Top Neurotechnology Breakthroughs of 2012-2013

The past two years proved to be very fruitful in the world of neuroscience, with both academia and industry exposing new secrets of the mind and unveiling yet more awe-inspiring gadgets. The year has not only delivered incredible breakthroughs in neuroprosthetics, visual stimulation and mind-reading, but also witnessed a substantial leap forward in our understanding of the “connectome” – the complex universe of neuronal pathways and interactions which shape the mind. Most remarkably, it is becoming increasingly clear that our practical knowledge of grey matter is improving at electric speeds, as more and more life-saving technologies contest to humanity’s neuro-scientific accomplishments.  

Below is a collection of some of last year’s prominent advancements, starting with perhaps the most celebrated: the thought-powered leg. 

Having lost his limb in a motorcycle accident, 31-year-old Zac Vawter was fitted with a bionic replacement, called electromyeloid prosthesis—operated entirely by his mind. The neuroprosthetic was initially developed at the Rehabilitation Institute of Chicago (RIC) in 2005, and has reached the peak of its performance last year, when Vawter demonstrated the bionic leg’s awesome powers by climbing 103 flights of stairs of Chicago’s Willis Tower—even skipping two steps at a time.  The device works owing to “targeted muscle reinnervation” (TMR) –essentially a re-wiring of the patient’s neuronal pathways. When Vawter’s leg was amputated, the nerves of his lower leg were surgically rerouted to his hamstring, where muscle signals powering his neuro-robotic leg now originate. Legs have not been the sole limb eligible for neuro-replacement: in 2001 researchers at the Rehabilitation Centre awed the public when they fitted bionic arms for Jesse Sullivan, a 40-year-old electrician who lost both limbs in a work accident. Hundreds of neuroprosthetics have since been implanted, getting incredibly nifty from year to year. 

Therapeutic neurostimulation has also been hot off the conveyor belt last year. Israeli Brainsway is a developer of a Transcranial Magnetic Stimulation (TMS) device which, in essence, is a fancy name for a deep brain tissue massager. Brainsway’s key technology—Deep TMS System—exploits our knowledge about areas of the brain responsible for depression and other neurological disorders, the likes of which are Alzheimers and schizophrenia. The system comes in the shape of a brain helmet which offers completely non-invasive electromagnetic neurostimulation of grey matter. By stimulating areas responsible for depression, the TMS helmet offers an effective 15-minute anti-depression “cranial massage”. Sounds a little sci-fi? The FDA does not think so—the agency has recently approved Brainsway’s TMS system for the treatment of depression patients who have not responded well to other treatments, and the company is working on expanding their therapeutic targets towards autism and Parkinson’s disease in the near future. 

Not any less important on the list of last year’s breakthrough neuro-developments is our newfound mind-reading ability. Using electrodes to detect spikes in brain activity, scientists have been able to map areas of the brain responsible for a plethora of thoughts, actions and emotions. They have now put that knowledge to use, quite literally communicating with a comatose patient with the use of an fMRI scanner. A man believed to be in a vegetative state for 12 years was able to tell doctors he was not in pain, kick-starting what has since become a revolution in our understanding of the comatose state. The occurrence caused medical books to be rewritten, as it gave us the ability to communicate with thousands of patients previously deemed unresponsive.

Since its inception mind-reading wasted no time expanding beyond hospital walls. Last year has brought up the phenomenon of mind-controlled gaming (MCG)—and the dangers this form of entertainment carries with it. Despite its early stages of existence, MCG has gained popularity in recent years, and developers like NeuroSky and Emotiv are already marketing devices which detect and interpret brain waves via external electrodes. The issue is—our understanding of this type of interface is akin to our familiarity with the brain—the foundations are certainly in place, but hardly solid enough to embark on an elaborate build. With that said, an important finding emerged at last year’s Usenix security conference in Seattle: mind-controlled interfaces pose a very realistic threat of “brain leaks”. In other words, in what is probably the most fearsome of worldly exploits, a hacker who gains access to an MCG device can potentially access the user’s thoughts. Particularly at stake is private information such as pin codes and passwords, which can be deduced via spikes in electroencephalography (EEG) readings in response to words and images familiar to the user.

And it looks like the burgeoning thought-stealing market comes with its very own weapon: a memory chip now exists in its literal form. Scientists at the Wake Forest University and the University of Southern California have, in an ingenious set of experiments, demonstrated successful thought implantation in mice. Having observed specific brain activity in mice familiarizing themselves with a maze, scientists then implanted a microchip in the subjects’ brains which could be programmed to stimulate the same set of neurons in a different setting. Thus, once a mouse memorized mazeA, for instance, and was then moved to mazeB, a specific memory pattern could be triggered by the implanted microchip which would bring up memories of the familiar maze. Much to the scientists’ astonishment, the mouse would follow the same familiar trail in any new environment—but only if its “familiarity neurons” were triggered by the microchip. Even more bizarrely, the same implant in a completely new subject’s brain brought up the same hybrid memories. The implications of this research are unfathomable: starting with interfering with harmful memories of trauma or disease, all the way down to sci-fi manipulation of the mind we have for so long anticipated in fear.

And just when you thought neuroscience couldn’t get any more awesomely frightening, false memory implants can now be completed with a full set of artificially-controlled decision making. As a harbinger of what forward-looking science authors have previously dubbed the menticide, scientists have demonstrated the ability to correct the decision-making process in cognitively impaired non-human primates. The MIMO (or multi-input multi-output) prosthesis is able to learn from correct decision-making patterns in the brain, and to “replay” them in primates which were mentally impaired following drug administration. The MIMO was able to improve decision making 10% above the norm—and that is just the beginning. Researchers hope that in the future this type of device will benefit people who have suffered strokes and brain injuries which resulted in diminished cognitive ability.

A similarly wonderful technology which neuroscientists claim is only 5 years away is “webcam vision”—a technology which is based on artificial stimulation of the visual cortex in visually impaired patients. For some time now it has been known that blind people are able to “see” just with their brains, and a prosthetic device which could detect the external environment and generate basic images in the brain is only half a decade away. Currently, a team of scientists at the University of Texas are generating a detailed map of the visual cortex, and are hoping to begin working on a visual prosthetic device in the near future.

And last but certainly not least, alongside the fascinating annual developments in the sphere of neuroscience runs our continuous effort to fathom the complex macrocosm which unites every neuron, synapse and chemical signal in the brain. A massively ambitious effort to map brain synapses, titled “The Human Connectome Project” has been underway in the neuroscientific community. Not only does the initiative hope to re-create a complex 3D neuronal map of the brain, but it also aims to answer the very basic question of how neuronal synapses—or nerve crossroads—are formed, and what influences this formation. A breakthrough milestone was achieved in this sphere in 2012: scientists were able to unveil key principles which guide the formation of neuronal interceptions, and applied these principles to a computational structural prediction model. In this way they were able to demonstrate that brain neurons grow independently of each other, and form connections once they intercept each other’s paths in the brain. The implications of such a development are not negligible: the breakthrough has brought us eons closer to a realistic possibility of an in silico brain reconstruction.

Last years' key advancements showcased here would probably sound like yet another science fiction novel to the untrained ear, but ironically they are mere specks in the rich and succulent broth of neurotech progress today.  The pace with which the field of neuroscience has been advancing in recent years is unparalleled by any other sphere of knowledge, and the coming decade will inevitably bring about exponential leaps in our abilities to treat, shape and harness the mind. One thing is clear: if the past is any indication of the future, the future is absolutely neuro-tastic. 

The (understandable) Confusion in Brain Mapping Terminology

The blind can see, the deaf can hear, and the paralyzed can walk—without a doubt, the Golden Age of Neuroscience is upon us. And if that weren’t enough, mind control, telepathy and in fact elaborate real-life Avatar scenarios are so nigh that scores of the neurotech-savvy have begun to pre-order their titanium thought defense helmets. So awesome have the leaps of neurotechnology been in recent years that the media has struggled to deliver this industry a deserved timely coverage, and public awareness has just barely caught up with humanity’s neuro-prowess of late. And what came about was the usual by-product of a much-too-quickly advancing technology: terminology fails. 

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On April 2, 2013 President Barack Obama unveiled the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, whose final and uttermost objective is to visualize, map, understand and reconstruct the activity of every single neuron in the brain. This knowledge will in the future be applied to the development of new technologies and the treatment of quickly expanding array of neurological disorders.

BRAIN’s near-sighted primary goal will be to sponsor ongoing brain mapping projects, such as the Human Connectome Project, which the initiative claims will help us visualize every neuron in the brain and understand the formation of synapnses (connections) between neurons in live brain tissues. As the Human Connectome Project deals primarily with brain scans of live humans and their brains, this happens to be a feat which, for the time being, any knowledgeable neuroscientists will tell you is utter nonsense.

Here is why. 

The Human Connectome Project (HCP) has been dubbed one of the greatest neuroscience ambitions of the new millennium, much akin to the Human Genome Project a decade ago. The project showcases efforts to fathom the complex macrocosm which unites every axon bundle in the brain with the use of high-resolution fMRI or other non-invasive techniques, and symbolizes the positive level of trust which neuroscientists now assign to neurotechnology. HCP precedes and perhaps supersedes the BRAIN initiative, as already in 2010 it secured grants collectively worth over $40 million from the NIH. Initial 1200 Connectome subjects will be scanned for hours using an fMRI scanner 4 to 8 times as powerful as a standard one, utilizing the power of one nuclear submarine per scan, in hopes to yield insight into the connectivity of nerves within a brain, and how this connectivity varies throughout species and in disease. 

With novel neuro-terminology threatening to become its own language, much confusion and mis-representation surrounds HCP, and naturally the media hype it triggered has seemingly gotten lost in translation –or, rather, in literary terms. In bold truth, the techniques which the HCP is set to exploit are entirely non-invasive brain scans whose resolution is equivalent to that of a rusty security camera. Although general brain regions of humans will be clearly visible, local inter-region synapses, which form 80% of connections in the cerebral cortex, are entirely inaccessible to supracranial scans, as even a light microscope of the highest magnification is insufficient to visualize a single neuron. 

In other words, an fMRI scanner does not, and probably never will, visualize single cells and local synapses in the brain. However, HCP may yield great insights into the "connective visuality" of the brain, as vibrant HCP images (such as the one below) show thousands of connections between particular brain regions via axonal bundles (which are cables composed of many nerve cells, a bit like your landline telephone wire, not single brain cells). Scientists say that it is this inter-region connectivity which is responsible for our superior intelligence to other species, as preliminary scans clearly show a much more "connected" human brain in comparison with that of a chimpanzee, for instance. Scientists also believe that comparing such deep brain scan images between healthy and ailed individuals can help us understand neurological disease in the future.

Does this imply that we shall never be able to dwell into the microscopic ecosystem of grey matter? Not at all, although it may take some time until we are able to do so in humans. Non-human species, however can now be studied with a dozen of other, much more invasive techniques you probably wouldn't want performed on yourself. These techniques' findings collectively contribute to the general brain Connectome (note the unnecessary similarity to the Human Connectome Project) across all species-which is, in essence, a brain equivalent of the genome. To make matters more ponderous, Connectomics is the study of the connectome with all the research techniques available today, comprising MRI, electron microscopy, fluorescent cell staining, rendering brains see-through and a fantastical endeavor which goes by the name of optogenetics. 

One rather straight-forward technique used to visualize individual neurons and synapses in the cortical column is, literally, brain carving. A team of researchers at Harvard, led by prominent brain explorer Dr. Lichtman, have been working towards creating the most efficient contraption for slicing off pastrami-thin slices of mouse brain and observing them under a powerful electron microscope. Theoretically, this process may yield a complete 3D cellular reconstruction of a brain, but it would require creating and aligning thousands, if not millions, of brain slices. 

Amongst other, less brute-force neuronal visualization technique is the Clarity Project, which helps visualize neurons in brains of live mice. The Clarity project revolves around scientists' ability to chemically produce completely transparent brains (or other organs) in mice--a technique which was recently developed by Prof Karl Deisseroth and his team at Stanford. The chemical treatment strips away lipids which normally block the passage of light using the detergent SDS.

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To help them through the treacherous cranial terrain scientists at Dr Lichtman's Dr Diesseroth's labs utilize fluorescent staining of neurons, which helps isolate single cells spanning a number of brain areas. The staining produces images such as this, termed BrainBows: 

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But perhaps the most compelling technique developed at Deisseroth's lab is optogenetics - a research tool which revolves around a gene discovered in 2002, encoding light-gated ion channels, or Channelrhodopsins, found in unicellular green algae. Upon activation with a specific-frequency light, the channels open, causing an ion influx into the cell much akin to the mechanism which causes our neurons to fire. Using a different light frequency can also activate a different set of channels—the Halorhodopsins which will cause a negative ion influx into the cell and thus inhibition of the neuron. For algae, this mechanism’s function is to orient the cells towards or away from light. But this mechanism can also be applied to mammalian cells.

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In recent years scientists succeeded in engineering rhodopsins from algae into nerve cells of mice, either grown externally or, in fact, in perfectly alive animals. In essence, genes encoding these channels can be “injected” into very specific areas of the brain, which will render those areas light-sensitive. By shining a light with the use of optic cables into those areas, scientists can trigger very specific neurons, and examine the animal’s behavior, thereby demonstrating the role of the specific neurons they are studying.

Click here for a video of an optogenetically-challenged mouse commanded by scientists to go in perpetual circles. 

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Ultimately, all the techniques which have armed neuroscience in recent years work towards one ambitious goal: to comptuationally simulate the workings of a brain, which would give us the ability to re-create, and perform "virtual healing", on neurological ailments. A breakthrough milestone was achieved in this sphere of connectomics in 2012: scientists were able to unveil key principles which guide the formation of neuronal interceptions, and applied these principles to a computational structural prediction model. In this way they were able to demonstrate that brain neurons grow independently of each other, and form connections once they intercept each other’s paths in the brain. 

Some might argue that virtually recreating a self-sufficient human brain capable of conscious thought like you and I might not be a great idea, but that's for later debates (we are not there yet).

Bioassociate will soon publish an in-depth report on the Global Neuroscience Revolution, where many recent fascinating developments, techniques and initiatives will be described. If you wish to receive a copy of the report please subscribe to our mailing list on our home page: www.bioassociate.com