Optic nerve neuroprosthetic approach

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The optic nerves provide the sole conduits of visual information from the retina to the lateral geniculate nucleus in the thalamus. In certain visual pathologies, such as age related macular degeneration or retinitis pigmentosa, where a subpopulation of ganglion cells has been spared, but in which cells of the outer retina are completely degenerate, the optic nerve offers a possible site for intervention via a neural interface.

A group of researchers from the Catholic University of Louvain in Brussels has seriously entertained this as a candidate intervention site for a visual prosthesis.49,50 They have tested the concept in a series of experiments conducted over the past 4 years in a single human volunteer with retinitis pigmentosa. The team has implanted a self-sizing spiral cuff electrode array around the right optic nerve of this volunteer. The electrode array consists of four surface electrodes on the inner surface of the cuff. When implanted around the optic nerve, currents can be passed in a bipolar fashion between groups of these surface electrodes in order to achieve some degree of stimulation selectivity in the population of nerve fibers. The use of cuff electrodes to stimulate peripheral nerves has a long history.51 In many cases, such electrodes can provide long-term stimulation, with little biological compli-cations.52 Recent improvements in the implanted system involve wireless telemetry of stimulus signals to the implanted array.

The surgical access used in the implantation is complex. The lead wires in the implant system were fed under the skin, down the neck to a telemetry unit implanted near the collarbone. In this one subject, there has been no report of complications from the surgery or breakage of the lead wires.

The subject has been stimulated intermittently over the 4-year period of the implantation, and studies of phosphene thresholds and their spatial location have been monitored. Wide ranges of phosphenes have been able to be evoked with this system. They span a region extending 85 horizontal degrees and 60 vertical degrees in front of the observer (the observer points to the perceived phosphene location). The phosphenes range in size from 1 to 50 square degrees, and for a given bipolar stimulation regime the location of the phosphene, its intensity, and its size are a function of the stimulation current. As the stimulus current is increased by a factor of three, the location of the perceived phosphene migrates from the edge of the phosphene space to the center of the space. The absolute thresholds for evoking a just perceptible phosphene vary with stimulus pulse duration and whether the stimulation is delivered as a train or as a single biphasic pulse. For single biphasic pulses of 213 |isec durations, the average thresholds were about 350 |A, while for 17 pulse trains, delivered at 160 Hz, the thresholds for perceptions dropped to about 15 |A. When the stimuli were delivered at a low repetition rate, the phosphenes were observed to flicker, but they fused into a steady percept when the stimulus rate was between 8 and 10 Hz. The steady percept produced by these stimuli fades out after 1 to 3 seconds. The brightness of all evoked phosphenes varied with stimulus intensity, and ranged from "dim" to "average" as the current strength was increased by a factor of three.

The researchers claim that the phosphene space is sufficiently stable that they have been able to predict a phosphene's size, location, and intensity from the stimulation parameters used to evoke the phosphene. This is clearly a critical issue if optic nerve stimulation is expected to restore any form of useful vision.

A useful visual sense can only be built from multiple phosphenes, evoked at predictable locations. The Belgium team has used interleaved stimulation to evoke patterns of from 4 to 24 phosphenes, and the subject has been able to identify simple objects using these phosphene fields by scanning the objects using a head-mounted camera.

It is clear from these observations that this approach is unlikely to be able to recreate a high-resolution visual sense in those implanted with the four-electrode cuff. However, the researchers suggest that visually guided mobility and some forms of task performance do not necessarily require a high-resolution visual sense. They suggest that with sufficient training, a subject implanted with an optic nerve array could use this limited visual input to achieve simple visually guided mobility (at least in familiar environments). However, a number of issues require additional research before this approach could be considered tenable. Issues that relate to this potential intervention site are (1) how significant and how viable is the population of optic nerve fibers that are still functional; (2) does electrical stimulation of the optic nerve spare it from continued degeneration or does constant stimulation accelerate the process; (3) how many phosphenes, evoked by optic nerve stimulation, are required to produce given levels of visual task performance; and (4) would other electrode array designs that penetrate into the optic nerve produce more focal stimulation of optic nerve fibers and better control of phosphene location and intensity?

Researchers at the University of Utah have conducted experiments addressing this last issue. They have developed a unique electrode array architecture that was designed to provide highly selective electrical access to a number of the nerve fibers in the sciatic nerve.53 This device, the Utah Slanted Electrode Array (USEA), is shown in Figure 11.7, and its access to the fibers in the nerve is depicted in Figure 11.8. It is built from silicon and contains 100 electrodes designed to penetrate the epineurium that surrounds the nerve and the perineuria that surround the individual fascicles within the nerve. The length of each electrode varies along the length of the array, with 0.5-mm-long electrodes on one side of the array, and 1.5-mm-long electrodes on the opposite side of the array. Each electrode is electrically isolated from its neighboring electrodes with a moat of glass at its base, and each electrode has a lead wire connected to a bond pad at its base that is

Figure 11.7 Potential neural interface, the USEA, for access to the optic nerve. The array of 100 electrodes, shown to the left, has been successfully used in peripheral nerve of cats. As each row of 10 electrodes has a unique length, ranging from 0.5 to 1.5 mm, each row of electrodes accesses a unique depth in the nerve, as shown in the center panel. Thus, this structure could potentially access 100 unique axonal fibers within a nerve, as illustrated in the right panel. The distance between rows (and columns) of electrodes is 400 |im.

Figure 11.7 Potential neural interface, the USEA, for access to the optic nerve. The array of 100 electrodes, shown to the left, has been successfully used in peripheral nerve of cats. As each row of 10 electrodes has a unique length, ranging from 0.5 to 1.5 mm, each row of electrodes accesses a unique depth in the nerve, as shown in the center panel. Thus, this structure could potentially access 100 unique axonal fibers within a nerve, as illustrated in the right panel. The distance between rows (and columns) of electrodes is 400 |im.

Figure 11.8 Artist's concept of a cortically based visual neuroprosthesis. A small camera, located in the bridge of a pair of glasses, encodes the visual scene. This signal then drives a small array of electrodes implanted into primary visual cortex. The signal-processing electronics, not shown, convert the video signal into controlled current pulses on each of the electrodes, resulting in the percept of the same pattern seen by the camera.

Figure 11.8 Artist's concept of a cortically based visual neuroprosthesis. A small camera, located in the bridge of a pair of glasses, encodes the visual scene. This signal then drives a small array of electrodes implanted into primary visual cortex. The signal-processing electronics, not shown, convert the video signal into controlled current pulses on each of the electrodes, resulting in the percept of the same pattern seen by the camera.

brought out to a percutaneous connector. The tips of each electrode are metalized with platinum or iridium to facilitate the transduction of electrons in the wires into ions in the nerve. The entire structure, with the exception of the metalized tips, is insulated with silicon nitride or polymeric materials.

The Utah researchers have inserted the USEA into the sciatic nerve of the cat and measured the amount of electrical current required to evoke a twitch in the muscles innervated by the motor neurons of the sciatic nerve.53 They found that single biphasic current pulses in the 5- to 20-|A range were generally sufficient to evoke muscle twitches. They also studied selectivity of stimulation by monitoring which muscles were excited when currents were passed through each of the implanted electrodes. They found that each of the muscles of the lower leg and ankle could be individually stimulated with currents passed through appropriate electrodes in the implanted array, and that individual muscles often could be activated by multiple electrodes in the array. Finally, these electrodes appeared to activate specific independent subsets of motoneurons. Such an electrode array architecture holds promise for an optic nerve interface.

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