ALBERT

Description: When children grow up, the first word or first step in walking is always a significant event [...]

Description: To build a representation of what we see, the human brain recruits regions throughout the visual cortex in cascading sequence. Recently, an approach was proposed to evaluate the dynamics of visual perception in high spatiotemporal resolution at the scale of the whole brain. This method combined functional magnetic resonance imaging (fMRI) data with magnetoencephalography (MEG) data using representational similarity analysis and revealed a hierarchical progression from primary visual cortex through the dorsal and ventral streams. To assess the replicability of this method, we here present the results of a visual recognition neuro-imaging fusion experiment and compare them within and across experimental settings. We evaluated the reliability of this method by assessing the consistency of the results under similar test conditions, showing high agreement within participants. We then generalized these results to a separate group of individuals and visual input by comparing them to the fMRI-MEG fusion data of Cichy et al (2016), revealing a highly similar temporal progression recruiting both the dorsal and ventral streams. Together these results are a testament to the reproducibility of the fMRI-MEG fusion approach and allows for the interpretation of these spatiotemporal dynamic in a broader context.

Description: An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.

Description: Current evidence supports the view that the visual pulvinar of primates consists of at least five nuclei, with two large nuclei, lateral pulvinar ventrolateral (PLvl) and central lateral nucleus of the inferior pulvinar (PIcl), contributing mainly to the ventral stream of cortical processing for perception, and three smaller nuclei, posterior nucleus of the inferior pulvinar (PIp), medial nucleus of the inferior pulvinar (PIm), and central medial nucleus of the inferior pulvinar (PIcm), projecting to dorsal stream visual areas for visually directed actions. In primates, both cortical streams are highly dependent on visual information distributed from primary visual cortex (V1). This area is so vital to vision that patients with V1 lesions are considered “cortically blind”. When the V1 inputs to dorsal stream area middle temporal visual area (MT) are absent, other dorsal stream areas receive visual information relayed from the superior colliculus via PIp and PIcm, thereby preserving some dorsal stream functions, a phenomenon called “blind sight”. Non-primate mammals do not have a dorsal stream area MT with V1 inputs, but superior colliculus inputs to temporal cortex can be more significant and more visual functions are preserved when V1 input is disrupted. The current review will discuss how the different visual streams, especially the dorsal stream, have changed during primate evolution and we propose which features are retained from the common ancestor of primates and their close relatives.

Description: The sources of the reduced fixation stability exhibited by patients with central vision loss in the light are relatively well understood, but we have no information on how they control eye position in complete darkness, in the absence of visual error signals. We therefore explored the effect of visual feedback on eye position stability by testing patients with age-related macular degeneration (AMD) and controls with normal vision in the light and in complete darkness. Nine patients (ages 67 to 92 years) and 16 controls (ages 16 to 74 years) were tested binocularly in the light and in complete darkness while remembering the location of a now invisible target. Binocular eye position was recorded with a video-based eye tracker. Results show that eye position stability both in the light and in the dark is worse for patients than for controls and that, for the two groups, eye position stability in the dark is, on average, 5.9 times worse than in the light. Large instability of fixation in patients with AMD was found even in absolute darkness when the scotoma cannot impair vision. These data reflect permanent changes in the oculomotor reference of patients with AMD.

Description: In this paper, a range of open-source tools, datasets, and software that have been developed for quantitative and in-depth evaluation of eye gaze data quality are presented. Eye tracking systems in contemporary vision research and applications face major challenges due to variable operating conditions such as user distance, head pose, and movements of the eye tracker platform. However, there is a lack of open-source tools and datasets that could be used for quantitatively evaluating an eye tracker’s data quality, comparing performance of multiple trackers, or studying the impact of various operating conditions on a tracker’s accuracy. To address these issues, an open-source code repository named GazeVisual-Lib is developed that contains a number of algorithms, visualizations, and software tools for detailed and quantitative analysis of an eye tracker’s performance and data quality. In addition, a new labelled eye gaze dataset that is collected from multiple user platforms and operating conditions is presented in an open data repository for benchmark comparison of gaze data from different eye tracking systems. The paper presents the concept, development, and organization of these two repositories that are envisioned to improve the performance analysis and reliability of eye tracking systems.

Description: The horizontal raphe (HR) as a demarcation line dividing the retina and choroid into separate vascular hemispheres is well established, but its development has never been discussed in the context of new findings of the last decades. Although factors for axon guidance are established (e.g., slit-robo pathway, ephrin-protein-receptor pathway) they do not explain HR formation. Early morphological organization, too, fails to establish a HR. The development of the HR is most likely induced by the long posterior ciliary arteries which form a horizontal line prior to retinal organization. The maintenance might then be supported by several biochemical factors. The circulation separate superior and inferior vascular hemispheres communicates across the HR only through their anastomosing capillary beds resulting in watershed zones on either side of the HR. Visual field changes along the HR could clearly be demonstrated in vascular occlusive diseases affecting the optic nerve head, the retina or the choroid. The watershed zone of the HR is ideally protective for central visual acuity in vascular occlusive diseases but can lead to distinct pathological features.

Description: The seminal model by Laurent Itti and Cristoph Koch demonstrated that we can compute the entire flow of visual processing from input to resulting fixations. Despite many replications and follow-ups, few have matched the impact of the original model—so what made this model so groundbreaking? We have selected five key contributions that distinguish the original salience model by Itti and Koch; namely, its contribution to our theoretical, neural, and computational understanding of visual processing, as well as the spatial and temporal predictions for fixation distributions. During the last 20 years, advances in the field have brought up various techniques and approaches to salience modelling, many of which tried to improve or add to the initial Itti and Koch model. One of the most recent trends has been to adopt the computational power of deep learning neural networks; however, this has also shifted their primary focus to spatial classification. We present a review of recent approaches to modelling salience, starting from direct variations of the Itti and Koch salience model to sophisticated deep-learning architectures, and discuss the models from the point of view of their contribution to computational cognitive neuroscience.

Description: Purpose: To access retinal straylight in a Brazilian sample and to compare it with European norms. Methods: Absolute Straylight was assessed using C-Quant that uses an adaptive staircase based on a 2-Alternated Forced Choice task. A young (22.2 ± 2.4 yrs, n = 20) and an old group (53.8 ± 7.4 yrs, n = 21) of subjects were tested. All refractive errors were corrected in the C-Quant device, and no subjects had ocular diseases or vision-threatening conditions (e.g., diabetes, unregulated blood pressure, high intraocular pressure, visible cataract). Eighty-five percent of all subjects in each age group had dark-pigmented eyes. Each eye was tested 3 times, yielding 6 straylight values (s). Only data fulfilling C-Quant reliability criteria were included. Results: There were no statistical differences between the three attempts on each eye (ANOVA, F = 0.993, p 〉 0.936) and between the two groups (ANOVA, F = 0.893, p 〉 0.725). Straylight values (s) were fit with an empirical equation to compare to European norms. There were no statistical differences between Brazilian straylight values and European norms for either young or old age groups (ANOVA, F = 5.114, p 〉 0.993). However, there was a tendency for our s values to be higher than the European norms, consistent with young Brazilian eyes having more light-scattering than age-matched European eyes. Conclusions: Consistent with European norms, light-scattering increases with age in the Brazilian sample. This increase is thought to be due, in large part, to age-related changes in lens structure and density. Although the differences between the populations are not significant, the tendency for Brazilian data to have higher s values than European values, especially at young subjects, is in the opposite direction from that expected from a dark-eyed population. This suggests the hypothesis that latitude-dependent (Sao Paulo, latitude 23° S, European latitudes between 40° N to 55° N) differences in the light environment could be associated with differences in s values.

Description: Rigorous peer-review is the corner-stone of high-quality academic publishing [...]

Description: Existing research has found that spatial attention alters how various stimulus properties are perceived (e.g., luminance, saturation), but few have explored whether it improves the accuracy of perception. To address this question, we performed two experiments using modified Posner cueing tasks, wherein participants made speeded detection responses to peripheral colour targets and then indicated their perceived colours on a colour wheel. In E1, cues were central and endogenous (i.e., prompted voluntary attention) and the interval between cues and targets (stimulus onset asynchrony, or SOA) was always 800 ms. In E2, cues were peripheral and exogenous (i.e., captured attention involuntarily) and the SOA varied between short (100 ms) and long (800 ms). A Bayesian mixed-model analysis was used to isolate the effects of attention on the probability and the fidelity of colour encoding. Both endogenous and short-SOA exogenous spatial cueing improved the probability of encoding the colour of targets. Improved fidelity of encoding was observed in the endogenous but not in the exogenous cueing paradigm. With exogenous cues, inhibition of return (IOR) was observed in both RT and probability at the long SOA. Overall, our findings reinforce the utility of continuous response variables in the research of attention.

Description: The key determinants of the range of clear focus in pre-presbyopes and their relative contributions to the difference between subjective range of focus and objective accommodation assessments have not been previously quantified. Fifty participants (aged 33.0 ± 6.4 years) underwent simultaneous monocular subjective (visual acuity measured with an electronic test-chart) and objective (dynamic accommodation measured with an Aston open-field aberrometer) defocus curve testing for lenses between +2.00 to -10.00 DS in +0.50 DS steps in a randomized order. Pupil diameter and ocular aberrations (converted to visual metrics normalized for pupil size) at each level of blur were measured. The difference between objective range over which the power of the crystalline lens changes and the subjective range of clear focus was quantified and the results modelled using pupil size, refractive error, tolerance to blur, and ocular aberrations. The subjective range of clear focus was principally accounted for by age (46.4%) and pupil size (19.3%). The objectively assessed accommodative range was also principally accounted for by age (27.6%) and pupil size (15.4%). Over one-quarter (26.0%) of the difference between objective accommodation and subjective range of clear focus was accounted for by age (14.0%) and spherical aberration at maximum accommodation (12.0%). There was no significant change in the objective accommodative response (F=1.426, p=0.229) or pupil size (F=0.799, p=0.554) of participants for levels of defocus above their amplitude of accommodation. Pre-presbyopes benefit from an increased subjective range of clear vision beyond their objective accommodation due in part to neural factors, resulting in a measured depth-of-focus of, on average, 1.0D.

Description: Ocular equivocation was the term given by Brewster in 1844 to binocular contour rivalry seen with Wheatstone’s stereoscope. The rivalries between Wheatstone and Brewster were personal as well as perceptual. In the 1830s, both Wheatstone and Brewster came to stereoscopic vision armed with their individual histories of research on vision. Brewster was an authority on physical optics and had devised the kaleidoscope; Wheatstone extended his research on audition to render acoustic patterns visible with his kaleidophone or phonic kaleidoscope. Both had written on subjective visual phenomena, a topic upon which they first clashed at the inaugural meeting of the British Association for the Advancement of Science in 1832 (the year Wheatstone made the first stereoscopes). Wheatstone published his account of the mirror stereoscope in 1838; Brewster’s initial reception of it was glowing but he later questioned Wheatstone’s priority. They both described investigations of binocular contour rivalry but their interpretations diverged. As was the case for stereoscopic vision, Wheatstone argued for central processing whereas Brewster’s analysis was peripheral and based on visible direction. Brewster’s lenticular stereoscope and binocular camera were described in 1849. They later clashed over Brewster’s claim that the Chimenti drawings were made for a 16th-century stereoscope. The rivalry between Wheatstone and Brewster is illustrated with anaglyphs that can be viewed with red/cyan glasses and in Universal Freeview format; they include rivalling ‘perceptual portraits’ as well as examples of the stimuli used to study ocular equivocation.

Description: A brief tribute to Bela Julesz (1928–2003) is made in words and images. In addition to a conventional stereophotographic portrait, his major contributions to vision research are commemorated by two ‘perceptual portraits’, which try to capture the spirit of his main accomplishments in stereopsis and the perception of texture.

Description: Decisions about where to fixate are highly variable and often inefficient. In the current study, we investigated whether such decisions would improve with increased motivation. Participants had to detect a discrimination target, which would appear in one of two boxes, but only after they chose a location to fixate. The distance between boxes determines which location to fixate to maximise the probability of being able to see the target: participants should fixate between the two boxes when they are close together, and on one of the two boxes when they are far apart. We “gamified” this task, giving participants easy-to-track rewards that were contingent on discrimination accuracy. Their decisions and performance were compared to previous results that were gathered in the absence of this additional motivation. We used a Bayesian beta regression model to estimate the size of the effect and associated variance. The results demonstrate that discrimination accuracy does indeed improve in the presence of performance-related rewards. However, there was no difference in eye movement strategy between the two groups, suggesting this improvement in accuracy was not due to the participants making more optimal eye movement decisions. Instead, the motivation encouraged participants to expend more effort on other aspects of the task, such as paying more attention to the boxes and making fewer response errors.

Description: Perception of a complex visual scene requires that important regions be prioritized and attentionally selected for processing. What is the basis for this selection? Although much research has focused on image salience as an important factor guiding attention, relatively little work has focused on semantic salience. To address this imbalance, we have recently developed a new method for measuring, representing, and evaluating the role of meaning in scenes. In this method, the spatial distribution of semantic features in a scene is represented as a meaning map. Meaning maps are generated from crowd-sourced responses given by naïve subjects who rate the meaningfulness of a large number of scene patches drawn from each scene. Meaning maps are coded in the same format as traditional image saliency maps, and therefore both types of maps can be directly evaluated against each other and against maps of the spatial distribution of attention derived from viewers’ eye fixations. In this review we describe our work focusing on comparing the influences of meaning and image salience on attentional guidance in real-world scenes across a variety of viewing tasks that we have investigated, including memorization, aesthetic judgment, scene description, and saliency search and judgment. Overall, we have found that both meaning and salience predict the spatial distribution of attention in a scene, but that when the correlation between meaning and salience is statistically controlled, only meaning uniquely accounts for variance in attention.

Description: The use of eye movements to explore scene processing has exploded over the last decade. Eye movements provide distinct advantages when examining scene processing because they are both fast and spatially measurable. By using eye movements, researchers have investigated many questions about scene processing. Our review will focus on research performed in the last decade examining: (1) attention and eye movements; (2) where you look; (3) influence of task; (4) memory and scene representations; and (5) dynamic scenes and eye movements. Although typically addressed as separate issues, we argue that these distinctions are now holding back research progress. Instead, it is time to examine the intersections of these seemingly separate influences and examine the intersectionality of how these influences interact to more completely understand what eye movements can tell us about scene processing.

Description: This paper reconstructs the “Arnheim’s puzzle” over the psychology of art. It is argued that the long-established psychological theories of art do not account properly for the observable variability of art, which provide the phenomena of interest whose psychological factors need to be discovered. The general purpose principles of such theories, the ensuing selective sample of art phenomena, and assumption of conventional properties of aesthetic experience make the predictions and the findings of the theories unrepresentative of art. From the discussion of examples drawn from contemporary visual arts and the presentation of the debate on the emergence of the cognitive capacities of art in paleoanthropology, a construct is presented on the specificity of the cognitive capacities of art and its anchoring to perception, which solves the puzzle and has implications for research and teaching psychology of art.

Description: The binocular viewing of a fronto-parallel pendulum with a reduced luminance in one eye results in the illusory tridimensional percept of the pendulum following an elliptical orbit in depth, the so-called Pulfrich phenomenon. A small percentage of mild anisometropic amblyopes who have rudimentary stereo are known to experience a spontaneous Pulfrich phenomenon, which posits a delay in the cortical processing of information involving their amblyopic eye. The purpose of this study is to characterize this spontaneous Pulfrich phenomenon in the mild amblyopic population. In order to assess this posited delay, we used a paradigm where a cylinder rotating in depth, defined by moving Gabor patches at different disparities (i.e., at different interocular phases), generates a strong to ambiguous depth percept. This paradigm allows one to accurately measure a spontaneous Pulfrich phenomenon and to determine how it depends on the spatio-temporal properties of stimulus. We observed a spontaneous Pulfrich phenomenon in anisometropic, strabismic, and mixed amblyopia, which is posited to be due to an interocular delay associated with amblyopic processing. Surprisingly, the posited delay was not always observed in the amblyopic eye, was not a consequence of the reduced contrast sensitivity of the amblyopic eye, and displayed a large variability across amblyopic observers. Increasing the density, decreasing the spatial frequency, or increasing the speed of the stimulus tended to reduce the observed delay. The spontaneous Pulfrich phenomenon seen by some amblyopes was variable and depended on the spatio-temporal properties of the stimulus. We suggest it could involve two conflicting components: an amblyopic delay and a blur-based acceleration.

Description: We investigated contrast processing in relation to visual comfort from coloured light in individuals with migraine. In Experiment 1, 24 individuals who experienced migraine with aura (MA), 15 migraine without aura (MO), and 23 healthy controls, identified which of four patterns, one in each quadrant, had the greatest contrast. Although there were no significant differences between groups, contrast discrimination was superior in the visual field affected by aura in all eight participants in whom the aura was consistently lateralised. In Experiment 2, 20 participants without aura and 20 controls selected comfortable light with a chromaticity close to the daylight (Planckian) locus, whilst 20 individuals with aura chose more strongly saturated colours, mostly distant from the locus. In Experiment 3, nine participants with consistently unilateral aura undertook the contrast discrimination task wearing (a) lenses that provided a comfortable colour of light and (b) grey lenses of similar transmission. With grey lenses, seven of the nine individuals with unilateral aura showed a superior performance in the affected field, as before. With lenses providing a comfortable colour, however, the performance was relatively poor for the nine individuals with unilateral aura, but not for the 10 controls. This was the case in both visual fields. The cortical hyper-responsiveness with which migraine is associated may improve the perception of contrast. The perception is poorer (and more normal) with ophthalmic lenses having a comfortable colour.

Description: Attention is a process that alters how cognitive resources are allocated, and it allows individuals to efficiently process information at the attended location. The presence of visual or auditory cues in the environment can direct the focus of attention toward certain stimuli even if the cued stimuli are not the individual’s primary target. Samson et al. demonstrated that seeing another person in the scene (i.e., a person-like cue) caused a delay in responding to target stimuli not visible to that person: “alter-centric intrusion.” This phenomenon, they argue, is dependent upon the fact that the cue used resembled a person as opposed to a more generic directional indicator. The characteristics of the cue are the core of the debate of this special issue. Some maintain that the perceptual-directional characteristics of the cue are sufficient to generate the bias while others argue that the cuing is stronger when the cue has social characteristics (relates to what another individual can perceive). The research contained in this issue confirms that human attention is biased by the presence of a directional cue. We discuss and compare the different studies. The pattern that emerges seems to suggest that the social relevance of the cue is necessary in some contexts but not in others, depending on the cognitive demand of the experimental task. One possibility is that the social mechanisms are involved in perspective taking when the task is cognitively demanding, while they may not play a role in automatic attention allocation.

Description: Currently there are several computational models of eye movement control that provide a good account of oculomotor behavior during reading of English and other alphabetic languages. I will provide an overview of two dominant models: E-Z Reader and SWIFT, as well as a recently proposed model: OB1-Reader. I will evaluate a critical issue of controversy among models, namely, whether words are lexically processed serially or in parallel. I will then consider reading in Chinese, a character-based, unspaced language with ambiguous word boundaries. Finally, I will evaluate the concepts of serialism and parallelism of process central to these models, and how these models might function in relation to lexical processing that is operationalized over parafoveal multi-constituent units.

Description: Visual tests can be used as noninvasive tools to test models of the pathophysiology underlying neurological conditions, such as migraine. They may also be used to track changes in performance that vary with the migraine cycle or can track the efficacy of prophylactic treatments. This article reviews the literature on performance differences on two visual tasks, global motion discrimination and orientation, which, of the many visual tasks that have been used to compare differences between migraine and control groups, have yielded the most consistent patterns of group differences. The implications for understanding the underlying pathophysiology in migraine are discussed, but the main focus is on bringing together disparate areas of research and suggesting those that can reveal practical uses of visual tests to treat and manage migraine.

Description: We review all published eye-tracking studies to date that have used eye movements to examine multiple object (MOT) or multiple identity tracking (MIT). In both tasks, observers dynamically track multiple moving objects. In MOT the objects are identical, whereas in MIT they have distinct identities. In MOT, observers prefer to fixate on blank space, which is often the center of gravity formed by the moving targets (centroid). In contrast, in MIT observers have a strong preference for the target-switching strategy, presumably to refresh and maintain identity-location bindings for the targets. To account for the qualitative differences between MOT and MIT, two mechanisms have been posited, a position tracking (MOT) and an identity tracking (MOT & MIT) mechanism. Eye-tracking studies of MOT have also demonstrated that observers execute rescue saccades toward targets in danger of becoming occluded or are about to change direction after a collision. Crowding attracts the eyes close to it in order to increase visual acuity for the crowded objects to prevent target loss. It is suggested that future studies should concentrate more on MIT, as MIT more closely resembles tracking in the real world.

Description: Pulvino-cortical (PC) projections are a major source of extrinsic input to early visual areas in the macaque. From bulk injections of anterograde tracers, these are known to terminate in layer 1 of V1 and densely in the middle cortical layers of extrastriate areas. Finer, single axon analysis, as reviewed here for projections from the lateral pulvinar (PL) in two macaque monkeys (n = 25 axons), demonstrates that PL axons have multiple arbors in V2 and V4, and that these are spatially separate and offset in different layers. In contrast, feedforward cortical axons, another major source of extrinsic input to extrastriate areas, are less spatially divergent and more typically terminate in layer 4. Functional implications are briefly discussed, including comparisons with the better investigated rodent brain.

Description: In motor imagery (MI), internal models may predict the action effects. A mismatch between predicted and intended action effects may result in error detection. To compare error detection in MI and motor execution (ME), ten-finger typists and hunt-and-peck typists performed a copy-typing task. Visibility of the screen and visibility of the keyboard were manipulated. Participants reported what type of error occurred and by which sources they detected the error. With covered screen, fewer errors were reported, showing the importance of distal action effects for error detection. With covered screen, the number of reported higher-order planning errors did not significantly differ between MI and ME. However, the number of reported motor command errors was lower in MI than in ME. Hence, only errors that occur in advance to internal modeling are equally observed in MI and ME. MI may require more attention than ME, leaving fewer resources to monitor motor command errors in MI. In comparison to hunt-and-peck typists, ten-finger typists detected more higher-order planning errors by kinesthesis/touch and fewer motor command errors by vision of the keyboard. The use of sources for error detection did not significantly differ between MI and ME, indicating similar mechanisms.

Description: Change blindness is a striking shortcoming of our visual system which is exploited in the popular `Spot the difference’ game, as it makes us unable to notice large visual changes happening right before our eyes. Change blindness illustrates the fact that we see much less than we think we do. In this paper, we introduce a fully automated model to predict colour change blindness in cartoon images based on image complexity, change magnitude and observer experience. Using linear regression with only three parameters, the predictions of the proposed model correlate significantly with measured detection times. We also demonstrate the efficacy of the model to classify stimuli in terms of difficulty.

Description: The purpose of the present study is to investigate the effect of congruence between music and paintings on the aesthetic preference of paintings. Congruence was specified as the similarity in perceived regularity and the complexity of jazz compositions and abstract paintings (the ratings of regularity and complexity in both sets of stimuli were obtained in the pilot study). In the main experiment, 32 participants rated the aesthetic pleasantness of paintings with congruent, incongruent, and no music background. In addition, they rated the music-paintings matching (how well the music goes with the painting). The results show no effect of congruence on aesthetic pleasantness ratings. The effect on the perceived matching was significant; matching is higher in the congruent compared to the incongruent condition. These findings suggest that congruency has a strong effect on the perceptual aspect of the music-paintings compatibility (visuo-auditory similarity) and no effect on the aesthetic aspect (liking).

Description: Like many predators, humans have forward-facing eyes that are set a short distance apart so that an extensive region of the visual field is seen from two different points of view. The human visual system can establish a three-dimensional (3D) percept from the projection of images into the left and right eye. How the visual system integrates local motion and binocular depth in order to accomplish 3D motion perception is still under investigation. Here, we propose a geometric-statistical model that combines noisy velocity constraints with a spherical motion prior to solve the aperture problem in 3D. In two psychophysical experiments, it is shown that instantiations of this model can explain how human observers disambiguate 3D line motion direction behind a circular aperture. We discuss the implications of our results for the processing of motion and dynamic depth in the visual system.

Description: Across saccades, small displacements of a visual target are harder to detect and their directions more difficult to discriminate than during steady fixation. Prominent theories of this effect, known as saccadic suppression of displacement, propose that it is due to a bias to assume object stability across saccades. Recent studies comparing the saccadic effect to masking effects suggest that suppression of displacement is not saccade-specific. Further evidence for this account is presented from two experiments where participants judged the size of displacements on a continuous scale in saccade and mask conditions, with and without blanking. Saccades and masks both reduced the proportion of correctly perceived displacements and increased the proportion of missed displacements. Blanking improved performance in both conditions by reducing the proportion of missed displacements. Thus, if suppression of displacement reflects a bias for stability, it is not a saccade-specific bias, but a more general stability assumption revealed under conditions of impoverished vision. Specifically, I discuss the potentially decisive role of motion or other transient signals for displacement perception. Without transients or motion, the quality of relative position signals is poor, and saccadic and mask-induced suppression of displacement reflects performance when the decision has to be made on these signals alone. Blanking may improve those position signals by providing a transient onset or a longer time to encode the pre-saccadic target position.

Description: We developed a temporal population receptive field model to differentiate the neural and hemodynamic response functions (HRF) in the human lateral geniculate nucleus (LGN). The HRF in the human LGN is dominated by the richly vascularized hilum, a structure that serves as a point of entry for blood vessels entering the LGN and supplying the substrates of central vision. The location of the hilum along the ventral surface of the LGN and the resulting gradient in the amplitude of the HRF across the extent of the LGN have made it difficult to segment the human LGN into its more interesting magnocellular and parvocellular regions that represent two distinct visual processing streams. Here, we show that an intrinsic clustering of the LGN responses to a variety of visual inputs reveals the hilum, and further, that this clustering is dominated by the amplitude of the HRF. We introduced a temporal population receptive field model that includes separate sustained and transient temporal impulse response functions that vary on a much short timescale than the HRF. When we account for the HRF amplitude, we demonstrate that this temporal response model is able to functionally segregate the residual responses according to their temporal properties.

Description: Mental imagery is the ability to generate images in the mind in the absence of sensory input. Both perceptual visual processing and internally generated imagery engage large, overlapping networks of brain regions. However, it is unclear whether they are characterized by similar temporal dynamics. Recent magnetoencephalography work has shown that object category information was decodable from brain activity during mental imagery, but the timing was delayed relative to perception. The current study builds on these findings, using electroencephalography to investigate the dynamics of mental imagery. Sixteen participants viewed two images of the Sydney Harbour Bridge and two images of Santa Claus. On each trial, they viewed a sequence of the four images and were asked to imagine one of them, which was cued retroactively by its temporal location in the sequence. Time-resolved multivariate pattern analysis was used to decode the viewed and imagined stimuli. Although category and exemplar information was decodable for viewed stimuli, there were no informative patterns of activity during mental imagery. The current findings suggest stimulus complexity, task design and individual differences may influence the ability to successfully decode imagined images. We discuss the implications of these results in the context of prior findings of mental imagery.

Description: We report two psychophysical experiments that investigate a visual illusion that is considered common knowledge among type designers, but has never been studied scientifically. Specifically, the thickness of a horizontal line is overestimated in relation to that of a vertical line. Experiment 1 confirmed the existence of the illusion. In Experiment 2, we replicated the effect and showed that the illusion is closely related to the vertical-horizontal illusion, in which the length of a vertical line is overestimated in comparison to a horizontal one. Both the overestimation of thickness and length is larger when the stimulus is surrounded by a horizontally elongated frame, as opposed to a vertically elongated frame. We discuss potential explanations for the thickness illusion and its relation to the vertical-horizontal illusion.

Description: According to theories of anticipatory behavior control, actions are initiated by predicting their sensory outcomes. From the perspective of event-predictive cognition and active inference, predictive processes activate currently desired events and event boundaries, as well as the expected sensorimotor mappings necessary to realize them, dependent on the involved predicted uncertainties before actual motor control unfolds. Accordingly, we asked whether peripersonal hand space is remapped in an uncertainty anticipating manner while grasping and placing bottles in a virtual reality (VR) setup. To investigate, we combined the crossmodal congruency paradigm with virtual object interactions in two experiments. As expected, an anticipatory crossmodal congruency effect (aCCE) at the future finger position on the bottle was detected. Moreover, a manipulation of the visuo-motor mapping of the participants’ virtual hand while approaching the bottle selectively reduced the aCCE at movement onset. Our results support theories of event-predictive, anticipatory behavior control and active inference, showing that expected uncertainties in movement control indeed influence anticipatory stimulus processing.

Description: Interocular suppression plays an important role in the visual deficits experienced by individuals with amblyopia. Most neurophysiological and functional MRI studies of suppression in amblyopia have used dichoptic stimuli that overlap within the visual field. However, suppression of the amblyopic eye also occurs when the dichoptic stimuli do not overlap, a phenomenon we refer to as long-range suppression. We used functional MRI to test the hypothesis that long-range suppression reduces neural activity in V1, V2 and V3 in adults with amblyopia, indicative of an early, active inhibition mechanism. Five adults with amblyopia and five controls viewed monocular and dichoptic quadrant stimuli during fMRI. Three of five participants with amblyopia experienced complete perceptual suppression of the quadrants presented to their amblyopic eye under dichoptic viewing. The blood oxygen level dependant (BOLD) responses within retinotopic regions corresponding to amblyopic and fellow eye stimuli were analyzed for response magnitude, time to peak, effective connectivity and stimulus classification. Dichoptic viewing slightly reduced the BOLD response magnitude in amblyopic eye retinotopic regions in V1 and reduced the time to peak response; however, the same effects were also present in the non-dominant eye of controls. Effective connectivity was unaffected by suppression, and the results of a classification analysis did not differ significantly between the control and amblyopia groups. Overall, we did not observe a neural signature of long-range amblyopic eye suppression in V1, V2 or V3 using functional MRI in this initial study. This type of suppression may involve higher level processing areas within the brain.

Description: When dissimilar images are presented to each eye, the images will alternate every few seconds in a phenomenon known as binocular rivalry. Recent research has found evidence of a bias towards one image at the initial ‘onset’ period of rivalry that varies across the peripheral visual field. To determine the role that visual field location plays in and around the fovea at onset, trained observers were presented small orthogonal achromatic grating patches at various locations across the central 3° of visual space for 1-s and 60-s intervals. Results reveal stronger bias at onset than during continuous rivalry, and evidence of temporal hemifield dominance across observers, however, the nature of the hemifield effects differed between individuals and interacted with overall eye dominance. Despite using small grating patches, a high proportion of mixed percept was still reported, with more mixed percept at onset along the vertical midline, in general, and in increasing proportions with eccentricity in the lateral hemifields. Results show that even within the foveal range, onset rivalry bias varies across visual space, and differs in degree and sensitivity to biases in average dominance over continuous viewing.

Description: Readers occasionally move their eyes to prior text. We distinguish two types of these movements (regressions). One type consists of relatively large regressions that seek to re-process prior text and to revise represented linguistic content to improve comprehension. The other consists of relatively small regressions that seek to correct inaccurate or premature oculomotor programming to improve visual word recognition. Large regressions are guided by spatial and linguistic knowledge, while small regressions appear to be exclusively guided by knowledge of spatial location. There are substantial individual differences in the use of regressions, and college-level readers often do not regress even when this would improve sentence comprehension.

Description: This paper presents a new mathematical model along with a measurement platform for accurate detection and monitoring of various visual distortions (VD) caused by macular disorders such as central serous chorioretinopathy (CSR) and age-related macular degeneration (AMD). This platform projects a series of graphical patterns on the patient’s retina and calculates the severity of VDs accordingly. The accuracy of this technique relies on the accurate detection of distorted lines by the patient. We also propose a simple mathematical model to evaluate the VD created by CSR. The model is used as a control for the test results achieved from the proposed platform. The proposed platform consists of the required hardware and software for the generation and projection of patterns along with the collection and processing of patients against their standard optical coherence tomography (OCT) images. Based on these results, the OCT images agree with the VD test results, and the proposed platform can be used as an alternative home monitoring method for various macular disorders.

Description: Processing of both a word’s orthography (its printed form) and phonology (its associated speech sounds) are critical for lexical identification during reading, both in beginning and skilled readers. Theories of learning to read typically posit a developmental change, from early readers’ reliance on phonology to more skilled readers’ development of direct orthographic-semantic links. Specifically, in becoming a skilled reader, the extent to which an individual processes phonology during lexical identification is thought to decrease. Recent data from eye movement research suggests, however, that the developmental change in phonological processing is somewhat more nuanced than this. Such studies show that phonology influences lexical identification in beginning and skilled readers in both typically and atypically developing populations. These data indicate, therefore, that the developmental change might better be characterised as a transition from overt decoding to abstract, covert recoding. We do not stop processing phonology as we become more skilled at reading; rather, the nature of that processing changes.

Description: The dynamic nature of the real world poses challenges for predicting where best to allocate gaze during object interactions. The same object may require different visual guidance depending on its current or upcoming state. Here, we explore how object properties (the material and shape of objects) and object state (whether it is full of liquid, or to be set down in a crowded location) influence visual supervision while setting objects down, which is an element of object interaction that has been relatively neglected in the literature. In a liquid pouring task, we asked participants to move empty glasses to a filling station; to leave them empty, half fill, or completely fill them with water; and then move them again to a tray. During the first putdown (when the glasses were all empty), visual guidance was determined only by the type of glass being set down—with more unwieldy champagne flutes being more likely to be guided than other types of glasses. However, when the glasses were then filled, glass type no longer mattered, with the material and fill level predicting whether the glasses were set down with visual supervision: full, glass material containers were more likely to be guided than empty, plastic ones. The key finding from this research is that the visual system responds flexibly to dynamic changes in object properties, likely based on predictions of risk associated with setting-down the object unsupervised by vision. The factors that govern these mechanisms can vary within the same object as it changes state.

Description: Two major uses of linear perspective are in planar paintings—the flat canvas is incongruent with the painted 3-D scene—and in forced perspectives, such as theater stages that are concave truncated pyramids, where the physical geometry and the depicted scene are congruent. Patrick Hughes pioneered a third major art form, the reverse perspective, where the depicted scene opposes the physical geometry. Reverse perspectives comprise solid forms composed of multiple planar surfaces (truncated pyramids and prisms) jutting toward the viewer, thus forming concave spaces between the solids. The solids are painted in reverse perspective: as an example, the left and right trapezoids of a truncated pyramid are painted as rows of houses; the bottom trapezoid is painted as the road between them and the top forms the sky. This elicits the percept of a street receding away, even though it physically juts toward the viewer. Under this illusion, the concave void spaces between the solids are transformed into convex volumes. This depth inversion creates a concomitant motion illusion: when a viewer moves in front of the art piece, the scene appears to move vividly. Two additional contributions by the artist are discussed, in which he combines reverse-perspective parts with forced and planar-perspective parts on the same art piece. The effect is spectacular, creating objects on the same planar surface that move in different directions, thus “breaking” the surface apart, demonstrating the superiority of objects over surfaces. We conclude with a discussion on the value of these art pieces in vision science.

Description: Saccadic eye movements are simple, visually guided actions. Operant conditioning of specific saccade directions can reduce the latency of eye movements in the conditioned direction. However, it is not clear to what extent this learning transfers from the conditioned task to novel tasks. The purpose of this study was to investigate whether the effects of operant conditioning of prosaccades to specific spatial locations would transfer to more complex oculomotor behaviours, specifically, prosaccades made in the presence of a distractor (Experiment 1) and antisaccades (Experiment 2). In part 1 of each experiment, participants were rewarded for making a saccade to one hemifield. In both experiments, the reward produced a significant facilitation of saccadic latency for prosaccades directed to the rewarded hemifield. In part 2, rewards were withdrawn, and the participant made a prosaccade to targets that were accompanied by a contralateral distractor (Experiment 1) or an antisaccade (Experiment 2). There were no hemifield-specific effects of the reward on saccade latency on the remote distractor effect or antisaccades, although the reward was associated with an overall slowing of saccade latency in Experiment 1. These data indicate that operant conditioning of saccadic eye movements does not transfer to similar but untrained tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor system.

Description: Geometric differences between the images seen by each eye enable the perception of depth. Additionally, depth is produced in the absence of geometric disparities with binocular disparities in either the average luminance or contrast, which is known as the Venetian blind effect. The temporal dynamics of the Venetian blind effect are much slower (1.3 Hz) than those for geometric binocular disparities (4–5 Hz). Sine-wave modulations of luminance and contrast disparity, however, can be discriminated from square-wave modulations at 1 Hz, which suggests a non-linearity. To measure this non-linearity, a luminance or contrast disparity modulation was presented at a particular frequency and paired with a geometric disparity modulation that cancelled the perceived rotation induced by the luminance or contrast modulation. Phases between the luminance or contrast and the geometric modulation varied in 50 ms increments from −200 and 200 ms. When phases were aligned, observers perceived little or no rotation. When not aligned, a perceived rotation was induced by a contrast or luminance disparity that was then cancelled by the geometric disparity. This causes the perception of a slight jump. The Generalized Difference Model, which is linear in time, predicted a minimal probability in cases when luminance or contrast disparities occurred before the geometric disparities due to the slower dynamics of the Venetian blind effect. The Gated Generalized Difference Model, which is non-linear in time, predicted a minimal probability for offsets of 0 ms. Results followed the Gated model, which further suggests a non-linearity in time for the Venetian blind effect.

Description: Attention is classically classified according to mode of engagement into voluntary and reflexive, and type of operation into covert and overt. The first distinguishes whether attention is elicited intentionally or by unexpected events; the second, whether attention is directed with or without eye movements. Recently, this taxonomy has been expanded to include automated orienting engaged by overlearned symbols and combined attention engaged by a combination of several modes of function. However, so far, combined effects were demonstrated in covert conditions only, and, thus, here we examined if attentional modes combined in overt responses as well. To do so, we elicited automated, voluntary, and combined orienting in covert, i.e., when participants responded manually and maintained central fixation, and overt cases, i.e., when they responded by looking. The data indicated typical effects for automated and voluntary conditions in both covert and overt data, with the magnitudes of the combined effect larger than the magnitude of each mode alone as well as their additive sum. No differences in the combined effects emerged across covert and overt conditions. As such, these results show that attentional systems combine similarly in covert and overt responses and highlight attention’s dynamic flexibility in facilitating human behavior.

Description: Illusory line motion (ILM) refers to the perception of motion in a line that is, in fact, presented in full at one time. One form of this illusion (flashILM) occurs when the line is presented between two objects following a brief luminance change in one of them and flashILM is thought to result from exogenous attention being captured by the flash. Exogenous attention fades with increasing delays, which predicts that flashILM should show a similar temporal pattern. Exogenous attention appears to follow flashILM to become more or less equally distributed along the line.The current study examines flashILM in order to test these predictions derived from the attentional explanation for flashILM and the results were consistent with them. The discussion then concludes with an exploratory analysis approach concerning states of consciousness and decision making and suggests a possible role for attention.

Description: The majority of eye tracking studies in reading are on issues dealing with word level or sentence level comprehension. By comparison, relatively few eye tracking studies of reading examine questions related to higher level comprehension in processing of longer texts. We present data from an eye tracking study of anaphor resolution in order to examine specific issues related to this discourse phenomenon and to raise more general methodological and theoretical issues in eye tracking studies of discourse processing. This includes matters related to the design of materials as well as the interpretation of measures with regard to underlying comprehension processes. In addition, we provide several examples from eye tracking studies of discourse to demonstrate the kinds of questions that may be addressed with this methodology, particularly with respect to the temporality of processing in higher level comprehension and how such questions correspond to recent theoretical arguments in the field.

Description: Inhibition of return is characterized by delayed responses to previously attended locations when the cue-target onset asynchrony (CTOA) is long enough. However, when cues are predictive of a target’s location, faster reaction times to cued as compared to uncued targets are normally observed. In this series of experiments investigating saccadic reaction times, we manipulated the cue predictability to 25% (counterpredictive), 50% (nonpredictive), and 75% (predictive) to investigate the interaction between predictive endogenous facilitatory (FCEs) and inhibitory cueing effects (ICEs). Overall, larger ICEs were seen in the counterpredictive condition than in the nonpredictive condition, and no ICE was found in the predictive condition. Based on the hypothesized additivity of FCEs and ICEs, we reasoned that the null ICEs observed in the predictive condition are the result of two opposing mechanisms balancing each other out, and the large ICEs observed with counterpredictive cueing can be attributed to the combination of endogenous facilitation at uncued locations with inhibition at cued locations. Our findings suggest that the endogenous activity contributed by cue predictability can reduce the overall inhibition observed when the mechanisms occur at the same location, or enhance behavioral inhibition when the mechanisms occur at opposite locations.

Description: Ganel, Freud, Chajut, and Algom (2012) demonstrated that maximum grip apertures (MGAs) differ significantly when grasping perceptually identical objects. From this finding they concluded that the visual size information used by the motor system is more accurate than the visual size information available to the perceptual system. A direct comparison between the accuracy in the perception and the action system is, however, problematic, given that accuracy in the perceptual task is measured using a dichotomous variable, while accuracy in the visuomotor task is determined using a continuous variable. We addressed this problem by dichotomizing the visuomotor measures. Using this approach, our results show that size discrimination in grasping is in fact inferior to perceptual discrimination therefore contradicting the original suggestion put forward by Ganel and colleagues.

Description: Visual search is a popular tool for studying a range of questions about perception and attention, thanks to the ease with which the basic paradigm can be controlled and manipulated. While often thought of as a sub-field of vision science, search tasks are significantly more complex than most other perceptual tasks, with strategy and decision playing an essential, but neglected, role. In this review, we briefly describe some of the important theoretical advances about perception and attention that have been gained from studying visual search within the signal detection and guided search frameworks. Under most circumstances, search also involves executing a series of eye movements. We argue that understanding the contribution of biases, routines and strategies to visual search performance over multiple fixations will lead to new insights about these decision-related processes and how they interact with perception and attention. We also highlight the neglected potential for variability, both within and between searchers, to contribute to our understanding of visual search. The exciting challenge will be to account for variations in search performance caused by these numerous factors and their interactions. We conclude the review with some recommendations for ways future research can tackle these challenges to move the field forward.

Description: Recent advances of computerized graphical methods have received significant attention for detection and home monitoring of various visual distortions caused by macular disorders such as macular edema, central serous chorioretinopathy, and age-related macular degeneration. After a brief review of macular disorders and their conventional diagnostic methods, this paper reviews such graphical interface methods including computerized Amsler Grid, Preferential Hyperacuity Perimeter, and Three-dimensional Computer-automated Threshold Amsler Grid. Thereafter, the challenges of these computerized methods for accurate and rapid detection of macular disorders are discussed. The early detection and progress assessment of macular disorders can significantly enhance the required clinical procedure for the diagnosis and treatment of macular disorders.

Description: The Irish Astronomical Tract is a 14th–15th century Gaelic document, based mainly on a Latin translation of the eighth-century Jewish astronomer Messahala. It contains a passage about the sun illusion—the apparent enlargement of celestial bodies when near the horizon compared to higher in the sky. This passage occurs in a chapter concerned with proving that the Earth is a globe rather than flat. Here the author denies that the change in size is caused by a change in the sun’s distance, and instead ascribes it (incorrectly) to magnification by atmospheric vapours, likening it to the bending of light when looking from air to water or through glass spectacles. This section does not occur in the Latin version of Messahala. The Irish author may have based the vapour account on Aristotle, Ptolemy or Cleomedes, or on later authors that relied on them. He seems to have been unaware of alternative perceptual explanations. The refraction explanation persists today in folk science.

Description: Autism spectrum disorder (ASD) is neurodevelopmental condition principally characterised by impairments in social interaction and communication, and repetitive behaviours and interests. This article reviews the eye movement studies designed to investigate the underlying sampling or processing differences that might account for the principal characteristics of autism. Following a brief summary of a previous review chapter by one of the authors of the current paper, a detailed review of eye movement studies investigating various aspects of processing in autism over the last decade will be presented. The literature will be organised into sections covering different cognitive components, including language and social communication and interaction studies. The aim of the review will be to show how eye movement studies provide a very useful on-line processing measure, allowing us to account for observed differences in behavioural data (accuracy and reaction times). The subtle processing differences that eye movement data reveal in both language and social processing have the potential to impact in the everyday communication domain in autism.

Description: Social attention describes how observers orient to social information and exhibit behaviors such as gaze following. These behaviors are examples of how attentional orienting may differ when in the presence of other people, although they have typically been studied without actual social presence. In the present study we ask whether orienting, as measured by head and eye movements, will change when participants are trying to mislead or hide their attention from a bystander. In two experiments, observers performed a preference task while being video-recorded, and subsequent participants were asked to guess the response of the participant based on a video of the head and upper body. In a second condition, observers were told to try to mislead the “guesser”. The results showed that participants’ preference responses could be guessed from videos of the head and, critically, that participants spontaneously changed their orienting behavior in order to mislead by reducing the rate at which they made large head movements. Masking the eyes with sunglasses suggested that head movements were most important in our setup. This indicates that head and eye movements can be used flexibly according to the socio-communicative context.

Description: When the head is tilted, an objectively vertical line viewed in isolation is typically perceived as tilted. We explored whether this shift also occurs when viewing global motion displays perceived as either object-motion or self-motion. Observers stood and lay left side down while viewing (1) a static line, (2) a random-dot display of 2-D (planar) motion or (3) a random-dot display of 3-D (volumetric) global motion. On each trial, the line orientation or motion direction were tilted from the gravitational vertical and observers indicated whether the tilt was clockwise or counter-clockwise from the perceived vertical. Psychometric functions were fit to the data and shifts in the point of subjective verticality (PSV) were measured. When the whole body was tilted, the perceived tilt of both a static line and the direction of optic flow were biased in the direction of the body tilt, demonstrating the so-called A-effect. However, we found significantly larger shifts for the static line than volumetric global motion as well as larger shifts for volumetric displays than planar displays. The A-effect was larger when the motion was experienced as self-motion compared to when it was experienced as object-motion. Discrimination thresholds were also more precise in the self-motion compared to object-motion conditions. Different magnitude A-effects for the line and motion conditions—and for object and self-motion—may be due to differences in combining of idiotropic (body) and vestibular signals, particularly so in the case of vection which occurs despite visual-vestibular conflict.

Description: Performance on random-dot global motion tasks may reach adult-like levels before 4 or as late as 16 years of age, depending on the specific parameters used to create the stimuli. Later maturation has been found for slower speeds, smaller spatial displacements, and sparser dot arrays. This protracted development on global motion tasks may depend on limitations specific to spatial aspects of a motion stimulus rather than to motion mechanisms per se. The current study investigated the impact of varying stimulus area (9, 36, and 81 deg2) on the global motion coherence thresholds of children 4–6 years old and adults for three signal dot displacements (∆x = 1, 5, and 30 arcmin). We aimed to determine whether children could achieve mature performance for the smallest displacements, a condition previously found to show late maturation, when a larger stimulus area was used. Coherence thresholds were higher in children compared to adults in the 1 and 5 arcmin displacement conditions, as reported previously, and this did not change as a function of stimulus area. However, both children and adults performed better with a larger stimulus area in the 30 arcmin displacement condition only. This suggests that immature spatial integration, as measured by stimulus area, cannot account for immaturities in global motion perception.

Description: There has been an increasing drive to understand failures in searches for weapons and explosives in X-ray baggage screening. Tracking eye movements during the search has produced new insights into the guidance of attention during the search, and the identification of targets once they are fixated. Here, we review the eye-movement literature that has emerged on this front over the last fifteen years, including a discussion of the problems that real-world searchers face when trying to detect targets that could do serious harm to people and infrastructure.

Description: In grapheme-color synesthesia, letters and numbers evoke abnormal colored perceptions. Although the underlying mechanisms are not known, it is largely thought that the synesthetic brain is characterized by atypical connectivity throughout various brain regions, including the visual areas. To study the putative impact of synesthesia on the visual brain, we assessed lateral interactions (i.e., local functional connectivity between neighboring neurons in the visual cortex) by recording steady-state visual evoked potentials (ssVEPs) over the occipital region in color-grapheme synesthetes (n = 6) and controls (n = 21) using the windmill/dartboard paradigm. Discrete Fourier Transform analysis was conducted to extract the fundamental frequency and the second harmonics of ssVEP responses from contrast-reversing stimuli presented at 4.27 Hz. Lateral interactions were assessed using two amplitude-based indices: Short-range and long-range lateral interactions. Results indicated that synesthetes had a statistically weaker signal coherence of the fundamental frequency component compared to the controls, but no group differences were observed on lateral interaction indices. However, a significant correlation was found between long-range lateral interactions and the type of synesthesia experience (projector versus associator). We conclude that the occipital activity related to lateral interactions in synesthetes does not substantially differ from that observed in controls. Further investigation is needed to understand the impact of synesthesia on visual processing, specifically in relation to subjective experiences of synesthete individuals.

Description: The eye movements of experts, reading medical images, have been studied for many years. Unlike topics such as face perception, medical image perception research needs to cope with substantial, qualitative changes in the stimuli under study due to dramatic advances in medical imaging technology. For example, little is known about how radiologists search through 3D volumes of image data because they simply did not exist when earlier eye tracking studies were performed. Moreover, improvements in the affordability and portability of modern eye trackers make other, new studies practical. Here, we review some uses of eye movements in the study of medical image perception with an emphasis on newer work. We ask how basic research on scene perception relates to studies of medical ‘scenes’ and we discuss how tracking experts’ eyes may provide useful insights for medical education and screening efficiency.

Description: Facial recognition is widely thought to involve a holistic perceptual process, and optimal recognition performance can be rapidly achieved within two fixations. However, is facial identity encoding likewise holistic and rapid, and how do gaze dynamics during encoding relate to recognition? While having eye movements tracked, participants completed an encoding (“study”) phase and subsequent recognition (“test”) phase, each divided into blocks of one- or five-second stimulus presentation time conditions to distinguish the influences of experimental phase (encoding/recognition) and stimulus presentation time (short/long). Within the first two fixations, several differences between encoding and recognition were evident in the temporal and spatial dynamics of the eye-movements. Most importantly, in behavior, the long study phase presentation time alone caused improved recognition performance (i.e., longer time at recognition did not improve performance), revealing that encoding is not as rapid as recognition, since longer sequences of eye-movements are functionally required to achieve optimal encoding than to achieve optimal recognition. Together, these results are inconsistent with a scan path replay hypothesis. Rather, feature information seems to have been gradually integrated over many fixations during encoding, enabling recognition that could subsequently occur rapidly and holistically within a small number of fixations.

Description: Under optimal conditions, just 3–6 ms of visual stimulation suffices for humans to see motion. Motion perception on this timescale implies that the visual system under these conditions reliably encodes, transmits, and processes neural signals with near-millisecond precision. Motivated by in vitro evidence for high temporal precision of motion signals in the primate retina, we investigated how neuronal and perceptual limits of motion encoding relate. Specifically, we examined the correspondence between the time scale at which cat retinal ganglion cells in vivo represent motion information and temporal thresholds for human motion discrimination. The timescale for motion encoding by ganglion cells ranged from 4.6 to 91 ms, and depended non-linearly on temporal frequency, but not on contrast. Human psychophysics revealed that minimal stimulus durations required for perceiving motion direction were similarly brief, 5.6–65 ms, and similarly depended on temporal frequency but, above ~10%, not on contrast. Notably, physiological and psychophysical measurements corresponded closely throughout (r = 0.99), despite more than a 20-fold variation in both human thresholds and optimal timescales for motion encoding in the retina. The match in absolute values of the neurophysiological and psychophysical data may be taken to indicate that from the lateral geniculate nucleus (LGN) through to the level of perception little temporal precision is lost. However, we also show that integrating responses from multiple neurons can improve temporal resolution, and this potential trade-off between spatial and temporal resolution would allow for loss of temporal resolution after the LGN. While the extent of neuronal integration cannot be determined from either our human psychophysical or neurophysiological experiments and its contribution to the measured temporal resolution is unknown, our results demonstrate a striking similarity in stimulus dependence between the temporal fidelity established in the retina and the temporal limits of human motion discrimination.

Description: Research suggests that pattern complexity (number of strokes) limits the visual span for Chinese characters, and that this may have important consequences for reading. With the present research, we investigated age differences in the visual span for Chinese characters by presenting trigrams of low, medium or high complexity at various locations relative to a central point to young (18–30 years) and older (60+ years) adults. A sentence reading task was used to assess their reading speed. The results showed that span size was smaller for high complexity stimuli compared to low and medium complexity stimuli for both age groups, replicating previous findings with young adult participants. Our results additionally showed that this influence of pattern complexity was greater for the older than younger adults, such that while there was little age difference in span size for low and medium complexity stimuli, span size for high complexity stimuli was almost halved in size for the older compared to the young adults. Finally, our results showed that span size correlated with sentence reading speed, confirming previous findings taken as evidence that the visual span imposes perceptual limits on reading speed. We discuss these findings in relation to age-related difficulty reading Chinese.

Description: The formation of structure in the visual system, that is, of the connections between cellswithin neural populations, is by and large an unsupervised learning process. In the primary visualcortex of mammals, for example, one can observe during development the formation of cells selectiveto localized, oriented features, which results in the development of a representation in area V1 ofimages’ edges. This can be modeled using a sparse Hebbian learning algorithms which alternatea coding step to encode the information with a learning step to find the proper encoder. A majordifficulty of such algorithms is the joint problem of finding a good representation while knowingimmature encoders, and to learn good encoders with a nonoptimal representation. To solve thisproblem, this work introduces a new regulation process between learning and coding which ismotivated by the homeostasis processes observed in biology. Such an optimal homeostasis ruleis implemented by including an adaptation mechanism based on nonlinear functions that balancethe antagonistic processes that occur at the coding and learning time scales. It is compatible witha neuromimetic architecture and allows for a more efficient emergence of localized filters sensitiveto orientation. In addition, this homeostasis rule is simplified by implementing a simple heuristicon the probability of activation of neurons. Compared to the optimal homeostasis rule, numericalsimulations show that this heuristic allows to implement a faster unsupervised learning algorithmwhile retaining much of its effectiveness. These results demonstrate the potential application of sucha strategy in machine learning and this is illustrated by showing the effect of homeostasis in theemergence of edge-like filters for a convolutional neural network.

Description: The central nervous system can respond to threat via the induction of an inflammatory response. Under normal circumstances this response is tightly controlled, however uncontrolled neuroinflammation is a hallmark of many neurological disorders. MicroRNAs are small non-coding RNA molecules that are important for regulating many cellular processes. The ability of microRNAs to modulate inflammatory signaling is an area of ongoing research, which has gained much attention in recent years. MicroRNAs may either promote or restrict inflammatory signaling, and either exacerbate or ameliorate the pathological consequences of excessive neuroinflammation. The aim of this review is to summarize the mode of regulation for several important and well-studied microRNAs in the context of neuroinflammation, including miR-155, miR-146a, miR-124, miR-21 and let-7. Furthermore, the pathological consequences of miRNA deregulation during disorders that feature neuroinflammation are discussed, including Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease, Prion diseases, Japanese encephalitis, Herpes encephalitis, ischemic stroke and traumatic brain injury. There has also been considerable interest in the use of altered microRNA signatures as biomarkers for these disorders. The ability to modulate microRNA expression may even serve as the basis for future therapeutic strategies to help treat pathological neuroinflammation.

Description: Multiple myeloma (MM) is the second most common hematooncological disease of malignant plasma cells in the bone marrow. While new treatment brought unprecedented increase of survival of patients, MM pathogenesis is yet to be clarified. Increasing evidence of expression of long non-coding RNA molecules (lncRNA) linked to development and progression of many tumors suggested their important role in tumorigenesis. To date, over 15,000 lncRNA molecules characterized by diversity of function and specificity of cell distribution were identified in the human genome. Due to their involvement in proliferation, apoptosis, metabolism, and differentiation, they have a key role in the biological processes and pathogenesis of many diseases, including MM. This review summarizes current knowledge of non-coding RNAs (ncRNA), especially lncRNAs, and their role in MM pathogenesis. Undeniable involvement of lncRNAs in MM development suggests their potential as biomarkers.

Description: MicroRNAs play functional roles in the etiology of type 2 diabetes mellitus (T2DM) and complications, and extracellular microRNAs have attracted interest as potential biomarkers of these conditions. We aimed to identify a set of plasma microRNAs, which could serve as biomarkers of T2DM and complications in a mixed Israeli Arab/Jewish patient sample. Subjects included 30 healthy volunteers, 29 early-stage T2DM patients, and 29 late-stage T2DM patients with renal and/or vascular complications. RNA was isolated from plasma, and the levels of 12 candidate microRNAs were measured by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). MicroRNA levels were compared between the groups and correlated to clinical measurements, followed by stepwise regression analysis and discriminant analysis. Plasma miR-486-3p and miR-423 were respectively up- and down-regulated in T2DM patients compared to healthy controls. MiR-28-3p and miR-423 were up-regulated in patients with complicated T2DM compared to early T2DM, while miR-486-3p was down-regulated. Combined, four microRNAs (miR-146a-5p, miR-16-2-3p, miR-126-5p, and miR-30d) could distinguish early from complicated T2DM with 77% accuracy and 79% sensitivity. In male patients only, the same microRNAs, with the addition of miR-423, could distinguish early from complicated T2DM with 83.3% accuracy. Furthermore, plasma microRNA levels showed significant correlations with clinical measurements, and these differed between men and women. Additionally, miR-183-5p levels differed significantly between the ethnic groups. Our study identified a panel of specific plasma microRNAs which can serve as biomarkers of T2DM and its complications and emphasizes the importance of sex differences in their clinical application.

Description: Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field.COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu).

Description: Rigorous peer-review is the corner-stone of high-quality academic publishing [...]

Description: The conservation of intronic sequences was studied in the mitochondrial solute carrier (SLC25A*) genes of Zebrafish, Chicken, Mouse and Human. These genes are homologous and the coding sequences have been well conserved throughout Vertebrates, but the corresponding intronic sequences have been extensively re-edited. However, significant segments of Zebrafish introns are conserved in Chicken, Mouse and Human in carriers SLC25A3, SLC25A21, SLC25A25, SLC25A26, and SLC25A36; Chicken intron segments are conserved in Mouse or Human in three additional carriers, namely SLC25A12, SLC25A13, and SLC25A29. Thus, a quota of the intronic sequences of Euteleostomi has been transferred (through Sarcopterygii) to Birds and (through Sarcopterygii and ancestral Mammals) to Mouse and Human. The degree of conservation of Euteleostomi-derived sequences is low and quite similar in Chicken, Mouse and Human (0.23–0.27%). The overall degree of conservation of Sarcopterygii-derived sequences in Mammals is higher, and it is significantly higher in Human than in Mouse (4.4% and 3.2%, respectively). Some of the conserved intronic sequences of SLC25A3, SLC25A21, SLC25A25, and SLC25A29 are exonized in some transcript variants of Zebrafish, Chicken, Mouse, and Human and, with minor nucleotide changes, in other Birds or Mammals.

Description: Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI provide molecular insights into this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches, integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicted that 13 miRNAs and 3 of these miRNAs would be validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicted that 24 miRNAs among 1310 molecules and 6 of these miRNAs would be selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.

Description: Cardiovascular diseases are the most prominent cause of death in Western society, especially in the elderly. With the increasing life expectancy, the number of patients with cardiovascular diseases will rise in the near future, leading to an increased healthcare burden. There is a need for new therapies to treat this growing number of patients. The discovery of long non-coding RNAs has led to a novel group of molecules that could be considered for their potential as therapeutic targets. This review presents an overview of long non-coding RNAs that are regulated in vascular disease and aging and which might therefore give insight into new pathways that could be targeted to diagnose, prevent, and/or treat vascular diseases.

Description: Enclosed by two membranes, the nucleus itself is comprised of various membraneless compartments, including nuclear bodies and chromatin domains. These compartments play an important though still poorly understood role in gene regulation. Significant progress has been made in characterizing the dynamic behavior of nuclear compartments and liquid-liquid phase separation (LLPS) has emerged as a prominent mechanism governing their assembly. However, recent work reveals that certain nuclear structures violate key predictions of LLPS, suggesting that alternative mechanisms likely contribute to nuclear organization. Here, we review the evidence for and against LLPS for several nuclear compartments and discuss experimental strategies to identify the mechanism(s) underlying their assembly. We propose that LLPS, together with multiple modes of protein-nucleic acid binding, drive spatiotemporal organization of the nucleus and facilitate functional diversity among nuclear compartments.

Description: Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery.

Description: Gammaherpesviruses, including the human pathogens Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are oncogenic viruses that establish lifelong infections in hosts and are associated with the development of lymphoproliferative diseases and lymphomas. Recent studies have shown that the majority of the mammalian genome is transcribed and gives rise to numerous long non-coding RNAs (lncRNAs). Likewise, the large double-stranded DNA virus genomes of herpesviruses undergo pervasive transcription, including the expression of many as yet uncharacterized lncRNAs. Murine gammaperherpesvirus 68 (MHV68, MuHV-4, HV68) is a natural pathogen of rodents, and is genetically and pathogenically related to EBV and KSHV, providing a highly tractable model for studies of gammaherpesvirus biology and pathogenesis. Through the integrated use of parallel data sets from multiple sequencing platforms, we previously resolved transcripts throughout the MHV68 genome, including at least 144 novel transcript isoforms. Here, we sought to molecularly validate novel transcripts identified within the M3/M2 locus, which harbors genes that code for the chemokine binding protein M3, the latency B cell signaling protein M2, and 10 microRNAs (miRNAs). Using strand-specific northern blots, we validated the presence of M3-04, a 3.91 kb polyadenylated transcript that initiates at the M3 transcription start site and reads through the M3 open reading frame (ORF), the M3 poly(a) signal sequence, and the M2 ORF. This unexpected transcript was solely localized to the nucleus, strongly suggesting that it is not translated and instead may function as a lncRNA. Use of an MHV68 mutant lacking two M3-04-antisense pre-miRNA stem loops resulted in highly increased expression of M3-04 and increased virus replication in the lungs of infected mice, demonstrating a key role for these RNAs in regulation of lytic infection. Together these findings suggest the possibility of a tripartite regulatory relationship between the lncRNA M3-04, antisense miRNAs, and the latency gene M2.

Description: Non-coding antisense transcripts arise from the strand opposite the sense strand. Over 70% of the human genome generates non-coding antisense transcripts while less than 2% of the genome codes for proteins. Antisense transcripts and/or the act of antisense transcription regulate gene expression and genome integrity by interfering with sense transcription and modulating histone modifications or DNA methylation. Hence, they have significant pathological and physiological relevance. Indeed, antisense transcripts were found to be associated with various diseases including cancer, diabetes, cardiac and neurodegenerative disorders, and, thus, have promising potentials for prognostic and diagnostic markers and therapeutic development. However, it is not clearly understood how antisense transcription is initiated and epigenetically regulated. Such knowledge would provide new insights into the regulation of antisense transcription, and hence disease pathogenesis with therapeutic development. The recent studies on antisense transcription initiation and its epigenetic regulation, which are limited, are discussed here. Furthermore, we concisely describe how antisense transcription/transcripts regulate gene expression and genome integrity with implications in disease pathogenesis and therapeutic development.

Description: As part of their innate immune response against viral infections, mammals activate the expression of type I interferons to prevent viral replication and dissemination. An antiviral RNAi-based response can be also activated in mammals, suggesting that several mechanisms can co-occur in the same cell and that these pathways must interact to enable the best antiviral response. Here, we will review how the classical type I interferon response and the recently described antiviral RNAi pathways interact in mammalian cells. Specifically, we will uncover how the small RNA biogenesis pathway, composed by the nucleases Drosha and Dicer can act as direct antiviral factors, and how the type-I interferon response regulates the function of these. We will also describe how the factors involved in small RNA biogenesis and specific small RNAs impact the activation of the type I interferon response and antiviral activity. With this, we aim to expose the complex and intricate network of interactions between the different antiviral pathways in mammals.

Description: In the cell nuclei, various types of nuclear domains assemble as a result of transcriptional activity at specific chromosomal loci. Giant transcriptionally active lampbrush chromosomes, which form in oocyte nuclei of amphibians and birds enable the mapping of genomic sequences with high resolution and the visualization of individual transcription units. This makes avian and amphibian oocyte nuclei an advantageous model for studying locus-specific nuclear domains. We developed two strategies for identification and comprehensive analysis of the genomic loci involved in nuclear domain formation on lampbrush chromosomes. The first approach was based on the sequential FISH-mapping of BAC clones containing genomic DNA fragments with a known chromosomal position close to the locus of a nuclear domain. The second approach involved mechanical microdissection of the chromosomal region adjacent to the nuclear domain followed by the generation of FISH-probes and DNA sequencing. Furthermore, deciphering the DNA sequences from the dissected material by high throughput sequencing technologies and their mapping to the reference genome helps to identify the genomic region responsible for the formation of the nuclear domain. For those nuclear domains structured by nascent transcripts, identification of genomic loci of their formation is a crucial step in the identification of scaffold RNAs.

Description: MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV1 and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.

Description: The impact of population variation in the analysis of regulatory interactions is an underdeveloped area. MicroRNA target recognition occurs via pairwise complementarity. Consequently, a number of computational prediction tools have been developed to identify potential target sites that can be further validated experimentally. However, as microRNA target predictions are done mostly considering a reference genome sequence, target sites showing variation among populations are neglected. Here, we studied the variation at microRNA target sites in human populations and quantified their impact in microRNA target prediction. We found that African populations carry a significant number of potential microRNA target sites that are not detectable in the current human reference genome sequence. Some of these targets are conserved in primates and only lost in Out-of-Africa populations. Indeed, we identified experimentally validated microRNA/transcript interactions that are not detected in standard microRNA target prediction programs, yet they have segregating target alleles abundant in non-European populations. In conclusion, we show that ignoring population diversity may leave out regulatory elements essential to understand disease and gene expression, particularly neglecting populations of African origin.

Description: Management of chronic diabetic complications remains a major medical challenge worldwide. One of the characteristic features of all chronic diabetic complications is augmented production of extracellular matrix (ECM) proteins. Such ECM proteins are deposited in all tissues affected by chronic complications, ultimately causing organ damage and dysfunction. A contributing factor to this pathogenetic process is glucose-induced endothelial damage, which involves phenotypic transformation of endothelial cells (ECs). This phenotypic transition of ECs, from a quiescent state to an activated dysfunctional state, can be mediated through alterations in the synthesis of cellular proteins. In this review, we discussed the roles of non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in such processes. We further outlined other epigenetic mechanisms regulating the biogenesis and/or function of non-coding RNAs. Overall, we believe that better understanding of such molecular processes may lead to the development of novel biomarkers and therapeutic strategies in the future.

Description: The Transcribed-Ultra Conserved Regions (T-UCRs) are a class of novel non-coding RNAs that arise from the dark matter of the genome. T-UCRs are highly conserved between mouse, rat, and human genomes, which might indicate a definitive role for these elements in health and disease. The growing body of evidence suggests that T-UCRs contribute to oncogenic pathways. Neuroblastoma is a type of childhood cancer that is challenging to treat. The role of non-coding RNAs in the pathogenesis of neuroblastoma, in particular for cancer development, progression, and therapy resistance, has been documented. Exosmic non-coding RNAs are also involved in shaping the biology of the tumor microenvironment in neuroblastoma. In recent years, the involvement of T-UCRs in a wide variety of pathways in neuroblastoma has been discovered. Here, we present an overview of the involvement of T-UCRs in various cellular pathways, such as DNA damage response, proliferation, chemotherapy response, MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) amplification, gene copy number, and immune response, as well as correlate it to patient survival in neuroblastoma.

Description: Recent studies in cancer diagnostics have identified microRNAs (miRNAs) as promising cancer biomarkers. Single nucleotide polymorphisms (SNPs) in miRNA binding sites, seed regions, and coding sequences can help predict breast cancer risk, aggressiveness, response to stimuli, and prognosis. This review also documents significant known miR-SNPs in miRNA biogenesis genes and their effects on gene regulation in breast cancer, taking into account the genetic background and ethnicity of the sampled populations. When applicable, miR-SNPs are evaluated in the context of other patient factors, including mutations, hormonal status, and demographics. Given the power of miR-SNPs to predict patient cancer risk, prognosis, and outcomes, further study of miR-SNPs is warranted to improve efforts towards personalized medicine.

Description: Adolescence is hallmarked by two parallel processes of sexual maturation and adult patterning of the brain. Therefore, adolescence represents a vulnerable postnatal period for neurodevelopment where exogenous factors can negatively impact adult brain function. For example, alcohol exposure during pubertal development can lead to long-term and widespread neurobiological dysfunction and these effects have been shown to persist even in the absence of future alcohol exposure. However, the molecular mechanisms mediating the persistent effects of alcohol are unclear. We propose that dysregulation of microRNAs (miR) could be a unifying epigenetic mechanism underlying these widespread long-term changes. We tested the hypothesis that repeated alcohol exposure during pubertal development would cause disruption of normal miR expression profiles during puberty and, subsequently, their downstream mRNA target genes in the ventral hippocampus using an established rat model of adolescent binge drinking. We found 6 alcohol-sensitive miRs that were all downregulated following alcohol exposure and we also investigated the normal age-dependent changes in those miRs throughout the pubertal period. Interestingly, these miRs were normally decreased throughout the process of puberty, but alcohol prematurely exacerbated the normal decline in miR expression levels. The work presented herein provides foundational knowledge about the expression patterns of miRs during this critical period of neurodevelopment. Further, this regulation of miR and mRNA expression by alcohol exposure presents a complex regulatory mechanism by which perturbation in this time-sensitive period could lead to long-term neurological consequences.

Description: In recent years, long noncoding RNAs (lncRNAs) have emerged as multifaceted regulators of gene expression, controlling key developmental and disease pathogenesis processes. However, due to the paucity of lncRNA loss-of-function mouse models, key questions regarding the involvement of lncRNAs in organism homeostasis and (patho)-physiology remain difficult to address experimentally in vivo. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 platform provides a powerful genome-editing tool and has been successfully applied across model organisms to facilitate targeted genetic mutations, including Caenorhabditis elegans, Drosophila melanogaster, Danio rerio and Mus musculus. However, just a few lncRNA-deficient mouse lines have been created using CRISPR/Cas9-mediated genome engineering, presumably due to the need for lncRNA-specific gene targeting strategies considering the absence of open-reading frames in these loci. Here, we describe a step-wise procedure for the generation and validation of lncRNA loss-of-function mouse models using CRISPR/Cas9-mediated genome engineering. In a proof-of-principle approach, we generated mice deficient for the liver-enriched lncRNA Gm15441, which we found downregulated during development of metabolic disease and induced during the feeding/fasting transition. Further, we discuss guidelines for the selection of lncRNA targets and provide protocols for in vitro single guide RNA (sgRNA) validation, assessment of in vivo gene-targeting efficiency and knockout confirmation. The procedure from target selection to validation of lncRNA knockout mouse lines can be completed in 18–20 weeks, of which

Description: Meiotic silencing by unpaired DNA (MSUD) is a gene silencing process that occurs within meiotic cells of Neurospora crassa and other fungi. We have previously developed a high-throughput screen to identify suppressors of this silencing pathway. Here, a list of MSUD suppressor candidates from a single pass of the first 84 plates of the Neurospora knockout library is provided.

Description: Skeletal muscle is a highly plastic tissue and decreased skeletal muscle mass (muscle atrophy) results in deteriorated motor function and perturbed body homeostasis. Myogenin promoter-associated long non-coding RNA (lncRNA) Myoparr promotes skeletal muscle atrophy caused by surgical denervation; however, the precise molecular mechanism remains unclear. Here, we examined the downstream genes of Myoparr during muscle atrophy following denervation of tibialis anterior (TA) muscles in C57BL/6J mice. Myoparr knockdown affected the expression of 848 genes. Sixty-five of the genes differentially regulated by Myoparr knockdown coded secretory proteins. Among these 65 genes identified in Myoparr-depleted skeletal muscles after denervation, we focused on the increased expression of growth/differentiation factor 5 (GDF5), an inhibitor of muscle atrophy. Myoparr knockdown led to activated bone morphogenetic protein (BMP) signaling in denervated muscles, as indicated by the increased levels of phosphorylated Smad1/5/8. Our detailed evaluation of downstream genes of Myoparr also revealed that Myoparr regulated differential gene expression between myogenic differentiation and muscle atrophy. This is the first report demonstrating the in vivo role of Myoparr in regulating BMP signaling in denervated muscles. Therefore, lncRNAs that have inhibitory activity on BMP signaling may be putative therapeutic targets for skeletal muscle atrophy.

Description: The non-coding genome has previously been regarded as “junk” DNA; however, emerging evidence suggests that the non-coding genome accounts for some of the greater biological complexity observed in mammals. Research into long non-coding RNAs (lncRNAs) has gathered speed in recent years, and a growing body of evidence has implicated lncRNAs in a vast range of cellular functions including gene regulation, chromosome organisation and splicing. T helper cells offer an ideal platform for the study of lncRNAs given they function as part of a complex cellular network and undergo remarkable and finely regulated gene expression changes upon antigenic stimulation. Using various knock down and RNA interaction studies several lncRNAs have been shown to be crucial for T helper cell differentiation, activation and function. Given that RNA targeting therapeutics are rapidly gaining attention, further understanding the mechanistic role of lncRNAs in a T helper context is an exciting area of research, as it may unearth a wide range of new candidate targets for treatment of CD4+ mediated pathologies.

Description: The function of microRNAs (miRNAs) during fibrosis and the downstream regulation of gene expression by these miRNAs have become of great biological interest. miR-155 is consistently upregulated in fibrotic disorders, and its ablation downregulates collagen synthesis. Studies demonstrate the integral role of miR-155 in fibrosis, as it mediates TGF-β1 signaling to drive collagen synthesis. In this review, we summarize recent findings on the association between miR-155 and fibrotic disorders. We discuss the cross-signaling between macrophages and fibroblasts that orchestrates the upregulation of collagen synthesis mediated by miR-155. As miR-155 is involved in the activation of the innate and adaptive immune systems, specific targeting of miR-155 in pathologic cells that make excessive collagen could be a viable option before the depletion of miR-155 becomes an attractive antifibrotic approach.

Description: Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of regulatory non-coding RNAs that play important roles in post-transcriptional regulation across a variety of biological processes. Here, we review the recent advances in tsRNA biogenesis and regulatory functions from the perspectives of functional and evolutionary genomics, with a focus on the tsRNA biology of Drosophila. We first summarize our current understanding of the biogenesis mechanisms of different categories of tsRNAs that are generated under physiological or stressed conditions. Next, we review the conservation patterns of tsRNAs in all domains of life, with an emphasis on the conservation of tsRNAs between two Drosophila species. Then, we elaborate the currently known regulatory functions of tsRNAs in mRNA translation that are independent of, or dependent on, Argonaute (AGO) proteins. We also highlight some issues related to the fundamental biology of tsRNAs that deserve further study.

Description: Intensive research has been undertaken during the last decade to identify the implication of microRNAs (miRNAs) in the pathogenesis of multiple myeloma (MM). The expression profiling of miRNAs in MM has provided relevant information, demonstrating different patterns of miRNA expression depending on the genetic abnormalities of MM and a key role of some miRNAs regulating critical genes associated with MM pathogenesis. However, the underlying causes of abnormal expression of miRNAs in myeloma cells remain mainly elusive. The final expression of the mature miRNAs is subject to multiple regulation mechanisms, such as copy number alterations, CpG methylation or transcription factors, together with impairment in miRNA biogenesis and differences in availability of the mRNA target sequence. In this review, we summarize the available knowledge about the factors involved in the regulation of miRNA expression and functionality in MM.

Description: We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...]

Description: A growing number of recent studies have revealed that non-coding RNAs play a wide variety of roles beyond expectation. A lot of non-coding RNAs have been shown to function by forming intracellular structures either in the nucleus or the cytoplasm. In the fission yeast Schizosaccharomyces pombe, a non-coding RNA termed meiRNA has been shown to play multiple vital roles in the course of meiosis. meiRNA is tethered to its genetic locus after transcription and forms a peculiar intranuclear dot structure. It ensures stable expression of meiotic genes in cooperation with an RNA-binding protein Mei2. Chromosome-associated meiRNA also facilitates recognition of homologous chromosome loci and induces robust pairing. In this review, the quarter-century history of meiRNA, from its identification to functional characterization, will be outlined.

Description: Gastrotrichs—'hairy bellies’—are microscopic free-living animals inhabiting marine and freshwater habitats. Based on morphological and early molecular analyses, gastrotrichs were placed close to nematodes, but recent phylogenomic analyses have suggested their close relationship to flatworms (Platyhelminthes) within Spiralia. Small non-coding RNA data on e.g., microRNAs (miRNAs) and PIWI-interacting RNAs (piRNA) may help to resolve this long-standing question. MiRNAs are short post-transcriptional gene regulators that together with piRNAs play key roles in development. In a ‘multi-omics’ approach we here used small-RNA sequencing, available transcriptome and genomic data to unravel the miRNA- and piRNA complements along with the RNAi (RNA interference) protein machinery of Lepidodermella squamata (Gastrotricha, Chaetonotida). We identified 52 miRNA genes representing 35 highly conserved miRNA families specific to Eumetazoa, Bilateria, Protostomia, and Spiralia, respectively, with overall high similarities to platyhelminth miRNA complements. In addition, we found four large piRNA clusters that also resemble flatworm piRNAs but not those earlier described for nematodes. Congruently, transcriptomic annotation revealed that the Lepidodermella protein machinery is highly similar to flatworms, too. Taken together, miRNA, piRNA, and protein data support a close relationship of gastrotrichs and flatworms.

Description: Background: Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are still unknown and new studies to improve diagnosis, therapy, and the utilization of canine species as spontaneous animal tumor models are undeniably needed. Recent work using human DLBCL transcriptomes has suggested that long non-coding RNAs (lncRNAs) play a key role in lymphoma pathogenesis and pinpointed a restricted number of lncRNAs as potential targets for further studies. Results: To expand the knowledge of non-coding molecules involved in canine BCL, we used transcriptomes obtained from a cohort of 62 dogs with newly-diagnosed multicentric DLBCL, MZL and FL that had undergone complete staging work-up and were treated with chemotherapy or chemo-immunotherapy. We developed a customized R pipeline performing a transcriptome assembly by multiple algorithms to uncover novel lncRNAs, and delineate genome-wide expression of unannotated and annotated lncRNAs. Our pipeline also included a new package for high performance system biology analysis, which detects high-scoring network biological neighborhoods to identify functional modules. Moreover, our customized pipeline quantified the expression of novel and annotated lncRNAs, allowing us to subtype DLBCLs into two main groups. The DLBCL subtypes showed statistically different survivals, indicating the potential use of lncRNAs as prognostic biomarkers in future studies. Conclusions: In this manuscript, we describe the methodology used to identify lncRNAs that differentiate B-cell lymphoma subtypes and we interpreted the biological and clinical values of the results. We inferred the potential functions of lncRNAs to obtain a comprehensive and integrative insight that highlights their impact in this neoplasm.

Description: Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as putative regulators of IL-24. This study elucidates the expression profile and role of miR-4719 and miR-6756-5p as regulators of IL-24 in PCa. qRT-PCR analysis shows miR-4719 and miR-6756-5p overexpression significantly decreases the expression of IL-24 in PCa cells compared to the negative control. Compared to the indolent PCa and normal prostate epithelial cells, miR-4719 and miR-6756-5p are significantly overexpressed in castration-resistant prostate cancer (CRPC) cell lines, indicating that their gain may be an early event in PCa progression. Moreover, miR-4719 and miR-6756-5p are significantly overexpressed in the CRPC cell line of African-American males (E006AA-hT) compared to CRPC cell lines of Caucasian males (PC-3 and DU-145), indicating that miR-4719 and miR-6756-5p may also play a role in racial disparity. Lastly, the inhibition of expression of miR-4719 and miR-6756-5p significantly increases IL-24 expression and inhibits proliferation and migration of CRPC cell lines. Our findings indicate that miR-4719 and miR-6756-5p may regulate CRPC progression through the targeting of IL-24 expression and may be biomarkers that differentiate between indolent and CRPC. Strategies to inhibit miR-4719 and miR-6756-5p expression to increase IL-24 in PCa may have therapeutic efficacy in aggressive PCa.

Description: The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will present a nonexhaustive list of referenced small non-coding RNAs (ncRNAs) derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs). We will focus on the rRFs that are experimentally verified, and discuss their origin, length, structure, biogenesis, association with known regulatory proteins, and potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because no one could believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Description: The identification of exosomes, their link to multivesicular bodies and their potential role as a messenger vehicle between cancer and healthy cells opens up a new approach to the study of intercellular signaling. Furthermore, the fact that their main cargo is likely to be microRNAs (miRNAs) provides the possibility of the transfer of such molecules to control activities in the recipient cells. This review concerns a brief overview of the biogenesis of both exosomes and miRNAs together with the movement of such structures between cells. The possible roles of miRNAs in the development and progression of breast, ovarian and prostate cancers are discussed.

Description: MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (miR-205) expression is controversial in different types of human cancers, it is generally observed that miR-205-5p expression level is downregulated in breast cancer and that miR-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of miR-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of miR-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate miR-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of miR-205-5p in breast cancer is also discussed. A comprehensive list of validated miR-205-5p direct targets is presented. It is concluded that miR-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. MiR-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer.

Description: The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain.

Description: The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.

Description: Innate immunity provides the initial defence against infection and it is now clear that long non-coding RNAs (lncRNAs) are important regulators of this response. Following activation of the innate response, we commonly see rapid induction of these lncRNAs and this is often mediated via the pro-inflammatory transcription factor, nuclear factor-κB (NF-κB). Knockdown studies have shown that lncRNAs tend to act in trans to regulate the expression of multiple inflammatory mediators and other responses. Mechanistically, many lncRNAs have demonstrated acting through heterogeneous nuclear ribonucleoproteins, complexes that are implicated chromatin re-modelling, transcription process and translation. In addition, these lncRNAs have also been shown to interact with multiple other proteins involved in the regulation of chromatin re-modelling, as well as those proteins involved in intracellular immune signalling, which include NF-κB. In this review, we will describe the evidence that supports this emerging role of lncRNA in the innate immune response.