Enhanced Ablation of Cornea Doped with a Fluorescein Dye Using a Visible Wavelength Laser.

Myopia (nearsightedness) and presbyopia (aging eye) are the most common refractive errors of the human eye. Technology has advanced toward correcting aberration using various surgical procedures, including laser surgery, as well as prescribing corrective lenses. Hence, the effect of various laser wavelengths on the eye has been extensively studied over the last few decades. Usually, excimer lasers are used for this purpose, which increases the cost of the procedure because they are unique and difficult to manufacture and require regular maintenance. Due to the absorption properties, visible wavelengths do not interact with the corneal layers and hence are currently not used for eye surgery. This study presents the first clinical evidence that a 532 nm laser in combination with an eye-safe fluorescein dye that is in wide clinical use in ophthalmology can be utilized for high-precision ablation purposes due to the photochemical reaction that occurs on an ex vivo porcine eye. Our results show the promise of utilizing inexpensive visible wavelength lasers in the ablation of biological tissues, reducing the high costs of ophthalmological surgical procedures, as well as in other applications.

Spatial visual function in anomalous trichromats: Is less more?

Color deficiency is a common inherited disorder affecting 8% of Caucasian males with anomalous trichromacy (AT); it is the most common type of inherited color vision deficiency. Anomalous trichromacy is caused by alteration of one of the three cone-opsins' spectral sensitivity; it is usually considered to impose marked limitations for daily life as well as for choice of occupation. Nevertheless, we show here that anomalous trichromat subjects have superior basic visual functions such as visual acuity (VA), contrast sensitivity (CS), and stereo acuity, compared with participants with normal color vision. Both contrast sensitivity and stereo acuity performance were correlated with the severity of color deficiency. We further show that subjects with anomalous trichromacy exhibit a better ability to detect objects camouflaged in natural gray scale figures. The advantages of color-deficient subjects in spatial vision performance could explain the relatively high prevalence of color-vision polymorphism in humans.

Vision improvement in pilots with presbyopia following perceptual learning.

Israeli Air Force (IAF) pilots continue flying combat missions after the symptoms of natural near-vision deterioration, termed presbyopia, begin to be noticeable. Because modern pilots rely on the displays of the aircraft control and performance instruments, near visual acuity (VA) is essential in the cockpit. We aimed to apply a method previously shown to improve visual performance of presbyopes, and test whether presbyopic IAF pilots can overcome the limitation imposed by presbyopia. Participants were selected by the IAF aeromedical unit as having at least initial presbyopia and trained using a structured personalized perceptual learning method (GlassesOff application), based on detecting briefly presented low-contrast Gabor stimuli, under the conditions of spatial and temporal constraints, from a distance of 40 cm. Our results show that despite their initial visual advantage over age-matched peers, training resulted in robust improvements in various basic visual functions, including static and temporal VA, stereoacuity, spatial crowding, contrast sensitivity and contrast discrimination. Moreover, improvements generalized to higher-level tasks, such as sentence reading and aerial photography interpretation (specifically designed to reflect IAF pilots' expertise in analyzing noisy low-contrast input). In concert with earlier suggestions, gains in visual processing speed are plausible to account, at least partially, for the observed training-induced improvements.

Increased gamma band activity for lateral interactions in humans.

Collinear facilitation of contrast sensitivity supported by lateral interactions within primary visual cortex is implicated in contour and object perception, with neural correlates in several frequency bands. Although higher component of the ERP power spectrum, the gamma-band, is postulated to reflect object representation, attention and memory, its neuronal source has been questioned, suggesting it is an artifact reflecting saccadic eye movements. Here we explored the gamma-band activity during collinear facilitation with no saccade-related confounds. We used single-trial spectral analysis of ERP in occipital channels in a time-window of nearly complete saccadic suppression and discarded sporadic trials containing saccades, in order to avoid saccadic artifacts. Although converging evidence suggests that gamma-band oscillations emerge from local excitatory-inhibitory balance involving GABAergic inhibition, here we show activity amplification during facilitatory collinear interactions, presumably dominated by excitations, in the gamma-band 150-350 milliseconds following onset of low near-threshold contrast stimulus. This result highlights the potential role of gamma-band oscillations in neuronal encoding of basic processes in visual perception. Thus, our findings suggest that gamma-band ERP spectrum analysis may serve as a useful and reliable tool for exploring basic perception, both in normal adults and in special populations.

Gains following perceptual learning are closely linked to the initial visual acuity.

The goal of the present study was to evaluate the dependence of perceptual learning gains on initial visual acuity (VA), in a large sample of subjects with a wide range of VAs. A large sample of normally sighted and presbyopic subjects (N = 119; aged 40 to 63) with a wide range of uncorrected near visual acuities (VA, -0.12 to 0.8 LogMAR), underwent perceptual learning. Training consisted of detecting briefly presented Gabor stimuli under spatial and temporal masking conditions. Consistent with previous findings, perceptual learning induced a significant improvement in near VA and reading speed under conditions of limited exposure duration. Our results show that the improvements in VA and reading speed observed following perceptual learning are closely linked to the initial VA, with only a minor fraction of the observed improvement that may be attributed to the additional sessions performed by those with the worse VA.

Binocular summation of chance decisions.

Seeing with two eyes usually helps one respond faster. Here we show that with ambiguous stimuli, binocular viewing can paradoxically slow down reaction time. This is explained by the observers basing their decision on a noisy neuronal representation within the visual system, with the added noise breaking the symmetry between the two possible interpretations. Binocular integration improves the representation by reducing the noise, increasing ambiguity, and decision time. The neuronal Accumulator (Race) model is applied to quantify the underlying binocular integration. The model accounts for the distributions of reaction times, and predicts suboptimal integration between eyes. We conclude that under ambiguous stimulation neuronal noise within the visual system determines responses.

Crowding is proportional to visual acuity in young and aging eyes.

Spatial crowding decreases object recognition and conscious visual perception in clutter. In a previous study we used brief presentation times to reveal the effects of a crowded presentation in the fovea. Here we aimed to test the relationships between varying visual acuity (VA) and crowding in the fovea, under the assumption that in uncorrected presbyopia, the processing is relatively normal, whereas the retinal input is blurred. We tested whether normal participants whose near VA is gradually reduced due to age-related deterioration (presbyopia, or "aging eye") will show an acuity-dependent increase in foveal crowding. We used brief presentations and acuity-threshold letter targets in order to magnify the crowding-effect amplitude in the fovea. A total of 195 participants with an age range of 20-68 years and an average of 44.3 ± 11.7 years (M ± SD) were divided into four age groups, all without any optical correction for the near distance. Our findings show that crowding is proportional to VA. This proportionality is affected by VA-age dependency, with a nonlinear S-shaped pattern: A steep VA reduction begins to develop, which is compatible with the normal onset age of presbyopia symptoms and a saturation in the VA-age dependency in the oldest age group, for which we propose a VA-eccentricity account. Finally, there is a high variance in the crowding amplitude in the young, even before the onset age of presbyopia symptoms, suggesting crowding conditions with limited presentation times as a highly sensitive measure of VA, which predicts visual performance in complex tasks, such as reading.

Training on spatiotemporal masking improves crowded and uncrowded visual acuity.

Spatial crowding impairs conscious visual perception and object recognition in clutter.Short presentation times produce crowding in the normal fovea, in young participants and in uncorrected presbyopes ("aging eye"), measured as reduced visual acuity (VA). On the other hand, perceptual learning improves near VA in healthy young adults, in presbyopia, and in amblyopia. Here we aimed at exploring the effects of perceptual training on crowded VA in uncorrected presbyopes with naturally decreased VA, with two specific objectives: (a) to objectively measure crowded VA, taking advantage of the natural deterioration of near visual acuity from being normal or better than normal (i.e., 20/20 or better) in young participants to naturally decreasing in uncorrected presbyopes; and (b) to explore whether perceptual training previously shown to improve visual functions as complex as reading will affect crowded VA. Visual acuity was measured under crowded and uncrowded conditions by having subjects identify letters presented for short durations ranging from 34 to 116 msec. Training consisted of detecting brief Gabor stimuli under spatial and temporal masking conditions, using the GlassesOff mobile application (GlassesOff, Inc., New York, NY)on iOS devices from a distance of 40 cm. Before training, a robust reduction in crowded VA was found in the fovea of presbyopes. Training resulted in significant improvement of letter identification under both crowded and uncrowded VA conditions for all stimulus durations. After training, the crowded condition threshold reached the level of the uncrowded threshold measured before training. Thus, training enabled the subjects to overcome the effect of reduced VA under the crowded condition. We suggest that more efficient spatial and temporal processing induced by perceptual learning allows one to improve crowded VA, including that found on naturally reduced near VA, and that this effect may transfer to improve complex visual functions, such as reading and object recognition.

ADHD subjects fail to suppress eye blinks and microsaccades while anticipating visual stimuli but recover with medication.

Oculomotor behavior and parameters are known to be affected by the allocation of attention and could potentially be used to investigate attention disorders. We explored the oculomotor markers of Attention-deficit/hyperactivity disorder (ADHD) that are involuntary and quantitative and that could be used to reveal the core-affected mechanisms, as well as be used for differential diagnosis. We recorded eye movements in a group of 22 ADHD-diagnosed patients with and without medication (methylphenidate) and in 22 control observers while performing the test of variables of attention (t.o.v.a.). We found that the average microsaccade and blink rates were higher in the ADHD group, especially in the time interval around stimulus onset. These rates increased monotonically over session time for both groups, but with significantly faster increments in the unmedicated ADHD group. With medication, the level and time course of the microsaccade rate were fully normalized to the control level, regardless of the time interval within trials. In contrast, the pupil diameter decreased over time within sessions and significantly increased above the control level with medication. We interpreted the suppression of microsaccades and eye blinks around the stimulus onset as reflecting a temporal anticipation mechanism for the transient allocation of attention, and their overall rates as inversely reflecting the level of arousal. We suggest that ADHD subjects fail to maintain sufficient levels of arousal during a simple and prolonged task, which limits their ability to dynamically allocate attention while anticipating visual stimuli. This impairment normalizes with medication and its oculomotor quantification could potentially be used for differential diagnosis.

The activity in the contralateral primary motor cortex, dorsal premotor and supplementary motor area is modulated by performance gains.

There is growing experimental evidence that the engagement of different brain areas in a given motor task may change with practice, although the specific brain activity patterns underlying different stages of learning, as defined by kinematic or dynamic performance indices, are not well understood. Here we studied the change in activation in motor areas during practice on sequences of handwriting-like trajectories, connecting four target points on a digitizing table "as rapidly and as accurately as possible" while lying inside an fMRI scanner. Analysis of the subjects' pooled kinematic and imaging data, acquired at the beginning, middle, and end of the training period, revealed no correlation between the amount of activation in the contralateral M1, PM (dorsal and ventral), supplementary motor area (SMA), preSMA, and Posterior Parietal Cortex (PPC) and the amount of practice per-se. Single trial analysis has revealed that the correlation between the amount of activation in the contralateral M1 and trial mean velocity was partially modulated by performance gains related effects, such as increased hand motion smoothness. Furthermore, it was found that the amount of activation in the contralateral preSMA increased when subjects shifted from generating straight point-to-point trajectories to their spatiotemporal concatenation into a smooth, curved trajectory. Altogether, our results indicate that the amount of activation in the contralateral M1, PMd, and preSMA during the learning of movement sequences is correlated with performance gains and that high level motion features (e.g., motion smoothness) may modulate, or even mask correlations between activity changes and low-level motion attributes (e.g., trial mean velocity).

Training the brain to overcome the effect of aging on the human eye.

Presbyopia, from the Greek for aging eye, is, like death and taxes, inevitable. Presbyopia causes near vision to degrade with age, affecting virtually everyone over the age of 50. Presbyopia has multiple negative effects on the quality of vision and the quality of life, due to limitations on daily activities - in particular, reading. In addition presbyopia results in reduced near visual acuity, reduced contrast sensitivity, and slower processing speed. Currently available solutions, such as optical corrections, are not ideal for all daily activities. Here we show that perceptual learning (repeated practice on a demanding visual task) results in improved visual performance in presbyopes, enabling them to overcome and/or delay some of the disabilities imposed by the aging eye. This improvement was achieved without changing the optical characteristics of the eye. The results suggest that the aging brain retains enough plasticity to overcome the natural biological deterioration with age.

Learning to be fast: gain accuracy with speed.

Our recent neurophysiological findings provided evidence for collinear facilitation in detecting low-contrast Gabor patches (GPs) and for the abolishment of these collinear interactions by backward masking (BM) (Sterkin et al., 2008; Sterkin, Yehezkel, Bonneh, et al., 2009). We suggested that the suppression induced by the BM eliminates the collinear facilitation. Moreover, our recent study showed that training on a BM task overcomes the BM effect, hence, improves the processing speed (Polat, 2009). Here we applied training on detecting a target that is followed by BM in order to study whether reinforced facilitatory interactions can overcome the suppressive effects induced by BM. Event-Related Potentials (ERPs) were recorded before and after ten training sessions performed on different days. Low-contrast, foveal target GP was simultaneously flanked by two collinear high-contrast GPs. In the BM task, another identical mask was presented at different time-intervals (ISIs). Before training, BM induced suppression of target detection, at the ISI of 50 ms, in agreement with earlier behavioral findings. This ISI coincides with the active time-window of lateral interactions. After training, our results show a remarkable improvement in all behavioral measurements, including percent of correct responses, sensitivity (d'), reaction time (RT) and the decision criterion for this ISI. The ERP results show that before training,BM attenuated the physiological markers of facilitation at the same ISI of 50 ms, measured as the amplitude of the negative N1 peak (latency of 260 ms). After the training, the sensory representation, reflected by P1 peak, has not changed, consistent with the unchanged physical parameters of the stimulus. Instead, the shorter latency (by 20 ms, latency of 240 ms) and the increased amplitude of N1 represent the development of faster and stronger facilitatory lateral interactions between the target and the collinear flankers. Thus, previously effective backward masking became ineffective in disrupting the collinear facilitation. Moreover, a high-amplitude late peak (P4, latency of 610-630 ms) was not affected by training, however its high correlation with RT (95%) before training was significantly decreased (to 76%), consistent with a lower-level representation of a trained skill. We suggest that perceptual learning that strengthens collinear facilitation results in a faster processing speed.

Learning to adapt: Dynamics of readaptation to geometrical distortions.

The visual system can adapt to optical blur, whereby the adapted image is perceived as sharp. Here we show that adaptation reduces blur-induced biases in shape perception, with repeated adaptations (perceptual learning), leading to unbiased perception upon re-exposure to blur. Observers wore a cylindrical lens of +1.00 D on one eye, thus simulating monocular astigmatism. The other eye was either masked with a translucent blurred lens (monocular) or unmasked (dichoptic). Adaptation was tested in several repeated sessions with a proximity-grouping task, using horizontally or vertically arranged dot-arrays, without feedback, before, after, and throughout the adaptation period. A robust bias in global-orientation judgment was observed with the lens, in accordance with the blur axes. After the observer wore the lens for 2 h, there was no significant change in the bias, but after 4 h, the monocular condition, but not the dichoptic, resulted in reduced bias. The adaptation effect of the monocular 4-h adaptation was preserved, and even improved, when the lens was re-applied the next day, indicating learning. After-effects were observed under all experimental conditions except for the 4-h monocular condition, where learning took place. We suggest that, with long experience, adaptation is transferred to a long-term memory that can be instantly engaged when blur is re-applied, or disengaged when blur is removed, thus leaving no after-effects. The comparison between the monocular and dichoptic conditions indicates a binocular cortical site of plasticity.

Backward masking suppresses collinear facilitation in the visual cortex.

Perceptual facilitation in detecting low-contrast Gabor patches (GPs) is induced by collinearly oriented high-contrast flankers. Our recent Visual Evoked Potentials (VEPs) study provided new physiological evidence for these collinear interactions, reflected by nonlinear modulation of multiple waveform components and frequencies [Sterkin, A., Yehezkel, O., Bonneh, Y. S., Norcia, A., & Polat, U. (2008). Multi-component correlate for lateral collinear interactions in the human visual cortex. Vision Research, 48(15), 1641-1647]. Here we used VEPs to study the temporal structure of this process. Low-contrast, foveal target GP (T) was simultaneously flanked by two collinear high-contrast GPs with a spatial separation that induces facilitation of T (lateral masking, LM). Another mask, identical to LM, was presented at different time-intervals (ISIs) after LM (backward masking, BM-on-LM). The responses were compared to separate waveforms evoked by T-alone and mask-alone at different ISIs. BM canceled the physiological markers of facilitation at an ISI of 50 ms, in agreement with earlier psychophysical findings, whereas no BM effect on T-alone was observed. This ISI coincides with the active time-window of lateral interactions, confirming our working model. The waveform amplitude of the negative N1 peak of LM was modulated toward the linear prediction of no interactions and the spectrum was shifted toward suppression, with no evidence of facilitation. Moreover, the P1 peak amplitude of BM was decreased at the same ISI, indicating that there is a mutual interference in cortical representation of both events. Waveform subtraction between BM-on-LM and LM suggests a mechanism of extended persistence of the target representation underlying facilitation in LM. We suggest an explanation for the role of improved detection of collinear stimuli in grouping of contours.

Multi-component correlate for lateral collinear interactions in the human visual cortex.

Perceptual facilitation, a decrease in detection threshold for low-contrast Gabor patches (GPs) occurs when the GP is flanked by collinearly oriented high-contrast patches. There is earlier evidence suggesting a spatial architecture of excitatory and inhibitory interactions. Here we used Visual Evoked Potentials (VEPs) to study the temporal structure of this process. We measured VEPs elicited by a foveal near-threshold target GP presented in isolation (T), T in the presence of two flanking collinear high-contrast GPs (lateral masking, LM), or the flankers alone (F). Stimuli were presented for 50 ms every 1000 ms. The choice of the set parameters elicited behavioral facilitation of T detection. Significant modulation of peak amplitudes in LM compared with linearly summed waveforms elicited by T and F was found for five alternating polarity components, ranging from 65 to 290 ms after stimulus onset. In the frequency domain, suppression at lower frequencies (up to 0.8 log units) was followed by facilitation at higher frequencies (4-6 Hz, up to 0.8 log units). Although no differences in the latencies were found, lateral interactions were reflected by non-linear waveform modulation of multiple components and frequencies, including components as early as 65-75 ms. Spectrum analysis suggests that both suppression and facilitation may be found for the same configuration of stimuli, simultaneously, distributed at different temporal frequencies and/or sources. The physiological correlates of lateral interactions may thus originate at multiple sources, only some of which are explicitly facilitatory. The final perceptual outcome of this complex spatio-temporal representation is determined by combining sensory and cognitive factors.

Response similarity as a basis for perceptual binding.

Detection of low-contrast Gabor patches (GPs) is improved when flanked by collinear GPs, whereas suppression is observed for high-contrast GPs. The facilitation resembles the principles of Gestalt theory of perceptual organization. We propose a model for contour integration in the context of noise that incorporates a temporal element into this spatial architecture. The basic principles are (1) the response increases with increasing contrast, whereas the latency decreases; (2) activity-dependent interactions: facilitation for low and suppression for high activity; (3) the variance increases with contrast for responses, rates, and latency; and (4) inhibition has a shorter time constant than excitation. When a texture of randomly oriented GPs is presented, the response to every element decreases due to fast inhibition between the neighboring elements, shifting the activity toward the range of collinear facilitation. Next, the slower excitation induces selective facilitation along the contour elements. Consequently, the response to the contour increases, whereas the variance of the rate and latency decreases, providing better temporal correlation between the contour elements. Thus, collinear facilitation increases the saliency of contours. Our model may suggest a solution to the binding problem by bridging between the temporal and spatial aspects of lateral interactions that determine the encoding of perceptual grouping.

Spatio-temporal low-level neural networks account for visual masking.

T emporal masking is a paradigm that is widely used to study visual information processing. When a mask is presented, typically within less than 100 msec before or after the target, the response to the target is reduced. The results of our psychophysical and visual evoked potential (VEP) experiments show that the masking effect critically depends on a combination of several factors: (1) the processing time of the target, (2) the order of presentation of the target and the mask, and (3) the spatial arrangement of the target and the mask. Thus, the masking effect depends on the spatial-temporal combination of these factors. Suppression was observed when the mask was positioned within a spatial range that was found to evoke inhibition, and when the temporal separation between the target and the mask was short. In contrast, lateral facilitation was observed when the mask was presented at a spatial separation that did not evoke inhibition from the target's vicinity and with a temporal sequence that preceded the target, or when it was presented simultaneously with it, but not when the target preceded the mask. We propose that masking effects, either suppression or facilitation, reflect integration into the spatial and the temporal domains of the feedforward response to the target and the lateral inputs evoked by the mask (excitatory and/or inhibitory). Because the excitation evoked by the mask develops and propagates slowly from the mask's location to the target's location, it lags behind the response to the target. On the other hand, inhibition that is produced in the vicinity of the target evolves more rapidly and follows the onset and offset of the stimulus more closely. Thus, lateral excitation that overcomes the inhibition may facilitate the grouping of local elements into a global percept by increasing the survivability of the object and its accessibility for perceptual awareness.

Retinotopic axis specificity and selective clustering of feedback projections from V2 to V1 in the owl monkey.

Cortical maps and feedback connections are ubiquitous features of the visual cerebral cortex. The role of the feedback connections, however, is unclear. This study was aimed at revealing possible organizational relationships between the feedback projections from area V2 and the functional maps of orientation and retinotopy in area V1. Optical imaging of intrinsic signals was combined with cytochrome oxidase histochemistry and connectional anatomy in owl monkeys. Tracer injections were administered at orientation-selective domains in regions of pale and thick cytochrome oxidase stripes adjacent to the border between these stripes. The feedback projections from V2 were found to be more diffuse than the intrinsic horizontal connections within V1, but they nevertheless demonstrated clustering. The clusters of feedback axons projected preferentially to interblob cytochrome oxidase regions. The distribution of preferred orientations of the recipient domains in V1 was broad but appeared biased toward values similar to the preferred orientation of the projecting cells in V2. The global spatial distribution of the feedback projections in V1 was anisotropic. The major axis of anisotropy was systematically parallel to a retinotopic axis in V1 corresponding to the preferred orientation of the cells of origin in V2. We conclude that the feedback connections from V2 to V1 might play a role in enhancing the response in V1 to collinear contour elements.