Perceptual restoration fails to recover unconscious processing for smooth eye movements after occipital stroke

  1. Sunwoo Kwon
  2. Berkeley K Fahrenthold
  3. Matthew R Cavanaugh
  4. Krystel R Huxlin
  5. Jude F Mitchell

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    Evaluation Summary:

    This study investigates oculomotor behavior of cortically-blind patients (with lesions in area V1) performing a saccade and ocular following response toward a cued moving target placed either in their intact or in their blind visual field. Whereas perceptual training led to a good recovery of perceptual performance in the blind field, the ocular following response did not appear to benefit from this training. The authors conclude that V1 lesions result in impaired transmission of signals selectively driving the ocular following response. The manuscript is based on a valuable patient dataset, well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and clinical neurologists. However, some major weaknesses in the analysis and interpretation of data call into question the conclusion that the selective eye movement deficit reveals a true perception-action dissociation.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

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Abstract

The visual pathways that guide actions do not necessarily mediate conscious perception. Patients with primary visual cortex (V1) damage lose conscious perception but often retain unconscious abilities (e.g. blindsight). Here, we asked if saccade accuracy and post-saccadic following responses (PFRs) that automatically track target motion upon saccade landing are retained when conscious perception is lost. We contrasted these behaviors in the blind and intact fields of 11 chronic V1-stroke patients, and in 8 visually intact controls. Saccade accuracy was relatively normal in all cases. Stroke patients also had normal PFR in their intact fields, but no PFR in their blind fields. Thus, V1 damage did not spare the unconscious visual processing necessary for automatic, post-saccadic smooth eye movements. Importantly, visual training that recovered motion perception in the blind field did not restore the PFR, suggesting a clear dissociation between pathways mediating perceptual restoration and automatic actions in the V1-damaged visual system.

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  1. Version published to 10.7554/elife.67573 on eLife
  2. eLife

    Author Response

    Reviewer #1 (Public Review):

    Kwon, Huxlin and Mitchell compared motion perception and oculomotor responses in eight patients with post-stroke lesions in the primary visual cortex (V1). Motion perception was measured as peripheral motion discrimination thresholds (NDR) separately in the affected and the intact visual field. Due to restoration training, the NDR thresholds were below chance even in the affected visual field, indicating that some residual motion discrimination was possible. Oculomotor responses were measured as the gain of eye drifts (PFR) after saccades to dot patterns that are coherently drifting inside peripheral, stationary apertures. The authors distinguish between a predictive, open loop component up to 100 ms after the saccade that is entirely based on presaccadic motion processing in the peripheral visual field and a visually-driven component from 100 ms after the saccade that is based on postsaccadic motion processing in the fovea. While the PFR gain of patients in the intactfield was comparable to the data of healthy control subjects from a previous study (Kwon et al., 2019), the predictive, open-loop PFR gain of patients in the affected field was close to zero. This was not the case for the visually-driven PFR. The authors interpret their findings in terms of a dissociation between residual motion perception and absent predictive oculomotor control in patients with V1 lesions.

    Strengths:
    The study contains a rare and valuable set of perceptual and oculomotor data from eight patients with lesions in V1, who underwent restoration training. The direct comparison between peripheral motion discrimination and predictive oculomotor responses is interesting and innovative. Also, the distinction between the predictive, open-loop and the closed-loop component of PFR is important. A potential dissociation between motion perception and oculomotor control would be very relevant for the understanding of different pathways of motion processing for perception and oculomotor control and also for the understanding of the effects of restoration trainings after lesions of V1.

    Weaknesses:
    The dissociation between perception and oculomotor control in the affected field is primarily based on two results: First, the combination of low PFR gain (Figure 4A) on the one hand and low to medium NDR thresholds (Table 1) on the other hand. Second, the absence of a correlation between NDR thresholds and PFR gain (Figure 4B). However, the data are not as clear-cut. The regression of PRF gain on NDR thresholds in the intact-field predicts that there should be a substantial PRF gain only at NDR thresholds below about 0.3. For the affected field this applies only to three data points of which one shows a substantial PFR and is fully compatible with the data in the intact-field. Hence, the evidence of a dissociation between motion perception and oculomotor control is based on a very small number of data points. This also allows for a different interpretation: instead of assuming separate pathways for motion perception and oculomotor control in patients, the results might also be explained by a different read-out of the same motion signal for perception and oculomotor control, where oculomotor control applies a more conservative threshold and requires a higher internal signal strength than the motion perception.

    The comparison of the patients' data to the data in the previous study (Kwon et al., 2019) is not very informative. First, the patients were considerably older than the participants in the previous study, and an age-matched control group would be favourable. That being said, the fact that the PFR gain was comparable for the intact-field of the patients and the previous study renders age-effects rather unlikely.

    Second, there is no control data for the motion discrimination task, so we don't know what the NDR thresholds and even more importantly what the relationship between NDR thresholds and PFR gain in healthy observers would be.

    We thank the reviewer for their evaluation. We have attempted to address concerns about sufficient sampling from blind-fields with recovery that reached the normal range by collecting additional data, doubling our sample size within that range. This is discussed above in “Essential revisions”, along with the alternative interpretation that perception and oculomotor control might rely on a different threshold in readout. The role of age differences was considered in the original manuscript, but this remains an unlikely factor, as the reviewer notes. With regard to normative NDR threshold data, surprisingly, this has not been published in visually-intact controls in a manner that is identical to that in the present study. However, prior work has established that performance in CB patients’ intact visual fields is normal across a wide range of behavioral measures that include luminance contrast sensitivity, processing of form, color and motion, as well as spatial and temporal frequencies (e.g. Barbur et al., 1980; Morland et al., 1999; Sahraie et al., 2006; Huxlin et al., 2009; Das et al., 2014; Levi et al., 2015). In the present study, we have thus used the intact-field as an internal control for blind-field performance in the same participant, as is standard in the field, expecting that intact-field NDR thresholds should be within the normal range. Verifying this is outside the scope of the present paper, but is now planned for our subsequent studies. Other detailed responses appear below to point by point for the reviewer’s “Recommendations for authors”.

    Reviewer #2 (Public Review):

    This study addresses the oculomotor behaviour of cortically-blind patients (with lesions in V1) who are instructed to perform a saccade toward a cued target placed either in their intact or in the blind visual field. The saccadic target consists in an aperture containing random-dot motion at 75% direction discrimination threshold ("NDR"), and is presented with iso-eccentric similar distractor apertures: with this kind of stimulus, the gaze of normally-sighted participants drifts smoothly in the direction of the target random dot motion immediately after the end of the saccade. Importantly, for some patients, a perceptual training had led to a good recovery of perceptual performance in the blind-field, as documented by the reduction of motion direction discrimination threshold to levels similar to the control healthy participants. Cortically-blind (CB) patients are shown to perform very similarly to control participants in terms of saccade accuracy, but they have longer latency. As for the postsaccadic ocular following response ("PFR"), the eye velocity component projected on the random-dot motion direction Is comparable to controls when the saccade was directed to the intactfield, but the mean PFR is significantly lower for saccades directed toward the blind-field. The authors conclude that V1 lesions result in a previously ignored selective impairment of the automatic transaccadic transmission of visual information that drive the ocular following response. In the supplementary information, it is also shown and the shift of saccadic landing position which is induced by the presaccadic target motion is strongly reduced (yet different from zero) for saccades to the blind-field locations in CB patients.

    The manuscript is very well written and illustrated, and the addressed question is novel and highly interesting. The inclusion in the experiment of locations of the patients' blind-field for which some perceptual abilities had been recovered is particularly interesting. However some major weaknesses fragilize part of the results and undermine the interpretation of results (see below). I also list a series of other minor issues to be clarified or improved.

    Main weaknesses:

    1. Unfortunately, the present data do not allow to strongly support the conclusion that the reduced PFR gain in patients is decorrelated from the motion discrimination performance. As a matter of fact, in Figure 4B the function describing the relation between PFR gain and NDR is reasonably linear in a very limited interval of NDR values (say <0.3), and it should rather be described as a decreasing exponential, or similar, approaching 0 already for NDR~0.3. On the other hand, it is presumably hard to appropriately fit a similar exponential function to the blind-field datapoints, as the majority of the latter lay in the range of NDR threshold (say > 0.4) where the PFR gain would in any case be flat and close to 0. In other terms, in my view there aren't enough blind-field datapoints with low NDR threshold to assess a quantitative difference in the relation between PFR and NDR between CB patients and Control participants.

    Finally, and probably just a misunderstanding of mine, shouldn't the empty circles in Figure 4A and 4B have the same y-coordinate (the PFR gain value)? It does not seem so when looking at these figures.

    1. A second weak point, in my opinion, concerns the interpretation of the results and in particular the exclusion of a role for presaccadic attentional mechanisms. The authors claim (lines 356-358): "That the FEF and its projections to area MT are intact in V1-stroke patients suggests preservation of presaccadic planning and attention selection for the saccade target even when visual input is weak or abnormal in a blind-field" and this is definitely a valuable point. However a number of other physiological mechanisms involving V1 could play a role in the spatially-selective processing of motion and the argument that (lines 368 and ff) "other aspects of saccade pre-planning related to perceptual shifts in the position of motion targets, remain in the blind-field" is not very robust here, considering that the reduction in the angular deviation is very strong in the blind-field (Supplementary Figure 2).

    Here is a speculative alternative interpretation: V1-lesioned patients suffer among others of a specific impairment for spatially-selective motion processing. Unfortunately, the training in peripheral motion discrimination does not test this particular possibility, if I understand correctly, as there was no other distractor aperture containing distracting motion information (see Fig 2A). In contrast, in the main experiment, a lack of spatial selectivity for motion integration may have strongly affected the presaccadic motion discrimination (being more global than local) as well as PFR and postsaccadic landing position shift (although the latter was partly spared). According to this possibility, a simple prediction is that depending on the (randomly determined) motion direction in the distracting apertures, the PFR (the true eye movement, not the projection according to the stimulus motion axis) should be deviated in different directions, coherent with a global integration of motion. Do the available data allow to verify this possibility? In general, I think that it would be interesting to analyse post-saccadic smooth eye velocity beyond the "projected" velocity.

    We thank the reviewer for their evaluation, several parts of which overlap with Reviewers 1 and 3. In particular, the concerns about sufficient sampling from blind-fields that recover motion integration (NDR < 0.35) have been addressed by collecting additional data and performing new analyses, and we have also addressed possible impairments to spatial attention (see above in “Essential revisions”). The discrepancy noted in the y-ordinate between 4A and B is related to those analyses being by subject (4A) versus by visual field location (4B), which we already addressed above, in response to Reviewer 1. Other detailed responses appear below.

    Reviewer #3 (Public Review):

    The human visual system comprises a tangle of neural pathways that subserve different perceptual, cognitive, and motor functions. Unfortunate cases of brain damage can reveal surprising dissociations between the functions of damaged and spared tissue. Perhaps the most famous example is blindsight, when damage to visual regions of occipital cortex leads to subjective blindness in parts of the visual field while sparing some visually-guided actions. Kwon, Huxlin and Mitchell had a rare opportunity to study eight individuals with that type of cortical blindness due to stroke, and put them through a carefully designed regimen of visual training and oculomotor testing.

    The main focus was a particular oculomotor behavior that they term the "post-saccadic following response": when a neurotypical person makes a saccade to an object moving in the periphery, their eyes immediately begin smoothly following the stimulus motion, due to an oculomotor plan made before the saccade began. In this case, the stroke patients were able to regain their ability to discriminate stimulus motion in the "blind" parts of the visual field, but upon saccading to those stimuli they did not show the immediate post-saccadic following response. This surprising result shows yet another splintering dissociation between perception and action, demonstrating that the effects of stroke can be very specific to certain motor actions.

    Strengths:

    • The authors masterfully combined several techniques in a rare and carefully chosen sample of participants: neuropsychiatric evaluations, rehabilitation training, psychophysics and eye-movement analyses.
    • The analyses that link all those measures together, while complicated and precise, and elegantly and clearly presented.
      The study provides a twist on blindsight that is interesting philosophically, while also constraining our models of neural circuitry and informing approaches to rehabilitation after stroke.

    Weakness:

    • The unique nature of this study is a strength but also potentially limits its impact: the authors studied one particular type of eye movement with a complicated, unnatural stimulus arrangement. For example, the stimuli were groups of random moving dots windowed through static apertures. These stimuli, which move but also don't, are quite different from real moving objects that people track with their eyes (flying birds, for example). A related issue, which the authors briefly acknowledge, is that the training was specifically directed towards explicit perceptual reports. We therefore don't know if the oculomotor behavior (the PFR) could also be trained.
    • The authors rely on traditional null-hypothesis tests (t-tests and correlations) to make binary judgements of whether each effect or difference is "significant" (p<0.05). Some of the conclusions would be more convincing if supplemented with power analyses, bootstrapped confidence intervals, and Bayes factors to evaluate the strength of evidence.

    We thank Reviewer 3 for their evaluation. The choice of stimuli/task and their “naturalness” is addressed in our point by point responses to the “Recommendations for authors” below. We have also revised the manuscript to include boot-strapped confidence intervals, along with other statistics suggested by other reviewers, as noted under “Essential revisions for authors”. Other detailed responses appear below point by point.

  3. eLife

    Evaluation Summary:

    This study investigates oculomotor behavior of cortically-blind patients (with lesions in area V1) performing a saccade and ocular following response toward a cued moving target placed either in their intact or in their blind visual field. Whereas perceptual training led to a good recovery of perceptual performance in the blind field, the ocular following response did not appear to benefit from this training. The authors conclude that V1 lesions result in impaired transmission of signals selectively driving the ocular following response. The manuscript is based on a valuable patient dataset, well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and clinical neurologists. However, some major weaknesses in the analysis and interpretation of data call into question the conclusion that the selective eye movement deficit reveals a true perception-action dissociation.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

  4. eLife

    Reviewer #1 (Public Review):

    Kwon, Huxlin and Mitchell compared motion perception and oculomotor responses in eight patients with post-stroke lesions in the primary visual cortex (V1). Motion perception was measured as peripheral motion discrimination thresholds (NDR) separately in the affected and the intact visual field. Due to restoration training, the NDR thresholds were below chance even in the affected visual field, indicating that some residual motion discrimination was possible. Oculomotor responses were measured as the gain of eye drifts (PFR) after saccades to dot patterns that are coherently drifting inside peripheral, stationary apertures. The authors distinguish between a predictive, open loop component up to 100 ms after the saccade that is entirely based on presaccadic motion processing in the peripheral visual field and a visually-driven component from 100 ms after the saccade that is based on postsaccadic motion processing in the fovea. While the PFR gain of patients in the intact field was comparable to the data of healthy control subjects from a previous study (Kwon et al., 2019), the predictive, open-loop PFR gain of patients in the affected field was close to zero. This was not the case for the visually-driven PFR. The authors interpret their findings in terms of a dissociation between residual motion perception and absent predictive oculomotor control in patients with V1 lesions.

    Strengths:

    The study contains a rare and valuable set of perceptual and oculomotor data from eight patients with lesions in V1, who underwent restoration training. The direct comparison between peripheral motion discrimination and predictive oculomotor responses is interesting and innovative. Also, the distinction between the predictive, open-loop and the closed-loop component of PFR is important. A potential dissociation between motion perception and oculomotor control would be very relevant for the understanding of different pathways of motion processing for perception and oculomotor control and also for the understanding of the effects of restoration trainings after lesions of V1.

    Weaknesses:

    The dissociation between perception and oculomotor control in the affected field is primarily based on two results: First, the combination of low PFR gain (Figure 4A) on the one hand and low to medium NDR thresholds (Table 1) on the other hand. Second, the absence of a correlation between NDR thresholds and PFR gain (Figure 4B). However, the data are not as clear-cut. The regression of PRF gain on NDR thresholds in the intact field predicts that there should be a substantial PRF gain only at NDR thresholds below about 0.3. For the affected field this applies only to three data points of which one shows a substantial PFR and is fully compatible with the data in the intact field. Hence, the evidence of a dissociation between motion perception and oculomotor control is based on a very small number of data points. This also allows for a different interpretation: instead of assuming separate pathways for motion perception and oculomotor control in patients, the results might also be explained by a different read-out of the same motion signal for perception and oculomotor control, where oculomotor control applies a more conservative threshold and requires a higher internal signal strength than the motion perception.

    The comparison of the patients' data to the data in the previous study (Kwon et al., 2019) is not very informative. First, the patients were considerably older than the participants in the previous study, and an age-matched control group would be favourable. That being said, the fact that the PFR gain was comparable for the intact field of the patients and the previous study renders age-effects rather unlikely. Second, there is no control data for the motion discrimination task, so we don't know what the NDR thresholds and even more importantly what the relationship between NDR thresholds and PFR gain in healthy observers would be.

  5. eLife

    Reviewer #2 (Public Review):

    This study addresses the oculomotor behaviour of cortically-blind patients (with lesions in V1) who are instructed to perform a saccade toward a cued target placed either in their intact or in the blind visual field. The saccadic target consists in an aperture containing random-dot motion at 75% direction discrimination threshold ("NDR"), and is presented with iso-eccentric similar distractor apertures: with this kind of stimulus, the gaze of normally-sighted participants drifts smoothly in the direction of the target random dot motion immediately after the end of the saccade. Importantly, for some patients, a perceptual training had led to a good recovery of perceptual performance in the blind field, as documented by the reduction of motion direction discrimination threshold to levels similar to the control healthy participants. Cortically-blind (CB) patients are shown to perform very similarly to control participants in terms of saccade accuracy, but they have longer latency. As for the postsaccadic ocular following response ("PFR"), the eye velocity component projected on the random-dot motion direction Is comparable to controls when the saccade was directed to the intact field, but the mean PFR is significantly lower for saccades directed toward the blind field. The authors conclude that V1 lesions result in a previously ignored selective impairment of the automatic transaccadic transmission of visual information that drive the ocular following response. In the supplementary information, it is also shown and the shift of saccadic landing position which is induced by the presaccadic target motion is strongly reduced (yet different from zero) for saccades to the blind field locations in CB patients.

    The manuscript is very well written and illustrated, and the addressed question is novel and highly interesting. The inclusion in the experiment of locations of the patients' blind field for which some perceptual abilities had been recovered is particularly interesting. However some major weaknesses fragilize part of the results and undermine the interpretation of results (see below). I also list a series of other minor issues to be clarified or improved.

    Main weaknesses:

    1. Unfortunately, the present data do not allow to strongly support the conclusion that the reduced PFR gain in patients is decorrelated from the motion discrimination performance. As a matter of fact, in Figure 4B the function describing the relation between PFR gain and NDR is reasonably linear in a very limited interval of NDR values (say <0.3), and it should rather be described as a decreasing exponential, or similar, approaching 0 already for NDR~0.3. On the other hand, it is presumably hard to appropriately fit a similar exponential function to the blind-field datapoints, as the majority of the latter lay in the range of NDR threshold (say > 0.4) where the PFR gain would in any case be flat and close to 0. In other terms, in my view there aren't enough blind-field datapoints with low NDR threshold to assess a quantitative difference in the relation between PFR and NDR between CB patients and Control participants. Finally, and probably just a misunderstanding of mine, shouldn't the empty circles in Figure 4A and 4B have the same y-coordinate (the PFR gain value)? It does not seem so when looking at these figures.

    2. A second weak point, in my opinion, concerns the interpretation of the results and in particular the exclusion of a role for presaccadic attentional mechanisms. The authors claim (lines 356-358): "That the FEF and its projections to area MT are intact in V1-stroke patients suggests preservation of pre-saccadic planning and attention selection for the saccade target even when visual input is weak or abnormal in a blind field" and this is definitely a valuable point. However a number of other physiological mechanisms involving V1 could play a role in the spatially-selective processing of motion and the argument that (lines 368 and ff) "other aspects of saccade pre-planning related to perceptual shifts in the position of motion targets, remain in the blind-field" is not very robust here, considering that the reduction in the angular deviation is very strong in the blind field (Supplementary Figure 2).

    Here is a speculative alternative interpretation : V1-lesioned patients suffer among others of a specific impairment for spatially-selective motion processing. Unfortunately the training in peripheral motion discrimination does not test this particular possibility, if I understand correctly, as there was no other distractor aperture containing distracting motion information (see Fig 2A). In contrast, in the main experiment, a lack of spatial selectivity for motion integration may have strongly affected the presaccadic motion discrimination (being more global than local) as well as PFR and postsaccadic landing position shift (although the latter was partly spared). According to this possibility, a simple prediction is that depending on the (randomly determined) motion direction in the distracting apertures, the PFR (the true eye movement, not the projection according to the stimulus motion axis) should be deviated in different directions, coherent with a global integration of motion. Do the available data allow to verify this possibility? In general, I think that it would be interesting to analyse post-saccadic smooth eye velocity beyond the "projected" velocity.

  6. eLife

    Reviewer #3 (Public Review):

    The human visual system comprises a tangle of neural pathways that subserve different perceptual, cognitive, and motor functions. Unfortunate cases of brain damage can reveal surprising dissociations between the functions of damaged and spared tissue. Perhaps the most famous example is blindsight, when damage to visual regions of occipital cortex leads to subjective blindness in parts of the visual field while sparing some visually-guided actions. Kwon, Huxlin and Mitchell had a rare opportunity to study eight individuals with that type of cortical blindness due to stroke, and put them through a carefully designed regimen of visual training and oculomotor testing.

    The main focus was a particular oculomotor behavior that they term the "post-saccadic following response": when a neurotypical person makes a saccade to an object moving in the periphery, their eyes immediately begin smoothly following the stimulus motion, due to an oculomotor plan made before the saccade began. In this case, the stroke patients were able to regain their ability to discriminate stimulus motion in the "blind" parts of the visual field, but upon saccading to those stimuli they did not show the immediate post-saccadic following response. This surprising result shows yet another splintering dissociation between perception and action, demonstrating that the effects of stroke can be very specific to certain motor actions.

    Strengths:

    - The authors masterfully combined several techniques in a rare and carefully chosen sample of participants: neuropsychiatric evaluations, rehabilitation training, psychophysics and eye-movement analyses.
    - The analyses that link all those measures together, while complicated and precise, and elegantly and clearly presented.
    The study provides a twist on blindsight that is interesting philosophically, while also constraining our models of neural circuitry and informing approaches to rehabilitation after stroke.

    Weakness:

    - The unique nature of this study is a strength but also potentially limits its impact: the authors studied one particular type of eye movement with a complicated, unnatural stimulus arrangement. For example, the stimuli were groups of random moving dots windowed through static apertures. These stimuli, which move but also don't, are quite different from real moving objects that people track with their eyes (flying birds, for example). A related issue, which the authors briefly acknowledge, is that the training was specifically directed towards explicit perceptual reports. We therefore don't know if the oculomotor behavior (the PFR) could also be trained.
    - The authors rely on traditional null-hypothesis tests (t-tests and correlations) to make binary judgements of whether each effect or difference is "significant" (p<0.05). Some of the conclusions would be more convincing if supplemented with power analyses, bootstrapped confidence intervals, and Bayes factors to evaluate the strength of evidence.

  7. Version published to 10.1101/2021.02.16.431524v2 on bioRxiv
  8. Version published to 10.1101/2021.02.16.431524v1 on bioRxiv