brain stimulator that could temporarily modulate neural activity would potentially be a platform for entirely new kinds of “therapies.”
Imagine if (as seems superficially plausible) you could get an anti-anxiety effect from “turning down the volume” on the amygdala.
Instead of having to take an anti-anxiety drug (which affects every part of the brain and body it reaches, needs to be metabolized, typically has side effects, and lasts for a fixed duration) you could simply alter only the brain regions you want to, for exactly as long as you want to.
Imagine a “thinking cap” that you could control, to tune your mental state at will to whatever you wanted it to be in a given situation.
This is a technology that could fundamentally change the human condition.
Could the right patterns of neuromodulation be used for cognitive enhancement? For reliably inducing the kinds of mental states that meditators report experiencing? For inducing positive emotions or pleasure, or blocking negative emotions or pain? There’s some reason to believe all of these might be possible.
In later posts I’ll go into more detail about what’s known about neuromodulatory ultrasound so far, how it works, what it’s been shown to do, what its risks are, and what we might reasonably hope to find from a systematic search for human enhancements.
Fry, F. J., H. W. Ades, and W. J. Fry. "Production of reversible changes in the central nervous system by ultrasound." Science 127.3289 (1958): 83-84.
Have you seen any comparisons of this technique with that of electromagnetic stimulation? I suspect that each has its pluses and minuses, and ideally physicians should be able to select between them or combine them as part of a treatment:
"Neuron matters: neuromodulation with electromagnetic stimulation must consider neurons as dynamic identities"
https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-022-01094-4
This topic is relevant to me, but in reverse. I have a condition that is caused by a LACK of connection between some areas of the brain, instead of an excess. It's the opposite of the cause of epilepsy and many other conditions where the brain is flooded by signals.
I don't know of any treatment to fix what I have. I suspect the eventual treatment will be chemical, not something similar to ultrasound or electromagnetic.
My family and I (all of my siblings, my mother, and some of my nieces and nephews) were born with "aphantasia". We are completely cut off from voluntary recall of or the ability to generate a visualization of the senses. Ours is "total", beyond its basic definition of "the inability to form mental images of objects that are not present". So when I close my eyes, I literally see nothing. I can't recall anything I've ever seen or heard or touched or tasted or smelled, with just the exception of hearing songs (but not voices or sounds). I conceptually remember them, but the visualization can't happen.
And I can't imagine them, either. To create an image, I have to do it in Photoshop or on paper, since I literally can't "see it in my mind". While I don't have "face blindness", I don't know what anybody looks like until I see them. I typically recognize people, but could never provide any details for a "sketch artist". I don't know what pizza or chocolate tastes like (though I know I like them). I don't know what a flower looks like. I have no idea what sandpaper feels like. No clue what perfume smells like.
Tied to that, we also have SDAM (Severely Deficient Autobiographical Memory), which is a lifelong condition characterized by the inability to vividly relive past experiences from a first-person perspective. There are times in movies or TV where somebody's amnesia leaves them capable, but they can't recall their past. It's like that, but not due to an accident. We're like that from day one.
In both cases, it's not that our minds don't record everything. It's that the pipeline is cut off. The rare times I remember a dream, my dream is vivid, fully visual and with sound, and may be based on people I hadn't seen in decades. But while I might remember conceptually what happened in the dream, I can't picture any of it once I'm awake.
It isn't all bad. People with aphantasia are largely immune to PTSD. We tend to be better at engineering and inventing than other people, digging deep into topics. We are extremely overrepresented in sciences and engineering. We have fewer distractions in our work and other activities, since we are never replaying something from the past, nor fantasizing about something in our mind.
But it's a lonely, different kind of existence.
I have too many hobbies, since I can't recall scenes nor fantasize to fill my time. While I'm a fast reader (for example, I read book #6 of Harry Potter in a single evening), it's unfulfilling, since I can't fantasize about what's in the scenes, so I mainly read nonfiction. I probably enjoy seeing the movie version of a book far more than most people. For many years I had a recording studio. I compose, and I play many instruments. But in practice, I often enjoy a good rehearsal more than a performance in front of a large audience, since I don't remember enough about the big show for it to have an impact on me (I mainly remember the technical issues).
Typical of aphantasia, I work in research and engineering, specifically as a "software architect". Aphantasia often causes an intense desire to understand how everything works, since we can't just recall basic images. We need something deeper. As a youth, when the video game Mario Brothers came out, I was in junior high, and I literally re-created much of the game on my pre-Windows home computer (becoming a programmer and the beginnings of being a digital artist in the process). Due to my need to put things on paper to "make them real", I eventually became a software architect, where I'm paid to reverse engineer things, diagram them, and come up with new ways for how to do things better (or do things that are entirely new). I reverse engineer the world as a hobby (psychology, medicine, science, ...), so having a job that pays me to do that is great (other than dealing with office politics).
As for relationships, those of us with aphantasia are "in the now". My wife never needs to worry about me fantasizing about somebody else, or some impossible situation. I live in and prioritize the moment. But if I don't see you, you almost don't exist. My wife had to get used to doing lengthy video calls with me when one of us is out of town, since voice-only is far too impersonal for me.
When British psychologist Francis Galton first documented aphantasia in 1880, it turned out that most scientists in Europe at that time had aphantasia. Ed Catmull, co-founder of Pixar, has aphantasia, and found that production managers tended to have stronger visualizations than artists, because some of the artists in fact have aphantasia (while I should note that it's far more common for them to have the opposite extreme, hyperphantasia). As an example, Glen Keane, a key animator of Disney's "Little Mermaid", has aphantasia. I've seen an example of where when he's working he makes faces in a mirror as a reference for what he wants to draw, since he literally can't visualize what it will look like in his head. Aphantasia isn't a barrier, but it can definitely be inconvenient.
I have to laugh when people suggest meditation. While I have no issue in "clearing my mind" (my mind is truly a blank slate), the whole "visualize a sphere in your mind" or similar is truly impossible for me. I couldn't imagine things in my head when instructed to do so in elementary school, let alone now.
There have been cases where somebody with "acquired" aphantasia (e.g., due to trauma) has been able to cure it with ayahuasca or similar. But in my case, there isn't something to repair, it would be a signal to add. My memory feels like the equivalent of having lived every day of my life in a sensory deprivation chamber, knowing facts, but unable to recall or fantasize any of the senses. I was born this way, so any chemical treatment would be experimental at best. To the 96-98% of you who don't have aphantasia, it probably sounds bizarre that my fantasy is to be able to remember or imagine what ANYTHING looks or sounds like. My fantasy is to be able to have a fantasy.
What would be a workaround if there's no treatment for congenital aphantasia? What occurs to me is something that's a political hot topic right now. Almost twenty years ago, I was able to simulate video of real people in 3D on a computer to a disturbing level of realism. This was long before "deep fake" tools, or the simulations of long-dead actors in the movie "Rogue One". Why did I do it? It was towards the concept of creating avatars to re-create the audio/visual of somebody who isn't present, since I literally can't see or hear them in my mind. So while the Screen Actors Guild has been on strike to block the simulation of Robin Williams and other actors, in real life many of us have a need for a tool to visualize people due to our 100% lack of recall of their faces. There are big pluses, and big minuses. For me, after a loved one dies, since they are already largely erased from my mind, it's soon as if they never existed. If I could talk to a realistic simulation of that person (a "full A/V" experience), wrapped over something like ChatGPT, problem solved. But that's a huge political mess.
Personally, I would be happy to leave behind an accurate software simulation of myself for my family. Simulated people were frequently shown in the "Holodeck" in the series "Stark Trek Next Generation", demonstrating how it can be a useful tool. Just three decades later, far sooner than we could have imagined, we are reaching the point that we will soon have that software on a home computer, or even on a cellphone (how long until it's a holograph? Probably not that far...). We're crossing that bridge soon, like it or not.
I'll admit, I'm "part of the problem" (or is it "the solution"?). I wrote software for the NIMH two decades ago to help psychiatrists diagnose all types of mental conditions, and recently have been working on creating software-based rules to simulate how different types of people react and behave, and what their drives and priorities are. While only intended for sessions with a psychologist or similar, it could just as easily be used for arbitrary situations, good or bad.
I'm sorry I hit so many topics! Lots of subjects came to mind when I read this article. ;-)
(Maybe a stupid comment. Not an expert. I spent some time in an adjacent area several years ago, but my memory is hazy.) I have the impression that ultrasound weakens the blood-brain barrier. There might even be a line of research where that was the whole point of it—use ultrasound to open the barrier and thus allow drugs into the brain. Anyway, IF in fact ultrasound weakens the blood-brain barrier, it makes me a bit nervous about very-long-term use in the context of mental health, BCIs, etc. Like, the blood-brain barrier has gotta be there for a good reason, right??? (Maybe people have looked into this, I never checked.)