Tag Archives: brain

Getting your brain cells to glow in the dark

The extraordinary effort to colonize our brains continues apace with a new sensor from Vanderbilt University. From an Oct. 27, 2016 news item on ScienceDaily,

A new kind of bioluminescent sensor causes individual brain cells to imitate fireflies and glow in the dark.

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. …

The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain.

“For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time,” said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort.

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

An Oct. 27, 2016 Vanderbilt University news release (also on EurekAlert) by David Salisbury, which originated the news item, explains the work in more detail,

“Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive,” he [Carl Johnson] said.

Based on their research on bioluminescence in “a scummy little organism, the green alga Chlamydomonas, that nobody cares much about” Johnson and his colleagues realized that if they could combine luminescence with optogenetics – a new biological technique that uses light to control cells, particularly neurons, in living tissue – they could create a powerful new tool for studying brain activity.

“There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells,” said Johnson. “Luminescence, on the other hand, works in the dark!”

Johnson and his collaborators – Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics – genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior.

The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors.

They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron’s outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light.

To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell’s ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming.

“We’ve shown that the approach works,” Johnson said. “Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability.”

Here’s a link to and a citation for the paper,

Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing by Jie Yang, Derrick Cumberbatch, Samuel Centanni, Shu-qun Shi, Danny Winder, Donna Webb, & Carl Hirschie Johnson. Nature Communications 7, Article number: 13268 (2016)  doi:10.1038/ncomms13268 Published online: 27 October 2016

This paper is open access.

Stretchy optical materials for implants that could pulse light

An Oct. 17, 2016 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert) by Emily Chu describes research that could lead to long-lasting implants offering preventive health strategies,

Researchers from MIT and Harvard Medical School have developed a biocompatible and highly stretchable optical fiber made from hydrogel — an elastic, rubbery material composed mostly of water. The fiber, which is as bendable as a rope of licorice, may one day be implanted in the body to deliver therapeutic pulses of light or light up at the first sign of disease. [emphasis mine]

The researchers say the fiber may serve as a long-lasting implant that would bend and twist with the body without breaking down. The team has published its results online in the journal Advanced Materials.

Using light to activate cells, and particularly neurons in the brain, is a highly active field known as optogenetics, in which researchers deliver short pulses of light to targeted tissues using needle-like fibers, through which they shine light from an LED source.

“But the brain is like a bowl of Jell-O, whereas these fibers are like glass — very rigid, which can possibly damage brain tissues,” says Xuanhe Zhao, the Robert N. Noyce Career Development Associate Professor in MIT’s Department of Mechanical Engineering. “If these fibers could match the flexibility and softness of the brain, they could provide long-term more effective stimulation and therapy.”

Getting to the core of it

Zhao’s group at MIT, including graduate students Xinyue Liu and Hyunwoo Yuk, specializes in tuning the mechanical properties of hydrogels. The researchers have devised multiple recipes for making tough yet pliable hydrogels out of various biopolymers. The team has also come up with ways to bond hydrogels with various surfaces such as metallic sensors and LEDs, to create stretchable electronics.

The researchers only thought to explore hydrogel’s use in optical fibers after conversations with the bio-optics group at Harvard Medical School, led by Associate Professor Seok-Hyun (Andy) Yun. Yun’s group had previously fabricated an optical fiber from hydrogel material that successfully transmitted light through the fiber. However, the material broke apart when bent or slightly stretched. Zhao’s hydrogels, in contrast, could stretch and bend like taffy. The two groups joined efforts and looked for ways to incorporate Zhao’s hydrogel into Yun’s optical fiber design.

Yun’s design consists of a core material encased in an outer cladding. To transmit the maximum amount of light through the core of the fiber, the core and the cladding should be made of materials with very different refractive indices, or degrees to which they can bend light.

“If these two things are too similar, whatever light source flows through the fiber will just fade away,” Yuk explains. “In optical fibers, people want to have a much higher refractive index in the core, versus cladding, so that when light goes through the core, it bounces off the interface of the cladding and stays within the core.”

Happily, they found that Zhao’s hydrogel material was highly transparent and possessed a refractive index that was ideal as a core material. But when they tried to coat the hydrogel with a cladding polymer solution, the two materials tended to peel apart when the fiber was stretched or bent.

To bond the two materials together, the researchers added conjugation chemicals to the cladding solution, which, when coated over the hydrogel core, generated chemical links between the outer surfaces of both materials.

“It clicks together the carboxyl groups in the cladding, and the amine groups in the core material, like molecular-level glue,” Yuk says.

Sensing strain

The researchers tested the optical fibers’ ability to propagate light by shining a laser through fibers of various lengths. Each fiber transmitted light without significant attenuation, or fading. They also found that fibers could be stretched over seven times their original length without breaking.

Now that they had developed a highly flexible and robust optical fiber, made from a hydrogel material that was also biocompatible, the researchers began to play with the fiber’s optical properties, to see if they could design a fiber that could sense when and where it was being stretched.

They first loaded a fiber with red, green, and blue organic dyes, placed at specific spots along the fiber’s length. Next, they shone a laser through the fiber and stretched, for instance, the red region. They measured the spectrum of light that made it all the way through the fiber, and noted the intensity of the red light. They reasoned that this intensity relates directly to the amount of light absorbed by the red dye, as a result of that region being stretched.

In other words, by measuring the amount of light at the far end of the fiber, the researchers can quantitatively determine where and by how much a fiber was stretched.

“When you stretch a certain portion of the fiber, the dimensions of that part of the fiber changes, along with the amount of light that region absorbs and scatters, so in this way, the fiber can serve as a sensor of strain,” Liu explains.

“This is like a multistrain sensor through a single fiber,” Yuk adds. “So it can be an implantable or wearable strain gauge.”

The researchers imagine that such stretchable, strain-sensing optical fibers could be implanted or fitted along the length of a patient’s arm or leg, to monitor for signs of improving mobility.

Zhao envisions the fibers may also serve as sensors, lighting up in response to signs of disease.

“We may be able to use optical fibers for long-term diagnostics, to optically monitor tumors or inflammation,” he says. “The applications can be impactful.”

Here’s a link to and a citation for the paper,

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers by Jingjing Guo, Xinyue Liu, Nan Jiang, Ali K. Yetisen, Hyunwoo Yuk, Changxi Yang, Ali Khademhosseini, Xuanhe Zhao, and Seok-Hyun Yun. Advanced Materials DOI: 10.1002/adma.201603160 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

A guide to producing transparent electronics

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

Read this Oct. 13, 2016 news item on ScienceDaily if you want to find out how to make your own transparent electronics,

When University of Wisconsin-Madison engineers announced in the journal Nature Communications that they had developed transparent sensors for use in imaging the brain, researchers around the world took notice.

Then the requests came flooding in. “So many research groups started asking us for these devices that we couldn’t keep up,” says Zhenqiang (Jack) Ma, the Lynn H. Matthias Professor and Vilas Distinguished Achievement Professor in electrical and computer engineering at UW-Madison.

As a result, in a paper published in the journal Nature Protocols, the researchers have described in great detail how to fabricate and use transparent graphene neural electrode arrays in applications in electrophysiology, fluorescent microscopy, optical coherence tomography, and optogenetics. “We described how to do these things so we can start working on the next generation,” says Ma.

Although he and collaborator Justin Williams, the Vilas Distinguished Achievement Professor in biomedical engineering and neurological surgery at UW-Madison, patented the technology through the Wisconsin Alumni Research Foundation, they saw its potential for advancements in research. “That little step has already resulted in an explosion of research in this field,” says Williams. “We didn’t want to keep this technology in our lab. We wanted to share it and expand the boundaries of its applications.”

An Oct. 13, 2016 University of Wisconsin-Madison news release, which originated the news item, provides more detail about the paper and the researchers,

‘This paper is a gateway for other groups to explore the huge potential from here,’ says Ma. ‘Our technology demonstrates one of the key in vivo applications of graphene. We expect more revolutionary research will follow in this interdisciplinary field.’

Ma’s group is a world leader in developing revolutionary flexible electronic devices. The see-through, implantable micro-electrode arrays were light years beyond anything ever created.

Here’s a link to and a citation for the paper,

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics by Dong-Wook Park, Sarah K Brodnick, Jared P Ness, Farid Atry, Lisa Krugner-Higby, Amelia Sandberg, Solomon Mikael, Thomas J Richner, Joseph Novello, Hyungsoo Kim, Dong-Hyun Baek, Jihye Bong, Seth T Frye, Sanitta Thongpang, Kyle I Swanson, Wendell Lake, Ramin Pashaie, Justin C Williams, & Zhenqiang Ma. Nature Protocols 11, 2201–2222 (2016) doi:10.1038/nprot.2016.127 Published online 13 October 2016

Of course this paper is open access. The team’s previous paper published in 2014 was featured here in an Oct. 23, 2014 posting.

The memristor as the ‘missing link’ in bioelectronic medicine?

The last time I featured memrisors and a neuronal network it was in an April 22, 2016 posting about Russian research in that field. This latest work comes from the UK’s University of Southampton. From a Sept. 27, 2016 news item on phys.org,

New research, led by the University of Southampton, has demonstrated that a nanoscale device, called a memristor, could be the ‘missing link’ in the development of implants that use electrical signals from the brain to help treat medical conditions.

Monitoring neuronal cell activity is fundamental to neuroscience and the development of neuroprosthetics – biomedically engineered devices that are driven by neural activity. However, a persistent problem is the device being able to process the neural data in real-time, which imposes restrictive requirements on bandwidth, energy and computation capacity.

In a new study, published in Nature Communications, the researchers showed that memristors could provide real-time processing of neuronal signals (spiking events) leading to efficient data compression and the potential to develop more precise and affordable neuroprosthetics and bioelectronic medicines.

A Sept. 27, 2016 University of Southampton press release, which originated the news item, expands on the theme,

Memristors are electrical components that limit or regulate the flow of electrical current in a circuit and can remember the amount of charge that was flowing through it and retain the data, even when the power is turned off.

Lead author Isha Gupta, Postgraduate Research Student at the University of Southampton, said: “Our work can significantly contribute towards further enhancing the understanding of neuroscience, developing neuroprosthetics and bio-electronic medicines by building tools essential for interpreting the big data in a more effective way.”

The research team developed a nanoscale Memristive Integrating Sensor (MIS) into which they fed a series of voltage-time samples, which replicated neuronal electrical activity.

Acting like synapses in the brain, the metal-oxide MIS was able to encode and compress (up to 200 times) neuronal spiking activity recorded by multi-electrode arrays. Besides addressing the bandwidth constraints, this approach was also very power efficient – the power needed per recording channel was up to 100 times less when compared to current best practice.

Co-author Dr Themis Prodromakis, Reader in Nanoelectronics and EPSRC Fellow in Electronics and Computer Science at the University of Southampton said: “We are thrilled that we succeeded in demonstrating that these emerging nanoscale devices, despite being rather simple in architecture, possess ultra-rich dynamics that can be harnessed beyond the obvious memory applications to address the fundamental constraints in bandwidth and power that currently prohibit scaling neural interfaces beyond 1,000 recording channels.”

The Prodromakis Group at the University of Southampton is acknowledged as world-leading in this field, collaborating among others with Leon Chua (a Diamond Jubilee Visiting Academic at the University of Southampton), who theoretically predicted the existence of memristors in 1971.

Here’s a link to and a citation for the paper,

Real-time encoding and compression of neuronal spikes by metal-oxide memristors by Isha Gupta, Alexantrou Serb, Ali Khiat, Ralf Zeitler, Stefano Vassanelli, & Themistoklis Prodromakis. Nature Communications 7, Article number: 12805 doi:10.1038/ncomms12805 Published  26 September 2016

This is an open access paper.

For anyone who’s interested in better understanding memristors, there’s an interview with Forrest H Bennett III in my April 7, 2010 posting and you can always check Wikipedia.

A bionic hybrid neurochip from the University of Calgary (Canada)

The University of Calgary is publishing some very exciting work these days as can be seen in my Sept. 21, 2016 posting about quantum teleportation. Today, the university announced this via an Oct. 26, 2016 news item on Nanowerk (Note: A link has been removed),

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large networks and groups of neurons. Conventional methods have allowed scientists to record the activity of neurons for minutes, but a new technology, developed by University of Calgary researchers, known as a bionic hybrid neuro chip, is able to record activity in animal brain cells for weeks at a much higher resolution. The technological advancement was published in the journal Scientific Reports(“A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording”).

There’s more from an Oct. 26, 2016 University of Calgary news release on EurekAlert, which originated the news item,

“These chips are 15 times more sensitive than conventional neuro chips,” says Naweed Syed, PhD, scientific director of the University of Calgary, Cumming School of Medicine’s Alberta Children’s Hospital Research Institute, member of the Hotchkiss Brain Institute and senior author on the study. “This allows brain cell signals to be amplified more easily and to see real time recordings of brain cell activity at a resolution that has never been achieved before.”

The development of this technology will allow researchers to investigate and understand in greater depth, in animal models, the origins of neurological diseases and conditions such as epilepsy, as well as other cognitive functions such as learning and memory.

“Recording this activity over a long period of time allows you to see changes that occur over time, in the activity itself,” says Pierre Wijdenes, a PhD student in the Biomedical Engineering Graduate Program and the study’s first author. “This helps to understand why certain neurons form connections with each other and why others won’t.”

The cross-faculty team created the chip to mimic the natural biological contact between brain cells, essentially tricking the brain cells into believing that they are connecting with other brain cells. As a result, the cells immediately connect with the chip, thereby allowing researchers to view and record the two-way communication that would go on between two normal functioning brain cells.

“We simulated what mother-nature does in nature and provided brain cells with an environment where they feel as if they are at home,” says Syed. “This has allowed us to increase the sensitivity of our readings and help neurons build a long-term relationship with our electronic chip.”

While the chip is currently used to analyze animal brain cells, this increased resolution and the ability to make long-term recordings is bringing the technology one step closer to being effective in the recording of human brain cell activity.

“Human brain cell signals are smaller and therefore require more sensitive electronic tools to be designed to pick up the signals,” says Colin Dalton, Adjunct Professor in the Department of Electrical and Computer Engineering at the Schulich School of Engineering and a co-author on this study. Dalton is also the Facility Manager of the University of Calgary’s Advanced Micro/nanosystems Integration Facility (AMIF), where the chips were designed and fabricated.

Researchers hope the technology will one day be used as a tool to bring personalized therapeutic options to patients facing neurological disease.

Here’s a link to and a citation for the paper,

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording by Pierre Wijdenes, Hasan Ali, Ryden Armstrong, Wali Zaidi, Colin Dalton & Naweed I. Syed. Scientific Reports 6, Article number: 34553 (2016) doi:10.1038/srep34553
Published online: 12 October 2016

This paper is  open access.

Breathing nanoparticles into your brain

Thanks to Dexter Johnson and his Sept. 8, 2016 posting (on the Nanoclast blog on the IEEE [Institute for Electrical and Electronics Engineers]) for bringing this news about nanoparticles in the brain to my attention (Note: Links have been removed),

An international team of researchers, led by Barbara Maher, a professor at Lancaster University, in England, has found evidence that suggests that the nanoparticles that were first detected in the human brain over 20 years ago may have an external rather an internal source.

These magnetite nanoparticles are an airborne particulate that are abundant in urban environments and formed by combustion or friction-derived heating. In other words, they have been part of the pollution in the air of our cities since the dawn of the Industrial Revolution.

However, according to Andrew Maynard, a professor at Arizona State University, and a noted expert on the risks associated with nanomaterials,  the research indicates that this finding extends beyond magnetite to any airborne nanoscale particles—including those deliberately manufactured.

“The findings further support the possibility of these particles entering the brain via the olfactory nerve if inhaled.  In this respect, they are certainly relevant to our understanding of the possible risks presented by engineered nanomaterials—especially those that are iron-based and have magnetic properties,” said Maynard in an e-mail interview with IEEE Spectrum. “However, ambient exposures to airborne nanoparticles will typically be much higher than those associated with engineered nanoparticles, simply because engineered nanoparticles will usually be manufactured and handled under conditions designed to avoid release and exposure.”

A Sept. 5, 2016 University of Lancaster press release made the research announcement,

Researchers at Lancaster University found abundant magnetite nanoparticles in the brain tissue from 37 individuals aged three to 92-years-old who lived in Mexico City and Manchester. This strongly magnetic mineral is toxic and has been implicated in the production of reactive oxygen species (free radicals) in the human brain, which are associated with neurodegenerative diseases including Alzheimer’s disease.

Professor Barbara Maher, from Lancaster Environment Centre, and colleagues (from Oxford, Glasgow, Manchester and Mexico City) used spectroscopic analysis to identify the particles as magnetite. Unlike angular magnetite particles that are believed to form naturally within the brain, most of the observed particles were spherical, with diameters up to 150 nm, some with fused surfaces, all characteristic of high-temperature formation – such as from vehicle (particularly diesel) engines or open fires.

The spherical particles are often accompanied by nanoparticles containing other metals, such as platinum, nickel, and cobalt.

Professor Maher said: “The particles we found are strikingly similar to the magnetite nanospheres that are abundant in the airborne pollution found in urban settings, especially next to busy roads, and which are formed by combustion or frictional heating from vehicle engines or brakes.”

Other sources of magnetite nanoparticles include open fires and poorly sealed stoves within homes. Particles smaller than 200 nm are small enough to enter the brain directly through the olfactory nerve after breathing air pollution through the nose.

“Our results indicate that magnetite nanoparticles in the atmosphere can enter the human brain, where they might pose a risk to human health, including conditions such as Alzheimer’s disease,” added Professor Maher.

Leading Alzheimer’s researcher Professor David Allsop, of Lancaster University’s Faculty of Health and Medicine, said: “This finding opens up a whole new avenue for research into a possible environmental risk factor for a range of different brain diseases.”

Damian Carrington’s Sept. 5, 2016 article for the Guardian provides a few more details,

“They [the troubling magnetite particles] are abundant,” she [Maher] said. “For every one of [the crystal shaped particles] we saw about 100 of the pollution particles. The thing about magnetite is it is everywhere.” An analysis of roadside air in Lancaster found 200m magnetite particles per cubic metre.

Other scientists told the Guardian the new work provided strong evidence that most of the magnetite in the brain samples come from air pollution but that the link to Alzheimer’s disease remained speculative.

For anyone who might be concerned about health risks, there’s this from Andrew Maynard’s comments in Dexter Johnson’s Sept. 8, 2016 posting,

“In most workplaces, exposure to intentionally made nanoparticles is likely be small compared to ambient nanoparticles, and so it’s reasonable to assume—at least without further data—that this isn’t a priority concern for engineered nanomaterial production,” said Maynard.

While deliberate nanoscale manufacturing may not carry much risk, Maynard does believe that the research raises serious questions about other manufacturing processes where exposure to high concentrations of airborne nanoscale iron particles is common—such as welding, gouging, or working with molten ore and steel.

It seems everyone is agreed that the findings are concerning but I think it might be good to remember that the percentage of people who develop Alzheimer’s Disease is much smaller than the population of people who have crystals in their brains. In other words, these crystals might (they don’t know) be a factor and likely there would have to be one or more factors to create the condition for developing Alzheimer’s.

Here’s a link to and a citation for the paper,

Magnetite pollution nanoparticles in the human brain by Barbara A. Maher, Imad A. M. Ahmed, Vassil Karloukovski, Donald A. MacLaren, Penelope G. Fouldsd, David Allsop, David M. A. Mann, Ricardo Torres-Jardón, and Lilian Calderon-Garciduenas. PNAS [Proceedings of the National Academy of Sciences] doi: 10.1073/pnas.1605941113

This paper is behind a paywall but Dexter’s posting offers more detail for those who are still curious.

Long-term brain mapping with injectable electronics

Charles Lieber and his team at Harvard University announced a success with their work on injectable electronics last year (see my June 11, 2015 posting for more) and now they are reporting on their work with more extensive animal studies according to an Aug. 29, 2016 news item on psypost.org,

Scientists in recent years have made great strides in the quest to understand the brain by using implanted probes to explore how specific neural circuits work.

Though effective, those probes also come with their share of problems as a result of rigidity. The inflammation they produce induces chronic recording instability and means probes must be relocated every few days, leaving some of the central questions of neuroscience – like how the neural circuits are reorganized during development, learning and aging- beyond scientists’ reach.

But now, it seems, things are about to change.

Led by Charles Lieber, The Mark Hyman Jr. Professor of Chemistry and chair of the Department of Chemistry and Chemical Biology, a team of researchers that included graduate student Tian-Ming Fu, postdoctoral fellow Guosong Hong, graduate student Tao Zhou and others, has demonstrated that syringe-injectable mesh electronics can stably record neural activity in mice for eight months or more, with none of the inflammation

An Aug. 29, 2016 Harvard University press release, which originated the news item, provides more detail,

“With the ability to follow the same individual neurons in a circuit chronically…there’s a whole suite of things this opens up,” Lieber said. “The eight months we demonstrate in this paper is not a limit, but what this does show is that mesh electronics could be used…to investigate neuro-degenerative diseases like Alzheimer’s, or processes that occur over long time, like aging or learning.”

Lieber and colleagues also demonstrated that the syringe-injectable mesh electronics could be used to deliver electrical stimulation to the brain over three months or more.

“Ultimately, our aim is to create these with the goal of finding clinical applications,” Lieber said. “What we found is that, because of the lack of immune response (to the mesh electronics), which basically insulates neurons, we can deliver stimulation in a much more subtle way, using lower voltages that don’t damage tissue.”

The possibilities, however, don’t end there.

The seamless integration of the electronics and biology, Lieber said, could open the door to an entirely new class of brain-machine interfaces and vast improvements in prosthetics, among other fields.

“Today, brain-machine interfaces are based on traditional implanted probes, and there has been some impressive work that’s been done in that field,” Lieber said. “But all the interfaces rely on the same technique to decode neural signals.”

Because traditional rigid implanted probes are invariably unstable, he explained, researchers and clinicians rely on decoding what they call the “population average” – essentially taking a host of neural signals and applying complex computational tools to determine what they mean.

Using tissue-like mesh electronics, by comparison, researchers may be able to read signals from specific neurons over time, potentially allowing for the development of improved brain-machine interfaces for prosthetics.

“We think this is going to be very powerful, because we can identify circuits and both record and stimulate in a way that just hasn’t been possible before,” Lieber said. “So what I like to say is: I think therefore it happens.”

Lieber even held out the possibility that the syringe-injectable mesh electronics could one day be used to treat catastrophic injuries to the brain and spinal cord.

“I don’t think that’s science-fiction,” he said. “Other people may say that will be possible through, for example, regenerative medicine, but we are pursuing this from a different angle.

“My feeling is that this is about a seamless integration between the biological and the electronic systems, so they’re not distinct entities,” he continued. “If we can make the electronics look like the neural network, they will work together…and that’s where you want to be if you want to exploit the strengths of both.”

In the 2015 posting, Lieber was discussing cyborgs, here he broaches the concept without using the word, “… seamless integration between the biological and the electronic systems, so they’re not distinct entities.”

Here’s a link to and a citation for the paper,

Stable long-term chronic brain mapping at the single-neuron level by Tian-Ming Fu, Guosong Hong, Tao Zhou, Thomas G Schuhmann, Robert D Viveros, & Charles M Lieber. Nature Methods (2016) doi:10.1038/nmeth.3969 Published online 29 August 2016

This paper is behind a paywall.

US white paper on neuromorphic computing (or the nanotechnology-inspired Grand Challenge for future computing)

The US has embarked on a number of what is called “Grand Challenges.” I first came across the concept when reading about the Bill and Melinda Gates (of Microsoft fame) Foundation. I gather these challenges are intended to provide funding for research that advances bold visions.

There is the US National Strategic Computing Initiative established on July 29, 2015 and its first anniversary results were announced one year to the day later. Within that initiative a nanotechnology-inspired Grand Challenge for Future Computing was issued and, according to a July 29, 2016 news item on Nanowerk, a white paper on the topic has been issued (Note: A link has been removed),

Today [July 29, 2016), Federal agencies participating in the National Nanotechnology Initiative (NNI) released a white paper (pdf) describing the collective Federal vision for the emerging and innovative solutions needed to realize the Nanotechnology-Inspired Grand Challenge for Future Computing.

The grand challenge, announced on October 20, 2015, is to “create a new type of computer that can proactively interpret and learn from data, solve unfamiliar problems using what it has learned, and operate with the energy efficiency of the human brain.” The white paper describes the technical priorities shared by the agencies, highlights the challenges and opportunities associated with these priorities, and presents a guiding vision for the research and development (R&D) needed to achieve key technical goals. By coordinating and collaborating across multiple levels of government, industry, academia, and nonprofit organizations, the nanotechnology and computer science communities can look beyond the decades-old approach to computing based on the von Neumann architecture and chart a new path that will continue the rapid pace of innovation beyond the next decade.

A July 29, 2016 US National Nanotechnology Coordination Office news release, which originated the news item, further and succinctly describes the contents of the paper,

“Materials and devices for computing have been and will continue to be a key application domain in the field of nanotechnology. As evident by the R&D topics highlighted in the white paper, this challenge will require the convergence of nanotechnology, neuroscience, and computer science to create a whole new paradigm for low-power computing with revolutionary, brain-like capabilities,” said Dr. Michael Meador, Director of the National Nanotechnology Coordination Office. …

The white paper was produced as a collaboration by technical staff at the Department of Energy, the National Science Foundation, the Department of Defense, the National Institute of Standards and Technology, and the Intelligence Community. …

The white paper titled “A Federal Vision for Future Computing: A Nanotechnology-Inspired Grand Challenge” is 15 pp. and it offers tidbits such as this (Note: Footnotes not included),

A new materials base may be needed for future electronic hardware. While most of today’s electronics use silicon, this approach is unsustainable if billions of disposable and short-lived sensor nodes are needed for the coming Internet-of-Things (IoT). To what extent can the materials base for the implementation of future information technology (IT) components and systems support sustainability through recycling and bio-degradability? More sustainable materials, such as compostable or biodegradable systems (polymers, paper, etc.) that can be recycled or reused,  may play an important role. The potential role for such alternative materials in the fabrication of integrated systems needs to be explored as well. [p. 5]

The basic architecture of computers today is essentially the same as those built in the 1940s—the von Neumann architecture—with separate compute, high-speed memory, and high-density storage components that are electronically interconnected. However, it is well known that continued performance increases using this architecture are not feasible in the long term, with power density constraints being one of the fundamental roadblocks.7 Further advances in the current approach using multiple cores, chip multiprocessors, and associated architectures are plagued by challenges in software and programming models. Thus,  research and development is required in radically new and different computing architectures involving processors, memory, input-output devices, and how they behave and are interconnected. [p. 7]

Neuroscience research suggests that the brain is a complex, high-performance computing system with low energy consumption and incredible parallelism. A highly plastic and flexible organ, the human brain is able to grow new neurons, synapses, and connections to cope with an ever-changing environment. Energy efficiency, growth, and flexibility occur at all scales, from molecular to cellular, and allow the brain, from early to late stage, to never stop learning and to act with proactive intelligence in both familiar and novel situations. Understanding how these mechanisms work and cooperate within and across scales has the potential to offer tremendous technical insights and novel engineering frameworks for materials, devices, and systems seeking to perform efficient and autonomous computing. This research focus area is the most synergistic with the national BRAIN Initiative. However, unlike the BRAIN Initiative, where the goal is to map the network connectivity of the brain, the objective here is to understand the nature, methods, and mechanisms for computation,  and how the brain performs some of its tasks. Even within this broad paradigm,  one can loosely distinguish between neuromorphic computing and artificial neural network (ANN) approaches. The goal of neuromorphic computing is oriented towards a hardware approach to reverse engineering the computational architecture of the brain. On the other hand, ANNs include algorithmic approaches arising from machinelearning,  which in turn could leverage advancements and understanding in neuroscience as well as novel cognitive, mathematical, and statistical techniques. Indeed, the ultimate intelligent systems may as well be the result of merging existing ANN (e.g., deep learning) and bio-inspired techniques. [p. 8]

As government documents go, this is quite readable.

For anyone interested in learning more about the future federal plans for computing in the US, there is a July 29, 2016 posting on the White House blog celebrating the first year of the US National Strategic Computing Initiative Strategic Plan (29 pp. PDF; awkward but that is the title).

Graphene and neurons in a UK-Italy-Spain collaboration

There’s been a lot of talk about using graphene-based implants in the brain due to the material’s flexibility along with its other properties. A step forward has been taking according to a Jan. 29, 2016 news item on phys.org,

Researchers have successfully demonstrated how it is possible to interface graphene – a two-dimensional form of carbon – with neurons, or nerve cells, while maintaining the integrity of these vital cells. The work may be used to build graphene-based electrodes that can safely be implanted in the brain, offering promise for the restoration of sensory functions for amputee or paralysed patients, or for individuals with motor disorders such as epilepsy or Parkinson’s disease.

A Jan. 29, 2016 Cambridge University press release (also on EurekAlert), which originated the news item, provides more detail,

Previously, other groups had shown that it is possible to use treated graphene to interact with neurons. However the signal to noise ratio from this interface was very low. By developing methods of working with untreated graphene, the researchers retained the material’s electrical conductivity, making it a significantly better electrode.

“For the first time we interfaced graphene to neurons directly,” said Professor Laura Ballerini of the University of Trieste in Italy. “We then tested the ability of neurons to generate electrical signals known to represent brain activities, and found that the neurons retained their neuronal signalling properties unaltered. This is the first functional study of neuronal synaptic activity using uncoated graphene based materials.”

Our understanding of the brain has increased to such a degree that by interfacing directly between the brain and the outside world we can now harness and control some of its functions. For instance, by measuring the brain’s electrical impulses, sensory functions can be recovered. This can be used to control robotic arms for amputee patients or any number of basic processes for paralysed patients – from speech to movement of objects in the world around them. Alternatively, by interfering with these electrical impulses, motor disorders (such as epilepsy or Parkinson’s) can start to be controlled.

Scientists have made this possible by developing electrodes that can be placed deep within the brain. These electrodes connect directly to neurons and transmit their electrical signals away from the body, allowing their meaning to be decoded.

However, the interface between neurons and electrodes has often been problematic: not only do the electrodes need to be highly sensitive to electrical impulses, but they need to be stable in the body without altering the tissue they measure.

Too often the modern electrodes used for this interface (based on tungsten or silicon) suffer from partial or complete loss of signal over time. This is often caused by the formation of scar tissue from the electrode insertion, which prevents the electrode from moving with the natural movements of the brain due to its rigid nature.

Graphene has been shown to be a promising material to solve these problems, because of its excellent conductivity, flexibility, biocompatibility and stability within the body.

Based on experiments conducted in rat brain cell cultures, the researchers found that untreated graphene electrodes interfaced well with neurons. By studying the neurons with electron microscopy and immunofluorescence the researchers found that they remained healthy, transmitting normal electric impulses and, importantly, none of the adverse reactions which lead to the damaging scar tissue were seen.

According to the researchers, this is the first step towards using pristine graphene-based materials as an electrode for a neuro-interface. In future, the researchers will investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons, and whether tuning the material properties of graphene might alter the synapses and neuronal excitability in new and unique ways. “Hopefully this will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer unwanted side effects,” said Ballerini.

“We are currently involved in frontline research in graphene technology towards biomedical applications,” said Professor Maurizio Prato from the University of Trieste. “In this scenario, the development and translation in neurology of graphene-based high-performance biodevices requires the exploration of the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is only a first step in that direction.”

“These initial results show how we are just at the tip of the iceberg when it comes to the potential of graphene and related materials in bio-applications and medicine,” said Professor Andrea Ferrari, Director of the Cambridge Graphene Centre. “The expertise developed at the Cambridge Graphene Centre allows us to produce large quantities of pristine material in solution, and this study proves the compatibility of our process with neuro-interfaces.”

The research was funded by the Graphene Flagship [emphasis mine],  a European initiative which promotes a collaborative approach to research with an aim of helping to translate graphene out of the academic laboratory, through local industry and into society.

Here’s a link to and a citation for the paper,

Graphene-Based Interfaces Do Not Alter Target Nerve Cells by Alessandra Fabbro, Denis Scaini, Verónica León, Ester Vázquez, Giada Cellot, Giulia Privitera, Lucia Lombardi, Felice Torrisi, Flavia Tomarchio, Francesco Bonaccorso, Susanna Bosi, Andrea C. Ferrari, Laura Ballerini, and Maurizio Prato. ACS Nano, 2016, 10 (1), pp 615–623 DOI: 10.1021/acsnano.5b05647 Publication Date (Web): December 23, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

There are a couple things I found a bit odd about this project. First, all of the funding is from the Graphene Flagship initiative. I was expecting to see at least some funding from the European Union’s other mega-sized science initiative, the Human Brain Project. Second, there was no mention of Spain nor were there any quotes from the Spanish researchers. For the record, the Spanish institutions represented were: University of Castilla-La Mancha, Carbon Nanobiotechnology Laboratory, and the Basque Foundation for Science.

Nanotechnology and cybersecurity risks

Gregory Carpenter has written a gripping (albeit somewhat exaggerated) piece for Signal, a publication of the  Armed Forces Communications and Electronics Association (AFCEA) about cybersecurity issues and  nanomedicine endeavours. From Carpenter’s Jan. 1, 2016 article titled, When Lifesaving Technology Can Kill; The Cyber Edge,

The exciting advent of nanotechnology that has inspired disruptive and lifesaving medical advances is plagued by cybersecurity issues that could result in the deaths of people that these very same breakthroughs seek to heal. Unfortunately, nanorobotic technology has suffered from the same security oversights that afflict most other research and development programs.

Nanorobots, or small machines [or nanobots[, are vulnerable to exploitation just like other devices.

At the moment, the issue of cybersecurity exploitation is secondary to making nanobots, or nanorobots, dependably functional. As far as I’m aware, there is no such nanobot. Even nanoparticles meant to function as packages for drug delivery have not been perfected (see one of the controversies with nanomedicine drug delivery described in my Nov. 26, 2015 posting).

That said, Carpenter’s point about cybersecurity is well taken since security features are often overlooked in new technology. For example, automated banking machines (ABMs) had woefully poor (inadequate, almost nonexistent) security when they were first introduced.

Carpenter outlines some of the problems that could occur, assuming some of the latest research could be reliably  brought to market,

The U.S. military has joined the fray of nanorobotic experimentation, embarking on revolutionary research that could lead to a range of discoveries, from unraveling the secrets of how brains function to figuring out how to permanently purge bad memories. Academia is making amazing advances as well. Harnessing progress by Harvard scientists to move nanorobots within humans, researchers at the University of Montreal, Polytechnique Montreal and Centre Hospitalier Universitaire Sainte-Justine are using mobile nanoparticles inside the human brain to open the blood-brain barrier, which protects the brain from toxins found in the circulatory system.

A different type of technology presents a risk similar to the nanoparticles scenario. A DARPA-funded program known as Restoring Active Memory (RAM) addresses post-traumatic stress disorder, attempting to overcome memory deficits by developing neuroprosthetics that bridge gaps in an injured brain. In short, scientists can wipe out a traumatic memory, and they hope to insert a new one—one the person has never actually experienced. Someone could relish the memory of a stroll along the French Riviera rather than a terrible firefight, even if he or she has never visited Europe.

As an individual receives a disruptive memory, a cyber criminal could manage to hack the controls. Breaches of the brain could become a reality, putting humans at risk of becoming zombie hosts [emphasis mine] for future virus deployments. …

At this point, the ‘zombie’ scenario Carpenter suggests seems a bit over-the-top but it does hearken to the roots of the zombie myth where the undead aren’t mindlessly searching for brains but are humans whose wills have been overcome. Mike Mariani in an Oct. 28, 2015 article for The Atlantic has presented a thought-provoking history of zombies,

… the zombie myth is far older and more rooted in history than the blinkered arc of American pop culture suggests. It first appeared in Haiti in the 17th and 18th centuries, when the country was known as Saint-Domingue and ruled by France, which hauled in African slaves to work on sugar plantations. Slavery in Saint-Domingue under the French was extremely brutal: Half of the slaves brought in from Africa were worked to death within a few years, which only led to the capture and import of more. In the hundreds of years since, the zombie myth has been widely appropriated by American pop culture in a way that whitewashes its origins—and turns the undead into a platform for escapist fantasy.

The original brains-eating fiend was a slave not to the flesh of others but to his own. The zombie archetype, as it appeared in Haiti and mirrored the inhumanity that existed there from 1625 to around 1800, was a projection of the African slaves’ relentless misery and subjugation. Haitian slaves believed that dying would release them back to lan guinée, literally Guinea, or Africa in general, a kind of afterlife where they could be free. Though suicide was common among slaves, those who took their own lives wouldn’t be allowed to return to lan guinée. Instead, they’d be condemned to skulk the Hispaniola plantations for eternity, an undead slave at once denied their own bodies and yet trapped inside them—a soulless zombie.

I recommend reading Mariani’s article although I do have one nit to pick. I can’t find a reference to brain-eating zombies until George Romero’s introduction of the concept in his movies. This Zombie Wikipedia entry seems to be in agreement with my understanding (if I’m wrong, please do let me know and, if possible, provide a link to the corrective text).

Getting back to Carpenter and cybersecurity with regard to nanomedicine, while his scenarios may seem a trifle extreme it’s precisely the kind of thinking you need when attempting to anticipate problems. I do wish he’d made clear that the technology still has a ways to go.