Sequential epiretinal stimulation improves discrimination in simple shape discrimination tasks only
Open accessPublished version of a preprint
Abstract
Objective . Electrical stimulation of the retina can elicit flashes of light called phosphenes, which can be used to restore rudimentary vision for people with blindness. Functional sight requires stimulation of multiple electrodes to create patterned vision, but phosphenes tend to merge together in an uninterpretable way. Sequentially stimulating electrodes in human visual cortex has recently demonstrated that shapes could be ‘drawn’ with better perceptual resolution relative to simultaneous stimulation. The goal of this study was to evaluate if sequential stimulation would also form clearer shapes when the retina is the neural target. Approach . Two human participants with retinitis pigmentosa who had Argus ® II epiretinal prostheses participated in this study. We evaluated different temporal parameters for sequential stimulation and performed phosphene shape mapping and forced choice discrimination tasks. For the discrimination tasks, performance was compared between stimulating electrodes simultaneously versus sequentially. Main results . Phosphenes elicited by different electrodes were reported as vastly different shapes. For sequential stimulation, the optimal pulse train duration was 200 ms when stimulating at 20 Hz and the optimal gap interval was tied between 0 and 50 ms. Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3–4 electrodes, but not in more complex discrimination tasks involving ≥5 electrodes. The efficacy of sequential stimulation depended strongly on selecting electrodes that elicited phosphenes with similar shapes and sizes. Significance . An epiretinal prosthesis can produce coherent simple shapes with a sequential stimulation paradigm, which can be used as rudimentary visual feedback. However, success in creating more complex shapes, such as letters of the alphabet, is still limited. Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as novel object identification.
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Written from the paper’s full text.
TL;DR
Sequential epiretinal stimulation improved discrimination over simultaneous stimulation for simple shapes but not for more complex letter shapes. It helped prevent phosphenes from merging, yet its benefit declined as more electrodes were used and as phosphene shape/size variability increased.
Key findings
- In two Argus II participants with retinitis pigmentosa, sequential stimulation significantly improved arrow-direction discrimination: both were correct on 19/20 trials versus 4/20 for S1 and 8/20 for S2 with simultaneous stimulation (p<0.001 for both); simultaneous performance was not better than chance.
- For square-size discrimination, sequential stimulation yielded 27/36 correct for both participants, significantly above 50% chance (p=0.001); the improvement over simultaneous stimulation was statistically significant only for S1 (p=0.01). Simultaneous stimulation was 17/36 for S1 (not above chance) and 25/36 for S2 (p=0.001).
- For complex letter discrimination, only S2 completed the task and only with sequential stimulation: 34/80 correct (significantly above 25% chance, p<0.001), with 40% for K, 35% for O, 50% for V, and 45% for Z.
- Optimal sequential parameters: 200 ms train duration at 20 Hz gave highest direction-classification accuracy (92% correct); gap interval was tied between 0 and 50 ms, with 78%–81% correct across gap conditions.
Methods
- Two human participants (83-year-old male S1, 71-year-old female S2) with retinitis pigmentosa and unilateral Argus II retinal prostheses participated; the protocol was approved by the Johns Hopkins Medicine Institutional Review Board.
- Phosphene shape mapping tested 25 electrodes per participant with 12 repetitions each; participants drew perceived phosphenes on a tablet. Pulse frequency was initially 20 Hz but lowered to 6 Hz due to rapid perceptual adaptation; train length was 200 ms. Shapes were quantified with MATLAB regionprops for area and elongation, with ANOVAs, linear regression, and resampling analyses.
- Forced-choice tasks compared sequential versus simultaneous stimulation. Parameter evaluation varied train durations (50, 100, 150, 200 ms) and gaps (0, 50, 100 ms) over 48 trials per participant. Size discrimination used four electrodes and 36 trials per paradigm; simple arrow discrimination used three electrodes and 20 trials per paradigm; complex letter discrimination used 5–8 electrodes to form Sloan letters O, V, K, Z, with 20 trials per paradigm. Statistical tests included tests of proportions.
Limitations
- Stated: only two Argus II recipients were tested, limiting generalizability; Argus II users are becoming rarer. The authors also note that phosphene shape/size differences made tasks difficult, that no control task quantified drawing accuracy, and that brightness differences, perceptual adaptation, gaze direction, and phosphene mislocalization may have influenced results.
- Evident from the text: the complex letter task was completed only by S2 and only under sequential stimulation, so no direct sequential-versus-simultaneous comparison was possible for letters. Trial counts were small (e.g., 20 trials per paradigm for arrow and letter tasks), and electrode selection for larger shapes was constrained because some electrodes fell outside the mapped set.
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- Findingown data
For participant S1, phosphene area and elongation differed significantly between electrodes (p<0.001).
“Phosphene area and elongation were significantly different between electrodes for participant S1 (p<0.001) but not S2 (Figure 3b,c).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
- Findingown data
Participant S1 could not initially perform the arrow task until electrodes with similar phosphene shapes and sizes were selected.
“Participant S1 could not originally perform this task until we selected electrodes that elicited similar phosphene shapes and sizes.”
Quote in the paperNot a substantial claim - Findingown data
When three electrodes were stimulated simultaneously and participants drew arrow shapes, the three phosphenes merged in an unpredictable way.
“When the participants were asked to draw the shapes of the arrows, the three phosphenes merged together in an unpredictable manner during simultaneous stimulation (Figure 5).”
Quote in the paperSubstantial claim - Findingcitation
Phosphene appearance varied greatly across electrodes and participants.
“The appearance of phosphenes was highly variable across electrodes and participants, which is consistent with prior studies (D. Nanduri et al. 2008; Beyeler et al. 2019; Luo et al. 2016).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Findingown data
In the arrow discrimination task, performance was significantly better with sequential than simultaneous stimulation for both participants (p<0.001).
“The participants’ performance on the arrow discrimination task was significantly better when using sequential compared to simultaneous stimulation paradigms (p<0.001 for both participants, Table 2).”
Quote in the paperSubstantial claim
- Findingown data
For participant S1, many electrodes produced similar phosphene shapes across trials.
“Many of participant S1’s electrodes elicited similar phosphene shapes across trials (Figure 2a).”
Quote in the paperNot a substantial claim - Findingown data
Sequential stimulation did not outperform simultaneous stimulation in more complex discrimination tasks involving 5 or more electrodes.
“Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3–4 electrodes, but not in more complex discrimination tasks involving 5+ electrodes.”
Quote in the paperSubstantial claim - Findingown data
When drawing their perceptions in the size task, participants reported four discrete phosphenes forming the square's corners only during sequential stimulation.
“When asked to draw what they perceived during sequential and simultaneous stimulation, the participants reported seeing four discrete phosphenes (forming the four “corners” of the square) during sequential stimulation only (Figure 4).”
Quote in the paperNot a substantial claim - Findingown data
For participant S1 only, detection threshold had a statistically significant positive relationship with phosphene area (p<0.001).
“For participant S1 only, there was a statistically significant positive relationship between detection threshold and phosphene area (p<0.001, Figure 3d).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
- Findingown data
Across the arrays, individual electrodes produced a wide range of phosphene shapes for each participant.
“We found that different electrodes within each participant’s array elicited a variety of different phosphene shapes.”
- Also stated in: § Main results: · plain
“Phosphenes elicited by different electrodes were reported as vastly different shapes.”
Quote in the paperSubstantial claim - Also stated in: § Main results: · plain
- Findingown data
In the size discrimination task with simultaneous stimulation, participant S2 correctly answered 25 of 36 trials, which was better than chance (p=0.001).
“and participant S2 got 25/36 trials correct, which was better than chance (p=0.001).”
Quote in the paperNot a substantial claim - Findingown data
Across both participants, only seven electrodes produced two or more phosphenes in at least half of the trials.
“Between the two participants, just seven electrodes produced 2+ phosphenes in at least 50% of trials.”
Quote in the paperNot a substantial claim - Findingown data
The variability in area and elongation was not more consistent within electrodes than across electrodes for either participant (p>0.05).
“The variability in area and elongation was not more consistent within versus across electrodes for either participant (p>0.05).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
- Findingown data
For participant S2, 18 out of 25 electrodes elicited at least three common geometric shapes.
“18/25 electrodes elicited at least three common geometric shapes, such as triangles, rectangles, ovals, trapezoids, and half circles.”
Quote in the paperNot a substantial claim - Findingown data
For participant S1, simultaneous stimulation with a right-pointing arrow caused two phosphenes to merge into a single larger phosphene on the right side of his visual field.
“When participant S1 was presented with a right-pointing arrow using simultaneous stimulation, two phosphenes merged into one larger phosphene on the right-hand side of his visual field.”
Quote in the paperNot a substantial claim - Findingnone given
In every case, sequential stimulation helped prevent multiple phosphenes from merging into a single uninterpretable phosphene.
“In all cases, sequential stimulation helped to prevent multiple phosphenes from merging into one uninterpretable phosphene.”
Quote in the paperSubstantial claim - Findingcitation
Sometimes electrodes did not produce phosphenes in the expected visual field location, even after accounting for the electrode array angle on the retina.
“Moreover, sometimes the electrodes did not elicit phosphenes in the expected location in the visual field, even when accounting for the angle of the electrode array on the retina.”
Quote in the paperNot a substantial claim - Findingown data
Even with sequential stimulation, participants did not always perceive the presented images as specific shapes.
“Additionally, even with sequential stimulation, the participants did not necessarily perceive the presented images as specific shapes.”
Quote in the paperNot a substantial claim - Findingreasoning
When more electrodes were used to create a more complex shape, it was hard to choose electrodes whose phosphenes were similar in size and shape.
“As additional electrodes were utilized to create a more complex shape, it was difficult to select electrodes that elicited phosphenes that were similar in size and shape.”
Quote in the paperSubstantial claim - Findingown data
Only a small number of electrodes produced phosphenes that looked like focal spots of light.
“Only a small cohort of electrodes elicited phosphenes that appeared as focal spots of light.”
Quote in the paperNot a substantial claim - Premisecitation
When multiple electrodes are stimulated simultaneously, phosphenes tend to merge together in complex ways.
“However, it is not typically that simple: when multiple electrodes are stimulated simultaneously, phosphenes tend to merge together in complex ways (Bosking et al. 2018; Rizzo et al. 2003; Horsager et al. 2011; Horsager, Greenberg, and Fine 2010; Wilke et al. 2011).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
The effectiveness of sequential stimulation depended strongly on choosing electrodes that produced phosphenes with similar shapes and sizes.
“Efficacy of sequential stimulation also depended strongly on selecting electrodes that elicited phosphenes with similar shapes and sizes.”
- Also stated in: § Simple shape discrimination task · plain
“Participant S1 could not originally perform this task until we selected electrodes that elicited similar phosphene shapes and sizes.”
Quote in the paperSubstantial claim - Also stated in: § Simple shape discrimination task · plain
- Interpretationown data
Creating more complex shapes, such as letters of the alphabet, remains limited.
“However, success in creating more complex shapes, such as letters of the alphabet, is still limited.”
Quote in the paperSubstantial claim - Premisecitation
The highest visual acuity achieved with the Argus II is only about 20/1260, which is dictated by the 550 μm electrode spacing.
“Moreover, the highest level of visual acuity achieved is only about 20/1260 (Humayun et al. 2012), which is dictated by the 550 μm electrode spacing.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Humayun et al. 2012 source
Not checked in the free run.
- Premisecitation
People with blindness using an Argus device improved on orientation and mobility tasks involving walking toward a high-contrast target and along a high-contrast line on the floor.
“When receiving visual input from an Argus device, people with blindness improved on orientation and mobility tasks based on walking towards a high-contrast target and walking along a high-contrast line on the floor (Humayun et al. 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Humayun et al. 2012 source
Not checked in the free run.
- Premisecitation
Argus II users also improved on object localization and motion discrimination tasks.
“Their performance also improved for object localization and motion discrimination tasks (Ahuja et al. 2011; Barry, Dagnelie, and Argus II Study Group 2012; Dorn et al. 2013; Dagnelie et al. 2017).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationown data
Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as object identification.
“Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as object identification.”
Quote in the paperSubstantial claim - Interpretationown data
Sequential stimulation outperformed simultaneous stimulation in simple discrimination tasks where shapes were made by stimulating 3-4 electrodes.
“Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3–4 electrodes, but not in more complex discrimination tasks involving 5+ electrodes.”
Quote in the paperSubstantial claim - Interpretationreasoning
The usefulness of sequential stimulation declined as the presented shape became more complex.
“However, the utility of sequential stimulation decreased as the complexity of the presented shape increased.”
Quote in the paperSubstantial claim - Interpretationreasoning
Mislocalization could turn a common geometric shape into an unrecognizable polygon, often requiring the authors to choose a different electrode set.
“Mislocalization could easily turn a common geometric shape into an unrecognizable polygon, which often required us to select a different set of electrodes.”
Quote in the paperNot a substantial claim - Interpretationcitation
The diversity of phosphene shapes is likely due to epiretinal stimulation activating both cell bodies beneath the electrode in the ganglion cell layer and axon bundles passing over the retinal surface in the nerve fiber layer toward the optic nerve.
“It is likely that there are a variety of phosphene shapes because stimulating through an epiretinal electrode not only activates the cell bodies that are just beneath the electrode in the ganglion cell layer, but it also activates axon bundles that pass over the surface of the retina in the nerve fiber layer while en route to the optic nerve (Beyeler et al. 2019; Esler et al. 2018; Tahayori et al.”
Quote in the paperNot a substantial claim0 of 3 sources checked
- May combine two claims. 32
- Classified as probably not a substantial claim. 13
May combine two claims.
Findingown dataParticipant S2 selected the correct alphabet letter in 34 of 80 trials, significantly above the 25% chance level (p<0.001).
“Participant S2 was able to correctly choose which alphabet letter was presented in 34/80 trials, which was significantly higher than the 25% chance (p<0.001), but not optimal for functional use.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFor participant S2, phosphene area and elongation did not differ significantly between electrodes.
“Phosphene area and elongation were significantly different between electrodes for participant S1 (p<0.001) but not S2 (Figure 3b,c).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
May combine two claims.
Findingown dataAcross the discrimination tasks, sequential stimulation was not consistently better than simultaneous stimulation, contrary to the authors' original hypothesis.
“Contrary to our original hypothesis, sequential stimulation did not consistently outperform simultaneous stimulation in these discrimination tasks.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataChanging the gap interval between electrodes produced only negligible performance differences, with accuracy ranging from 78% correct for 100 ms gaps to 81% correct for 0 or 50 ms gaps.
“There were only negligible differences in performance as a result of changing the gap intervals between electrodes: classification accuracy had a minimum of 78% correct for 100 ms gaps and a maximum of 81% correct for 0 or 50 ms gaps.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFor sequential stimulation at 20 Hz, the optimal pulse train duration was 200 ms and the optimal gap interval was tied between 0 and 50 ms.
“For sequential stimulation, the optimal pulse train duration was 200 ms when stimulating at 20 Hz and the optimal gap interval was tied between 0 and 50 ms.”
- Also stated in: § Sequential stimulation parameter evaluation · plain
“The best combination of stimulation parameters across both participants was a 200 ms train duration with either a 0 ms or 50 ms gap.”
Quote in the paperNot a substantial claim- Also stated in: § Sequential stimulation parameter evaluation · plain
May combine two claims.
Findingown dataFor participant S2, the phosphene shapes across trials were much less reliable and showed no clear patterns.
“The shapes across trials for participant S2 were far less reliable and did not follow any noticeable patterns (Figure 2b);”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the arrow task, both participants correctly identified direction in 19 of 20 trials with sequential stimulation, significantly above 50% chance (p<0.001).
“Both participants correctly identified arrow direction in 19/20 trials when using sequential stimulation, which was significantly higher than 50% chance (p<0.001).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the size discrimination task, both participants correctly answered 27 of 36 trials with sequential stimulation, significantly above 50% chance (p=0.001).
“Both participants achieved 27 out of 36 trials correct using sequential stimulation, which was significantly higher than 50% chance (p=0.001).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the square size discrimination task, performance was better with sequential than simultaneous stimulation, but the improvement was statistically significant only for participant S1 (p=0.01).
“The participants’ performance on the square size discrimination task was better when using sequential versus simultaneous stimulation paradigms (Table 2), but the improvement was statistically significant only for participant S1 (p=0.01).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOnly participant S2 completed the alphabet letter discrimination task, and she did so only with sequential stimulation.
“Only participant S2 was successfully able to complete the alphabet letter discrimination task, and only when using the sequential stimulation paradigm.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataParticipant S2's identification accuracy was 40% for K, 35% for O, 50% for V, and 45% for Z.
“She had a 40% accuracy for identifying letter ‘K,’ 35% for ‘O,’ 50% for ‘V,’ and 45% for ‘Z.’”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe shapes most often reported were circles, ovals, lines, and rectangles, although many were irregular.
“The most commonly elicited shapes were circles, ovals, lines, and rectangles, though many shapes were irregular.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataWhen three electrodes were stimulated sequentially, direction classification accuracy was highest at 92% correct with a 200 ms train duration per electrode and lowest at 71% correct with 100 ms.
“Classification accuracy of phosphene direction was highest (92% correct) when the train duration was set to 200 ms per electrode and lowest (71% correct) at 100 ms (Table 1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataWith simultaneous stimulation of the four electrodes in the size task, the phosphenes merged and participants reported only one or two large phosphenes.
“When the four electrodes were simultaneously stimulated, the phosphenes merged and participants reported seeing only one or two large phosphenes.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataParticipants most often reported one phosphene per electrode.
“It was most common for participants to report one phosphene per electrode (Figure 3a).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataParticipant S1 performed far below chance in the arrow task with simultaneous stimulation; when shown a right-pointing arrow, he reported left in 9 of 10 trials.
“In fact, participant S1’s accuracy was far below chance; when presented with a right-pointing arrow using simultaneous stimulation, he reported that it was pointing to the left in 9/10 trials.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataParticipants perceived three separate phosphenes under sequential stimulation but only one or two phosphenes when the same three electrodes were stimulated simultaneously.
“Though the participants saw three discrete phosphenes during the sequential stimulation paradigm, they reported seeing only 1–2 phosphenes when the three electrodes were simultaneously stimulated.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataParticipant S2 tended to have larger phosphene areas and lower detection thresholds than participant S1.
“Compared to participant S1, participant S2 tended to have larger phosphene areas and lower detection thresholds.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
May combine two claims.
Findingown dataIn the arrow task with simultaneous stimulation, participant S1 correctly answered 4 of 20 trials and participant S2 correctly answered 8 of 20 trials, neither significantly above chance (p>0.05).
“When using simultaneous stimulation, participant S1 achieved 4/20 trials correct and participant S2 achieved 8/20 trials correct, neither of which were significantly better than chance (p>0.05).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the size discrimination task with simultaneous stimulation, participant S1 correctly answered 17 of 36 trials, which was not significantly above chance.
“When performing the task using simultaneous stimulation, participant S1 got 17/36 trials correct, which was not significantly higher than chance”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe authors also found large trial-to-trial variability within individual electrodes, particularly for participant S2, which differed from prior studies.
“Unlike prior studies, we also noticed a substantial amount of variation between trials within a single electrode, especially for participant S2.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe composite image from several electrodes was sometimes intuitive or quickly understood, yet most cases needed practice trials, particularly for participant S1.
“The overall image created by multiple electrodes was sometimes intuitive or explained and quickly understood, but most instances required practice trials, especially for participant S1.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSequential stimulation performed better than simultaneous stimulation for size discrimination and simple shape discrimination, but not for complex shape discrimination.
“Sequential electrode stimulation outperformed simultaneous stimulation on the size discrimination task and the simple shape discrimination task, but not on the complex shape discrimination task.”
- Also stated in: § Conclusion · plain
“In conclusion, sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, but not in more complex discrimination tasks.”
Quote in the paperSubstantial claim- Also stated in: § Conclusion · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataStimulation produced irregular phosphene shapes as well as circles, ovals, lines, and rectangles.
“Stimulation elicited irregular shapes in addition to circles, ovals, lines, and rectangles.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataAn epiretinal prosthesis can produce coherent simple shapes using a sequential stimulation paradigm, which can serve as rudimentary visual feedback.
“An epiretinal prosthesis can produce coherent simple shapes with a sequential stimulation paradigm, which can be used as rudimentary visual feedback.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationArgus II devices allowed only about half of test subjects to reliably read large-print letters, and single-letter recognition took between six seconds and 3.5 minutes.
“For example, Argus II devices enabled only ~50% of test subjects to reliably read large-print letters (41° or ~22.6 cm letters viewed from 30 cm away), and single-letter recognition took anywhere between six seconds to 3.5 minutes (da Cruz et al. 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites da Cruz et al. 2013 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenSignificance levels in all statistical analyses were set to α=0.05, and Bonferroni corrections were applied.
“Significance levels in all statistical analyses were set to α=0.05 and Bonferroni corrections were applied.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe study protocol was approved by the Johns Hopkins Medicine Institutional Review Board, and informed consent was obtained before participation.
“The study protocol was approved by the Johns Hopkins Medicine Institutional Review Board. Informed consent was obtained prior to participation in research-related activities.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningParticipant S1 may have interpreted the larger merged phosphene as the arrow's wider base and the smaller phosphene as its narrower tip, which could explain his tendency to report right-pointing arrows as left-pointing during simultaneous trials.
“It is possible that participant S1 interpreted the larger phosphene as being the wider base of the arrow, and the smaller phosphene as the narrower tip of the arrow, and was inclined to report right-pointing arrows as left-pointing arrows during simultaneous stimulation trials.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationPhosphene shapes and sizes differ between electrodes and across participants.
“Since phosphene shapes and sizes differ between electrodes and across participants (D. Nanduri et al. 2008; Beyeler et al. 2019; Luo et al. 2016), which could influence the overall image produced by multi-electrode stimulation, we performed a systematic mapping experiment.”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationVisual neuroprostheses have been implanted in the retina, optic nerve, and visual cortex of human subjects.
“To date, visual neuroprostheses have been implanted in the retina (Humayun et al. 2012; Stingl et al. 2013; Fujikado et al. 2016; Petoe et al. 2021; Barnes et al. 2016; Palanker et al. 2022; Xu et al. 2021), optic nerve (Veraart et al. 2003), and visual cortex of human subjects (Beauchamp et al. 2020; Fernández et al. 2021).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationPhosphene shape variation across trials could also have been affected by perceptual adaptation and gaze direction.
“Phosphene shape variation across trials also could have been influenced by perceptual adaptation (Pérez Fornos et al. 2012) and gaze direction (Barry and Dagnelie 2016; Sabbah et al. 2014; Caspi et al. 2017; 2021).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductreasoningThe authors took frequent breaks to reduce the chance of perceptual adaptation and instructed participants to keep the same head and eye position between trials.
“However, we took frequent breaks to minimize the likelihood of adaptation, and we asked the participants to maintain the same head and eye position between trials.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningBecause daily-life visual scenes are complicated, sequential stimulation may be most useful for epiretinal prostheses in basic navigation rather than difficult tasks like object identification.
“Because our surroundings in daily life are visually complicated, sequential stimulation may be most beneficial for epiretinal prostheses in basic navigational applications rather than difficult tasks such as object identification.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationEven though each electrode was stimulated in proportion to its detection threshold and pulse frequency was constant, perceived brightness may have differed between electrodes.
“Additionally, though we stimulated each electrode in proportion to its detection threshold and held pulse frequency constant, it is possible that there were differences in the perceived brightness of phosphenes elicited by different electrodes (Devyani Nanduri et al. 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Devyani Nanduri et al. 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningSmall trial-to-trial variations were likely caused by participants drawing without visual feedback of their finger traces on the tablet screen.
“In general, small variations between trials were likely due to the fact that the participants were drawing without any visual feedback of traces made by their finger on the tablet screen.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningBecause inadvertent axon bundle recruitment occurs, targeting the visual cortex may be advantageous for visual neuroprostheses, since its cellular makeup differs from that of the retina.
“The inadvertent recruitment of axon bundles is one reason why it may be advantageous to target the visual cortex for visual neuroprostheses, because it has a different cellular makeup than the retina.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationMislocalization may be due to eye movements affecting phosphene location or to inconsistencies in phosphene size and brightness.
“Mislocalization can be attributed to eye movements that influence the location of the phosphene (Sabbah et al. 2014; Caspi et al. 2017; 2021), or inconsistencies in phosphene size and brightness.”
Quote in the paperNot a substantial claim0 of 3 sources checked
The authors state this as an assumption.
When more than one phosphene was perceived in a trial, the first drawn phosphene was assumed to be the most noticeable.
“If two or more phosphenes were perceived in a single trial, only the first drawn phosphene was included when calculating elongation; it was assumed to be the most noticeable, and the computation cannot account for multiple phosphenes.”
The paper relies on this without support.
The information from a single phosphene is minimal, so patterned vision is needed to maximize real-time visual understanding of the environment.
“The information delivered by a single phosphene is minimal, so patterned vision is used to maximize real-time visual understanding of one’s environment.”
The paper relies on this without support.
Participants' drawings and reports accurately reflect their phosphene percepts.
“When the participants were asked to draw the shapes of the arrows, the three phosphenes merged together in an unpredictable manner during simultaneous stimulation (Figure 5).”
“Though the participants saw three discrete phosphenes during the sequential stimulation paradigm, they reported seeing only 1–2 phosphenes when the three electrodes were simultaneously stimulated.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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).”
From Axonal stimulation affects the linear summation of single-point perception in three Argus II users (2024) · cites this paper as Christie et al 2022
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).”
From Axonal stimulation affects the linear summation of single-point perception in three Argus II users (2024) · cites this paper as Christie et al 2022
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Trial count does not match the stated repetitions
MinorFour pulse-train durations, three gap intervals, and three repetitions per combination give 36 trials per participant, not 48.
Reported 48 · recomputed 36
“We set the pulse train duration of each electrode to 50, 100, 150, or 200 ms. We also tested gap intervals, or the amount of time between electrode stimulations, of 0, 50, and 100 ms. We performed three repetitions for each combination of train duration and gap interval, for a total of 48 trials per participant.”
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“In future work, it could be worthwhile to implement a control task to quantify the ability of human subjects to draw phosphenes accurately and consistently across trials (Nanduri et al 2012).”
BackgroundImproving the spatial resolution of epiretinal implants by increasing stimulus pulse duration
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Self-citationTesting vision is not testing for vision
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Self-citation
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Overcoming failure: improving acceptance and success of implanted neural interfaces
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Evaluating Deep Human-in-the-Loop Optimization for Retinal Implants Using Sighted Participants
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Perception of Dynamic Displays by People with Argus® II Retinal Prostheses
Christie, B. P., Sadeghi, R., Kartha, A., Ewulum, C., Caspi, A., Tenore, F. V., Klatzky, R. L., Dagnelie, G., & Billings, S. (2023) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/ner52421.2023.10123765 · Cited by 2 · see citing works
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Object recognition from sparse simulated phosphenes and curved segments
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Irregular Artificial Vision Optimization Strategies Based on Transformer Saliency Detection
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A Dynamic Virtual Channel Approach to Enhance Retinal Prosthetic Precision
Liu, Z., Guo, T., He, Y., Zheng, S., Song, X., Dai, C., Li, J., Chai, X., Chen, Y., & Li, L. (2026) · Biomimetics · doi:10.3390/biomimetics11050307
- Authors
- Christie, B., Sadeghi, R., Kartha, A., Caspi, A., Tenore, F. V., Klatzky, R. L., Dagnelie, G., & Billings, S.
- Affiliations
- Johns Hopkins University (US)
- Jerusalem College of Technology (IL)
- Carnegie Mellon University (US)
- Corresponding author
- Christie, Breanne
- ORCID
- Venue
- Journal of Neural Engineering
- Publisher
- IOP Publishing
- Published
- 2022-06-01
- Volume
- 19
- Issue
- 3
- Pages
- 036033
- ISSN
- 1741-2552 (ISSN-L)
- 1741-2560
- PMC
- PMC9440621
- OpenAlex
- W4281489008
- Semantic Scholar
- 9a30d345211f7eca084620db19af29f12c965d70
- Cited by
- 10
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 2
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neural Engineering (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins Hospital
- National Institutes of Health (R01EY029741)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- epiretinal prosthesis, sequential stimulation, phosphenes, retinitis pigmentosa, Argus II, shape discrimination, stimulation timing, electrode selection, vision restoration
- MeSH terms
- Blindness, Electric Stimulation, Electrodes, Implanted, Humans, Phosphenes, Retina, Retinitis Pigmentosa, Vision Disorders, Visual Prosthesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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