BAVRD 2023 Program

Felice Dunn began her studies in neuroscience as an undergraduate at Brown University where she worked with David Berson in the discovery of intrinsically photosensitive ganglion cells. She then continued her studies in vision at the University of Washington with Fred Rieke as a graduate student and with Rachel Wong as a postdoctoral fellow. With Fred Rieke, she examined retinal gain controls that enable vision across a broad range of mean light levels. With Rachel Wong, she uncovered developmental patterns of synapse formation. In between, she studied the fidelity of olfactory processing at the NIH with Mark Stopfer. Currently at UCSF, her lab examines retinal circuits under healthy and diseased conditions.

'Of the dozens of channels coursing from retinal ganglion cells to the rest of the visual system, several are dedicated to non-perceptual functions such as image stabilization. Image stabilization is controlled by both the vestibulo-ocular reflex as well as the optokinetic reflex. I will present work from our lab about the retinal pathways underlying the optokinetic reflex, which is controlled by the accessory optic system. The accessory optic system receives input from specific populations of motion sensitive ON direction selective ganglion cells.

First, I will show how synaptic differences to the ganglion cells signaling superior vs. inferior motion result in asymmetries at the level of the reflexive eye movements. Next, I will demonstrate that a simple computation across the ganglion cell populations accurately predicts features of the eye movements. Finally, I will present how perturbations to retinal circuits influence the behavior. Overall, I would like to convey the advantages of using the accessory optic system, which is relatively simpler than other pathways for conscious visual perception, to understand the relationships between stimulus input, cellular physiology, and a behavioral output.'

Yvette Fisher is an Assistant Professor in Neurobiology at the University of California Berkeley and an investigator of the Chan Zuckerberg Biohub. She received her PhD from Stanford University and completed Postdoctoral training at Harvard Medical School. Her laboratory at Berkeley combines advanced genetic approaches in Drosophila with high resolution neuronal recordings during behavior to investigate how brains flexibly form a sense of direction. Her discoveries about nervous system computation have been recognized by honors including an HHMI Hanna Gray Fellowship, a Klingenstein-Simons Fellowship, a Sloan Research Fellowship, and an NIH Director’s New Innovator award.

'In the Drosophila brain, head direction neurons form a network whose activity tracks the angular position of the fly using both external visual signals and internal self-motion information. Our previous work discovered that synaptic plasticity allows these external signals to be combined with internal cues to form a coherent sense of direction. In this talk I will discuss a role for the neuromodulator dopamine in shaping visual plasticity.

We hypothesize that dopamine provides a “when-to-learn” signal that allows the head direction network to update synaptic weights when new spatial information is available—that is, when a fly is rotating. We show that dopamine neurons that innervate the head direction network are active when the fly turns. Pairing dopamine release with a visual cue persistently strengthens the cue’s influence on head direction cells. Conversely, inhibiting these dopamine neurons decreases the influence of the cue. This mechanism should accelerate learning during moments when orienting movements are providing a rich stream of head direction information, allowing learning rates to be low at other times to protect stored information.'

Lee Stone is the NASA Senior Researcher for Human-Systems Integration at Ames Research Center. He received a BA in Biophysics from The Johns Hopkins University, an MS in Engineering from UC Berkeley, and a Ph.D. in Neuroscience from UC San Francisco. After a post-doctoral associateship in the Human Factors Division at NASA Ames, he was hired as a Research Physiologist in the Life Sciences Division in 1990. He later joined the Human-Systems Integration Division and established the Visuomotor Control Laboratory to examine human capabilities in visual-vestibular perception and sensorimotor control with a scientific eye towards understanding the impacts of altered environments on human performance and an engineering focus on non-invasive eye-movement-based technologies for detecting and characterizing of sub-clinical impairment.

Photo by The Physiological Society.

'It has long been known that qualitative abnormalities in eye movements can be used to diagnose overt brain pathologies (Diefendorf & Dodge, 1908; Fox & Holmes, 1926; Leigh & Zee, 2015). Here, we will examine the use of a set of quantitative measures of the human behavioral response (oculometrics) in a 5-minute radial ocular tracking task (Krukowski & Stone, 2005) with sufficient temporal, spatial, and directional uncertainty to minimize the contribution of a priori prediction or anticipation, and to emphasize the use of a posteriori visual processing of the stimulus trajectory (Liston & Stone, 2014).

The derived oculometrics provide a largely independent, reliable set of metrics that are sensitive enough to detect mild sub-clinical impairment across a range of possible neural loci (Stone et al., 2019) with the pattern of impairment across the set providing specificity as to its nature (Tyson et al., 2023). We will review our earlier findings where oculometrics have been used to detect mild impairment due to traumatic brain injury, sleep loss, and low-dose alcohol (Liston et al., 2017; Stone et al., 2019; Tyson et al., 2021). We will also report on a recent clinical study of asymptomatic patients at risk of retinal pathology (Leung et al., 2022) and show that oculometrics can detect and characterize substantive loss of visual function in the absence of clinical indicators of pathology. We conclude that oculometric testing could be used as a routine non-invasive ophthalmological or neurological tool to aid in the early detection and diagnosis of neural injury, toxicity, or disease.'

Dr. Matilda F. Chan is a Professor and a clinician-scientist in the Department of Ophthalmology and the Francis I. Proctor Foundation at the University of California, San Francisco. She completed her undergraduate studies the University of California, Berkeley and obtained her combined MD/PhD degrees from the Keck School of Medicine of the University of Southern California. She completed her ophthalmology residency at the Flaum Eye Institute of the University of Rochester, which was followed by a fellowship in cornea and external diseases at the Francis I. Proctor Foundation/University of California, San Francisco.

Her basic/translational research program focuses on cellular and molecular mechanisms related to corneal repair and corneal endothelial dystrophies with a goal of developing novel therapies. She has received research funding from the NIH/National Eye Institute (K08 and R01 awards), Research to Prevent Blindness (Physician-Scientist Award), among other foundations. She has served on several committees of the Association for Research in Vision and Ophthalmology (ARVO), including the Annual Meeting Program Committee, educational working group, Advocacy and Outreach Committee, and Leadership Development Program for Women. She currently serves as an Associate Editor for Cornea Open and as an editorial board member for Cornea and Ophthalmology Science.

'Inherited mutations in eye proteins are known to give rise to severe, early-onset ocular diseases. Many of these mutations are located in the protein’s coding region, causing protein folding defects. Mutations in the SLC4A11 gene have been linked to corneal endothelial dystrophies, including Fuchs endothelial corneal dystrophy (FECD), congenital hereditary endothelial corneal dystrophy (CHED), and Harboyan Syndrome. The cellular effects of SLC4A11 protein misfolding and how correctors of protein misfolding may regulate FECD development and progression will be discussed.'

As Sr. Director, Vision Sciences, Paul Chamberlain is currently responsible for the strategic direction and execution of CooperVision’s research in all aspects of vision and myopia. His team are committed to deliver evidence-based novel solutions to enhance vision and wearer experience of patients across their life. Prior to this, he managed a team of optometrists who supported all clinical product development activities within R&D. Before joining CooperVision in 2011, Paul spent five years managing industry sponsored research studies at Eurolens Research at the University of Manchester. Prior to that, he was part of Michel Guillon’s research team at Optometric Technology Group in London. Paul earned his bachelor’s degree in optometry from City University in London.

'Combined use of concurrent and virtual control untreated myopic eyes, enables efficacy of myopia control therapies to be monitored over multiple years offering the opportunity to quantify the accumulation of long term treatment effects. Slowing of axial elongation of children treated with a dual focus (DF) myopia control contact lens was assessed over 6-years.

Methods: Axial lengths of eyes measured annually with an optical biometer were either treated for 6 consecutive years with a DF myopia control contact lens (MiSight 1 day, CooperVision Inc.) or fit with a control single vision contact lens for 3 years and switched to the DF lens for 3 years. Treatment effects were quantified by the difference in average axial growth of treated eyes to (1) growth of study control eyes; (2) expected growth of untreated age-matched myopic eyes and (3) expected growth of age-matched emmetropic eyes.

Results: Treated eyes showed annual growths slower than control eyes during each of the 6 treatment years (p is less than 0.05), accumulating to an average difference in growth of 0.52mm for eyes treated for 6 years and 0.19mm when treatment was initiated 3 years later. Treated eyes grew at rates comparable to those expected of age-matched emmetropic eyes. Conclusion: Use of estimated growth of age-matched untreated myopic eyes provided evidence of sustained slowing of axial elongation accumulating to 0.52 mm over 6 years. Treated growth levels remained close to those expected of emmetropic eyes.'

Dr. Feldheim was born and raised in Ventura California. He went to college at UC San Diego and worked in the laboratory of Milton Saier studying sugar transport in bacteria. Dr. Feldheim completed his PhD at UC Berkeley in the lab of Randy Schekman and studied mechanisms of protein translocation across the endoplasmic reticulum membrane. He moved east of Interstate 5 for the first time for his post-doc in John Flanagan’s lab at Harvard Medical School, where he obtained his passion for axon guidance, and neural development primarily using the mouse visual system as a model. Dr. Feldheim has been at UC Santa Cruz since 2002.

'Determining the location of an object in a complex environment and evaluating its saliency is a fundamental and necessary brain function. To achieve this, the brain needs to receive, process, and integrate sensory information from multiple sensory modalities. A model to study spatial sensory integration is the superior colliculus (SC), the only structure in the brain that contains both visual and auditory maps of space. In the primate and cat, spatial maps of both vision and hearing align in the adult SC, and individual bimodal neurons have overlapping visual and auditory receptive fields (RFs).

This same topographic alignment of visual-auditory RFs in the barn owl is sensitive to sensory experience during specific developmental phases and is linked to changes in orienting behavior. We and others have shown that a combination of graded molecular cues and activity-dependent refinement is used to create the point-to-point map of visual space in the superficial layers of the SC; however, it remains unknown how the computed auditory map of space in the mammalian SC forms and how this map becomes aligned and integrated with the visual map. In this talk I will share our recent work that aims to determine the mechanisms used to form and align the visual and auditory maps of azimuth in the mouse SC.'

E.J. Chichilnisky received his BA in mathematics from Princeton University, and MS in mathematics and PhD in neuroscience from Stanford University. He is the John R. Adler Professor of Neurosurgery, and a Professor of Ophthalmology, at Stanford University, where he has worked since 2013. Previously, he worked with the Salk Institute for Biological Studies for 15 years. His research has focused on understanding the spatiotemporal patterns of electrical activity in the retina that convey visual information to the brain, and their origins in retinal circuitry, using large-scale multi-electrode recordings from primate and human retina.

His ongoing work now focuses on using basic science knowledge along with electrical stimulation to develop a novel high-fidelity artificial retina for treating incurable blindness. He is the recipient of an Alfred P. Sloan Research Fellowship, a McKnight Scholar Award, a McKnight Technological Innovation in Neuroscience Award, and a Research to Prevent Blindness Stein Innovation Award.

'The visual processing properties of most of the ~20 retinal ganglion cell (RGC) types in the human and non-human primate retina remain largely unknown. We combined large-scale high-density multi-electrode recordings from isolated retina with several technical advances – multi-resolution spatial analysis of light responses, electrical imaging, modern spike-sorting, and large-scale data mining – to obtain a functional overview of the cell types in the macaque and human retina. At least 22 RGC types and 10 polyaxonal amacrine cell (PAC) types were clearly distinguished.

Cell type identification was confirmed by mosaic organization within each retina and reproducible types across retinas. Novel RGC and PAC types exhibited striking and diverse non-classical receptive fields that served as distinct functional fingerprints. Cell types in the human retina exhibited similar properties as in macaque. The unusual receptive field structure of novel cell types suggest that they may sample inputs from ON and OFF bipolar cells over space in unexpected ways, and that blue-sensitive cone signals are represented in a greater diversity of cell types than was known.'

'Subretinal prostheses can restore vision in patients with atrophic age-related macular degeneration by electrically stimulating the remaining bipolar cells. Microglia activation, Müller cell gliosis, and glial scarring in response to implantation could form a physical barrier against electrical stimulation. Here, we assessed the effect of anti-inflammatory drugs during the implantation surgery on retinal integration with the implant.

Flat and 3-D honeycomb-shaped subretinal prostheses were implanted in Royal College of Surgeons rats. Four medications were compared to a control group: 1. Triamcinolone, 2. Dexamethasone 3. Ketorolac, which were introduced subretinally with the implants, 4. Topical Dexamethasone (n=4-6 per group). Retinal tissue was collected 5 days after surgery and microglial activation was quantified by immunohistochemistry using IBA1 antibody.

Dexamethasone was found to be the most efficient in reducing microglial activation. In both flat and 3-D implants, the number of IBA1-stained cells at electrode-retina interface in Dexamethasone group was significantly lower compared to control: by 65% with flat implants and by 61% with 3-D implants.

Perioperative anti-inflammatory treatment can prevent microglia activation right after implantation. Further analysis of the cell migration into the implant as well as physiological response to electrical stimulation should be conducted to assess long-term benefits of subretinal immune suppression during implantation.'

'Following photoreceptor loss, parallel pathways within the retina undergo structural and functional modifications that impact fundamental computations, e.g., temporal and spatial filtering through center-surround receptive fields. Our previous work demonstrated that partial cone loss triggers inhibition to increase spatiotemporal integration, recover contrast gain, and increase synaptic release onto ON ganglion cells. However, it is unclear how functionally distinct microcircuits, e.g., ON vs. OFF pathways or specific ganglion cell types, are affected by partial cone loss. We ask (1) whether two OFF ganglion cell types, alpha OFF-sustained (AOFF-S) and OFF-transient (AOFF-T) cells, exhibit common or unique reactions to partial cone loss, and (2) which inhibitory circuits, i.e., glycinergic or GABAergic inhibition, compensate for fewer cones.

To test these possibilities, we recorded the activity of AOFF-S and AOFF-T ganglion cells. We found that while OFF pathways show greater capacity for inhibition to modify spatiotemporal processing with fewer cone inputs, the extent of functional adjustments was unique between two cell types. We also revealed a mechanism for increased inhibitory inputs caused by cone loss from pharmacology. These findings demonstrate that partial cone loss induced circuitry changes that occur after the divergence of OFF pathways, which receive a serial GABA-to-glycine inhibition to recover from cone loss.'

'Transcranial ultrasound stimulation (TUS) is an emerging tool to noninvasively modulate neural activity in deep brain areas. In preparation for our first in-human TUS studies, we targeted TUS to the lateral geniculate nucleus (visual thalamus) in a large mammal (sheep). Full-field light flash stimuli were presented with or without concomitant TUS in randomly interleaved trials. Similar to what has previously observed by Fry et al (Nature 1959) in cats, EEG visual-evoked potentials (VEPs) were reversibly suppressed by TUS to the LGN (n=6). No changes in VEPs were observed in sheep who received sham-TUS to a control site in the basal ganglia (n=5), ruling out potential transducer auditory-somatosensory confounds.

Magnetic resonance acoustic radiation force imaging (MR-ARFI), a technique to measure the ultrasound focus in situ, showed a focal volume of microscopic displacement at the expected target. Excitingly, MR-ARFI predicted the suppressive effect on VEPs in individual subjects, suggesting that MR-ARFI can be used to confirm TUS targeting and estimate neurophysiological impact. We are now translating this paradigm into human, targeting TUS to the LGN while participants perform a contrast detection task with EEG recording of steady-state VEPs. MR-ARFI will be measured to evaluate targeting and estimate TUS dosage. This work provides the foundation for a dissection of the roles of different subcortical nuclei in different aspects of human vision.'

'One key feature of the cortex is its flexibility to adapt the neuronal representation of sensory stimuli in a context and manner. Inhibitory circuits are thought to play a critical role in learning-dependent representational adaptation, but the precise targets of this plasticity remain elusive. To address this question, I combined two-photon calcium imaging with patterned optogenetic illumination to recreate visual activity with high accuracy in the cortex of awake mice. I mapped the feature-dependent functional microarchitecture of naïve and expert mice trained in an orientation discrimination task. I dissected both excitatory (E) E-E interactions and as well as interactions with inhibitory Parvalbumin interneurons (PVs).

The responses in non-targeted E cells followed an orientation-specific “like-excites-like” connectivity pattern convolved with spatially structured suppression. Strikingly, although naïve E-PV connections were not orientation-specific, a “like-excites-like” connectivity pattern emerged in expert mice, suggesting that this inhibitory population can become integrated into feature-specific ensembles in an experience-dependent manner. This circuit recongifuraiton can help explain the two signature changes in visual processing that emerge in expert mice: sparsening of population vectors and enhanced selectivity of PV interneurons. Thus, our findings provide critical evidence that mechanistically links microcircuit architecture to learned cortical computations.'

'This study examined if typical age-related increase in visual dependence for spatial referencing persists in older adults with central field loss (CFL). Twenty individuals with CFL were grouped into those with age-related binocular CFL (CFL, N=9), age-related monocular CFL/relative scotomata (mCFL, N=8), and CFL occurring at a young age (yCFL, N=3). Controls included 17 age-matched to the older CFL groups (OA) and 3 matched to the yCFL group (yOA). Participants judged the tilt direction of a rod presented at various orientations in conditions with and without an orienting visual context. Visual dependence was defined as the difference in judgement bias between conditions with and without the context. All older groups performed similarly in the no context condition.

The CFL group was significantly more visually dependent than OA. However, there was no group difference when all three older groups were considered. Poorer contrast sensitivity was significantly correlated with greater visual dependence. Visual dependence persists in older adults with CFL and seems exacerbated in those with dense binocular scotomata. This may be due to the spared peripheral retina, providing cues for orientation and motion perception. The relationship with contrast sensitivity further suggests that decline in visual function is associated with increase in visual dependence beyond the effects of normal aging. These observations can guide tailored care and rehabilitation in older adults with CFL.'

'Visual acuity can remain unaffected after dysfunction of up to half of all cones, suggesting compensatory mechanisms within the visual system. Partial cone loss alters spatiotemporal altering of ON-sustained alpha retinal ganglion cells (RGCs), however the reaction of ON-direction selective ganglion cells (oDSGCs) remains unknown. We use a mouse model (cone-DTR) that selectively ablates 25% or 50% cones and retrograde labeling to target two types of oDSGCs, sensitive to upward- (Superior) and downward- (Inferior) motion. We hypothesize that cone loss causes reduced responses in oDSGCs from reduced cone inputs.

We measured spike responses to all directions (tuning curve area) and direction selectivity indices (DSI) using cell-attached recordings of oDSGCs from dark-adapted retinas. In 50% cone-DTR retinas, oDSGCs had smaller tuning curve areas and fewer spikes in their preferred directions. Superior and Inferior oDSGC populations had lower tuning curve areas, and the variance of preferred direction increased in Superior oDSGCs. Tuning curve area and preferred direction responses were not significantly different between oDSGCs in 25% cone-DTR and WT retinas. oDSGCs in both cone loss conditions had larger DSI than WT controls. These results indicate that the severity of cone loss differentially affects tuning of oDSGCs, where minor cone loss increases direction selectivity and further disruption reduces response gain.'

'The ON and OFF retinocortical processing pathways may be differently affected by ocular pathology. So, a measure that can describe ON and OFF pathway function is desirable. Here we develop a Steady-State Visually Evoked Potential method that measures ON and OFF pathway responses from the upper and lower visual fields simultaneously. We do so at several luminance contrasts in 21 observers with normal vision using a 128 channel EEG system. Probes were luminance modulated at 3.0Hz (upper) and 3.75Hz (lower) with a sawtooth profile, the polarity of which was set to bias responses towards the ON or OFF pathways. Spectral analysis can separate upper and lower visual field responses.

Each observer’s 128 channel data was algorithmically reduced to a small number of stimulus-tracking components, separately for the upper and lower fields. Signal amplitudes were then fit with a transducer function at the group-level, the parameters of which describe neural sensitivity to changes in contrast. Parameters for the ON and OFF pathways in the upper and lower visual field were compared. We find that OFF-favoring stimuli generated larger responses overall. Response functions in the upper visual field were shallower and continued to increase over a wider range of contrast levels. This difference was significant when comparing the ON pathway in the upper visual field to the OFF pathway in the lower visual field, and the OFF upper pathway to the OFF lower pathway.'

'Electroencephalography (EEG) is used abundantly in research and applied settings because it has high temporal resolution, is portable, inexpensive, and non-invasive. EEG requires direct contact between the electrode and the scalp to detect neural signals. However, the caps that hold the electrodes in place are not compatible with coarse and curly hair because the electrode sits over the hair, not on the scalp. Here, we test clips that we developed to improve contact with the scalp. EEG data were collected from 6 individuals: 2 of type 1 hair (straight), 2 of type 3 hair (wavy), and 2 of type 8 hair (curly). Participants were presented with a grating stimulus that reversed contrast at 4Hz while EEG data were collected, once with the clips and again with the EEG cap. The 4Hz pattern generated a steady-state response that is detectable at the level of the individual. The root-mean-square signal-to-noise ratios (SNRs) were calculated for the 4Hz signal and the following 4 harmonics for the cap and the clip data separately.

For hair type 1, there was a 61% increase in SNR with the clips compared to the cap and an 82% increase in SNR for hair type 3. For hair type 8, there was no difference in SNR between the cap and the clips, despite high power overall. These findings suggest that the clips measure signal that is at least as strong if not stronger than the cap. However, the clips are currently not performing better with curly hair. Prospective solutions will be discussed.'

'The mixed rod-cone “duplex” retina is well studied, but we still know little about retinas with monotypic photoreceptor populations, termed “simplex”. The Little skate (Leucoraja erinacea) is a cartilaginous fish, which has a rod-only retina. The skate retina can function under both scotopic and photopic conditions, but we know little about its molecular composition in adulthood and development. It is also unknown if the birth order of neurons in skate resembles that of neurons in duplex retinas. It has been established that the first elements of duplex retinal circuitry to be born are ganglion cells, followed by horizontal cells, cones, and amacrine cells. Rods, bipolar cells, and Müller cells do not appear until later.

Here, we have performed RNA-seq and in situ hybridization on developing and adult skate retinal tissue in an effort to fill these gaps in knowledge. We were able to clone out skate Rho and localize the mRNA via in situ hybridization to its expected location in the inner segments of rods in adult retina. However, Rho is missing in St32 retinas and a signal for the GABA transporter GAT (found in horizontal and/or amacrine cells) is present in adult and St32 retina.

These findings suggest a birth order of retinal neurons that is similar to duplex retina. We were also able to detect transcript signals for some common bipolar cell proteins, like PKCα and TRPM1, in their expected locations in the INL. Localization of other important mRNAs is ongoing.'

'Glaucoma, an irreversible blindness disorder, is characterized by death of retinal ganglion cells (RGC’s). Recently, Lipoxin (LX) B4 was discovered as a resident retinal lipid mediator that protects against RGC death in rodent models of glaucoma. Lipoxins are a product of arachidonic acid metabolism which requires the interaction of enzymes 5-lipoxygenase (5-LOX) and 15-LOX. In ocular hypertension-induced glaucoma-like pathogenesis, disruption of microglia homeostatic function is an early event that leads to RGC death. The impact of the lipoxin pathway on microglia homeostatic functions remains largely unexplored. Here, we used a silicon oil-based ocular hypertension mouse model to establish the neuroprotective action of LXB4 by ocular coherence tomography. To study changes in microglia phenotype, we used morphOMICs, a novel morphology analysis tool. Our data suggests that the neuroprotective actions of LXB4 include preventing reactivity of microglia and restoring homeostasis.

Additionally, the pseudotime trajectory denotes that microglia in 5-LOX knockout mice with ocular hypertension have the greatest morphological variation from homeostatic WT microglia. In conclusion, our data highlights the importance of the retinal lipoxin pathway in regulating the response and homeostatic function of microglia in the optic nerve. Further studies are required to establish the role of 5-LOX and 15-LOX enzymes in the retina and optic nerve during ocular hypertension-induced neuropathy.'

'Psychedelics (e.g., LSD, DMT) alter visual perception, but the extent to which subjective visual effects reliably vary by substance is unknown. Visual effects of a given psychedelic range widely across and within individuals, so large qualitative datasets are required to address this question with adequate sensitivity. Here we present an observational study with narrative self-report texts, leveraging the massive scale of the Erowid dataset. Erowid Center archives self-reported narrative texts of experiences with psychoactive substances, submitted by users and accessible to the public at Erowid.org.

In our study, we analyzed texts associated with 103 different psychoactive substances (30 psychedelics, 73 comparators; median number of reports per substance: 216). We represented each sentence from these reports with a vector using the text-embedding-ada-002 model (OpenAI) and then used logistic regression to identify the subset of sentences that describe visual effects. We found that the proportion of visual effect sentences varies across substances, even within psychedelics. Next, we identified categories of visual experience (e.g., surfaces shifting, colors changing). We calculated the proportion of visual effect sentences within each category for each substance and found that psychedelics systematically differ in their visual effect profiles. Our findings indicate significant variation across psychedelic substances’ propensities to affect vision and in their visual effects.'

'The physiological basis of amblyopia has been attributed to abnormal processes in primary visual cortex (V1). While research has shown that abnormalities extend beyond V1, others have examined oculomotor behavior as another possible explanation for amblyopic deficits. Previous research has shown that large fixational instabilities found in amblyopic eyes are highly correlated with worsening acuity in these patients. However, no significant correlation was found in the neurotypical population, which begs the question: does poor acuity cause fixational instability or vice versa, or if the two are correlated as a byproduct of abnormal processes in V1. We investigated whether visual acuity is truly a limiting factor in oculomotor behavior.

We simulated reduced visual acuity observed in the amblyopic eye in the non-dominant eyes (NDEs) of corrected-to-normal observers by using convex lenses to induce retinal-defocus. We tested a set of logMAR acuity differences as observed in amblyopic patients and compared the oculomotor behavior of the normal eye with lens induced acuity loss. We found that lens induced acuity loss had a significant impact on the observer’s drift magnitude and fixational instabilities compared to the no blur condition in the NDE; however, further reductions in visual acuity did not have any impact. We conclude that the reduced visual acuity of patients with amblyopia cannot be fully accounted for by abnormal fixational eye movements and fixational instabilities.'

'Photophobia is a hallmark symptom of migraine. Visual stimulation can trigger migraines, linking visual processing and migraine pathophysiology. Photophobia is typically linked to cortical hyper-excitability in migraine; however, abnormal retinal activity has also recently been identified, challenging this theory, and has implications for targeted treatment. We measured electroencephalography (EEG) from visual cortex and electroretinography (ERG) activity in migraine (MG) and headache-free (HF) individuals to localize abnormal neural activity. EEG was measured in response to flicker. To assess rod and cone activity, we presented dark adapted low luminance light and bright high frequency flicker, respectively. To assess retinal ganglion activity, we identified the photopic negative responses (PhNR) using red and blue light. Stimuli intensities were modulated according to pupil diameter to maintain consistent stimulation.

As expected, MG exhibited greater neural responses to visual flicker than HF (d=0.78), consistent with cortical hyper-excitability. At the retina, MG expressed larger rod-driven a- (d=0.38) and b-waves (d=0.54), and greater cone-driven responses (d=0.24) to fast flicker. There were no differences in the PhNR between MG and HF. Our findings suggest that there may be some retinal involvement in photophobia in migraine, but the effects are small, and it is unknown whether they cause photophobia.'

'The human visual system is thought to be divided into two anatomically and functionally distinct pathways: a ventral pathway that subserves object perception and a dorsal pathway that subserves goal-directed action and spatial vision. Most fMRI studies of visual perception use two-dimensional images projected onto a mirror as stimuli. But because such stimuli neither afford action nor occupy a definite egocentric location, they may drive cortical responses differently than physical stimuli placed within the observer’s grasp –especially in dorsal cortex.

Here, we presented participants in the scanner with meaningful real objects and closely matched, printed 2-D pictures of those objects. The stimuli were placed either within reach of participants’ hands or beyond their reach. Univariate contrasts identified regions in both ventral and dorsal cortex that responded more strongly to real objects than to pictures. In these regions and others, reachability modulated fMRI activation more strongly for real objects than it did for pictures. Representational similarity analysis showed that dorsal regions represented object shape only when stimuli were within reach, while ventral regions did so independently of stimulus distance.

These results suggest that stimuli that lack a definite egocentric position may fail to capture the dorsal stream’s involvement in object perception. Distance from the observer appears especially consequential in the context of real, naturalistic stimuli.'

'Photoreceptor loss often evades detection until a significant deficit occurs, primarily due to the absence of a well-defined connection between the quantity of photoreceptors and a specific psychophysical measurement (Foote et al., 2018; Ratnam et al., 2013). We sought to define a relationship between controlled degrees of photoreceptor death and ganglion cell response properties as a step towards identifying a physiological signature that indicates degrees of photoreceptor loss. To determine this, we have induced 25%, 50%, and 75% rod loss in Rho-DTR mice by varying the dosage of diphtheria toxin. Circuit function was assessed with patch-clamp recordings from alpha ON sustained (AON-S) ganglion cells.

We found that up to 50% rod loss, rod-mediated excitatory and inhibitory currents compensate but spike responses reflect the degree of rod loss. Next, we determined if adaptational properties can reveal the degrees of rod loss. Threshold, which takes into account both the gain and noise properties, were calculated to be degraded only after 50% rod loss. Taken together, our results demonstrate that rod loss induces adaptational changes at the level of AON-S ganglion cells.'

'Our study aims to enhance the analysis of Meibomian glands (MGs) in the context of dry eye (DE) research by leveraging artificial intelligence (AI). We tackle the limitations of manual assessment methods and bridge the gap between curated and real-world datasets to elevate the accuracy and standardization of Meibomian gland (MG) analysis. Our approach involves a two-stage process: automated eyelid detection and tarsal plate segmentation. Utilizing a model trained on curated UCB-CRC data, the initial stage detects meibography image features within non-curated datasets. The subsequent phase employs automated tarsal plate segmentation, refining meibography image features from the initial stage for precise comparison between normal and DE subjects. The methodology addresses data imbalances and incorporates key steps such as reflection removal and mask refinement.

Our results demonstrate promising instance-wise accuracy of 80.8% in distinguishing MG features from 400 DE and 235 NonDE subjects. The integrated diverse datasets and refined analysis steps improve MG feature extraction accuracy. The utilization of UMAP visualization provides profound insights into the relationships among the extracted meibography image features. Our AI-driven methodology quantifies, classifies, and standardizes MG characteristics, overcoming manual assessment limitations. By integrating diverse datasets, we enhance accuracy, robustness, and clinical relevance in MG analysis.'

'Visual crowding is a phenomenon of visual perception characterized by our decreased ability to identify an object when it is surrounded by other objects. Previous research has shown that the ‘crowding effect,’ which is greatest in the peripheral visual field, is stronger in patients with glaucoma compared with healthy controls. Additionally, crowding scores of patients with glaucoma are correlated with their retinal nerve fiber layer (RNFL) thickness scores.

We hypothesized that the same may be true for optic disc drusen (ODD), which are associated with RNFL thinning and peripheral visual field defects resembling those detected in glaucoma. We investigated visual crowding using a flanked “E” stimulus fixed at 10 degrees eccentricity. We assessed contrast sensitivity across 10 randomized trials of 5 conditions per eye (unflanked, 3.2, 2.4, 1.8, and 1.4 degrees of target-flanker separation). Contrast threshold elevation represented the magnitude of the crowding effect relative to the baseline unflanked condition. Critical spacing (Scritical) was calculated by plotting threshold elevation as a function of target-flanker separation.

In our study, the average Scritical for patients with ODD (n = 11) was not significantly different from that of healthy, age-matched controls (n = 11). Among patients with ODD who provided results from optical coherence tomography (n = 5) and visual field analysis (n = 6), Scritical was not correlated with RNFL thickness, mean sensitivity, or pattern standard deviation. Larger studies are warranted: (1) to validate these findings, and (2) to investigate whether crowding may represent a difference in the presentation of ODD and glaucoma on functional vision testing.'