Sitting at the bed side of a loved one who has slipped into a coma and simply reading a story, talking about the day, or just holding hands most likely feels like a pointless and endless effort for the recovery of the vegetative patient. There can only be the glimmer of hope that maybe they can sense your presence, but there is no definitive way to know for sure if your interactions are falling on a deaf brain.

We all can make personal judgments that we are conscious right here and right now. But, making this sort of judgment for another individual when their interactions with the world are limited or apparently absent is not only challenging, but also ethically dangerous as your decision can mean life or death. But now, a new, low-cost study on the interactions of patients who are considered to be in a "minimally conscious state" (MCS) is showing a very exciting result that basic learning seems to take place in some individuals.

The type of learning is simple--the sort of classic conditioning demonstrated by Pavlov's dog who salivated at the sound of a bell. Here, a tone is sounded followed by a light air puff to the eye. This is certainly an annoyance, so a conscious observer would tend to squeeze their eyelid shut to protect the pupil. After a short time of the repeated events, patients who physically responded to the air puff and who were seemingly unconscious demonstrated the same eyelid reaction after only the sounding of the tone.

The open question is to wonder if this sort of basic learning is so fundamental that true human consciousness is not required. So, Pavlov's dog might be somewhat smart, but still not conscious. Or, if only a minimum level of consciousness is needed for basic learning (as the result of new, functional connections developing in the brain's neural network), then a simple test of a successful Pavlovian response could be an important benchmark for determining the state of a patient who cannot communicate with the world. The hope would be that if simple learning is still possible, then further recovery and improvement in the brain's responses could also be anticipated with additional therapies.

It's certainly not a clear test of consciousness, but the approach is so simple and does not carry the enormous costs of brain imaging technologies. Therefore, essentially any hospital with low-conscious patients can perform this sort of experiment, which can further develop our weak understanding of human consciousness, and to improve the successful predictions required by doctors when dealing with patients on the verge of life or unconscious death.

When peripheral nerves are damaged or even severed due to injury or disease, then dramatic disabilities can result in the affected individual. This may range from local paralysis of senses to the painful disorder of neuropathy.

Neurons that loose their primary connections to one another through the axon--the main nerve fiber that transports electrical signals from the cell body to other neurons--are very slow to re-grow, and will likely die due to inactivity. If they do re-develop and connect, then the nervous system can re-learn how to have a reasonably-functioning network, but full recovery to its original condition is difficult.

To encourage and guide this re-growth process, a European collaboration of researchers are developing a new neurotechnology based on fabricated polymer microtubes that can be implanted and monitored during axon regeneration. Centered at the University of Glasgow's Centre for Cell Engineering and Department of Electronics and Electrical Engineering under Dr. Mathis Riehle, the team plans to surgically insert these specialized tubes between two neurons whose axon fibers are severed. With a little electrical stimulation along the tube, they anticipate that the fibers will begin to grow along the length of the tube and establish a new neural connection on the other side... the neuronal equivalent of the "light at the end of the tunnel."

The successful development of this technique will certainly mean significant improvements in recovery for patients with peripheral nerve damage. It may also pave the way for a more focused neuroengineering method for creating new connections in the human nervous system, and even helping living nerves functionally connect to implanted devices. Controlling the development and re-development of neuron networks will become a major leap for future neurotechnological advances.

The BrainGate collaboration, lead by Dr. John Donoghue from the Department of Neuroscience at Brown University, recently announced they have began recruiting patients to join in the clinical trials of the second iteration of their neural interface system.

The first round of trials was run by Cyberkinetics, an independent neurotech company founded by Dr. Donoghue, but they have pulled out of this next phase due to funding difficulties. Now, a purely academic team based at the Massachusetts General Hospital, these exciting trials will help guide the next generation of neurotechnological interfaces between human brain activity and direct actions on a computer and, eventually, control of prosthetic devices.

The near-term goal of this research is to develop a technology that can assist patients with degenerative neurological paralysis where their brain is trying to talk to its body, but the body just isn't listening. The BrainGate system trains itself to decode electrical activity in the brain and translate recorded signals into a computer for control of an external device. In effect, BrainGate is a bridge that re-routes neural communication to a device that would be designed to replace lost function.

With previous work, the critical success was converting brain activity into the control of a cursor on a computer screen. Although this seems to be a trivial activity, the understanding of the neuroscience behind the actual relationship between specific brain activity and the mechanical control of our environment remains a vital bit of understanding required for the future of neurotechnology. Now, with the BrainGate2 trials starting soon, opportunities to discover new science will hopefully bring us closer to successful devices for assisting patients with ALS, spinal cord injuries, stroke patients, and many others with empowering technologies to live their lives to the fullest.

Recently, we discussed the developments from the Wadsworth Center of a minimally-invasive, thin-film technology to enhance electrocorticography (ECoG) recordings (read). Similar to the more common electroencephalogram (EEG) method, which uses an array of electrodes stuck on your outer skull to receive electrical signals from your neurons, the ECoG uses an array of electrodes embedded just on the surface of your brain allowing for a more direct electrical view of neural activity. This view still covers an averaged signal from a large number of talking neurons and still does not see individual electrical signals. However, by having the bony skull out of the way, the electrodes sure have a more clear shot for picking up the electric fields.

The importance of this work from Wadsworth is that the brain and it's violent bodyguard, the immune system, doesn't really like to have things hanging around that the body didn't make on its own. So, typical implanted devices will quickly be destroyed by attacking antibodies. Here, the specialized implanted ECoG devices are lasting six to twelve months in human patients, but their goal is to improve the device life-cycle to five to ten years.

Through their collaboration with clinical neurologists and biomedical engineers at Washington University in St. Louis, Missouri, the Wadsworth group, lead by Gerwin Schalk, is taking the technology to the next step by integrating the recording activity with specialized software that maps the brain activity with computer control. The implanted ECoG providing its more detailed map of brain activity allows for a specific correlation to be observed between physically clicking a computer mouse button, for example, and the resulting pattern of neural firings in the brain. The patient can then train their thoughts to reproduce similar neuron activity and, with a direct connection to the computer, the mouse click appears without the click.

The interfacing process is being licensed to a start-up company in St. Louis called Neurolutions, who will be working to improve the software and training process to bring it to market for applications in neuroprosthetics. The challenge for further advancement begins with the unfortunately situation that just clicking a mouse button doesn't get us very far in life. Just moving fingers and arms requires multi-dimensional spatial control, and with that comes an an unknown number of different neural patterns being required to simply raise your arm to reach the mouse on top of the desk. All of the corresponding neural activity--move shoulder up, rotate elbow, lift index finger, shift arm to the right, etc.-- will need to be mapped, trained, and accessed to control a prosthetic device... and each human might have different neural patterns for the same physical motion.

Sticking sharp, pointy metal needles into your brain is never an idea for a good time (image, deep brain stimulation). Future successful developments in neurotechnology, however, will be dependent on discovering ways to directly access our neurons without damaging surrounding brain tissue.

The mechanisms of how neural stimulation affects a human is still largely misunderstood, but therapeutic deep brain stimulation is used to relieve symptoms in patients with Parkinson's Disease, dystonia (a disorder involving continuous muscle contraction), and even severe cases of depression. This technique is still highly experimental and carries risks from the invasive nature of implanting electrodes into your brain.

Although still invasive, a new approach is being developed at Case Western Reserve University by the Strowbridge Lab, where a specially coated glass needle containing tons of metallic nanoparticles is inserted into the brain. Typically, electrical wires are needed to connect to implanted stimulating devices, but these nanoparticles are designed to generate electric fields when illuminated by infrared laser light (at 830 nm wavelength). No wires needed, just a non-invasive laser zap. The infrared wavelength is a useful selection because it easily passes through brain tissue, but can then be absorbed by the nanoparticles and re-radiated as an electric field.

Another key advantage to this technique is that the tiny electric fields from the particles will superimpose and extend out into the surrounding tissue stimulating the neurons in the field's wake to either generate their own electrical signals or possibly suppress their activity. The range of this wireless approach allows for a broader swath of neurons to be affected, whereas direct electrode stimulation can only influence a small cluster of nearby cells.

Indirectly activating neurons with laser light has been performed on cells in culture (read more), but this is the first attempt at working in actual brain tissue. So far, these experiments are applied only to extracted tissue from rat brains, but it is an important first step toward developing the technology further to learn how to best apply it into a living brain.

When our peripheral nerves fire anywhere in our body's extremety... they are usually trying to tell our brain something rather important: "Hey, that stove top is a little too hot for your finger tips... pull away!" or, "I think that's kind of sharp... it might be a nail... it is! it is a nail!... step away!"

While this extended network of vital warning zaps to our brain are not enjoyable as we sense them as intense pain, the function is critical to our survival and helps keep us from doing stupid things and warn us about problems that our visual perception might be missing. However, what if these warning zaps misfire? And, what if they keep misfiring constantly? They might be trying to tell us that something is wrong... possibly internally... and sure this might be useful, but what if you can't do anything to fix the problem and they just keep on zapping?

This ongoing misfiring of localized sections in the peripheral nervous system is so much more than an annoyance, and is a serious and painful disorder for millions of humans. [ Read more about Peripheral Nerve Disorders ] One major problem in particular is peripheral neuropathy, where actual damage has occurred to the peripheral nerves. Although damage to these nerves certainly would be problematic -- maybe you don't notice that sharp nail pressing into your heel as quickly as you once did -- but, the chronic problem is the damaged nerves seem to incessantly scream at the brain like a teenager who just learned she can't stay out past midnight with her friends.

Wouldn't it be nice to just tell those nerves to shut up and go to bed?

This is an important example of chronic pain that so many people suffer continuously through their day-to-day activities. Drugs have been used to combat the screaming nerves, but mostly measure up to over-the-counter pain medications. To date, there has been no systematic treatment developed, although there are several dedicated research centers located throughout the United States working on the problem.

Now, there is very early stage research on a new technological approach to quieting the broken nerves. A Dallas, TX-based startup called MicroTransponder is applying a very popular technology for powering and controlling electrical devices wirelessly. This technique, called "RFID" (radio-frequency identification), is a device that detects a remote radio signal to activate its internal circuitry to perform some function. The technology is already embedded in our culture, from automated highway toll collection (EZPass) to product tracking in inventory systems and even to checking in your library book.

For this application of remote neural stimulation, the idea is to inject tiny RFID devices to float around the damaged fingers or toes. When the nerve start to scream, an external signal generator will send out a radio-frequency message to the internal devices which will then power up and provide a polite zap back to the nerve endings. The anticipation is that applying just the right pattern of miniature jolts will quiet the screaming teenager and provide some relief to the 20 million Americans suffering today.

Many research groups have been working on the challenging aspects of controlling the growth of living neural networks. Of course, the ultimate hope is to eventually develop the technology to design electrical devices that will directly integrate with the human nervous system. A variety of important approaches are being considered, including surface patterning techniques used in conventional microfluidic technology ( learn more ), optical guidance from focused laser beams called "optical tweezers"--other wise known as present-day tractor beams--( learn more ), as well as various chemical coating methods like the use of novel "self-assembled monolayers" (SAMs). Here, a specialized two-ended molecule coats a surface with one end that likes to "stick" to the surface, like a silicon chip, and the other end likes to "stick" to neurons. Where ever the SAMs stick so will a neuron.

Recently at the Division of Solid State Physics at Lund University in Sweden, an advanced approach to surface patterning has been developed using electron-beam lithography to create rows of nanowires sitting on the surface of a substrate that influences the directional growth of the neuron's axons and bundles of nerve fibers. You might imagine future neurotech device developers using this idea to pattern a silicon wafer with a specific highway map to force the exact growth of neurons in order to generate the correct network structure for a desired neuro-device's function.

All of this pioneering work in patterning the growth of neurons into a structured network has a long road ahead. These early developments are so critical, and progress along several, competing paths are important for developing effective methods to design and create real neurotechnolgocial devices.

And, to emphasize the importance of this research, we are beginning to develop a new Neuron News Review section to cover the past, present, and future directions in living neuron network pattern techniques.