Mapping Visual Contrast Sensitivity and Vision Loss Across the Visual Field with Model-Based fMRI

Reviewer #1 (Public review):

Summary:

Integrating large-field stimulation with a retinotopic atlas, this study introduces an fMRI-based method for measuring contrast sensitivity across the visual field. Retinotopy was assessed using pRF mapping and a calibrated Benson atlas. The authors validate their method by replicating known patterns of contrast sensitivity across eccentricities and visual field quadrants in healthy subjects and demonstrate its potential clinical utility through case studies of both simulated and real visual field loss.

Strengths:

The new method is promising, with potential clinical utility in assessing visual field loss.

Weaknesses:

The current claims should be better supported by more evidence.

In the first experiment, have the statistics undergone multiple comparison corrections (e.g., Line 441-442)? Given the small sample size, incorporating additional statistical tests (such as the Bayes Factor) could strengthen the analysis.

The authors claim that "structure-based atlases can replace the need for pRF mapping in cases where it might otherwise be difficult or impossible to collect pRF data." This claim needs further scrutiny. Currently, only one simulated condition of visual field loss was examined in one subject. Also, in Figure 7, contrast sensitivity in the periphery differs between pRF mapping and the Benson atlas. How do the authors explain this discrepancy?

Overall, the writing could be significantly improved.

Reviewer #2 (Public review):

Summary:

This study uses functional MRI to evaluate visual contrast sensitivity across the visual field at the level of the visual cortex, testing the method in a small group of normally sighted individuals and one with sight loss as proof of principle. The results suggest a promising technique to measure vision objectively across the visual field and overcomes the requirement for careful fixation which is often challenging in those with low vision or sight loss.

Strengths:

(1) Objective measure of central vision: The proposed method may provide a more comprehensive and objective assessment of residual visual function in individuals with sight loss. This may be particularly useful for those with central visual field loss without the requirement of stable fixation or subjective motor responses.

(2) More sensitive measure: The use of slope to calculate contrast sensitivity across a range of contrasts within the brain is clever and likely more sensitive than single threshold measurements or standard clinical measures of visual acuity using letter charts. Standard supra-threshold (high contrast) tests are not ideal for capturing residual vision or partial vision loss.

(3) Good agreement with standard atlas: The Benson atlas provides a good estimate of visual field maps within V1 based on anatomical landmarks, and the authors take steps to refine this informed by cortical magnification and V1 surface area (brain size) for each individual participant. This could allow the technique to be generalised without the need to collect lengthy individual mapping data from every participant.

(4) Within-subject reproducibility: The measurements appear to be sensitive and reproducible, particularly in those with normal vision, and are consistent with known features of visual sensitivity differences in different parts of the visual field.

(5) Potential tool to measure visual field sensitivity in controls: Even if the proposed methods are not ideal for widespread clinical translation, they do offer an exciting tool to test hypotheses about visual field differences in healthy controls. For example, there seems to be an increase in sensitivity on either side of the simulated ring scotoma (Figure 6 - perhaps due to the release of lateral inhibition?). Reliability measures suggest that individual differences are consistent in healthy controls (although not tested statistically, perhaps due to the small sample size?). Whether they reflect behaviourally meaningful differences in visual field sensitivity could be tested in individuals by comparing them to behavioural measures across the visual field.

(6) Potential tool to test novel treatments: The proposed techniques could be used to test within-subject changes in visual function in environments that are equipped to measure and analyse fMRI data, including clinical trials aimed at determining the success of novel treatments. Further testing should reveal whether the method is suitable for testing low-vision patients with unstable fixation (e.g., nystagmus) and whether this affects slope and contrast sensitivity estimates. In theory, it should not have a substantial effect, except perhaps in regions near the stimulus edges.

Weaknesses:

(1) Questionable sensitivity to differences in patients. The variability in heat maps across healthy control participants is somewhat surprising. Do differences between individuals represent actual visual sensitivity differences, or are they an artifact of the measurement technique, e.g., due to signal-to-noise differences introduced by local variations in brain anatomy? Will the substantial variance across controls allow for a sufficiently stable baseline to detect meaningful differences in individual patients? Also, as the authors rightly point out, Benson atlas does not model differences along meridians, so upper/lower field differences might not be detectable.

(2) Effects of unstable fixation/eye movements not explicitly tested: The methods state, 'In all tasks, participants were asked to report when the color of a central fixation dot changed', suggesting participants maintained fairly good fixation. Most of the results seem to pertain to measurements where central fixation is required. How does unstable fixation affect measurements?

(3) Potential for clinical translation. Although it is a sensitive measure, functional MRI is costly, is not available in all clinical settings, requires significant post-processing analyses, and may be contraindicated in some individuals due to safety (e.g., metallic implants) or other concerns (e.g., claustrophobia). These could present significant barriers to widespread clinical translation if this were the ultimate goal of the study.

(4) Limited range of spatial frequencies. The spatial frequencies tested were still quite low (0.3 and 3cpd) compared to measures such as visual acuity. Extending the measurements to higher spatial frequencies could allow better characterization of central vision, although necessarily for peripheral vision.

Reviewer #3 (Public review):

Summary:

Chow-Wing-Bom et al. introduce an innovative wide-field visual stimulation setup for 3T experiments that enables stimulation up to a diameter of 40{degree sign} visual angle while allowing continuous gaze tracking. Using this setup, the authors systematically investigate contrast sensitivity across the visual field by presenting subjects with sinusoidal gratings varying in contrast and spatial frequency. Their findings confirm the expected organization of contrast sensitivity, demonstrating a preference for high spatial frequencies in the central field and lower frequencies in the periphery. They also extend these measurements to eccentricities up to 20{degree sign}, which exceeds previous fMRI-based reports. Moreover, the study explores the potential of using contrast sensitivity calculations as a method for detecting visual field defects, as demonstrated in both a healthy subject with an artificial, ring-shaped scotoma and a patient with LHON.

Strengths:

(1) The manuscript is well written and provides comprehensive methodological details, ensuring high transparency and reproducibility.

(2) The visual stimulation setup represents a significant technical advance by enabling wide-field stimulation with continuous eye tracking, which is crucial for both research and potential clinical applications.

(3) The study confirms established findings regarding the organization of contrast sensitivity while extending them to a larger eccentricity range.

(4) The efforts to establish a measure for visual field losses align with current efforts to develop objective alternatives to conventional perimetry.

Weaknesses:

(1) The authors should more strongly emphasize their findings on the organization of contrast sensitivity, particularly in light of the stimulation extent provided by the wide-field setup.

(2) Certain methodological aspects require further clarification, particularly regarding the correction of eccentricity values from the Benson atlas. It's not clear which V1 masks are used for the specific analysis which could have a substantial impact on the reported differences between the two approaches of pRF mapping and atlas-based pRF parameters.

(3) Minor inconsistencies in reporting, e.g., the introduction of a second session in the Results section.

(4) The conclusion that high-contrast patterns as in pRF mapping are not optimal to test for subtle but potentially clinically relevant changes in the visual field coverage is very valid. The suggested use of contrast sensitivity can therefore be a potentially well-suited parameter for estimating visual field losses. The presented work is an interesting starting point and the proposed method of using contrast sensitivity as a measure for partial vision loss should further be explored.