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Abstract Purpose To compare the characteristics of the quantitative contrast sensitivity function (qCSF) in eyes with early keratoconus (Early-KC) and normal control (NC) eyes and investigate the associated factors. Design A cross-sectional study. Methods This study included 43 eyes of 43 patients with Early-KC (including subclinical keratoconus [SKC] and forme fruste keratoconus [FFKC]) and 77 NC eyes of 77 participants with corrected distance visual acuity (CDVA) all ≥ 20/20. Contrast sensitivity (CS) was assessed using the qCSF tests. Subgroup analysis was performed according to keratoconus type(SKC and FFKC) and astigmatism(cylindrical refraction >-1.0D or ≤-1.0D). Results Sex ratio, spherical refraction, and spherical equivalent (SE) varied significantly between the two groups (all P

Abstract We developed and validated digital twins (DTs) for contrast sensitivity function (CSF) across 12 prediction tasks using a data-driven, generative model approach based on a hierarchical Bayesian model (HBM). For each prediction task, we utilized the HBM to compute the joint distribution of CSF hyperparameters and parameters at the population, subject, and test levels. This computation was based on a combination of historical data (N = 56), any new data from additional subjects (N = 56), and “missing data” from unmeasured conditions. The posterior distributions of the parameters in the unmeasured conditions were used as input for the CSF generative model to generate predicted CSFs. In addition to their accuracy and precision, these predictions were evaluated for their potential as informative priors that enable generation of synthetic quantitative contrast sensitivity function (qCSF) data or rescore existing qCSF data. The DTs demonstrated high accuracy in group level predictions across all tasks and maintained accuracy at the individual subject level when new data were available, with accuracy comparable to and precision lower than the observed data. DT predictions could reduce the data collection burden by more than 50% in qCSF testing when using 25 trials. Although further research is necessary, this study demonstrates the potential of DTs in vision assessment. Predictions from DTs could improve the accuracy, precision, and efficiency of vision assessment and enable personalized medicine, offering more efficient and effective patient care solutions.

BackgroundAge-related vision changes significantly contribute to fatal crashes at night among older drivers. However, the effects of lighting conditions on age-related vision changes and associated driving performance remain unclear. ObjectiveThis pilot study examined the associations between visual function and driving performance assessed by a high-fidelity driving simulator among drivers 60 and older across 3 lighting conditions: daytime (photopic), nighttime (mesopic), and nighttime with glare. MethodsActive drivers aged 60 years or older participated in visual function assessments and simulated driving on a high-fidelity driving simulator. Visual acuity (VA), contrast sensitivity function (CSF), and visual field map (VFM) were measured using quantitative VA, quantitative CSF, and quantitative VFM procedures under photopic and mesopic conditions. VA and CSF were also obtained in the presence of glare in the mesopic condition. Two summary metrics, the area under the log CSF (AULCSF) and volume under the surface of VFM (VUSVFM), quantified CSF and VFM. Driving performance measures (average speed, SD of speed [SDspeed], SD of lane position (SDLP), and reaction time) were assessed under daytime, nighttime, and nighttime with glare conditions. Pearson correlations determined the associations between visual function and driving performance across the 3 lighting conditions. ResultsOf the 20 drivers included, the average age was 70.3 years; 55% were male. Poor photopic VA was significantly correlated with greater SDspeed (r=0.26; P

Iconic memory and short-term memory are not only crucial for perception and cognition, but also of great importance to mental health. Here, we first showed that both types of memory could be improved by improving limiting processes in visual processing through perceptual learning. Normal adults were trained in a contrast detection task for ten days, with their higher-order aberrations (HOA) corrected in real-time. We found that the training improved not only their contrast sensitivity function (CSF), but also their iconic memory and baseline information maintenance for short-term memory, and the relationship between memory and CSF improvements could be well-predicted by an observer model. These results suggest that training the limiting component of a cognitive task with visual perceptual learning could improve visual cognition. They may also provide an empirical foundation for new therapies to treat people with poor sensory memory.

Abstract We make use of expected information gain to quantify the amount of knowledge obtained from measurements in a population. In the first application, we compared the expected information gain in the Snellen, ETDRS, and qVA visual acuity (VA) tests, as well as in the Pelli–Robson, CSV-1000, and qCSF contrast sensitivity (CS) tests. For the VA tests, ETDRS generated more expected information gain than Snellen. Additionally, the qVA test with 15 rows (or 45 optotypes) generated more expected information gain than ETDRS, whether scored with VA threshold alone or with both VA threshold and VA range. Regarding the CS tests, CSV-1000 generated more expected information gain than Pelli–Robson, and the qCSF test with 25 trials generated more expected information gain than CSV-1000, whether scored with AULCSF or with CSF at six spatial frequencies. The active learning-based qVA and qCSF tests have the potential to generate more expected information gain than traditional paper chart tests. Although we have specifically applied it to compare VA and CS tests, expected information gain is a general concept that can be used to compare measurements in any domain.

Abstract Background To assess the accuracy of contrast sensitivity function (CSF) in detecting dysthyroid optic neuropathy (DON) at an early stage in thyroid-associated ophthalmopathy (TAO) patients and to examine potential factors that may be linked to early visual impairments in these individuals. Methods A total of 81 TAO patients (50 non-DON and 31 DON), and 24 control subjects participated in the study. CSF was measured with the quick CSF (qCSF) method. Optical coherence tomography angiography (OCTA) images of the ganglion cell complex layer (GCCL), superficial and deep retinal capillary plexuses (SRCP and DRCP) in a 3 mm diameter area around the macula were evaluated. Results Compared with the controls, the area under the log contrast sensitivity function (AULCSF) and SRCP density were significantly reduced in non-DON and DON patients (all P

Abstract Background Quick contrast sensitivity function (qCSF) method is an advanced quick method for contrast sensitivity function (CSF) evaluation. This study evaluated the contrast sensitivity (CS) of eyes undergoing cataract surgery with multifocal intraocular lens (IOL) implantation and its tolerance to IOL tilt and IOL decentration using the qCSF method. Methods Patients undergoing uneventful phacoemulsification and a trifocal IOL (Zeiss AT LISA tri 839MP, Carl Zeiss, Germany) or an extended depth-of-focus (EDOF) IOL (Tecnis Symfony ZXR00, Johnson & Johnsons, USA) implantation were included. Monocular contrast sensitivity was measured using the qCSF method at one month post-surgery. IOL tilt and decentration were measured using an optical aberrometer (OPD-Scan III, NIDEK, Japan). Results Seventy-two patients/eyes with the 839MP IOL and 64 patients/eyes with the ZXR00 IOL were included. Area under the log CSF (AULCSF) and CS acuity did not differ significantly between the two groups. The ZXR00 IOL group showed better CS at 1 cpd (1.137 ± 0.164 vs. 1.030 ± 0.183 logCS) and 1.5 cpd (1.163 ± 0.163 vs. 1.071 ± 0.161 logCS), while the 839MP IOL group had better CS at 6 cpd (0.855 ± 0.187 vs. 0.735 ± 0.363 logCS). In the 839MP IOL group, all CSF metrics were negatively correlated with IOL tilt (all P 0.05). Among myopic eyes, fewer CSF metrics were negatively correlated with IOL tilt in the ZXR00 IOL group than in the 839MP IOL group. No significant correlation was found between CSF metrics and IOL decentration. Conclusions The ZXR00 and the 839MP IOL groups presented comparable CSF. CS was negatively correlated with IOL tilt, instead of decentration in multifocal IOLs, particularly among myopic eyes. The ZXR00 IOL had better tolerance to IOL tilt in myopic eyes.

Summary: High-field functional magnetic resonance imaging generates in vivo retinotopic maps, but quantifying them remains challenging. Here, we present a pipeline based on conformal geometry and Teichmüller theory for the quantitative characterization of human retinotopic maps. We describe steps for cortical surface parameterization and surface-spline-based smoothing. We then detail Beltrami coefficient-based mapping, which provides a quantitative and re-constructible description of the retinotopic maps. This framework has been successfully used to analyze the Human Connectome Project’s V1 retinotopic maps.For complete details on the use and execution of this protocol, please refer to Ta et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Zhang et al. present evidence that action video games facilitate learning to learn, the logic being that the rate of learning in new tasks can be increased via certain activities. Compared to a control group, action video game players exhibit a faster learning rate in both perceptual and working memory tasks.

PurposeCompare peripheral contrast sensitivity functions (CSF) between myopes and emmetropes to reveal potential myogenic risks during emmetropization.Materials and methodsThis observational, cross-sectional, non-consecutive case study included data from 19 myopes (23.42 ± 4.03 years old) and 12 emmetropes (22.93 ± 2.91 years old) who underwent central and peripheral quick CSF (qCSF) measurements. Summary CSF metrics including the cut-off spatial frequency (cut-off SF), area under log CSF (AULCSF), low-, intermediate-, and high-spatial-frequency AULCSFs (l-, i-, and h-SF AULCSFs), and log CS at 19 SFs in the fovea and 15 peripheral locations (superior, inferior, temporal, and nasal quadrants at 6, 12, 18, and 24° eccentricities, excluding the physiological scotoma at 18°) were analyzed with 3-way and 4-way between-subjects analysis of variance (ANOVA) (α = 0.05).ResultsThree-way ANOVA showed that myopes had significantly increased AULCSF at 6° (mean difference, 0.08; 95% CI, 0.02–0.13; P = 0.007) and 12° (mean difference, 0.09; 95% CI, 0.03–0.14; P = 0.003). Log CS at all 19 SFs were higher in the myopia group compared to the normal group (mean differencesuperior, 0.02; 95% CI, 0.01–0.20; P = 0.02 and mean differenceinferior, 0.11; 95% CI, 0.02–0.21; P = 0.01) at 12°. The h-SF AULCSF at 6° (mean differenceinferior, 1.27; 95% CI, 0.32–2.22; P = 0.009) and i-SF AULCSF at 12° (mean differencesuperior, 5.31; 95% CI, 4.35–6.27; P < 0.001; mean differenceinferior, 1.14; 95% CI, 0.19–2.10; P = 0.02) were higher in myopia vs. normal group.ConclusionWe found myopia increased contrast sensitivity in superior and inferior visual field locations at 6° parafoveal and 12° perifoveal regions of the retina. The observation of increased contrast sensitivities within the macula visual field in myopia might provide important insights for myopia control during emmetropization.

Summary: The hierarchical organization of the visual system preserves topology, which is often lost in the “raw” human retinotopic maps derived from BOLD fMRI recordings. Here, we present the protocol for generating topology-preserving and smooth retinotopic maps from human retinotopy fMRI data. We describe data pre-processing, 3D surface flattening, and selection of the region of interest (ROI), followed by smoothing of the retinotopic maps within the ROI. This approach can be applied to visual cortical areas V1, V2, and V3 simultaneously.For complete details on the use and execution of this protocol, please refer to Tu et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ObjectiveTo evaluate the contrast sensitivity function (CSF), chorioretinal thickness and vascular density as well as their relationships in subjects with simple early-stage high myopia.MethodsEighty-one young subjects were enrolled in this study. They were categorized into the simple high myopia group (sHM, n = 51) and the low-moderate myopia group (control group, n = 30). Monocular CSF under best correction was measured with the qCSF method. Retinal superficial and deep vascular density, inner and outer retinal thickness and choroidal thickness were measured using optical coherence tomography angiography.ResultsThe area under log CSF (AULCSF) and cutoff spatial frequency (Cutoff SF) of the sHM group were significantly reduced compared to those of the control group (P = 0.003 and P < 0.001, respectively). The parafoveal and perifoveal retinal thickness, deep vascular density and choroidal thickness were also significantly reduced in the sHM group (all P < 0.05). Multiple regression analysis revealed that AULCSF was significantly correlated with retinal deep vascular density, outer retinal thickness in the parafoveal and perifoveal areas (all P < 0.05).ConclusionCompared to low to moderate myopic eyes, patients with simple high myopia have thinner retinal and choroidal thickness, lower retinal vascular density, and reduced contrast sensitivity. Moreover, the CSF was correlated with the measures of chorioretinal structure and vasculature. The results suggest that the CSF is a sensitive functional endpoint in simple early-stage high myopia.

A series of multifunctional compounds (MFCs) 1a–1e based on 1,8-naphthalimide and [12]aneN3 building blocks were designed and synthesized. They were used as not only fluorescent probes for recognition of Cu2+ ions but also as non-viral gene vectors for DNA and RNA delivery. Furthermore, their complexes with Cu2+ (1-Cu) could also selectively stain lysosome in HeLa cells. In order to achieve high performance multifunctional materials, structure-performance relationship of MFCs 1a–1e was studied. It was found that MFCs 1a–1e exhibited highly selective fluorescence turn-off for Cu2+, without interference by other metal ions in aqueous solution. The fluorescence emission of 1a–1e was quenched by a factor of 10-fold, 47-fold, 6-fold, 64-fold, and 15-fold respectively in the presence of Cu2+ ions. Due to high sensitivity, good water solubility, and low cytotoxicity, MFCs 1a–1d were successfully applied in the recognition of Cu2+ and selectively staining lysosome in HeLa cells. Most importantly, MFCs 1a and 1b had excellent HeLa cell selectivity in RNA delivery, and their performances were far better than lipofectamine 2000 and 25 kDa PEI.

Summary: To explore the relative contributions of higher-order and primary visual cortex (V1) to visual perception, we compared cats' behavioral and V1 neuronal contrast sensitivity functions (CSF) and threshold versus external noise contrast (TvC) functions before and after top-down influence of area 7 (A7) was modulated with transcranial direct current stimulation (tDCS). We found that suppressing top-down influence of A7 with cathode-tDCS, but not sham-tDCS, reduced behavioral and neuronal contrast sensitivity in the same range of spatial frequencies and increased behavioral and neuronal contrast thresholds in the same range of external noise levels. The neuronal CSF and TvC functions were highly correlated with their behavioral counterparts both before and after the top-down suppression. Analysis of TvC functions using the Perceptual Template Model (PTM) indicated that top-down influence of A7 increased both behavioral and V1 neuronal contrast sensitivity by reducing internal additive noise and the impact of external noise.

Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.

PurposeAmblyopia affects not only spatial vision but also temporal vision. In this study, we aim to investigate temporal processing deficits in amblyopia.MethodsTwenty amblyopic patients (age: 27.0 ± 5.53 years, 15 males), and 25 normal observers (age: 25.6 ± 4.03 years, 15 males) were recruited in this study. Contrast thresholds in an orientation discrimination task in five target-mask stimulus onset asynchronies (SOA) conditions (16.7 ms, 33.4 ms, 50.0 ms, 83.4 ms, and ∞/no noise) were measured. An elaborated perceptual template model (ePTM) was fit to the behavioral data to derive the temporal profile of visual processing for each participant.ResultsThere were significant threshold differences between the amblyopic and normal eyes [F(1,43) = 10.6, p = 0.002] and a significant group × SOA interaction [F(2.75,118) = 4.98, p = 0.004], suggesting different temporal processing between the two groups. The ePTM fitted the data well (χ2 test, all ps > 0.50). Compared to the normal eye, the amblyopic eye had a lower template gain (p = 0.046), and a temporal window with lower peak and broader width (all ps < 0.05). No significant correlation was found between the observed temporal deficits and visual acuity in amblyopia (ps > 0.50). Similar results were found in the anisometropic amblyopia subgroup. No significant difference was found between the fellow eyes of the monocular amblyopia and the normal eyes.ConclusionAmblyopia is less efficient in processing dynamic visual stimuli. The temporal deficits in amblyopia, represented by a flattened temporal window, are likely independent of spatial vision deficits.

PurposeRecently, we developed a novel active learning framework, qVFM, to map visual functions in the visual field. The method has been implemented and validated in measuring light sensitivity and contrast sensitivity visual field maps (VFMs) of normal observers. In this study, we evaluated the performance of the qVFM method in mapping the light sensitivity VFM of simulated patients with peripheral scotoma, glaucoma, age-related macular degeneration (AMD), and cataract.MethodsFor each simulated patient, we sampled 100 locations (60 × 60 degrees) of the visual field and compared the performance of the qVFM method with a procedure that tests each location independently (the qYN method) in a cued Yes/No task. Two different switch modules, the distribution sampling method (DSM) and parameter delivering method (PDM), were implemented in the qVFM method. Simulated runs of 1,200 trials were used to compare the accuracy and precision of the qVFM-DSM, qVFM-PDM and qYN methods.ResultsThe qVFM method with both switch modules can provide accurate, precise, and efficient assessments of the light sensitivity VFM for the simulated patients, with the qVFM-PDM method better at detecting VFM deficits in the simulated glaucoma.ConclusionsThe qVFM method can be used to characterize residual vision of simulated ophthalmic patients. The study sets the stage for further investigation with real patients and potential translation of the method into clinical practice.

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia (MA). Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function (CSF) and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism (AST group, 20 eyes) and thirteen participants with (MA group, 19 eyes) were recruited in the current study. CSFs and spatial sweep visual evoked potentials (sVEP) were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF (AULCSF), spatial frequency threshold corresponding to 80% contrast gratings (SF threshold at 80% ctr), and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian (measured with horizontal gratings) was lower than that along strong meridian (measured with vertical gratings) in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions.

Factors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central β/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisting of β-alanine (β-Ala) and glycine (Gly), and L-β-homophenylalanine (L-β-homoPhe) and Gly residues, respectively, that are flanked by γAr residues, fold into well-defined, expanded β-turns with doubly H-bonded γAr residues. Replacing the γAr residues of 1 and 2 with L-Val and L-Leu residues results in tetrapetides 1′ and 2′ that fail to fold into defined conformations, which confirms the decisive role played by the H-bonded γAr residues in the promoting folding of 1 and 2. Attaching L-Val and L-Leu residues to the termini of 1 affords hexapeptide 1a. With an additional H-bond between its L-Val and L-Leu residues, peptide 1a folds into a hairpin with higher stability than that of 1, indicating that the expanded β-turn can nucleate and stabilize β-hairpin with longer β-strands. Attaching L-Val and L-Leu residues to the termini of 2 affords hexapeptide 2a. Substituting the L-β-homoPhe residue of 2a with a D-β-homoPhe residue gives hexapeptide 2b. Surprisingly, hexapeptide 2a fold into a hairpin showing the similar stability as those of tetrapeptides 1 and 2. Hexapeptide 2b, with its combination of a D-β-homoPhe residue and the L-Val/L-Leu pair, fold into a hairpin that is significantly more stable than the other hybrid peptides, demonstrating that a combination of hetero-chirality between the β-amino acid residue of the dipeptide loop and the α-amino acid residues of the β-strands enhances the stability of the resultant β-hairpin.

Reading is a primary problem for low vision patients and a common functional endpoint for eye disease. However, there is limited agreement on reading assessment methods for clinical outcomes. Many clinical reading tests lack standardized materials for repeated testing and cannot be self-administered, which limit their use for vision rehabilitation monitoring and remote assessment. We compared three different reading assessment methods to address these limitations. Normally sighted participants (N = 12) completed MNREAD, and two forced-choice reading tests at multiple font sizes in counterbalanced order. In a word identification task, participants indicated whether 5-letter pentagrams, syntactically matched to English, were words or non-words. In a true/false reading task, participants indicated whether four-word sentences presented in RSVP were logically true or false. The reading speed vs. print size data from each experiment were fit by an exponential function with parameters for reading acuity, critical print size and maximum reading speed. In all cases, reading speed increased quickly as an exponential function of text size. Reading speed and critical print size significantly differed across tasks, but not reading acuity. Reading speeds were faster for word/non-word and true/false reading tasks, consistent with the elimination of eye movement load in RSVP but required larger text sizes to achieve those faster reading speeds. These different reading tasks quantify distinct aspects of reading behavior and the preferred assessment method may depend on the goal of intervention. Reading performance is an important clinical endpoint and a key quality of life indicator, however, differences across methods complicate direct comparisons across studies.

Current clinical evaluation, which focuses on central vision, could be improved through characterization of residual vision with peripheral testing of visual acuity, contrast sensitivity, color vision, crowding, and reading speed. Assessing visual functions in addition to light sensitivity, a comprehensive visual field map (VFM) would be valuable for detecting and managing eye diseases. In a previous study, we developed a Bayesian adaptive qVFM method that combines a global module for preliminary assessment of the VFM's shape and a local module for assessment at individual retinal locations. The method was validated in measuring the light sensitivity VFM. In this study, we extended the qVFM method to measure contrast sensitivity across the visual field. In both simulations and psychophysics, we sampled 64 visual field locations (48 x 48 deg) and compared the qVFM method with a procedure that tested each retinal location independently (qFC; Lesmes et al., 2015). In each trial, subjects were required to identify a single optotype (size: 2.5 x 2.5 deg), one of 10 filtered Sloan letters. To compare the accuracy and precision of the two methods, three simulated eyes were tested in 1,280 trials with each method. In addition, data were collected from 10 eyes (5 OS, 5 OD) of five normal observers. For simulations, the average RMSE of the estimated contrast sensitivity with the qVFM and qFC methods were 0.057 and 0.100 after 320 trials, and 0.037 and 0.041 after 1,280 trials [all in log10 units, represent as log(sensitivity)], respectively. The average SD of the qVFM and qFC estimates were 0.054 and 0.096 after 320 trials, and 0.032 and 0.041 after 1,280 trials, respectively. The within-run variability (68.2% HWCIs) were comparable to the cross-run variability (SD). In the psychophysics experiment, the average HWCI of the estimated contrast sensitivity from the qVFM and qFC methods across the visual field decreased from 0.33 on the first trial to 0.072 and 0.16 after 160, and to 0.060 and 0.10 after 320 trials. The RMSE between the qVFM and qFC estimates started at 0.26, decreased to 0.12 after 160 and to 0.11 after 320 qVFM trials. The qVFM provides an accurate, precise, and efficient mapping of contrast sensitivity across the entire visual field. The method might find potential clinical applications in monitoring vision loss, evaluating therapeutic interventions, and developing effective rehabilitation for visual diseases.

Summary: Re-establishing normal binocular visual processing is the key to amblyopia recovery beyond the critical period of visual development. Here, by combining perceptual learning, behavioral testing, and steady-state visually evoked potentials (SSVEPs), we examined how monocular perceptual learning in the amblyopic eye could change binocular visual processing in the adolescent and adult amblyopic visual system. We found that training reduced the interocular difference between amblyopic and fellow eyes and increased the amplitude of a binocular SSVEP component, with a significant negative correlation between the two measures. Our results demonstrate that training in the amblyopic eye primarily improves binocular rather than monocular visual processing in the amblyopic visual system, suggesting that behavioral training could potentially address key neural deficits in adolescent and adult amblyopia. : Biological Sciences; Behavioral Neuroscience; Sensory Neuroscience Subject Areas: Biological Sciences, Behavioral Neuroscience, Sensory Neuroscience

Many studies have focused on patients with schizophrenia with or without auditory verbal hallucinations (AVHs), but due to the complexity of schizophrenia, biologically based diagnosis of patients with schizophrenia remains unsolved. The objectives of this study are to classify between first-episode drug-naïve patients with schizophrenia and healthy controls, and to classify between patients with and without AVHs. Resting state fMRI data from 41 patients with schizophrenia (22 with and 19 without AVHs) and 23 normal controls (NC) were included to compute functional connectivity between brain regions. Classifiers based on support vector machine (SVM) were developed to classify patients with schizophrenia from NC, as well as between the two subgroups of patients. The classification accuracy was evaluated with a leave-one-out cross-validation (LOOCV) strategy. The accuracy in discriminating both subgroups of patients from NC was 81.3%, with 92.0% (sensitivity) and 65.2% (specificity) for the patients and NC, respectively. The classification accuracy in discriminating patients with and without AVHs was 75.6%, with 77.3% (sensitivity) and 73.9% (specificity) for patients with and without AVHs, respectively. The results suggest that functional connectivity provided good discriminative power not only for identifying patients with schizophrenia among NC, but also in discriminating patients with schizophrenia with and without AVHs. Keywords: First episode schizophrenia, Auditory verbal hallucinations, Functional connectivity, Support vector machine

Abstract The sense of vision allows us to discriminate fine details across a wide range of tasks. How to improve this perceptual skill, particularly within a short training session, is of substantial interest. Emerging evidence suggests that mixing easy trials can quickly improve performance in hard trials, but it is equivocal whether the improvement is short-lived or long-lasting, and additionally what accounts for this improvement. Here, by tracking objective performance (accuracy) and subjective experience (ratings of target visibility and choice confidence) over time and in a large sample of participants, we demonstrate the coexistence of transient and sustained effects of mixing easy trials, which differ markedly in their timescales, in their effects on subjective awareness, and in individual differences. In particular, whereas the transient effect was found to be ubiquitous and manifested similarly across objective and subjective measures, the sustained effect was limited to a subset of participants with weak convergence from objective and subjective measures. These results indicate that mixture of easy trials enables two distinct, co-existing forms of rapid perceptual improvements in hard trials, as mediated by robust priming and fragile learning. Placing constraints on theory of brain plasticity, this finding may also have implications for alleviating visual deficits.

Purpose: Amblyopia and strabismus affect 2%–5% of the population and cause a broad range of visual deficits. The response to treatment is generally assessed using visual acuity, which is an insensitive measure of visual function and may, therefore, underestimate binocular vision gains in these patients. On the other hand, the contrast sensitivity function (CSF) generally takes longer to assess than visual acuity, but it is better correlated with improvement in a range of visual tasks and, notably, with improvements in binocular vision. The present study aims to assess monocular and binocular CSFs in amblyopia and strabismus patients.Methods: Both monocular CSFs and the binocular CSF were assessed for subjects with amblyopia (n = 11), strabismus without amblyopia (n = 20), and normally sighted controls (n = 24) using a tablet-based implementation of the quick CSF, which can assess a full CSF in

To better characterize the neural correlates of the full spectrum of reading ability, this fMRI study examined how variations in reading ability correlate with task-based brain activity during reading among a large community sample of adolescents (N = 234). In addition, complimentary approaches taking advantage of empirical as well as independent meta-analytic information were employed to isolate neural substrates of domain-general executive processes that are predictive of reading ability. Age-related differences in brain activity were also examined. Better reading was associated with increased activation in left anterior and inferior temporal regions and parts of orbitofrontal cortex, along with reduced activation in the thalamus and left frontal eye field (FEF). Converging evidence suggests that FEF activity corresponds to executive processes during reading. In contrast, activity in temporal regions is likely to reflect cognitive processes specific to reading. Older adolescents also demonstrated increased activation in an orbitofrontal region that overlaps with the aforementioned age-independent, reading-related regions, along with reduced activity in parietal and occipital regions. These results suggest that comparedto poor readers, proficient readers benefit from efficient reading-specific processes and require less executive effort, implemented via the FEF, during a reading comprehension task. Keywords: Executive Function, Reading, Frontal eye field, fMRI, Individual differences

Neuroadaptations caused by chronic methamphetamine (MA) use are likely major contributors to high relapse rate following treatment. Thus, focusing intervention efforts at pre-empting addiction in vulnerable populations, thereby preventing MA-use-induced neurological changes that make recovery so challenging, may prove more effective than targeting chronic users. One approach is studying casual/recreational users, not diagnosed with substance use disorder. This group may be at high risk for addiction due to their experience with MA. On the other hand, they may be resilient against addiction since they were able to maintain casual use over the years and not become addicted. Understanding their neuro-cognitive characteristics during decision-making and risk-taking would help solve this dilemma and, may help identify intervention strategies. Unfortunately, research on neuro-cognitive characteristics of casual MA users is currently lacking. In this work we begin to address this deficit.This study was part of a larger investigation of neural correlates of risky sexual decision-making in men who have sex with men. While undergoing functional magnetic resonance imaging, 31 casual MA users and 66 non-users performed the CUPS task, in which they decided to accept or refuse a series of mixed gambles. Convergent results from whole brain, region of interest and psychophysiological interaction (PPI) analyses are presented.Whole brain analysis identified an amygdala-striatal cluster with weaker activation in casual MA users compared to non-users during decision-making. Activity in that cluster inversely correlated with decisions to gamble: lower activation corresponded to higher risk taking. Using this cluster as a seed in PPI analyses, we identified a wide range of neural network differences between casual MA users and non-users. Parametric whole brain analyses identified clusters in the ventral striatum, posterior insula and precuneus where activations modulated by risk and reward were significantly weaker in casual MA users than in non-users. The striatal cluster identified in these analyses overlapped with the amygdala-striatal cluster.This work identified neural differences in casual MA users' reward processing and outcome learning systems which may underlie their increased real-world risk-taking. It suggests that while making decisions casual MA users focus primarily on potential gain unlike non-users who also take the riskiness of the choice into consideration. Keywords: Methamphetamine, Risk taking, Decision, fMRI, Amygdala, Striatum, Insula

Perceptual learning (PL) can significantly improve human performance in perceptual tasks primarily through template reweighting. Previous studies have documented how PL changes perceptual template in stimulus feature space. We investigated how PL reweights visual information in time. With a dynamic external noise paradigm and the elaborated perceptual template model (ePTM) analysis, we found that training with an orientation identification task in the zero external noise condition reduced contrast thresholds in both zero and high external noise conditions, whereas training in the high external noise condition only reduced contrast thresholds in high external noise conditions. The ePTM analysis showed that training in both zero and high external noise changed the overall amplitude, but not the shape of the temporal window of the perceptual template to exclude external noise across time, and training in zero external noise additionally reduced additive internal noise. Our results provided additional constraints for models of PL.

To measure binocular interaction in amblyopes using a rapid and patient-friendly computer-based method, and to test the feasibility of the assessment in the clinic.Binocular interaction was assessed in subjects with strabismic amblyopia (n = 7), anisometropic amblyopia (n = 6), strabismus without amblyopia (n = 15) and normal vision (n = 40). Binocular interaction was measured with a dichoptic phase matching task in which subjects matched the position of a binocular probe to the cyclopean perceived phase of a dichoptic pair of gratings whose contrast ratios were systematically varied. The resulting effective contrast ratio of the weak eye was taken as an indicator of interocular imbalance. Testing was performed in an ophthalmology clinic under 8 mins. We examined the relationships between our binocular interaction measure and standard clinical measures indicating abnormal binocularity such as interocular acuity difference and stereoacuity. The test-retest reliability of the testing method was also evaluated.Compared to normally-sighted controls, amblyopes exhibited significantly reduced effective contrast (∼20%) of the weak eye, suggesting a higher contrast requirement for the amblyopic eye compared to the fellow eye. We found that the effective contrast ratio of the weak eye covaried with standard clincal measures of binocular vision. Our results showed that there was a high correlation between the 1st and 2nd measurements (r = 0.94, p

Although behavioral and neuropsychological studies have suggested two distinct routes of phonological access, their neural substrates have not been clearly elucidated. Here, we designed an artificial language (based on Korean Hangul) that can be read either through addressed (i.e., whole word mapping) or assembled (i.e., grapheme-to-phoneme mapping) phonology. Two matched groups of native English-speaking participants were trained in one of the two conditions, one hour per day for eight days. Behavioral results showed that both groups correctly named more than 90% of the trained words after training. At the neural level, we found a clear dissociation of the neural pathways for addressed and assembled phonologies: There was greater involvement of the anterior cingulate cortex, posterior cingulate cortex, right orbital frontal cortex, angular gyrus and middle temporal gyrus for addressed phonology, but stronger activation in the left precentral gyrus/inferior frontal gyrus and supramarginal gyrus for assembled phonology. Furthermore, we found evidence supporting the strategy-shift hypothesis, which postulates that, with practice, reading strategy shifts from assembled to addressed phonology. Specifically, compared to untrained words, trained words in the assembled phonology group showed stronger activation in the addressed phonology network and less activation in the assembled phonology network. Our results provide clear brain-imaging evidence for the dual-route models of reading.

The three-dimension (3D) magnetization-prepared rapid gradient-echo (MP-RAGE) sequence is one of the most popular sequences for structural brain imaging in clinical and research settings. The sequence captures high tissue contrast and provides high spatial resolution with whole brain coverage in a short scan time. In this paper, we first computed the optimal k-space sampling by optimizing the contrast of simulated images acquired with the MP-RAGE sequence at 3.0 Tesla using computer simulations. Because the software of our scanner has only limited settings for k-space sampling, we then determined the optimal k-space sampling for settings that can be realized on our scanner. Subsequently we optimized several major imaging parameters to maximize normal brain tissue contrasts under the optimal k-space sampling. The optimal parameters are flip angle of 12°, effective inversion time within 900 to 1100 ms, and delay time of 0 ms. In vivo experiments showed that the quality of images acquired with our optimal protocol was significantly higher than that of images obtained using recommended protocols in prior publications. The optimization of k-spacing sampling and imaging parameters significantly improved the quality and detection sensitivity of brain images acquired with MP-RAGE.

Sensitivity to luminance difference, or contrast sensitivity, is critical for animals to survive in and interact with the external world. The contrast sensitivity function (CSF), which measures visual sensitivity to spatial patterns over a wide range of spatial frequencies, provides a comprehensive characterization of the visual system. Despite its popularity and significance in both basic research and clinical practice, it hasn't been clear what determines the CSF and how the factors underlying the CSF change in different conditions. In the current study, we applied the external noise method and perceptual template model to a wide range of external noise and spatial frequency (SF) conditions, and evaluated how the various sources of observer inefficiency changed with SF and determined the limiting factors underlying the CSF. We found that only internal additive noise and template gain changed significantly with SF, while the transducer non-linearity and coefficient for multiplicative noise were constant. The 12-parameter model provided a very good account of all the data in the 200 tested conditions (86.5%, 86.2%, 89.5%, and 96.4% for the four subjects, respectively). Our results suggest a re-consideration of the popular spatial vision model that employs the CSF as the front-end filter and constant internal additive noise across spatial frequencies. The study will also be of interest to scientists and clinicians engaged in characterizing spatial vision deficits and/or developing rehabilitation methods to restore spatial vision in clinical populations.

Many real-life decisions in complex and changing environments are guided by the decision maker's beliefs, such as her perceived control over decision outcomes (i.e., agency), leading to phenomena like the "illusion of control". However, the neural mechanisms underlying the "agency" effect on belief-based decisions are not well understood. Using functional imaging and a card guessing game, we revealed that the agency manipulation (i.e., either asking the subjects (SG) or the computer (CG) to guess the location of the winning card) not only affected the size of subjects' bets, but also their "world model" regarding the outcome dependency. Functional imaging results revealed that the decision-related activation in the lateral and medial prefrontal cortex (PFC) was significantly modulated by agency and previous outcome. Specifically, these PFC regions showed stronger activation when subjects made decisions after losses than after wins under the CG condition, but the pattern was reversed under the SG condition. Furthermore, subjects with high external attribution of negative events were more affected by agency at the behavioral and neural levels. These results suggest that the prefrontal decision-making system can be modulated by abstract beliefs, and are thus vulnerable to factors such as false agency and attribution.

Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.

Humans demonstrate an inherent bias towards making maladaptive decisions, as shown by a phenomenon known as the gambler's fallacy (GF). The GF has been traditionally considered as a heuristic bias supported by the fast and automatic intuition system, which can be overcome by the reasoning system. The present study examined an intriguing hypothesis, based on emerging evidence from neuroscience research, that the GF might be attributed to a weak affective but strong cognitive decision making mechanism. With data from a large sample of college students, we found that individuals' use of the GF strategy was positively correlated with their general intelligence and executive function, such as working memory and conflict resolution, but negatively correlated with their affective decision making capacities, as measured by the Iowa Gambling Task. Our result provides a novel insight into the mechanisms underlying the GF, which highlights the significant role of affective mechanisms in adaptive decision-making.

Anatomical and physiological differences between the central and peripheral visual systems are well documented. Recent findings have suggested that vision in the periphery is not just a scaled version of foveal vision, but rather is relatively poor at representing spatial and temporal phase and other visual features. Shapiro, Lu, Huang, Knight, and Ennis (2010) have recently examined a motion stimulus (the "curveball illusion") in which the shift from foveal to peripheral viewing results in a dramatic spatial/temporal discontinuity. Here, we apply a similar analysis to a range of other spatial/temporal configurations that create perceptual conflict between foveal and peripheral vision.To elucidate how the differences between foveal and peripheral vision affect super-threshold vision, we created a series of complex visual displays that contain opposing sources of motion information. The displays (referred to as the peripheral escalator illusion, peripheral acceleration and deceleration illusions, rotating reversals illusion, and disappearing squares illusion) create dramatically different perceptions when viewed foveally versus peripherally. We compute the first-order and second-order directional motion energy available in the displays using a three-dimensional Fourier analysis in the (x, y, t) space. The peripheral escalator, acceleration and deceleration illusions and rotating reversals illusion all show a similar trend: in the fovea, the first-order motion energy and second-order motion energy can be perceptually separated from each other; in the periphery, the perception seems to correspond to a combination of the multiple sources of motion information. The disappearing squares illusion shows that the ability to assemble the features of Kanisza squares becomes slower in the periphery.The results lead us to hypothesize "feature blur" in the periphery (i.e., the peripheral visual system combines features that the foveal visual system can separate). Feature blur is of general importance because humans are frequently bringing the information in the periphery to the fovea and vice versa.

We examined whether the characteristic impairments of dyslexia are due to a deficit in excluding external noise or a deficit in taking advantage of repeated stimulus presentation. We compared non-impaired adults and adults with poor reading performance on a visual letter detection task that varied two aspects: the presence or absence of background visual noise, and a small or large stimulus set. There was no interaction between group and stimulus set size, indicating that the poor readers took advantage of repeated stimulus presentation as well as the non-impaired readers. The poor readers had higher thresholds than non-impaired readers in the presence of high external noise, but not in the absence of external noise. The results support the hypothesis that an external noise exclusion deficit, not a perceptual anchoring deficit, impairs reading for adults.

How the visual system combines information from the two eyes to form a unitary binocular representation of the external world is a fundamental question in vision science that has been the focus of many psychophysical and physiological investigations. Ding & Sperling (2006) measured perceived phase of the cyclopean image, and developed a binocular combination model in which each eye exerts gain control on the other eye's signal and over the other eye's gain control. Critically, the relative phase of the monocular sine-waves plays a central role.We used the Ding-Sperling paradigm but measured both the perceived contrast and phase of cyclopean images in three hundred and eighty combinations of base contrast, interocular contrast ratio, eye origin of the probe, and interocular phase difference. We found that the perceived contrast of the cyclopean image was independent of the relative phase of the two monocular gratings, although the perceived phase depended on the relative phase and contrast ratio of the monocular images. We developed a new multi-pathway contrast-gain control model (MCM) that elaborates the Ding-Sperling binocular combination model in two ways: (1) phase and contrast of the cyclopean images are computed in separate pathways, although with shared cross-eye contrast-gain control; and (2) phase-independent local energy from the two monocular images are used in binocular contrast combination. With three free parameters, the model yielded an excellent account of data from all the experimental conditions.Binocular phase combination depends on the relative phase and contrast ratio of the monocular images but binocular contrast combination is phase-invariant. Our findings suggest the involvement of at least two separate pathways in binocular combination.

The left midfusiform and adjacent regions have been implicated in processing and memorizing familiar words, yet its role in memorizing novel characters has not been well understood.Using functional MRI, the present study examined the hypothesis that the left midfusiform is also involved in memorizing novel characters and spaced learning could enhance the memory by enhancing the left midfusiform activity during learning. Nineteen native Chinese readers were scanned while memorizing the visual form of 120 Korean characters that were novel to the subjects. Each character was repeated four times during learning. Repetition suppression was manipulated by using two different repetition schedules: massed learning and spaced learning, pseudo-randomly mixed within the same scanning session. Under the massed learning condition, the four repetitions were consecutive (with a jittered inter-repetition interval to improve the design efficiency). Under the spaced learning condition, the four repetitions were interleaved with a minimal inter-repetition lag of 6 stimuli. Spaced learning significantly improved participants' performance during the recognition memory test administered one hour after the scan. Stronger left midfusiform and inferior temporal gyrus activities during learning (summed across four repetitions) were associated with better memory of the characters, based on both within- and cross-subjects analyses. Compared to massed learning, spaced learning significantly reduced neural repetition suppression and increased the overall activities in these regions, which were associated with better memory for novel characters.These results demonstrated a strong link between cortical activity in the left midfusiform and memory for novel characters, and thus challenge the visual word form area (VWFA) hypothesis. Our results also shed light on the neural mechanisms of the spacing effect in memorizing novel characters.

The human visual system does not treat all parts of an image equally: the central segments of an image, which fall on the fovea, are processed with a higher resolution than the segments that fall in the visual periphery. Even though the differences between foveal and peripheral resolution are large, these differences do not usually disrupt our perception of seamless visual space. Here we examine a motion stimulus in which the shift from foveal to peripheral viewing creates a dramatic spatial/temporal discontinuity.The stimulus consists of a descending disk (global motion) with an internal moving grating (local motion). When observers view the disk centrally, they perceive both global and local motion (i.e., observers see the disk's vertical descent and the internal spinning). When observers view the disk peripherally, the internal portion appears stationary, and the disk appears to descend at an angle. The angle of perceived descent increases as the observer views the stimulus from further in the periphery. We examine the first- and second-order information content in the display with the use of a three-dimensional Fourier analysis and show how our results can be used to describe perceived spatial/temporal discontinuities in real-world situations.The perceived shift of the disk's direction in the periphery is consistent with a model in which foveal processing separates first- and second-order motion information while peripheral processing integrates first- and second-order motion information. We argue that the perceived distortion may influence real-world visual observations. To this end, we present a hypothesis and analysis of the perception of the curveball and rising fastball in the sport of baseball. The curveball is a physically measurable phenomenon: the imbalance of forces created by the ball's spin causes the ball to deviate from a straight line and to follow a smooth parabolic path. However, the curveball is also a perceptual puzzle because batters often report that the flight of the ball undergoes a dramatic and nearly discontinuous shift in position as the ball nears home plate. We suggest that the perception of a discontinuous shift in position results from differences between foveal and peripheral processing.

To explore the relationship between category and perceptual learning, we examined both category and perceptual learning in patients with treated Wilson's disease (WD), whose basal ganglia, known to be important in category learning, were damaged by the disease. We measured their learning rate and accuracy in rule-based and information-integration category learning, and magnitudes of perceptual learning in a wide range of external noise conditions, and compared the results with those of normal controls. The WD subjects exhibited deficits in both forms of category learning and in perceptual learning in high external noise. However, their perceptual learning in low external noise was relatively spared. There was no significant correlation between the two forms of category learning, nor between perceptual learning in low external noise and either form of category learning. Perceptual learning in high external noise was, however, significantly correlated with information-integration but not with rule-based category learning. The results suggest that there may be a strong link between information-integration category learning and perceptual learning in high external noise. Damage to brain structures that are important for information-integration category learning may lead to poor perceptual learning in high external noise, yet spare perceptual learning in low external noise. Perceptual learning in high and low external noise conditions may involve separate neural substrates.

In the title compound [systematic name: (tert-butyldimethylsilyl)methanetriyl tris(4-methylbenzenesulfonate)], C32H44O10S3Si, the central C atom and the SiIV center are in a tetrahedral configuration. The interplanar angles between pairs of the three benzene rings of the 4-methylphenylsulfonyl units are 41.15 (10), 18.11 (10) and 44.09 (10)°. C—H...π interactions are observed in the crystal structure. Molecules are linked into screw chains along the b axis by weak C—H...O interactions. Weak intramolecular C—H...O hydrogen bonds are also present.

Aims To evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG). Methods A cross-sectional study was performed with 103 patients (103 eyes) aged 25-50 years who had POAG without any other ocular disease. CSF measurements were obtained by the quick CSF method, a novel active learning algorithm that covers 19 spatial frequencies and 128 contrast levels. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (mGCC), radial peripapillary capillary (RPC) and macular vasculature were measured by optical coherence tomography and angiography. Correlation and regression analyses were used to assess the association of area under log CSF (AULCSF), CSF acuity and contrast sensitivities at multiple spatial frequencies with structural parameters. Results AULCSF and CSF acuity were positively associated with pRNFL thickness, RPC density, mGCC thickness and superficial macular vessel density (p<0.05). Those parameters were also significantly associated with contrast sensitivity at 1, 1.5, 3, 6, 12, 18 cycles per degree spatial frequencies (p<0.05) and, the lower the spatial frequency, the higher the correlation coefficient. RPC density (p=0.035, p=0.023) and mGCC thickness (p=0.002, p=0.011) had significant predictive value for contrast sensitivity at 1 and 1.5 cycles per degree, with adjusted R2 of 0.346 and 0.343, respectively. Conclusions Full spatial frequency contrast sensitivity impairment, most notably at low spatial frequencies, is a characteristic change in POAG. Contrast sensitivity is a potential functional endpoint for the measurement of glaucoma severity. [ABSTRACT FROM AUTHOR]