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No Implants Needed for Precise Control Deep into the Brain
- memming 6y agoPHP virus? What??? (looking up) Oh, it's a subtype of AAV.
- Ericson2314 6y agoI'm really glad someone decided to name a virus that.
- hprotagonist 6y ago7 millimeters deep is staggering. Holy crap! Just a few years ago I remember being very impressed by 500 microns. I am curious to see how well this is tolerated in the long term. It is possible to damage tissues with very intense light, especially over time, but there are ways around this like 2-photon.
- caycep 6y agoI am just a interested observer - I remember the issue w/ the old viral vectors were concern re longevity of the cells, i.e. the optogenetically active ones you could do experiments on for several weeks, but then they'd poop out and die off for some reason, but this was just word of mouth chitchat with a postdoc who was working on this. Not sure if this was because of the light intensity or that mutating the cell with channelrhodopsin just made it weaker in general.... granted, not sure how intense of a light you'd need; I'd think the channelrhodopsins activate w/ just a few photons at the right wavelength... Coming from the clinical/Parkinsons' disease world, if someone made a stable viral vector specific for the basal ganglia though, that would certainly help w/ one of the biggest problems of clinical DBS - after 30 years of doing this, the biggest biggest biggest problem in whether the implant will work or not is still the +/- 2mm accuracy of the stereotactic frame implanting the electrode...(no matter what surgeons/stereotactic engineers claim...)
- hprotagonist 6y agosupplimentary figure 4 has data at +7 months.
- tbenst 6y agoGreat question! See the supplementary note on tissue heating: https://web.stanford.edu/group/dlab/media/papers/chenNBT2020supp.pdf https://web.stanford.edu/group/dlab/media/papers/chenNBT2020...
- hprotagonist 6y agothat is properly impressive. cheers to the team for sure! I have done a little bit of corticofugal recording where we'd stimulate thalamus and record from cortex, and i was impressed enough at that. This opens up whole new frontiers in the game, though.
- blovescoffee 6y agoI'm almost completely unfamiliar with brain science. Could you explain the basic idea of what they're signalling 7mm deep? The brain is a good deal larger than 7mm, so are they just targeting certain areas towards the surface of the brain?
- deleted 6y ago[deleted]
- hprotagonist 6y agomore or less, all the "compute" stuff is towards the surface of the brain. The last time I did any of this work, in about 2017, 500 um was considered "deep brain" for optical stimulation. This is an order of magnitude deeper in one shot.
- greesil 6y agoWhy not try far infrared, or radio?
- whymauri 6y agoI don't know much about far infrared, but the 6-7mm penetration in this paper seems deeper than the ~4mm penetration I recall reading about for UCNP-NIR.
- Balgair 6y agoTo add: Water has an absorption band that is clear to most visible light and the near IR, but it starts to absorb as you go deeper into IR. Many tissues and their light absorption curves can be seen here: https://en.wikipedia.org/wiki/Near-infrared_window_in_biological_tissue https://en.wikipedia.org/wiki/Near-infrared_window_in_biolog...
- tbenst 6y agoYou need an actuator to induce current into the neuron. In this case, a light-sensitive ion channel, which have proved highly effective.
- mattkrause 6y agoPeople have actually used infrared to stimulate neurons directly. The mechanism is a little weird, and may be a combination of direct heating (e.g., causing chemical reactions to run faster) and activation of temperature-dependent ion channels. https://www.sciencedirect.com/science/article/pii/S105381191100379X https://www.sciencedirect.com/science/article/pii/S105381191... Radio is probably much too fast--the time constant of a neuron is on the order of 10ms, so unless you're pumping a lot of instantaneous power into the neuron, the net effect is likely to be zero.
- dr_dshiv 6y agoOr, using temporal interference patterns of intersecting electrical waves to produce deep stimulation in humans - - without genetic modificatiom https://www.biorxiv.org/content/10.1101/2019.12.25.888412v2.full https://www.biorxiv.org/content/10.1101/2019.12.25.888412v2....
- whymauri 6y agoI haven't read this bioRxiv paper, but what's the difference between it and this Cell paper from 2017? https://pubmed.ncbi.nlm.nih.gov/28575667/ https://pubmed.ncbi.nlm.nih.gov/28575667/
- mattkrause 6y ago"Deep" in the mouse is a few millimeters, while deep brain structures in primates are 10-15x deeper. In primates, the fields would be harder to precisely interfere because of our thicker skulls and larger, more convoluted brains. The level of c-fos activation in the Cell paper is also a little crazy--it seems way too intense to be correct, especially when compared against direct electrophysiological measurements. It's also not 100% clear that the high frequency fields do nothing--there are some claims that they have DC-like effects due to hysteresis in the neurons' membrane potentials.
- whymauri 6y agoOh snap, I didn't notice the animal model changed. Thanks for the heads up and rundown!
- mattkrause 6y agoYou don't even necessarily need the temporal interference--we got it to work reasonably well in awake, behaving monkeys (where we could measure single-neuron activity directly). https://www.pnas.org/content/116/12/5747.abstract https://www.pnas.org/content/116/12/5747.abstract
- dr_dshiv 6y ago
- tbenst 6y agoI sit next to Ritchie Chen, the first author on this paper. Let me know if any questions and I’ll try to get them answered :) Edit: for anyone that wants to read the paper, here’s a non-paywall link: https://web.stanford.edu/group/dlab/media/papers/chenNBT2020.pdf https://web.stanford.edu/group/dlab/media/papers/chenNBT2020...
- whymauri 6y agoAny thoughts on the immunogenicity of optogenetic approaches? Anecdotally, it was a major pain when working with optogenetic stimulation in the PNS.
- tbenst 6y agoKarl has said publicly a few times that he sees optogenetics as a tool for basic scientific discovery, that then inform treatment of human patients, ie where to use transcranial magnetic stimulation. Any method that requires genetic manipulation in humans will be tricky. PNS seems likely to be the first application in humans, although there are also clinical trials going in the retina, not sure how they’ve progressed though.
- whymauri 6y agoThat's unfortunate, because the resolution and fine control you get with optogenetics are really good in the periphery, offering high therapeutic potential for amputees and paraplegics. The main roadblock is the understudied immunogenicity problem, IMO.
- echelon 6y agoWhat is Ritchie's take on Neuralink? (Sorry to stray onto topics not related to optogenetics. I hope it doesn't irk him that Elon Musk has steered/captured public consciousness regarding neuroscience.) To stray into sci-fi territory a bit, if money gets poured into the field, is there a chance we might see the Matrix or brain uploads in our lifetimes? And if not in our lifetime, is it ever achievable? I'm extremely skeptical, but human BCI could be the best/most important development in our history. Any problem gradient with a chance of unlocking immortality should be leaned into. It's way more important than Angry Birds or iOS N+1. With regard to studying already-alive organisms (we can't splice in the genes required for optogenetics), are there non-invasive techniques that can produce signal from humans? Deuterium NMR cerebral imaging seems low resolution and awkward to deploy. Could ML / signal processing increase the resolution of EEGs? Could we ever extract video signal from an EEG? Can an EEG induce perception into a brain? With regard to optogenetics, what are the things currently being studied with the technique? What pressing questions can it be used to answer? Are there any improvements to the technique that could push it further? Sorry for so many off-topic questions, but I'd love to know what an expert in the field thinks. I'd especially like to get a grasp of the future of the field.
- alantrrs 6y agoThis + OpenWater(https://www.openwater.cc/ https://www.openwater.cc/) will be a way better approach than Neuralink.
- bserge 6y agoWow, very interesting project, I hope they succeed.
- wcoenen 6y agoSince genetic engineering is necessary to first put light sensitive ion channels in the brain, I don't see how this is "way better" if you're targeting applications in humans like neuralink.
- alantrrs 6y agoI'd much rather get an injection than get brain surgery.
- bduerst 6y agoI would think a brain virus has a higher risk than a one-time surgery.
- qayxc 6y agoI wouldn't even try to guess either way - there's zero statistics for genetic manipulation of the human brain and some stats for brain surgery. Comparing few data points to none just doesn't allow for any intuition about the safety of either compared to the other.
- pvarangot 6y agoOpenWater doesn't have enough resolution. I find their PR kinda sketchy because it makes a lot of emphasis on laser and optical things, which they use, but rarely mentions that the fact that they rely on an ultrasound beacon makes their best-case temporal and spatial resolution not as exciting. The tech is really cool, as in a portable MRI-like device is really cool even if it's resolution is way worse than a big MRI machine. But it's nowhere near "brain scanning for brain upload" territory because of fundamental physical laws that they actually choose to work withing the constraints of. I would really like to see something like OpenWater but used to help with de-scattering LiDAR on rainy/foggy days. I'm not sure if it's possible but from my limited understanding I think it's worth the try.
- Cancan82 6y agoThis is really cool - reminds me of a technology that uses MRI machines to do incisionless brain surgery. It’s amazing what we can do. This is the MRI-based brain surgery: https://www.minthilltimes.com/featured/medical-surgical-procedure-breakthrough-treats-parkinsons-tremors/ https://www.minthilltimes.com/featured/medical-surgical-proc...
- superkuh 6y agoI don't know about you but I consider sticking a needle deep through the brain to be a surgery. I guess the authors are using a more technical definition. No doubt this will help speed up research in labs. For actual no surgery stimulation of deep brain tissues there's arrays of low powered ultrasound and interferometric transcranial alternating current. And if 4.5 mm deep is the goal-line even the current practice transcranial magnetic stimulation with a butterfly coil can do the job (more awkwardly).
- richdougherty 6y ago"To avoid this, the Stanford team used a type of PHP virus developed at CalTech that can be injected in the blood. The virus then crosses the blood-brain barrier to deliver its payload, an opsin gene, to brain cells. In this case, even the delivery of the gene is noninvasive—no needle penetrates the brain."
- superkuh 6y agoOh. So I missed the entire point of the paper. Yikes. Thanks for the correction. But how is the transfection localized to the VTA if it's administered peripherally and not within the target tissue?
- OpticalWindows 6y agoAlarm bells should be ringing about this. If they can breach the blood brain barrier with viruses, imagine what they can do with contaminated food, gas, and drink.
- deleted 6y ago[deleted]
- superkuh 6y agoI've spent more time actually reading the papers and extended data. This statement written above is factually untrue. This procedure does involve needles in the brain. It is invasive. It is surgery. The press writers you quote misunderstood.
- skybrian 6y agoIn mice!
- politician 6y agoWell, this is terrifying. The next advertising gimmick involves a virus with a payload that stimulates dopamine when a licensee's TV/Facebook spot is seen. You could hit the entire population with this kind of thing.
- scotty79 6y agoIf they could find opsins that react to submilimiter radiowaves and if we could design emiter/reciever array that you could put on your skull, we could have really amazing man/machine brain interface.
- nootropicat 6y ago>Then, they shined a red light outside the skull and were able to activate neural circuits in the midbrain and brainstem at depths of up to 7 millimeters This appears to be extremely dangerous. One strong NIR lamp in a public space would drive people with this insane. Everyone would have to wear special hats. What if it was possible to implant memories this way? A new type of crime: catch someone, take their hats off, reprogram their brains and make them forget the hijacking occurred. A surgical implant seems way safer in practice.
- OpticalWindows 6y agoWireless reading and intrusion of brainwaves or worse make people drones Brain mapping [1] + opsin gene delivery to brain using virus that crosses blood brain barrier [2] + advanced network tracking using phone ect to determine location of head [3] + ??sensitive networks to constantly scan a users head?? + ???networked lasers, em waves to alter thought or behavior in public??? = Telepathy and brain bullying [1] Brain mapping https://www.youtube.com/watch?feature=youtu.be&v=Ecvv-EvOj8M https://www.youtube.com/watch?feature=youtu.be&v=Ecvv-EvOj8M "in the future we will have very cheap and very ubiquitous brain reading systems" [2] opsin gene delivery https://spectrum.ieee.org/the-human-os/biomedical/devices/deep-brain-control-without-implants https://spectrum.ieee.org/the-human-os/biomedical/devices/de... [3] human tracking http://www.hitl.washington.edu/projects/knowledge_base/virtual-worlds/EVE/I.D.1.b.TrackingDevices.html http://www.hitl.washington.edu/projects/knowledge_base/virtu... Imagine using media such as popular netflix shows, meme's, and other attention grabbing media to map someones brain passively and retain that data. Dope individuals with food, water, air that have virus. bam mind reading/bullying Again the science (brain science, sensors, and em netowrks) probably need to be done to do this We 10000000% need more monitoring of vectors like this. Viruses et all need to be constantly monitored for public safety. Sure we probably do it in wastewater but thats terribly imprecise and a stupid high LOD. Wonder if there are automated jigs that do this in waste water.