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#437543 This Is How We’ll Engineer Artificial ...

Take a Jeopardy! guess: this body part was once referred to as the “consummation of all perfection as an instrument.”

Answer: “What is the human hand?”

Our hands are insanely complex feats of evolutionary engineering. Densely-packed sensors provide intricate and ultra-sensitive feelings of touch. Dozens of joints synergize to give us remarkable dexterity. A “sixth sense” awareness of where our hands are in space connects them to the mind, making it possible to open a door, pick up a mug, and pour coffee in total darkness based solely on what they feel.

So why can’t robots do the same?

In a new article in Science, Dr. Subramanian Sundaram at Boston and Harvard University argues that it’s high time to rethink robotic touch. Scientists have long dreamed of artificially engineering robotic hands with the same dexterity and feedback that we have. Now, after decades, we’re at the precipice of a breakthrough thanks to two major advances. One, we better understand how touch works in humans. Two, we have the mega computational powerhouse called machine learning to recapitulate biology in silicon.

Robotic hands with a sense of touch—and the AI brain to match it—could overhaul our idea of robots. Rather than charming, if somewhat clumsy, novelties, robots equipped with human-like hands are far more capable of routine tasks—making food, folding laundry—and specialized missions like surgery or rescue. But machines aren’t the only ones to gain. For humans, robotic prosthetic hands equipped with accurate, sensitive, and high-resolution artificial touch is the next giant breakthrough to seamlessly link a biological brain to a mechanical hand.

Here’s what Sundaram laid out to get us to that future.

How Does Touch Work, Anyway?
Let me start with some bad news: reverse engineering the human hand is really hard. It’s jam-packed with over 17,000 sensors tuned to mechanical forces alone, not to mention sensors for temperature and pain. These force “receptors” rely on physical distortions—bending, stretching, curling—to signal to the brain.

The good news? We now have a far clearer picture of how biological touch works. Imagine a coin pressed into your palm. The sensors embedded in the skin, called mechanoreceptors, capture that pressure, and “translate” it into electrical signals. These signals pulse through the nerves on your hand to the spine, and eventually make their way to the brain, where they gets interpreted as “touch.”

At least, that’s the simple version, but one too vague and not particularly useful for recapitulating touch. To get there, we need to zoom in.

The cells on your hand that collect touch signals, called tactile “first order” neurons (enter Star Wars joke) are like upside-down trees. Intricate branches extend from their bodies, buried deep in the skin, to a vast area of the hand. Each neuron has its own little domain called “receptor fields,” although some overlap. Like governors, these neurons manage a semi-dedicated region, so that any signal they transfer to the higher-ups—spinal cord and brain—is actually integrated from multiple sensors across a large distance.

It gets more intricate. The skin itself is a living entity that can regulate its own mechanical senses through hydration. Sweat, for example, softens the skin, which changes how it interacts with surrounding objects. Ever tried putting a glove onto a sweaty hand? It’s far more of a struggle than a dry one, and feels different.

In a way, the hand’s tactile neurons play a game of Morse Code. Through different frequencies of electrical beeps, they’re able to transfer information about an object’s size, texture, weight, and other properties, while also asking the brain for feedback to better control the object.

Biology to Machine
Reworking all of our hands’ greatest features into machines is absolutely daunting. But robots have a leg up—they’re not restricted to biological hardware. Earlier this year, for example, a team from Columbia engineered a “feeling” robotic finger using overlapping light emitters and sensors in a way loosely similar to receptor fields. Distortions in light were then analyzed with deep learning to translate into contact location and force.

Although a radical departure from our own electrical-based system, the Columbia team’s attempt was clearly based on human biology. They’re not alone. “Substantial progress is being made in the creation of soft, stretchable electronic skins,” said Sundaram, many of which can sense forces or pressure, although they’re currently still limited.

What’s promising, however, is the “exciting progress in using visual data,” said Sundaram. Computer vision has gained enormously from ubiquitous cameras and large datasets, making it possible to train powerful but data-hungry algorithms such as deep convolutional neural networks (CNNs).

By piggybacking on their success, we can essentially add “eyes” to robotic hands, a superpower us humans can’t imagine. Even better, CNNs and other classes of algorithms can be readily adopted for processing tactile data. Together, a robotic hand could use its eyes to scan an object, plan its movements for grasp, and use touch for feedback to adjust its grip. Maybe we’ll finally have a robot that easily rescues the phone sadly dropped into a composting toilet. Or something much grander to benefit humanity.

That said, relying too heavily on vision could also be a downfall. Take a robot that scans a wide area of rubble for signs of life during a disaster response. If touch relies on sight, then it would have to keep a continuous line-of-sight in a complex and dynamic setting—something computer vision doesn’t do well in, at least for now.

A Neuromorphic Way Forward
Too Debbie Downer? I got your back! It’s hard to overstate the challenges, but what’s clear is that emerging machine learning tools can tackle data processing challenges. For vision, it’s distilling complex images into “actionable control policies,” said Sundaram. For touch, it’s easy to imagine the same. Couple the two together, and that’s a robotic super-hand in the making.

Going forward, argues Sundaram, we need to closely adhere to how the hand and brain process touch. Hijacking our biological “touch machinery” has already proved useful. In 2019, one team used a nerve-machine interface for amputees to control a robotic arm—the DEKA LUKE arm—and sense what the limb and attached hand were feeling. Pressure on the LUKE arm and hand activated an implanted neural interface, which zapped remaining nerves in a way that the brain processes as touch. When the AI analyzed pressure data similar to biological tactile neurons, the person was able to better identify different objects with their eyes closed.

“Neuromorphic tactile hardware (and software) advances will strongly influence the future of bionic prostheses—a compelling application of robotic hands,” said Sundaram, adding that the next step is to increase the density of sensors.

Two additional themes made the list of progressing towards a cyborg future. One is longevity, in that sensors on a robot need to be able to reliably produce large quantities of high-quality data—something that’s seemingly mundane, but is a practical limitation.

The other is going all-in-one. Rather than just a pressure sensor, we need something that captures the myriad of touch sensations. From feather-light to a heavy punch, from vibrations to temperatures, a tree-like architecture similar to our hands would help organize, integrate, and otherwise process data collected from those sensors.

Just a decade ago, mind-controlled robotics were considered a blue sky, stretch-goal neurotechnological fantasy. We now have a chance to “close the loop,” from thought to movement to touch and back to thought, and make some badass robots along the way.

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#437416 Robotics firm expands autonomous data ...

Back in 2013, local Brooklyn papers were excitedly reporting on a new initiative aimed at getting residents involved in cleaning up the highly polluted Gowanus Canal. Brooklyn Atlantis, as the project was known, was the brainchild of NYU Tandon Professor of Mechanical and Aerospace Engineering Maurizio Porfiri, who envisioned building and launching robotic boats to collect water-quality data and capture images of the infamous canal, which citizen scientists would then view and help classify. Those robotic boats ultimately led to the formation of the company Manifold Robotics, which aimed to further develop the unmanned surface vehicles (USVs) with sensor technology. (The fledgling company received support from PowerBridgeNY, a collaborative initiative to bring university research to market.) More recently, the startup has now branched out to develop a mobile data collection platform that allows unmanned aerial vehicles (UAVs) to operate safely in the sky near power lines. Continue reading

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#437293 These Scientists Just Completed a 3D ...

Human brain maps are a dime a dozen these days. Maps that detail neurons in a certain region. Maps that draw out functional connections between those cells. Maps that dive deeper into gene expression. Or even meta-maps that combine all of the above.

But have you ever wondered: how well do those maps represent my brain? After all, no two brains are alike. And if we’re ever going to reverse-engineer the brain as a computer simulation—as Europe’s Human Brain Project is trying to do—shouldn’t we ask whose brain they’re hoping to simulate?

Enter a new kind of map: the Julich-Brain, a probabilistic map of human brains that accounts for individual differences using a computational framework. Rather than generating a static PDF of a brain map, the Julich-Brain atlas is also dynamic, in that it continuously changes to incorporate more recent brain mapping results. So far, the map has data from over 24,000 thinly sliced sections from 23 postmortem brains covering most years of adulthood at the cellular level. But the atlas can also continuously adapt to progress in mapping technologies to aid brain modeling and simulation, and link to other atlases and alternatives.

In other words, rather than “just another” human brain map, the Julich-Brain atlas is its own neuromapping API—one that could unite previous brain-mapping efforts with more modern methods.

“It is exciting to see how far the combination of brain research and digital technologies has progressed,” said Dr. Katrin Amunts of the Institute of Neuroscience and Medicine at Research Centre Jülich in Germany, who spearheaded the study.

The Old Dogma
The Julich-Brain atlas embraces traditional brain-mapping while also yanking the field into the 21st century.

First, the new atlas includes the brain’s cytoarchitecture, or how brain cells are organized. As brain maps go, these kinds of maps are the oldest and most fundamental. Rather than exploring how neurons talk to each other functionally—which is all the rage these days with connectome maps—cytoarchitecture maps draw out the physical arrangement of neurons.

Like a census, these maps literally capture how neurons are distributed in the brain, what they look like, and how they layer within and between different brain regions.

Because neurons aren’t packed together the same way between different brain regions, this provides a way to parse the brain into areas that can be further studied. When we say the brain’s “memory center,” the hippocampus, or the emotion center, the “amygdala,” these distinctions are based on cytoarchitectural maps.

Some may call this type of mapping “boring.” But cytoarchitecture maps form the very basis of any sort of neuroscience understanding. Like hand-drawn maps from early explorers sailing to the western hemisphere, these maps provide the brain’s geographical patterns from which we try to decipher functional connections. If brain regions are cities, then cytoarchitecture maps attempt to show trading or other “functional” activities that occur in the interlinking highways.

You might’ve heard of the most common cytoarchitecture map used today: the Brodmann map from 1909 (yup, that old), which divided the brain into classical regions based on the cells’ morphology and location. The map, while impactful, wasn’t able to account for brain differences between people. More recent brain-mapping technologies have allowed us to dig deeper into neuronal differences and divide the brain into more regions—180 areas in the cortex alone, compared with 43 in the original Brodmann map.

The new study took inspiration from that age-old map and transformed it into a digital ecosystem.

A Living Atlas
Work began on the Julich-Brain atlas in the mid-1990s, with a little help from the crowd.

The preparation of human tissue and its microstructural mapping, analysis, and data processing is incredibly labor-intensive, the authors lamented, making it impossible to do for the whole brain at high resolution in just one lab. To build their “Google Earth” for the brain, the team hooked up with EBRAINS, a shared computing platform set up by the Human Brain Project to promote collaboration between neuroscience labs in the EU.

First, the team acquired MRI scans of 23 postmortem brains, sliced the brains into wafer-thin sections, and scanned and digitized them. They corrected distortions from the chopping using data from the MRI scans and then lined up neurons in consecutive sections—picture putting together a 3D puzzle—to reconstruct the whole brain. Overall, the team had to analyze 24,000 brain sections, which prompted them to build a computational management system for individual brain sections—a win, because they could now track individual donor brains too.

Their method was quite clever. They first mapped their results to a brain template from a single person, called the MNI-Colin27 template. Because the reference brain was extremely detailed, this allowed the team to better figure out the location of brain cells and regions in a particular anatomical space.

However, MNI-Colin27’s brain isn’t your or my brain—or any of the brains the team analyzed. To dilute any of Colin’s potential brain quirks, the team also mapped their dataset onto an “average brain,” dubbed the ICBM2009c (catchy, I know).

This step allowed the team to “standardize” their results with everything else from the Human Connectome Project and the UK Biobank, kind of like adding their Google Maps layer to the existing map. To highlight individual brain differences, the team overlaid their dataset on existing ones, and looked for differences in the cytoarchitecture.

The microscopic architecture of neurons change between two areas (dotted line), forming the basis of different identifiable brain regions. To account for individual differences, the team also calculated a probability map (right hemisphere). Image credit: Forschungszentrum Juelich / Katrin Amunts
Based on structure alone, the brains were both remarkably different and shockingly similar at the same time. For example, the cortexes—the outermost layer of the brain—were physically different across donor brains of different age and sex. The region especially divergent between people was Broca’s region, which is traditionally linked to speech production. In contrast, parts of the visual cortex were almost identical between the brains.

The Brain-Mapping Future
Rather than relying on the brain’s visible “landmarks,” which can still differ between people, the probabilistic map is far more precise, the authors said.

What’s more, the map could also pool yet unmapped regions in the cortex—about 30 percent or so—into “gap maps,” providing neuroscientists with a better idea of what still needs to be understood.

“New maps are continuously replacing gap maps with progress in mapping while the process is captured and documented … Consequently, the atlas is not static but rather represents a ‘living map,’” the authors said.

Thanks to its structurally-sound architecture down to individual cells, the atlas can contribute to brain modeling and simulation down the line—especially for personalized brain models for neurological disorders such as seizures. Researchers can also use the framework for other species, and they can even incorporate new data-crunching processors into the workflow, such as mapping brain regions using artificial intelligence.

Fundamentally, the goal is to build shared resources to better understand the brain. “[These atlases] help us—and more and more researchers worldwide—to better understand the complex organization of the brain and to jointly uncover how things are connected,” the authors said.

Image credit: Richard Watts, PhD, University of Vermont and Fair Neuroimaging Lab, Oregon Health and Science University Continue reading

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#437209 A Renaissance of Genomics and Drugs Is ...

The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.

With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to turn those answers into practical ways to extend our healthspan.

In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.

Genome Sequencing and Editing
Your genome is the software that runs your body. A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity for disease, your lifespan, and so on.

Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean. Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $1,500 in 2015.

Today, the cost of genome sequencing has dropped below $600, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.

This represents one of the most powerful and transformative technology revolutions in healthcare. When we understand your genome, we’ll be able to understand how to optimize “you.”

We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later article).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).

CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally occurring biological system discovered in 1987 called CRISPR/Cas9.

Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.

Here’s how it works. The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.

Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome. A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.

2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.

Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.

With great power comes great responsibility, and the opportunity for moral and ethical dilemmas. In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera. Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.

To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.

Coupled with significant ethical conversations necessary for progress, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.

Senolytics, Nutraceuticals, and Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely. These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse. Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification to localized inflammatory conditions such as osteoarthritis to diminished lung function.

Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.

Prominent companies in the field include the following:

Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology, and pulmonary disease.

Oisin Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.

SIWA Therapeutics is working on an immunotherapy approach to the problem of senescent cells.

In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.

(1) Rapamycin

Originally extracted from bacteria found on Easter Island, rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division. Currently, rapamycin derivatives are widely used for immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.

PureTech Health subsidiary resTORbio (which went public in 2018) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.

Results of the drug’s recent clinical trial include decreased incidence of infection, improved influenza vaccination response, and a 30.6 percent decrease in respiratory tract infection.

Impressive, to say the least.

(2) Metformin

Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients. Researchers have found that metformin also reduces oxidative stress and inflammation, which otherwise increase as we age. There is strong evidence that metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.

Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of metformin’s protective effect against cancer.

(3) Nutraceuticals and NAD+

Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.

NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.

The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.

Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.

The next article in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.

We are edging closer toward a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?

Join Me
(1) A360 Executive Mastermind: If you’re an exponentially and abundance-minded entrepreneur who would like coaching directly from me, consider joining my Abundance 360 Mastermind, a highly selective community of 360 CEOs and entrepreneurs who I coach for 3 days every January in Beverly Hills, Ca. Through A360, I provide my members with context and clarity about how converging exponential technologies will transform every industry. I’m committed to running A360 for the course of an ongoing 25-year journey as a “countdown to the Singularity.”

If you’d like to learn more and consider joining our 2021 membership, apply here.

(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.

(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)

This article originally appeared on diamandis.com. Read the original article here.

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#437202 Scientists Used Dopamine to Seamlessly ...

In just half a decade, neuromorphic devices—or brain-inspired computing—already seem quaint. The current darling? Artificial-biological hybrid computing, uniting both man-made computer chips and biological neurons seamlessly into semi-living circuits.

It sounds crazy, but a new study in Nature Materials shows that it’s possible to get an artificial neuron to communicate directly with a biological one using not just electricity, but dopamine—a chemical the brain naturally uses to change how neural circuits behave, most known for signaling reward.

Because these chemicals, known as “neurotransmitters,” are how biological neurons functionally link up in the brain, the study is a dramatic demonstration that it’s possible to connect artificial components with biological brain cells into a functional circuit.

The team isn’t the first to pursue hybrid neural circuits. Previously, a different team hooked up two silicon-based artificial neurons with a biological one into a circuit using electrical protocols alone. Although a powerful demonstration of hybrid computing, the study relied on only one-half of the brain’s computational ability: electrical computing.

The new study now tackles the other half: chemical computing. It adds a layer of compatibility that lays the groundwork not just for brain-inspired computers, but also for brain-machine interfaces and—perhaps—a sort of “cyborg” future. After all, if your brain can’t tell the difference between an artificial neuron and your own, could you? And even if you did, would you care?

Of course, that scenario is far in the future—if ever. For now, the team, led by Dr. Alberto Salleo, professor of materials science and engineering at Stanford University, collectively breathed a sigh of relief that the hybrid circuit worked.

“It’s a demonstration that this communication melding chemistry and electricity is possible,” said Salleo. “You could say it’s a first step toward a brain-machine interface, but it’s a tiny, tiny very first step.”

Neuromorphic Computing
The study grew from years of work into neuromorphic computing, or data processing inspired by the brain.

The blue-sky idea was inspired by the brain’s massive parallel computing capabilities, along with vast energy savings. By mimicking these properties, scientists reasoned, we could potentially turbo-charge computing. Neuromorphic devices basically embody artificial neural networks in physical form—wouldn’t hardware that mimics how the brain processes information be even more efficient and powerful?

These explorations led to novel neuromorphic chips, or artificial neurons that “fire” like biological ones. Additional work found that it’s possible to link these chips up into powerful circuits that run deep learning with ease, with bioengineered communication nodes called artificial synapses.

As a potential computing hardware replacement, these systems have proven to be incredibly promising. Yet scientists soon wondered: given their similarity to biological brains, can we use them as “replacement parts” for brains that suffer from traumatic injuries, aging, or degeneration? Can we hook up neuromorphic components to the brain to restore its capabilities?

Buzz & Chemistry
Theoretically, the answer’s yes.

But there’s a huge problem: current brain-machine interfaces only use electrical signals to mimic neural computation. The brain, in contrast, has two tricks up its sleeve: electricity and chemicals, or electrochemical.

Within a neuron, electricity travels up its incoming branches, through the bulbous body, then down the output branches. When electrical signals reach the neuron’s outgoing “piers,” dotted along the output branch, however, they hit a snag. A small gap exists between neurons, so to get to the other side, the electrical signals generally need to be converted into little bubble ships, packed with chemicals, and set sail to the other neuronal shore.

In other words, without chemical signals, the brain can’t function normally. These neurotransmitters don’t just passively carry information. Dopamine, for example, can dramatically change how a neural circuit functions. For an artificial-biological hybrid neural system, the absence of chemistry is like nixing international cargo vessels and only sticking with land-based trains and highways.

“To emulate biological synaptic behavior, the connectivity of the neuromorphic device must be dynamically regulated by the local neurotransmitter activity,” the team said.

Let’s Get Electro-Chemical
The new study started with two neurons: the upstream, an immortalized biological cell that releases dopamine; and the downstream, an artificial neuron that the team previously introduced in 2017, made of a mix of biocompatible and electrical-conducting materials.

Rather than the classic neuron shape, picture more of a sandwich with a chunk bitten out in the middle (yup, I’m totally serious). Each of the remaining parts of the sandwich is a soft electrode, made of biological polymers. The “bitten out” part has a conductive solution that can pass on electrical signals.

The biological cell sits close to the first electrode. When activated, it dumps out boats of dopamine, which drift to the electrode and chemically react with it—mimicking the process of dopamine docking onto a biological neuron. This, in turn, generates a current that’s passed on to the second electrode through the conductive solution channel. When this current reaches the second electrode, it changes the electrode’s conductance—that is, how well it can pass on electrical information. This second step is analogous to docked dopamine “ships” changing how likely it is that a biological neuron will fire in the future.

In other words, dopamine release from the biological neuron interacts with the artificial one, so that the chemicals change how the downstream neuron behaves in a somewhat lasting way—a loose mimic of what happens inside the brain during learning.

But that’s not all. Chemical signaling is especially powerful in the brain because it’s flexible. Dopamine, for example, only grabs onto the downstream neurons for a bit before it returns back to its upstream neuron—that is, recycled or destroyed. This means that its effect is temporary, giving the neural circuit breathing room to readjust its activity.

The Stanford team also tried reconstructing this quirk in their hybrid circuit. They crafted a microfluidic channel that shuttles both dopamine and its byproduct away from the artificial neurons after they’ve done their job for recycling.

Putting It All Together
After confirming that biological cells can survive happily on top of the artificial one, the team performed a few tests to see if the hybrid circuit could “learn.”

They used electrical methods to first activate the biological dopamine neuron, and watched the artificial one. Before the experiment, the team wasn’t quite sure what to expect. Theoretically, it made sense that dopamine would change the artificial neuron’s conductance, similar to learning. But “it was hard to know whether we’d achieve the outcome we predicted on paper until we saw it happen in the lab,” said study author Scott Keene.

On the first try, however, the team found that the burst of chemical signaling was able to change the artificial neuron’s conductance long-term, similar to the neuroscience dogma “neurons that fire together, wire together.” Activating the upstream biological neuron with chemicals also changed the artificial neuron’s conductance in a way that mimicked learning.

“That’s when we realized the potential this has for emulating the long-term learning process of a synapse,” said Keene.

Visualizing under an electron microscope, the team found that, similar to its biological counterpart, the hybrid synapse was able to efficiently recycle dopamine with timescales similar to the brain after some calibration. By playing with how much dopamine accumulates at the artificial neuron, the team found that they loosely mimic a learning rule called spike learning—a darling of machine learning inspired by the brain’s computation.

A Hybrid Future?
Unfortunately for cyborg enthusiasts, the work is still in its infancy.

For one, the artificial neurons are still rather bulky compared to biological ones. This means that they can’t capture and translate information from a single “boat” of dopamine. It’s also unclear if, and how, a hybrid synapse can work inside a living brain. Given the billions of synapses firing away in our heads, it’ll be a challenge to find-and-replace those that need replacement, and be able to control our memories and behaviors similar to natural ones.

That said, we’re inching ever closer to full-capability artificial-biological hybrid circuits.

“The neurotransmitter-mediated neuromorphic device presented in this work constitutes a fundamental building block for artificial neural networks that can be directly modulated based on biological feedback from live neurons,” the authors concluded. “[It] is a crucial first step in realizing next-generation adaptive biohybrid interfaces.”

Image Credit: Gerd Altmann from Pixabay Continue reading

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