INTRODUCTION

Unexpected accidents, war wounds and disease are just a few of the possible means by which an individual may lose a limb. The short and long-term effects of amputation (intentional or not) are neither pleasant or convenient. Approximately 1.7 million people are currently living with limb loss in the U.S. (Ziegler-Graham, 2008). Although the lifetime cost of losing a limb is difficult to estimate we can consider some obvious consequences such as a possible job loss, ongoing medical bills and perhaps even extended medical assistance due to a lack of mobility. All this being said, it is obvious that the loss of any limb has rarely, if ever, resulted in a positive outcome. With these thoughts in mind, neuroscientists, mechanical engineers, software engineers, medical doctors and many more professionals have teamed up in an effort to replace an amputees old prosthetic limb(s) with new neural prosthetics. These neural prosthetics are somewhat similar in appearance to the old blocky and immobile prosthetics but one key difference sets them apart: neural prosthetics are integrated with the patients nervous system. This difference upgrades a prosthetic from a simple place-holder to a moving and usable limb. Sounds a bit sci-fi doesn’t it? You may be surprised to learn that this technology is much closer than you think. Not only that, but it extends beyond limb prosthetics and on into restoring sight, hearing and other sensory modalities. Make no mistake, integrating any form of technology with the human body is an incredibly difficult feat. Bioengineering research has only reached this point with the help of many teams of scientists from around the world. In this post I will discuss some of the basics of neural prosthetics. I will discuss how the technology and biology partners must communicate and how the communication will extend into full cognitive control. Additionally, I will address some of the limitations and possible risks to incorporating technology into the human body. I will conclude with some of my own thoughts on how future neural prosthetics may be improved.

COMMUNICATION

A common misconception of the human nervous system is that electricity freely flows through it. Though a form of ‘electric’ communication is used, the nervous system cannot simply be ‘hooked up’ to a piece of technology and expect to power it. Instead, the nervous system is powered by what is called electrochemical energy. In more simple terms, the energy used to pass on a message is derived from the movement of chemicals. These messenger chemicals are called neurotransmitters.

As seen in the image to the left, neurotransmitters are packaged into small vesicles (small enclosed fatty droplets) and delivered from the cell body of a neuron to the end of its axon. Each neuron has one more more axons, a long arm-like projection, always near the cell body of a nearby neuron. In this way, neurons have no trouble finding a communication partner. Upon receiving a signal from a nearby neuron, the next neuron will release its package of neurotransmitters into the space between its axon and the next neurons cell body. This space is called a synapse. On the cell body of the next neuron you will find receptors for these neurotransmitters. These receptors clue the next neuron to pass on the same signal. Though the passing of neurotransmitters is far from the nitty-gritty of cell-to-cell communication in the nervous system, this education is enough to understand the basics of neural prosthetics. For a more complete understanding on the topic of neural communication I would suggest studying the concepts behind the neuronal action potential and the flow of ions (Sodium and Potassium in particular) across the cell membranes. In short I will simply say that the reception of neurotransmitters signals a chemical cascade across the outer membrane (or shell) of a neuron until it again reaches the next axon and there releasing a new set of neurotransmitters. A question someone would have to ask when trying to incorporate technology into the nervous system is: where do I plug it in? Everyday microchips are obviously not built to read and interpret chemical signals, let alone those as complex as neurotransmitters. Herein lies possibly the most difficult challenge scientists in this line of research have faced. There are two forms of communication that must be addressed when considering the technology and biological relationship. The first form of communication is sensory. A sensory signal would proceed from a prosthetic limb into the neural circuitry and be interpreted by the brain. We can call this Tech-to-Bio communication. The second form of communication is motor. Motor signals begin in the brain with a plan of movement and then send the corresponding orders to the appropriate body part. This communication proceeds in the opposite direction of sensory communication. Therefore, we can call it Bio-to-tech communication.

Tech-to-Bio Communication

The tech-to-bio connection is necessary for the carrying of sensory information from receptors or sensors on the prosthetic limb to the sensory integration area of the brain (more formally known as the primary somatosensory area). This direction in communication is actually the easier of the two by a significant degree. It has been well known for a number of years that stimulation from an electrode is enough to stimulate a neural impulse. In fact, electrodes like this are frequently used in research when investigating complex neural networks and trying to determine which neurons are connected to one another. Electrodes also exist on a microscopic scale to investigate the behavior of a neuron once it has been excited and is transmitting or transducing a signal. Microscopic electrodes are a great means by which sensory information can accurately be delivered to the brain. Although the amputation of a limb takes all of the corresponding nerves with it, neural material still remains up to the amputation point. While it still remains, these remaining nerves still possess connections to the appropriate brain areas. Therefore, the connection between tech-to-bio can be made at the amputation point. (Note: This may only be true for recent amputees. Unused neural systems are eventually naturally ‘trimmed’ or reallocated to other nervous system components. If this occurs, it will be more difficult to make the tech to bio connection).

Outfitting each of the nerve fiber bundles with electrodes would present the possibility of activating these neural circuits. The challenge of course is attaching the correct electrode to the correct nerve fiber so that touching the palm of a hand is actually interpreted in the same way in the brain and not as a sensation on the forearm. Fortunately, neuroanatomists have some experience in this effort and have mapped many neural pathways from point A to point B. I’ll take this opportunity to blow your mind a bit on this topic. Even if the electrodes were attached to the wrong nerve fiber tracts, our brain has the capacity to rearrange and correct neurons where appropriate. So if we accidentally connected a palm sensory neuron to the nerve fiber tract that was associated with forearm sensation, the brain would eventually learn the disconnect and would adapt and modify as necessary. This is called neural plasticity. Awesome, right?

To take this one step further, image the use for this type of technology in a more complex sensory modality, such as sight. In fact, this technology (know as ocular prosthetics) currently exists in prototype format and full medical models will likely reach the public in the next 5 years. Small microchips are placed on the surface of the eye and have the capacity to detect and correctly identify the specific wavelengths of light entering the eye. Each wavelength of light has a slightly different amount of energy to it than the next. This microchip can then decipher the ‘light code’ being delivered and stimulate the appropriate neurons at the back of the eye for activation. The visual system is activated as it naturally would and visual interpretation is performed in the occipital lobe of the brain. Long story short, this microchip will give sight to individuals who have been blind since birth. Even shorter story, this invention may have cured blindness. Refinement will of course be necessary to expand the scope of color identification and improving three dimensional viewing but the possibilities are incredible.

In summary, the advances in tech-to-bio communication are astounding to say the least. It seems that the greatest of hurdles have been jumped. The remaining difficulties lie in perfecting the technology while minimizing, or even eliminating, the risks associated with incorporating technology into the body.

Bio-to-Tech Communication

While tech-to-bio communication has seen impressive progress, bio-to-tech communication has lagged behind significantly. Bio-to-tech communication is seen in motor initiation and control. When I decide to move my fingers to type out this post, my brain is constantly planning and initiating skilled movements to place my fingers on the specific keys I choose. To some, this is miraculous enough by itself. When a limb is severed, the neural pathways remain intact up until the amputation point. Axons (the long arm-like projections of neurons) will likely ‘shrivel’ to some degree and retract but they could still be considered viable connection points if accessed soon after the amputation. The impasse many researchers have arrived at is devising a connection point between the neuron and microchip or other receiving device. Tech-to-bio communication is possible because neurons respond well to simple electrical impulses. Computer-like devices, however, do not respond well to chemical signals. The release of neurotransmitter needs a specific receiver that will be able to determine both the type and amount of transmitter released. An alternative involves using a voltmeter to measure the ionic gradient that is created when neurotransmitters are released and received. This too is difficult and likely not reliable since the placement of the reader has to be in just the right place so as to prevent oversampling. In the end, this is where the heaviest degree of research is currently underway. I would estimate that for this technology to work as well as we would hope, it would need to rely on nanotechnology so as to capture the true activity seen in a neuron and replicate it accurately.

Another more creative strategy is to the neuromuscular systems in other parts of the body that still function well. As a scenario, let’s consider a soldier named Paul who recently lost an arm during combat. As stated previously, although Paul has lost his arm, his brain still contains a reserved area for the receiving and sending of signals between his brain and arm. This remaining functionality explains the ‘phantom limb’ sensation some amputees experience, an odd experience of sensing the missing limb when it’s not really there. Paul decides to sign up for a new procedure to implement a neural prosthetic to replace his arm. Medical professionals surgically locate and move the nerve fibers associated with his arm to his right chest. Carefully mapped ahead of time, each nerve fiber is surgically attached to a specific location on the muscle. After about 6 months, the nerve endings will grow around the muscle and will achieve full functionality. When Paul thinks about clenching his fist, one specific portion of his chest muscle flexes in response. If he thinks about flexing his bicep, a different section of his chest flexes. Essentially, the doctors have turned his right chest into an arm without the actual arm being attached. After success has been declared, Paul is outfitted with a new prosthetic arm that is capable of detecting changes in tension and intensity in his chest muscles. When changes are detected in the chest, the prosthetic responds accordingly with impressive accuracy. Of course this type of procedures requires extremely accurate mapping of the nerve fibers and the similarly accurate placement on chest muscles so that the correct systems are communicating to one another. Nonetheless, without actually accomplishing a direct bio to tech link, this system of neural prosthetics is impressive and has potential.

DEEP BRAIN SYSTEMS

Though the primary application of neural prosthetics is in arm and leg amputation treatment, the usefulness does not end there. I have previously discussed tech-to-bio and bio-to-tech communication at the amputation point. What if, instead, the loss of motor control is not due to the loss of a limb but something more internal such as a brain lesion or neurodegenerative disease? In this case motor or sensory systems have degraded and, for lack of better words, the wire has been cut. A gap in neuron to neuron communication understandably results in disconnected systems and networks. Suppose we apply the same principles we discussed earlier and built a bio-to-tech-to-bio interface. Were both types of communications (tech-to-bio and bio-to-tech) fully available to us today, this type of solution may actually be possible. A prime example of this is Parkinson’s disease. Caused by the degeneration of modulating motor neurons, Parkinson’s disease results in the death of whole neural groups. Currently one of the best solutions used by medical professionals is the implantation of an electrode that behaves as the modulating motor neurons would have. Sound a bit familiar? This is a simple example of tech-to-bio integration. When the technology becomes available we will be able to take this one step further. Instead of a stand-alone electrode constantly shocking target neurons, a microchip type of device could be implanted that would be controlled by higher-order neurons and used to communicate with the downstream motor neurons.

Let’s use the limb movement scenario again to explore how this type of technology could help in the real world. Let’s say our friend Frank recently went shooting and had an accident. A piece of shrapnel deflected off a target and struck Frank in the head near the cranial mid-line and embedded into his head. Not a pretty sight for sure. However, accidents like these are very much survivable when it comes to brain damage. Unfortunately for Frank, though, the shrapnel penetrated the skull and struck a part of his brain where his right arm motor control was located. From this single piece of shrapnel, he has lost all cognitive functionality in his arm even though the arm itself is fine. Even after removal of the shrapnel, new neurons will not grow back into the place. Sensory stimulation on his arm constantly sends signals up to his brain informing him of where his arm is and how it feels, but none of it will translate into reflexive or controlled movement. How can Frank regain control of his arm again? A neural chip placed in the lesion area could interface with both sensory and motor systems and bridge that gap created by the shrapnel. As is always the case in these types of treatments, extensive anatomical mapping would be necessary to align the correct networks producing controlled and intended movement. With communication restored between sensory systems and higher-order motor neurons, Frank’s arm could become functional again.

RISKS AND LIMITATIONS

The idea of potentially creating human body part replacements sounds incredible. Of course there are many benefits to replacing lost limbs and returning functionality to an individual. As is the case in any medical procedure, however, limitations and risks do exist. Some of those risks are even life threatening. I will name just two of the most important risks associated with neural prosthetics. First, the implantation of any foreign object into the body will generate some sort of immune response. Think about donor organs and the common risk of rejection that is associated with that procedure. If the implanted technology is labeled as foreign, the body will respond with inflammatory chemicals that could lead to cellular death around the area of implantation. Not only is the cell death bad in of itself, those nearby cells are obviously necessary for creating the tech-to-bio or bio-to-tech connection. Current research is exploring means by which to ‘fool’ the human immune system by coating electrodes or other embedded technology in a biofriendly protectant. This coating would persuade the immune system that the technology is made up of friendly components and not harmful substances. The hope is that this method of ‘cloaking’ technology in the body would allow it to remain there for the remainder of the hosts life. Something to consider though is whether or not that protectant can persist for an extended amount of time. What if the protectant is slowly broken down? Recoating may be possible but it would certainly be difficult.

A second risk associated with neural prosthetics has to do with a phenomenon called pruning. The term pruning may remind you of the process of trimming down plants or flowers in order to facilitate improved growth. In reality, this is not far from the same process of pruning seen in the nervous system. Neural tracts or regions that go unused for a significant amount of time eventually undergo a similar process of pruning or trimming back. This is especially seen in early childhood development. Newborns are naturally born with an excess of neural networks and connections. After some experience with common movements and behaviors, neural networks are trimmed down to only the base need required for everyday life. In adulthood, unused neurons or networks of neurons are reallocated to areas of heavier use. What does this have to do with prosthetics? Well, suppose a prosthetic is given to our friend Paul and he uses it on a daily basis. However, as time goes on, Paul becomes dependent on some arm movements more than others and becomes lax in the way he uses his prosthetic. As use is reduced in certain neural groups, the potential for reallocation increases. If reallocation occurs, entire connections are lost. If Paul one day decides he needs to exercise that long neglected muscle group, he may be surprised to find that he no longer has the capacity to do so anymore. In order to regain that muscle group Paul cannot simply exercise as you or I do. Instead, he will have to have a new nerve ending re-attached to the technological component responsible for executing movement in his limb. In summary, neglect leads to loss of function and loss of function leads to the requirement of surgical replacement. It is possible that a simple daily exercise routine could be enough to maintain the neural connections. An exercise routine that is consistently adhered to could prevent reallocation or trimming and thereby maintain functionality. Falling out of the routine, however, would have dangerous consequences. Hopefully our friend Paul will develop the necessary habits to fully appreciate the gift he’s received through neural prosthetics.

CONCLUSION

We live in an age of rapid improvement and progress. The field of science, especially neuroscience, is no exception to that. Multiple key discoveries have made it possible for technologies such as neural prosthetics to become possible. Though still in its infancy, I believe the implementation of this technology will one day be commonly found in medical practices dealing with amputations. Of course replacing a lost limb with a prosthetic is never a perfect alternative for what we were born with. Even so, if the choice were between having no limb and having a functioning and reliable neural prosthetic, I would certainly choose the option that returns my life to as close to normal as possible. In this post I attempted to provide a reasonable summary of the science and technology behind neural prosthetics. The topic is much much more complex than what I discussed here and I encourage all interested readers to look into this topic further.

REFERENCES

Kathryn Ziegler-Graham, PhD, et al. “Estimating the Prevalence of Limb Loss in the United States – 2005 to 2050,” Archives of Physical Medicine and Rehabilitation 89 (2008): 422-429.