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

May combine two claims.

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.

“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.”

May combine two claims.

Stimulus frequency had no significant effect on phosphene shape in participants 1 and 2, but strongly (β > .3, r > .6) and significantly (p < .001) modulated phosphene perimeter, major axis length, and minor axis length in Participant 3.

“Stimulus frequency had no significant effect on phosphene shape in participants 1 and 2, but strongly (β > .3, r > .6) and significantly (p < .001) modulated phosphene perimeter, major axis length, and minor axis length in Participant 3.”

May combine two claims.

In a linear mixed-effects model across all participants, larger stimulus amplitudes tended to elicit larger (p < .001) and 'blobbier' phosphenes (by means of increased minor axis length; p < .001).

“This analysis revealed that larger stimulus amplitudes tended to elicit larger (p < .001) and ‘blobbier’ phosphenes (by means of increased minor axis length; p < .001).”

May combine two claims.

Single-electrode stimulation reliably elicited phosphenes in all three participants, who reported seeing a single phosphene on 86.8% of trials, two phosphenes on 13.0% of trials, and three or more phosphenes on the remaining trials.

“Single-electrode stimulation reliably elicited phosphenes in all three participants, who reported seeing a single phosphene on 86.8% of trials, two phosphenes on 13.0% of trials, and three or more phosphenes on the remaining trials.”

May combine two claims.

When two electrodes were stimulated simultaneously, participants reported seeing a single phosphene on 53.1% of trials, two phosphenes on 43.4% of trials, and three or more phosphenes on the remaining trials.

“When two electrodes were stimulated simultaneously, participants reported seeing a single phosphene on 53.1% of trials, two phosphenes on 43.4% of trials, and three or more phosphenes on the remaining trials.”

May combine two claims.

Phosphenes located close to the center of vision did not noticeably change in shape with frequency, while more eccentric phosphenes changed shape (e.g., blobs at 6 Hz to rectangles at 60 Hz for Participant 1; short streaks at 6 Hz to orders-of-magnitude longer arcs at 60 Hz for participant 3).

“Whereas phosphenes that were located close to the center of vision (denoted by in figure 6) did not noticeably change in shape, more eccentric phosphenes turned from blobs at 6 Hz to rectangles at 60 Hz (Participant 1), or from short streaks at 6 Hz to orders-of-magnitude longer arcs at 60 Hz (participant 3).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Phosphene shape greatly varied across participants and electrodes, but was relatively consistent across trials of a single electrode.

“Consistent with the literature on single-electrode phosphene drawings (Nanduri et al 2008, Luo et al 2016, Beyeler et al 2019b), phosphene shape greatly varied across participants and electrodes, but was relatively consistent across trials of a single electrode.”

• cites Nanduri et al 2008 sourceNot checked yet

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• cites Luo et al 2016Not checked yet

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• cites Beyeler et al 2019bNot checked yet

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May combine two claims.

Stimulus amplitude strongly affected phosphene area in two out of three participants (p < .001) and minor axis length (p < .001), suggesting that phosphenes tended to get larger with increasing amplitude.

“Consistent with Nanduri et al (2012), we found that stimulus amplitude strongly affected phosphene area in two out of three participants (p < .001) and minor axis length (p < .001), suggesting that phosphenes tended to get larger with increasing amplitude.”

• cites Nanduri et al 2012 sourceNot checked yet

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May combine two claims.

For participant 1, more eccentric phosphenes tended to be more elongated (p < .001) but not necessarily larger.

“For participant 1, more eccentric phosphenes tended to be more elongated (p < .001) but not necessarily larger.”

May combine two claims.

Electrode-retina distances were non-zero only in participant 1, where larger ERDs led to smaller phosphenes (p < .05).

“Electrode-retina distances (labeled ‘ERD’ in table 4) were non-zero only in participant 1, where larger ERDs led to smaller phosphenes (p < .05).”

May combine two claims.

Participant 1 mostly drew blobs and wedges, which grew larger as the stimulus amplitude was increased.

“Whereas participant 1 mostly drew blobs and wedges, which grew larger as the stimulus amplitude was increased, participant 2 reported seeing exclusively lines and arcs, which got longer with increasing amplitude.”

May combine two claims.

Participant 2 reported seeing exclusively lines and arcs, which got longer with increasing amplitude.

“Whereas participant 1 mostly drew blobs and wedges, which grew larger as the stimulus amplitude was increased, participant 2 reported seeing exclusively lines and arcs, which got longer with increasing amplitude.”

May combine two claims.

Models relying on between-axon distance (Model B) significantly outperformed models relying on along-axon distance (Model A) in two out of three participants, as well as in the all-participant analysis.

“As is evident in table 8, we found strong evidence that models relying on between-axon distance (Model B) significantly outperformed models relying on along-axon distance (Model A) in two out of three participants, as well as in the all-participant analysis.”

• AssumptionRests on an assumption: The participants' drawings accurately represent their perceived phosphenes.

Probably not a substantial claim: may not pass S3 (load-bearing).

A simple computational model can predict phosphene shape across a wide range of stimulus parameters.

“In addition, phosphene appearance varies systematically with stimulus amplitude and frequency (Horsager et al 2009, Nanduri et al 2012, Sinclair et al 2016) to the extent that a simple computational model can predict phosphene shape across a wide range of stimulus parameters (Granley and Beyeler 2021).”

• cites Granley and Beyeler 2021Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Electric crosstalk between electrodes is important in determining the response to simultaneous stimulation of multiple electrodes.

“For instance, Wilke et al (2011b) highlighted the importance of electric crosstalk between electrodes in determining the response to simultaneous stimulation of multiple electrodes.”

• cites Wilke et al 2011bNot checked yet

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Classified as probably not a substantial claim.

Elicited percepts are affected by other stimulating electrodes even after temporally staggering pulses to remove electric field interactions.

“Horsager et al (2011) found that elicited percepts were affected by other stimulating electrodes (even after temporally staggering pulses to remove electric field interactions) and demonstrated a linear combination of threshold currents for simultaneous stimulation.”

• cites Horsager et al 2011 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Single-electrode phosphenes elicited by stimulating a single Argus II electrode have a distinctive shape that is relatively consistent over time.

“A series of papers demonstrated that phosphenes elicited by stimulating a single Argus II electrode have a distinctive shape that is relatively consistent over time (Nanduri et al 2008, Luo et al 2016, Beyeler et al 2019b).”

• cites Nanduri et al 2008 sourceNot checked yet

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• cites Luo et al 2016Not checked yet

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• cites Beyeler et al 2019bNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Data from sessions where the false alarm rate exceeded 20% were deemed unreliable and excluded from the analysis.

“Data from sessions where the false alarm rate exceeded 20% were deemed unreliable and excluded from the analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Early research suggested that repeated paired stimulation resulted in reproducible phosphenes, with participants perceiving 'similar' phosphenes on 66% of trials.

“Early research suggested that repeated paired stimulation resulted in reproducible phosphenes as participants perceived ‘similar’ phosphenes on 66% of trials (Rizzo et al 2003).”

• cites Rizzo et al 2003 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Bipolar electrode configurations produced percepts similar in appearance to the summation of phosphenes elicited from the two individual electrodes using a monopolar configuration.

“Using a suprachoroidal prosthesis, Sinclair et al (2016) found that bipolar electrode configurations produced percepts that were similar in appearance to the summation of the phosphenes that were elicited from the two individual electrodes using a monopolar configuration.”

• cites Sinclair et al 2016 sourceNot checked yet

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Classified as probably not a substantial claim.

A control task was conducted where participants felt six different tactile shapes and drew them on a touchscreen to determine each participant's drawing error and bias.

“Since the validity and reliability of the experiment relied on the ability of our participants to accurately draw the perceived phosphenes, a control task was conducted where participants were asked to feel six different tactile shapes made of felt with a cardboard background, and then draw them on a touchscreen (Beyeler et al 2019b).”

• cites Beyeler et al 2019bNot checked yet

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May combine two claims.

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 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.”

Classified as probably not a substantial claim.

Recent computational models of prosthetic vision assume linear summation of phosphenes.

“Moreover, recent computational models of prosthetic vision assume linear summation of phosphenes (Spencer et al 2019, de Ruyter van Steveninck et al 2022), but this has yet to be demonstrated empirically.”

• cites Spencer et al 2019 sourceNot checked yet

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• cites de Ruyter van Steveninck et al 2022 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

All paired-electrode drawings were collected at 20 Hz, so stimulus frequency could not be included in the analysis.

“Unfortunately, all paired-electrode drawings were collected at 20 Hz, thus stimulus frequency could not be included in the analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study was approved by the Institutional Review Board at each participant's clinical site and was conducted under the tenets of the Declaration of Helsinki.

“The study was approved by the Institutional Review Board (IRB) at each participant’s clinical site and was conducted under the tenets of the Declaration of Helsinki.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All residuals were verified for normality using Quantile-Quantile plots.

“All residuals were verified for normality using Quantile-Quantile plots (see figures E1 and E2).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Informed consent was obtained from the participants after explanation of the nature and possible consequences of the study.

“Informed consent was obtained from the participants after explanation of the nature and possible consequences of the study.”

May combine two claims.

The β values suggest that phosphenes elicited by paired-electrode stimulation appeared larger than the average of their single-electrode counterparts, but smaller than their sum.

“Across all participants, shape descriptors tended to sum linearly, with the β values suggesting that phosphenes elicited by paired-electrode stimulation appeared larger than the average of their single-electrode counterparts, but smaller than their sum.”

• AssumptionRests on an assumption: The participants' drawings accurately represent their perceived phosphenes.

Classified as probably not a substantial claim.

More recent studies indicated that phosphenes tend to merge in nontrivial ways.

“But more recent studies indicated that phosphenes tend to merge in nontrivial ways.”

Probably not a substantial claim: may not pass S1 (asserted).

The axon map model predicts that the probability of seeing two phosphenes should increase with increasing distance between their axon bundles (as opposed to distance on the retinal surface).

“Specifically, the axon map model (Beyeler et al 2019b, Granley and Beyeler 2021) predicts that the probability of seeing two phosphenes should increase with increasing distance between their axon bundles (as opposed to distance on the retinal surface), but no empirical studies have validated this hypothesis.”

• cites Beyeler et al 2019bNot checked yet

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• cites Granley and Beyeler 2021Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Phosphene appearance varies systematically with stimulus amplitude and frequency.

“In addition, phosphene appearance varies systematically with stimulus amplitude and frequency (Horsager et al 2009, Nanduri et al 2012, Sinclair et al 2016) to the extent that a simple computational model can predict phosphene shape across a wide range of stimulus parameters (Granley and Beyeler 2021).”

• cites Horsager et al 2009 sourceNot checked yet

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• cites Nanduri et al 2012 sourceNot checked yet

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• cites Sinclair et al 2016 sourceNot checked yet

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Classified as probably not a substantial claim. May combine two claims.

Sequential stimulation does not always lead to perceptually intelligible forms or objects; participants often can only trace an outline of the perceived shape, and their interpretation relies heavily on this basic outline.

“However, sequential stimulation does not always lead to perceptually intelligible forms or objects; often participants are only able to trace an outline of the perceived shape, and their interpretation of the shape relies heavily on this basic outline (Christie et al 2022).”

• cites Christie et al 2022 sourceNot checked yet

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Classified as probably not a substantial claim.

There is a linear combination of threshold currents for simultaneous stimulation.

“Horsager et al (2011) found that elicited percepts were affected by other stimulating electrodes (even after temporally staggering pulses to remove electric field interactions) and demonstrated a linear combination of threshold currents for simultaneous stimulation.”

• cites Horsager et al 2011 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Data points that fell more than 2.5 standard deviations away from the mean were considered outliers and were removed from all further analyses.

“Data points that fell more than 2.5 standard deviations away from the mean were considered outliers and were removed from all further analyses.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Several factors might limit the spatial resolution of prosthetic vision, including retinal damage, electrode-retina distance, and inadvertent stimulation of nerve fiber bundles.

“Most recently, Yücel et al (2022) identified several factors that might limit the spatial resolution of prosthetic vision, which included retinal damage, electrode-retina distance, and the inadvertent stimulation of nerve fiber bundles.”

• cites Yücel et al 2022 sourceNot checked yet

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Classified as probably not a substantial claim.

Phosphene shape depends strongly on the retinal location of the stimulating electrode, predominantly elongated along the trajectory of the underlying nerve fiber bundle.

“Phosphene shape has been shown to depend strongly on the retinal location of the stimulating electrode, predominantly elongated along the trajectory of the underlying nerve fiber bundle (Rizzo et al 2003, Beyeler et al 2019b).”

• cites Rizzo et al 2003 sourceNot checked yet

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• cites Beyeler et al 2019bNot checked yet

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Classified as probably not a substantial claim.

The probability of perceiving two distinct phosphenes increases with inter-electrode distance.

“Yücel et al (2022) previously demonstrated that the probability of perceiving two distinct phosphenes increases with inter-electrode distance.”

• cites Yücel et al (2022) sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Phosphene orientation was previously shown to depend mostly on the retinal location of the stimulating electrode and was thus excluded from the main analysis.

“Phosphene orientation was previously shown to depend mostly on the retinal location of the stimulating electrode (Beyeler et al 2019b) and was thus excluded from the main analysis.”

• cites Beyeler et al 2019bNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

During the preliminary stage, experimenting with a number of similar formulations of splitting the two components gave similar results.

“During the preliminary stage of this study, we experimented with a number of similar formulations of splitting these two components, and all of them gave similar results.”

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

Electrodes that stimulate the same axon bundle (i.e. with zero between-axon distance) are redundant and should therefore be avoided.

“In other words, electrodes that stimulate the same axon bundle (i.e. with zero between-axon distance) are redundant and should therefore be avoided (Beyeler et al 2017b).”

• cites Beyeler et al 2017bNot checked yet

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• AssumptionRests on an assumption: The participants' drawings accurately represent their perceived phosphenes.

Probably not a substantial claim: may not pass S1 (asserted).

Under the axon map model, paired-electrode stimulation with a short between-axon distance should activate the same nerve fiber bundles and lead to a single phosphene, even if the electrodes are far apart on the retina.

“Under this model, paired-electrode stimulation with a short between-axon distance should activate the same nerve fiber bundles and thus lead to a single phosphene, even though the two electrodes may be far apart on the retina.”

• cites Beyeler et al 2019bNot checked yet

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Classified as probably not a substantial claim.

The axon map model predicts that participants should be more likely to see two distinct phosphenes as the distance between two nerve fiber bundles increases ('between-axon' distance).

“However, the axon map model (Beyeler et al 2019b) makes a more nuanced prediction: participants should be more likely to see two distinct phosphenes as the distance between two nerve fiber bundles increases (‘between-axon’ distance; as opposed to distance on the retinal surface; see Methods).”

• cites Beyeler et al 2019bNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

In suprachoroidal prostheses, phosphenes tend to appear thicker or rounder as the stimulation rate increases.

“This relationship between stimulus frequency and phosphene size partially agrees with data from suprachoroidal prostheses, where phosphenes tend to appear thicker or rounder as the stimulation rate increases (Sinclair et al 2016).”

• cites Sinclair et al 2016 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

More eccentric phosphenes may be elongated along the trajectory of the underlying nerve fiber bundles.

“While more eccentric phosphenes may be elongated along the trajectory of the underlying nerve fiber bundles (Beyeler et al 2019b), the increased size may be a consequence of ganglion cell receptive fields increasing with eccentricity (Curcio and Allen 1990).”

• cites Beyeler et al 2019bNot checked yet

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• AssumptionRests on an assumption: The participants' drawings accurately represent their perceived phosphenes.

Probably not a substantial claim: may not pass S3 (load-bearing).

Significant effects were corrected for multiple comparisons using the Bonferroni method.

“Significant effects are marked in bold (corrected for multiple comparisons using the Bonferroni method).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Our linear analyses cannot identify nonlinear predictors of phosphene shape.

“Despite the ability of our work to highlight important factors that guide the appearance of phosphenes elicited by retinal implants, it is important to note that our linear analyses cannot identify nonlinear predictors of phosphene shape.”

Classified as probably not a substantial claim.

Many computational models of prosthetic vision assume a linear relationship between stimulus parameters (e.g. amplitude) and phosphene appearance (e.g. brightness).

“Many computational models of prosthetic vision (Chen et al 2009, Perez-Yus et al 2017, Sanchez-Garcia et al 2019, Granley and Beyeler 2021) assume a linear relationship between stimulus parameters (e.g. amplitude) and phosphene appearance (e.g. brightness).”

• cites Chen et al 2009 sourceNot checked yet

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• cites Perez-Yus et al 2017 sourceNot checked yet

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• cites Sanchez-Garcia et al 2019 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Our analyses are currently limited to single- and paired-electrode stimulation in three participants.

“In addition, due to data availability, our analyses are currently limited to single- and paired-electrode stimulation in three participants.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Most phosphene models assume a constant scaling factor between retinal and visual field coordinates.

“Indeed, most phosphene models assume a constant scaling factor between retinal and visual field coordinates (Horsager et al 2009, Nanduri 2011, Beyeler et al 2019b).”

• cites Horsager et al 2009 sourceNot checked yet

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• cites Nanduri 2011Not checked yet

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• cites Beyeler et al 2019bNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Multiple phosphene patterns may not automatically group into perceptually intelligible objects.

“However, it should be noted that multiple phosphene patterns may not automatically group into perceptually intelligible objects (Stingl et al 2015, Shivdasani et al 2017, Christie et al 2022).”

• cites Stingl et al 2015 sourceNot checked yet

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• cites Shivdasani et al 2017Not checked yet

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• cites Christie et al 2022 sourceNot checked yet

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