Tag Archives: brain

Nanoscale imaging of a mouse brain

Researchers have developed a new brain imaging tool they would like to use as a founding element for a national brain observatory. From a July 30, 2015 news item on Azonano,

A new imaging tool developed by Boston scientists could do for the brain what the telescope did for space exploration.

In the first demonstration of how the technology works, published July 30 in the journal Cell, the researchers look inside the brain of an adult mouse at a scale previously unachievable, generating images at a nanoscale resolution. The inventors’ long-term goal is to make the resource available to the scientific community in the form of a national brain observatory.

A July 30, 2015 Cell Press news release on EurekAlert, which originated the news item, expands on the theme,

“I’m a strong believer in bottom up-science, which is a way of saying that I would prefer to generate a hypothesis from the data and test it,” says senior study author Jeff Lichtman, of Harvard University. “For people who are imagers, being able to see all of these details is wonderful and we’re getting an opportunity to peer into something that has remained somewhat intractable for so long. It’s about time we did this, and it is what people should be doing about things we don’t understand.”

The researchers have begun the process of mining their imaging data by looking first at an area of the brain that receives sensory information from mouse whiskers, which help the animals orient themselves and are even more sensitive than human fingertips. The scientists used a program called VAST, developed by co-author Daniel Berger of Harvard and the Massachusetts Institute of Technology, to assign different colors and piece apart each individual “object” (e.g., neuron, glial cell, blood vessel cell, etc.).

“The complexity of the brain is much more than what we had ever imagined,” says study first author Narayanan “Bobby” Kasthuri, of the Boston University School of Medicine. “We had this clean idea of how there’s a really nice order to how neurons connect with each other, but if you actually look at the material it’s not like that. The connections are so messy that it’s hard to imagine a plan to it, but we checked and there’s clearly a pattern that cannot be explained by randomness.”

The researchers see great potential in the tool’s ability to answer questions about what a neurological disorder actually looks like in the brain, as well as what makes the human brain different from other animals and different between individuals. Who we become is very much a product of the connections our neurons make in response to various life experiences. To be able to compare the physical neuron-to-neuron connections in an infant, a mathematical genius, and someone with schizophrenia would be a leap in our understanding of how our brains shape who we are (or vice versa).

The cost and data storage demands for this type of research are still high, but the researchers expect expenses to drop over time (as has been the case with genome sequencing). To facilitate data sharing, the scientists are now partnering with Argonne National Laboratory with the hopes of creating a national brain laboratory that neuroscientists around the world can access within the next few years.

“It’s bittersweet that there are many scientists who think this is a total waste of time as well as a big investment in money and effort that could be better spent answering questions that are more proximal,” Lichtman says. “As long as data is showing you things that are unexpected, then you’re definitely doing the right thing. And we are certainly far from being out of the surprise element. There’s never a time when we look at this data that we don’t see something that we’ve never seen before.”

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

Saturated Reconstruction of a Volume of Neocortex by Narayanan Kasthuri, Kenneth Jeffrey Hayworth, Daniel Raimund Berger, Richard Lee Schalek, José Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio Vázquez-Reina, Verena Kaynig, Thouis Raymond Jones, Mike Roberts, Josh Lyskowski Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Tzvi Vogelstein, Randal Burns, Daniel Lewis Sussman, Carey Eldin Priebe, Hanspeter Pfister, Jeff William Lichtman. Cell Volume 162, Issue 3, p648–661, 30 July 2015 DOI: http://dx.doi.org/10.1016/j.cell.2015.06.054

This appears to be an open access paper.

Brain data (neuroscience) crowdsourced at Toronto’s (Canada) 2013 Nuit Blanche event

The brain data was crowdsourced in 2013 in Toronto but only recently published according to a July 8, 2015 Baycrest Centre for Geriatric Care news release (also on EurekAlert),

Neuroscientists in Toronto have shown that crowdsourcing brain data with hundreds of adults in a short period of time could be a new frontier in neuroscience and lead to new insights about the brain.

More than 500 adults aged 18 and older participated in the experiment at the 2013 Scotiabank Nuit Blanche arts event in Toronto. Baycrest, in partnership with the University of Toronto and industry partners, created a large-scale art-science installation called My Virtual Dream. Festival-goers were invited to wear a Muse™ wireless electroencephalography (EEG) headband and participate in a brief collective neurofeedback experience in groups of 20 inside a 60-foot geodesic dome. The group’s collective EEG signals triggered a specific catalogue of artistic imagery displayed on the dome’s 360-degree interior, along with spontaneous musical interpretation by live musicians on stage.

The installation was one of the most popular at Nuit Blanche, with an average lineup wait time of two hours.

Studying brains in a social and multi-sensory environment is closer to real life and may help scientists to approach questions of complex real-life social cognition that otherwise are not accessible in traditional labs that study one person’s cognitive functions at a time.

“In traditional lab settings, the environment is so controlled that you can lose some of the fine points of real-time brain activity that occur in a social life setting,” said Dr. Kovacevic, creative producer of My Virtual Dream and program manager of the Centre for Integrative Brain Dynamics at Baycrest’s Rotman Research Institute.

“What we’ve done is taken the lab to the public. We collaborated with multi-media artists, made this experiment incredibly engaging, attracted highly motivated subjects which is not easy to do in the traditional lab setting, and collected useful scientific data from their experience.”

Results from the experiment not only demonstrated the scientific viability of collective neurofeedback as a potential new avenue of neuroscience research that takes into account individuality, complexity and sociability of the human mind, but yielded new evidence that neurofeedback learning can have an effect on the brain almost immediately.

Neurofeedback learning supports mindful awareness and joins a growing market for wearable biofeedback devices. The device used in this study, Muse™, is a clinical-grade EEG brain computer interface (BCI) headband that helps individuals to be more aware of their brain states (relaxed versus focused versus distracted) and learn self-regulation of brain function to fit their personal goals.

A total of 523 adults (209 males, 314 females), ranging in age from 18 to 89, with an average age of 31, contributed their EEG brain data for the study. Each session involved 20 participants being seated in a semicircle in front of a stage and divided into four groups (“pods”) of five. They played a collective neurofeedback computer game where they were required to manipulate their mental states of relaxation and concentration. The neurofeedback training lasted 6.5 minutes, which is much shorter than typical neurofeedback training experiments.

The massive amount of EEG data collected in one night yielded an interesting and statistically relevant finding – that subtle brain activity changes were taking place within approximately one minute of the neurofeedback learning exercise – unprecedented speed of learning changes that have not been demonstrated before.

“These results really open up a whole new domain of neuroscience study that actively engages the public to advance our understanding of the brain,” said Dr. Randy McIntosh, director of the Rotman Research Institute and vice-president of Research at Baycrest. He is a senior author on the paper.

The idea for the Nuit Blanche art -science experiment was inspired by Baycrest’s ongoing international project to build the world’s first functional, virtual brain – a research and diagnostic tool that could one day revolutionize brain healthcare.

Baycrest cognitive neuroscientists collaborated with artists and gaming and wearable technology industry partners for over a year to create the My Virtual Dream installation. Partners included the University of Toronto, Scotiabank Nuit Blanche, Muse™ and Uken Games.

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

‘My Virtual Dream’: Collective Neurofeedback in an Immersive Art Environment by Natasha Kovacevic, Petra Ritter, William Tays, Sylvain Moreno, and Anthony Randal McIntosh. DOI: 10.1371/journal.pone.0130129 PLOS Published: July 8, 2015

This is an open access paper.

A few final words, I last wrote about MUSE (a Canadian technology company) in a March 6, 2015 posting. Uken Games , also a Canadian company, is new to this blog.

Injectable electronics

Having taught a course on bioelectronics for Simon Fraser University’s (Vancouver, Canada) Continuing Studies Program, this  latest work from Harvard University (US) caught my attention. A Harvard research team has developed a technique which could allow doctors to inject us with electronics, should we need them. From a June 8, 2015 news item on phys.org,

It’s a notion that might be pulled from the pages of science-fiction novel – electronic devices that can be injected directly into the brain, or other body parts, and treat everything from neurodegenerative disorders to paralysis.

It sounds unlikely, until you visit Charles Lieber’s lab.

A team of international researchers, led by Lieber, the Mark Hyman, Jr. Professor of Chemistry, an international team of researchers developed a method for fabricating nano-scale electronic scaffolds that can be injected via syringe. Once connected to electronic devices, the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons. …

Here’s an image provided by the researchers,

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

A June 8, 2015 Harvard University new release by Peter Reuell (also on EurekAlert), which originated the news item, describes the work in more detail,

“I do feel that this has the potential to be revolutionary,” Lieber said. “This opens up a completely new frontier where we can explore the interface between electronic structures and biology. For the past thirty years, people have made incremental improvements in micro-fabrication techniques that have allowed us to make rigid probes smaller and smaller, but no one has addressed this issue – the electronics/cellular interface – at the level at which biology works.”

The idea of merging the biological with the electronic is not a new one for Lieber.

In an earlier study, scientists in Lieber’s lab demonstrated that the scaffolds could be used to create “cyborg” tissue – when cardiac or nerve cells were grown with embedded scaffolds. [emphasis mine] Researchers were then able to use the devices to record electrical signals generated by the tissues, and to measure changes in those signals as they administered cardio- or neuro-stimulating drugs.

“We were able to demonstrate that we could make this scaffold and culture cells within it, but we didn’t really have an idea how to insert that into pre-existing tissue,” Lieber said. “But if you want to study the brain or develop the tools to explore the brain-machine interface, you need to stick something into the body. When releasing the electronics scaffold completely from the fabrication substrate, we noticed that it was almost invisible and very flexible like a polymer and could literally be sucked into a glass needle or pipette. From there, we simply asked, would it be possible to deliver the mesh electronics by syringe needle injection, a process common to delivery of many species in biology and medicine – you could go to the doctor and you inject this and you’re wired up.'”

Though not the first attempts at implanting electronics into the brain – deep brain stimulation has been used to treat a variety of disorders for decades – the nano-fabricated scaffolds operate on a completely different scale.

“Existing techniques are crude relative to the way the brain is wired,” Lieber explained. “Whether it’s a silicon probe or flexible polymers…they cause inflammation in the tissue that requires periodically changing the position or the stimulation. But with our injectable electronics, it’s as if it’s not there at all. They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes. They’re what I call “neuro-philic” – they actually like to interact with neurons..”

Despite their enormous potential, the fabrication of the injectable scaffolds is surprisingly easy.

“That’s the beauty of this – it’s compatible with conventional manufacturing techniques,” Lieber said.

The process is similar to that used to etch microchips, and begins with a dissolvable layer deposited on a substrate. To create the scaffold, researchers lay out a mesh of nanowires sandwiched in layers of organic polymer. The first layer is then dissolved, leaving the flexible mesh, which can be drawn into a syringe needle and administered like any other injection.

After injection, the input/output of the mesh can be connected to standard measurement electronics so that the integrated devices can be addressed and used to stimulate or record neural activity.

“These type of things have never been done before, from both a fundamental neuroscience and medical perspective,” Lieber said. “It’s really exciting – there are a lot of potential applications.”

Going forward, Lieber said, researchers hope to better understand how the brain and other tissues react to the injectable electronics over longer periods.

Lieber’s earlier work on “cyborg tissue” was briefly mentioned here in a Feb. 20, 2014 posting.

Getting back to the most recent work, here’s a link to and a citation for the paper,

Syringe-injectable electronics by Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter Kruskal, Chong Xie, Zhigang Suo, Ying Fang, & Charles M. Lieber. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.115 Published online 08 June 2015

This paper is behind a paywall but there is a free preview via ReadCube Access.

One final note, the researchers have tested the injectable electronics (or mesh electronics) in vivo (live animals).

A more complex memristor: from two terminals to three for brain-like computing

Researchers have developed a more complex memristor device than has been the case according to an April 6, 2015 Northwestern University news release (also on EurekAlert),

Researchers are always searching for improved technologies, but the most efficient computer possible already exists. It can learn and adapt without needing to be programmed or updated. It has nearly limitless memory, is difficult to crash, and works at extremely fast speeds. It’s not a Mac or a PC; it’s the human brain. And scientists around the world want to mimic its abilities.

Both academic and industrial laboratories are working to develop computers that operate more like the human brain. Instead of operating like a conventional, digital system, these new devices could potentially function more like a network of neurons.

“Computers are very impressive in many ways, but they’re not equal to the mind,” said Mark Hersam, the Bette and Neison Harris Chair in Teaching Excellence in Northwestern University’s McCormick School of Engineering. “Neurons can achieve very complicated computation with very low power consumption compared to a digital computer.”

A team of Northwestern researchers, including Hersam, has accomplished a new step forward in electronics that could bring brain-like computing closer to reality. The team’s work advances memory resistors, or “memristors,” which are resistors in a circuit that “remember” how much current has flowed through them.

“Memristors could be used as a memory element in an integrated circuit or computer,” Hersam said. “Unlike other memories that exist today in modern electronics, memristors are stable and remember their state even if you lose power.”

Current computers use random access memory (RAM), which moves very quickly as a user works but does not retain unsaved data if power is lost. Flash drives, on the other hand, store information when they are not powered but work much slower. Memristors could provide a memory that is the best of both worlds: fast and reliable. But there’s a problem: memristors are two-terminal electronic devices, which can only control one voltage channel. Hersam wanted to transform it into a three-terminal device, allowing it to be used in more complex electronic circuits and systems.

The memristor is of some interest to a number of other parties prominent amongst them, the University of Michigan’s Professor Wei Lu and HP (Hewlett Packard) Labs, both of whom are mentioned in one of my more recent memristor pieces, a June 26, 2014 post.

Getting back to Northwestern,

Hersam and his team met this challenge by using single-layer molybdenum disulfide (MoS2), an atomically thin, two-dimensional nanomaterial semiconductor. Much like the way fibers are arranged in wood, atoms are arranged in a certain direction–called “grains”–within a material. The sheet of MoS2 that Hersam used has a well-defined grain boundary, which is the interface where two different grains come together.

“Because the atoms are not in the same orientation, there are unsatisfied chemical bonds at that interface,” Hersam explained. “These grain boundaries influence the flow of current, so they can serve as a means of tuning resistance.”

When a large electric field is applied, the grain boundary literally moves, causing a change in resistance. By using MoS2 with this grain boundary defect instead of the typical metal-oxide-metal memristor structure, the team presented a novel three-terminal memristive device that is widely tunable with a gate electrode.

“With a memristor that can be tuned with a third electrode, we have the possibility to realize a function you could not previously achieve,” Hersam said. “A three-terminal memristor has been proposed as a means of realizing brain-like computing. We are now actively exploring this possibility in the laboratory.”

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

Gate-tunable memristive phenomena mediated by grain boundaries in single-layer MoS2 by Vinod K. Sangwan, Deep Jariwala, In Soo Kim, Kan-Sheng Chen, Tobin J. Marks, Lincoln J. Lauhon, & Mark C. Hersam. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.56 Published online 06 April 2015

This paper is behind a paywall but there is a few preview available through ReadCube Access.

Dexter Johnson has written about this latest memristor development in an April 9, 2015 posting on his Nanoclast blog (on the IEEE [Institute for Electrical and Electronics Engineers] website) where he notes this (Note: A link has been removed),

The memristor seems to generate fairly polarized debate, especially here on this website in the comments on stories covering the technology. The controversy seems to fall along the lines that the device that HP Labs’ Stan Williams and Greg Snider developed back in 2008 doesn’t exactly line up with the original theory of the memristor proposed by Leon Chua back in 1971.

It seems the ‘debate’ has evolved from issues about how the memristor is categorized. I wonder if there’s still discussion about whether or not HP Labs is attempting to develop a patent thicket of sorts.

Brain Talks: Robotics and Rehabilitation at Vancouver (Canada) General Hospital

The latest Brain Talk will take place tomorrow, Jan. 21, 2015 at 6 pm at Vancouver (Canada) General Hospital. More logistical details follow this description of the talk (from the Robotics and Rehabilitation webpage),

Presenter:  AJung Moon, Nick Snow, and Navid Shirzad

As interactive robots become substantially more accessible to the general public in the near future, one of the main concerns for designers  is in implementing socially acceptable and ethical human-robot interaction for non-expert users.  One approach to addressing this concern is to develop a robot that can take advantage of human moral decision making – much of which are suggested to be based on intuition and strongly connected with the emotional part of the human brain, rather than the rational part of the brain.  In this talk, A. Jung will present the promising, yet cautionary, tales of the moral synergy robots and humans can create.

Speaker details:

  • AJung Moon, PhD Candidate in Mechanical Engineering, Vanier Scholar, CARIS Lab: Robo-Ethics
  • Nick Snow, Masters Candidate in Rehabilitation Sciences, Brain Behaviour Lab: Robo-Wrist Rehabilitation
  • Navid Shirzad, PhD Candidate in Biomedical Engineering, RREACH Lab: Rehabilitation Robotics

Here are the details,

6:00pm-8:00pm, Jan 21, 2015
Paetzold Auditorium, Jim Pattison Pavilion North, 899 West 12th Avenue, Vancouver, BC

Free wine and cheese reception to follow

Please RSVP here.

Maybe I’ll see you there, eh?

Nanoparticle-based radiogenetics to control brain cells

While the title for this post sounds like an opening for a zombie-themed story, this Oct. 8, 2014 news item on Nanowerk actually concerns brain research at Rockefeller University (US), Note: A link has been removed,

A proposal to develop a new way to remotely control brain cells from Sarah Stanley, a Research Associate in Rockefeller University’s Laboratory of Molecular Genetics, headed by Jeffrey M. Friedman, is among the first to receive funding from the BRAIN initiative. The project will make use of a technique called radiogenetics that combines the use of radio waves or magnetic fields with nanoparticles to turn neurons on or off.

An Oct. 7, 2014 Rockefeller University news release, which originated the news item, further describes the BRAIN initiative and the research (Note: Links have been removed),

The NIH [National Institutes of Health]  is one of four federal agencies involved in the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative. Following in the ambitious footsteps of the Human Genome Project, the BRAIN initiative seeks to create a dynamic map of the brain in action, a goal that requires the development of new technologies. The BRAIN initiative working group, which outlined the broad scope of the ambitious project, was co-chaired by Rockefeller’s Cori Bargmann, head of the Laboratory of Neural Circuits and Behavior.

Stanley’s grant, for $1.26 million over three years, is one of 58 projects to get BRAIN grants, the NIH announced. The NIH’s plan for its part of this national project, which has been pitched as “America’s next moonshot,” calls for $4.5 billion in federal funds over 12 years.

The technology Stanley is developing would enable researchers to manipulate the activity of neurons, as well as other cell types, in freely moving animals in order to better understand what these cells do. Other techniques for controlling selected groups of neurons exist, but her new nanoparticle-based technique has a unique combination of features that may enable new types of experimentation. For instance, it would allow researchers to rapidly activate or silence neurons within a small area of the brain or dispersed across a larger region, including those in difficult-to-access locations. Stanley also plans to explore the potential this method has for use treating patients.

“Francis Collins, director of the NIH, has discussed the need for studying the circuitry of the brain, which is formed by interconnected neurons. Our remote-control technology may provide a tool with which researchers can ask new questions about the roles of complex circuits in regulating behavior,” Stanley says.

Here’s an image that Rockefeller University has used to illustrate the concept of radio-controlled brain cells,


BRAIN control: The new technology uses radio waves to activate or silence cells remotely. The bright spots above represent cells with increased calcium after treatment with radio waves, a change that would allow neurons to fire. [downloaded from: http://newswire.rockefeller.edu/2014/10/07/rockefeller-neurobiology-lab-is-awarded-first-round-brain-initiative-grant/]

BRAIN control: The new technology uses radio waves to activate or silence cells remotely. The bright spots above represent cells with increased calcium after treatment with radio waves, a change that would allow neurons to fire. [downloaded from: http://newswire.rockefeller.edu/2014/10/07/rockefeller-neurobiology-lab-is-awarded-first-round-brain-initiative-grant/]

You can find out more about the US BRAIN initiative here.

DARPA (US Defense Advanced Research Projects Agency) awards funds for implantable neural interface

I’m not a huge fan of neural implantable devices (at least not the ones that facilitate phone calls directly to and from the brain as per my April 30, 2010 posting; scroll down about 40% of the way) but they are important from a therapeutic perspective. On that  note, the Lawrence Livermore National Laboratory (LLNL) has received an award of $5.6M from the US Defense Advanced Research Projects Agency (DARPA) to advance their work on neural implantable interfaces. From a June 13, 2014 news item on Azonano,

Lawrence Livermore National Laboratory recently received $5.6 million from the Department of Defense’s Defense Advanced Research Projects Agency (DARPA) to develop an implantable neural interface with the ability to record and stimulate neurons within the brain for treating neuropsychiatric disorders.

The technology will help doctors to better understand and treat post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), chronic pain and other conditions.

Several years ago, researchers at Lawrence Livermore in conjunction with Second Sight Medical Products developed the world’s first neural interface (an artificial retina) that was successfully implanted into blind patients to help partially restore their vision. The new neural device is based on similar technology used to create the artificial retina.

An LLNL June 11, 2014 news release, which originated the news item, provides some fascinating insight into the interrelations between various US programs focused on the brain and neural implants,

“DARPA is an organization that advances technology by leaps and bounds,” said LLNL’s project leader Satinderpall Pannu, director of the Lab’s Center for Micro- and Nanotechnology and Center for Bioengineering, a facility dedicated to fabricating biocompatible neural interfaces. “This DARPA program will allow us to develop a revolutionary device to help patients suffering from neuropsychiatric disorders and other neural conditions.”

The project is part of DARPA’s SUBNETS (Systems-Based Neurotechnology for Emerging Therapies) program. The agency is launching new programs to support President Obama’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, a new research effort aimed to revolutionize our understanding of the human mind and uncover ways to treat, prevent and cure brain disorders.

LLNL and Medtronic are collaborating with UCSF, UC Berkeley, Cornell University, New York University, PositScience Inc. and Cortera Neurotechnologies on the DARPA SUBNETS project. Some collaborators will be developing the electronic components of the device, while others will be validating and characterizing it.

As part of its collaboration with LLNL, Medtronic will consult on the development of new technologies and provide its investigational Activa PC+S deep brain stimulation (DBS) system, which is the first to enable the sensing and recording of brain signals while simultaneously providing targeted DBS. This system has recently been made available to leading researchers for early-stage research and could lead to a better understanding of how various devastating neurological conditions develop and progress. The knowledge gained as part of this collaboration could lead to the next generation of advanced systems for treating neural disease.

As for what LLNL will contribute (from the news release),

The LLNL Neural Technology group will develop an implantable neural device with hundreds of electrodes by leveraging their thin-film neural interface technology, a more than tenfold increase over current Deep Brain Stimulation (DBS) devices. The electrodes will be integrated with electronics using advanced LLNL integration and 3D packaging technologies. The goal is to seal the electronic components in miniaturized, self-contained, wireless neural hardware. The microelectrodes that are the heart of this device are embedded in a biocompatible, flexible polymer.

Surgically implanted into the brain, the neural device is designed to help researchers understand the underlying dynamics of neuropsychiatric disorders and re-train neural networks to unlearn these disorders and restore proper function. This will enable the device to be eventually removed from the patient instead of being dependent on it.

This image from LLNL illustrates their next generation neural implant,

This rendering shows the next generation neural device capable of recording and stimulating the human central nervous system being developed at Lawrence Livermore National Laboratory. The implantable neural interface will record from and stimulate neurons within the brain for treating neuropsychiatric disorders.

This rendering shows the next generation neural device capable of recording and stimulating the human central nervous system being developed at Lawrence Livermore National Laboratory. The implantable neural interface will record from and stimulate neurons within the brain for treating neuropsychiatric disorders.

i expect there will be many more ‘brain’ projects to come with the advent of the US BRAIN initiative (funds of $100M in 2014 and $200M in 2015) and the European Union’s Human Brain Project (1B Euros to be spent on research over a 10 year period).

Wireless nano for remotely activating neurons

Every once in a while, there’s a piece of research that disconcerts me and this would be one of those pieces. From a May 22, 2014 news item on Nanowerk,

Yang Xiang, PhD, assistant professor of neurobiology at University of Massachusetts Medical School, has received a three-year, $900,000 grant from the Human Frontiers Science Program to lead an international team of scientists, including Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology, in the development and implementation of a new optogenetic platform that can remotely activate neurons inside a free-moving organism.

Using a new class of nanoparticles developed by Dr. Han, Dr. Xiang and colleagues propose to selectively turn on non-image forming photoreceptors (NIFP) inside mice and Drosophila unencumbered by the fiber optic wires used in currently available optogenetic technologies. By wirelessly stimulating these photoreceptors, which are able to sense light even though they don’t generate vision, scientists can better understand their role in regulating physiological functions such as circadian rhythm, sleep and melatonin secretion. The hope is that this new technology can also be used to study the links between other types of neurons, physiology and behavior.

A May 22, 2014 University of Massachusetts Medical School news release by Jim Fessenden, which originated the news item, describes optogenetics and some of its challenges,

“Current optogenetic technologies are limited in their application because they require using ‘wired’ fiber optic implants to deliver blue light to activate neuron activities,” said Xiang. “This is a major technological problem that has become an obstacle to understanding the physiological role NIFP play in animal behavior. If we’re able to overcome this hurdle by using the nanoparticles developed by Dr. Han, it would open the door to more informed investigations of not only NIFP but a wide range of neurons and their effect on behavior.”

In use for only about a decade, optogenetic technology combines techniques from optics and genetics, allowing scientists to precisely control activities of individual neurons using light. By genetically inserting light-activated biological molecules such as channelrhodopsins, a family of proteins found in algae, into neurons, scientists can instantaneously turn them on using beams of blue light with millisecond precision.

A limiting factor to the wider application of this technology, however, is that blue wavelengths are unable to penetrate skin, bone and other tissues deep enough to activate the neurons inside free-moving animals. To overcome this obstacle, current techniques require the insertion of fiber optic wires close enough to the neurons so the light that activates them can be delivered. This technique restricts animal movement and makes it difficult to observe behavioral responses in natural conditions. This fiber optic approach further limits scientists’ ability to study behavior over longer periods of time as the effectiveness of light delivery is relatively short due to scarring.

The news release describes the new technique proposed by Xiang and his associates,

Han has developed an “upconversion nanoparticle” (UCNP) that has the potential to solve the limitations of wired optogenetic techniques. These nanoparticles are capable of absorbing infrared light that can’t be seen and converting it into visible blue light. In contrast to blue light, infrared light is capable of penetrating skin and tissue to a depth of several centimeters. Xiang and Han believe these nanoparticles, tuned to emit blue light, can be inserted into the brain and used as a substitute for traditional fiber optics to wirelessly activate neurons in animals.

The hope is that the nanoparticles will absorb infrared light that passes through the tissue, and convert it to blue light inside the animal. This blue light would then activate the NFIPs. If successful, Xiang and colleagues will be able to observe any changes in animal behavior brought about by activating these non-image forming photoreceptors.

“The nanoparticles act as a kind of relay station,” said Han. “They convert the low-energy red light into a high-energy blue light that can activate the neurons. This technique completely alleviates the need to use intrusive fiber optic wires. It vastly simplifies the technology and expands the potential uses for optogenetics.”

Xiang said, “In many ways, this is the perfect bridge between a technological advancement and an important biological question. With these nanoparticles it’s possible for us to begin answering fundamental neurobiological questions about NIFPs.

“More broadly, it would open up the possibility of using other model organisms, such as Drosophila, that can’t be used with the current wired optogenetic technologies, to investigate and answer important questions about how neural activities regulate behavior.”

Illogical as it is, the idea that neurons could be wirelessly and remotely activated by someone other the owner of those neurons disturbs me even though I know drugs are commonly used to do much the same thing in humans.

In any event, the news release provides this final paragraph about the funding,

HFSP [Human Frontiers Science Program] awards are given to highly innovative teams that demonstrate that they have developed and can test a paradigm-shifting idea that holds promise for the development of new approaches to problems in the life sciences with potential to advance the field of research significantly.

I looked up the HFSP online and found this on the About Us page on the HFSP website,

The Human Frontier Science Program is a program of funding for frontier research in the life sciences. It is implemented by the International Human Frontier Science Program Organization (HFSPO) with its office in Strasbourg.

The members of the HFSPO, the so-called Management Supporting Parties (MSPs) are the contributing countries and the European Union, which contributes on behalf of the non-G7 EU members.

The current MSPs are Australia, Canada, France, Germany, India, Italy, Japan, Republic of Korea, Norway, New Zealand, Switzerland the United Kingdom, the United States of America and the European Union. [emphasis mine]

I was not expecting to find Canada on that list.

Controversial theory of consciousness confirmed (maybe)

There’s a very interesting event taking place today (Jan. 16, 2014) in Amsterdam, Netherlands titled: NEW PROOF OF REVOLUTIONARY THEORY OF CONSCIOUSNESS (programme).,which is one of a month’s worth of events themed around the brain (The Brainstorming Sessions).  The speakers at this event have recently published a paper and a Jan. 16, 2014 news item on ScienceDaily gives some insight into why theirbrainstorming session has the word revolutionary in the title,

A review and update of a controversial 20-year-old theory of consciousness published in Physics of Life Reviews claims that consciousness derives from deeper level, finer scale activities inside brain neurons. The recent discovery of quantum vibrations in “microtubules” inside brain neurons corroborates this theory, according to review authors Stuart Hameroff and Sir Roger Penrose. They suggest that EEG rhythms (brain waves) also derive from deeper level microtubule vibrations, and that from a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions.

A Jan. 16, 2014 Elsevier press release,which originated the news item, provides more details about the theory,

The theory, called “orchestrated objective reduction” (‘Orch OR’), was first put forward in the mid-1990s by eminent mathematical physicist Sir Roger Penrose, FRS, Mathematical Institute and Wadham College, University of Oxford, and prominent anesthesiologist Stuart Hameroff, MD, Anesthesiology, Psychology and Center for Consciousness Studies, The University of Arizona, Tucson. They suggested that quantum vibrational computations in microtubules were “orchestrated” (“Orch”) by synaptic inputs and memory stored in microtubules, and terminated by Penrose “objective reduction” (‘OR’), hence “Orch OR.” Microtubules are major components of the cell structural skeleton.

Orch OR was harshly criticized from its inception, as the brain was considered too “warm, wet, and noisy” for seemingly delicate quantum processes. However, evidence has now shown warm quantum coherence in plant photosynthesis, bird brain navigation, our sense of smell, and brain microtubules. The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair’s theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations. In addition, work from the laboratory of Roderick G. Eckenhoff, MD, at the University of Pennsylvania, suggests that anesthesia, which selectively erases consciousness while sparing non-conscious brain activities, acts via microtubules in brain neurons.

“The origin of consciousness reflects our place in the universe, the nature of our existence. Did consciousness evolve from complex computations among brain neurons, as most scientists assert? Or has consciousness, in some sense, been here all along, as spiritual approaches maintain?” ask Hameroff and Penrose in the current review. “This opens a potential Pandora’s Box, but our theory accommodates both these views, suggesting consciousness derives from quantum vibrations in microtubules, protein polymers inside brain neurons, which both govern neuronal and synaptic function, and connect brain processes to self-organizing processes in the fine scale, ‘proto-conscious’ quantum structure of reality.”

After 20 years of skeptical criticism, “the evidence now clearly supports Orch OR,” continue Hameroff and Penrose. “Our new paper updates the evidence, clarifies Orch OR quantum bits, or “qubits,” as helical pathways in microtubule lattices, rebuts critics, and reviews 20 testable predictions of Orch OR published in 1998 – of these, six are confirmed and none refuted.”

An important new facet of the theory is introduced. Microtubule quantum vibrations (e.g. in megahertz) appear to interfere and produce much slower EEG “beat frequencies.” Despite a century of clinical use, the underlying origins of EEG rhythms have remained a mystery. Clinical trials of brief brain stimulation aimed at microtubule resonances with megahertz mechanical vibrations using transcranial ultrasound have shown reported improvements in mood, and may prove useful against Alzheimer’s disease and brain injury in the future.

Lead author Stuart Hameroff concludes, “Orch OR is the most rigorous, comprehensive and successfully-tested theory of consciousness ever put forth. From a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions.

The review is accompanied by eight commentaries from outside authorities, including an Australian group of Orch OR arch-skeptics. To all, Hameroff and Penrose respond robustly.

The press release ends with this information about the event in Amsterdam,

Penrose, Hameroff and Bandyopadhyay will explore their theories during a session on “Microtubules and the Big Consciousness Debate” at the Brainstorm Sessions, a public three-day event at the Brakke Grond in Amsterdam, the Netherlands, January 16-18, 2014. They will engage skeptics in a debate on the nature of consciousness, and Bandyopadhyay and his team will couple microtubule vibrations from active neurons to play Indian musical instruments. “Consciousness depends on anharmonic vibrations of microtubules inside neurons, similar to certain kinds of Indian music, but unlike Western music which is harmonic,” Hameroff explains.

I wasn’t able to locate information about the three-day event in the press release but I did find this about the month-long series, The Brainstorm Sessions (Dutch language first, scroll down for English language version),

Europe and the USA are looking to completely unravel the secrets of our brains within the next ten years. Europe has designated 2014 as The Year of the Brain. We have decided to dedicate a month to the grey matter. A month in which guest curator Frank Theys – filmmaker, philosopher and visual artist – i.c.w. Damiaan Denys (neuroscientist, philosopher and professor of psychiatry at the AMC-UvA, the Amsterdam Medical Centre of the University of Amsterdam) will bring together elements he considers interesting from an artistic and philosophical viewpoint related to this theme.

Featuring an exhibition at the intersection between artistic and scientific experiments; the first ever performance by ‘stand-up scientist’ Damiaan Denys, Head of Psychiatry at the AMC hospital; a ‘neuro-concert’ by nanoscientist Anirban Bandyopadyay and a film programme in the Kriterion cinema in cooperation with Patricia Pisters, author of The Neuro-Image.

Fri 13 Dec – Sun 19 Jan: Exhibition Neurons Firing
Thur 09 Jan / 20h30: Sonic Soirée #22 a musical pillaging of the brain
Mon 13 Jan / 20h30: Lecture: Film and the Brain in Digital Era, by Patricia Pisters
Thu 16 Jan / 20h30: Lecture: Microtubules & the Big Consciousness Debate, by Roger Penrose & Anirban Bandyopadhyay
Fr 17 Jan / 20h30: Scientific demonstration Sapta Rishi (The Seven Stars)
Sa 18 Jan / 20h30: Scientific concert: Ajeya Chhandam – The Invincible Rhythm

I’m not sure what your chances are for attending the events on Jan. 17 or Jan. 18 but I wish you good luck! For those of us who weren’t able to attend the Jan.16, 2014 event featuring Penrose amd Hameroff, there are recently published papers.

First, the researchers offer a review of their theory along with some refinements,

Consciousness in the universe: A review of the ‘Orch OR’ theory by Stuart Hameroff and Roger Penrose. Physics of Life Reviews Available online 20 August 2013, Phys Life Rev. 2013 Aug 20. pii: S1571-0645(13)00118-8. doi: 10.1016/j.plrev.2013.08.002.

This paper is open access as of Jan. 16, 2014.

The next two papers have similar titles and were published at about the same time,

Reply to criticism of the ‘Orch OR qubit’ – ‘Orchestrated objective reduction’ is scientifically justified by Stuart Hameroff and Roger Penrose. Physics of Life Reviews Available online 12 December 2013. Phys Life Rev. 2013 Dec 12. pii: S1571-0645(13)00191-7. doi: 10.1016/j.plrev.2013.11.014.

Reply to seven commentaries on “Consciousness in the universe: Review of the ‘Orch OR’ theory by Stuart Hameroff and Roger Penrose. Physics of Life Reviews Available online 12 December 2013 Phys Life Rev. 2013 Dec 12. pii: S1571-0645(13)00190-5. doi: 10.1016/j.plrev.2013.11.013.

These papers are behind a paywall.

Two bits about the brain: fiction affects your brain and the US’s BRAIN Initiative is soliciting grant submissions

As a writer I love to believe my words have a lasting impact and while this research is focused on fiction, something I write more rarely than nonfiction, hope springs eternal that one day nonfiction too will be proved as having an impact (in a good way) on the brain. From a Jan. 3, 2014 news release on EurekAlert (or you can read the Dec. 17, 2013 Emory University news release by Carol Clark),

Many people can recall reading at least one cherished story that they say changed their life. Now researchers at Emory University have detected what may be biological traces related to this feeling: Actual changes in the brain that linger, at least for a few days, after reading a novel.

“Stories shape our lives and in some cases help define a person,” says neuroscientist Gregory Berns, lead author of the study and the director of Emory’s Center for Neuropolicy. “We want to understand how stories get into your brain, and what they do to it.”

His co-authors included Kristina Blaine and Brandon Pye from the Center for Neuropolicy, and Michael Prietula from Emory’s Goizueta Business School.

Neurobiological research using functional magnetic resonance imaging (fMRI) has begun to identify brain networks associated with reading stories. Most previous studies have focused on the cognitive processes involved in short stories, while subjects are actually reading them while they are in the fMRI scanner.

All of the study subjects read the same novel, “Pompeii,” a 2003 thriller by Robert Harris that is based on the real-life eruption of Mount Vesuvius in ancient Italy.

“The story follows a protagonist, who is outside the city of Pompeii and notices steam and strange things happening around the volcano,” Berns says. “He tries to get back to Pompeii in time to save the woman he loves. Meanwhile, the volcano continues to bubble and nobody in the city recognizes the signs.”

The researchers chose the book due to its page-turning plot. “It depicts true events in a fictional and dramatic way,” Berns says. “It was important to us that the book had a strong narrative line.”

For the first five days, the participants came in each morning for a base-line fMRI scan of their brains in a resting state. Then they were fed nine sections of the novel, about 30 pages each, over a nine-day period. They were asked to read the assigned section in the evening, and come in the following morning. After taking a quiz to ensure they had finished the assigned reading, the participants underwent an fMRI scan of their brain in a non-reading, resting state. After completing all nine sections of the novel, the participants returned for five more mornings to undergo additional scans in a resting state.

The results showed heightened connectivity in the left temporal cortex, an area of the brain associated with receptivity for language, on the mornings following the reading assignments. “Even though the participants were not actually reading the novel while they were in the scanner, they retained this heightened connectivity,” Berns says. “We call that a ‘shadow activity,’ almost like a muscle memory.”

Heightened connectivity was also seen in the central sulcus of the brain, the primary sensory motor region of the brain. Neurons of this region have been associated with making representations of sensation for the body, a phenomenon known as grounded cognition. Just thinking about running, for instance, can activate the neurons associated with the physical act of running.

“The neural changes that we found associated with physical sensation and movement systems suggest that reading a novel can transport you into the body of the protagonist,” Berns says. “We already knew that good stories can put you in someone else’s shoes in a figurative sense. Now we’re seeing that something may also be happening biologically.”

The neural changes were not just immediate reactions, Berns says, since they persisted the morning after the readings, and for the five days after the participants completed the novel.

“It remains an open question how long these neural changes might last,” Berns says. “But the fact that we’re detecting them over a few days for a randomly assigned novel suggests that your favorite novels could certainly have a bigger and longer-lasting effect on the biology of your brain.”

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

Short- and Long-Term Effects of a Novel on Connectivity in the Brain by Gregory S. Berns, Kristina Blaine, Michael J. Prietula, and Brandon E. Pye. Brain Connectivity. 2013, 3(6): 590-600. doi:10.1089/brain.2013.0166.

This is an open access paper where you’ll notice the participants cover a narrow range of ages (from the Materials and Methods section of the paper,

A total of 21 participants were studied. Two were excluded from the fMRI analyses: one for insufficient attendance, and the other for image abnormalities. Before the experiment, participants were screened for the presence of medical and psychiatric diagnoses, and none were taking medications. There were 12 female and 9 male participants between the ages of 19 and 27 (mean 21.5). Emory University’s Institutional Review Board approved all procedures, and all participants gave written informed consent.

It’s always good to remember that university research often draws from student populations and the question one might want to ask is whether or not those results will remain the same, more or less, throughout someone’s life span.In any event, I find this research intriguing and hope they follow this up.

Currently known as the BRAIN (Brain Research through Advancing Innovative Neurotechnologies), I first wrote about the project under its old name BAM (Brain Activity Map) in two postings, first in a March 4, 2013 posting featuring brain-to-brain communication and other brain-related tidbits, then again, in an April 2, 2013 posting featuring an announcement about its federal funding. Today (Jan. 6, 2014), I stumbled across some BRAIN funding opportunities for researchers, from the BRAIN Initiative funding opportunities webpage,

NIH released six funding opportunity announcements in support of the President’s BRAIN Initiative. Collectively, these opportunities focus on building a new arsenal of tools and technologies for helping scientists unlock the mysteries of the brain. NIH [US National Institutes of Health] plans to invest $40 million in Fiscal Year 2014 through these opportunities, contingent upon the submission of a sufficient number of scientifically meritorious applications.

The opportunities currently available are as follows:

  • Transformative Approaches for Cell-Type Classification in the Brain (U01) (RFA-MH-14-215) – aims to pilot classification strategies to generate a systematic inventory/cell census of cell types in the brain, integrating molecular identity of cell types with connectivity, morphology, and location. These pilot projects and methodologies should be designed to demonstrate their utility and scalability to ultimately complete a comprehensive cell census of the human brain.
    Contact Email: BRAIN-info-NIMH@mail.nih.gov
    Application Receipt: March 13, 2014
  • Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain (U01) (RFA-MH-14-216) – aims to develop and validate novel tools that possess a high degree of cell-type and/or circuit-level specificity to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. A particular emphasis is the development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest; new approaches are also expected to target specific cell types and or circuits in the nervous system with greater precision and sensitivity than currently established methods.
    Contact Email: BRAIN-info-NIMH@mail.nih.gov
    Application Receipt: March 13, 2014
  • New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (U01) (RFA-NS-14-007) – focuses on development and proof-of-concept testing of new technologies and novel approaches for large scale recording and manipulation of neural activity, with cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. The proposed research may be high risk, but if successful could profoundly change the course of neuroscience research.
    Contact Email: NINDS-Brain-Initiative@nih.gov
    Application Receipt: March 24, 2014
  • Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (U01) (RFA-NS-14-008) – aims to optimize existing and emerging technologies and approaches that have the potential to address major challenges associated with recording and manipulating neural activity. This FOA is intended for the iterative refinement of emergent technologies and approaches that have already demonstrated their transformative potential through initial proof-of-concept testing, and are appropriate for accelerated engineering development with an end-goal of broad dissemination and incorporation into regular neuroscience research.
    Contact Email: NINDS-Brain-Initiative@nih.gov
    Application Receipt: March 24, 2014
  • Integrated Approaches to Understanding Circuit Function in the Nervous System (U01) (RFA-NS-14-009) – focuses onexploratory studies that use new and emerging methods for large scale recording and manipulation to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration, for integrated development of experimental, analytic and theoretical capabilities in preparation for a future competition for large-scale awards.
    Contact Email: NINDS-Brain-Initiative@nih.gov
    Application Receipt: March 24, 2014
  • Planning for Next Generation Human Brain Imaging (R24) (RFA-MH-14-217) – aims to create teams of imaging scientist together with other experts from a range of disciplines such as engineering, material sciences, nanotechnology and computer science, to plan for a new generation of non-invasive imaging techniques that would be used to understand human brain function. Incremental improvements to existing technologies will not be funded under this announcement.
    Contact Email: sgrant@nida.nih.gov
    Application Receipt: March 13, 2014

For the interested, in the near future there will be some informational conference calls regarding these opportunities,

Informational Conference Calls for Prospective Applicants

NIH will be hosting a series of informational conference calls to address technical questions regarding applications to each of the RFAs released under the BRAIN Initiative.   Information on dates and contacts for each of the conference calls is as follows:

January 10, 2014, 2:00-3:00 PM EST
RFA-MH-14-215, Transformative Approaches for Cell-Type Classification in the Brain

For call-in information, contact Andrea Beckel-Mitchener at BRAIN-info-NIMH@mail.nih.gov.

January 13, 2014, 2:00-3:00 PM EST
RFA-MH-14-216, Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain

For call-in information, contact Michelle Freund at BRAIN-info-NIMH@mail.nih.gov.

January 15, 2014, 1:00-2:00 PM EST
RFA-MH-14-217, Planning for Next Generation Human Brain Imaging

For call-in information, contact Greg Farber at BRAIN-info-NIMH@mail.nih.gov.

February 4, 2014, 1:00-2:30 PM EST
RFA-NS-14-007, New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System
RFA-NS-14-008, Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System
RFA-NS-14-009, Integrated Approaches to Understanding Circuit Function in the Nervous System

For call-in information, contact Karen David at NINDS-Brain-Initiative@nih.gov.
In addition to accessing the information provided in the upcoming conference calls, applicants are strongly encouraged to consult with the Scientific/Research Contacts listed in each of the RFAs to discuss the alignment of their proposed work with the goals of the RFA to which they intend to apply.

Good luck!

It’s kind of fascinating to see this much emphasis on brains what with the BRAIN Initiative in the US and the Human Brain Project in Europe (my Jan. 28, 2013 posting announcing the European Union’s winning Future and Emerging Technologies (FET) research projects, The prizes (1B Euros to be paid out over 10 years to each winner) had been won by the Human Brain FET project and the Graphene FET project, respectively