Individual variation in inter-ocular suppression and sensory eye dominance

The competitive and inhibitory interactions between the two eyes’ images are a pervasive aspect of binocular vision. Over the last decade, our understanding of the neural processes underpinning binocular rivalry (BR) and continuous flash suppression CFS) has increased substantially, but we still have little understanding of the relationship between these two effects and their variation in the general population. Studies that pool data across individuals and eyes risk masking substantial variations in binocular vision that exist in the general population. To investigate this issue we compared the depth of inter-ocular suppression evoked by BR with that elicited by CFS, in a group (N=25) of visually normal individuals. A noise pattern (either static for BR or dynamic for CFS) was presented to one eye and its suppressive influence on a probe grating presented simultaneously to the other eye was measured. We found substantial individual differences in the magnitude of suppression (a 10-fold variation in probe detection threshold) evoked by each task, but performance on BR was a significant predictor of performance on the CFS task. However many individuals showed marked asymmetries between the two eyes’ ability to detect a suppressed target, that were not necessarily the same for the two tasks. There was a tendency for the magnitude of the asymmetry to increase as the refresh rate of the dynamic noise increased. The results suggest a common underlying mechanism is likely to be responsible, at least in part, for driving inter-ocular suppression under BR and CFS. The marked asymmetries in inter-ocular suppression at higher noise refresh rates, may be indicative of a difference in temporal processing between the eyes

Collective plasticity of binocular interactions in the adult visual system

Binocular visual plasticity can be initiated via either bottom-up or top-down mechanisms, but it is unknown if these two forms of adult plasticity can be independently combined. In seven participants with normal binocular vision, sensory eye dominance was assessed using a binocular rivalry task, before and after a period of monocular deprivation and with and without selective attention directed towards one eye. On each trial, participants reported the dominant monocular target and the inter-ocular contrast difference between the stimuli was systematically altered to obtain estimates of ocular dominance. We found that both monocular light- and pattern-deprivation shifted dominance in favour of the deprived eye. However, this shift was completely counteracted if the non-deprived eye’s stimulus was selectively attended. These results reveal that shifts in ocular dominance, driven by bottom-up and top-down selection, appear to act independently to regulate the relative contrast gain between the two eyes

Short-term monocular deprivation reduces inter-ocular suppression of the deprived eye

The adult visual system was traditionally thought to be relatively hard-wired, but recent studies have challenged this view by demonstrating plasticity following brief periods of monocular deprivation (Lunghi, Burr, & Morrone, 2011; Lunghi, Burr, & Morrone, 2013). When one eye was deprived of spatial information for 2-3 hours, sensory dominance was shifted in favour of the previously deprived eye. However, the mechanism underlying this phenomenon is unclear. The present study sought to address this issue and determine the consequences of short-term monocular deprivation on inter-ocular suppression of each eye. Sensory eye dominance was examined before and after depriving an eye of all visual input using a light-tight opaque patch for 2.5 hours, in a group of adult participants with normal binocular vision (N=6). We used a percept tracking task during experience of binocular rivalry (BR) to assess the relative dominance of the two eyes, and an objective probe detection task under continuous flash suppression (CFS) to quantify each eye’s susceptibility to inter-ocular suppression. In addition, the monocular contrast increment threshold of each eye was also measured using the probe detection task to ascertain if the altered eye dominance is accompanied by changes in monocular perception. Our BR results replicated Lunghi and colleagues’ findings of a shift of relative dominance towards the eye that has been deprived of form information with translucent patching. More crucially, using CFS we demonstrated reduced inter ocular suppression of the deprived eye with no complementary changes in the other eye, and no monocular changes in increment threshold. These findings imply that short-term monocular deprivation alters binocular interactions. The differential effect on inter-ocular suppression between eyes may have important implications for the use of patching as a therapy to recover visual function in amblyopia

Assessing the reliability of web-based measurements of visual function

Many behavioural phenomena have been replicated using web-based experiments, but evaluation of the agreement between objective measures of web- and lab-based performance is required if scientists and clinicians are to reap the benefits of web-based testing. In this study, we investigated the reliability of a task which assesses early visual cortical function by evaluating the well-known ‘oblique effect’ (we are better at seeing horizontal and vertical edges than tilted ones) and the levels of agreement between remote, web-based measures and lab-based measures. Sixty-nine young participants (mean age, 21.8 years) performed temporal and spatial versions of a web-based, two-alternative forced choice (2AFC) orientation-identification task. In each case, orientation-identification thresholds (the minimum orientation difference at which a standard orientation could be reliably distinguished from a rotated comparison) were measured for cardinal (horizontal and vertical) and oblique orientations. Reliability was assessed in a subsample of 18 participants who performed the same tasks under laboratory conditions. Robust oblique effects were found, such that thresholds were substantially lower for cardinal orientations compared to obliques, for both web- and lab-based measures of the temporal and spatial 2AFC tasks. Crucially, web- and lab-based orientation-identification thresholds showed high levels of agreement, demonstrating the suitability of web-based testing for assessments of early visual cortical function. Future studies should assess the reliability of similar web-based tasks in clinical populations to evaluate their adoption into clinical settings, either to screen for visual anomalies or to assess changes in performance associated with progression of disease severity

Orientation tuning and contrast dependence of continuous flash suppression in amblyopia and normal vision

Purpose: Suppression in amblyopia may be an unequal form of normal interocular suppression or a distinct pathophysiology. To explore this issue, we examined the orientation tuning and contrast dependence of continuous flash suppression (CFS) in adults with amblyopia and visually normal controls.Methods: Nine patients (mean age, 26.9 ± SD 4.7 years) and 11 controls (mean age, 24.8 ± SD 5.3 years) participated. In the CFS paradigm, spatially one-dimensional noise refreshing at 10 Hz was displayed in one eye to induce suppression of the other eye, and suppression strength was measured by using a grating contrast increment detection task. In experiment 1, noise contrast was fixed and the orientation difference between the noise and the grating was varied. In experiment 2, noise and grating orientations were identical and noise contrast was varied.Results: Suppression patterns varied in both groups. In experiment 1, controls showed consistently orientation-tuned CFS (mean half-height bandwidth, 35.8° ± SD 21.5°) with near-equal strength between eyes. Five of nine patients with amblyopia exhibited orientation-independent CFS. Eight patients had markedly unequal suppression between eyes. Experiment 2 found that increasing the noise contrast to the amblyopic eye may produce suppression of the fellow eye, but suppression remained unequal between eyes.Conclusions: Our data revealed that orientation specificity in CFS was very broad or absent in some patients with amblyopia, which could not be predicted by clinical measures. Suppression was unbalanced across the entire contrast range for most patients. This suggests that abnormal early visual experience disrupts the development of interocular suppression mechanisms

Hydrogen bond network topology in liquid water and methanol: a graph theory approach

Networks are increasingly recognized as important building blocks of various systems in nature and society. Water is known to possess an extended hydrogen bond network, in which the individual bonds are broken in the sub-picosecond range and still the network structure remains intact. We investigated and compared the topological properties of liquid water and methanol at various temperatures using concepts derived within the framework of graph and network theory (neighbour number and cycle size distribution, the distribution of local cyclic and local bonding coefficients, Laplacian spectra of the network, inverse participation ratio distribution of the eigenvalues and average localization distribution of a node) and compared them to small world and Erdős–Rényi random networks. Various characteristic properties (e.g. the local cyclic and bonding coefficients) of the network in liquid water could be reproduced by small world and/or Erdős–Rényi networks, but the ring size distribution of water is unique and none of the studied graph models could describe it. Using the inverse participation ratio of the Laplacian eigenvectors we characterized the network inhomogeneities found in water and showed that similar phenomena can be observed in Erdős–Rényi and small world graphs. We demonstrated that the topological properties of the hydrogen bond network found in liquid water systematically change with the temperature and that increasing temperature leads to a broader ring size distribution. We applied the studied topological indices to the network of water molecules with four hydrogen bonds, and showed that at low temperature (250 K) these molecules form a percolated or nearly-percolated network, while at ambient or high temperatures only small clusters of four-hydrogen bonded water molecules exist

Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise

Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin. We further show that exogenous osteocalcin is sufficient to enhance the exercise capacity of young mice and to restore to 15-month-old mice the exercise capacity of 3-month-old mice. This study uncovers a bone-to-muscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity

A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

ABSTRACT Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories