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Editing living memories demonstrated for the first time


We all have memories we’d like to change, keep, or even, perhaps, edit, embellish, or erase, and now the technology to do all of these and more, including correcting blindness and reversing dementia, has just been demonstrated in living subjects.


Recently scientists transferred memories between two snails, but what if we could edit the sensations you feel, paste pictures into your brain that you’ve never seen before, edit out unwanted memories or even insert non-existent scents into an existing memory in a way that’s not too dissimilar to the way you might, for example, use Microsoft Word to create and edit different documents? Except here we’re talking about using the same principles to edit memories… Sounds like science fiction, right? Well, like telepathy used to be, it’s not so much any more, and it comes hot on the heels of other neuro-research that’s already helping people erase fear, and other memories, from their brains and “forget” their addictions.


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This week researchers at the University of California Berkeley announced they’ve tested the equipment to do just that, using holographic projection into the brain to activate or suppress dozens and ultimately thousands of neurons at once, hundreds of times each second, that allow the researchers to paste, using computer jargon, real patterns of brain activity onto them in order to fool the brain into thinking it has felt, seen or sensed something when it hasn’t. And in short, while what follows in the rest of this article is mind bending neuroscience speak, this is technology that one day will allow us to program the human brain and edit our memories and sensations in all manner of new ways. Yes fellow readers, Wonderland awaits…

The teams ultimate goal is to be able to design a machine that can constantly read an individual’s neural activity and decide, based on the activity, which sets of neurons to activate in order to simulate the pattern and rhythm of a “real” brain response so ultimately they can use these pasted or fake memories and responses to simulate sensations that might have been lost as the result of a trauma, or, for example, to better control neuroprosthetic limbs.


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“This has great potential for neural prostheses, since it has the precision needed for the brain to interpret the pattern of activation. If you can read and write the language of the brain, you can speak to it in its own language and it can interpret the message much better,” said Alan Mardinly, a postdoctoral fellow in the UC Berkeley lab of Hillel Adesnik, and an assistant professor of molecular and cell biology, “this is one of the first steps in a long road to develop a technology that could be a virtual brain implant with additional senses or enhanced senses.”


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Mardinly is one of three first authors of a paper appearing online April 30 in advance of publication in the journal Nature Neuroscience that describes the teams holographic brain modulator, which at the moment can activate up to 50 neurons at once in a 3D chunk of brain containing several thousand neurons, and repeat that up to 300 times a second with different sets of 50 neurons.

“The ability to talk to the brain has the incredible potential to help compensate for neurological damage caused by degenerative diseases or injury,” said Ehud Isacoff, a UC Berkeley professor of molecular and cell biology and director of the Helen Wills Neuroscience Institute, who was not involved in the research project, “by encoding perceptions into the human cortex, you could allow the blind to see or the paralysed to feel touch.”


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During the teams experiment each of the 2,000 to 3,000 neurons in the chunk of brain they were editing was augmented with a protein that, when hit by a flash of light, turns the cell on to create a brief spike of activity, and one of their key breakthroughs was finding a way to target each cell individually without hitting them all at once.

To focus the light onto just the cell body, a target that’s smaller than the width of a human hair, of nearly all cells in a chunk of brain, they turned to computer generated holography, which is a method of bending and focusing light to form a 3D spatial pattern. The effect is as if a 3D image were floating in space.

In this case, the holographic image was projected into a thin layer of brain tissue at the surface of the cortex, about a tenth of a millimeter thick, though a clear window into the brain.

“The major advance [here] is the ability to control individual neurons precisely in space and time,” said postdoc Nicolas Pégard, “in other words, to shoot the very specific sets of neurons you want to activate and do it at the characteristic scale and the speed at which they normally work.”


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The researchers have already tested the prototype in the touch, vision and motor areas of the brains of mice as they walk on a treadmill with their heads immobilised, and while they didn’t notice any behavioural changes in the mice when their brains were edited in this way Mardinly said that their brain activity, which is measured in real-time with two-photon imaging of calcium levels in the neurons, showed patterns similar to a response to a real sensory stimulus. They’re now training mice so they can detect behaviour changes after stimulation.

At the moment the team are focusing on an area of the brain which is a slice one-half millimeter square and one-tenth of a millimeter thick that can be scaled up to read from and write to more neurons in the brain’s outer layer, or cortex, Pégard said. And the laser holography setup could eventually be miniaturised to fit in a backpack a person could haul around, and then eventually all of this could be administered using equipment much smaller than is possible today.

Mardinly, Pégard and the other first author, postdoc Ian Oldenburg, constructed the holographic brain modulator by making technological advances in a number of areas.


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Mardinly and Oldenburg, together with Savitha Sridharan, a research associate in the lab, developed better optogenetic switches to insert into cells to turn them on and off. The switches, which are light-activated ion channels on the cell surface that open briefly when triggered, turn on strongly and then quickly shut off, all in about 3 milliseconds, so they’re ready to be re-stimulated up to 50 or more times per second, which is consistent with normal firing rates in the cortex.

Pégard developed the holographic projection system using a liquid crystal screen that acts like a holographic negative to sculpt the light from 40W lasers into the desired 3D pattern. The lasers are pulsed in 300 femtosecond-long bursts every microsecond. He, Mardinly, Oldenburg and their colleagues published a paper last year describing the device, which they call 3D-SHOT, for 3D scanless holographic optogenetics with temporal focusing.

“This is the culmination of a mix of different technologies that researchers have been working on for a while, but that up until now have been impossible to put together,” Mardinly said, “we solved numerous technical problems at the same time to bring it all together and finally realize the potential of this technology.”


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As they improve their technology, they plan to start capturing real patterns of activity in the cortex in order to learn how to reproduce sensations and perceptions to play back through their holographic system.

The work was supported by The New York Stem Cell Foundation, Arnold and Mabel Beckman Foundation, National Institute of Neurological Disorders and Stroke, McKnight Foundation, Simon’s Foundation, David and Lucille Packard Foundation and DARPA.


Source: UC Berkeley

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