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.

Flap its wing in the Brazilian rainforest, trigger a hurricane in the Gulf of Mexico...

This is the classic example of how small perturbations in a complex system poised near chaos can have dramatic effects throughout the entire system. The brain is certainly a complex system, although still minimally understood, so discovering physical evidence of the theoretical characteristcs of complex systems is quite exciting.

Researchers from the Howard Hughes Medical Institute lead by Yang Dan of the University of California, Berkeley have presented evidence of a complex system in an anesthetized rat brain. They tried to stimilate a single cortical brain cell and then monitor the change in global neuronal activity elsewhere in the brain.

And global change there was. Each neuron can have thousands of interconnections, so the structural network is amazingly complicated. However, the system can be resting in a state that if the network activity just crosses a certain threshold, then the entire system can undergo what might be compared to a phase transition. And the hurricane can begin to form in the brain.

The absolute key to ultimately understanding how the brain works is developing a complete structural map of the neuron network and relating this structure to the overall network function.

As a comparison for example only, the Internet continues to develop as a complex network, but it still does not compare to the immensity of the lump of cells in our head. The structure of the neuron network directly leads to the resulting functionality of the human brain.

A wonderful visualization of a single neuron buried deep inside a network was created by the Blue Brain Project group from the Ecole Polytechnique Federale de Lausanne in Switzerland. Reflect for a while with the animation presented below, and then learn more about EPFL with their feature video presentation.

Neuron communication is not a trivial language and it has yet to be fully understood. This so-called "neural code" is certainly not as simple as a single electrical impulse each time a brain cell wants to say "Hi!" to a neighbor. There can be continuous signals, of varying strengths, and with the latest research from Prof. Anthony Zador at Cold Spring Harbor Laboratory, varying timings.

Understanding how neurons communicate is fundamental to developing neuron-based technologies that will embed and integrate living neural devices into the human system. Of significant importance is the physical structure of the neuron network and how its patterning results in the overall network's function. But, at a more basic level, it is being realized that the electrical signaling patterns between individual neurons is potentially even more complex with amplitude (signal strength), frequency, and even small-scale variations in frequency all being a critical component in the language... which ultimately guides the behavior of the neuron network and the organism.

How neurons develop their vast networks of axons and dendrites with apparently accurate targeting to generate a functioning brain remains a core question in neuroscience. Although some of the interconnections might be partially "random" with the resulting complex network still managing to generate meaningful neural function, it still seems that the network connects in a directed way. How neurons know with whom to connect remains mostly unclear.

Image from Salk Institute for Biological Studies

Using genetically-modified neurons from a mouse, the O'Leary research group from the Salk Institute for Biological Studies found a surprising additional function of a well-known protein called "p75." Also involved in the regulation of keeping a neuron alive, it has now been observed to affect and direct axon growth.

And the function is rather interesting: the protein apparently does not act to attract an axon to follow a certain path... ("come follow me to the promised land!"), but rather it repulses the growth cone to head in another direction... ("yer git on outta here!").

The important aspect of this research is leading to a complete understanding of neuron network growth and development, in particular the understanding of what controls how and where the network connections develop. If we know what are the biological controls, then we can in turn control or influence these factors to guide neurons implanted on a neurotechnological device to connect in specific ways that might be needed for a particular application.

Read more about this interesting work, and think about how this p75 protein might be involved in your next neurotech implant....

Here at Neuron News we will preach until the End of Days and beyond that it's all about the network when it comes to fully understanding brain function. This knowledge will thereby lead to someday better understanding how to develop neuron devices that directly interconnect with the brain.

Researchers at the Max Planck Institute of Neurobiology recently reported on their observations of how versatile and amazing our neuron networks actually are, and how powerful the system really can be when trauma strikes.

After a literal tear in the retina, the research group watched as the remaining neurons, who lost their original network connections, re-wired to other neurons in the system with up to three-times the amount of brand-new interconnectivity. The network compensated for its breakdown, and re-worked itself to attempt to regain new functionality.

The observation of this sort of restructuring activity in an adult brain is extremely exciting for further research into efforts to help patients recover after serious brain injuries. Even more so, this network adaptability is key to understanding how to best design and develop cultured neuron networks in ways that will most likely and most successfully connect with a host brain.

Just throwing a plate of neurons onto a host brain is not quite enough to create a useful and functional neuron device; we must have a deep understanding of how neurons network themselves and how we might tailor the cultured devices to better link in with the brain. If this form of "hyper-networking" is a result of neurons sensing a local trauma, then we might even be able to manipulate stronger, more complex interconnections between device and brain by introducing faux "traumas" in the cultured neuron networks of implanted devices.

Let our readers know what you think by responding after reading the following articles.

Much research into brain function looks at large-scale electrical behavior of the brain. For example, fMRI is a wonderful tool and can peer deep into our brain's function while we are alert and making decisions that might be detected by the machine.

Although this sort of information and attempt at a broad understanding of brain activity is valuable, a pure understanding of how our complex minds truly work is still locked away at a lower level of structure. Not as low as the individual neuron itself, but at the level of the interconnectivity of enormous collections of neurons.

A single neuron is impressive, but is biologically rudimentary in function (and this is such an understatement!). A ball of 10^11 neurons is a biological mess. However, a vast, interconnected network of 10^11 neurons is really something, and it somehow produces something else truly special: our minds.

The following two articles provide a crucial reminder of the importance that a global view doesn't quite get us to the deepest answers... and that the specific interactivity of the neuron networks themselves presents some interesting behaviors.

But, even this latter work (as you must read by following the links below) is entirely based on mathematical modeling, which is certainly an important method for creating hypothesis of how neuron networks might work in the real world. This theoretical computational approach also offers new inspirations to what to look for during actual experiments on living neural communication. It's "just" a model, however, and not quite the real world. So, we're still far from complete understanding.

As has already been said here on Neuron News before (and will be written about many more times because it is so critical!), the future of neurotechnology will rely on our deep understanding of the network behavior of neurons because it is the network -- in particular, the structure of this network -- that is the underlying physics of higher brain functioning.

To understand the network is to understand the brain. With this understanding, we will be able to develop the technology to externally connect into the brain.

It might not be immediately obvious how research developments in Amyotrophic Lateral Sclerosis (ALS -- or, Lou Gehrig's Disease) would be appropriate to follow here on Neuron News. However, this author has a personal family member currently dealing with the devastating disease, so we've been personally reviewing the progress in the field. And, with a little trivial forward thinking, there is an important connection with the advancement of neurotechnology.

Yesterday, a collaboration between Columbia and Harvard Universities announced in Science a fabulous new development that offers promise in the short-term discovery of drugs as well as longer term neuro-therapeutic technologies.

Credit: J. T. Dimos et al., Science Express

The key problem with ALS patients is that motor neurons--particularly those affecting function in breathing and swallowing--degenerate and die off for unknown reasons. So, the general idea of this research program is to develop a technique to take skins cells of a patient and convert them into stem cells, or the "universal cell" that can potentially turn itself into any other cell given just the right biochemical nudge. Now, with a vast supply of genetically appropriate stem cells that will agree with the personal biology of the patient, convert them into motor neurons and implant them into regions of the body to integrate into neural systems that have been severely degraded by the disease.

This is certainly an exciting development for nearing potential therapies for ALS, although real clinical progress is likely still many years away. If you know of anyone affected by ALS or are interested in supporting the research, please thoroughly read the articles referenced below and consider a donation to The ALS Association.

In addition, this research provides experimental evidence of a new technique developed just last Fall called induced pluripotent stem (iPS) cells. This is a very important fundamental technological advance that should guide the future of neurotechnologies.

Specifically, if neuroprosthetic devices are to be successfully integrated into the nervous system of a human being, it seems reasonable that the genetic make-up of the neurons living on the implanted device should compatible, if not identical, to the genetics of the host neurons. There might be unrealized neuro-communication factors that are influenced by genetic coding, and a fully successful device might need to be grown using neurons developed directly from the human host.

Visualize a computer chip for a moment... it's a "flat", 2-dimensional piece of electronics that does some fancy electron dance somewhere within the green-toned plastic. Now, visualize what a neurological computer chip might look like... how about we start with the same flat, green-toned plastic electrical processing unit and toss on a bunch of living neural cells scrambled all over the surface.

This sort of technological device--which is not entirely science fiction--is this idea of a two-dimensional, cultured neuron network interfaced with a microfabricated electrical circuit. This system in no way resembles the network structuring seen in the human brain, so the first immediate question would be to ask why would this living, 2-D neuron network successfully electrically interface with the brain?

Well, that is a good question... but this 2-D world was (and still is) a reasonable starting point for developing the technology. In fact, because the 2-D world is still an important system for developing merged devices composed of electrical circuits and living networked neurons, developing an understanding of the fundamental neuron network function--in two dimensions--is still critical and valuable for neurotechnological research.

But, the brain is still in three dimensions, so advancing the technology to grow cultured neuron networks in controlled ways in 3-D is quite exciting. With a current published article in Nature Methods, researchers from the University of California Berkeley and Lawrence Berkeley National Lab have begun some initial work on controlling the cultured growth of neurons in three dimensions along the bumps of blobs of colloidal crystals.

Micron-sized colloidal particles (i.e., really tiny balls made of clear plastic) are interesting for patterning neuron networks, because there has been a great deal of work on learning how to manipulate these objects using focused laser light called optical tweezers. If the wavelength of the laser beam is selected appropriately, then the living neurons will not absorb the wavelength and heat up and die. So, additional modifications to the underlying colloidal matrix could be made to the system while the neurons were growing and interconnecting along the 3-D lattice.

Q: What do you get when you interconnect billions and billions of transistors?

A: A whole lot of ON/OFF switches.

The brain is a ridiculously complicated network of electrochemically active cells (a.k.a. neurons), which are individually influenced by a large number of greatly complicated chemical machines (a.k.a. synapses), which are in turn individually activated by more particular chemicals and hormones, and even further influenced by microscopic structures which are coupled at the quantum level.

This is not the hierarchy of your typical computing machine. Technologists have long anticipated the future of vast computer networks--built upon the electrical transistor--that pass some unknown critical point of interconnections and become "conscious". Welcome Hal.

Neurobiologists have long been frustrated by this expectation because the level of complexity of the brain as a whole and the level of complexity of its individual parts no where matches that of the computer chip. In fact, this expectation is still so unreasonable because of the remaining immense lack of understanding of how the brain works as a sum of all of its parts to generate the emergent behavior we experience every moment of our lives.

Lee Gomes of WSJ.com provides us with a nice reminder of how far we really still have to go to fully understand the brain... but, it is also a wonderful stimulus to excite us to push further on in the quest to understanding the mass in our skull... and understanding the nature of our existence.

The NIH is certainly serious about making real things happen in neurotechnologies. Setting up large awards for significant steps forward in science and technology has been a tried and true method of encouraging the human race to make a leap from Lindberg to the X Prize. Here is another government-funded opportunity aimed at developing plans for the next-generation technologies for non-invasive imaging of brain function. Mapping detailed  live neuron interactions without the need for drilling through the skull is a holy-grail for reaching a deeper understanding of complete brain function, and it's time to get real serious about making real progress with new technology.

[Read the entire Request for Information]

"NIH requests input on non-invasive brain imaging techniques" BioOptics World :: June 24,  2008 :: [READ]

A new experiment at New York University slightly altered the genetic make-up of cells in a small neuron network forcing them to hang up the phone.

Although this technique may not provide real-time, or dynamic control of neuron behaviors, it brings a new understanding in the relationship between genetic structure and neuron function. It also might lead to new treatments for diseases related by run away electrical activity.