In the eighteenth century, Luigi Galvani, an Italian physician, observed that dissimilar metals, attached to a frog's leg and connected together, can cause the frog's skeletal muscles to contract. Subsequently, natural philosophers, and later physiologists, have come to appreciate that electricity is one of the key features associated with the control of the body. Based upon the pioneering work of Einthoven in studying the role of electricity in the sensory and motor parts of the body, it has become clear that the contraction of all muscle is associated with local electrical fields and that, by the discriminate application of externally applied electrical fields, one can intervene with damaged or diseased parts of the nervous system and thereby restore lost functions. The first, and most lifesaving, example of this electrical intervention is the cardiac pacemaker, which was developed in the middle of the last century and has become a standard therapeutic approach to a variety of cardiac arrhythmias and pathologies.

The extension of this successful therapy to other sensory and motor systems has fostered the neuroprosthetic field. This field is in its infancy but is experiencing great interest in both academic and commercial sectors. With the widespread availability of VLSI (very-large-scale integration) circuitry and with the emergence of microfabrication technologies, researchers are now able to build interfaces to the nervous system with greater complexity than could have been imagined only a few decades ago. These interfaces are being built of highly biocompatible materials that contain feature sizes comparable to the neurons that the devices are intended to interact with. Further, our understanding of the function and dysfunction of the nervous system has improved to the point that, in many cases, researchers have suggested plausible interventional routes whereby neuroprosthetic systems could expect to be efficacious. It is clearly the right time for this technology.

About a half century ago, Brindley, at Cambridge University in England, conducted a bold set of experiments wherein he tried to restore a visual sense to a few individuals who had become profoundly blind. These pioneering experiments did not result in the restoration of useful vision in these subjects, but they did indicate that the concept could be entertained seriously. Thus, the visual neuroprosthetic field was born. Because the technological innovations described above had yet to be developed, little progress was made in the field up until the last decade. Over this last 15

years, many individuals have begun working in this field, and, while clinical systems are still probably a decade away, it is becoming clear that such systems will likely find their way into the operating rooms of major hospitals around the world.

This chapter provides an overview of some of the progress that has been made in this field. We will describe the anatomy and physiology of the visual pathways and human-engineered systems that have been designed to interface with neuronal ensembles at the levels of the retina, the optic nerve, and the visual cortex. We describe animal experiments that support the safety of these systems, and preliminary human experiments that are beginning to demonstrate the efficacy of the approach. It is stressed that the human experimentation is still in its infancy, and as a result the findings are mixed and inconclusive, but encouraging. However, the increased numbers of experimenters working in the area, the acceleration of technological innovation, and the commercial impetus to develop successful clinical systems make it clear that visual neuroprosthetic systems will provide, perhaps, the first interventional systems that could restore useful vision to those with profound blindness. Useful vision in this context will not be vision as enjoyed by normally sighted individuals. First-generation systems will be pixelized, will contain small numbers of pixels, and will recreate narrow field views of the visual world in front of the blind subject. However, it is hoped that such systems will allow the subject independent mobility without requiring a guide dog or a family member or friend, at least in familiar environments, and perhaps even in unfamiliar visual environments.

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