Comparison of Tiling Artifact Removal Methods in Secondary Ion Mass Spectrometry Images.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is used across many fields for the atomic and molecular characterization of surfaces, with both high sensitivity and high spatial resolution. When large analysis areas are required, standard ToF-SIMS instruments allow for the acquisition of adjoining tiles, which are acquired by rastering the primary ion beam. For such large area scans, tiling artifacts are a ubiquitous challenge, manifesting as intensity gradients across each tile and/or sudden changes in intensity between tiles. Such artifacts are thought to be related to a combination of sample charging, local detector sensitivity issues, and misalignment of the primary ion gun, among other instrumental factors. In this work, we investigated six different computational tiling artifact removal methods: tensor decomposition, multiplicative linear correction, linear discriminant analysis, seamless stitching, simple averaging, and simple interpolating. To ensure robustness in the study, we applied these methods to three hyperspectral ToF-SIMS data sets and one OrbiTrapSIMS data set. Our study includes a carefully designed statistical analysis and a quantitative survey that subjectively assessed the quality of the various methods employed. Our results demonstrate that while certain methods are useful and preferred more often, no one particular approach can be considered universally acceptable and that the effectiveness of the artifact removal method is strongly dependent on the particulars of the data set analyzed. As examples, the multiplicative linear correction and seamless stitching methods tended to score more highly on the subjective survey; however, for some data sets, this led to the introduction of new artifacts. In contrast, simple averaging and interpolation methods scored subjectively poorly on the biological data set, but more highly on the microarray data sets. We discuss and explore these findings in depth and present general recommendations given our findings to conclude the work.

The Influence of Light Wavelength on Human HPA Axis Rhythms: A Systematic Review.

Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens).

Sex and stress hormone dysregulation as clinical manifestations of hypothalamic function in migraine disorder: A meta-analysis.

Migraine is a leading cause of disability in young adults. It occurs more frequently in females, often comorbidly with stress disorders, suggesting an association with hypothalamic sex and stress hormonal function and a likely interaction with autonomic nervous system activation. Thus, this study aimed to meta-analyse current literature pertaining to female and male sex hormones (estrogen, progesterone and testosterone concentration), hypothalamic-pituitary-adrenal axis (HPA axis) cortisol responses and heart rate variability (HRV) in migraineurs and controls aged 13-65 years. A systematic search of MEDLINE, Embase, PsycINFO, PubMed, CINAHL and Web of Science databases on 29/08/2022 identified 29 studies for meta-analysis (encompassing 719 migraineur and 592 control participants) that met inclusion and NHLBI risk of bias criteria. Results demonstrated that estrogen concentrations of female migraineurs were reduced (g = -.60, 95% CI [-.91, -.29], p < .001) in the luteal phase of the menstrual cycle, compared to controls. No differences were found in progesterone levels overall in female migraineurs, nor in testosterone levels in male migraineurs compared to controls. Further, early diurnal cortisol concentrations were elevated (g = .32, 95% CI [.00, .63], p = .036) in female and male migraineurs compared to controls, though no differences were found in HRV of female or male migraineurs compared to controls. These findings of dysregulation of estrogen in females and cortisol dysregulation in female and male migraineurs indicate perturbed hypothalamic function and highlight the association of migraine with stress and the need for further rigorous investigation of hypothalamic neuroendocrine functions in migraineurs of both sexes.

Visual Motor Reaction Times Predict Receptive and Expressive Language Development in Early School-Age Children.

Proficiency of multisensory processing and motor skill are often associated with early cognitive, social, and language development. However, little research exists regarding the relationship between multisensory motor reaction times (MRTs) to auditory, visual and audiovisual stimuli, and classical measures of receptive language and expressive vocabulary development in school-age children. Thus, this study aimed to examine the concurrent development of performance in classical tests of receptive (Peabody Picture Vocabulary Test; abbreviated as PPVT) and expressive vocabulary (Expressive Vocabulary Test; abbreviated as EVT), nonverbal intelligence (NVIQ) (determined with the aid of Raven's Colored Progressive Matrices; abbreviated as RCPM), speed of visual-verbal processing in the Rapid Automatic Naming (RAN) test, Eye-Hand Co-ordination (EHC) in the SLURP task, and multisensory MRTs, in children (n = 75), aged between 5 and 10 years. Bayesian statistical analysis showed evidence for age group differences in EVT performance, while PPVT was only different for the youngest group of children aged 5-6, supporting different developmental trajectories in vocabulary acquisition. Bayesian correlations revealed evidence for associations between age, NVIQ, and vocabulary measures, with decisive evidence and a higher correlation (r = 0.57 to 0.68) between EVT, MRT tasks, and EHC visuomotor processing. This was further supported by regression analyses indicating that EVT performance was the strongest unique predictor of multisensory MRTs, EHC, and RAN time. Additionally, visual MRTs were found to predict both receptive and expressive vocabulary. The findings of the study have important implications as accessible school-based assessments of the concurrent development of NVIQ, language, and multisensory processing; and hence as rapid and timely measures of developmental and neurodevelopmental status.

Flash Electroretinography as a Measure of Retinal Function in Myopia and Hyperopia: A Systematic Review.

Refractive errors (myopia and hyperopia) are the most common visual disorders and are severe risk factors for secondary ocular pathologies. The development of refractive errors has been shown to be associated with changes in ocular axial length, suggested to be induced by outer retinal elements. Thus, the present study systematically reviewed the literature examining retinal function as assessed using global flash electroretinograms (gfERGs) in human clinical refractive error populations. Electronic database searching via Medline, PubMed, Web of Science, Embase, Psych INFO, and CINAHL retrieved 981 unique records (last searched on the 29 May 2022). Single case studies, samples with ocular comorbidities, drug trials, and reviews were excluded. Demographic characteristics, refractive state, gfERG protocol details, and waveform characteristics were extracted for the eight studies that met the inclusion criteria for the review and were judged to have acceptable risk of bias using the OHAT tool (total N = 552 participants; age 7 to 50). Study synthesis suggests that myopia in humans involves attenuation of gfERG photoreceptor (a-wave) and bipolar cell (b-wave) function, consistent with the animal literature. Meaningful interpretation of the overall findings for hyperopia was limited by inconsistent reporting, highlighting the need for future studies to report key aspects of gfERG research design and outcomes more consistently for myopic and hyperopic refractive errors.

The Contribution of Visual and Auditory Working Memory and Non-Verbal IQ to Motor Multisensory Processing in Elementary School Children.

Although cognitive abilities have been shown to facilitate multisensory processing in adults, the development of cognitive abilities such as working memory and intelligence, and their relationship to multisensory motor reaction times (MRTs), has not been well investigated in children. Thus, the aim of the current study was to explore the contribution of age-related cognitive abilities in elementary school-age children (n = 75) aged 5-10 years, to multisensory MRTs in response to auditory, visual, and audiovisual stimuli, and a visuomotor eye-hand co-ordination processing task. Cognitive performance was measured on classical working memory tasks such as forward and backward visual and auditory digit spans, and the Raven's Coloured Progressive Matrices (RCPM test of nonverbal intelligence). Bayesian Analysis revealed decisive evidence for age-group differences across grades on visual digit span tasks and RCPM scores but not on auditory digit span tasks. The results also showed decisive evidence for the relationship between performance on more complex visually based tasks, such as difficult items of the RCPM and visual digit span, and multisensory MRT tasks. Bayesian regression analysis demonstrated that visual WM digit span tasks together with nonverbal IQ were the strongest unique predictors of multisensory processing. This suggests that the capacity of visual memory rather than auditory processing abilities becomes the most important cognitive predictor of multisensory MRTs, and potentially contributes to the expected age-related increase in cognitive abilities and multisensory motor processing.

Osmotic gradients and transretinal water flow-a quantitative elemental microanalytical study of frozen hydrated chick eyes.

Optical clarity and efficient phototransduction are necessary for optimal vision, however, how the associated processes of osmoregulation and continuous fluid drainage across the whole eye are achieved remains relatively unexplored. Hence, we have employed elemental microanalysis of planed surfaces of light-adapted bulk frozen-hydrated chick eyes to determine the unique intracellular elemental localization, compositions, and hydration states that contribute to maintaining osmotic gradients and water flow from the vitreous, across the retina, retinal pigment epithelium (RPE), to choroid and sclera. As expected, the greatest difference in resultant osmotic concentration gradients, [calculated using the combined concentrations of sodium (Na) and potassium (K)] and tissue hydration [oxygen-defined water concentration], occurs in the outer retina and, in particular, in the RPE where the apical and basal membranes are characterized by numerous bioenergetically active, osmoregulating ion transport mechanisms, aquaporins, and chloride (Cl) channels. Our results also demonstrate that the high intracellular Na+ and K+ concentrations in the apical region of the RPE are partially derived from the melanosomes. The inclusion of the ubiquitous osmolyte taurine to the calculation of the osmotic gradients suggests a more gradual increase in the osmotic transport of water from the vitreous into the ganglion cell layer across the inner retina to the outer segments of the photoreceptor/apical RPE region where the water gradient increases rapidly towards the basal membrane. Thus transretinal water is likely to cross the apical membrane from the retina into the RPE cells down the Na+ and K+ derived osmotic concentration gradient and leave the RPE for the choroid across the basal membrane down the Cl- derived osmotic concentration gradient that is sustained by the well-described bioenergetically active RPE ion transporters and channels.

A Role for Visual Memory in Vocabulary Development: A Systematic Review and Meta-Analysis.

Although attention and early associative learning in preverbal children is predominantly driven by rapid eye-movements in response to moving visual stimuli and sounds/words (e.g., associating the word "bottle" with the object), the literature examining the role of visual attention and memory in ongoing vocabulary development across childhood is limited. Thus, this systematic review and meta-analysis examined the association between visual memory and vocabulary development, including moderators such as age and task selection, in neurotypical children aged 2-to-12 years, from the brain-based perspective of cognitive neuroscience. Visual memory tasks were classified according to the visual characteristics of the stimuli and the neural networks known to preferentially process such information, including consideration of the distinction between the ventral visual stream (processing more static visuo-perceptual details, such as form or colour) and the more dynamic dorsal visual stream (processing spatial temporal action-driven information). Final classifications included spatio-temporal span tasks, visuo-perceptual or spatial concurrent array tasks, and executive judgment tasks. Visuo-perceptual concurrent array tasks, reliant on ventral stream processing, were moderately associated with vocabulary, while tasks measuring spatio-temporal spans, associated with dorsal stream processing, and executive judgment tasks (central executive), showed only weak correlations with vocabulary. These findings have important implications for health professionals and researchers interested in language, as they advocate for the development of more targeted language learning interventions that include specific and relevant aspects of visual processing and memory, such as ventral stream visuo-perceptual details (i.e., shape or colour).

Visual Processing During the Interictal Period Between Migraines: A Meta-Analysis.

Migraine is a poorly understood neurological disorder and a leading cause of disability in young adults, particularly women. Migraines are characterized by recurring episodes of severe pulsating unilateral headache and usually visual symptoms. Currently there is some disagreement in the electrophysiological literature regarding the universality of all migraineurs exhibiting physiological visual impairments also during interictal periods (i.e., the symptom free period between migraines). Thus, this meta-analysis investigated the evidence for altered visual function as measured electrophysiologically via pattern-reversal visual evoked potential (VEP) amplitudes and habituation in adult migraineurs with or without visual aura and controls in the interictal period. Twenty-three studies were selected for random effects meta-analysis which demonstrated slightly diminished VEP amplitudes in the early fast conducting P100 component but not in N135, and substantially reduced habituation in the P100 and the N135 in migraineurs with and without visual aura symptoms compared to controls. No statistical differences were found between migraineurs with and without aura, possibly due to inadequate studies. Overall, insufficient published data and substantial heterogeneity between studies was observed for all latency components of pattern-reversal VEP, highlighting the need for further electrophysiological experimentation and more targeted temporal analysis of visual function, in episodic migraineurs.

Age-related decrease in motor contribution to multisensory reaction times in primary school children.

Traditional measurement of multisensory facilitation in tasks such as speeded motor reaction tasks (MRT) consistently show age-related improvement during early childhood. However, the extent to which motor function increases with age and hence contribute to multisensory motor reaction times in young children has seldom been examined. Thus, we aimed to investigate the contribution of motor development to measures of multisensory (auditory, visual, and audiovisual) and visuomotor processing tasks in three young school age groups of children (n = 69) aged (5-6, n = 21; 7-8, n = 25.; 9-10 n = 18 years). We also aimed to determine whether age-related sensory threshold times for purely visual inspection time (IT) tasks improved significantly with age. Bayesian results showed decisive evidence for age-group differences in multisensory MRT and visuo-motor processing tasks, though the evidence showed that threshold time for visual identification IT performance was only slower in the youngest age group children (5-6) compared to older groups. Bayesian correlations between performance on the multisensory MRT and visuo-motor processing tasks indicated moderate to decisive evidence in favor of the alternative hypothesis (BF10 = 4.71 to 91.346), though not with the threshold IT (BF10 < 1.35). This suggests that visual sensory system development in children older than 6 years makes a less significant contribution to the measure of multisensory facilitation, compared to motor development. In addition to this main finding, multisensory facilitation of MRT within race-model predictions was only found in the oldest group of children (9-10), supporting previous suggestions that multisensory integration is likely to continue into late childhood/early adolescence at least.

Functional Deficits and Structural Changes Associated With the Visual Attention Network During Resting State in Adult Strabismic and Anisometropic Amblyopes.

Our previous study has shown impaired blood oxygen level-dependent (BOLD)/functional magnetic resonance imaging (fMRI) activation of the visual attention network in strabismic amblyopia (SA). However, there has been no comparison of resting state fMRI activation and functional connectivity (FC) in brain regions of interest (ROIs) along the visual attention network including visual cortex (V1), intraparietal sulcus (IPS), and frontal eye fields (FEFs) during closed eye resting across the SA (n = 20, 13LE), or anisometropic amblyopes (AA) (n = 20, 13LE) groups. Hence, we compared, gray matter volume (GMV), amplitude of low frequency fluctuations (ALFFs), regional homogeneity (ReHo), and FC in the left and right hemisphere ROIs of the visual attention network in SA, AA, and healthy controls (HCs) (n = 21). Correlation analyses of corrected visual acuity (cVA) of amblyopic eye and MRI results were also performed and showed that the LogMAR cVA of the amblyopic eye positively correlated with right zALFF and zReHo FEF of SA and right IPS of AA only. GMV of both left and right hemisphere V1 areas was significantly greater but ALFF was significantly lower for SA compared to AA and HC groups. zALFF and zReHo analyses in the AA and SA groups indicated significantly higher activation than that in the HC group in the right FEF and IPS but lower than that in the HC group in the left FEF, and only the SA group showed lower activation in both V1 areas than the HC group. FC values of the right FEF-left V1, right FEF-right V1, and right FEF-right IPS pathways in the SA and AA groups were also significantly higher than those in the HC group whereas all other FC values were non-significant. Thus, this study indicates that even during resting-state the visual attention network function is impaired in SA and AA participants with only right hemisphere FEF showing significant activation in SA and IPS in AA suggesting that the slower saccade activation times characteristic of amblyopic eyes lead to the dominant eye controlling activation of the visual attention network.

Vision and Visuomotor Performance Following Acute Ischemic Stroke.

BACKGROUND: As measurable sensory and motor deficits are key to the diagnosis of stroke, we investigated the value of objective tablet based vision and visuomotor capacity assessment in acute mild-moderate ischemic stroke (AIS) patients. METHODS: Sixty AIS patients (65 ± 14 years, 33 males) without pre-existing visual/neurological disorders and acuity better than 6/12 were tested at their bedside during the first week post-stroke and were compared to 40 controls (64 ± 11 years, 15 males). Visual field sensitivity, quantified as mean deviation (dB) and visual acuity (with and without luminance noise), were tested on MRFn (Melbourne Rapid Field-Neural) iPad application. Visuomotor capacity was assessed with the Lee-Ryan Eye-Hand Coordination (EHC) iPad application using a capacitive stylus for iPad held in the preferred hand.Time to trace 3 shapes and displacement errors (deviations of >3.5 mm from the shape) were recorded. Diagnostic capacity was considered with Receiver Operating Characteristics. Vision test outcomes were correlated with National Institutes of Health Stroke Scale (NIHSS) score at the admission. RESULTS: Of the 60 AIS patients, 58 grasped the iPad stylus in their preferred right hand even though 31 had left hemisphere lesions. Forty-one patients (68%) with better than 6/12 visual acuity (19 right, 19 left hemisphere and 3 multi-territorial lesions) returned significantly abnormal visual fields. The stroke group took significantly longer (AIS: 93.4 ± 60.1 s; Controls: 33.1 ± 11.5 s, p < 0.01) to complete EHC tracing and made larger displacements (AIS: 16,388 ± 36,367 mm; Controls: 2,620 ± 1,359 mm, p < 0.01) although both control and stroke groups made similar numbers of errors. EHC time was not significantly different between participants with R (n = 26, 84.3 ± 55.3 s) and L (n = 31, 101.3 ± 64.7 s) hemisphere lesions. NIHSS scores and EHC measures showed low correlations (Spearman R: -0.15, L: 0.17). ROC analysis of EHC and vision tests found high diagnostic specificity and sensitivity for a fail at EHC time, or visual field, or Acuity-in-noise (sensivity: 93%, specificity: 83%) that shows little relationship to NIHSS scores. CONCLUSIONS: EHC time and vision test outcomes provide an easy and rapid bedside measure that complements existing clinical assessments in AIS. The low correlation between visual function, NIHSS scores and lesion site offers an expanded clinical view of changes following stroke.

The effect of anxiety on working memory and language abilities in elementary schoolchildren with and without Additional Health and Developmental Needs.

Although excessive childhood anxiety is recognised as a significant public health, education and socioeconomic concern, the specific effects of such anxiety on language development and working memory, particularly visual working memory, are relatively unknown. Thus, this study aimed to examine parent-reported trait anxiety, parent-reported functional language (daily communication skills) and clinical measures of non-verbal intelligence, receptive and expressive vocabulary, phonological awareness, and visual and auditory-verbal short-term and working memory in elementary schoolchildren. The final sample included 41 children categorised as Additional Health and Developmental Needs (AHDN) due to medical, neurodevelopmental or educational concerns and 41 age- and IQ-matched neurotypical (NT) children, aged 5- to 9-years. Results showed that 26% of all children in our entire sample (AHDN and NT) experienced moderate, sub-clinical anxiety (as reported by parents), and that AHDN children were 10.5 times more likely to experience high anxiety than the NT group (odds ratio). Parents of AHDN children reported lower functional language in their children than parents of NT children. Cognitive testing indicated that the AHDN group also had poorer visual and auditory-verbal working memory than the NT group. Further, High Anxiety children (drawn from both AHDN and NT groups) showed poorer parent-reported functional language skills, and lower visual and auditory-verbal working memory capacities. Our findings are amongst the first to confirm that the presence of high parent-rated trait anxiety is associated with reduced visual working memory in children, which is consistent with biological and theoretical expectations of the impact of anxiety on visually driven, goal-directed attention and working memory. Our results regarding the high prevalence of sub-clinical anxiety in both ADHD and neurotypical children highlight the need for early assessment of anxiety in all schoolchildren, especially those classified as AHDN.

Faster social attention disengagement in individuals with higher autism traits.

INTRODUCTION: Atypical visual and social attention has often been associated with clinically diagnosed autism spectrum disorder (ASD), and with the broader autism phenotype. Atypical social attention is of particular research interest given the importance of facial expressions for social communication, with faces tending to attract and hold attention in neurotypical individuals. In autism, this is not necessarily so, where there is debate about the temporal differences in the ability to disengage attention from a face. METHOD: Thus, we have used eye-tracking to record saccadic latencies as a measure of time to disengage attention from a central task-irrelevant face before orienting to a newly presented peripheral nonsocial target during a gap-overlap task. Neurotypical participants with higher or lower autism-like traits (AT) completed the task that included central stimuli with varied expressions of facial emotion as well as an inverted face. RESULTS: High AT participants demonstrated faster saccadic responses to detect the nonsocial target than low AT participants when disengaging attention from a face. Furthermore, faster saccadic responses were recorded when comparing disengagement from upright to inverted faces in low AT but not in high AT participants. CONCLUSIONS: Together, these results extend findings of atypical social attention disengagement in autism and highlight how differences in attention to faces in the broader autism phenotype can lead to apparently superior task performance under certain conditions. Specifically, autism traits were linked to faster attention orienting to a nonsocial target due to the reduced attentional hold of the task irrelevant face stimuli. The absence of an inversion effect in high AT participants also reinforces the suggestion that they process upright or inverted faces similarly, unlike low AT participants for whom inverted faces are thought to be less socially engaging, thus allowing faster disengagement.

The Age-Related Changes in Speed of Visual Perception, Visual Verbal and Visuomotor Performance, and Nonverbal Intelligence During Early School Years.

Speed of sensory information processing has long been recognized as an important characteristic of global intelligence, though few studies have concurrently investigated the contribution of different types of information processing to nonverbal IQ in children, nor looked at whether chronological age vs. months of early schooling plays a larger role. Thus, this study investigated the speed of visual information processing in three tasks including a simple visual inspection time (IT) task, a visual-verbal processing task using Rapid Automatic Naming (RAN) of objects as an accepted preschool predictor of reading, and a visuomotor processing task using a game-like iPad application, (the "SLURP" task) that requires writing like skills, in association with nonverbal IQ (Raven's Coloured Progressive Matrices) in children (n = 100) aged 5-7 years old. Our results indicate that the rate and accuracy of information processing for all three tasks develop with age, but that only RAN and SLURP rates show significant improvement with years of schooling. RAN and SLURP also correlated significantly with nonverbal IQ scores, but not with IT. Regression analyses demonstrate that months of formal schooling provide additional contributions to the speed of dual-task visual-verbal (RAN) and visuomotor performance and Raven's scores supporting the domain-specific hypothesis of processing speed development for specific skills as they contribute to global measures such as nonverbal IQ. Finally, RAN and SLURP are likely to be useful measures for the early identification of young children with lower intelligence and potentially poor reading.

Action video game training improves text reading accuracy, rate and comprehension in children with dyslexia: a randomized controlled trial.

Dynamic visual attention training using Action Video Games (AVGs) is a promising intervention for dyslexia. This study investigated the efficacy of 5 h (10 × 30 min) of AVG training in dyslexic children (aged 8-13) using 'Fruit Ninja', while exploring whether increasing attentional and eye movement demands enhanced AVG effectiveness. Regular (AVG-R; n = 22) and enhanced AVG training (AVG+; n = 23) were compared to a treatment-as-usual comparison group (n = 19) on reading, rapid naming, eye movements and visuo-temporal processing. Playing 'Fruit Ninja' for only 5 h significantly improved reading accuracy, rate, comprehension and rapid naming of both AVG groups, compared to the comparison group, though increasing attentional demands did not enhance AVG efficacy. Participants whose low contrast magnocellular-temporal processing improved most following training also showed significantly greater improvement in reading accuracy. The findings demonstrate a clear role for visual attention in reading and highlight the clinical applicability of AVGs as a fun, motivational and engaging intervention for dyslexia.

Long-Wavelength-Filtered Light Transiently Inhibits Negative Lens-Induced Axial Eye Growth in the Chick Myopia Model.

Purpose: Eye growth and myopia development in chicks, and some other animal models, can be suppressed by rearing under near-monochromatic, short-wavelength blue light. We aimed to determine whether similar effects could be achieved using glass filters that transmit a broader range of short and middle wavelengths. Methods: On day 6 or 7 post-hatch, 169 chicks were assigned to one of three monocular lens conditions (-10 D, +10 D, plano) and reared for 7 or 10 days under one of four 201-lux lighting conditions: (1) B410 long-wavelength-filtered light, (2) B460 long-wavelength-filtered light, (3) Y48 short-wavelength-filtered light, or (4) HA50 broadband light. Results: At 7 days, B410 (but not B460) long-wavelength-filtered light had significantly inhibited negative lens induced axial growth relative to Y48 short-wavelength-filtered light (mean difference in experimental eye = -0.249 mm; P = 0.006) and HA50 broadband light (mean difference = -0.139 mm; P = 0.038). B410 filters also inhibited the negative lens-induced increase in vitreous chamber depth relative to all other filter conditions. Corresponding changes in refraction did not occur, and biometric measurements in a separate cohort of chicks suggested that the axial dimension changes were transient and not maintained at 10 days. Conclusions: Chromatic effects on eye growth can be achieved using filters that transmit a broad range of wavelengths even in the presence of strong cues for myopia development. Translational Relevance: Broad-wavelength filters that provide a more "naturalistic" visual experience relative to monochromatic light have potential to alter myopia development, although the effects shown here were modest and transient and require exploration in further species.

Electroretinography and Gene Expression Measures Implicate Phototransduction and Metabolic Shifts in Chick Myopia and Hyperopia Models.

The Retinal Ion-Driven Fluid Efflux (RIDE) model theorizes that phototransduction-driven changes in trans-retinal ion and fluid transport underlie the development of myopia (short-sightedness). In support of this model, previous functional studies have identified the attenuation of outer retinal contributions to the global flash electroretinogram (gfERG) following weeks of myopia induction in chicks, while discovery-driven transcriptome studies have identified changes to the expression of ATP-driven ion transport and mitochondrial metabolism genes in the retina/RPE/choroid at the mid- to late-induction time-points. Less is known about the early time-points despite biometric analyses demonstrating changes in eye growth by 3 h in the chick lens defocus model. Thus, the present study compared gfERG and transcriptome profiles between 3 h and 3 days of negative lens-induced myopia and positive lens-induced hyperopia in chicks. Photoreceptor (a-wave and d-wave) and bipolar (b-wave and late-stage d-wave) cell responses were suppressed following negative lens-wear, particularly at the 3-4 h and 3-day time-points when active shifts in the rate of ocular growth were expected. Transcriptome measures revealed the up-regulation of oxidative phosphorylation genes following 6 h of negative lens-wear, concordant with previous reports at 2 days in this model. Signal transduction pathways, with core genes involved in glutamate and G-protein coupled receptor signalling, were down-regulated at 6 h. These findings contribute to a growing body of evidence for the dysregulation of phototransduction and mitochondrial metabolism in animal models of myopia.

An x-ray microanalytical method for measuring in vivo element and water concentrations, relating to osmoregulation, in cells and tissues of the posterior eye.

Osmoregulation is critical for cell and tissue survival yet there are relatively few methods available to determine osmotic gradients from water and elemental concentration either in single cells or across multiple cellular layers of tissue. X-ray microanalysis of frozen-hydrated preparations in a scanning electron microscope is one such powerful, sensitive, nondestructive technique. Here we use x-ray microanalysis to quantitatively analyse intracellular element concentrations and oxygen concentrations, as a proxy for water concentrations, in selected individual cells of the posterior eye. Using frozen-hydrated preparations of the retinal complex of chicken eyes, it is shown that structural preservation is sufficient to identify cell layers and individual cells. The quantitative analysis of selected areas in the photoreceptor layer, inner nuclear layer and ganglion cell layer, where specific cell types were known to be present, provided measurements of intracellular element concentrations comparable with the analysis of individual cells. It is also shown that in the cells of the retinal pigment epithelium and outer photoreceptor segments elemental analyses were reasonably consistent at the cellular level in different depth levels of the same sample. Comparison of oxygen concentrations, as a proxy for water concentration, at two accelerating voltages (15 and 5 kV) indicated that at 15 kV oxygen concentration was largely derived from intracellular water. Water concentrations could be calculated and concentrations of diffusible elements (Na, K) could be defined in mmol/L. From the latter it is possible to calculate osmotic concentrations of individual cells and osmotic gradients across the tissue. LAY DESCRIPTION: Understanding many cellular processes, in both healthy and diseased states, depends on knowing how the water content of cells and their surrounding fluids is controlled. The transport of water is generally down its concentration gradient or against the osmotic concentration gradient defined by solutes such as sodium, potassium and chloride dissolved in the water. We have refined a microanalytical method, that detects the x-rays emitted from specific elements when they are bombarded by electrons in a scanning electron microscope, to apply it to the analysis of the retina of the eye. The method facilitates the measurement of the elemental composition, water and osmotic concentration gradients of cells and tissues in the eye, that may be involved in the development of myopia, or short sightedness, a condition that afflicts many people including some 80 - 90% of children in Asia.