Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

Objective.Retinal implants use electrical stimulation to elicit perceived flashes of light ('phosphenes'). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation.Approach.We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ('between-axon') and along axon bundles ('along-axon'). Statistical analyses were conducted using linear regression and partial correlation analysis.Main results.Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants.Significance.The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.

Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

Purpose: Retinal implants use electrical stimulation to elicit perceived flashes of light ("phosphenes"). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation. Methods: We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ("between-axon") and along axon bundles ("along-axon"). Statistical analyses were conducted using linear regression and partial correlation analysis. Results: Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants. Conclusions: The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The notable impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.

A model of ganglion axon pathways accounts for percepts elicited by retinal implants.

Degenerative retinal diseases such as retinitis pigmentosa and macular degeneration cause irreversible vision loss in more than 10 million people worldwide. Retinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts ('phosphenes'). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products Inc.) to draw electrically elicited percepts on a touchscreen. Using ophthalmic fundus imaging and computational modeling, we show that elicited percepts can be accurately predicted by the topographic organization of optic nerve fiber bundles in each subject's retina, successfully replicating visual percepts ranging from 'blobs' to oriented 'streaks' and 'wedges' depending on the retinal location of the stimulating electrode. This provides the first evidence that activation of passing axon fibers accounts for the rich repertoire of phosphene shape commonly reported in psychophysical experiments, which can severely distort the quality of the generated visual experience. Overall our findings argue for more detailed modeling of biological detail across neural engineering applications.

Inaccuracy of Urine Output Measurements due to Urinary Retention in Catheterized Patients in the Burn ICU.

Electronic urinary output monitors, intended to provide urine output information to guide fluid therapy during burn resuscitation, can be inaccurate because of airlocks causing urine retention in the drainage tube and bladder. In this study, the authors explore the effects of airlock formation on urine output measured using an electronic urinary output monitor connected to either a standard commercial drainage tubing system or a drainage tubing system with an automated airlock clearing mechanism. In a multicenter study in the burn intensive care unit, urine output was compared between 10 control patients with a standard commercial drainage tubing system and 10 test patients with a novel automated airlock clearing drainage tubing system. The comparison was focused on identifying the number and magnitude of surges in urinary output because of airlocks and associated periods of false oliguria. In the control group, 5 of 10 (50%) patients had drainage line flow impediments from 8 airlocks. In addition, control patients experienced six associated periods of false oliguria. Airlock surge volumes ranged from 50 to 329 ml, and false oliguria duration ranged from 39.4 to 185.2 minutes. In the test group, 0 of 10 (0%) patients had drainage line impediments from airlocks (P < .01), and hence, there were no periods of false oliguria. Airlocks and associated periods of false oliguria occur with standard commercial drainage tubing and are eliminated using an automated airlock clearing drainage tube. Electronic urinary output monitoring with self-clearing drainage has the potential to improve tracking of real-time urine output and decrease caregiver workload.

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration.

Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, with each electrode acting as a pixel. Unintended stimulation of retinal ganglion cell axons causes patients to see large oblong shapes of light, rather than focal spots, making it difficult to perceive forms. To address this problem, we performed calcium imaging in isolated retinas and mapped the patterns of cells activated by different electrical stimulation protocols. We found that pulse durations two orders of magnitude longer than those typically used in existing implants stimulated inner retinal neurons while avoiding activation of ganglion cell axons, thus confining retinal responses to the site of the electrode. Multielectrode stimulation with 25-ms pulses can pattern letters on the retina corresponding to a Snellen acuity of 20/312. We validated our findings in a patient with an implanted epiretinal prosthesis by demonstrating that 25-ms pulses evoke focal spots of light.

Frequency and amplitude modulation have different effects on the percepts elicited by retinal stimulation.

PURPOSE: In an effort to restore functional form vision, epiretinal prostheses that elicit percepts by directly stimulating remaining retinal circuitry were implanted in human subjects with advanced retinitis pigmentosa RP). In this study, manipulating pulse train frequency and amplitude had different effects on the size and brightness of phosphene appearance. METHODS: Experiments were performed on a single subject with severe RP (implanted with a 16-channel epiretinal prosthesis in 2004) on nine individual electrodes. Psychophysical techniques were used to measure both the brightness and size of phosphenes when the biphasic pulse train was varied by either modulating the current amplitude (with constant frequency) or the stimulating frequency (with constant current amplitude). RESULTS: Increasing stimulation frequency always increased brightness, while having a smaller effect on the size of elicited phosphenes. In contrast, increasing stimulation amplitude generally increased both the size and brightness of phosphenes. These experimental findings can be explained by using a simple computational model based on previous psychophysical work and the expected spatial spread of current from a disc electrode. CONCLUSIONS: Given that amplitude and frequency have separable effects on percept size, these findings suggest that frequency modulation improves the encoding of a wide range of brightness levels without a loss of spatial resolution. Future retinal prosthesis designs could benefit from having the flexibility to manipulate pulse train amplitude and frequency independently (clinicaltrials.gov number, NCT00279500).