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  • [Derek] How do you fix a brain that's not working properly?

  • Well, until now the only real option has been to open up the skull,

  • implant electrical or optical fibers, or even remove parts of the brain.

  • If you do something like surgery or ablation, even with ultrasound, that's an irreversible one-time procedure.

  • But this scientist has a different idea.

  • Do you wanna introduce yourself?

  • Yeah, sure. Yeah, I'm Mikhail Shapiro. Where should I look?

  • [Derek] You can look at me, yeah!

  • [Mikhail] Yeah, I'm Mikhail Shapiro. I'm a professor of chemical engineering at Caltech.

  • Everything that we try to do is to make it non-invasive,

  • meaning that we don't want to have any kind of surgery to open up the skull and implant an electrode,

  • or we don't want to have to open up the skull to shine light onto the neurons.

  • We want to do it using sound waves,

  • which is one of the few forms of energy that can be focused deep inside of the tissue

  • and can actually permeate through things like the skull, even the human skull.

  • This is a curved transducer, so you can see there is a slight curvature in it

  • that will cause the sound waves to get concentrated a few centimeters in front of the face of this transducer.

  • [Derek] For now, the research is being conducted on mice,

  • and the idea is to be able to turn on and off specific brain regions at will, without invasive surgery.

  • [Mikhail] So the trick that we employ here,

  • is that we take something that's traditionally been a really big problem in neuroscience drugs,

  • and we turn it into an advantage.

  • So the problem is that the brain has what's called the blood-brain barrier

  • which lines the blood vessels of the brain and prevents molecules moving from the bloodstream into the brain.

  • [Derek] But in their procedure, they open the blood-brain barrier in carefully targeted regions of the brain.

  • [Mikhail] So to do this, we introduce little bubbles into the blood stream.

  • [Derek] Air bubbles.

  • [Mikhail] Bubbles of air, but they are safe bubbles.

  • So this is an FDA-approved clinically used-

  • [Derek] Like tiny bubbles?

  • [Mikhail] They're microns in scale.

  • [Derek] Okay. Tiny air bubbles.

  • [Mikhail] So tiny little air bubbles,

  • that we introduce into the into the bloodstream and so they're circulating everywhere.

  • And then wherever we apply the ultrasound, the sound waves cause the bubbles to expand and contract in size,

  • and as they're doing that they push against the blood vessel walls, and kind of massage them open.

  • So they get that blood-brain barrier that's normally caused by really tight

  • junctions between cells to open just a crack,

  • so that now molecules can get out, into the brain.

  • [Derek] And by using the ultrasound you can target just specific areas of the brain

  • where you want to open the blood-brain barrier and leave the rest of the brain alone.

  • [Mikhail] Exactly.

  • [Derek] Once the blood-brain barrier is open, the scientists inject a specially made virus

  • that would normally not be able to pass into the brain.

  • [Mikhail] These viral vectors, which are viruses that we have hijacked,

  • so that instead of them introducing their DNA to the cells,

  • they're going to introduce the DNA that we want

  • and what this gene produces are these receptors that will go on to the neuron.

  • These receptors have been modified so they no longer respond

  • to neurotransmitters that are natively present inside the brain

  • and will instead respond to a drug that we can inject

  • that will activate just those receptors and not act on anything else.

  • I'll tell you when we get to a part where your camera's going to get sucked into the magnet before it happens.

  • [Derek] Thank you.

  • I appreciate that.

  • [Mikhail] So this big machine here is what generates the sound waves that we use.

  • This little device will get installed on here, and then we're gonna have a mouse underneath,

  • and then this entire thing is going to go into the MRI scanner.

  • [Derek] Is this a special ultrasound for... mice?

  • [Mikhail] Both the MRI is special for mice, because as you can see from the bore that's in the middle of it

  • [Derek] Yeah. A human's not gonna fit in there!

  • [Mikhail] Yeah, well it'd have to be a really small human.

  • And then our ultrasound system also is designed for these kind of small animals

  • [Derek] And that squeaking sound that I'm hearing. That's not actually mice in there-

  • That's the MRI?

  • [Mikhail] Yeah.

  • [Derek] How strong is the magnetic field in there?

  • [Mikhail] Inside the scanner it's 7 Tesla.

  • [Derek] Whoa!

  • [Mikhail] Yeah. So it's going to give us an image of the anatomy of the brain

  • and allow us to target the focus of this ultrasound transducer

  • to precisely the part of the brain where we want to open the blood-brain barrier.

  • [Jerzy] There will be four bright spots that will appear on the brain just about here

  • So this is the opening of the barrier between the blood and the brain.

  • That allows a diffusion of what is essentially a

  • magnetic resonance imaging dye that shows up during the MRI imaging.

  • This is the hippocampus.

  • The hippocampus is a fairly large structure that's important in the formation of memory

  • and this is the one that we targeted in our recent study to modulate the memory of mice.

  • [Mikhail] We targeted the hippocampus,

  • which is this part of the brain that's necessary for the formation of certain kinds of memories,

  • and using our technique, we can address just the neurons within the hippocampus,

  • and when we give a drug those neurons get shut down

  • And then we can do behavioral experiments where we did a memory task,

  • where we put the mice into a particular environment and check to the next day

  • by bringing the mice back into that same environment whether or not they could remember it.

  • And for the mice that were treated with the ultrasound,

  • with the receptors through the viral vectors, and given the drug that activates these receptors,

  • that shut down the hippocampus.

  • Those mice were not able to remember,

  • so we could tell that we were successfully able to inhibit or prevent memory formation.

  • Because the effect depends on when you give this drug, and how much of the drug you give,

  • you can have reversible, turning on or off of the effect that you're trying to produce.

  • So for example, shutting down the part of the brain that's causing a seizure.

  • So another part of the brain that we're pretty interested in is called the ventral tegmental area,

  • which is a part of the brain that uses the neurotransmitter dopamine,

  • and is involved in things like motivation, and addiction, and initiation and control of movement.

  • And if we can gain control over the neurons in that area,

  • it might someday be useful treatments for some of these

  • motivational or affective disorders like addiction and our depression.

  • [Derek] Could you use this to control people's brains?

  • Like by playing ultrasound, into some area?

  • [Mikhail] No, there is not a chance, at least using our technology,

  • that you could be walking around and we could be controlling your brain remotely.

  • ... if that's what you're worried about.

  • [Derek] Not yet, anyway.

  • [Mikhail] That is not our goal!

  • [Derek] Right.

  • Hey, this video was supported by viewers like you on Patreon and by Skillshare.

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  • and I personally found that class really informative and helpful.

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[Derek] How do you fix a brain that's not working properly?

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How Ultrasound Can Deactivate Parts of the Brain

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    林宜悉 posted on 2020/03/28
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