Biology subjects

Roorda, A.

Publications and source records attributed to Roorda, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Revealing the benefit of eye motion for acuity under emulated cone loss

Retinal degenerative diseases progressively erode the cone photoreceptor mosaic, reducing the retinas spatial sampling power, yet visual acuity is remarkably resilient to cone loss. Prior work has shown that clinically normal visual acuity (20/25 or better) can persist despite up to 50% of cone cells being lost (Ratnam et al. 2013, Foote et al. 2018). However, studies on individuals with retinal degeneration cannot control for patients stage of disease progression, creating the need for an experimental paradigm that can mimic these diseases in healthy subjects. The Oz Vision system creates visual percepts through programmable, per-cell stimulation of thousands of cone cells. We reprogram this system to emulate cone loss in healthy eyes by withholding stimulation from a subset of randomly-selected cones, rendering them inactive, in a method we term "cone dropout." Using this approach, we characterize the visual systems robustness to cone loss, showing that visual acuity declines nonlinearly with increasing cone dropout. Importantly, we uncover the compensatory benefit that eye motion provides under cone-deprived conditions, finding that at the highest level of dropout, a visual system with eye motion has an equivalent acuity to a static dropout condition with nearly twice as many sampling elements. Through analysis of eye motion and stimulation data, we find that this benefit arises from the additional information accumulated by "surviving" cones as they sample more of the letter through fixational eye motion.

neuroscience↗

bioRxiv2025

Subfoveal scotomas trigger fine-scale fixation reorganization: insights from retinal imaging and retinal-contingent stimulation

Fine spatial vision relies on the foveola, the 1-degree retinal region with highest cone density. Despite its importance, the relationship between retinal anatomy, fixational behavior, and visual perception in the foveola is not fully understood. Using an Adaptive Optics Scanning Light Ophthalmoscope for high-resolution retinal imaging and stimulation, we studied the effect of a simulated subfoveolar ({approx}0.03 degrees2) scotoma on fine spatial vision and fixation behavior in healthy observers. Our findings show that the visuomotor system adapts to the scotoma with striking precision by shifting the preferred locus of fixation in a systematic fashion by minute ({approx}5 arcmin) amounts to bring stimuli into a region of visibility. These results reveal an unprecedented level of fine-scale plasticity in the human visuomotor system. Interestingly, this new retinal locus of fixation is characterized by lower cone density among those surrounding the scotoma, indicating that factors beyond spatial sampling maximization influence these fine-scale adjustments.

neuroscience↗

bioRxiv2025

A discontinuity in motion perception during fixational drift

The human visual system is tasked with perceiving stable and moving objects despite ever-present eye movements. Normally, our visual system performs this task exceptionally well; indeed, under conditions with frames of reference, our ability to detect relative motion exceeds the sampling limits of foveal cones. However, during fixational drift, if an image is programmed to move in a direction consistent with retinal slip, little to no motion is perceived, even if this motion is amplified. We asked: Would a stimulus moving in a direction consistent with retinal slip, but with a smaller magnitude across the retina, also appear relatively stable? We used an adaptive optics scanning light ophthalmoscope to deliver stimuli that moved contingent to retinal motion and measured subjects perceived motion, under conditions with world-fixed background content. We also tested under conditions with background content closer and farther from the stimuli. We found a sharp discontinuity in motion perception. Stimuli moving in a direction consistent with retinal slip, no matter how small, appear to have relatively little to no motion; while, stimuli moving in the same direction as eye motion appear to be moving. Displacing background content to greater than 4{degrees} from the stimuli diminishes the effects of this phenomenon.

neuroscience↗

bioRxiv2025

The Optimal Retinal Locus for High-Resolution Vision in Space and Time

Humans exhibit machine-like eye-movement behavior in space and time while performing challenging visual resolution tasks. Fewer microsaccades occur as stimulus presentation is imminent. Drifts and microsaccades combine to confine the landing location of an anticipated visual stimulus to a tiny retinal region: the preferred retinal locus (PRL). We find that this location confers the best visual acuity despite it being offset from the anatomical fovea (the location of maximum cone density). We also find that acuity is best when the last microsaccade occurs 400msec or longer before stimulus presentation. The machine-like eye movements are involuntary and not perceived. Our findings thus reveal a highly evolved oculomotor system such that gaze direction during fixation is rarely far enough from the PRL to cause a decline in visual resolution. TeaserHumans exhibit machine-like eye-movement behavior during fine visual tasks that rarely deviates from an optimal retinal location.

neuroscience↗

bioRxiv2024

A paradoxical misperception of relative motion

Motion perception is considered a hyperacuity. The presence of a visual frame of reference to compute relative motion is necessary to achieve this sensitivity [Legge, Gordon E., and F. W. Campbell. "Displacement detection in human vision." Vision Research 21.2 (1981): 205-213.]. However, there is a special condition where humans are unable to accurately detect relative motion: images moving in a direction consistent with retinal slip where the motion is unnaturally amplified can, under some conditions, appear stable [Arathorn, David W., et al. "How the unstable eye sees a stable and moving world." Journal of Vision 13.10.22 (2013)]. In this study, we asked: Is world-fixed retinal image background content necessary for the visual system to compute the direction of eye motion to render in the percept images moving with amplified slip as stable? Or, are non-visual cues sufficient? Subjects adjusted the parameters of a stimulus moving in a random trajectory to match the perceived motion of images moving contingent to the retina. Experiments were done with and without retinal image background content. The perceived motion of stimuli moving with amplified retinal slip was suppressed in the presence of visual content; however, higher magnitudes of motion were perceived under conditions with no visual cues. Our results demonstrate that the presence of retinal image background content is essential for the visual system to compute its direction of motion. The visual content that might be thought to provide a strong frame of reference to detect amplified retinal slips, instead paradoxically drives the misperception of relative motion.

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bioRxiv2022

It's not easy seeing green: the veridical perception of small spots

When single cones are stimulated with spots of 543-nm light presented against a white background, subjects report percepts that vary between predominately red, white, and green. However, light of the same spectral composition viewed over a large field under normal viewing conditions looks invariably green and highly saturated. It remains unknown what stimulus parameters are most important for governing the color appearance in the transition between these two extreme cases. The current study varied the size, intensity and retinal motion of stimuli presented in an adaptive optics scanning laser ophthalmoscope. Stimuli were either stabilized on target locations or allowed to drift across the retina with the eyes natural motion. Increasing both stimulus size and intensity led to higher likelihoods that monochromatic spots of light were perceived as green, while only higher intensities led to increases in perceived saturation. The data also show an interaction between size and intensity, suggesting that the balance between magnocellular and parvocellular activation may be critical factors for color perception. Surprisingly, under the range of conditions tested, color appearance did not depend on whether stimuli were stabilized or not. Sequential activation of many cones does not appear to drive hue and saturation perception as effectively as simultaneous activation of many cones.

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bioRxiv2022

Alignment, calibration, and validation of an adaptive optics scanning laser ophthalmoscope optimized for resolving human cones in the central fovea

Advances in adaptive optics scanning laser ophthalmoscope (AOSLO) technology have enabled cones in the human fovea to be reliably resolved, providing new insight into human foveal anatomy, visual perception, and retinal degenerative diseases. These high-resolution ophthalmoscopes require careful alignment of each optical subsystem to ensure diffraction-limited imaging performance, which is necessary for resolving the smallest foveal cones. This paper presents a systematic and rigorous methodology for building, aligning, calibrating, and testing an AOSLO designed for imaging the cone mosaic of the central fovea in humans with cellular resolution. This methodology uses a two-stage alignment procedure and thorough system testing to achieve diffraction-limited performance. Results from retinal imaging of healthy human subjects show that the system can resolve cones at the very center of the fovea, the region where the cones are smallest and most densely packed.

bioengineering↗

bioRxiv2022

Characterizing Cone Spectral Classification by Optoretinography

Light propagation in photoreceptor outer segments is affected by photopigment absorption and the phototransduction amplification cascade. Photopigment absorption has been studied using retinal densitometry, while recently, optoretinography (ORG) has provided an avenue to probe changes in outer segment optical path length due to phototransduction. With adaptive optics (AO), both densitometry and ORG have been used for cone spectral classification, based on the differential bleaching signatures of the three cone types. Here, we characterize cone classification by ORG, implemented in an AO line-scan OCT and compare it against densitometry. The cone mosaics of five color normal subjects were classified using ORG showing high probability ([~]0.99), low error (<0.22%), high test-retest reliability ([~]97%) and short imaging durations (< 1 hour). Of these, the cone spectral assignments in two subjects were compared against AOSLO densitometry. High agreement (mean: 91%) was observed between the two modalities in these 2 subjects, with measurements conducted 6-7 years apart. Overall, ORG benefits from higher sensitivity and dynamic range to probe cone photopigments compared to densitometry, and thus provides greater fidelity for cone spectral classification.

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bioRxiv2021

Fixational Eye Movements Depend on Task and Target

Human fixational eye movements are so small and precise that they require high-speed, accurate tools to fully reveal their properties and functional roles. Where the fixated image lands on the retina and how it moves for different levels of visually demanding tasks is the subject of the current study. An Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) was used to image, track and present Maltese cross, disk, concentric circles, Vernier and tumbling-E letter fixation targets to healthy subjects. During these different passive (static) or active (discriminating) fixation tasks under natural eye motion, the landing position of the target on the retina was tracked in space and time over the retinal image directly. We computed both the eye motion and the exact trajectory of the fixated targets motion over the retina. We confirmed that compared to passive fixation, active tasks elicited a partial inhibition of microsaccades, leading to longer drifts periods compensated by larger corrective saccades. Consequently the fixation stability during active tasks was larger overall than during passive tasks. The preferred retinal locus of fixation was the same for each task and did not coincide with the location of the peak cone density.

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bioRxiv2020

Wide-vergence, multi-spectral adaptive optics scanning laser ophthalmoscope with diffraction-limited illumination and collection

Visualizing and assessing the function of microscopic retinal structures in the human eye is a challenging task that has been greatly facilitated by ophthalmic adaptive optics (AO). Yet, as AO imaging systems advance in functionality by employing multiple spectral channels and larger vergence ranges, achieving optimal resolution and signal-to-noise ratios (SNR) becomes difficult and is often compromised. While current-generation AO retinal imaging systems have demonstrated excellent, near diffraction-limited imaging performance over wide vergence and spectral ranges, a full theoretical and experimental analysis of an AOSLO that includes both the light delivery and collection optics has not been done, and neither has the effects of extending wavefront correction from one wavelength to imaging performance in different spectral channels. Here, we report a methodology and system design for simultaneously achieving diffraction-limited performance in both the illumination and collection paths for a wide-vergence, multi-spectral AO scanning laser ophthalmoscope (SLO) over a 1.2 diopter vergence range while correcting the wavefront in a separate wavelength. To validate the design, an AOSLO was constructed to have three imaging channels spanning different wavelength ranges (543 {+/-} 11 nm, 680 {+/-} 11 nm, and 840 {+/-} 6 nm, respectively) and one near-infrared wavefront sensing channel (940 {+/-} 5 nm). The AOSLO optics and their alignment were determined via simulations in optical and optomechanical design software and then experimentally verified by measuring the AOSLOs illumination and collection point spread functions (PSF) for each channel using a phase retrieval technique. The collection efficiency was then measured for each channel as a function of confocal pinhole size when imaging a model eye achieving near-theoretical performance. Imaging results from healthy human adult volunteers demonstrate the systems ability to resolve the foveal cone mosaic in all three imaging channels despite a wide spectral separation between the wavefront sensing and imaging channels. OCIS codes(110.1080) Active or adaptive optics; (170.4460) Ophthalmic optics and devices; (170.4470) Ophthalmology

bioengineering↗

bioRxiv2020

The optoretinogram reveals how human photoreceptors deform in response to light

Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo has restricted studies of their signaling to in-vitro preparations and animal models. Physiological changes underlying neural activity are mediated by variations in electrical potential that alter the surface tension of the cell membrane. In addition, physiological processes affect concentration of the cells constituents that results in variation of osmotic pressure. Both these phenomena affect the neurons shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of physiological activity in-vivo with cellular resolution. Here, we apply high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors in vivo. We demonstrate that individual cones exhibit a biphasic response to light: an early ms-scale fast contraction of the outer segment immediately after the onset of the flash stimulus followed by a gradual (hundreds of ms) expansion. We demonstrate that the contraction can be explained by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential observed in the electroretinogram and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recording of light-induced activity in the human retina, namely the optoretinogram, across a range of spatiotemporal scales. This approach incorporates functional evaluation into a routine clinical examination of retinal structure and thus holds enormous potential to serve as a biomarker for early disease diagnosis and monitoring therapeutic efficacy.

neuroscience↗

bioRxiv2019

Human Foveal Cone Photoreceptor Topography and its Dependence on Eye Length

We provide the first measures of foveal cone density as a function of axial length in living eyes and discuss the physical and visual implications of our findings. We used a new generation Adaptive Optics Scanning Laser Ophthalmoscope to image cones at and near the fovea in 28 eyes of 16 subjects. Cone density and other metrics were computed in units of visual angle and linear retinal units. The foveal cone mosaic in longer eyes is expanded at the fovea, but not in proportion to eye length. Despite retinal stretching (decrease in cones/mm2), myopes generally have a higher angular sampling density (increase in cones/deg2) in and around the fovea compared to emmetropes, offering the potential for better visual acuity. Reports of deficits in best-corrected foveal vision in myopes compared to emmetropes cannot be explained by increased spacing between photoreceptors caused by retinal stretching during myopic progression.

neuroscience↗

bioRxiv2019

Spatial summation of individual cones in human color vision

The human retina contains three classes of cone photoreceptors each sensitive to different portions of the visual spectrum: long (L), medium (M) and short (S) wavelengths. Color information is computed by downstream neurons that compare relative activity across the three cone types. How cone signals are combined at a cellular scale has been more difficult to resolve. This is especially true near the fovea, where spectrally-opponent neurons in the parvocellular pathway draw excitatory input from a single cone and thus even the smallest stimulus will engage multiple color-signaling neurons. We used an adaptive optics microstimulator to target individual and pairs of cones with light. Consistent with prior work, we found that color percepts elicited from individual cones were predicted by their spectral sensitivity, although there was considerable variability even between cones within the same spectral class. The appearance of spots targeted at two cones were predicted by an average of their individual activations. However, two cones of the same subclass elicited percepts that were systematically more saturated than predicted by an average. Together, these observations suggest both spectral opponency and prior experience influence the appearance of small spots.

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bioRxiv2018

Transverse chromatic offsets with pupil displacements in the human eye: Sources of variability and methods for real-time correction

Tracking SLO systems equipped to perform retinally targeted stimulus delivery typically use near-IR wavelengths for retinal imaging and eye tracking and visible wavelengths for stimulation. The lateral offsets between wavelengths caused by transverse chromatic aberration (TCA) must be carefully corrected in order to deliver targeted stimuli to the correct location on the retina. However, both the magnitude and direction of the TCA offset is dependent on the position of the eyes pupil relative to the incoming beam, and thus can change dynamically within an experimental session without proper control of the pupil position. The goals of this study were twofold: 1) To assess sources of variability in TCA alignments as a function of pupil displacements in an SLO and 2) To demonstrate a novel method for real-time correction of chromatic offsets. To summarize, we found substantial between- and within-subject variability in TCA in the presence of monochromatic aberrations. When adaptive optics was used to fully correct for monochromatic aberrations, variability both within and between observers was minimized. In a second experiment, we demonstrate that pupil tracking can be used to update stimulus delivery in the SLO in real time to correct for variability in chromatic offsets with pupil displacements.

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bioRxiv2018

Versatile Multi-Detector Scheme for Adaptive Optics Scanning Laser Ophthalmoscopy

Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) is a powerful tool for imaging the retina at high spatial and temporal resolution. In this paper, we present a multi-detector scheme for AOSLO which has two main configurations: pixel reassignment and offset aperture imaging. In this detection scheme, the single element detector of the standard AOSLO is replaced by a fiber bundle which couples the detected light into multiple detectors. The pixel reassignment configuration allows for more light throughput while maintaining optimal confocal resolution. The increase in signal-to-noise ratio (SNR) from this configuration can improve the accuracy of motion registration techniques. The offset aperture imaging configuration enhances the detection of multiply scattered light, which improves the contrast of retinal vasculature and inner retinal layers similar to methods such as nonconfocal split-detector imaging and multi-offset aperture imaging.

bioengineering↗

bioRxiv2018

The effects of fixational tremor on the retinal image

The study of fixational eye motion (FEM) has implications for the neural and computational underpinnings of vision. One component of FEM is tremor, a high-frequency oscillatory jitter reported to be anywhere from [~]5 to 60 seconds of arc in amplitude. In order to isolate the effects of tremor on the retinal image directly and in the absence of optical blur, high-frequency, high-resolution eye traces were collected in 6 subjects from videos recorded with an Adaptive Optics Scanning Laser Ophthalmoscope. Videos were acquired while subjects engaged in an active fixation task where they fixated on a tumbling E stimulus and reported changes in its orientation. Spectral analysis was conducted on isolated segments of optical drift. The resultant amplitude spectra showed a slight deviation from the traditional 1/f nature of optical drift in the frequency range of 50-100 Hz, which is indicative of tremor; however, the amplitude of this deviation rarely exceeded one second of arc, smaller than any magnitude previously reported.

neuroscience↗

bioRxiv2018

The spectral identity of foveal cones is preserved in hue perception

Organisms are faced with the challenge of making inferences about the physical world from incomplete incoming sensory information. One strategy to combat ambiguity in this process is to combine new information with prior experiences. We investigated the strategy of combining these information sources in color vision. Single cones in human subjects were stimulated and the associated percepts were recorded. Subjects rated each flash for brightness, hue and saturation. Brightness ratings were proportional to stimulus intensity. Saturation was independent of intensity, but varied between cones. Hue, in contrast, was assigned in a stereotyped manner that was predicted by cone type. These experiments revealed that, near the fovea, long (L) and middle (M) wavelength sensitive cones produce sensations that can be reliably distinguished on the basis of hue, but not saturation or brightness. Taken together, these observations implicate the high-resolution, color-opponent parvocellular pathway in this low-level visual task.

neuroscience↗

bioRxiv2018

Spatial summation in the human fovea: the effect of optical aberrations and fixational eye movements

Psychophysical inferences about the neural mechanisms supporting spatial vision can be undermined by uncertainties introduced by optical aberrations and fixational eye movements, particularly in fovea where the neuronal grain of the visual system is fine. We examined the effect of these pre-neural factors on photopic spatial summation in the human fovea using a custom adaptive optics scanning light ophthalmoscope that provided control over optical aberrations and retinal stimulus motion. Consistent with previous results, Riccos area of complete summation encompassed multiple photoreceptors when measured with ordinary amounts of ocular aberrations and retinal stimulus motion. When both factors were minimized experimentally, summation areas were essentially unchanged, suggesting that foveal spatial summation is limited by post-receptoral neural pooling. We compared our behavioral data to predictions generated with a physiologically-inspired front-end model of the visual system, and were able to capture the shape of the summation curves obtained with and without pre-retinal factors using a single post-receptoral summing filter of fixed spatial extent. Given our data and modeling, neurons in the magnocellular visual pathway, such as parasol ganglion cells, provide a candidate neural correlate of Riccos area in the central fovea.

neuroscience↗