INTRODUCTION

A visual prosthetic or bionic eye is a form of neural prosthesis

intended to partially restore lost vision or amplify existing vision. It usually takes the

form of an externally-worn camera that is attached to a stimulator on the retina, optic

nerve, or in the visual cortex, in order to produce perceptions in the visual cortex.

Visual percepts are the final product of a rich interplay of stimulus

processing that occurs without the intervention of one's consciousness. While this is a

fascinating issue to consider, especially as it pertains to the philosophical and practical

definitions of ideas like the "self," the converse is equally interesting to me. In this

modern era of exploding technological ingenuity, the sum of which is a product of the

conscious brain, increasingly more opportunities exist for the brain to design the input

it receives. One method by which this occurs is observable in the treatment of visual

pathologies. A development of particular interest to me is the use of visual prosthetic

devices in the treatment of some forms of progressive blindness. Research in this area

raises numerous conflicts within the realm of bioengineering, but promises, at least, to

challenge the boundaries of current microtechnology and instigate further integration

of the rapidly expanding fields of electronics and medicine.

In 1988, a multidisciplinary research team called the "Retinal

Implant Project," spanning the knowledge bases of Harvard Medical School, the

Massachusetts Eye and Ear Infirmary, and the Massachusetts Institute of Technology's

Department of Electrical Engineering and Computer Science, was formed with the

explicit goal of creating an intraocular retinal prosthetic device to combat the effects
of certain types of progressive blindness. The prostheses are intended to stimulate

retinal ganglion cells whose associated photoreceptor cells have fallen victim to

degradation by macular degeneration or retinitis pigmentosa, two currently incurable

but widespread conditions. Their most recent work has been to orchestrate short -term

clinical trials in which blind volunteers receive a temporary intraocular prosthetic

implant and undergo a series of tests to determine the quality of visual percepts

experienced over a two- to three-hour period . The leaders of the Retinal Implant

Project, while enthusiastic about their progress, do not anticipate the realization of a

workable prosthetic within the next five years.

The goal of retinal prosthetic proposed by the collaborators is to

bypass degenerate photoreceptors by providing electrical stimulation directly to the

underlying ganglion cells. The ganglion cell axons compose the optic nerve, which

travels from the eye and terminates in various regions of the brain, where the

combined input is processed along multiple routes and ultimately results in the

experience of sight . Ganglion cell excitation will be accomplished by attaching a two -

silicon-microchip system onto the surface of the retina, which will be powered by a

specially designed laser mounted on a pair of glasses worn by the patient . This laser

will also be receiving visual data input from a small, charge-coupled camera, whose

output will dictate the pattern intensity of the laser beam . The laser's emitted radiation

will be collected by the first microchip within the eye on an array of photo diodes and

transferred to the second chip, which will be responsible for electrically stimulating a

set of retinal ganglion cells via fine microelectrodes . Because the ganglion cells in a

healthy retina are stimulated by photoreceptors, this activation process is designed to

stimulus, with the hope that some measure of sight can be restored to individuals with

faulty photoreceptors.

The team selected the retina as the site of artificial stimulation

after careful consideration of the effects of the target diseases and the successes and

limitations of electrical excitation at various regions along the visual pathway. Dr. T.

Hambrecht of the National Institutes of Health and Dr. R. Normann of the University

of Utah are two neurobiologists examining the effects of microelectrode stimulation of

various regions of the visual cortex, a portion of the brain believed to be involved in

visual perception. Upon administration of electrical stimuli to subsurface regions of

the visual cortex of a blind patient, the patient identified spots of light, called

phosphenes, which varied in color and depth, depending on the location of the

stimulus. While this is exciting in its implications for elucidating the physical

arrangement of the neuronal cells involved in the visual pathway, it fails to replicate

the experience of sight because the stimuli are independent of external factors. Also,

the visual percept is the product of neuronal activity in more than one brain region, a

fact that renders the proposition that artificial stimulation in any single cortical area

(or small collection of cortical areas) could recreate the elaborate perception of vision

rather dubious.

The researchers involved with the Retinal Implant Project

hypothesize that higher quality visual perceptions will be experienced with retinal

than with intracortical stimulation. Joseph Wyatt and John Rizzo, III, the co-heads of
the Retinal Implant Project write, ". . . in principle, the earlier the electronic input is

fed into the nerves along the visual pathway, the better, inasmuch as neural signals

farther down the pathway are processed and modified in ways not entirely well

understood". This hypothesis is validated by the observation that photoreceptors are

the sole neurons decimated by macular degeneration and retinitis pigmentosa, leaving

the remaining cells involved in the visual process unharmed. Therefore, with the

proper artificial input, it is reasonable to expect that those with prosthetic

photoreceptive apparatuses will experience some returned vision.

While this proposal is exciting in its scope and purpose, it is not

without drawbacks and complications. While the prosthetic's design offsets many

potential biological problems by having most of its functional parts external to the

body, this fails to solve every obstacle attendant upon the insertion of an inorganic and

electrically active device into a living eye. Rizzo and Wyatt explain,

"Biocompatibility, which encompasses biological, material, mechanical, and

electrochemical issues, is the most significant obstacle to the development of a visual

prosthesis".

Specifically, the electrical components of the prosthesis must be

sequestered from all intraocular fluids, which could corrode the thin metal of the

diodes and ruin the chips' ability to transmit electrical impulses from the laser t o the

retinal ganglion cells. Likewise, the by-products of electrical impulse transmission

through metallic electrodes are toxic to living cells, and must be diminished in order

to insure minimal chemical devastation of the retina. The electrodes themselve s must
also be anchored to the retina with sufficient strength to accommodate physical

agitation due to daily activity. This promises to be a trying procedure. The retina is a

slim 0.25 millimeters thick, a dauntingly thin fabric onto which to stitch a complex,

albeit tiny, piece of machinery. As in all retinal surgical procedures, the implantation

of a prosthetic poses a risk of retinal detachment and infection of the associated

membranes, both of which would exacerbate, rather than prevent, vision loss. These

concerns have not been seriously addressed in this stage of the research, because no

long-term clinical trials of the prosthesis have been undertaken.

A final barrier to the project, and perhaps the most complex to

troubleshoot, is determining whether the engineered apparatus will be effective in

restoring sight with chronic implantation. Although short-term tests of the photodiode

array have been undertaken, their success was only measured in the ability of the

diodes to generate output once inserted into the eye. While this was a necessary

experimental step to prove the short-term mechanical soundness of the diode

apparatus to fluids of the inner eye, the diodes have never been attached to the retinal

tissue, and therefore, their viability as conduits of visual information has not been

examined. The data the researchers cite in their preliminary investigations and those

of their colleagues report that the single visual percept accomplished by artificial

stimulation to date is phosphene recognition. This, however, is not equivalent to true

sight, and certainly falls short of the lofty goal claimed by its spearheads: to "improve

quality of life by providing gross perception with some geometric detail that would

increase independence by making it easier for a blind person to walk down the street,

for instance".
 THE BIONIC EYE SYSTEM

In the past 20 years, biotechnology has become the fastest-growing

area of scientific research, with new devices going into clinical trials at a breakneck

pace. A bionic arm allows amputees to control movements of the prosthesis with their

thoughts. A training system called BrainPort is letting people with visual and balance

disorders bypass their damaged sensory organs and instead send information to their

brain through the tongue. Now, a company called Second Sight has received FDA

approval to begin U.S. trials of a retinal implant system that gives blind people a

limited degree of vision.

The Argus II Retinal Prosthesis System can provide sight -- the

detection of light -- to people who have gone blind from degenerative eye diseases

like macular degeneration and retinitis pigmentosa. Ten percent of people over the age

of 55 suffer from various stages of macular degeneration. Retinitis pigmentosa is an

inherited disease that affects about 1.5 million people around the globe. Both diseases

damage the eyes' photoreceptors, the cells at the back of the retina that perceive light

patterns and pass them on to the brain in the form of nerve impulses, where the

impulse patterns are then interpreted as images. The Argus II system takes the place of

these photoreceptors.

The second incarnation of Second Sight's retinal prosthesis consists of five main parts:
  A digital camera that's built into a pair of glasses. It captures images in

real time and sends images to a microchip.

 A video-processing microchip that's built into a handheld unit. It

processes images into electrical pulses representing patterns of light and

dark and sends the pulses to a radio transmitter in the glasses.

 A radio transmitter that wirelessly transmits pulses to a receiver

implanted above the ear or under the eye

 A radio receiver that sends pulses to the retinal implant by a hair-thin

implanted wire

 A retinal implant with an array of 60 electrodes on a chip measuring 1

mm by 1 mm

The entire system runs on a battery pack that's housed with the video

processing unit. When the camera captures an image -- of, say, a tree -- the image is in

the form of light and dark pixels. It sends this image to the video processor, which

converts the tree-shaped pattern of pixels into a series of electrical pulses that

represent "light" and "dark." The processor sends these pulses to a radio transmitter on

the glasses, which then transmits the pulses in radio form to a receiver implanted

underneath the subject's skin. The receiver is directly connected via a wire to the

electrode array implanted at the back of the eye, and it sends the pulses down the wire.

When the pulses reach the retinal implant, they excite the electrode

array. The array acts as the artificial equivalent of the retina's photoreceptors. The

electrodes are stimulated in accordance with the encoded pattern of light and dark that

represents the tree, as the retina's photoreceptors would be if they were working
(except that the pattern wouldn't be digitally encoded). The electrical signals

generated by the stimulated electrodes then travel as neural signals to the visual center

of the brain by way of the normal pathways used by healthy eyes -- the optic nerves.

In macular degeneration and retinitis pigmentosa, the optical neural pathways aren't

damaged. The brain, in turn, interprets these signals as a tree and tells the subject,

"You're seeing a tree."

It takes some training for subjects to actually see a tree. At first, they

see mostly light and dark spots. But after a while, they learn to interpret what the brain

is showing them, and they eventually perceive that pattern of light and dark as a tree.

The first version of the system had 16 electrodes on the implant and is still in clinical

trials at the University of California in Los Angeles. Doctors implanted the retinal

chip in six subjects, all of whom regained some degree of sight. They are now able to

perceive shapes (such as the shaded outline of a tree) and detect movement to varying

degrees. The newest version of the system should offer greater image resolution

because it has far more electrodes. If the upcoming clinical trials, in which doctors

will implant the second-generation device into 75 subjects, are successful, the retinal

prosthesis could be commercially available by 2010. The estimated cost is $30,000.

Researchers are already planning a third version that has a thousand

electrodes on the retinal implant, which they believe could allow for facial-recognition

capabilities
 HISTORY

Scientific research since at least the 1950s has investigated interfacing

electronics at the level of the retina, optic nerve, thalamus, and cortex. Visual

prosthetics, which have been implanted in patients around the world both acutely and

chronically, have demonstrated proof of principle, but do not yet offer the visual

acuity of a normally sighted eye.

ARTIFICIAL VISION

There are a number of blinding disorders which are primarily due to

photoreceptor or outer retinal degeneration/destruction. These include but are not

exclusive to diseases such as retinitis pigmentosa and age related related macular

degeneration. We have tested the feasibility of developing a retinal implant/Chip

which could provide form vision to this subset of blind patients. This visual prosthesis

would be situated in the eye cavity on the retinal surface. It would create the sensation

of seeing light by electrical stimulation of the remaining retinal cells which remain

relatively intact despite severe photoreceptor loss. Moreover, by converting images

into pixels and then electrically stimulating the retina by a pattern of electrodes, this

device would recreate at least in part the visual information/scene.

the devices that use either ultrasonic sound or a camera to sample the environment

ahead of an individual and render the results into either a series of sounds or a tactile

display. From this the person is supposed to be able to discern the shape and

proximity of objects in their path. The second major form is retina enhancers. These

machines supplement functions of the retina by stimulating the retina with electrical

signals which in turn causes the retina to send the results through the optic nerve to the

brain. The third major category of visual prosthetic is a digital camera that samples an

image and stimulates the brain with electrical signals--either by penetrating into or

placing electrodes on the surface of the visual cortex.

The ability to give sight to a blind person via a bionic eye depends

on the circumstances surrounding the loss of sight. For retinal prostheses, which are

the most prevalent visual prosthetic under development (due to ease of access to the

retina among other considerations), vision loss due to degeneration of photoreceptor s

(retinitis pigmentosa, choroideremia, geographic atrophy macular degeneration) is the

best candidate for treatment. Candidates for visual prosthetic implants find the

procedure most successful if the optic nerve was developed prior to the onset of

blindness. Persons born with blindness may lack a fully developed optical nerve,

which typically develops prior to birth.

TECHNOLOGICAL CONSIDERATIONS

Visual prosthetics are being developed as a potentially valuable aide

for individuals with visual degradation. The visual prosthetic in humans remains

investigational.
 DEVICE

The device consists of a tiny camera and transmitter mounted in

eyeglasses, an implanted receiver, and an electrode-studded array that is secured to the

retina with a microtack the width of a human hair. A wireless microprocessor and

battery pack worn on the belt powers the entire device.

The camera on the glasses captures an image and sends the information

to the video processor, which converts the image to an electronic signal and sends it to

the transmitter on the sunglasses. The implanted receiver wirelessly receives this data

and sends the signals through a tiny cable to the electrode array, stimulating it to emit

electrical pulses. The pulses induce responses in the retina that travel through the optic

nerve to the brain, which perceives patterns of light and dark spots corresponding to
the electrodes stimulated. Patients learn to interpret the visual patterns produced into

meaningful images.

Second Sight’s first generation Argus 16 implant consists of a 16

electrode array and a relatively large implanted receiver implanted behind the ear. The

second generation Argus II is designed with a 60 electrode array and a much smaller

receiver that is implanted around the eye.

WORKING

Normal vision begins when light enters and moves through the eye to

strike specialized photoreceptor (light-receiving) cells in the retina called rods and

cones. These cells convert light signals to electric impulses that are sent to the optic

nerve and the brain. Retinal diseases like age-related macular degeneration and

retinitis pigmentosa destroy vision by annihilating these cells.

With the artificial retina device, a miniature camera mounted in

eyeglasses captures images and wirelessly sends the information to a microprocessor

(worn on a belt) that converts the data to an electronic signal and transmits it to a

receiver on the eye. The receiver sends the signals through a tiny, thin cable to the

microelectrode array, stimulating it to emit pulses. The artificial retina device thus

bypasses defunct photoreceptor cells and transmits electrical signals directly to the

retina’s remaining viable cells. The pulses travel to the optic nerve and, ultimately, to

the brain, which perceives patterns of light and dark spots corresponding to the

electrodes stimulated. Patients learn to interpret these visual patterns.

2: Signals are sent to hand-held device

3: Processed information is sent back to glasses and wirelessly

transmitted to receiver under surface of eye

4: Receiver sends information to electrodes in retinal implant

5: Electrodes stimulate retina to send information to brain

TECHNOLOGY OVERVIEW:

INFORMATION PROCESSING IN THE VISUAL

PATHWAY :

The global goal of our research program is to understand

how information about the outside world is encoded in the neuronal activity in

the central nervous system. The effects of a continuous exogenous input (the
visual world) are manifest through discrete electrical events in the early visual

pathway. The basic anatomy is shown in Figure 1, where light entering the eye

falls onto the photoreceptors of the retina and is transduced into electrical

signals that are processed through layers in the retina, and then passed through

the lateral geniculate nucleus (LGN) to the visual cortex. Individual neurons in

each of these areas respond to light within a restricted region of visual space,

known as the receptive field (RF). More generally, we refer to the

spatiotemporal RF as the characteristics of the integration of visual input over

space and time, giving rise to the neuronal response.

Figure 1. The early mammalian visual pathway.

It is important to quantify the manner in which information is

encoded in these stages of the early visual pathway, so that we may, in turn,

precisely control neural function to produce desired visual percepts, in

situations where function has been lost to trauma or disease. Note that current

attempts at visual prosthetics are still in the nascent stages, and there are major
signal processing, estimation, prediction, and control-related problems that must

be overcome before such technology becomes truly viable. Despite the fact that

the anatomy and physiology of the visual pathway have been studied for some

time, much is still not known about the true nature of the neural code that

enables us to interact with the external visual world.

ENCODING OF NATURAL SCENES:

Our early work led us to study encoding in the early visual

pathway through experimental and computational approaches. Neurons in the

visual pathway encode information about the outside visual world in a causal

manner, but the task of higher centers in the brain is to somehow interpret the

outside world from the spiking activity of neurons that project to them.

Taking this perspective, we decoded or reconstructed natural

visual inputs from population activity in the visual thalamus (which is an

intermediate stage of processing between the retina and cortex) (Stanley et al.,

1999), providing a description of the information about raw light intensity being

encoded in specific cell types within the early pathway. Figure 1 shows the

reconstructed light intensity of 4 adjacent pixels from 8 LGN neurons on the

left, and a reconstruction of a much larger region of visual space on the right

(from Stanley et al., 1999)

the next several years. The large majority of experimental work on the

functional aspects of coding in the visual pathway has utilized artificial classes

of visual stimuli. To understand the true functionality of the visual pathway and

thus to make long term clinical impact, it is absolutely imperative that we

explore more behaviorally and practically relevant scenarios. Despite the

surprising amount of detail that was extracted from the ensemble neuronal

activity in the LGN, as shown in Figure 2, there are many unresolved issues.

Specifically, when studying neural encoding in the natural environment,

questions are raised concerning the role of adaptation in the transient natural

environment, the effects of spatial and temporal correlation structure on neural

coding, the relationship between functional encoding properties and the

information carrying properties of the pathway, and the role of the early visual

pathway in the detection of salient features in the environment. Figure 3 shows

examples of the differences between the evolution of the light intensity at a

point in visual space for natural vs. artificial (white noise) visual stimuli, along

with the corresponding second order statistics (power spectra) in both temporal

The overall perspective that we have taken in this work is that

the early visual pathway has (at least) two distinct roles in processing of

information about the outside world: transmission and detection, as shown in

Figure 4.
Figure 4. The early visual pathway serves to detect changes in the outside visual world, and to transmit

fine details about relevant features.

In certain contexts, it is important for the visual pathway to

transmit fine details concerning features of the outside visual world. We may

think of this as the what question: given that something of interest is in my

visual field, what is it? Is it predator or prey, or perhaps a potential mate? In

other ethologically relevant contexts, it is important to detect the presence of an

object or to signal novelty, in a "bottom-up" context, potentially for the "top-

down" allocation of attentional resources. We may think of this as a yes or no

question: is something of interest there or not? The fast and robust detection of

changes in the external environment may be critical for the survival of the

organism. The startling aspect of this dichotomy is that the seemingly disparate

tasks may in fact be accomplished by the same neuronal circuitry.

A common thread through much of our current work is in

understanding how encoding properties of the neuronal pathways change over

time. One of the most striking properties of the visual system is that it can

faithfully encode visual stimuli over an enormous operating range of light

intensity. This important property exists as a result of adaptive mechanisms that

effectively shift the neuronal sensitivity in response to changes in the light level.

The adaptive mechanisms are continually active in all but the most artificial of

laboratory conditions, as we move our eyes across the visual field, and objects

move in and out of our view. These aspects of encoding are ignored in many

studies, and are the subject of much controversy as to what the functional

significance might be. This is an extremely critical issue in prosthetics, and in

other types of biomimetic applications which seek to process visual information

with the efficiency of the true biological systems.

Adaptation mechanisms affect the encoding of information in

the pathway, which is reflected in the properties of the spatio-temporal receptive

field and corresponding spatial and temporal frequency properties. We have

developed novel approaches to track changes in the linear and nonlinear

encoding dynamics in the visual pathway through adaptive estimation schemes

(Stanley, 2002; Lesica et al., 2003; Lesica and Stanley, 2005a; Lesica and

Stanley 2005b), testing in the retina, LGN, and visual cortex. A block diagram
of the encoding framework is shown in Figure 5, along with the evolution of a

spatial receptive field (RF) of an LGN X cell over several seconds of exposure

to a visual stimulus that induces adaptation.

Specifically, this particular example is of a retinal ganglion cell

response in a contrast switching experiment (data provided by Baccus and

Meister). The left column demonstrates that the gain and offset (theta) of the

imposed model (top of figure) can be estimated over a single trial of

experimental data, as the contrast switching in panel A invokes dramatic

adaptation. The second column illustrates that the proper

estimation/representation of linear and nonlinear components of the encoding

process is necessary to accurately capture the true dynamics of the adaptation

process.

We have established a recent collaboration with the laboratory

of Dr. Jose-Manuel Alonso in the Department of Optometry at SUNY, in

Manhattan. In this collaboration, we have been able to design experiments and

collect data from the early visual pathway that specifically address issues

related to encoding during adaptation, both with artificial stimuli designed to

specifically probe contrast adaptation, and with natural scene stimuli.

DETECTION:
 The lateral geniculate nucleus (LGN) of the thalamus is the

gateway to the visual cortex, controlling the flow of visual information from the

retina [for a review of LGN function, see Sherman (2001a)]. Understanding the

neural code of the LGN is an essential first step in characterizing the proc essing

of visual information in higher-level neurons.

After prolonged periods of hyperpolarization, voltage-

dependent calcium channels in the membrane of the neuron are de-inactivated,

and subsequent depolarization causes a stereotyped burst of closely spaced

action potentials. It has been suggested that bursts serve to signal the

appearance of a salient stimulus (detection), whereas tonic firing relays detailed

features of the stimulus (transmission) (Crick, 1984; Guido et al., 1995). Bursts

may serve as a wake-up call, alerting the visual cortex to the presence of a

stimulus in the receptive field (RF) and signaling the beginning of tonic relay

(Sherman, 2001b).

We investigated the role of LGN bursts in encoding

correlated natural stimuli by analyzing the responses of LGN neurons to natural

scene movies. Across a sample of LGN X-cells, a significant increase in

bursting was observed during natural scene stimulation (relative to white noise

stimulation).
 The stimulus features preceding burst events and tonic spikes

were characterized, revealing that the type of visual stimulus evoking a burst

was fundamentally different from that evoking tonic activity, and was in fact a

feature characteristic of the correlation structure of natural scenes. Taken

together, our results support the detect/transmit framework described above, and

suggest that LGN bursts may be an important part of the neural code of the

LGN, providing an amplification of stimulus features that are typical of

correlated natural scenes.

The LGN resting membrane potential can vary widely

according to behavioral state, from its lowest level during sleep to its highest

level during active waking (Hirsch et al., 1983). We hypothesized that the

resting potential would affect the particular features of the visual stimulus that

evoke bursts, and therefore be a function of behavioral state. In a recent study

with our collaborators (the laboratory of Dr. Jose-Manuel Alonso at SUNY), we

characterized the visual features that evoke bursts at different resting potentials

using simulated and experimental LGN responses to natural scene movies, and

our results support this claim. To investigate the functional consequences of the

effects of resting potential on burst generation, we tested the effects of changes

in resting potential on the extent to which bursts enhance the detection of

different visual features (Guido et al., 1995; Sherman, 2001a; Smith and

Sherman, 2002). Although comparing the LGN response with and without
bursts in vivo is not possible (Porcello et al., 2003), these experiments can be

simulated using an integrate-and-fire-or burst (IFB) model, which can

accurately reproduce the LGN response during both tonic and burst firing

(Smith et al., 2000; Lesica and Stanley, 2004). We simulated the LGN response

to different visual features at different resting potentials with and without the

burst mechanism, and compared the results using signal detection theory. Our

results show that bursts enhance detection of the onset of excitatory features at

low resting potentials and the offset of inhibitory features at high resting

potentials, suggesting that bursts may play a dynamic role in visual processing

that changes with behavioral state.

Most recently, we have also developed algorithms that are

inspired by the transmit/detect framework of the early visual pathway,

specifically for the robust relay of visual information in situations with

constraints on bandwidth.

INFORMATION TRANSMISSION :

For decades, the visual receptive field (RF) has served as the

fundamental building block for our current understanding of the visual pathway

(Kuffler, 1953; Hubel and Weisel, 1962). Spatiotemporal integration of visual

stimuli, when combined with functional mechanisms representative of non-

linear spike generation, has been shown to be a good predictor of firing rate for
many neurons in the early visual pathway (Dan et al., 1996; Stanley, 2002).

However, the temporal resolution of the stimulus representation is limited by

the photoreceptor transduction process and takes place over a time course of

tens to hundreds of milliseconds (Barlow, 1952), limiting a receptive-field-

based description of the firing rate to this relatively coarse temporal scale.

In contrast, information theoretic studies of these same

neurons reveal significant temporal structure in the neural responses on the

order of one millisecond (Reinagel and Reid, 2000; Liu et al., 2001). The

discrepancy of temporal scales between stimulus representation and neural

response has been the seed of a far ranging debate concerning temporal

precision and variability of neural responses, and their corresponding role in

neural coding of dynamic stimuli (e.g., de Ruyter van Steveninck et al. (1997);

Warzecha and Egelhaaf (1999)). Figure 8 shows the ability of a simple linear-

nonlinear (LN) model to capture the firing activity of an LGN neuron at a

coarse temporal resolution (bottom), while failing at finer time resolutions

(middle).
Figure 8. Raster of the spike times of a simulated LGN neuron to full-field Gaussian white noise, with the

resulting instantaneous spike rate (below, solid line) and LN prediction (dashed line), at a binsize of 0.3

ms. Dashed horizontal line shows the mean firing rate. Bottom, actual (solid) and LN model prediction

(dashed) of firing rate at binsize of 8.3 ms.

In recent work, we have established a direct link between

receptive field descriptions of neurons and their information encoding

properties by incorporating elements that capture finer time resolutions into the

relatively coarse representation of the receptive field. Such a framework results

in “sparse” representations with large fluctuations in firing rates that match

experimental observations, and thus provides an understanding of how elements

of neural encoding directly relate to information transmission.

Furthermore, these sparse representations translate into

structure in the neuronal response on time scales of the order of a millisecond.

We have demonstrated that such structure conveys a significant fraction of the

total information about the stimulus. As a result, two neurons with subtle
differences in their receptive fields could produce distinct responses that would

be indistinguishable at coarse times scales, allowing information about small

differences in visual stimuli to be easily read out by downstream neurons.

ONGOING PROJECTS:

ARGUS RETINAL PROSTHESIS:

Drs. Mark Humayun and Eugene DeJuan at the Doheny Eye

Institute (USC) were the original inventors of the active epi-retinal prosthesis

and demonstrated proof of principle in acute patient investigations at Johns Hopkins

University in the early 90s. In the late 90s the company Second Sight was formed

to develop a chronically implantable retinal prosthesis. Their first generation

implant had 16 electrodes and was implanted in 6 subjects between 2002 and

2004. Five of these subjects still use the device in their homes today. These

subjects, who were all completely blind prior to implantation, can now perform

a surprising array of tasks using the device. More recently, the company

announced that it has received FDA approval to begin a trial of its second

generation, 60 electrode implant, in the US. Additionally they have planned

clinical trials worldwide, all getting underway in 2007. Three major US

government funding agencies (National Eye Institute, Department of Energy,

and National Science Foundation) have supported the work at Second Sight and

USC.
MICROSYSTEM-BASED VISUAL PROSTHESIS

(MIVIP):

Designed by Claude Veraart at the University of Louvain, this is a

spiral cuff electrode around the optic nerve at the back of the eye. It is

connected to a stimulator implanted in a small depression in the skull. The

stimulator receives signals from an externally-worn camera, which are

translated into electrical signals that stimulate the optic nerve directly.

IMPLANTABLE MINIATURE TELESCOPE:

Although not truly an active prosthesis, an Implantable Miniature

Telescope is one type of visual implant that has met with some success in the

treatment of end-stage age-related macular degeneration. This type of device is

implanted in the eye's posterior chamber and works by increasing (by about three

times) the size of the image projected onto the retina in order to overcome a

centrally-located scotoma or blind spot.

TÜBINGEN MPDA PROJECT:

A Southern German team led by the University Eye Hospital in

Tübingen, was formed in 1995 by Eberhart Zrenner to develop a subretinal

prosthesis. The chip is located behind the retina and utilizes microphotodiode
arrays (MPDA) which collect incident light and transform it into electrical

current stimulating the retinal ganglion cells. As natural photoreceptors are far more

efficient than photodiodes, visible light is not powerful enough to stimulate the

MPDA. Therefore, an external power supply is used to enhance the stimulation

current. The German team commenced in vivo experiments in 2000, when

evoked cortical potentials were measured from Yucatan micropigs and rabbits.

At 14 months post implantation, the implant and retina surrounding it were

examined and there were no noticeable changes to anatomical integrity. The

implants were successful in producing evoked cortical potentials in half of the

animals tested. The thresholds identified in this study were similar to those

required in epiretinal stimulation. The latest reports from this group concern the

results of a clinical pilot study on eight participants suffering from RP. The

results will be presented in detail on the ARVO 2007 congress in Fort

Lauderdale.

HARVARD/MIT RETINAL IMPLANT:

Joseph Rizzo and John Wyatt at MIT and the Massachusetts Eye

and Ear Infirmary have developed a stimulator chip that sits on the retina and is

in turn stimulated by signals beamed from a camera mounted on a pair of

camera and stimulates retinal ganglion cells accordingly.

ARTIFICIAL SILICON RETINA (ASR):

The brothers Alan Chow and Vincent Chow have developed a

microchip containing 3500 solar cells, which detect light and convert it into

electrical impulses, which stimulate healthy retinal ganglion cells. The ASR

requires no externally-worn devices.

OPTOELECTRONIC RETINAL PROSTHESIS:

Daniel Palanker and his group at Stanford University have

developed an optoelectronic system for visual prosthesis that includes a

subretinal photodiode array and an infrared image projection system mounted

on video goggles. Information from the video camera is processed in a pocket

PC and displayed on pulsed near-infrared (IR, 850-900 nm) video goggles. IR

image is projected onto the retina via natural eye optics, and activates
photodiodes in the subretinal implant that convert light into pulsed bi-phasic

electric current in each pixel. Current can be further increased by approximately

an order of magnitude using a common bias voltage provided by a

radiofrequency-driven implantable power supply Close proximity between

electrodes and neural cells necessary for high resolution stimulation can be

achieved utilizing effect of retinal migration.

THE DOBELLE EYE:

Similar in function to the Harvard/MIT device, except the

stimulator chip sits in the primary visual cortex, rather than on the retina. Many

subjects have been implanted with a high success rate and limited negative

effects. Still in the developmental phase, upon the death of Dr. Dobelle, selling

the eye for profit was ruled against in favor of donating it to a publicly funded

research team.

INTRACORTICAL VISUAL PROSTHESIS:

The Laboratory of Neural Prosthesis at Illinois Institute Of

Technology (IIT), Chicago, is developing a visual prosthetic using Intracortical

Iridium Oxide (AIROF) electrodes arrays. These arrays will be implanted on the

occipital lobe. External hardware will capture images, process them and

generate instructions which will then be transmitted to implanted circuitry via a

electrodes, in turn stimulating the visual cortex. The group is developing a

wearable external image capture and processing system. Studies on animals and

psyphophysical studies on humans are being conducted to test the feasibility of

a human volunteer implant.

CONCLUSION:

This is a revolutionary piece of technology and really has the

potential to change people's lives. Artificial Eye is such a revolution in medical

science field. It’s good news for patients who suffer from retinal diseases. A

bionic eye implant that could help restore the sight of millions of blind people

could be available to patients within two years. Retinal implants are able to

partially restore the vision of people with particular forms of blindness caused

by diseases such as macular degeneration or retinitis pigmentosa. About 1.5

million people worldwide have retinitis pigmentosa, and one in 10 people over

the age of 55 have age-related macular degeneration. The invention and

implementation of artificial eye could help those people.