Cortical Reorganization After Optical Alignment in Strabismic Patients Outside of Critical Period.

Purpose: To measure visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortex organization, in older children and adults with horizontal concomitant strabismus before and after strabismus surgery. Methods: Using real-time eye tracking to ensure gaze-contingent display, we examined the peripheral visual crowding effects in older children and adults with horizontal concomitant strabismus but without amblyopia before and after strabismus surgery. Patients were asked to discriminate the orientation of the central tumbling E target letter with flankers arranged along the radial or tangential axis in the nasal or temporal hemifield at different eccentricities (5° or 10°). The critical spacing value, which is the minimum space between the target and the flankers required for correct discrimination, was obtained for comparisons before and after strabismus surgery. Results: Twelve individuals with exotropia (6 males, 21.75 ± 7.29 years, mean ± SD) and 15 individuals with esotropia (6 males, 24.13 ± 5.96 years) participated in this study. We found that strabismic individuals showed significantly larger critical spacing with nasotemporal asymmetry along the radial axis that related to the strabismus pattern, with exotropes exhibiting stronger temporal field crowding and esotropes exhibiting stronger nasal field crowding before surgical alignment. After surgery, the critical spacing was reduced and rebalanced between the nasal and temporal hemifields. Furthermore, the postoperative recovery of stereopsis was associated with the extent of nasotemporal balance of critical spacing. Conclusions: We find that optical realignment (i.e., strabismus surgery) can normalize the enlarged visual crowding effects, a reliable psychophysical index of cortical organization, in the peripheral visual field of older children and adults with strabismus and rebalance the nasotemporal asymmetry of crowding, promoting the recovery of postoperative stereopsis. Our results indicated a potential of experience-dependent cortical organization after axial alignment even for individuals who are out of the critical period of visual development, illuminating the capacity and limitations of optics on sensory plasticity and emphasizing the importance of ocular correction for clinical practice.

Visual Crowding Reveals Field- and Axis-Specific Cortical Miswiring After Long-Term Axial Misalignment in Strabismic Patients Without Amblyopia.

Purpose: Inspired by physiological and neuroimaging findings that revealed squint-induced modification of cortical volume and visual receptive field in early visual areas, we hypothesized that strabismic eyes without amblyopia manifest an increase in critical spacing of visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortical organization. Methods: We used real-time eye tracking to ensure gaze-contingent display and examined visual crowding in patients with horizontal concomitant strabismus (both esotropia and exotropia) but without amblyopia and age-matched normal controls. Results: Nineteen patients with exotropia (12 men, mean ± SD = 22.89 ± 7.82 years), 21 patients with esotropia (10 men, mean ± SD = 23.48 ± 6.95 years), and 14 age-matched normal controls (7 men, mean ± SD = 23.07 ± 1.07 years) participated in this study. We found that patients with strabismus without amblyopia showed significantly larger critical spacing with nasotemporal asymmetry in only the radial axis that related to the strabismus pattern, with exotropia exhibiting stronger temporal hemifield crowding and esotropia exhibiting stronger nasal hemifield crowding, in both the deviated and fixating eyes. Moreover, the magnitude of crowding change was related to the duration and degree of strabismic deviation. Conclusions: Using visual crowding as a psychophysical index of cortical organization, our study demonstrated significantly greater peripheral visual crowding with nasotemporal asymmetry in only the radial axis in patients with strabismus without amblyopia, indicating the existence of hemifield- and axis-specific miswiring of cortical processing in object recognition induced by long-term adaptation to ocular misalignment.

Psychophysical Reverse Correlation Revealed Broader Orientation Tuning and Prolonged Reaction Time in Amblyopia.

Purpose: Neural selectivity of orientation is a fundamental property of visual system. We aim to investigate whether and how the orientation selectivity changes in amblyopia. Methods: Seventeen patients with amblyopia (27.1 ± 7.1 years) and 18 healthy participants (25.1 ± 2.7 years) took part in this study. They were asked to continuously detect vertical gratings embedded in a stream of randomly oriented gratings. Using a technique of subspace reverse correlation, the orientation-time perceptive field (PF) for the atypical grating detection task was derived for each participant. Detailed comparisons were made between the PFs measured with the amblyopic and healthy eyes. Results: The PF of the amblyopic eyes showed significant differences in orientation and time domain compared with that of the normal eyes (cluster-based permutation test, ps < 0.05), with broader bandwidth of orientation tuning (31.41 ± 10.59 degrees [mean ± SD] vs. 24.76 ± 6.85 degrees, P = 0.039) and delayed temporal dynamics (483 ± 68 ms vs. 425 ± 58 ms, P = 0.015). None of the altered PF properties correlated with the contrast sensitivity at 1 cycle per degree (c/deg) in amblyopia. No difference in PFs between the dominant and non-dominant eyes in the healthy group was found. Conclusions: The altered orientation-time PF to the low spatial frequency and high contrast stimuli suggests amblyopes had coarser orientation selectivity and prolonged reaction time. The broader orientation tuning probably reflects the abnormal lateral interaction in the primary visual cortex, whereas the temporal delay might indicate a high level deficit.

Identifying Long- and Short-Term Processes in Perceptual Learning.

Practice makes perfect in almost all perceptual tasks, but how perceptual improvements accumulate remains unknown. Here, we developed a multicomponent theoretical framework to model contributions of both long- and short-term processes in perceptual learning. Applications of the framework to the block-by-block learning curves of 49 adult participants in seven perceptual tasks identified ubiquitous long-term general learning and within-session relearning in most tasks. More importantly, we also found between-session forgetting in the vernier-offset discrimination, face-view discrimination, and auditory-frequency discrimination tasks; between-session off-line gain in the visual shape search task; and within-session adaptation and both between-session forgetting and off-line gain in the contrast detection task. The main results of the vernier-offset discrimination and visual shape search tasks were replicated in a new experiment. The multicomponent model provides a theoretical framework to identify component processes in perceptual learning and a potential tool to optimize learning in normal and clinical populations.

General and Specific Effects of Stereo Learning.

Technological advancements in virtual reality challenge the human vision, especially stereopsis, a function, which characterizes how two eyes coordinate to form a unified three-dimensional (3D) representation of the external world and is found to be deficient in 30% of the normal population. Although a few previous studies have consistently found that the perceptual learning of stereopsis significantly improved stereoacuity, an underlying mechanism of stereo learning remains heavily debated. Here, we trained subjects with normal stereo vision (assessed with the FLY Stereo Acuity Test) to judge stereopsis containing three types of binocular disparity orders (i.e., zero-, first-, and second-order), aiming to systematically examine the characteristics and plasticity of stereo learning. Thirty subjects were randomly assigned to the three training groups (each for the zero-, first-, or second-order disparity separately). The disparity thresholds were measured before and after training. The disparity threshold was measured in 10 additional control subjects only at the pre- and post-training phase. Stereoscopic images were displayed through a shutter goggle, which is synchronized to a monitor. We found that the training significantly improved the zero-, first-, and second-order disparity threshold by 52.42, 36.28, and 14.9% in the zero-order training condition; 30.44, 63.74, and 21.07% in the first-order training condition; and 30.77, 25.19, and 75.12% in the second-order training condition, respectively. There was no significant improvement in the control group. Interestingly, the greatest improvements in the first- and second-order disparity threshold were found in the corresponding disparity training group; on the contrary, the improvements in the zero-order disparity threshold were comparable across all the three disparity training groups. Our findings demonstrated both general (related to the zero-order disparity) and specific improvements (related to the first- and second-order disparity) in stereo learning, suggesting that stereo training occurs at different visual processing stages and its effects might depend on the specific training sites.

Effect of physiological aging on binocular vision.

We see the world with two eyes. Binocular vision provides more ample information through interocular interaction. Previous studies have shown that aging impairs a variety of visual functions, but how aging affects binocular vision is still unclear. In this study, we measured three typical binocular functions-binocular combination, binocular rivalry, and stereo vision-to investigate aging-related effects on binocular vision in a relatively large sample (48 younger adults and 27 older adults) with normal or corrected-to-normal distance vision and no ophthalmological and mental diseases. We found that there were no consistent aging-related declines in binocular vision, with the worst effect on alternation frequency in binocular rivalry and no effect on binocular phase combination and stereo vision tested by Titmus. In addition, aging changed the correlation pattern among some of these binocular functions. These results reflected (at least partially) different aging-related mechanism(s) in binocular vision.

The effects of short-term light exposure on subjective affect and comfort are dependent on the lighting time of day.

Light, one of the key environmental components for both life and work, played significant role in subjective feelings (e.g. affect and comfort), but the exact effects and mechanisms were still to be determined. The present study screened thirty healthy adults (13 females, 22.45 ± 3.26 years) and examined subjective affect and comfort under short-term white lights with different combination of correlated color temperature (CCT) and illuminance at different times of day (e.g. morning, afternoon, and evening). Our results showed a significant interaction between illuminance level and time-of-day on subjective comfort. Participants felt more comfortable under 50 lx and 100 lx instead of 500 lx in the evening, and more comfortable under 500 lx in the morning and afternoon. In addition, a positive correlation between illuminance and comfort in the morning and a negative correlation between them in the evening were found. No significant effect of CCT on any subjective feeling was revealed. Our results necessitate the consideration of time-of-day in understanding lighting effects and application of healthy lighting in daily life.

A New Dichoptic Training Strategy Leads to Better Cooperation Between the Two Eyes in Amblyopia.

Recent clinical trials failed to endorse dichoptic training for amblyopia treatment. Here, we proposed an alternative training strategy that focused on reducing signal threshold contrast in the amblyopic eye under a constant and high noise contrast in the fellow eye (HNC), and compared it to a typical dichoptic strategy that aimed at increasing the tolerable noise contrast in the fellow eye (i.e., TNC strategy). We recruited 16 patients with amblyopia and divided them into two groups. Eight patients in Group 1 received the HNC training, while the other eight patients in Group 2 performed the TNC training first (Phase 1) and then crossed over to the HNC training (Phase 2). We measured contrast sensitivity functions (CSFs) separately in the amblyopic and fellow eyes when the untested eye viewed mean luminance (monocularly unmasked) or noise stimuli (dichoptically masked) before and after training at a particular frequency. The area under the log contrast sensitivity function (AULCSF) of masked and unmasked conditions, and dichoptic gain (the ratio of AULCSF of masked to unmasked condition) were calculated for each eye. We found that both dichoptic training paradigms substantially improved masked CSF, dichoptic gain, and visual acuity in the amblyopic eye. As opposed to the TNC paradigm, the HNC training produced stronger effects on masked CSFs, stereoacuity, dichoptic gain, and visual acuity in the amblyopic eye. Interestingly, the second-phase HNC training in Group 2 also induced further improvement in the masked contrast sensitivity and AULCSF in the amblyopic eye. We concluded that the HNC training strategy was more effective than the TNC training paradigm. Future design for dichoptic training should not only focus on increasing the tolerable noise contrast in the fellow eye but should also "nurture" the amblyopic eye under normal binocular viewing conditions and sustained interocular suppression.

General learning ability in perceptual learning.

Developing expertise in any field usually requires acquisition of a wide range of skills. Most current studies on perceptual learning have focused on a single task and concluded that learning is quite specific to the trained task, and the ubiquitous individual differences reflect random fluctuations across subjects. Whether there exists a general learning ability that determines individual learning performance across multiple tasks remains largely unknown. In a large-scale perceptual learning study with a wide range of training tasks, we found that initial performance, task, and individual differences all contributed significantly to the learning rates across the tasks. Most importantly, we were able to extract both a task-specific but subject-invariant component of learning, that accounted for 38.6% of the variance, and a subject-specific but task-invariant perceptual learning ability, that accounted for 36.8% of the variance. The existence of a general perceptual learning ability across multiple tasks suggests that individual differences in perceptual learning are not "noise"; rather, they reflect the variability of learning ability across individuals. These results could have important implications for selecting potential trainees in occupations that require perceptual expertise and designing better training protocols to improve the efficiency of clinical rehabilitation.

Aging affects gain and internal noise in the visual system.

Visual functions decline with age, but how aging degrades visual functions remains controversial. In the current study, the mechanisms underlying age-related visual declines were examined psychophysically. We developed an efficient method to quickly explore contrast sensitivity as a function of nine spatial frequencies at three levels of external noise in both young and old subjects. Fifty-two young and twenty-six old subjects have been screened for ophthalmological and mental diseases and participated in the experiment. Contrast sensitivity varied significantly with spatial frequency, age, and level of external noise. By adopting a nonlinear observer model, we decomposed contrast sensitivity into inefficiencies in internal additive noise, internal multiplicative noise, perceptual template gain, and/or system non-linearity. Model analysis revealed that aging impacts both internal additive noise and perceptual template gain, and such age-related degradation is tuned to spatial frequency, which is also a good predictor to discriminate old from young. The quick characterization of contrast sensitivity functions at different noise levels and the accompanying analysis developed in the current study may have profound application in other clinical populations.

Multi-Stage Cortical Plasticity Induced by Visual Contrast Learning.

Perceptual learning, the improved sensitivity via repetitive practice, is a universal phenomenon in vision and its neural mechanisms remain controversial. A central question is which stage of processing is changed after training. To answer this question, we measured the contrast response functions and electroencephalography (EEG) before and after ten daily sessions of contrast detection training. Behavioral results showed that training substantially improved visual acuity and contrast sensitivity. The learning effect was significant at the trained condition and partially transferred to control conditions. Event-related potential (ERP) results showed that training reduced the latency in both early and late ERPs at the trained condition. Specifically, contrast-gain-related changes were observed in the latency of P1, N1-P2 complex, and N2, which reflects neural changes across the early, middle, and high-level sensory stages. Meanwhile, response-gain-related changes were found in the latency of N2, which indicates stimulus-independent effect in higher-level stages. In sum, our findings indicate that learning leads to changes across different processing stages and the extent of learning and transfer may depend on the specific stage of information processing.

Author Correction: Efficient Characterization and Classification of Contrast Sensitivity Functions in Aging.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

No effects of anodal transcranial direct current stimulation on contrast sensitivity function.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a well-established non-invasive brain stimulation technique that has been widely applied to modulate cortical excitability in human brain. The results of previous tDCS studies on modulating contrast sensitivity, one of the most fundamental visual functions, were mixed. OBJECTIVE: We aim to systematically investigate the effects of anodal tDCS on contrast sensitivity functions (CSF), evaluate the responsiveness explanation of tDCS effects, and discuss results along with measurement precision. METHODS: We designed a single-blinded, sham-controlled within-subject study. Twenty-seven healthy adult subjects received three sets of 15 min tDCS (two 2-mA anodal and one sham) that delivered at Oz, with CSF measured before and after each tDCS stimulation. Experimental sessions were separated by at least twenty-four hours. CSF was assessed with a Bayesian procedure that accurately estimated CSF within minutes. The anodal tDCS-induced effect was gauged with the change in CSF after stimulation; responsiveness was indexed by correlation between CSF changes in different stimulation; precision was calculated from resampling. RESULTS: Our results indicated that neither the first nor the second session anodal tDCS altered the CSF significantly. Responsiveness was inconsistent between the two anodal sessions, indicating the usual responder/non-responder explanation of tDCS effects was unconvincing. Precision was less than 2 dB and constant throughout the whole experiment. CONCLUSIONS: The anodal tDCS, at least with two sessions, has no effect on modulating CSF. The absence of anodal tDCS effect on CSF was not due to subject's responsiveness to tDCS or measurement precision. More studies were needed to determine the optimal vision modulation configuration.

High reward enhances perceptual learning.

Studies of perceptual learning have revealed a great deal of plasticity in adult humans. In this study, we systematically investigated the effects and mechanisms of several forms (trial-by-trial, block, and session rewards) and levels (no, low, high, subliminal) of monetary reward on the rate, magnitude, and generalizability of perceptual learning. We found that high monetary reward can greatly promote the rate and boost the magnitude of learning and enhance performance in untrained spatial frequencies and eye without changing interocular, interlocation, and interdirection transfer indices. High reward per se made unique contributions to the enhanced learning through improved internal noise reduction. Furthermore, the effects of high reward on perceptual learning occurred in a range of perceptual tasks. The results may have major implications for the understanding of the nature of the learning rule in perceptual learning and for the use of reward to enhance perceptual learning in practical applications.

The effects of monocular training on binocular functions in anisometropic amblyopia.

Intensive monocular perceptual learning can improve visual acuity, contrast sensitivity, and vernier acuity in the amblyopic eye in adults with amblyopia. It is however not clear how much monocular training can enhance binocular visual functions. In the current study, we aimed to evaluate effects of monocular training on a variety of binocular functions. Nineteen anisometropic amblyopes (18.5±1.26yrs, mean±s.e.) were trained in a grating contrast detection task near each individual's cutoff spatial frequency for 6-10days (630 trials/day). Visual acuity, stereoacuity, monocular and binocular contrast sensitivity functions (CSF), binocular phase combination and binocular rivalry were tested before and after training. Although monocular training can improve visual acuity and contrast sensitivity and eye dominance of the amblyopic eye, the magnitudes of improvements did not correlate with each other; the impact of monocular training on binocular phase combination was not significant. The results strongly suggest that structured monocular and binocular training is needed to fully recover deficient visual functions in anisometropic amblyopia.

A complete investigation of monocular and binocular functions in clinically treated amblyopia.

The gold standard of a successful amblyopia treatment is full recovery of visual acuity (VA) in the amblyopic eye, but there has been no systematic study on both monocular and binocular visual functions. In this research, we aimed to quantify visual qualities with a variety of perceptual tasks in subjects with treated amblyopia. We found near stereoacuity and pAE dominance in binocular rivalry in "treated" amblyopia were largely comparable to those of normal subjects. CSF of the pAE remained deficient in high spatial frequencies. The binocular contrast summation ratio is significantly lower than normal standard. The interocular balance point is 34%, indicating that contrast in pAE is much less effective as the same contrast in pFE in binocular phase combination. Although VA, stereoacuity and binocular rivalry at low spatial frequency in treated amblyopes were normal or nearly normal, the pAE remained "lazy" in high frequency domain, binocular contrast summation, and interocular phase combination. Our results suggest that structured monocular and binocular training are necessary to fully recover deficient functions in amblyopia.

Efficient Characterization and Classification of Contrast Sensitivity Functions in Aging.

The contrast sensitivity function (CSF), delineating contrast sensitivity over a wide range of spatial frequencies, provides a comprehensive characterization of spatial vision and a sensitive test for many physiological and pathological processes. A precise CSF measurement tool for the aging population is of great theoretical and practical importance. In the current study, we tested whether the assumptions of the newly developed quick CSF method were valid and whether it can rapidly, reliably, and effectively evaluate CSFs in the aging population. The quick CSF method combines Bayesian adaptive inference with an information gain strategy to directly estimate four parameters that define the observer's CSF. Eighteen young and twenty-five old observers participated in the evaluation of the quick CSF method. All observers were screened for ophthalmological and mental diseases. Our results showed that the CSFs derived from the quick CSF method well matched with those from the traditional Ψ method, with excellent test-retest reliability. More importantly, the quick CSF method can accurately detect the difference of CSFs between the young and old groups. Aging significantly degrades contrast sensitivity. The quick CSF method demonstrates great potentials for both laboratory research and clinical applications in the aging population.

Frequency-dependent changes in the amplitude of low-frequency fluctuations in patients with Wilson's disease: a resting-state fMRI study.

To investigate the frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) in patients with Wilson's disease (WD). Resting-state function magnetic resonance imaging (R-fMRI) were employed to measure the amplitude of ALFF in 28 patients with WD and 27 matched normal controls. Slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) frequency bands were analyzed. Apart from the observation of atrophy in the cerebellum, basal ganglia, occipital gyrus, frontal gyrus, precentral gyrus, and paracentral lobule, we also found widespread differences in ALFF of the two bands in the medial frontal gyrus, inferior temporal gyrus, insula, basal ganglia, hippocampus/parahippocampal gyrus, and thalamus bilaterally. Compared to normal controls, WD patients had increased ALFF in the posterior lobe of the cerebellum, inferior temporal gyrus, brain stem, basal ganglia, and decreased ALFF in the anterior lobe of the cerebellum and medial frontal gyrus. Specifically, we observed that the ALFF abnormalities in the cerebellum and middle frontal gyrus were greater in the slow-5 than in the slow-4 band. Correlation analysis showed consistently positive correlations between urinary copper excretion (Cu), serum ceruloplasmin (CP) and ALFFs in the cerebellum. Our study suggests the accumulation of copper profoundly impaired intrinsic brain activity and the impairments seem to be frequency-dependent. These results provide further insights into the understanding of the pathophysiology of WD.

Perceptual learning improves neural processing in myopic vision.

Visual performance is jointly determined by the quality of optical transmission of the eye and neural processing in the visual system. An open question is: Can effects of optical defects be compensated by perceptual learning in neural processing? To address this question, we conducted a perceptual learning study on 23 observers with myopic vision, targeting high frequency deficits by training them in a monocular grating detection task in the non-dominant eye near their individual cutoff spatial frequencies. The contrast sensitivity function and visual acuity in both eyes (without optical correction) were assessed for all the observers in the training group before and after training, and for all the observers in the control group twice with a 10-day interval between the tests. In addition, the threshold versus external noise contrast function was measured for five observers in the training group before and after training. We found that (a) training significantly improved contrast sensitivity at the trained spatial frequency, visual acuity, and contrast sensitivity over a wide range of spatial frequencies in both eyes; (b) training did not lead to any significant refractive changes; (c) the mechanism of improvements was a combination of internal additive noise reduction and external noise exclusion; and (d) the improvements in visual acuity and contrast sensitivity were almost fully retained for at least four months in the three observers tested. These results suggest that perceptual learning may provide a potential noninvasive procedure to compensate for optical defects in mild to modest myopia.