Abstract:
A method for selective electrical stimulation of a retina for application in a visual neuralprosthesis. The method includes application of an asymmetrical, charge-balance biphasic waveform to increase the receptivity of selected cells to a subsequent stimulus, and then electrically stimulating to those selected cells to induce either a punctuate phosphene (perceived spot of light in the visual field) or a streak phosphene (streak of light in the visual field). A waveform having a sub-threshold anodic pulse followed by a supra-threshold cathodic pulse induces the punctuate phosphene, and a sub-threshold cathodic pulse followed by a supra-threshold anodic pulse induces the streak phosphene.

Description:
RELATED APPLICATIONS  
       [0001]     The inventors claim the benefit of U.S. Provisional Application No. 60/744,749, filed Apr. 13, 2006, which is hereby incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention relates generally to electrical stimulation of sensory nerves, and in particular electrical stimulation of retinal ganglion cells of an eye to induce visual perception.  
       BACKGROUND  
       [0003]     In many patients who are blinded by degenerative conditions, the photoreceptors of the retina may no longer function normally. For many of these patients, however, the retinal ganglion cells can continue to function and provide a signal pathway through the central nervous system to the brain.  
         [0004]     A typical eye  10  and the relative location of its components is schematically illustrated in  FIGS. 1 and 2 . The eye  10  is a generally circular globe filled with aqueous humour  12 , a clear liquid that is similar to water. The eye  10  also includes a cornea  14 , which is a transparent structure that admits light into the eye  10 . The amount of light passing into the eye  10  is controlled by an iris  16 , a muscle that moves to allow or block light from passing through a lens  20  behind the iris  16  to the interior of the eye  10 . The lens  20  focuses light passing therethrough onto the retina  22 . The retina  22  forms the interior surface of the eye opposite the lens. The output of the retina  22  is carried by retinal ganglion cells  30  that transmit action potentials to the brain via the optic nerve  24 .  
         [0005]     In the eye  10 , the retina  22  is a multilayered tissue that includes a layer of rods  26  and cones  28  which are the photoreceptors that detect the light falling thereon and help to convert the image projected on the retina  22  into electrical signals that can be interpreted by the brain as sight. The rods  26  provide vision in dim light and do not respond to bright light. Cones  28  on the other hand, do not respond to dim light, but provide color and fine detail vision. An inner nuclear layer separates the rods  26  and cones  28  from the ganglion cells  30  and includes amacrine cells  32 , bipolar cells  34  and horizontal cells  36 .  
         [0006]     A common structural feature of ganglion cells  30  is an approximately 90° bend  40  in the axon as the axon leaves the ganglion cell layer  42  and enters the nerve fiber layer  44 . The axons of the retinal ganglion cells  30  pass across the surface of the retina  22  and collect before exiting to form the optic nerve  24 . In a healthy eye, light detected by the rods  26  and cones  28  generate signals that are transmitted via the retinal ganglion cells  30  and the optic nerve  24  to the brain, which perceives the visual image.  
       SUMMARY  
       [0007]     An exemplary method for electrically stimulating a retina of an eye to induce visual perception includes the following steps: placing an electrode adjacent a retinal ganglion cell layer; effecting a change in the excitability of cells in the ganglion cell layer by selectively applying a biphasic asymmetrical waveform having a relatively long duration and a relatively low amplitude pre-pulse phase of a first polarity, and inducing visual perception by selectively applying a biphasic asymmetrical waveform having a relatively short duration and relatively high amplitude stimulation pulse phase that follows the pre-pulse phase. The stimulation pulse phase has a second polarity opposite the first polarity of the pre-pulse phase. A cathodic pre-pulse phase and an anodic stimulation phase induce the perception of a circular (punctuate) shape, and an anodic pre-pulse phase and a cathodic stimulation phase induce the perception of an elongated (streak) shape.  
         [0008]     The pre-pulse phase has a magnitude that is below a threshold value at which ganglion nerve cells are activated to pass a signal (sub-threshold magnitude), and has a duration that is sufficient to increase the excitability of the selected type of ganglion nerve cell. An anodic pre-pulse phase applied at a sub-threshold magnitude and for a duration that is sufficient to increase the excitability of a bending region of an axon helps to induce the perception of a circular shape in response to the stimulation phase. Applying a cathodic pre-pulse phase at a sub-threshold magnitude and for a duration sufficient to increase the excitability of the passing region of an axon helps to induce the perception of an elongated shape in response to the stimulation phase. Typically, the stimulation pulse phase has a supra-threshold magnitude that balances the charge injected by the pre-pulse phase. The pre-pulse phase typically lasts for no more than about one millisecond. The duration of the stimulation pulse phase to the duration of the pre-pulse phase is approximately 10:1.  
         [0009]     Another method includes the steps of placing an electrode adjacent a retinal ganglion cell layer and effecting a change in the excitability of cells in the ganglion cell layer by selectively applying a biphasic asymmetrical waveform. The waveform has a pre-pulse phase having a first polarity, a first amplitude and a first duration. The first amplitude and first duration together define a pre-pulse charge having a first magnitude and the first polarity. The waveform also includes a stimulation-pulse phase following the pre-pulse phase, the stimulation-pulse phase having a second polarity opposite the first polarity, a second amplitude and second duration less than the first duration. The second amplitude and second duration together define a stimulation charge having the second polarity and a second magnitude that equals the first magnitude.  
         [0010]     A visual neuroprosthesis for electrically stimulating a retina of an eye to induce visual perception generally includes an electrode positionable near a ganglion cell layer of the retina of an eye, and a waveform generator capable of generating a waveform for selectively stimulating either bending axons to induce the perception of a circular image or passing axons to induce the perception of a streak image.  
         [0011]     U.S. Pat. No. 6,560,490, which includes work performed by an inventor of the present invention in the field of central nervous system (CNS) stimulation, is hereby incorporated herein by reference. In contrast to this earlier patent, the present application recognizes the applicability of electrical stimulation to the eye and applies a biphasic asymmetrical waveform to produce selectively different types of perception, i.e., either spots or streaks, based on the polarity, duration and magnitude of the pre-pulse phase and the stimulation phase.  
         [0012]     The foregoing and other features of the invention are shown in the drawings and particularly pointed out in the claims. The following description and annexed drawings set forth detail one or more illustrated embodiments of the invention, as being indicative, however, but one or a few of the various ways in which the principles of the invention might be employed. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0013]      FIG. 1  is a schematic cross-sectional view of an eye.  
         [0014]      FIG. 2  is an enlarged schematic view of a portion of a retina portion of the eye.  
         [0015]      FIG. 3  is a schematic drawing of a neuroprosthesis that can be used in accordance with the present invention.  
         [0016]      FIG. 4  is a schematic representation of an electrode and retinal ganglion cells.  
         [0017]      FIGS. 5 and 6  are schematic illustrations of biphasic asymmetrical waveforms and the resulting visual perception induced thereby. 
     
    
     DETAILED DESCRIPTION  
       [0018]     Referring now to the drawings in detail, and initially to  FIGS. 1-4 , a visual neuroprosthesis  100  for electrically stimulating a retina  22  of an eye  10  to induce visual perception includes an electrode  102  that can be positioned near a ganglion cell layer  40  of a retina  22 , and a waveform generator  104  connected to the electrode  102 . The threshold for excitation of a retinal ganglion cell  30  with an epiretinal electrode generally is lower when the electrode is located in proximity to the characteristic 90° bend (bending region)  40  in the axon of the ganglion cell  30  than when it is located over a passing axon of the nerve fiber layer  44 . The waveform generator  104  is capable of generating a waveform in the electrode  102  for selectively stimulating either bending axons  40  of the retinal ganglion cell layer  42  to induce the perception of a circular image (punctuate, spot) or passing axons of the nerve fiber layer  44  to induce the perception of an elongate image (pie, streak, teardrop).  
         [0019]     The waveform generator  104  is configured or programmed to output biphasic, asymmetric waveforms to induce the desired visual perception. The waveform generator  104  also may have a ground or reference potential  106 , and may be implanted into a body or remotely located outside the body. The hardware of such a generator is conventional. Likewise, the electrode  102  may be a conventional electrode, such as a metal microelectrode or a multiple-contact electrode that can be placed adjacent the eye, including on the eye.  
         [0020]     A method for electrically stimulating a retina of an eye, using the aforementioned waveform generator  104  and electrode  102 , for example, may be performed to selectively induce visual perception of either an elongate image (sometimes referred to as a streak phosphene) or a spot image (sometimes referred to as a punctuate phosphene).  
         [0021]     The method includes the steps of placing an electrode  102  adjacent an eye, particularly near a retinal ganglion cell layer  42 , and effecting a change in the excitability of the cells  30  in the ganglion cell layer  42  or the nerve fiber layer  44 . After effecting the change in the excitability, the method includes inducing visual perception.  
         [0022]     The effecting and inducing steps are performed by selectively applying a biphasic asymmetrical waveform. The waveform has a relatively long duration and relatively low amplitude (sub-threshold) pre-pulse phase of a first polarity, and a relatively short duration and relatively high amplitude (supra-threshold) stimulation pulse phase of a second polarity opposite the first polarity. Further, an interphase delay may be introduced between the delivery of the pre-pulse phase and stimulation phase of the waveform. To preserve charge-balancing, the charge delivered by the pre-pulse phase is equal in magnitude and opposite in polarity relative to the charge delivered by the stimulation pulse phase.  
         [0023]     As shown in  FIG. 5 , a cathodic (positive) pre-pulse phase  110  and an anodic (negative) stimulation phase  112  following the pre-pulse phase  110  have been found to increase the excitation of a passing region of an axon in a nerve fiber layer  44  and to induce the perception of a circular or spot shape  114 . The same pre-pulse phase  110  of the waveform that increases the susceptibility of the passing region of the axon to stimulation decreases the susceptibility of a bending region  40  of an axon to excitation by the subsequent stimulation pulse phase  112  of the waveform. The opposite also applies when applying an anodic pre-pulse phase followed by a cathodic stimulation phase.  
         [0024]     Referring now to  FIG. 6 , an anodic pre-pulse phase  120  and a cathodic stimulation phase  122  increase the excitation of a bending region  40  of an axon and induce the perception of an elongate or streak shape  124 .  
         [0025]     The threshold for ganglion cell stimulation is the point at which the electrical pulse generates propagating action potentials in the axon. The stimulation threshold generally is lower when the electrode  102  is located in proximity to the characteristic ninety degree bend  40  in the axon than when it is located over a passing axon of the nerve fiber layer  44 . The stimulation pulse phase typically has a magnitude that balances the charge injected by the pre-pulse phase, and generally has a duration of no more than about one millisecond. The pulse width typically is about fifty microseconds to about five hundred microseconds. And the duration of the stimulation pulse phase to the duration of the pre-pulse phase is approximately 10:1.  
         [0026]     This approach may be applied across multiple electrodes, which may be contained within an electrode array, to produce multiple phosphenes (spots and streaks) and the perception of an image. Different waveforms (polarity, duration, intensity) would be delivered selectively to different electrodes within the array to produce the desired set of phosphenes and thereby the desired image.  
         [0027]     Exemplary stimulus waveforms are shown and described in U.S. Pat. No. 6,560,490, which is incorporated herein by reference. In addition to the aforementioned patent, C. C. McIntyre and W. M. Grill, “Selective Microstimulation of Central Nervous System Neurons,”  Annals of Biomedical Engineering  vol. 28, pp. 219-233, 2000, is hereby incorporated herein by reference.  
         [0028]     Although the invention has been shown and described with respect to certain preferred embodiments, equivalent alterations and modifications will occur to others skilled in the art upon reading and understanding the specification and the annexed drawings. In particular regard to the various functions performed by the above described integers (components, assemblies, devices, compositions, etc.), the terms (including a reference to “means”) used to describe such integers are intended to correspond, unless otherwise indicated, to any integer which performs the specified function of the described integer (i.e. that is functionally equivalent), even though not structurally equivalent to the disclosed structure which performs the function in the herein illustrated exemplary embodiment or embodiments of the invention. In addition, while a particular feature of the invention may have been described above with respect to only one of several illustrated embodiments, such feature can be combined with one or more other features of the other embodiments, as may be desired and advantageous for any given or particular application.