Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

BACKGROUND: In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. METHODS: AEPs were recorded to simple 100 Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. RESULTS: Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. CONCLUSIONS: To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Investigation of factors that may affect the foveal avascular zone: An optical coherence tomography angiography study.

SIGNIFICANCE: An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented. PURPOSE: The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants. METHODS: One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ. RESULTS: Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability. CONCLUSIONS: Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

Neural correlates of audiovisual narrative speech perception in children and adults on the autism spectrum: A functional magnetic resonance imaging study.

Autistic individuals show substantially reduced benefit from observing visual articulations during audiovisual speech perception, a multisensory integration deficit that is particularly relevant to social communication. This has mostly been studied using simple syllabic or word-level stimuli and it remains unclear how altered lower-level multisensory integration translates to the processing of more complex natural multisensory stimulus environments in autism. Here, functional neuroimaging was used to examine neural correlates of audiovisual gain (AV-gain) in 41 autistic individuals to those of 41 age-matched non-autistic controls when presented with a complex audiovisual narrative. Participants were presented with continuous narration of a story in auditory-alone, visual-alone, and both synchronous and asynchronous audiovisual speech conditions. We hypothesized that previously identified differences in audiovisual speech processing in autism would be characterized by activation differences in brain regions well known to be associated with audiovisual enhancement in neurotypicals. However, our results did not provide evidence for altered processing of auditory alone, visual alone, audiovisual conditions or AV- gain in regions associated with the respective task when comparing activation patterns between groups. Instead, we found that autistic individuals responded with higher activations in mostly frontal regions where the activation to the experimental conditions was below baseline (de-activations) in the control group. These frontal effects were observed in both unisensory and audiovisual conditions, suggesting that these altered activations were not specific to multisensory processing but reflective of more general mechanisms such as an altered disengagement of Default Mode Network processes during the observation of the language stimulus across conditions.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

Background: In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. Methods: AEPs were recorded to simple 100Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. Results: Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. Conclusions: To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

Background In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. Methods AEPs were recorded to simple 100Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. Results Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. Conclusions To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Ability to Process Multisensory Information Is Impaired in Open Angle Glaucoma.

PRCIS: Patients with glaucoma demonstrated deficiencies in their ability to process multisensory information when compared with controls, with those deficiencies being related to glaucoma severity. Impaired multisensory integration (MSI) may affect the quality of life in individuals with glaucoma and may contribute to the increased prevalence of falls and driving safety concerns. Therapeutic possibilities to influence cognition in glaucoma should be explored. PURPOSE: Glaucoma is a neurodegenerative disease of the optic nerve that has also been linked to cognitive health decline. This study explored MSI as a function of glaucoma status and severity. METHODS: MSI was assessed in 37 participants with open angle glaucoma relative to 18 age-matched healthy controls. The sound-induced flash illusion was used to assess MSI efficiency. Participants were presented with various combinations of simultaneous visual and/or auditory stimuli and were required to indicate the number of visual stimuli observed for each of the 96 total presentations. Central retinal sensitivity was assessed as an indicator of glaucoma severity (MAIA; CenterVue). RESULTS: Participants with glaucoma performed with equivalent capacity to healthy controls on unisensory trials ( F1,53 =2.222, P =0.142). Both groups performed equivalently on congruent multisensory trials involving equal numbers of auditory and visual stimuli F1,53 =1.032, P =0.314). For incongruent presentations, that is, 2 beeps and 1 flash stimulus, individuals with glaucoma demonstrated a greater influence of the incongruent beeps when judging the number of flashes, indicating less efficient MSI relative to age-matched controls ( F1,53 =11.45, P <0.002). In addition, MSI performance was positively correlated with retinal sensitivity ( F3,49 =4.042, P <0.025), adjusted R ²=0.15). CONCLUSIONS: Individuals with open angle glaucoma exhibited MSI deficiencies that relate to disease severity. The type of deficiencies observed were similar to those observed among older individuals with cognitive impairment and balance issues. Impaired MSI may, therefore, be relevant to the increased prevalence of falls observed among individuals with glaucoma, a concept that merits further investigation.

The Refractive Error and Vision Impairment Estimation with Spectacle Data Study.

Purpose: To investigate whether spectacle lens sales data can be used to estimate the population distribution of refractive error among patients with ametropia and hence to estimate the current and future risk of vision impairment. Design: Cross-sectional study. Participants: A total of 141 547 436 spectacle lens sales records from an international European lens manufacturer between 1998 and 2016. Methods: Anonymized patient spectacle lens sales data, including refractive error information, was provided by a major European spectacle lens manufacturer. Data from the Gutenberg Health Survey was digitized to allow comparison of a representative, population-based sample with the spectacle lens sales data. A bootstrap analysis was completed to assess the comparability of both datasets. The expected level of vision impairment resulting from myopia at 75 years of age was calculated for both datasets using a previously published risk estimation equation combined with a saturation function. Main Outcome Measures: Comparability of spectacle lens sales data on refractive error with typical population surveys of refractive error and its potential usefulness to predict vision impairment resulting from refractive error. Results: Equivalent estimates of the population distribution of spherical equivalent refraction can be provided from spectacle lens data within limits. For myopia, the population distribution was equivalent to the Gutenberg Health Survey (≤ 5% deviation) for levels of -2.0 diopters (D) or less, whereas for hyperopia, the distribution was equivalent (≤ 5% deviation) for levels of +3.0 D or more. The estimated rates of vision impairment resulting from myopia were not statistically significantly different (chi-square, 182; degrees of freedom, 169; P = 0.234) between the spectacle lens dataset and Gutenberg Health Survey dataset. Conclusions: The distribution of refractive error and hence the risk of vision impairment resulting from refractive error within a population can be determined using spectacle lens sales data. Pooling this type of data from multiple industry sources could provide a cost-effective, timely, and globally representative mechanism for monitoring the evolving epidemiologic features of refractive error and associated vision impairment.

Neural correlates of multisensory enhancement in audiovisual narrative speech perception: A fMRI investigation.

This fMRI study investigated the effect of seeing articulatory movements of a speaker while listening to a naturalistic narrative stimulus. It had the goal to identify regions of the language network showing multisensory enhancement under synchronous audiovisual conditions. We expected this enhancement to emerge in regions known to underlie the integration of auditory and visual information such as the posterior superior temporal gyrus as well as parts of the broader language network, including the semantic system. To this end we presented 53 participants with a continuous narration of a story in auditory alone, visual alone, and both synchronous and asynchronous audiovisual speech conditions while recording brain activity using BOLD fMRI. We found multisensory enhancement in an extensive network of regions underlying multisensory integration and parts of the semantic network as well as extralinguistic regions not usually associated with multisensory integration, namely the primary visual cortex and the bilateral amygdala. Analysis also revealed involvement of thalamic brain regions along the visual and auditory pathways more commonly associated with early sensory processing. We conclude that under natural listening conditions, multisensory enhancement not only involves sites of multisensory integration but many regions of the wider semantic network and includes regions associated with extralinguistic sensory, perceptual and cognitive processing.

Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum.

BACKGROUND: Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD. METHODS: We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n = 27), comparing them to a control cohort of neurotypical (NT) participants (n = 35). RESULTS: Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group. LIMITATIONS: The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability. CONCLUSIONS: Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition.

Big Data Analysis of Vision Screening Standards Used to Evaluate Fitness to Drive.

PURPOSE: Visual acuity (VA) assessment is the most commonly performed vision screening method for drivers. The standards and repeat assessment intervals used, however, are arbitrary, lack an evidence base and are highly variable across different countries. This study utilizes the power of Big Data to provide evidence-based recommendations for standardized driver vision screening. METHODS: Anonymized electronic medical record data were gathered from 40 Irish optometry practices comprising 81,184 unique patients. A Kaplan-Meier Survival (KMS) analysis was used to determine the effect of increasing age and time since screening on the likelihood of passing the VA standard for driving. A logistic function was fit to assess the effect of varying the minimum VA standard required to drive on the screening pass rate within the population. RESULTS: The likelihood of failing repeat screening increased as a function of time since initial screening for all age groups (χ2 =1447, df = 6, p<.001), with older patients most affected. Rescreening intervals for individuals who initially met the vision standard unaided reduced as a function of age. Using an 80% survivability threshold, intervals ranged from every eight years for drivers under 50, reducing to every two years for those aged over 80. Rescreening intervals for drivers requiring optical correction to meet the standard also decreased with age. Approximately, 1% of individuals are excluded from driving using a 0.3 logMAR VA standard with correction. CONCLUSIONS: VA-based screening should take place at regular intervals for all drivers, not just those over 70. Re-screening intervals should be based on age, with shorter intervals for older drivers due to the combined effect of age and time on the likelihood of passing the driving VA standards. The most commonly used standard of 0.3 logMAR results in a minimal number of potential drivers being excluded from driving.

Consistent Honor, Persistent Disadvantage: American Indian and Alaska Native Veteran Health in the National Survey of Veterans.

Objective: To examine self-rated health and activities of daily living (ADLs) limitations among American Indian and Alaska Native (AI/AN) veterans relative to white veterans. Methods: We use the 2010 National Survey of Veterans and limit the sample to veterans who identify as AI/AN or non-Hispanic white. We calculated descriptive statistics, confidence intervals, and used logistic regression. Results: AI/AN veterans are younger, have lower levels of income, and have higher levels of exposure to combat and environmental hazards compared to white veterans. We found that AI/AN veterans are significantly more likely to report fair/poor health controlling for socioeconomic status and experience an ADL controlling for age, health behaviors, socioeconomic status, and military factors. Discussion: The results indicate that AI/AN veterans are a disadvantaged population in terms of their health and disability compared to white veterans. AI/AN veterans may require additional support from family members and/or Veteran Affairs to address ADLs.

Application of big-data for epidemiological studies of refractive error.

PURPOSE: To examine whether data sourced from electronic medical records (EMR) and a large industrial spectacle lens manufacturing database can estimate refractive error distribution within large populations as an alternative to typical population surveys of refractive error. SUBJECTS: A total of 555,528 patient visits from 28 Irish primary care optometry practices between the years 1980 and 2019 and 141,547,436 spectacle lens sales records from an international European lens manufacturer between the years 1998 and 2016. METHODS: Anonymized EMR data included demographic, refractive and visual acuity values. Anonymized spectacle lens data included refractive data. Spectacle lens data was separated into lenses containing an addition (ADD) and those without an addition (SV). The proportions of refractive errors from the EMR data and ADD lenses were compared to published results from the European Eye Epidemiology (E3) Consortium and the Gutenberg Health Study (GHS). RESULTS: Age and gender matched proportions of refractive error were comparable in the E3 data and the EMR data, with no significant difference in the overall refractive error distribution (χ2 = 527, p = 0.29, DoF = 510). EMR data provided a closer match to the E3 refractive error distribution by age than the ADD lens data. The ADD lens data, however, provided a closer approximation to the E3 data for total myopia prevalence than the GHS data, up to age 64. CONCLUSIONS: The prevalence of refractive error within a population can be estimated using EMR data in the absence of population surveys. Industry derived sales data can also provide insights on the epidemiology of refractive errors in a population over certain age ranges. EMR and industrial data may therefore provide a fast and cost-effective surrogate measure of refractive error distribution that can be used for future health service planning purposes.

Smartphone use as a possible risk factor for myopia.

CLINICAL RELEVANCE: This study demonstrates an association between myopia and smartphone data usage. Youths now spend more time participating in near tasks as a result of smartphone usage. This poses an additional risk factor for myopia development/progression and is an important research question in relation to potential myopia management strategies. BACKGROUND: Children are now exposed to another possible environmental risk factor for myopia - smartphones. This study investigates the amount of time students spend on their smartphones and their patterns of smartphone usage from a myopia perspective. METHODS: Primary, secondary and tertiary level students completed a questionnaire exploring patterns of smartphone usage and assessing their attitudes toward potential myopia risk factors. Device-recorded data usage over an extended period was quantified as the primary and objective indicator of phone use. Average daily time spent using a smartphone was also quantified by self-reported estimates. Refractive status was verified by an optometrist. RESULTS: Smartphone ownership among the 418 students invited to participate was over 99-per cent. Average daily smartphone data and time usage was 800.37 ± 1,299.88-MB and 265.16 ± 168.02-minutes respectively. Myopic students used almost double the amount of smartphone data at 1,130.71 ± 1,748.14-MB per day compared to non-myopes at 613.63 ± 902.15-MB (p = 0.001). Smartphone time usage was not significantly different (p = 0.09, 12-per cent higher among myopes). Multinomial logistic regression revealed that myopic refractive error was statistically significantly associated with increasing daily smartphone data usage (odds ratio 1.08, 95% CI 1.03-1.14) as well as increasing age (odds ratio 1.09, 95% CI 1.02-1.17) and number of myopic parents (odds ratio 1.55, 95% CI 1.06-2.3). Seventy-three per cent of students believed that digital technology may adversely affect their eyes. CONCLUSION: This study demonstrates an association between myopia and smartphone data usage. Given the serious nature of the ocular health risks associated with myopia, our findings indicate that this relationship merits more detailed investigation.

The relationship between serum zinc levels and myopia.

CLINICAL SIGNIFICANCE: Nutritional status influences growth and development, including that of the eye. However, little attention has been given to possible dietary influences in myopia. This study demonstrates that serum zinc has no relationship with myopia development. BACKGROUND: Myopia is inherently associated with eye growth and thereby possibly amenable to nutritional influence. A number of Asian studies have reported lower levels of serum zinc in myopic children. This study was designed to assess the relationship between serum zinc and myopia in the Korean population - using a subsample of participants from nationally representative data. METHODS: Data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES) 2010 were used to explore zinc status in relation to refraction. A total of 304 participants were analysed, ranging in age from 12 to 19-years. Serum zinc levels were measured using inductively coupled plasma mass spectrometry, while refractive error was determined by non-cycloplegic autorefraction. Multivariate analysis was used to examine the association. RESULTS: A significant majority of participants (n = 255; 84 per cent) were myopic. There was no significant difference in serum zinc levels between myopic and non-myopic children (p = 0.81). In multivariate logistic regression, serum zinc was not significantly associated with myopia after adjustment for age, gender, residence, body mass index, family income and recreational activity. Similarly, no relationship was observed between spherical equivalent refraction and serum zinc within the myopic group (p = 0.46). CONCLUSION: In a subset of 12-19-year-old participants from the population-representative KNHANES study, no association was found between serum zinc and myopia. However, the lack of a sensitive biomarker for zinc status remains a major limitation in this, and all current studies.

Macular Pigment Optical Density Fluctuation as a Function of Pupillary Mydriasis: Methodological Considerations for Dual-Wavelength Autofluorescence.

PURPOSE OF THE STUDY: Macular pigment (MP), comprising the dietary carotenoids lutein, zeaxanthin and meso-zeaxanthin, is believed to benefit eye health and vision. Numerous clinical and research devices and techniques are currently available to facilitate MP optical density (MPOD) measurement. One of those techniques, dual-wavelength fundus autofluorescence (AF) is being increasingly used for measurement of MP in the eye. There is substantial methodological variation across the published studies that have employed this technique, including in relation to the use of mydriasis, the possible influence of which does not appear to have been addressed in the literature. This prospective cross-sectional study was designed to investigate the effect of mydriasis on MP measurement quality and MPOD values obtained with dual-wavelength AF using the Heidelberg Spectralis HRA+OCT device. MATERIALS AND METHODS: Twenty-one healthy participants were recruited to the study. The mean age of participants was 44.8 years (± 14.63). Pupil size and MPOD were measured in one eye for each participant, initially under natural pupil conditions and subsequently 30 minutes following instillation of one drop of 0.5% tropicamide. RESULTS: Despite providing MPOD measurements for the majority of undilated eyes (85.7% of eyes herein), pupillary dilation resulted in statistically significant changes in MPOD (p < .001 for central eccentricities). Our results indicate that the changes in MPOD were not uniform across the spatial profile. Marked improvements were also observed in image quality post-dilation (p < .002 for central eccentricities). CONCLUSIONS: This study clearly demonstrates that dual-wavelength AF measurements of MPOD in the same eye vary as a function of pupillary dilation status, with MPOD under-estimated across the entire spatial profile of MP for natural relative to dilated pupillary conditions. Mydriasis should, therefore, be used routinely for MPOD measurements using dual wavelength AF, pupil size should be reported and image quality optimized in order to ensure accurate MPOD quantification.

Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial.

Purpose: To evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes. Design: Double-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365). Participants: Sixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo. Methods: Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit. Main Outcome Measures: Change in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months. Results: A mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial. Conclusions: Macular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.

Neurophysiological correlates of dual tasking in people with Parkinson's disease and freezing of gait.

Freezing of gait in people with Parkinson's disease (PwP) is associated with executive dysfunction and motor preparation deficits. We have recently shown that electrophysiological markers of motor preparation, rather than decision-making, differentiate PwP with freezing of gait (FOG +) and without (FOG -) while sitting. To examine the effect of locomotion on these results, we measured behavioural and electrophysiological responses in PwP with and without FOG during a target response time task while sitting (single-task) and stepping-in-place (dual-task). Behavioural and electroencephalographic data were acquired from 18 PwP (eight FOG +) and seven young controls performing the task while sitting and stepping-in-place. FOG + had slower response times while stepping compared with sitting. However, response times were significantly faster while stepping compared with sitting for controls. Electrophysiological responses showed no difference in decision-making potentials (centroparietal positivity) between groups or conditions but there were differences in neurophysiological markers of response inhibition (N2) and motor preparation (lateralized readiness potential, LRP) in FOG + while performing a dual-task. This suggests that the addition of a second complex motor task (stepping-in-place) impacts automatic allocation of resources in FOG +, resulting in delayed response times. The impact of locomotion on the generation of the N2 and LRP potentials, particularly in freezers, indirectly implies that these functions compete with locomotion for resources. In the setting of multiple complex tasks or cognitive impairment, severe motor dysfunction may result, leading to freezing of gait.

Investigation of Surrogate Biomarkers Associated with Macular Pigment Status in a Group of Older Irish Adults.

SIGNIFICANCE: Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula; however, its optical density in the eye is not routinely measured in clinical practice. PURPOSE: This study explored a range of surrogate biomarkers including anthropometric, clinical, and plasma measures that may be associated with lower MP optical density (MPOD). METHODS: Two thousand five hundred ninety-four subjects completed a full MP assessment as part of wave 1 of The Irish Longitudinal Study of Aging. Macular pigment optical density was measured using customized heterochromatic flicker photometry. Clinical (blood pressure), plasma (lipoproteins, inflammatory markers), and anthropometric (waist, hip, height, weight) biomarkers were measured for each participant. RESULTS: Mean (standard deviation) MPOD for the study group was 0.223 (0.161), with a range of 0 to 1.08. One-way ANOVA revealed that MPOD was significantly lower among participants with low plasma high-density lipoprotein (HDL; P = .04), raised plasma triglyceride-to-HDL ratio (P = .003), and raised total cholesterol-to-HDL ratio (P = .03). Subjects with an elevated waist circumference (WC) had a significantly lower MPOD (mean, 0.216 [0.159]) compared with those with an ideal WC (mean, 0.229 [0.162]; P = .03). Significant correlates of MPOD on mixed linear model analysis included education, smoking status, and WC. CONCLUSIONS: Higher abdominal fat is associated with lower MPOD in this representative sample of older Irish adults. Although altered lipoprotein profiles (low HDL, raised triglyceride-to-HDL ratio, raised total cholesterol-to-HDL ratio) may affect the transport, uptake, and stabilization of carotenoids in the retina, these plasma biomarkers were not predictive of low MPOD after adjustment for abdominal circumference. Although WC emerged as a viable anthropometric predictor of lower MPOD, its effect size seems to be small.

Slowed Luminance Reaction Times in Cervical Dystonia: Disordered Superior Colliculus Processing.

BACKGROUND: Abnormal temporal discrimination in cervical dystonia is hypothesized to be attributable to disrupted processing in the superior colliculus. The fast, luminance-based, retinotectal pathway, projects to the superior colliculus; chromatic stimuli responses, by the retino-geniculo-calcarine pathway, are up to 30 ms longer. OBJECTIVES: We sought to interrogate visual processing and reaction times in patients with cervical dystonia compared with healthy controls. We hypothesized that cervical dystonia patients would have impaired reaction times to luminance based stimuli accessing the retino-tectal pathway in comparison to healthy control participants. METHODS: In 20 cervical dystonia and 20 age-matched control participants, we compared reaction times to two flashing visual stimuli: (1) a chromatic annulus and (2) a luminant, noncolored annulus. Participants pressed a joystick control when they perceived the annulus flashing. RESULTS: Reaction times in control participants were 20 ms significantly faster in the luminant condition than the chromatic (P = 0.017). Patients with cervical dystonia had no reaction time advantage in response to the luminant stimulus. CONCLUSION: Cervical dystonia patients (compared to control participants) demonstrated no reduction in their reaction time to luminant stimuli, processed through the retinotectal pathway. This finding is consistent with superior colliculus dysfunction in cervical dystonia. © 2020 International Parkinson and Movement Disorder Society.

Association of Total Zinc Intake with Myopia in U.S. Children and Adolescents.

SIGNIFICANCE: This present study advances our knowledge on the role of lifestyle factors in myopia (short-sightedness), specifically dietary factors. It has been suggested in previous studies that lower zinc status is associated with myopia; however, this article shows no relationship between dietary zinc intake and myopia in U.S. adolescents. PURPOSE: It has been suggested that low zinc levels may contribute to the development of myopia. The aim of the present study is to examine, for the first time in a Western population, the association of total dietary and supplement zinc intake with myopia. METHODS: A total of 1095 children/adolescents aged 12 to 19 years who participated in the U.S. National Health and Nutrition Examination Survey from 2007 to 2008 were enrolled in this study. Multivariate logistic regression analysis was performed to examine the relationship between total zinc intake and myopia after adjustment for potential confounders. In addition, the association between total zinc intake and spherical equivalent refractive error was examined in the myopia group through multiple linear regression. RESULTS: Among study participants, 30% were found to be myopic (≤-1.00 D). Although median total daily zinc intake was lower among myopes (10.8 [10.2] mg/d) than among nonmyopes (11.1 [10.8] mg/d), the difference was not statistically significant (P = .11). In multiple logistic regression analyses, zinc and copper intakes were not significantly associated with myopia after adjustment for age, sex, body mass index, ethnicity, family income, recreational activity, copper intake, and daily energy intake (in kilocalories per day). In multiple linear regression, spherical equivalent refractive error was not associated with total zinc intake in the myopic group after adjustment for confounding factors (P = .13). CONCLUSIONS: In contrast to previous Asian studies, total zinc intake is not associated with the presence of myopia in U.S. adolescents/children.