Biology subjects

Khan, A. Z.

Publications and source records attributed to Khan, A. Z..

5 recordsLinked to original sources

bioRxiv2026

Asymmetric Adaptation of Catch-up Saccades with Artificial Central Scotomas

In fully-sighted individuals, pursuit and saccadic eye movements work together to foveate moving targets; pursuit attempts to match target velocity, while catch-up saccades re-align the fovea to the target if it deviates during pursuit. Although saccade-pursuit interactions are well understood in healthy individuals, much less is known about how these mechanisms adapt in the presence of central vision loss. Here, we simulated central vision loss in healthy young adults to examine plasticity in saccade-pursuit mechanisms and investigated whether and how catch-up saccades adapted over five days of visual tracking. Twenty-five fully sighted participants performed a task in which they pursued a moving target that stepped position randomly (designed to elicit catch-up saccades) while viewing with a gaze-contingent central scotoma. The scotoma was shaped like a bitten cookie to encourage use of a specific preferred retinal locus (PRL) corresponding to the peripheral location with the highest acuity. By the end of the five days of repetition, most participants showed catch-up saccade endpoints shifted towards the PRL rather than the fovea. On average, endpoints shifted 0.5 deg towards the PRL between days 1 and 5 (range=0.3-1.5 deg), with significant shifts in 13 of the 25 participants. Adaptation was asymmetric; shifts were largest when the target moved in the direction opposite the scotoma bite and smallest when it moved towards it. In summary, we observed adaptation of saccade-pursuit interactive mechanisms through the re-referencing of catch-up saccades from the fovea to PRL. These results provide a promising avenue for rehabilitation in central vision loss aimed at improving eye movements and encouraging PRL use. Ultimately, such an approach may enhance residual visual function and quality of life.

neuroscience↗

bioRxiv2025

Mapping galectin-3 ligands in tear fluid establishes spliceoform-dependent lacritin binding

Galectin-3 (Gal-3) is a carbohydrate-binding protein which plays crucial roles in inflammation, immune response, cell migration, autophagy, and signaling. At the ocular surface, Gal-3 is also known to crosslink transmembrane mucins across the epithelial cell glycocalyx, forming lattice structures important for barrier function. However, the biological role of Gal-3 in circulating tear fluid remains largely unexplored. Similarly, whether Gal-3 engages extracellular glycoproteins in tears to affect downstream biological processes has yet to be investigated. As increased Gal-3 levels in tears are known to correlate with ocular pathologies such as dry eye disease (DED), we sought to elucidate the Gal-3 interactome in tear fluid and uncover biological insights into the function of Gal-3 beyond adhesion to the epithelial cell surface. Here, we combined ELISA, lectin affinity enrichment, mass spectrometry (MS)-based glycoproteomics, and lectin blotting to uncover Gal-3 interactors and their associated glycoepitopes. Overall, we report nearly 100 proteins enriched from tear fluid across 3 different patients, identifying proteins involved in immune response, inflammation, and antimicrobial activity. Most notably, we report lacritin as a novel ligand for Gal-3 and demonstrate that specific glycoforms of lacritin bearing core 2 O-glycans preferentially engage with Gal-3. Lastly, we show that the Gal-3-lacritin axis is spliceoform-specific and dependent on lacritin multimerization. Taken together, this study elucidates new ligands for Gal-3 in tear film and reveals mRNA splicing and multimerization as new biochemical mechanisms that fine-tune Gal-3 binding events.

biochemistry↗

bioRxiv2024

Timing and Amplitude of Catch-up Saccades to Accelerating Targets

To track moving targets, humans move their eyes using both saccades and smooth pursuit. If pursuit eye movements fail to accurately track the moving target, catch-up saccades are initiated to rectify the tracking error. It is well known that retinal position and velocity errors determine saccade timing and amplitude, but the extent to which retinal acceleration error influences these aspects is not well quantified. To test this, 13 adult human participants performed an experiment where they pursued accelerating / decelerating targets. During ongoing pursuit, we introduced a randomly sized target step to evoke a catch-up saccade and analyzed its timing and amplitude. We observed that retinal acceleration error was a statistically significant predictor of saccade amplitude and timing. A multiple linear regression supported our hypothesis that retinal acceleration errors influence saccade amplitude in addition to the influence of retinal position and velocity errors. We also found that saccade latencies were shorter when retinal acceleration error increased the tracking error and vice versa. In summary, our findings support a model in which retinal acceleration error is used to compute a predicted position error [~]100ms into the future to trigger saccades and determine saccade amplitude. Significance statementWhen visually tracking object motion, humans combine smooth pursuit and saccadic eye movements to maintain the target image on the fovea. Retinal position and velocity errors are known to determine catch-up saccade amplitude and timing, however it is unknown if retinal acceleration error is also used to predict future target position. This study provides evidence of a small but statistically significant contribution of retinal acceleration error in determining saccade amplitude and timing.

neuroscience↗

bioRxiv2023

Choice anticipation as gated accumulation of sensory expectations

Predictions are combined with sensory information when making choices. Accumulator models have conceptualized predictions as trial-by-trial updates to a baseline evidence level. These models have been successful in explaining the influence of choice history across-trials, however they do not account for how sensory information is transformed into choice evidence within-trials. Here, we derive a gated accumulator that models the onset of evidence accumulation as a combination of delayed sensory information and a prediction of sensory timing. To test how the delays interact with across-trial predictions, we designed a free choice saccade task where participants directed eye movements to either of two targets that appeared with variable delays and asynchronies. Despite instructions not to anticipate, participants responded prior to target onset on some trials. We reasoned that anticipatory responses may reflect a trade-off between inhibiting and facilitating the onset of evidence accumulation via a gating mechanism as target appearance became more likely. Using a choice history analysis, we found that anticipatory responses were more likely following repeated choices, despite task randomization, suggesting that the balance between anticipatory and sensory responses was driven by a prediction of sensory timing. By fitting the gated accumulator model to the data, we found that variance in within-trial fluctuations in baseline evidence best explained the joint increase of anticipatory responses and faster sensory-guided responses with longer delays. Thus, we conclude that a prediction of sensory timing is involved in balancing the costs of anticipation with lowering the amount of accumulated evidence required to trigger saccadic choice, which could be explained by history-dependence in the baseline dynamics of a gated accumulator. New and NoteworthyEvidence accumulation models are used to study how recent history impacts the processes underlying how we make choices. Biophysical evidence suggests that the accumulation of evidence is gated, however classic accumulator models do not account for this, so little is known about how recent history may influence the gating process. In this work, computational modeling and experimental data from a free choice saccade task argue that predictions of the timing of sensory information are important in controlling how evidence accumulation is gated, and that signatures of these predictions can be detected even in randomized task environments where history effects may not be expected.

neuroscience↗

bioRxiv2019

Saccadic adaptation in the presence of artificial central scotomas

Saccadic adaptation can occur over a short period of time through a constant adjustment of the saccade target during the saccade, resulting in saccadic re-referencing which directs the saccade to a location different from the target that elicited the saccade. Saccade re-referencing could be used to help patients with age-related macular degeneration (AMD) to optimally use their residual visual function. However, it remains unknown whether saccade adaptation can take place in the presence of central scotomas (i.e., without central vision). We tested participants in two experiments in a conventional double-step paradigm with a central gaze-contingent artificial scotoma. Experiment 1 (N = 12) comprised a backward adaptation paradigm with a visible and an invisible 3{degrees} diameter scotomas. Experiment 2 (N = 13) comprised a forward adaptation paradigm with invisible 2{degrees} and 4{degrees} diameter scotomas. In Experiment 1, we observed significant adaptation in both the visible and invisible scotoma conditions comparable to the control condition with no scotoma. This was the case even when the saccade landed such that the target was occluded by the scotoma. We observed that adaptation occurred based on peripheral viewing of the stepped target during the deceleration period. In Experiment 2, we found that both scotoma conditions showed adaptation again comparable to the control condition with no scotoma. We conclude that saccadic adaptation can occur with central scotomas, showing that it does not require central vision and is driven primarily by peripheral retinal error.

neuroscience↗