Tag Archives: brains

Blue Brain Project builds a digital piece of brain

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Caption: This is a photo of a virtual brain slice. Credit: Makram et al./Cell 2015

Caption: This is a photo of a virtual brain slice. Credit: Makram et al./Cell 2015

Here’s more *about this virtual brain slice* from an Oct. 8, 2015 Cell (magazine) news release on EurekAlert,

If you want to learn how something works, one strategy is to take it apart and put it back together again [also known as reverse engineering]. For 10 years, a global initiative called the Blue Brain Project–hosted at the Ecole Polytechnique Federale de Lausanne (EPFL)–has been attempting to do this digitally with a section of juvenile rat brain. The project presents a first draft of this reconstruction, which contains over 31,000 neurons, 55 layers of cells, and 207 different neuron subtypes, on October 8 [2015] in Cell.

Heroic efforts are currently being made to define all the different types of neurons in the brain, to measure their electrical firing properties, and to map out the circuits that connect them to one another. These painstaking efforts are giving us a glimpse into the building blocks and logic of brain wiring. However, getting a full, high-resolution picture of all the features and activity of the neurons within a brain region and the circuit-level behaviors of these neurons is a major challenge.

Henry Markram and colleagues have taken an engineering approach to this question by digitally reconstructing a slice of the neocortex, an area of the brain that has benefitted from extensive characterization. Using this wealth of data, they built a virtual brain slice representing the different neuron types present in this region and the key features controlling their firing and, most notably, modeling their connectivity, including nearly 40 million synapses and 2,000 connections between each brain cell type.

“The reconstruction required an enormous number of experiments,” says Markram, of the EPFL. “It paves the way for predicting the location, numbers, and even the amount of ion currents flowing through all 40 million synapses.”

Once the reconstruction was complete, the investigators used powerful supercomputers to simulate the behavior of neurons under different conditions. Remarkably, the researchers found that, by slightly adjusting just one parameter, the level of calcium ions, they could produce broader patterns of circuit-level activity that could not be predicted based on features of the individual neurons. For instance, slow synchronous waves of neuronal activity, which have been observed in the brain during sleep, were triggered in their simulations, suggesting that neural circuits may be able to switch into different “states” that could underlie important behaviors.

“An analogy would be a computer processor that can reconfigure to focus on certain tasks,” Markram says. “The experiments suggest the existence of a spectrum of states, so this raises new types of questions, such as ‘what if you’re stuck in the wrong state?'” For instance, Markram suggests that the findings may open up new avenues for explaining how initiating the fight-or-flight response through the adrenocorticotropic hormone yields tunnel vision and aggression.

The Blue Brain Project researchers plan to continue exploring the state-dependent computational theory while improving the model they’ve built. All of the results to date are now freely available to the scientific community at https://bbp.epfl.ch/nmc-portal.

An Oct. 8, 2015 Hebrew University of Jerusalem press release on the Canadian Friends of the Hebrew University of Jerusalem website provides more detail,

Published by the renowned journal Cell, the paper is the result of a massive effort by 82 scientists and engineers at EPFL and at institutions in Israel, Spain, Hungary, USA, China, Sweden, and the UK. It represents the culmination of 20 years of biological experimentation that generated the core dataset, and 10 years of computational science work that developed the algorithms and built the software ecosystem required to digitally reconstruct and simulate the tissue.

The Hebrew University of Jerusalem’s Prof. Idan Segev, a senior author of the research paper, said: “With the Blue Brain Project, we are creating a digital reconstruction of the brain and using supercomputer simulations of its electrical behavior to reveal a variety of brain states. This allows us to examine brain phenomena within a purely digital environment and conduct experiments previously only possible using biological tissue. The insights we gather from these experiments will help us to understand normal and abnormal brain states, and in the future may have the potential to help us develop new avenues for treating brain disorders.”

Segev, a member of the Hebrew University’s Edmond and Lily Safra Center for Brain Sciences and director of the university’s Department of Neurobiology, sees the paper as building on the pioneering work of the Spanish anatomist Ramon y Cajal from more than 100 years ago: “Ramon y Cajal began drawing every type of neuron in the brain by hand. He even drew in arrows to describe how he thought the information was flowing from one neuron to the next. Today, we are doing what Cajal would be doing with the tools of the day: building a digital representation of the neurons and synapses, and simulating the flow of information between neurons on supercomputers. Furthermore, the digitization of the tissue is open to the community and allows the data and the models to be preserved and reused for future generations.”

While a long way from digitizing the whole brain, the study demonstrates that it is feasible to digitally reconstruct and simulate brain tissue, and most importantly, to reveal novel insights into the brain’s functioning. Simulating the emergent electrical behavior of this virtual tissue on supercomputers reproduced a range of previous observations made in experiments on the brain, validating its biological accuracy and providing new insights into the functioning of the neocortex. This is a first step and a significant contribution to Europe’s Human Brain Project, which Henry Markram founded, and where EPFL is the coordinating partner.

Cell has made a video abstract available (it can be found with the Hebrew University of Jerusalem press release)

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

Reconstruction and Simulation of Neocortical Microcircuitry by Henry Markram, Eilif Muller, Srikanth Ramaswamy, Michael W. Reimann, Marwan Abdellah, Carlos Aguado Sanchez, Anastasia Ailamaki, Lidia Alonso-Nanclares, Nicolas Antille, Selim Arsever, Guy Antoine Atenekeng Kahou, Thomas K. Berger, Ahmet Bilgili, Nenad Buncic, Athanassia Chalimourda, Giuseppe Chindemi, Jean-Denis Courcol, Fabien Delalondre, Vincent Delattre, Shaul Druckmann, Raphael Dumusc, James Dynes, Stefan Eilemann, Eyal Gal, Michael Emiel Gevaert, Jean-Pierre Ghobril, Albert Gidon, Joe W. Graham, Anirudh Gupta, Valentin Haenel, Etay Hay, Thomas Heinis, Juan B. Hernando, Michael Hines, Lida Kanari, Daniel Keller, John Kenyon, Georges Khazen, Yihwa Kim, James G. King, Zoltan Kisvarday, Pramod Kumbhar, Sébastien Lasserre, Jean-Vincent Le Bé, Bruno R.C. Magalhães, Angel Merchán-Pérez, Julie Meystre, Benjamin Roy Morrice, Jeffrey Muller, Alberto Muñoz-Céspedes, Shruti Muralidhar, Keerthan Muthurasa, Daniel Nachbaur, Taylor H. Newton, Max Nolte, Aleksandr Ovcharenko, Juan Palacios, Luis Pastor, Rodrigo Perin, Rajnish Ranjan, Imad Riachi, José-Rodrigo Rodríguez, Juan Luis Riquelme, Christian Rössert, Konstantinos Sfyrakis, Ying Shi, Julian C. Shillcock, Gilad Silberberg, Ricardo Silva, Farhan Tauheed, Martin Telefont, Maria Toledo-Rodriguez, Thomas Tränkler, Werner Van Geit, Jafet Villafranca Díaz, Richard Walker, Yun Wang, Stefano M. Zaninetta, Javier DeFelipe, Sean L. Hill, Idan Segev, Felix Schürmann. Cell, Volume 163, Issue 2, p456–492, 8 October 2015 DOI: http://dx.doi.org/10.1016/j.cell.2015.09.029

This paper appears to be open access.

My most substantive description of the Blue Brain Project , previous to this, was in a Jan. 29, 2013 posting featuring the European Union’s (EU) Human Brain project and involvement from countries that are not members.

* I edited a redundant lede (That’s a virtual slice of a rat brain.), moved the second sentence to the lede while adding this:  *about this virtual brain slice* on Oct. 16, 2015 at 0955 hours PST.

On the verge of controlling neurons by wireless?

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Scientists have controlled a mouse’s neurons with a wireless device (and unleashed some paranoid fantasies? well, mine if no one else’s) according to a July 16, 2015 news item on Nanowerk (Note: A link has been removed),

A study showed that scientists can wirelessly determine the path a mouse walks with a press of a button. Researchers at the Washington University School of Medicine, St. Louis, and University of Illinois, Urbana-Champaign, created a remote controlled, next-generation tissue implant that allows neuroscientists to inject drugs and shine lights on neurons deep inside the brains of mice. The revolutionary device is described online in the journal Cell (“Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics”). Its development was partially funded by the [US] National Institutes of Health [NIH].

The researchers have made an image/illustration of the probe available,

Mind Bending Probe Scientists used soft materials to create a brain implant a tenth the width of a human hair that can wirelessly control neurons with lights and drugs. Courtesy of Jeong lab, University of Colorado Boulder.

A July 16, 2015 US NIH National Institute of Neurological Disorders and Stroke news release, which originated the news item, describes the study and notes that instructions for building the implant are included in the published study,

“It unplugs a world of possibilities for scientists to learn how brain circuits work in a more natural setting.” said Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology at Washington University School of Medicine and a senior author of the study.

The Bruchas lab studies circuits that control a variety of disorders including stress, depression, addiction, and pain. Typically, scientists who study these circuits have to choose between injecting drugs through bulky metal tubes and delivering lights through fiber optic cables. Both options require surgery that can damage parts of the brain and introduce experimental conditions that hinder animals’ natural movements.

To address these issues, Jae-Woong Jeong, Ph.D., a bioengineer formerly at the University of Illinois at Urbana-Champaign, worked with Jordan G. McCall, Ph.D., a graduate student in the Bruchas lab, to construct a remote controlled, optofluidic implant. The device is made out of soft materials that are a tenth the diameter of a human hair and can simultaneously deliver drugs and lights.

“We used powerful nano-manufacturing strategies to fabricate an implant that lets us penetrate deep inside the brain with minimal damage,” said John A. Rogers, Ph.D., professor of materials science and engineering, University of Illinois at Urbana-Champaign and a senior author. “Ultra-miniaturized devices like this have tremendous potential for science and medicine.”

With a thickness of 80 micrometers and a width of 500 micrometers, the optofluidic implant is thinner than the metal tubes, or cannulas, scientists typically use to inject drugs. When the scientists compared the implant with a typical cannula they found that the implant damaged and displaced much less brain tissue.

The scientists tested the device’s drug delivery potential by surgically placing it into the brains of mice. In some experiments, they showed that they could precisely map circuits by using the implant to inject viruses that label cells with genetic dyes. In other experiments, they made mice walk in circles by injecting a drug that mimics morphine into the ventral tegmental area (VTA), a region that controls motivation and addiction.

The researchers also tested the device’s combined light and drug delivery potential when they made mice that have light-sensitive VTA neurons stay on one side of a cage by commanding the implant to shine laser pulses on the cells. The mice lost the preference when the scientists directed the device to simultaneously inject a drug that blocks neuronal communication. In all of the experiments, the mice were about three feet away from the command antenna.

“This is the kind of revolutionary tool development that neuroscientists need to map out brain circuit activity,” said James Gnadt, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).  “It’s in line with the goals of the NIH’s BRAIN Initiative.”

The researchers fabricated the implant using semi-conductor computer chip manufacturing techniques. It has room for up to four drugs and has four microscale inorganic light-emitting diodes. They installed an expandable material at the bottom of the drug reservoirs to control delivery. When the temperature on an electric heater beneath the reservoir rose then the bottom rapidly expanded and pushed the drug out into the brain.

“We tried at least 30 different prototypes before one finally worked,” said Dr. McCall.

“This was truly an interdisciplinary effort,” said Dr. Jeong, who is now an assistant professor of electrical, computer, and energy engineering at University of Colorado Boulder. “We tried to engineer the implant to meet some of neurosciences greatest unmet needs.”

In the study, the scientists provide detailed instructions for manufacturing the implant.

“A tool is only good if it’s used,” said Dr. Bruchas. “We believe an open, crowdsourcing approach to neuroscience is a great way to understand normal and healthy brain circuitry.”

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

Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics by Jae-Woong Jeong, Jordan G. McCall, Gunchul Shin, Yihui Zhang, Ream Al-Hasani, Minku Kim, Shuo Li, Joo Yong Sim, Kyung-In Jang, Yan Shi, Daniel Y. Hong, Yuhao Liu, Gavin P. Schmitz, Li Xia, Zhubin He, Paul Gamble, Wilson Z. Ray, Yonggang Huang, Michael R. Bruchas, and John A. Rogers.  Cell, July 16, 2015. DOI: 10.1016/j.cell.2015.06.058

This paper is behind a paywall.

I last wrote about wireless activation of neurons in a May 28, 2014 posting which featured research at the University of Massachusetts Medical School.

Centralized depot (Wikipedia style) for data on neurons

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The decades worth of data that has been collected about the billions of neurons in the brain is astounding. To help scientists make sense of this “brain big data,” researchers at Carnegie Mellon University have used data mining to create http://www.neuroelectro.org, a publicly available website that acts like Wikipedia, indexing physiological information about neurons.

opens a March 30, 2015 news item on ScienceDaily (Note: A link has been removed),

The site will help to accelerate the advance of neuroscience research by providing a centralized resource for collecting and comparing data on neuronal function. A description of the data available and some of the analyses that can be performed using the site are published online by the Journal of Neurophysiology

A March 30, 2015 Carnegie Mellon University news release on EurekAlert, which originated the news item, describes, in more detail,  the endeavour and what the scientists hope to achieve,

The neurons in the brain can be divided into approximately 300 different types based on their physical and functional properties. Researchers have been studying the function and properties of many different types of neurons for decades. The resulting data is scattered across tens of thousands of papers in the scientific literature. Researchers at Carnegie Mellon turned to data mining to collect and organize these data in a way that will make possible, for the first time, new methods of analysis.

“If we want to think about building a brain or re-engineering the brain, we need to know what parts we’re working with,” said Nathan Urban, interim provost and director of Carnegie Mellon’s BrainHubSM neuroscience initiative. “We know a lot about neurons in some areas of the brain, but very little about neurons in others. To accelerate our understanding of neurons and their functions, we need to be able to easily determine whether what we already know about some neurons can be applied to others we know less about.”

Shreejoy J. Tripathy, who worked in Urban’s lab when he was a graduate student in the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition (CNBC) Program in Neural Computation, selected more than 10,000 published papers that contained physiological data describing how neurons responded to various inputs. He used text mining algorithms to “read” each of the papers. The text mining software found the portions of each paper that identified the type of neuron studied and then isolated the electrophysiological data related to the properties of that neuronal type. It also retrieved information about how each of the experiments in the literature was completed, and corrected the data to account for any differences that might be caused by the format of the experiment. Overall, Tripathy, who is now a postdoc at the University of British Columbia, was able to collect and standardize data for approximately 100 different types of neurons, which he published on the website http://www.neuroelectro.org.

Since the data on the website was collected using text mining, the researchers realized that it was likely to contain errors related to extraction and standardization. Urban and his group validated much of the data, but they also created a mechanism that allows site users to flag data for further evaluation. Users also can contribute new data with minimal intervention from site administrators, similar to Wikipedia.

“It’s a dynamic environment in which people can collect, refine and add data,” said Urban, who is the Dr. Frederick A. Schwertz Distinguished Professor of Life Sciences and a member of the CNBC. “It will be a useful resource to people doing neuroscience research all over the world.”

Ultimately, the website will help researchers find groups of neurons that share the same physiological properties, which could provide a better understanding of how a neuron functions. For example, if a researcher finds that a type of neuron in the brain’s neocortex fires spontaneously, they can look up other neurons that fire spontaneously and access research papers that address this type of neuron. Using that information, they can quickly form hypotheses about whether or not the same mechanisms are at play in both the newly discovered and previously studied neurons.

To demonstrate how neuroelectro.org could be used, the researchers compared the electrophysiological data from more than 30 neuron types that had been most heavily studied in the literature. These included pyramidal neurons in the hippocampus, which are responsible for memory, and dopamine neurons in the midbrain, thought to be responsible for reward-seeking behaviors and addiction, among others. The site was able to find many expected similarities between the different types of neurons, and some similarities that were a surprise to researchers. Those surprises represent promising areas for future research.

In ongoing work, the Carnegie Mellon researchers are comparing the data on neuroelectro.org with other kinds of data, including data on neurons’ patterns of gene expression. For example, Urban’s group is using another publicly available resource, the Allen Brain Atlas, to find whether groups of neurons with similar electrical function have similar gene expression.

“It would take a lot of time, effort and money to determine both the physiological properties of a neuron and its gene expression,” Urban said. “Our website will help guide this research, making it much more efficient.”

The researchers have produced a brief video describing neurons and their project,

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

Brain-wide analysis of electrophysiological diversity yields novel categorization of mammalian neuron types by Shreejoy J Tripathy, Shawn D. Burton, Matthew Geramita, Richard C. Gerkin, and Nathaniel N. Urban. Journal of Neurophysiology Published 25 March 2015 DOI: 10.1152/jn.00237.2015

This paper is behind a paywall.

Making 3D patches for the brain

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They’re not ready to start patching any brains yet but the research seems promising. From an April 1, 2015 news item on ScienceDaily,

Damage to neural tissue is typically permanent and causes lasting disability in patients, but a new approach has recently been discovered that holds incredible potential to reconstruct neural tissue at high resolution in three dimensions. Research recently published in the Journal of Neural Engineering demonstrated a method for embedding scaffolding of patterned nanofibers within three-dimensional (3D) hydrogel structures, and it was shown that neurite outgrowth from neurons in the hydrogel followed the nanofiber scaffolding by tracking directly along the nanofibers, particularly when the nanofibers were coated with a type of cell adhesion molecule called laminin. It was also shown that the coated nanofibers significantly enhanced the length of growing neurites, and that the type of hydrogel could significantly affect the extent to which the neurites tracked the nanofibers.

A March 31, 2015 Institute of Neural Regeneration & Tissue Engineering press release on EurekAlert, which originated the news item, describes the thinking underlying this research and future research plans,

“Neural stem cells hold incredible potential for restoring damaged cells in the nervous system, and 3D reconstruction of neural tissue is essential for replicating the complex anatomical structure and function of the brain and spinal cord,” said Dr. McMurtrey, author of the study and director of the research institute that led this work. “So it was thought that the combination of induced neuronal cells with micropatterned biomaterials might enable unique advantages in 3D cultures, and this research showed that not only can neuronal cells be cultured in 3D conformations, but the direction and pattern of neurite outgrowth can be guided and controlled using relatively simple combinations of structural cues and biochemical signaling factors.”

The next step will be replicating more complex structures using a patient’s own induced stem cells to reconstruct damaged or diseased sites in the nervous system. These 3D reconstructions can then be used to implant into the damaged areas of neural tissue to help reconstruct specific neuroanatomical structures and integrate with the proper neural circuitry in order to restore function. Successful restoration of function would require training of the new neural circuitry over time, but by selecting the proper neurons and forming them into native architecture, implanted neural stem cells would have a much higher chance of providing successful outcomes. The scaffolding and hydrogel materials are biocompatible and biodegradable, and the hydrogels can also help to maintain the microstructure of implanted cells and prevent them from washing away in the cerebrospinal fluid that surrounds the brain and spinal cord.

McMurtrey also noted that by making these site-specific reconstructions of neural tissue, not only can neural architecture be rebuilt, but researchers can also make models for studying disease mechanisms and developmental processes just by using skin cells that are induced into pluripotent stem cells and into neurons from patients with a variety of diseases and conditions. “The 3D constructs enable a realistic replication of the innate cellular environment and also enable study of diseased human neurons without needing to biopsy neurons from affected patients and without needing to make animal models that can fail to replicate the full array of features seen in humans,” said McMurtrey.

The ability to engineer neural tissue from stem cells and biomaterials holds great potential for regenerative medicine. The combination of stem cells, functionalized hydrogel architecture, and patterned and functionalized nanofiber scaffolding enables the formation of unique 3D tissue constructs, and these engineered constructs offer important applications in brain and spinal cord tissue that has been damaged by trauma, stroke, or degeneration. In particular, this work may one day help in the restoration of functional neuroanatomical pathways and structures at sites of spinal cord injury, traumatic brain injury, tumor resection, stroke, or neurodegenerative diseases of Parkinson’s, Huntington’s, Alzheimer’s, or amyotrophic lateral sclerosis.

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

Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control by Richard McMurtrey (Journal of Neural Engineering Volume 11 Number 6) 2014 J. J. Neural Eng. 11 066009 doi:10.1088/1741-2560/11/6/066009

This paper is open access.

A little unusually for me, here’s the abstract for the paper,

Objective. Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. Approach. A method of creating aligned electrospun nanofibers was implemented and fiber characteristics were analyzed using environmental scanning electron microscopy. Nanofibers were composed of polycaprolactone (PCL) polymer, PCL mixed with gelatin, or PCL with a laminin coating. Three-dimensional hydrogels were then integrated with embedded aligned nanofibers to support neuronal cell cultures. Microscopic images were captured at high-resolution in single and multi-focal planes with eGFP-expressing neuronal SH-SY5Y cells in a fluorescent channel and nanofiber scaffolding in another channel. Neuronal morphology and neurite tracking of nanofibers were then analyzed in detail. Main results. Aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. Specifically, the average length of neurites per cell in 3D HA constructs with laminin-functionalized nanofibers increased by 66% compared to the same laminin fibers on 2D laminin surfaces, increased by 59% compared to 2D laminin-coated surface without fibers, and increased by 1052% compared to HA constructs without fibers. Laminin functionalization of fibers also doubled average neurite length over plain PCL fibers in the same 3D HA constructs. In addition, neurites also demonstrated tracking directly along the fibers, with 66% of neurite lengths directly tracking laminin-coated fibers in 3D HA constructs, which was a 65% relative increase in neurite tracking compared to plain PCL fibers in the same 3D HA constructs and a 213% relative increase over laminin-coated fibers on 2D laminin-coated surfaces. Significance. This work demonstrates the ability to create unique 3D neural tissue constructs using a combined system of hydrogel and nanofiber scaffolding. Importantly, patterned and biofunctionalized nanofiber scaffolds that can control direction and increase length of neurite outgrowth in three-dimensions hold much potential for neural tissue engineering. This approach offers advancements in the development of implantable neural tissue constructs that enable control of neural development and reproduction of neuroanatomical pathways, with the ultimate goal being the achievement of functional neural regeneration.

I have a few comments, this work was performed in vitro and I imagine it will be several years before it is attempted in human clinical trials. As well, the ethics issues raised by this work are interesting. While the doctors are talking about repairs to injured tissues, it’s only a matter of time until someone tries to improve on the brain or human enhancement. After all, modern plastic surgery was developed as a form of repair for soldiers and others who were disfigured. These days, much of the practice is concerned with preserving youth or enhancing someone’s looks. Not altogether coincidentally, I wrote about the second volume of a report from the US Presidential Bioethics Commission in my April 2, 2015 post titled: Gray Matters volume 2: Integrative Approaches for Neuroscience, Ethics, and Society issued March 2015 by US Presidential Bioethics Commission.

Finally, you can find out more about the Institute of Neural Regeneration & Tissue Engineering here.

Université de Montréal (Canada) and nanobots breech blood-brain barrier to deliver drugs to the brain

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In the spirit of full disclosure, the March 25, 2014 news item on ScienceDaily describing the research about breeching the blood-brain barrier uses the term nanorobotic agents rather than nanobots, a term which makes my headline a lot catchier although less accurate. Getting back to the research,

Magnetic nanoparticles can open the blood-brain barrier and deliver molecules directly to the brain, say researchers from the University of Montreal, Polytechnique Montréal, and CHU Sainte-Justine. This barrier runs inside almost all vessels in the brain and protects it from elements circulating in the blood that may be toxic to the brain. The research is important as currently 98% of therapeutic molecules are also unable to cross the blood-brain barrier.

“The barrier is temporary [sic] opened at a desired location for approximately 2 hours by a small elevation of the temperature generated by the nanoparticles when exposed to a radio-frequency field,” explained first author and co-inventor Seyed Nasrollah Tabatabaei. “Our tests revealed that this technique is not associated with any inflammation of the brain. This new result could lead to a breakthrough in the way nanoparticles are used in the treatment and diagnosis of brain diseases,” explained the co-investigator, Hélène Girouard. “At the present time, surgery is the only way to treat patients with brain disorders. Moreover, while surgeons are able to operate to remove certain kinds of tumors, some disorders are located in the brain stem, amongst nerves, making surgery impossible,” added collaborator and senior author Anne-Sophie Carret.

A March 25, 2015 University of Montreal news release (also on EurekAlert), which originated the news item, notes that the technique was tested or rats or mice (murine model) and explains how the technology breeches the blood-brain barrier,

Although the technology was developed using murine models and has not yet been tested in humans, the researchers are confident that future research will enable its use in people. “Building on earlier findings and drawing on the global effort of an interdisciplinary team of researchers, this technology proposes a modern version of the vision described almost 40 years ago in the movie Fantastic Voyage, where a miniature submarine navigated in the vascular network to reach a specific region of the brain,” said principal investigator Sylvain Martel. In earlier research, Martel and his team had managed to manipulate the movement of nanoparticles through the body using the magnetic forces generated by magnetic resonance imaging (MRI) machines.

To open the blood-brain barrier, the magnetic nanoparticles are sent to the surface of the blood-brain barrier at a desired location in the brain. Although it was not the technique used in this study, the placement could be achieved by using the MRI technology described above. Then, the researchers generated a radio-frequency field. The nanoparticles reacted to the radio-frequency field by dissipating heat thereby creating a mechanical stress on the barrier. This allows a temporary and localized opening of the barrier for diffusion of therapeutics into the brain.

The technique is unique in many ways. “The result is quite significant since we showed in previous experiments that the same nanoparticles can also be used to navigate therapeutic agents in the vascular network using a clinical MRI scanner,” Martel remarked. “Linking the navigation capability with these new results would allow therapeutics to be delivered directly to a specific site of the brain, potentially improving significantly the efficacy of the treatment while avoiding systemic circulation of toxic agents that affect healthy tissues and organs,” Carret added. “While other techniques have been developed for delivering drugs to the blood-brain barrier, they either open it too wide, exposing the brain to great risks, or they are not precise enough, leading to scattering of the drugs and possible unwanted side effect,” Martel said.

Although there are many hurdles to overcome before the technology can be used to treat humans, the research team is optimistic. “Although our current results are only proof of concept, we are on the way to achieving our goal of developing a local drug delivery mechanism that will be able to treat oncologic, psychiatric, neurological and neurodegenerative disorders, amongst others,” Carret concluded.

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

Remote control of the permeability of the blood–brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery by Seyed Nasrollah Tabatabaei, Hélène Girouard, Anne-Sophie Carret, and Sylvain Martel.Journal of Controlled Release, Volume 206, 28 May 2015, Pages 49–57,  DOI: 10.1016/j.jconrel.2015.02.027  Available online 25 February 2015

This paper is behind a paywall.

For anyone unfamiliar with French, University of Montreal is Université de Montréal.

Spinal cords, brains, implants, and remote control

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I have two items about implants and brains and an item about being able to exert remote control of the brain, all of which hint at a cyborg future for at least a few of us.

e-Dura, the spinal column, and the brain

The first item concerns some research, at the École Polytechnique de Lausanne (EPFL) which features flexible electronics. From a March 24, 2015 article by Ben Schiller for Fast Company (Note: Links have been removed),

Researchers at the Swiss Federal Institute of Technology, in Lausanne, have developed the e-Dura—a tiny skinlike device that attaches directly to damaged spinal cords. By sending out small electrical pulses, it stimulates the cord as if it were receiving signals from the brain, thus allowing movement.

“The purpose of the neuro-prosthesis is to excite the neurons that are on the spinal cord below the site of the injury and activate them, just like if they were receiving information from the brain,” says Stéphanie Lacour, a professor at the institute.

A January 8, 2015 (?) EPFL press release provides more information about the research,

EPFL scientists have managed to get rats walking on their own again using a combination of electrical and chemical stimulation. But applying this method to humans would require multifunctional implants that could be installed for long periods of time on the spinal cord without causing any tissue damage. This is precisely what the teams of professors Stéphanie Lacour and Grégoire Courtine have developed. Their e-Dura implant is designed specifically for implantation on the surface of the brain or spinal cord. The small device closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and pharmacological substances. The risks of rejection and/or damage to the spinal cord have been drastically reduced. An article about the implant will appear in early January [2015] in Science Magazine.

So-called “surface implants” have reached a roadblock; they cannot be applied long term to the spinal cord or brain, beneath the nervous system’s protective envelope, otherwise known as the “dura mater,” because when nerve tissues move or stretch, they rub against these rigid devices. After a while, this repeated friction causes inflammation, scar tissue buildup, and rejection.

Here’s what the implant looks like,

Courtesy: EPFL

Courtesy: EPFL

The press release describes how the implant is placed (Note: A link has been removed),

Flexible and stretchy, the implant developed at EPFL is placed beneath the dura mater, directly onto the spinal cord. Its elasticity and its potential for deformation are almost identical to the living tissue surrounding it. This reduces friction and inflammation to a minimum. When implanted into rats, the e-Dura prototype caused neither damage nor rejection, even after two months. More rigid traditional implants would have caused significant nerve tissue damage during this period of time.

The researchers tested the device prototype by applying their rehabilitation protocol — which combines electrical and chemical stimulation – to paralyzed rats. Not only did the implant prove its biocompatibility, but it also did its job perfectly, allowing the rats to regain the ability to walk on their own again after a few weeks of training.

“Our e-Dura implant can remain for a long period of time on the spinal cord or the cortex, precisely because it has the same mechanical properties as the dura mater itself. This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury,” explains Lacour, co-author of the paper, and holder of EPFL’s Bertarelli Chair in Neuroprosthetic Technology.

The press release goes on to describe the engineering achievements,

Developing the e-Dura implant was quite a feat of engineering. As flexible and stretchable as living tissue, it nonetheless includes electronic elements that stimulate the spinal cord at the point of injury. The silicon substrate is covered with cracked gold electric conducting tracks that can be pulled and stretched. The electrodes are made of an innovative composite of silicon and platinum microbeads. They can be deformed in any direction, while still ensuring optimal electrical conductivity. Finally, a fluidic microchannel enables the delivery of pharmacological substances – neurotransmitters in this case – that will reanimate the nerve cells beneath the injured tissue.

The implant can also be used to monitor electrical impulses from the brain in real time. When they did this, the scientists were able to extract with precision the animal’s motor intention before it was translated into movement.

“It’s the first neuronal surface implant designed from the start for long-term application. In order to build it, we had to combine expertise from a considerable number of areas,” explains Courtine, co-author and holder of EPFL’s IRP Chair in Spinal Cord Repair. “These include materials science, electronics, neuroscience, medicine, and algorithm programming. I don’t think there are many places in the world where one finds the level of interdisciplinary cooperation that exists in our Center for Neuroprosthetics.”

For the time being, the e-Dura implant has been primarily tested in cases of spinal cord injury in paralyzed rats. But the potential for applying these surface implants is huge – for example in epilepsy, Parkinson’s disease and pain management. The scientists are planning to move towards clinical trials in humans, and to develop their prototype in preparation for commercialization.

EPFL has provided a video of researcher Stéphanie Lacour describing e-Dura and expressing hopes for its commercialization,

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

Electronic dura mater for long-term multimodal neural interfaces by Ivan R. Minev, Pavel Musienko, Arthur Hirsch, Quentin Barraud, Nikolaus Wenger, Eduardo Martin Moraud, Jérôme Gandar, Marco Capogrosso, Tomislav Milekovic, Léonie Asboth, Rafael Fajardo Torres, Nicolas Vachicouras, Qihan Liu, Natalia Pavlova, Simone Duis, Alexandre Larmagnac, Janos Vörös, Silvestro Micera, Zhigang Suo, Grégoire Courtine, Stéphanie P. Lacour. Science 9 January 2015: Vol. 347 no. 6218 pp. 159-163 DOI: 10.1126/science.1260318

This paper is behind a paywall.

Carbon nanotube fibres could connect to the brain

Researchers at Rice University (Texas, US) are excited about the possibilities that carbon nanotube fibres offer in the field of implantable electronics for the brain. From a March 25, 2015 news item on Nanowerk,

Carbon nanotube fibers invented at Rice University may provide the best way to communicate directly with the brain.

The fibers have proven superior to metal electrodes for deep brain stimulation and to read signals from a neuronal network. Because they provide a two-way connection, they show promise for treating patients with neurological disorders while monitoring the real-time response of neural circuits in areas that control movement, mood and bodily functions.

New experiments at Rice demonstrated the biocompatible fibers are ideal candidates for small, safe electrodes that interact with the brain’s neuronal system, according to the researchers. They could replace much larger electrodes currently used in devices for deep brain stimulation therapies in Parkinson’s disease patients.

They may also advance technologies to restore sensory or motor functions and brain-machine interfaces as well as deep brain stimulation therapies for other neurological disorders, including dystonia and depression, the researchers wrote.

A March 25, 2015 Rice University news release (also on EurekAlert*), which originated the news item, provides more details,

The fibers created by the Rice lab of chemist and chemical engineer Matteo Pasquali consist of bundles of long nanotubes originally intended for aerospace applications where strength, weight and conductivity are paramount.

The individual nanotubes measure only a few nanometers across, but when millions are bundled in a process called wet spinning, they become thread-like fibers about a quarter the width of a human hair.

“We developed these fibers as high-strength, high-conductivity materials,” Pasquali said. “Yet, once we had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body.”

The simultaneous arrival in 2012 of Caleb Kemere, a Rice assistant professor who brought expertise in animal models of Parkinson’s disease, and lead author Flavia Vitale, a research scientist in Pasquali’s lab with degrees in chemical and biomedical engineering, prompted the investigation.

“The brain is basically the consistency of pudding and doesn’t interact well with stiff metal electrodes,” Kemere said. “The dream is to have electrodes with the same consistency, and that’s why we’re really excited about these flexible carbon nanotube fibers and their long-term biocompatibility.”

Weeks-long tests on cells and then in rats with Parkinson’s symptoms proved the fibers are stable and as efficient as commercial platinum electrodes at only a fraction of the size. The soft fibers caused little inflammation, which helped maintain strong electrical connections to neurons by preventing the body’s defenses from scarring and encapsulating the site of the injury.

The highly conductive carbon nanotube fibers also show much more favorable impedance – the quality of the electrical connection — than state-of-the-art metal electrodes, making for better contact at lower voltages over long periods, Kemere said.

The working end of the fiber is the exposed tip, which is about the width of a neuron. The rest is encased with a three-micron layer of a flexible, biocompatible polymer with excellent insulating properties.

The challenge is in placing the tips. “That’s really just a matter of having a brain atlas, and during the experiment adjusting the electrodes very delicately and putting them into the right place,” said Kemere, whose lab studies ways to connect signal-processing systems and the brain’s memory and cognitive centers.

Doctors who implant deep brain stimulation devices start with a recording probe able to “listen” to neurons that emit characteristic signals depending on their functions, Kemere said. Once a surgeon finds the right spot, the probe is removed and the stimulating electrode gently inserted. Rice carbon nanotube fibers that send and receive signals would simplify implantation, Vitale said.

The fibers could lead to self-regulating therapeutic devices for Parkinson’s and other patients. Current devices include an implant that sends electrical signals to the brain to calm the tremors that afflict Parkinson’s patients.

“But our technology enables the ability to record while stimulating,” Vitale said. “Current electrodes can only stimulate tissue. They’re too big to detect any spiking activity, so basically the clinical devices send continuous pulses regardless of the response of the brain.”

Kemere foresees a closed-loop system that can read neuronal signals and adapt stimulation therapy in real time. He anticipates building a device with many electrodes that can be addressed individually to gain fine control over stimulation and monitoring from a small, implantable device.

“Interestingly, conductivity is not the most important electrical property of the nanotube fibers,” Pasquali said. “These fibers are intrinsically porous and extremely stable, which are both great advantages over metal electrodes for sensing electrochemical signals and maintaining performance over long periods of time.”

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

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes by Flavia Vitale, Samantha R. Summerson, Behnaam Aazhang, Caleb Kemere, and Matteo Pasquali. ACS Nano, Just Accepted Manuscript DOI: 10.1021/acsnano.5b01060 Publication Date (Web): March 24, 2015

Copyright © 2015 American Chemical Society

The paper is open access provided you register on the website.

Remote control for stimulation of the brain

Mo Costandi, neuroscientist and freelance science writer, has written a March 24, 2015 post for the Guardian science blog network focusing on neuronal remote control,

Two teams of scientists have developed new ways of stimulating neurons with nanoparticles, allowing them to activate brain cells remotely using light or magnetic fields. The new methods are quicker and far less invasive than other hi-tech methods available, so could be more suitable for potential new treatments for human diseases.

Researchers have various methods for manipulating brain cell activity, arguably the most powerful being optogenetics, which enables them to switch specific brain cells on or off with unprecedented precision, and simultaneously record their behaviour, using pulses of light.

This is very useful for probing neural circuits and behaviour, but involves first creating genetically engineered mice with light-sensitive neurons, and then inserting the optical fibres that deliver light into the brain, so there are major technical and ethical barriers to its use in humans.

Nanomedicine could get around this. Francisco Bezanilla of the University of Chicago and his colleagues knew that gold nanoparticles can absorb light and convert it into heat, and several years ago they discovered that infrared light can make neurons fire nervous impulses by heating up their cell membranes.

…

Polina Anikeeva’s team at the Massachusetts Institute of Technology adopted a slightly different approach, using spherical iron oxide particles that give off heat when exposed to an alternating magnetic field.

…

Although still in the experimental stages, research like this may eventually allow for wireless and minimally invasive deep brain stimulation of the human brain. Bezanilla’s group aim to apply their method to develop treatments for macular degeneration and other conditions that kill off light-sensitive cells in the retina. This would involve injecting nanoparticles into the eye so that they bind to other retinal cells, allowing natural light to excite them into firing impulses to the optic nerve.

Costandi’s article is intended for an audience that either understands the science or can deal with the uncertainty of not understanding absolutely everything. Provided you fall into either of those categories, the article is well written and it provides links and citations to the papers for both research teams being featured.

Taken together, the research at EPFL, Rice University, University of Chicago, and Massachusetts Institute of Technology provides a clue as to how much money and intellectual power is being directed at the brain.

* EurekAlert link added on March 26, 2015.

Nanoscale antioxidants

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A Feb. 10, 2015 news item on Azonano features injectable nanoparticles that act as antioxidants useful in case of injury, in particular, brain injury,

Injectable nanoparticles that could protect an injured person from further damage due to oxidative stress have proven to be astoundingly effective in tests to study their mechanism.

Scientists at Rice University, Baylor College of Medicine and the University of Texas Health Science Center at Houston (UTHealth) Medical School designed methods to validate their 2012 discovery that combined polyethylene glycol-hydrophilic carbon clusters — known as PEG-HCCs — could quickly stem the process of overoxidation that can cause damage in the minutes and hours after an injury.

A Feb. 9, 2015 Rice University news release (also on EurekAlert), which originated the news item, describe the benefits in more detail,

The tests revealed a single nanoparticle can quickly catalyze the neutralization of thousands of damaging reactive oxygen species molecules that are overexpressed by the body’s cells in response to an injury and turn the molecules into oxygen. These reactive species can damage cells and cause mutations, but PEG-HCCs appear to have an enormous capacity to turn them into less-reactive substances.

The researchers hope an injection of PEG-HCCs as soon as possible after an injury, such as traumatic brain injury or stroke, can mitigate further brain damage by restoring normal oxygen levels to the brain’s sensitive circulatory system.

…

“Effectively, they bring the level of reactive oxygen species back to normal almost instantly,” said Rice chemist James Tour. “This could be a useful tool for emergency responders who need to quickly stabilize an accident or heart attack victim or to treat soldiers in the field of battle.” Tour led the new study with neurologist Thomas Kent of Baylor College of Medicine and biochemist Ah-Lim Tsai of UTHealth.

The news release goes on to describe the antioxidant particles and previous research,

PEG-HCCs are about 3 nanometers wide and 30 to 40 nanometers long and contain from 2,000 to 5,000 carbon atoms. In tests, an individual PEG-HCC nanoparticle can catalyze the conversion of 20,000 to a million reactive oxygen species molecules per second into molecular oxygen, which damaged tissues need, and hydrogen peroxide while quenching reactive intermediates.

Tour and Kent led the earlier research that determined an infusion of nontoxic PEG-HCCs may quickly stabilize blood flow in the brain and protect against reactive oxygen species molecules overexpressed by cells during a medical trauma, especially when accompanied by massive blood loss.

Their research targeted traumatic brain injuries, after which cells release an excessive amount of the reactive oxygen species known as a superoxide into the blood. These toxic free radicals are molecules with one unpaired electron that the immune system uses to kill invading microorganisms. In small concentrations, they contribute to a cell’s normal energy regulation. Generally, they are kept in check by superoxide dismutase, an enzyme that neutralizes superoxides.

But even mild traumas can release enough superoxides to overwhelm the brain’s natural defenses. In turn, superoxides can form such other reactive oxygen species as peroxynitrite that cause further damage.

“The current research shows PEG-HCCs work catalytically, extremely rapidly and with an enormous capacity to neutralize thousands upon thousands of the deleterious molecules, particularly superoxide and hydroxyl radicals that destroy normal tissue when left unregulated,” Tour said.

“This will be important not only in traumatic brain injury and stroke treatment, but for many acute injuries of any organ or tissue and in medical procedures such as organ transplantation,” he said. “Anytime tissue is stressed and thereby oxygen-starved, superoxide can form to further attack the surrounding good tissue.”

These details about the research are also noted in the news release,

The researchers used an electron paramagnetic resonance spectroscopy technique that gets direct structure and rate information for superoxide radicals by counting unpaired electrons in the presence or absence of PEG-HCC antioxidants. Another test with an oxygen-sensing electrode, peroxidase and a red dye confirmed the particles’ ability to catalyze superoxide conversion.

“In sharp contrast to the well-known superoxide dismutase, PEG-HCC is not a protein and does not have metal to serve the catalytic role,” Tsai said. “The efficient catalytic turnover could be due to its more ‘planar,’ highly conjugated carbon core.”

The tests showed the number of superoxides consumed far surpassed the number of possible PEG-HCC bonding sites. The researchers found the particles have no effect on important nitric oxides that keep blood vessels dilated and aid neurotransmission and cell protection, nor was the efficiency sensitive to pH changes.

“PEG-HCCs have enormous capacity to convert superoxide to oxygen and the ability to quench reactive intermediates while not affecting nitric oxide molecules that are beneficial in normal amounts,” Kent said. “So they hold a unique place in our potential armamentarium against a range of diseases that involve loss of oxygen and damaging levels of free radicals.”

The study also determined PEG-HCCs remain stable, as batches up to 3 months old performed as good as new.

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

Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters by Errol L. G. Samuel, Daniela C. Marcano, Vladimir Berka, Brittany R. Bitner, Gang Wu, Austin Potter, Roderic H. Fabian, Robia G. Pautler, Thomas A. Kent, Ah-Lim Tsai, and James M. Tour. Published online before print February 9, 2015, doi: 10.1073/pnas.1417047112 PNAS February 9, 2015

This paper is behind a paywall.

Brain-on-a-chip 2014 survey/overview

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Michael Berger has written another of his Nanowerk Spotlight articles focussing on neuromorphic engineering and the concept of a brain-on-a-chip bringing it up-to-date April 2014 style.

It’s a topic he and I have been following (separately) for years. Berger’s April 4, 2014 Brain-on-a-chip Spotlight article provides a very welcome overview of the international neuromorphic engineering effort (Note: Links have been removed),

Constructing realistic simulations of the human brain is a key goal of the Human Brain Project, a massive European-led research project that commenced in 2013.

The Human Brain Project is a large-scale, scientific collaborative project, which aims to gather all existing knowledge about the human brain, build multi-scale models of the brain that integrate this knowledge and use these models to simulate the brain on supercomputers. The resulting “virtual brain” offers the prospect of a fundamentally new and improved understanding of the human brain, opening the way for better treatments for brain diseases and for novel, brain-like computing technologies.

Several years ago, another European project named FACETS (Fast Analog Computing with Emergent Transient States) completed an exhaustive study of neurons to find out exactly how they work, how they connect to each other and how the network can ‘learn’ to do new things. One of the outcomes of the project was PyNN, a simulator-independent language for building neuronal network models.

Scientists have great expectations that nanotechnologies will bring them closer to the goal of creating computer systems that can simulate and emulate the brain’s abilities for sensation, perception, action, interaction and cognition while rivaling its low power consumption and compact size – basically a brain-on-a-chip. Already, scientists are working hard on laying the foundations for what is called neuromorphic engineering – a new interdisciplinary discipline that includes nanotechnologies and whose goal is to design artificial neural systems with physical architectures similar to biological nervous systems.

Several research projects funded with millions of dollars are at work with the goal of developing brain-inspired computer architectures or virtual brains: DARPA’s SyNAPSE, the EU’s BrainScaleS (a successor to FACETS), or the Blue Brain project (one of the predecessors of the Human Brain Project) at Switzerland’s EPFL [École Polytechnique Fédérale de Lausanne].

Berger goes on to describe the raison d’être for neuromorphic engineering (attempts to mimic biological brains),

Programmable machines are limited not only by their computational capacity, but also by an architecture requiring (human-derived) algorithms to both describe and process information from their environment. In contrast, biological neural systems (e.g., brains) autonomously process information in complex environments by automatically learning relevant and probabilistically stable features and associations. Since real world systems are always many body problems with infinite combinatorial complexity, neuromorphic electronic machines would be preferable in a host of applications – but useful and practical implementations do not yet exist.

Researchers are mostly interested in emulating neural plasticity (aka synaptic plasticity), from Berger’s April 4, 2014 article,

Independent from military-inspired research like DARPA’s, nanotechnology researchers in France have developed a hybrid nanoparticle-organic transistor that can mimic the main functionalities of a synapse. This organic transistor, based on pentacene and gold nanoparticles and termed NOMFET (Nanoparticle Organic Memory Field-Effect Transistor), has opened the way to new generations of neuro-inspired computers, capable of responding in a manner similar to the nervous system  (read more: “Scientists use nanotechnology to try building computers modeled after the brain”).

One of the key components of any neuromorphic effort, and its starting point, is the design of artificial synapses. Synapses dominate the architecture of the brain and are responsible for massive parallelism, structural plasticity, and robustness of the brain. They are also crucial to biological computations that underlie perception and learning. Therefore, a compact nanoelectronic device emulating the functions and plasticity of biological synapses will be the most important building block of brain-inspired computational systems.

…

In 2011, a team at Stanford University demonstrates a new single element nanoscale device, based on the successfully commercialized phase change material technology, emulating the functionality and the plasticity of biological synapses. In their work, the Stanford team demonstrated a single element electronic synapse with the capability of both the modulation of the time constant and the realization of the different synaptic plasticity forms while consuming picojoule level energy for its operation (read more: “Brain-inspired computing with nanoelectronic programmable synapses”).

Berger does mention memristors but not in any great detail in this article,

Researchers have also suggested that memristor devices are capable of emulating the biological synapses with properly designed CMOS neuron components. A memristor is a two-terminal electronic device whose conductance can be precisely modulated by charge or flux through it. It has the special property that its resistance can be programmed (resistor) and subsequently remains stored (memory).

One research project already demonstrated that a memristor can connect conventional circuits and support a process that is the basis for memory and learning in biological systems (read more: “Nanotechnology’s road to artificial brains”).

You can find a number of memristor articles here including these: Memristors have always been with us from June 14, 2013; How to use a memristor to create an artificial brain from Feb. 26, 2013; Electrochemistry of memristors in a critique of the 2008 discovery from Sept. 6, 2012; and many more (type ‘memristor’ into the blog search box and you should receive many postings or alternatively, you can try ‘artificial brains’ if you want everything I have on artificial brains).

Getting back to Berger’s April 4, 2014 article, he mentions one more approach and this one stands out,

A completely different – and revolutionary – human brain model has been designed by researchers in Japan who introduced the concept of a new class of computer which does not use any circuit or logic gate. This artificial brain-building project differs from all others in the world. It does not use logic-gate based computing within the framework of Turing. The decision-making protocol is not a logical reduction of decision rather projection of frequency fractal operations in a real space, it is an engineering perspective of Gödel’s incompleteness theorem.

Berger wrote about this work in much more detail in a Feb. 10, 2014 Nanowerk Spotlight article titled: Brain jelly – design and construction of an organic, brain-like computer, (Note: Links have been removed),

In a previous Nanowerk Spotlight we reported on the concept of a full-fledged massively parallel organic computer at the nanoscale that uses extremely low power (“Will brain-like evolutionary circuit lead to intelligent computers?”). In this work, the researchers created a process of circuit evolution similar to the human brain in an organic molecular layer. This was the first time that such a brain-like ‘evolutionary’ circuit had been realized.

The research team, led by Dr. Anirban Bandyopadhyay, a senior researcher at the Advanced Nano Characterization Center at the National Institute of Materials Science (NIMS) in Tsukuba, Japan, has now finalized their human brain model and introduced the concept of a new class of computer which does not use any circuit or logic gate.

…

In a new open-access paper published online on January 27, 2014, in Information (“Design and Construction of a Brain-Like Computer: A New Class of Frequency-Fractal Computing Using Wireless Communication in a Supramolecular Organic, Inorganic System”), Bandyopadhyay and his team now describe the fundamental computing principle of a frequency fractal brain like computer.

“Our artificial brain-building project differs from all others in the world for several reasons,” Bandyopadhyay explains to Nanowerk. He lists the four major distinctions:
1) We do not use logic gate based computing within the framework of Turing, our decision-making protocol is not a logical reduction of decision rather projection of frequency fractal operations in a real space, it is an engineering perspective of Gödel’s incompleteness theorem.
2) We do not need to write any software, the argument and basic phase transition for decision-making, ‘if-then’ arguments and the transformation of one set of arguments into another self-assemble and expand spontaneously, the system holds an astronomically large number of ‘if’ arguments and its associative ‘then’ situations.
3) We use ‘spontaneous reply back’, via wireless communication using a unique resonance band coupling mode, not conventional antenna-receiver model, since fractal based non-radiative power management is used, the power expense is negligible.
4) We have carried out our own single DNA, single protein molecule and single brain microtubule neurophysiological study to develop our own Human brain model.

I encourage people to read Berger’s articles on this topic as they provide excellent information and links to much more. Curiously (mind you, it is easy to miss something), he does not mention James Gimzewski’s work at the University of California at Los Angeles (UCLA). Working with colleagues from the National Institute for Materials Science in Japan, Gimzewski published a paper about “two-, three-terminal WO3-x-based nanoionic devices capable of a broad range of neuromorphic and electrical functions”. You can find out more about the paper in my Dec. 24, 2012 posting titled: Synaptic electronics.

As for the ‘brain jelly’ paper, here’s a link to and a citation for it,

Design and Construction of a Brain-Like Computer: A New Class of Frequency-Fractal Computing Using Wireless Communication in a Supramolecular Organic, Inorganic System by Subrata Ghoshemail, Krishna Aswaniemail, Surabhi Singhemail, Satyajit Sahuemail, Daisuke Fujitaemail and Anirban Bandyopadhyay. Information 2014, 5(1), 28-100; doi:10.3390/info5010028

It’s an open access paper.

As for anyone who’s curious about why the US BRAIN initiative ((Brain Research through Advancing Innovative Neurotechnologies, also referred to as the Brain Activity Map Project) is not mentioned, I believe that’s because it’s focussed on biological brains exclusively at this point (you can check its Wikipedia entry to confirm).

Anirban Bandyopadhyay was last mentioned here in a January 16, 2014 posting titled: Controversial theory of consciousness confirmed (maybe) in  the context of a presentation in Amsterdam, Netherlands.

Chaos, brains, and ferroelectrics: “We started to see things that should have been completely impossible …”

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Given my interest in neuromorphic (mimicking the human brain) engineering, this work at the US Oak Ridge National Laboratories was guaranteed to catch my attention. From the Nov. 18, 2013 news item on Nanowerk,

Unexpected behavior in ferroelectric materials explored by researchers at the Department of Energy’s Oak Ridge National Laboratory supports a new approach to information storage and processing.

Ferroelectric materials are known for their ability to spontaneously switch polarization when an electric field is applied. Using a scanning probe microscope, the ORNL-led team took advantage of this property to draw areas of switched polarization called domains on the surface of a ferroelectric material. To the researchers’ surprise, when written in dense arrays, the domains began forming complex and unpredictable patterns on the material’s surface.

“When we reduced the distance between domains, we started to see things that should have been completely impossible,” said ORNL’s Anton Ievlev, …

The Nov. 18, 2013 Oak Ridge National Laboratory news release, which originated the news item, provides more details,

“All of a sudden, when we tried to draw a domain, it wouldn’t form, or it would form in an alternating pattern like a checkerboard.  At first glance, it didn’t make any sense. We thought that when a domain forms, it forms. It shouldn’t be dependent on surrounding domains.”  [said Ievlev]

After studying patterns of domain formation under varying conditions, the researchers realized the complex behavior could be explained through chaos theory. One domain would suppress the creation of a second domain nearby but facilitate the formation of one farther away — a precondition of chaotic behavior, says ORNL’s Sergei Kalinin, who led the study.

“Chaotic behavior is generally realized in time, not in space,” he said. ”An example is a dripping faucet: sometimes the droplets fall in a regular pattern, sometimes not, but it is a time-dependent process. To see chaotic behavior realized in space, as in our experiment, is highly unusual.”

Collaborator Yuriy Pershin of the University of South Carolina explains that the team’s system possesses key characteristics needed for memcomputing, an emergent computing paradigm in which information storage and processing occur on the same physical platform.

“Memcomputing is basically how the human brain operates: [emphasis mine] Neurons and their connections–synapses–can store and process information in the same location,” Pershin said. “This experiment with ferroelectric domains demonstrates the possibility of memcomputing.”

Encoding information in the domain radius could allow researchers to create logic operations on a surface of ferroelectric material, thereby combining the locations of information storage and processing.

The researchers note that although the system in principle has a universal computing ability, much more work is required to design a commercially attractive all-electronic computing device based on the domain interaction effect.

“These studies also make us rethink the role of surface and electrochemical phenomena in ferroelectric materials, since the domain interactions are directly traced to the behavior of surface screening charges liberated during electrochemical reaction coupled to the switching process,” Kalinin said.

For anyone who’s interested in exploring this particular approach to mimicking the human brain, here’s a citation for and a link to the researchers’ paper,

Intermittency, quasiperiodicity and chaos in probe-induced ferroelectric domain switching by A. V. Ievlev, S. Jesse, A. N. Morozovska, E. Strelcov, E. A. Eliseev, Y. V. Pershin, A. Kumar, V. Ya. Shur, & S. V. Kalinin. Nature Physics (2013) doi:10.1038/nphys2796 Published online 17 November 2013

This paper is behind a paywall although it is possible to preview it for free via ReadCube Access.

The brain and poetry; congratulations to Alice Munro on her 2013 Nobel prize

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There’s an intriguing piece of research from the University of Exeter (UK) about poetry and the brain. From an Oct. 9, 2013 University of Exeter news release (also on EurekAlert),

New brain imaging technology is helping researchers to bridge the gap between art and science by mapping the different ways in which the brain responds to poetry and prose.

Scientists at the University of Exeter used state-of-the-art functional magnetic resonance imaging (fMRI) technology, which allows them to visualise which parts of the brain are activated to process various activities. No one had previously looked specifically at the differing responses in the brain to poetry and prose.

In research published in the Journal of Consciousness Studies, the team found activity in a “reading network” of brain areas which was activated in response to any written material. But they also found that more emotionally charged writing aroused several of the regions in the brain which respond to music. These areas, predominantly on the right side of the brain, had previously been shown as to give rise to the “shivers down the spine” caused by an emotional reaction to music. .

When volunteers read one of their favourite passages of poetry, the team found that areas of the brain associated with memory were stimulated more strongly than ‘reading areas’, indicating that reading a favourite passage is a kind of recollection.

In a specific comparison between poetry and prose, the team found evidence that poetry activates brain areas, such as the posterior cingulate cortex and medial temporal lobes, which have been linked to introspection.

I did find the Journal of Consciousness Studies in two places (here [current issues] and here [archived issues]) but can’t find the article in my admittedly speedy searches on the website and via Google. Unfortunately the university news release did not include a citation (as so many of them now do); presumably the research will be published soon.

I’d like to point out a couple of things about the research, the sample was small (13) and not randomized (faculty and students from the English department). From the news release,

Professor Adam Zeman, a cognitive neurologist from the University of Exeter Medical School, worked with colleagues across Psychology and English to carry out the study on 13 volunteers, all faculty members and senior graduate students in English. Their brain activity was scanned and compared when reading literal prose such as an extract from a heating installation manual, evocative passages from novels, easy and difficult sonnets, as well as their favourite poetry.

Professor Zeman said: “Some people say it is impossible to reconcile science and art, but new brain imaging technology means we are now seeing a growing body of evidence about how the brain responds to the experience of art. This was a preliminary study, but it is all part of work that is helping us to make psychological, biological, anatomical sense of art.”

Arguably, people who’ve spent significant chunks of their lives studying and reading poetry and prose might have developed capacities the rest of us have not. For a case in point, there’s a Sept. 26, 2013 news item on ScienceDaily about research on ballet dancers’ brains and their learned ability to suppress dizziness,

The research suggests that years of training can enable dancers to suppress signals from the balance organs in the inner ear.

…

Normally, the feeling of dizziness stems from the vestibular organs in the inner ear. These fluid-filled chambers sense rotation of the head through tiny hairs that sense the fluid moving. After turning around rapidly, the fluid continues to move, which can make you feel like you’re still spinning.

Ballet dancers can perform multiple pirouettes with little or no feeling of dizziness. The findings show that this feat isn’t just down to spotting, a technique dancers use that involves rapidly moving the head to fix their gaze on the same spot as much as possible.

Researchers at Imperial College London recruited 29 female ballet dancers and, as a comparison group, 20 female rowers whose age and fitness levels matched the dancers’.

The volunteers were spun around in a chair in a dark room. They were asked to turn a handle in time with how quickly they felt like they were still spinning after they had stopped. The researchers also measured eye reflexes triggered by input from the vestibular organs. Later, they examined the participants’ brain structure with MRI scans.

In dancers, both the eye reflexes and their perception of spinning lasted a shorter time than in the rowers.

Yes, they too have a small sample. Happily, you can find a citation and a link to the research at the end of the ScienceDaily news item.

ETA Oct. 10, 2013 at 1:10 pm PDT: The ballet dancer research was not randomized but  that’s understandable as researchers were trying to discover why these dancers don’t experience dizziness. It should be noted the researchers did test the ballet dancers against a control group. By contrast, the researchers at the University of Exeter seemed to be generalizing results from a specialized sample to a larger population.

Alice Munro news

It was announced today (Thursday, Oct. 10, 2013) that Canada’s Alice Munro has been awarded the 2013 Nobel Prize for Literature. Here’s more from an Oct. 10, 2013 news item on the Canadian Broadcasting Corporation (CBC) news website,

Alice Munro wins the 2013 Nobel Prize in Literature, becoming the first Canadian woman to take the award since its launch in 1901.

Munro, 82, only the 13th woman given the award, was lauded by the Swedish Academy during the Nobel announcement in Stockholm as the “master of the contemporary short story.”

“We’re not saying just that she can say a lot in just 20 pages — more than an average novel writer can — but also that she can cover ground. She can have a single short story that covers decades, and it works,” said Peter Englund, permanent secretary of the Swedish Academy.

Reached in British Columbia by CBC News on Thursday morning, Munro said she always viewed her chances of winning the Nobel as “one of those pipe dreams” that “might happen, but it probably wouldn’t.”

Congratulations Ms. Munro! For the curious, there’s a lot more about Alice Munro and about her work in the CBC news item.