Vision Research

Reaction time is a measure of the speed of our response to stimuli in the environment. Even for a well-trained task, a subjects reaction time varies. One source of this variability is internal state fluctuations (such as changes in arousal). There are few studies that systematically quantify the extent to which reaction time varies across different timescales and link this to measures of systemic physiology associated with arousal. In much of the literature, it is assumed but not demonstrated that behavioral and systemic measurements associated with arousal will be consistently linked because both estimate a common underlying arousal process. In this work, we examined this assumption by simultaneously measuring reaction time, heart rate, and pupil diameter in rhesus macaque monkeys performing several visual tasks over hours and across hundreds of sessions. We found a portion of the variability in reaction time could be linked to systemic physiological signatures of arousal on fast timescales from second to second and slower timescales from minute to minute. This link between reaction time and systemic physiology was also present for different biomarkers of arousal (heart rate and pupil). However, the strength of this relationship varied depending on the arousal biomarker. Our findings support the conclusion that there are multiple arousal mechanisms that act simultaneously to influence behavior and multiple timescales at which they operate.

Dance is a core form of human-environment interaction and a powerful medium for emotional expression, yet dancers are routinely exposed to environmental affective cues that may shape their movement. We tested whether a negative emotional context induced immediately before improvisation alters dance biomechanics. Twenty professional dancers performed two 3-min improvised dances. Between dances, they viewed either Neutral or Negatively valenced pictures from the International Affective Picture System (IAPS; 2 min 40 s, 5 s per image). Eye tracking verified attention to the visual stream. Mood was assessed at four time points (PT1-PT4) using the Brazilian Mood Scale (BRAMS), and full-body, three-dimensional kinematics were captured at 300 Hz using a 9-camera optoelectronic system (Qualisys) and processed to measure global movement amplitude and expansion. Negative IAPS exposure increased tension, depression, fatigue, and decreased vigor from PT2 to PT3. Biomechanically, the Negative Stimulus dancers showed a significant reduction in global movement amplitude after negative IAPS exposure, with reduced movement amplitude of the body extremities. In contrast, global movement expansion remained unchanged; that is, the extremities were not positioned closer or farther from the pelvis. Neutral images produced no mood change and no measurable modulation of movement amplitude or expansion. Together, these results support the hypothesis that improvised dance carries biomechanical signatures of the dancers current affective state, beyond the intended expressive content, and provide an automated motion-capture workflow for studying emotion-movement coupling in spontaneous dance. HighlightsNegative visual context shifted dancers mood toward negative affect Negative images reduced movement amplitude in improvised dance Movement expansion remained stable despite mood induction Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/711707v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@aeaacdorg.highwire.dtl.DTLVardef@14f9bf5org.highwire.dtl.DTLVardef@18805fcorg.highwire.dtl.DTLVardef@1411256_HPS_FORMAT_FIGEXP M_FIG C_FIG

PurposeTo determine whether circadian timing defines critical molecular windows in myopia development and to assess the transferability of circadian gene programs across ocular tissues, disease stages, and species. MethodsPublicly available retinal and choroidal RNA-seq datasets from chick models of form-deprivation myopia were analyzed using unsupervised transcriptomic profiling and multistage machine-learning classification. Circadian windows were defined based on Zeitgeber time, and samples were grouped accordingly for downstream analyses. Classification model robustness was evaluated through cross-tissue and cross-stage validation and further assessed using external validation in an independent dataset. Functional translation to humans was examined using ortholog-based Gene Ontology enrichment analysis to identify conserved biological processes and higher-order regulatory pathways. ResultsA circadian critical window at ZT8-ZT12 exhibited the strongest transcriptional divergence during both myopia onset and progression. Gene signatures derived from this window generalized across retina and choroid and remained predictive across disease stages, supporting coordinated molecular regulation between ocular tissues. External validation confirmed the reproducibility of these signatures despite differences in experimental design and gene coverage. Functional mapping revealed that conserved molecular components in chicks are reorganized into more complex neuroendocrine and regulatory networks in humans, indicating cross-species conservation with increased functional complexity. ConclusionsCircadian timing strongly shapes myopia-related gene expression and underlies coordinated retina-choroid signaling. These findings highlight circadian biology as a key factor of refractive development and suggest that time-dependent mechanisms may influence myopia susceptibility, progression, and response to treatment.

Receptive fields provide a concise description of the stimulus selectivity of visual neurons. But this stimulus selectivity is neither static nor linear, and these nonlinear effects are not well captured by standard linear or pseudo-linear receptive field models. At the same time, receptive field models incorporating nonlinear effects are largely empirical, and are not easily interpreted in terms of underlying cellular and synaptic mechanisms. Here we show that two nonlinear mechanisms in the primate outer retina shape neural responses and that these contribute significantly to responses to natural stimuli and to the retinal output signals. Incorporating these outer retinal nonlinearities into models for visual function will improve our ability to identify the mechanistic origin of specific features of downstream visual responses.

Color is a prominent feature of visual experience, yet humans can recognize objects easily and accurately from grayscale images. We examined whether color becomes more useful when spatial information is degraded due to blurring. Participants viewed naturalistic scenes in color or grayscale, and reported whether a named target object was present across a range of blur levels that simulated optical defocus from 0-8 diopters. With unblurred images, performance did not differ between color and grayscale conditions, but as blur increased, recognition accuracy declined. Color provided a modest but reliable advantage at higher levels of blur, suggesting that color becomes increasingly useful when optical quality is degraded. We hypothesize that the evolutionary shift towards trichromacy may have been partially driven by the need to compensate for optical degradation due to aging and/or accumulated light exposure.

Numerical abilities are widespread in the animal kingdom and are not exclusive to humans. Domestic chicks (Gallus gallus) have been shown to discriminate numerosities spontaneously, but prior research has focused exclusively on the visual modality. Whether chicks can discriminate numerical information in the auditory domain remains unknown, despite evidence that they can perceive other auditory features such as tone and rhythm. In this study, we investigated spontaneous numerical discrimination in the auditory modality in naive domestic chicks. In Experiment 1, newly-hatched chicks were tested for their ability to discriminate between two auditory sequences differing in numerosity (4 vs. 12 identical sounds), with and without controlling for continuous variables such as duration and total sound amount. Experiment 2 examined chicks filial imprinting responses to familiar or unfamiliar numerosities. Experiment 3 controlled for potential spontaneous preferences for a single longer sound versus a shorter one. Our results showed a preference for the 12-sound sequence only when duration and total sound amount were not matched. When these continuous variables were controlled, no spontaneous numerical preference emerged. Experiment 2 revealed an overall preference for the 12-sound sequence regardless of imprinting conditions, while Experiment 3 confirmed that chicks do not have an inherent preference for longer sounds. These findings suggest that chicks are sensitive to overall magnitude in the auditory domain but do not spontaneously discriminate numerical differences when other continuous variables are held constant. Future studies will explore how specific stimulus features, such as heterogeneity of sounds, influence these preferences.

This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression profiles after intraperitoneal injections to Royal College of Surgeons (RCS) rats with Retinal Pigment Epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21 (p21), RCS rats received twice a week intraperitoneal injections of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with full field scotopic & photopic electroretinography (ERG) and optokinetic testing (OKT) 1 and 4 weeks after first injection (WAFI). The rats were euthanized after the ERG and OKT (1 or 4 WAFI) and the dissected retinas and RPE were collected for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results of our study showed that high dose (4mg/kg) HNG at 4 WAFI was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. Analysis of a and b waves from scotopic and photopic ERG showed no difference between either low or high dose of HNG and sham injection at 4 WAFI. However, at 4 WAFI, the visual acuity in rats treated with high dose HNG showed significant improvement as compared to the rats treated with low dose of HNG or saline. Most significantly, our findings support that HNG administered IP can modulate RPE/neuroretina cells and improve vision, thus may be a potential treatment for retinal degeneration diseases.

Saccadic eye movements sweep the visual scene across the retina, yet the resulting motion is rarely perceived. Visual factors alone, such as the presence of static pre- and post-saccadic images, can attenuate motion perception, suggesting a masking of the motion signal during early visual processing. Here, we isolated the visual component of this reduction in motion perception using simulated saccades presented to fixating observers. Across two experiments, we manipulated motion amplitude (6-18 dva), duration, and velocity profile and measured perceived amplitude and velocity at varying masking durations. Visual masking strongly reduced perceived motion amplitude and velocity, with short halftimes ([~]15 ms) that were largely invariant across saccade amplitudes. Critically, motion following a naturalistic saccadic velocity profile was perceived as smaller and slower than constant-velocity motion matched in amplitude and duration, even without explicit masking. This additional reduction increased with both amplitude and duration. These results show that visual mechanisms alone can account for substantial motion reduction across a large range of amplitudes and demonstrate a partially separable contribution of the saccadic velocity profile, suggesting that the temporal structure of retinal motion itself supports perceptual continuity across eye movements.

Binocular vision depends on the integration of matching visual features across the two eyes, while conflicting interocular signals can engage active inhibitory processes in the visual system. To investigate the temporal dynamics of these putative inhibitory processes, we examined how transitions between different binocular correlation states influence perceptual detectability and response speed. Using dynamic random-dot correlograms - free of monocular cues and allowing precise interocular manipulation - we presented brief target intervals embedded in longer background sequences. Stimuli varied in binocular correlation: correlated (C) patterns contained identical luminance profiles in both eyes, anticorrelated (A) patterns had inverted luminance dots, and uncorrelated (U) patterns had independent dot arrangements. Across three experiments, we measured (1) the presentation duration threshold required to detect a change in correlation, (2) simple reaction times (RTs) to the same transitions at suprathreshold levels, and (3) psychometric functions across durations for selected transitions. In Experiment 1, A[->]C transitions yielded significantly higher duration thresholds than C[->]A, indicating a suppressive influence associated with prior anticorrelation. In contrast, Experiment 2 showed that A[->]C transitions produced the shortest RTs, while C[->]U transitions were slowest, suggesting a rebound-like facilitation following prior suppression. Experiment 3 confirmed these temporal and contrast dependences, with opposite changes in contrast threshold and reaction times between transitions toward and away from the correlated fusional states. This divergence between perceptual onset and reaction time is consistent with a two-phase account in which binocular anticorrelation is associated with an initial suppressive phase followed by rebound-like facilitation that accelerates responses once the target becomes detectable. These findings are consistent with current models of binocular rivalry and fusion, and provide a temporally resolved behavioral perspective on how inhibitory control in sensory systems may dynamically influence subsequent responsiveness under conditions of perceptual ambiguity.

Spatialization in working memory refers to the spatial coding of non-spatial information along a mental horizontal line when encoding verbal material. This phenomenon is thought to support working memory by facilitating order encoding. Although it has been observed for both visually and auditorily presented stimuli, no direct comparison has yet examined whether these modalities rely on similar neural mechanisms. In this study, we investigated whether spatialization in visual and auditory modalities involves shared or distinct patterns of activity within the working-memory network. Forty-nine participants performed both a visual and an auditory working memory SPoARC task of the same verbal material, allowing to study the cortical patterns associated with distinct serial positions at both encoding and recognition across sensory modalities. Whole-brain analyses revealed similar frontoparietal networks across conditions. In addition, a representational similarity analysis (RSA) was conducted to assess the similarity of neural patterns between early and late serial positions in a sequence and across sensory modalities. This multivoxel pattern analysis revealed modality-dependent patterns distinguishing early and late positions in the inferior frontal gyrus. Additional modality-specific effects were observed in the anterior intraparietal sulcus in the visual modality and in the posterior hippocampus in the auditory modality. Drawing on the framework proposed by Bottini & Doeller (2020), we propose that order decoding in the IPS might reflect a low-dimensional spatial coding of order (e.g., along a horizontal axis), whereas order decoding in the hippocampus might reflect higher-dimensional spatial representations or temporal representations.

Vestibular schwannomas (VS) cause vestibular function loss by mechanisms still poorly understood. We evaluated the vestibulo-ocular reflex by the video-assisted Head Impulse Test (vHIT) in patients with planned tumour resection by a trans-labyrinthine approach. The vestibular sensory epithelia were collected and processed by immunofluorescent labelling for confocal microscopy analysis of sensory hair cell subtypes (type I, HCI, and type II, HCII), calyx endings of the pure-calyx afferents, and the calyceal junction normally found between HCI and the calyx (n=23). Comparing Normofunction and Hypofunction patients, we concluded that worse vestibular function associates with decreased HCI and HCII counts in the sensory epithelia and with increased proportion of damaged calyces. A decrease in the number of HCI and calyx endings of the pure-calyx afferents was recorded to associate with age increase. Partial least squares regression (PLSR) models indicated that VS and age had independent, additive effects on vestibular function. Correlation analyses indicated that lower vHIT gains associate with lower numbers of HCI and increased percentages of damaged calyces. These data support the hypothesis that the deleterious effect of VS on vestibular function is mediated, at least in part, by its damaging impact on the vestibular sensory epithelium. They also provide further evidence for the dependency of the vestibulo-ocular reflex on HCI function and for the calyceal junction pathology as a common response of the sensory epithelium to HC stress.

Functional near infrared spectroscopy (fNIRS) is increasingly used in hearing and communication research, with advantages such as robustness to movement artifacts, improved spatial resolution, and flexibility of contexts in which it can be applied. At the same time, the field is progressively moving towards more continuous, naturalistic listening paradigms resulting in the widespread adoption of speech tracking analyses such as temporal response functions (TRFs) in electroencephalography (EEG) and magnetoencephalography (MEG) studies. However, it remains unclear whether these analyses can be applied to slower haemodynamic signals measured by fNIRS. In the present study, we investigated whether a TRF framework can similarly be applied to fNIRS data recorded during continuous speech perception. Eight participants listened to speech simultaneously while fNIRS signals were acquired in a hyperscanning setup. Speech features were regressed onto the haemodynamic responses to test the feasibility and interpretability of fNIRS-based TRFs. Prediction correlations between observed and modelled fNIRS signals across speech features were higher than those typically reported for EEG- and comparable to those reported for MEG-TRF studies. Moreover, these correlations did not overlap with a null distribution generated from triallJmismatched fNIRS data, confirming statistical significance and were slightly greater than those obtained from a conventional GLM approach. Our findings support that TRF estimation method can yield meaningful and statistically significant responses from fNIRS data. HighlightsO_LITRF modelling can be meaningfully applied to fNIRS data acquired during speech listening tasks. C_LIO_LIPrediction correlations between actual and modelled fNIRS signals were above chance level, with values comparable to previous EEG/MEG studies. C_LIO_LITRFs explained more fNIRS variance than a conventional GLM approach. C_LI

Eye movement-related eardrum oscillations (EMREOs) appear to consist of a pulse of oscillation occurring in conjunction with saccades. However, this apparent pulse could occur either because there is an increase in energy at that frequency at the time of saccades (a true pulse), or because there is saccade-related phase resetting of ongoing energy at that frequency band, thus appearing like a pulse when averaged in the time domain across many trials. Here we conducted a spectral analysis at the individual trial level in humans performing a visually guided saccade task to determine whether the power at the EMREO frequency (30-45 Hz) is higher during saccades than during steady fixation. We found both an increase in sound power in the EMREO frequency band associated with saccades, i.e. sound pulses at the individual trial level, as well as, phase resetting at saccade onset/offset. While both factors contribute to the apparently pulse-like EMREO signal, phase resetting appears to be more prevalent across participants. The prevalence of phase resetting has implications for the underlying mechanism(s) producing EMREOs as well as functional consequences for how the ear might respond to incoming sound in an eye-position dependent fashion.

Despite substantial progress in understanding how visual features of food are processed in the brain, it remains unclear how subjective and nutritional properties, such as perceived palatability, caloric content, and health value, are reflected in neural representational structure. Using functional MRI and representational similarity analysis (RSA), we examined how visual, subjective, and nutritional food properties are encoded in ventral visual cortex. Univariate analyses revealed reliable activation differences between high- and low-calorie foods in lateral occipitotemporal cortex (LOTC) and fusiform gyrus. RSA further revealed a functional dissociation within the ventral stream: LOTC showed systematic correspondence with both visual and subjective dimensions, whereas fusiform cortex exhibited a selective association with perceived caloric content, with both effects persisting after controlling for visual similarity. These results suggest that food-related dimensions not fully captured by the tested visual models are reflected within visual representational spaces, and that LOTC and fusiform cortex show dissociable representational profiles with respect to subjective and perceived nutritional food dimensions.

Reverse correlation is a widely-used and well-established method for probing latent perceptual representations in which subjects render subjective preference responses to ambiguous stimuli. Stimuli are purposefully designed to have no direct relationship with the target representation (e.g., they are randomly-generated), a property which makes each individual stimulus minimally informative toward reconstructing the target, and often difficult to interpret for subjects. As a result, a large number of stimulus-response pairs must be gathered from a given subject in order for reconstructions to be of sufficient quality, making the task fatiguing. Recent work has demonstrated that the number of trials needed can be substantially reduced using a compressive sensing framework that incorporates the assumption that the target representation can be sparsely represented in some basis into the reconstruction process. Here, we introduce an alternative method that incorporates the sparsity assumption directly into stimulus generation, which holds promise not only for improving efficiency, but also for improving the interpretability of stimuli from subjects perspective. We develop this new method as a mathematical variation of the compressive sensing approach, before conducting one simulation study and two human subjects experiments to assess the benefits of this method to reconstruction quality, sample size efficiency, and subjective interpretability. Results show that sparse stimulus generation improves all three of these areas relative to conventional reverse correlation approaches, and also relative to compressive sensing in most conditions.

The rat vestibular system plays a critical role in anti-gravity responses such as the tail-lift reflex and the air-righting reflex. In a previous study in male rats, we obtained evidence that these two reflexes depend on the function of non-identical populations of vestibular sensory hair cells (HC). Here, we caused graded lesions in the vestibular system of female rats by exposing the animals to several different doses of an ototoxic chemical, 3,3-iminodipropionitrile (IDPN). After exposure, we assessed the anti-gravity responses of the rats and then assessed the loss of type I HC (HCI) and type II HC (HCII) in the central and peripheral regions of the crista, utricle and saccule. As expected, we recorded a dose-dependent loss of vestibular function and loss of HCs. The relationship between hair cell loss and functional loss was examined using non-linear models fitted by orthogonal distance regression. The results indicated that both the tail-lift reflex and the air-righting reflexes mostly depend on HCI function. However, a different dependency was found on the epithelium triggering the reflex: while the tail-lift response is sensitive to loss of crista and/or utricle HCIs, the air-righting response rather depends on utricular and/or saccular integrity.

The aim of this study was to improve our understanding of muscle contractions in the arm as a function of hand orientation for grasp. While there have been several reports on arm kinematics for reach and grasp movements, little has been done at the muscular level. To this end, we analyzed the modulation of shoulder, elbow and hand muscles for a reach and grasp task involving a target in either horizontal or vertical orientation. We hypothesized that unlike what has been observed for kinematics, at the muscular level we would see less correlation between the three muscle groups. A decoding approach with Machine Learning revealed adaptation patterns that were not visible using classical methods. Reach-and-grasp has traditionally been treated as being made of two components - the reach and the grasp components. Our dynamic decoding approach revealed a more complex picture with very different dynamics in the shoulder and elbow muscle groups during reach. All muscle groups showed peak capacity for predicting hand orientation before the start of grasp and followed the ubiquitous proximo-distal organization. The patterns of muscular modulation for hand orientation were strongly perturbed by the eyes closed and slow movement conditions, potentially decreasing the available degrees of freedom for adaptation.

SignificanceLaser speckle contrast imaging (LSCI) is widely used to measure blood flow, but speckle fluctuations may also encode biologically meaningful dynamics beyond perfusion. Foundational studies in dynamic light scattering (DLS) and micro-optical coherence tomography (OCT) have also demonstrated that slow coherent signal fluctuations can arise from energy-dependent intracellular motion in in vitro and ex vivo systems. Building upon these advances, recent work has shown that LSCI has the potential to detect slow speckle dynamics (SSD) correlated with cellular dynamics in vivo. However, the biophysical mechanisms underlying SSD in intact brain tissues remain insufficiently validated. Establishing a mechanistic bridge from controlled ex vivo and in vitro conditions to in vivo brain measurements is critical for translating speckle-based imaging beyond perfusion measurements to enable label-free assessment of cellular and metabolic activity in disease models. AimThe objective of this study is to investigate the biophysical origin of the SSD in vivo and evaluate its sensitivity to intracellular metabolic activity in brain tissue. ApproachWe utilize an epi-illumination LSCI system to measure speckle contrast as a function of camera exposure time and extract characteristic decorrelation time constants. SSD was investigated in acute mouse brain slices, where blood flow is absent, to eliminate vascular confounds. Cellular metabolism was systematically modulated using 2-deoxyglucose and glucose. Complementary in vivo measurements were performed to reveal SSDs response to hyperoxia and normoxia after ischemic stroke. ResultsSSD signals persisted in acute brain slices in the absence of blood flow. Inhibition of glycolysis significantly reduced SSD, while restoration of metabolic substrates partially recovered the signal. In in vivo measurements, SSD increased during hyperoxia compared to normoxia after ischemic stroke, suggesting increased oxygen-supported cellular metabolic activity. ConclusionsThese results indicate that SSD is sensitive to energy-dependent cellular processes closely tied to metabolic activity. SSD represents a previously uncharacterized, label-free in vivo optical contrast that enables assessment of cellular metabolic activity as well as vascular dynamics. This work establishes a mechanistic foundation for using SSD as a general optical marker of cellular viability in in vivo measurements.

Open-angle glaucoma (OAG) affects approximately 57.5 million individuals worldwide and is characterized by the progressive loss of retinal ganglion cells (RGC) and irreversible optic nerve damage resulting from chronic ocular hypertension. Intraocular pressure (IOP) is the only major modifiable risk factor in OAG and clinical treatments necessarily aim to lower IOP in order to preserve RGCs and prevent vison loss. Pharmacological therapies, such as prostaglandin analog containing eye drops, are known to be effective at reducing IOP, but are critically undermined by poor patient compliance and are unable to control for potentially damaging diurnal fluctuations in IOP, leading to vision loss even in patients diagnosed early. Herein we evaluate the effectiveness of a long-acting, single use, prostaglandin-based recombinant adeno-associated virus (rAAV)-mediated IOP-lowering gene therapy treatment in glaucomatous DBA/2J mice and demonstrate that sustained IOP reduction leads to preservation of both optic nerve anatomy and function in end-stage glaucomatous disease. One Sentence SummaryIOP-lowering gene therapy provides partial anatomical and functional rescue in glaucomatous mouse model following single dose treatment

ObjectiveTo determine whether non-axon optic nerve morphometric features correlate with clinical visual function as strongly as the traditional axon count gold standard. DesignCross-sectional histological analysis with longitudinal clinical correlation. SubjectsEighteen mice from three strains: C57BL/6J (n=6), BXD51 (n=6), and DBA/2J (n=6). MethodsLeft eye (OS) optic nerves from mice euthanized at 12 months of age were resin-embedded and stained with p-phenylenediamine. Bright-field cross-sectional images were segmented using an AxonDeepSeg-based workflow to generate axon, myelin, whole nerve, and glial coverage masks for morphometric quantification. Seven morphometrics were extracted: axon count (nAx), axon density (AxDen), glial coverage area ratio (GliaR), mean solidity (Sol), mean axon diameter (AxDiam), mean myelin area (MyArea), and mean axon-myelin area (AxMyArea). Morphometrics were correlated with longitudinal clinical data collected at 1, 3, 6, 9, and 12 months, including visual acuity (VA), contrast threshold, intraocular pressure (IOP), and pattern electroretinography P50 and N95 amplitudes (PERG P50 and N95). Main Outcome MeasuresPearson correlation coefficients were used to assess associations between morphometric features and clinical measures, and Fisher z-transformed meta-analytic correlations were used to aggregate these associations across ages. ResultsVA and contrast threshold demonstrated strong correlations with GliaR that matched or exceeded nAx. Meta-analysis across ages revealed GliaR correlated with VA (r = -0.84, p = 4.49 x 10-21) and contrast threshold (r = 0.86, p=7.55 x 10-23), comparable to nAx correlations with VA (r = 0.80, p=8.13x10-17) and contrast threshold (r = -0.80, p= 1.74x10-16). Structure-function relationships shifted with age: at 6 months, GliaR had the strongest correlation with contrast threshold (r = 0.96), while at 12 months, AxDiam became the dominant correlate of both VA (r = 0.77) and contrast threshhold (r = -0.74). IOP, PERG P50, and PERG N95 exhibited weak correlations with all morphometrics (|r| < 0.27). ConclusionsNon-axon morphometrics, particularly glial coverage area ratio, correlate with visual function as strongly as traditional axon count. Automated optic nerve assessment should incorporate glial and other non-axon features. Further, stage-aware biomarker selection may better capture structure-function relationships in glaucoma.