tRNS boosts visual perceptual learning in participants with bilateral macular degeneration.

Perceptual learning (PL) has shown promise in enhancing residual visual functions in patients with age-related macular degeneration (MD), however it requires prolonged training and evidence of generalization to untrained visual functions is limited. Recent studies suggest that combining transcranial random noise stimulation (tRNS) with perceptual learning produces faster and larger visual improvements in participants with normal vision. Thus, this approach might hold the key to improve PL effects in MD. To test this, we trained two groups of MD participants on a contrast detection task with (n = 5) or without (n = 7) concomitant occipital tRNS. The training consisted of a lateral masking paradigm in which the participant had to detect a central low contrast Gabor target. Transfer tasks, including contrast sensitivity, near and far visual acuity, and visual crowding, were measured at pre-, mid and post-tests. Combining tRNS and perceptual learning led to greater improvements in the trained task, evidenced by a larger increment in contrast sensitivity and reduced inhibition at the shortest target to flankers' distance. The overall amount of transfer was similar between the two groups. These results suggest that coupling tRNS and perceptual learning has promising potential applications as a clinical rehabilitation strategy to improve vision in MD patients.

Training With Simulated Scotoma Leads to Behavioral Improvements Through at Least Two Distinct Mechanisms.

Purpose: Individuals with central vision loss due to macular degeneration (MD) often spontaneously develop a preferred retinal locus (PRL) outside the area of retinal damage, which they use instead of the fovea. Those who develop a stable PRL are more successful at coping with their vision loss. However, it is unclear whether improvements in visual performance at the PRL are specific to that retinal location or are also observed in other parts of the retina. Perceptual learning literature suggests that the retinal specificity of these effects provides insight about the mechanisms involved. Better understanding of these mechanisms is necessary for the next generation of interventions and improved patient outcomes. Methods: To address this, we trained participants with healthy vision to develop a trained retinal locus (TRL), analogous to the PRL in patients. We trained 24 participants on a visual search task using a gaze-contingent display to simulate a central scotoma. Results: Results showed retinotopically specific improvements in visual crowding only at the TRL; however, visual acuity improved in both the TRL and in an untrained retinal locus. Conclusions: These results suggest that training with an artificial scotoma involves multiple mechanistic levels, some location-specific and some not, and that simulated scotoma training paradigms likely influence multiple mechanisms simultaneously. Eye movement analysis suggests that the non-retinotopic learning effects may be related to improvements in the capability to maintain a stable gaze during stimulus presentation. This work suggests that effective interventions promoting peripheral viewing may influence multiple mechanisms simultaneously.

Consistency of preferred retinal locus across tasks and participants trained with a simulated scotoma.

After loss of central vision following retinal pathologies such as macular degeneration (MD), patients often adopt compensatory strategies including developing a "preferred retinal locus" (PRL) to replace the fovea in tasks involving fixation. A key question is whether patients develop multi-purpose PRLs or whether their oculomotor strategies adapt to the demands of the task. While most MD patients develop a PRL, clinical evidence suggests that patients may develop multiple PRLs and switch between them according to the task at hand. To understand this, we examined a model of central vision loss in normally seeing individuals and tested whether they used the same or different PRLs across tasks after training. Nineteen participants trained for 10 sessions on contrast detection while in conditions of gaze-contingent, simulated central vision loss. Before and after training, peripheral looking strategies were evaluated during tasks measuring visual acuity, reading abilities and visual search. To quantify strategies in these disparate, naturalistic tasks, we measured and compared the amount of task-relevant information at each of 8 equally spaced, peripheral locations, while participants performed the tasks. Results showed that some participants used consistent viewing strategies across tasks whereas other participants' strategies differed depending on task. This novel method allows quantification of peripheral vision use even in relatively ecological tasks. These results represent one of the first examinations of peripheral viewing strategies across tasks in simulated vision loss. Results suggest that individual differences in peripheral looking strategies following simulated central vision loss may model those developed in pathological vision loss.

Oculomotor changes following learned use of an eccentric retinal locus.

People with bilateral central vision loss sometimes develop a new point of oculomotor reference called a preferred retinal locus (PRL) that is used for fixating and planning saccadic eye movements. How individuals develop and learn to effectively use a PRL is still debated; in particular, the time course of learning to plan saccades using a PRL and learning to stabilize peripheral fixation at the desired location. Here we address knowledge limitations through research describing how eye movements change as a person learns to adopt an eccentric retinal locus. Using a gaze-contingent, eye tracking-guided paradigm to simulate central vision loss, 40 participants developed a PRL by engaging in an oculomotor and visual recognition task. After 12 training sessions, significant improvements were observed in six eye movement metrics addressing different aspects involved in learning to use a PRL: first saccade landing dispersion, saccadic re-referencing, saccadic precision, saccadic latency, percentage of useful trials, and fixation stability. Importantly, our analyses allowed separate examination of the stability of target fixation separately from the dispersion and precision of the landing location of saccades. These measures explained 50% of the across-subject variance in accuracy. Fixation stability and saccadic precision showed a strong, positive correlation. Although there was no statistically significant difference in rate of learning, individuals did tend to learn saccadic precision faster than fixation stability. Saccadic precision was also more associated with accuracy than fixation stability for the behavioral task. This suggests effective intervention strategies in low vision should address both fixation stability and saccadic precision.

Perspectives on the Combined Use of Electric Brain Stimulation and Perceptual Learning in Vision.

A growing body of literature offers exciting perspectives on the use of brain stimulation to boost training-related perceptual improvements in humans. Recent studies suggest that combining visual perceptual learning (VPL) training with concomitant transcranial electric stimulation (tES) leads to learning rate and generalization effects larger than each technique used individually. Both VPL and tES have been used to induce neural plasticity in brain regions involved in visual perception, leading to long-lasting visual function improvements. Despite being more than a century old, only recently have these techniques been combined in the same paradigm to further improve visual performance in humans. Nonetheless, promising evidence in healthy participants and in clinical population suggests that the best could still be yet to come for the combined use of VPL and tES. In the first part of this perspective piece, we briefly discuss the history, the characteristics, the results and the possible mechanisms behind each technique and their combined effect. In the second part, we discuss relevant aspects concerning the use of these techniques and propose a perspective concerning the combined use of electric brain stimulation and perceptual learning in the visual system, closing with some open questions on the topic.

Contrast adaptation of flankers reduces collinear facilitation and inhibition.

Increase (facilitation) or decrease (inhibition) of contrast sensitivity for a Gabor patch presented between two collinear flankers is a well-studied contextual modulation phenomenon. It has been suggested that this effect has its neural bases in the primary visual cortex, specifically the horizontal connections between hypercolumns with similar orientation and spatial frequency selectivity. Another typical phenomenon dependent on early visual areas is contrast adaptation, in which the neural response to a contrast stimulus is decreased after exposure. Here, we investigated the effect of contrast adaptation of the flankers on the magnitude of collinear modulation by testing whether contrast adaptation reduced collinear facilitation and collinear inhibition. Results showed dissociation in the effect of collinear flanker adaptation, which increased contrast thresholds for the target in the facilitatory configuration and reduced them in the inhibitory configuration. Moreover, the effect was specific for the collinear configuration, since contrast adaptation of orthogonal flankers did not affect the contrast of the target, pointing towards the involvement of early visual units specific for orientation. Surprisingly, the same pattern of results was also confirmed when the inhibitory configuration was tested with low-contrast flankers, indicating that the effect of adaptation does not depend on a decrease in perceived contrast of the flankers. Taken together, these results suggest that contrast adaptation disrupts collinear modulation and that contrast thresholds can be affected by adapting portions of the visual field outside the receptive field of the units processing the contrast of the target (i.e., the flankers).

Perspective on Vision Science-Informed Interventions for Central Vision Loss.

Pathologies affecting central vision, and macular degeneration (MD) in particular, represent a growing health concern worldwide, and the leading cause of blindness in the Western World. To cope with the loss of central vision, MD patients often develop compensatory strategies, such as the adoption of a Preferred Retinal Locus (PRL), which they use as a substitute fovea. However, visual acuity and fixation stability in the visual periphery are poorer, leaving many MD patients struggling with tasks such as reading and recognizing faces. Current non-invasive rehabilitative interventions are usually of two types: oculomotor, aiming at training eye movements or teaching patients to use or develop a PRL, or perceptual, with the goal of improving visual abilities in the PRL. These training protocols are usually tested over a series of outcome assessments mainly measuring low-level visual abilities (visual acuity, contrast sensitivity) and reading. However, extant approaches lead to mixed success, and in general have exhibited large individual differences. Recent breakthroughs in vision science have shown that loss of central vision affects not only low-level visual abilities and oculomotor mechanisms, but also higher-level attentional and cognitive processes. We suggest that effective interventions for rehabilitation after central vision loss should then not only integrate low-level vision and oculomotor training, but also take into account higher level attentional and cognitive mechanisms.

Binding Mechanisms in Visual Perception and Their Link With Neural Oscillations: A Review of Evidence From tACS.

Neurophysiological studies in humans employing magneto- (MEG) and electro- (EEG) encephalography increasingly suggest that oscillatory rhythmic activity of the brain may be a core mechanism for binding sensory information across space, time, and object features to generate a unified perceptual representation. To distinguish whether oscillatory activity is causally related to binding processes or whether, on the contrary, it is a mere epiphenomenon, one possibility is to employ neuromodulatory techniques such as transcranial alternating current stimulation (tACS). tACS has seen a rising interest due to its ability to modulate brain oscillations in a frequency-dependent manner. In the present review, we critically summarize current tACS evidence for a causal role of oscillatory activity in spatial, temporal, and feature binding in the context of visual perception. For temporal binding, the emerging picture supports a causal link with the power and the frequency of occipital alpha rhythms (8-12 Hz); however, there is no consistent evidence on the causal role of the phase of occipital tACS. For feature binding, the only study available showed a modulation by occipital alpha tACS. The majority of studies that successfully modulated oscillatory activity and behavioral performance in spatial binding targeted parietal areas, with the main rhythms causally linked being the theta (~7 Hz) and beta (~18 Hz) frequency bands. On the other hand, spatio-temporal binding has been directly modulated by parieto-occipital gamma (~40-60 Hz) and alpha (10 Hz) tACS, suggesting a potential role of cross-frequency coupling when binding across space and time. Nonetheless, negative or partial results have also been observed, suggesting methodological limitations that should be addressed in future research. Overall, the emerging picture seems to support a causal role of brain oscillations in binding processes and, consequently, a certain degree of plasticity for shaping binding mechanisms in visual perception, which, if proved to have long lasting effects, can find applications in different clinical populations.

We don't all look the same; detailed examination of peripheral looking strategies after simulated central vision loss.

Loss of central vision can be compensated for in part by increased use of peripheral vision. For example, patients with macular degeneration or those experiencing simulated central vision loss tend to develop eccentric viewing strategies for reading or other visual tasks. The factors driving this learning are still unclear and likely involve complex changes in oculomotor strategies that may differ among people and tasks. Although to date a number of studies have examined reliance on peripheral vision after simulated central vision loss, individual differences in developing peripheral viewing strategies and the extent to which they transfer to untrained tasks have received little attention. Here, we apply a recently published method of characterizing oculomotor strategies after central vision loss to understand the time course of changes in oculomotor strategies through training in 19 healthy individuals with a gaze-contingent display obstructing the central 10° of the visual field. After 10 days of training, we found mean improvements in saccadic re-referencing (the percentage of trials in which the first saccade placed the target outside the scotoma), latency of target acquisition (time interval between target presentation and a saccade putting the target outside the scotoma), and fixation stability. These results are consistent with participants developing compensatory oculomotor strategies as a result of training. However, we also observed substantial individual differences in the formation of eye movement strategies and the extent to which they transferred to an untrained task, likely reflecting both variations in learning rates and patterns of learning. This more complete characterization of peripheral looking strategies and how they change with training may help us understand individual differences in rehabilitation after central vision loss.

Combining fixation and lateral masking training enhances perceptual learning effects in patients with macular degeneration.

Macular degeneration (MD), a retinal disease affecting central vision, represents the leading cause of visual impairment in the Western world, and MD patients face severe limitations in daily activities like reading and face recognition. A common compensation strategy adopted by these patients involves the use of a region in the spared peripheral retina as a new fixation spot and oculomotor reference (preferred retinal locus, or PRL). Still, peripheral vision is characterized by poorer visual acuity, fixation stability, and larger crowding zones that further hinder processes like object recognition, visual search, and reading. Perceptual learning (PL) has been successfully used to improve visual acuity in mild visual conditions (e.g., presbyopia, amblyopia and myopia), but results in MD are less clear, often showing limited generalization of learning, unlike what is observed in a healthy population. A possible reason is the suboptimal fixation in the PRL that might prevent patients from processing the briefly presented training stimuli. Following this hypothesis, we trained five MD patients and four age- and eccentricity-matched controls with a protocol that combined contrast detection and a task previously used to train fixation stability. Results showed transfer of learning to crowding reduction, reading speed, and visual acuity in both MD patients and controls. These results suggest that in the case of central vision loss, PL training might benefit from the integration of oculomotor components to optimize the effect of training and promote transfer of learning to other visual functions.

A method to characterize compensatory oculomotor strategies following simulated central vision loss.

Loss of central vision can be partially compensated by increased use of peripheral vision. For example, patients experiencing central vision loss due to disease (macular degeneration) or healthy participants trained with simulated central vision loss, tend to develop eccentric fixation spots for reading or other visual tasks. In both patients and in simulated conditions, there are substantial individual variations in the effective use of the periphery. The factors driving these individual differences are still unclear. Although early approaches have described some dimensions of these strategies, the field is still in its initial stages and important elements are often conflated when examining gaze patterns. Here, we propose a systematic approach to characterize oculomotor strategies in cases of central vision loss that distinguishes different components: saccadic re-referencing, saccadic precision, first saccade landing dispersion, fixation stability, latency of target acquisition, and percentage of trials that are useful. We tested this approach in healthy individuals trained with a gaze-contingent display obstructing the central 10 degrees of the visual field. The use of simulated scotoma helps overcome known challenges in clinical research, from recruitment and compliance to the diverse extent and nature of the visual loss. Importantly, this approach offers the ability to examine oculomotor strategies as they develop in controlled settings where viewing conditions are similar across participants. Results show substantial differences in characteristics of peripheral looking strategies, both across trials and individuals. This more complete characterization of peripheral looking strategies can help us understand individual differences in rehabilitation after central vision loss.

Short-term Perceptual Learning Game Does Not Improve Patching-Resistant Amblyopia in Older Children.

PURPOSE: To investigate self-administered, at-home use of a perceptual learning-based video game consisting of target detection of stimuli in different sizes, spatial frequency, orientation, and contrast as a potential dichoptic therapy to improve binocular function in amblyopic patients resistant to patching. METHODS: Children (ages 8 to 18 years) with strabismic and/or anisometropic amblyopia were recruited from a single institution. All participants (n = 25) were prescribed 6 weeks of patching for 2 hours per day, and those whose visual acuity did not improve were randomized to binocular perceptual learning (n = 7), monocular perceptual learning (n = 8), or patching (n = 10) groups for 8 weeks in this prospective cohort study. After an 8-week long period of treatment cessation, during which participants stopped patching or perceptual learning, participants in the patching group were randomized to binocular or monocular perceptual learning training; those in the perceptual learning groups remained the same. Visual function was assessed by visual acuity, low contrast acuity, reading speed, stereoacuity, and binocularity; compliance was evaluated by exercise logs. RESULTS: There were no significant improvements in visual function parameters, which did not vary by treatment group. However, some visual outcomes, such as binocular summation and reading speed, correlated positively with compliance to perceptual learning therapy. CONCLUSIONS: At-home, self-administered use of this perceptual learning-based video game-based visual training does not consistently add therapeutic benefit to those with amblyopia resistant to patching. Future investigation is required to determine whether methods to increase compliance will lead to more reliable outcomes. [J Pediatr Ophthalmol Strabismus. 2020;57(3):176-184.].

tRNS effects on visual contrast detection.

In recent years, transcranial electrical stimulation (tES) has been used to improve cognitive and perceptual abilities and to boost learning. In the visual domain, transcranial random noise stimulation (tRNS), a type of tES in which electric current is randomly alternating in between two electrodes at high frequency, has shown potential in inducing long lasting perceptual improvements when coupled with tasks such as contrast detection. However, its cortical mechanisms and online effects have not been fully understood yet, and it is still unclear whether these long-term improvements are due to early-stage perceptual enhancements of contrast sensitivity or later stage mechanisms such as learning consolidation. Here we tested tRNS effects on multiple spatial frequencies and orientation, showing that tRNS enhances detection of a low contrast Gabor, but only for oblique orientation and high spatial frequency (12 cycles per degree of visual angle). No improvement was observed for low contrast and vertical stimuli. These results indicate that tRNS can enhance contrast sensitivity already after one training session, however this early onset is dependent on characteristics of the stimulus such as spatial frequency and orientation. In particular, the shallow depth of tRNS is likely to affect superficial layers of the visual cortex where neurons have higher preferred spatial frequencies than cells in further layers, while the lack of effect on vertical stimuli might reflect the optimization of the visual system to see cardinally oriented low contrast stimuli, leaving little room for short-term improvement. Taken together, these results suggest that online tRNS effects on visual perception are the result of a complex interaction between stimulus intensity and cortical anatomy, consistent with previous literature on brain stimulation.

tRNS boosts perceptual learning in peripheral vision.

Visual crowding, the difficulty of recognizing elements when surrounded by similar items, is a widely studied perceptual phenomenon and a trademark characteristic of peripheral vision. Perceptual Learning (PL) has been shown to reduce crowding, although a large number of sessions is required to observe significant improvements. Recently, transcranial random noise stimulation (tRNS) has been successfully used to boost PL in low-level foveal tasks (e.g., contrast detection, orientation) in both healthy and clinical populations. However, no studies so far combined tRNS with PL in peripheral vision during higher-level tasks. Thus, we investigated the effect of tRNS on PL and transfer in peripheral high-level visual tasks. We trained two groups (tRNS and sham) of normal-sighted participants in a peripheral (8° of eccentricity) crowding task over a short number of sessions (4). We tested both learning and transfer to untrained spatial locations, orientations, and tasks (visual acuity). After training, the tRNS group showed greater learning rate with respect to the sham group. For both groups, learning generalized to the same extent to the untrained retinal location and task. Overall, this paradigm has potential applications for patients suffering from central vision loss but further research is needed to elucidate its effect (i.e., increasing transfer and learning retention).

A New Look at Visual System Plasticity.

Reward-based learning is known to induce cortical plasticity in primary sensory areas. A new study by Goltstein, Meijer, and Pennartz [1] (eLife2018;7:e37683), adopting a dual-scale approach (single-unit and population level), shows how associative learning in mice tunes cortical processing, but unlike other primary sensory cortices it does not modify the retinotopic map.

Multi-line Adaptive Perimetry (MAP): A New Procedure for Quantifying Visual Field Integrity for Rapid Assessment of Macular Diseases.

PURPOSE: In order to monitor visual defects associated with macular degeneration (MD), we present a new psychophysical assessment called multiline adaptive perimetry (MAP) that measures visual field integrity by simultaneously estimating regions associated with perceptual distortions (metamorphopsia) and visual sensitivity loss (scotoma). METHODS: We first ran simulations of MAP with a computerized model of a human observer to determine optimal test design characteristics. In experiment 1, predictions of the model were assessed by simulating metamorphopsia with an eye-tracking device with 20 healthy vision participants. In experiment 2, eight patients (16 eyes) with macular disease completed two MAP assessments separated by about 12 weeks, while a subset (10 eyes) also completed repeated Macular Integrity Assessment (MAIA) microperimetry and Amsler grid exams. RESULTS: Results revealed strong repeatability of MAP and high accuracy, sensitivity, and specificity (0.89, 0.81, and 0.90, respectively) in classifying patient eyes with severe visual impairment. We also found a significant relationship in terms of the spatial patterns of performance across visual field loci derived from MAP and MAIA microperimetry. However, there was a lack of correspondence between MAP and subjective Amsler grid reports in isolating perceptually distorted regions. CONCLUSIONS: These results highlight the validity and efficacy of MAP in producing quantitative maps of visual field disturbances, including simultaneous mapping of metamorphopsia and sensitivity impairment. TRANSLATIONAL RELEVANCE: Future work will be needed to assess applicability of this examination for potential early detection of MD symptoms and/or portable assessment on a home device or computer.

Fast random motion biases judgments of visible and occluded motion speed.

Human sensitivity to speed differences is very high, and relatively high when one has to compare the speed of an object that disappears behind an occluder with a standard. Nevertheless, different speed illusions (by contrast, adaptation, dynamic visual noise) affect proper speed judgment for both visible and occluded moving objects. In the present study, we asked whether an illusion due to non-directional motion noise (random dynamic visual noise, rDVN) intervenes at the level of speed encoding, thus affecting speed discrimination, or at the level of speed decoding by non-sensory decision-making mechanisms, indexed by speed overestimation of visible and invisible motion. In Experiment 1, participants performing a temporal two-Alternative Forced Choice task, judged the speed of a target moving in front of the rDVN or a static visual noise (SVN). In Experiment 2 and 3, the target disappeared behind the rDVN/SVN, and participants reported whether the target reappeared early or late (Experiment 2), or the time to contact (TTC) with the end of the occluded trajectory (Experiment 3). In Experiment 1 and 2, we found that rDVN affected the point of subjective equality (pse) of the individual's psychometric function in a way indicating speed overestimation, while not affecting speed discrimination threshold (just noticeable differences, jnd). In Experiment 3 the rDVN reduced the TTC. Though not entirely consistent, our results suggest that a similar speed decoding mechanism, which read-out motion information to form a perceptual decision, operates regarding of whether motion is visible or invisible.

Effect of Varying Levels of Glare on Contrast Sensitivity Measurements of Young Healthy Individuals Under Photopic and Mesopic Vision.

Contrast sensitivity (CS), the ability to detect small spatial changes of luminance, is a fundamental aspect of vision. However, while visual acuity is commonly measured in eye clinics, CS is often not assessed. At issue is that tests of CS are not highly standardized in the field and that, in many cases, optotypes used are not sensitive enough to measure graduations of performance and visual abilities within the normal range. Here, in order to develop more sensitive measures of CS, we examined how CS is affected by different combinations of glare and ambient lighting in young healthy participants. We found that low levels of glare have a relatively small impact on vision under both photopic and mesopic conditions, while higher levels had significantly greater consequences on CS under mesopic conditions. Importantly, we found that the amount of glare induced by a standard built-in system (69 lux) was insufficient to induce CS reduction, but increasing to 125 lux with a custom system did cause a significant reduction and shift of CS in healthy individuals. This research provides important data that can help guide the use of CS measures that yield more sensitivity to characterize visual processing abilities in a variety of populations with ecological validity for non-ideal viewing conditions such as night time driving.

Rewarding objects appear larger but not brighter.

Whether reward can accentuate the perception of visual objects, that is, makes them appear larger than they really are, is a long-standing and controversial question. Here, we revisit this issue with a novel two-alternative forced-choice paradigm combining asymmetric reward schedule and task reversal. In a first experiment, participants (n = 27) choose the larger of two unequally rewarded objects in some sessions and the smaller one in other sessions. Response biases toward the most rewarding object differ significantly between the reversed tasks, revealing an influence of reward on perceived sizes. In a second experiment, participants (n = 27) indicate either the brighter or darker object. In contrast with the first experiment, response biases are similar between those reversed tasks, indicating that the perceived luminance is immune to reward manipulation. Together, these results reveal that if two objects are associated with different amounts of reward, participants will perceive the more rewarded object to be slightly larger, but not brighter, than the less rewarded one.