Optical modulation goes deep in the brain

• Shuo Chen

Neurological disorders will affect more than one-third of us at some point in our lives. In just the next 10 years, the number of patients afflicted with a neurological disorder is projected to reach 1.1 billion worldwide. Yet safe and effective treatments for these conditions are largely lacking.

Deep brain stimulation (DBS) has proved to be one of the most effective therapies to date for neurological disorders ranging from Parkinson's disease to obsessive-compulsive disorder. However, such a treatment requires the implantation of electrodes deep in the brain to electrically stimulate the neurons that are thought to underlie these disorders. In addition to surgical and follow-up costs, which can reach up to $35,000, implantation is highly risky and invasive and the electrical stimulation lacks cell specificity. High-precision, minimally invasive technologies for the modulation of deep brain neurons are needed.

 

Potential candidates for noninvasive tissue-penetrating stimuli include electric, magnetic, acoustic, and optical signals. Transcranial brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been widely used in clinical research but lack spatial resolution and cell specificity, limiting their efficacy.

Optogenetics is a recently developed approach that harnesses genetically encoded light-gated ion channels called rhodopsins to achieve unprecedented precision in stimulating target neurons. The technique has hitherto required the insertion of invasive optical fibers for deep brain applications because the activating blue-green light is strongly scattered and absorbed by endogenous chromophores in brain tissue.

Overcoming the challenge of optical penetration depth will be the key to realizing noninvasive remote optogenetics with high clinical translation potential. Our recent study addressed this problem by applying a nanomaterial-assisted approach that “shifts” the existing optogenetic tools into the near-infrared region.

New Approach to Minimally Invasive DBS

To make optogenetics noninvasive, an obvious option is to use near-infrared light (NIR, 650 to 1350 nm), which can efficiently penetrate biological tissue and reach deep brain regions. However, the development of NIR-responsive rhodopsin variants has proved difficult: The optimal activation wavelengths of recently developed red-shifted rhodopsins all fall short of 650 nm.

We came up with a novel approach in which tissue-penetrating NIR light is locally converted to visible light in the deep brain to activate rhodopsin-expressing neurons (see the figure). To achieve this, we needed an optically unique material that functions much like a light bulb: Low-energy NIR photons turn the bulb on, leading to a high-energy visible emission. Such substances are called “upconversion materials.”

Exploiting “Upconversion” Nanoparticles

Ideal NIR-converting “light bulbs” must be small, efficient in light conversion, highly biocompatible, and have long-term stability. Lanthanide-doped upconversion nanoparticles (UCNPs) met these criteria. UCNPs are capable of converting incident NIR photons into visible emission at an efficiency that is orders of magnitude greater than that of multiphoton processes. As a result, a continuous-wave NIR laser diode of low power can drive intense UCNP-mediated upconversion emission.

To optimize their biocompatibility and long-term stability, we coated UCNPs with silica capable of chemically stabilizing the nanoparticles and preventing direct contact of their lanthanide-doped core with the tissue. The resulting monodispersed blue-emitting UCNPs (NaYF4:Yb/Tm@SiO2) of diameter ∼90 nm showed both minimum cytotoxicity and long-term stability: One month after injection, UCNPs still remained at the target site in the brain.

UCNPS Emit Blue Light Deep in the Brain

We reasoned that UCNP-mediated optogenetics would be feasible for transcranial stimulation of deep brain neurons, based on an evaluation of the upconversion efficiency of UCNPs and the transmittance of NIR light in brain tissue. To test this, we injected blue-emitting UCNPs into the ventral tegmental area (VTA) of the mouse brain, a region located ∼4.2 mm below the skull, and used in vivo fiber photometry to detect visible-light emission. Encouragingly, transcranial delivery of NIR pulses with a peak power of 2.0 W yielded upconverted blue emission of ∼0.063 mW/mm2. This emission strength is sufficient to activate the commonly used channelrhodopsin-2 (ChR2). We were thus motivated to harness UCNPs as optogenetic actuators of transcranial NIR to stimulate deep brain neurons.

Transcranial NIR Modulates Dopamine Release

We chose the VTA for an initial demonstration of transcranial NIR stimulation because of its medical implications. The VTA is a well-established node in the brain's reward system, and the dysregulation of dopamine (DA) release by VTA neurons is causally linked to many neurological disorders, such as major depression.

Science  02 Aug 2019:
Vol. 365, Issue 6452, pp. 456-457

This experiment won the Science and PINS Prize.

See also:from the big bang to strippers: why we need more scientists....

There are several quantum computer prototypes in the world, but so far none of them have been able to prove that they can actually be used to compute operations beyond the reach of traditional silicon-based machines.

Google has boasted of achieving "quantum supremacy" by successfully carrying out calculations on a quantum computer that are deemed impossible for regular ones, Financial Times reported, citing a research paper on NASA’s website that was removed soon after publication. Google has declined to comment on the matter and Sputnik has not been able to independently verify FT's report.

“To our knowledge, this experiment marks the first computation that can only be performed on a quantum processor”, the original publication reportedly said.

Google's report claimed that the company's quantum computer managed to finish calculations for a task that was unspecified in the document in 3 minutes and 20 seconds. The paper further claimed that the world's best supercomputer, Summit, capable of working at a speed of 200 petaflops (200x1015 operations with floating point often used in scientific computations), would take around 10,000 years to complete these calculations, meaning that the Google's computer was around 1.5 billion times faster than Summit.

However, despite Google reaching "quantum supremacy" when it comes to this specific task, it doesn't mean that quantum computers will replace regular ones anytime soon. As the paper points out, although the computer provided an "experimental realisation of quantum supremacy" and heralded the "advent of a much-anticipated computing paradigm", it was capable of performing only a single, highly technical calculation. The researchers noted that quantum computers are still years away from solving any practical problems.

 

 

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How does our predictable everyday world emerge from the hazy, probabilistic rules of quantum mechanics? That puzzle has vexed physicists since quantum theory emerged in the 1920s to explain the behavior of atoms and other infinitesimal things. Now, researchers fiddling with an electron trapped in a diamond have confirmed an essential prediction of a theory that strives to explain this transition from the quantum to classical realm. Called “quantum Darwinism,” the theory argues that classical states are simply the quantum ones that are most fit to survive interactions with their environment.

The experimenters “have a beautiful demonstration in a natural environment,” says Mauro Paternostro, a theorist at Queen's University in Belfast who was not involved in the work. Physicists caution, however, that the new study is far from the final word on the matter.

Atomic-scale objects behave differently from larger ones. Your coffee cup must be one place or another, but an electron can be in two places at once, in a so-called superposition state. Your cup's position and momentum also exist regardless of whether anyone observes them. Not so for an electron: If you know its position, then its momentum must be undefined, and vice versa, and which attribute the particle has emerges only when it is measured. The measurement “collapses” the electron's quantum state, or wave function—although how that happens remains obscure. Similarly, physicists assume a coffee cup cannot be here and there because something has collapsed its superposition one way or the other—perhaps contact with the surroundings.

Quantum Darwinism claims the truth is more subtle. In the 1980s, Wojciech Zurek, a theorist at Los Alamos National Laboratory in New Mexico, argued that the wave function of a here-and-there cup would inevitably meld with those of surrounding objects. That “entanglement” wouldn't collapse the cup's wave function, but it would obscure the exact relationship between the here and there parts of its quantum state. In quantum theory, that's enough to put the cup in one place or the other.

 

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Science  13 Sep 2019:
Vol. 365, Issue 6458, pp. 1070

 

 

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The famous feline-based thought experiment that describes the mysterious behaviour of subatomic particles might finally have a solution which doesn’t involve permanently killing the (hypothetical) animal.

The thought experiment described an imaginary cat which is simultaneously alive and dead inside a box with -  exists in a superposition of "dead" and "alive" states - just as subatomic particles exist in a superposition of many states at once. Only if one looked inside the box, the cat’s state would become permanent – either alive or dead.

However, a study published October 1 in the New Journal of Physics describes a way to potentially peek at the cat without forcing it to live or die, advancing scientists' understanding of one of the most fundamental paradoxes in physics. 

"We normally think the price we pay for looking is nothing," said study lead author Holger F. Hofmann, associate professor of physics at Hiroshima University in Japan. "That's not correct. In order to look, you have to have light, and light changes the object." That's because even a single photon of light transfers energy away from or to the object you're viewing. 

Hofmann and Kartik Patekar, who was a visiting undergraduate student at Hiroshima University at the time and is now at the Indian Institute of Technology Bombay, wondered if there was a way to look inside, and landed on a mathematical framework that separates the initial “interaction” - looking at the cat -  from the “readout” - knowing whether it's alive or dead.

"Our main motivation was to look very carefully at the way that a quantum measurement happens," Hofmann said. "And the key point is that we separate the measurement in two steps."

Hoffman and Patekar are able to assume that all the photons involved in the initial interaction, or peek at the cat, are captured without losing any information about the cat’s state. So before the readout, everything there is to know about the cat’s state (and about how looking at it has changed it) is still available. It’s only when we read out the information that we lose some of it.

Here's how they described their work in terms of Schrödinger's cat. The cat is still in the box, yet rather than looking inside to know whether the cat is alive or dead, you set up a camera outside the box that can somehow take a picture inside of it. Once the picture is taken, the camera has two kinds of information: how the cat changed as a result of the picture being taken and whether the cat is alive or dead after the interaction. None of that information has been lost yet. And depending on how you choose to "develop" the image, you retrieve one or the other piece of information.

 

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https://sputniknews.com/science/201911121077283972-physicists-solved-sch...

 

 

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THE QUEST FOR QUANTUM computers took off in 1994 when Peter Shor, a mathematician at the Massachusetts Institute of Technology, showed that such a machine—then hypothetical—should be able to quickly factor huge numbers. Shor's algorithm represents the possible factorizations of a number as quantum waves that can slosh simultaneously through the computer's qubits, thanks to the qubits' two-way states. The waves interfere so that the wrong factorizations cancel one another and the right one pops out. A machine running Shor's algorithm could, among other things, crack the encryption systems that now secure internet communications, which rely on the fact that searching for the factors of a huge number overwhelms any ordinary computer.

However, Shor assumed each qubit would maintain its state so the quantum waves could slosh around as long as necessary. Real qubits are far less stable. Google, IBM, and Rigetti use qubits made of tiny resonating circuits of superconducting metal etched into microchips, which so far have proved easier to control and integrate into circuits than other types of qubits. Each circuit has two distinct energy states, which can denote 0 or 1. By plying a circuit with microwaves, researchers can ease it into either state or any combination of the two—say, 30% 0 and 70% 1. But those inbetween states will fuzz out or “decohere” in a fraction of a second. Even before that happens, noise can jostle the state and alter it, potentially derailing a calculation.

Such noise nearly drowned out the signal in Google's quantum supremacy experiment. Researchers began by setting the 53 qubits to encode all possible outputs, which ranged from zero to 253. They implemented a set of randomly chosen interactions among the qubits that in repeated trials made some outputs more likely than others. Given the complexity of the interactions, a supercomputer would need thousands of years to calculate the pattern of outputs, the researchers said. So by measuring it, the quantum computer did something that no ordinary computer could match. But the pattern was barely distinguishable from the random flipping of qubits caused by noise. “Their demonstration is 99% noise and only 1% signal,” Kuperberg says.

To realize their ultimate dreams, developers want qubits that are as reliable as the bits in an ordinary computer. “You want to have a qubit that stays coherent until you switch off the machine,” Neven says.

Scientists' approach of spreading the information of one qubit—a “logical qubit”—among many physical ones traces its roots to the early days of ordinary computers in the 1950s. The bits of early computers consisted of vacuum tubes or mechanical relays, which were prone to flip unexpectedly. To overcome the problem, famed mathematician John von Neumann pioneered the field of error correction.

Von Neumann's approach relied on redundancy. Suppose a computer makes three copies of each bit. Then, even if one of the three flips, the majority of the bits will preserve the correct setting. The computer can find and fix the flipped bit by comparing the bits in pairs, in so-called parity checks. If the first and third bits match, but the first and second and second and third differ, then most likely, the second bit flipped, and the computer can flip it back. Greater redundancy means greater ability to correct errors. Ironically, the transistors, etched into microchips, that modern computers use to encode their bits are so reliable that error correction isn't much used.

But a quantum computer will depend on it, at least if it's made of superconducting qubits. (Qubits made of individual ions suffer less from noise, but are harder to integrate.) Unfortunately for developers, quantum mechanics itself makes their task much harder by depriving them of their simplest error-correcting tool, copying. In quantum mechanics, a no-cloning theorem says it's not possible to copy the state of one qubit onto another without altering the state of the first one. “This means that it's not possible to directly translate our classical error correction codes to quantum error correction codes,” says Joschka Roffe, a theorist at the University of Sheffield.

Even worse, quantum mechanics requires researchers to find errors blindfolded. Although a qubit can have a state that is both 0 and 1 at the same time, according to quantum theory, experimenters can't measure that two-way state without collapsing it into either 0 or 1. Checking a state obliterates it. “The simplest [classical error] correction is that you look at all the bits to see what's gone wrong,” Kuperberg says. “But if it's qubits then you have to find the error without looking.”

Those hurdles may sound insurmountable, but quantum mechanics points to a potential solution. Researchers cannot copy a qubit's state, but they can extend it to other qubits using a mysterious quantum connection called entanglement.

 

 

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Science  10 Jul 2020:

Vol. 369, Issue 6500, pp. 130-133

 

 

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