Evaluation of visual plasticity in patients with refractive amblyopia treated using a visual perceptual learning system.

BACKGROUND: Amblyopia is a neurological deficit in binocular vision that affects 3% of the population and is the result of disruptions in early visual development. OBJECTIVE: In this study, we used a visual perceptual learning system for the short-term treatment of children with ametropic amblyopia and evaluated the clinical efficacy of this system in terms of visual plasticity. METHODS: We conducted a retrospective analysis of the clinical data of 114 children (228 eyes) with refractive amblyopia, who were aged 6.51 ± 1.51 years. Prior to the treatment, we evaluated all children with amblyopia using the visual information processing test. We determined the type of amblyopic defect according to the type of amblyopia, corrected visual acuity, and advanced visual function test results. Based on the type of defect, each child with amblyopia was given short-term visual perception training for 10 days. Finally, we compared the results of visual acuity and visual information processing tests before and after the treatment. RESULTS: The best-corrected visual acuity of patients was better after 10 days of visual training than that before training (P< 0.05). The perceptual eye position after training improved with statistically significant differences in horizontal and vertical perceptual eye position (both P< 0.05) compared to that before training. The number of amblyopic children without suppression in both eyes was 81 cases (71.1%) after training which was higher than that (65 cases, or 57.0%) before training, with a statistically significant difference (P< 0.05). Binocular fine stereopsis and dynamic stereopsis improved after training with a statistically significant difference (both P< 0.05). CONCLUSION: In this study, it was found that patients with amblyopia showed visual plasticity. Moreover, continuous visual perceptual learning improved the best-corrected visual acuity and recovered stereopsis in children with refractive amblyopia.

Metaplasticity: Dark exposure boosts local excitability and visual plasticity in adult human cortex.

An interlude of dark exposure for about 1 week is known to shift excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting plasticity and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies to humans remains elusive. Here, we used magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60 min of dark exposure, and measured binocular combination as a behavioural assay to assess visual plasticity in 14 normally sighted human adults. To induce neuroplastic changes in the observers, we introduced 60 min of monocular deprivation, which is known to temporarily shift sensory eye balance in favour of the previously deprived eye. We report that prior dark exposure for 60 min strengthens local excitability in V1 and boosts visual plasticity in normal adults. However, we show that it does not promote plasticity in amblyopic adults. Nevertheless, our findings are surprising, given the fact that the interlude is very brief. Interestingly, we find that the increased concentration of the excitatory neurotransmitter is not strongly correlated with the enhanced functional plasticity. Instead, the absolute degree of change in its concentration is related to the boost, suggesting that the dichotomy of cortical excitation and inhibition might not explain the physiological basis of plasticity in humans. We present the first evidence that an environmental manipulation that shifts cortical E/I balance can also act as a metaplastic facilitator for visual plasticity in humans. KEY POINTS: A brief interlude (60 min) of dark exposure increased the local concentration of glutamine/glutamate but not that of GABA in the visual cortex of adult humans. After dark exposure, the degree of the shift in sensory eye dominance in favour of the previously deprived eye from short-term monocular deprivation was larger than that from only monocular deprivation. The neurochemical and behavioural measures were associated: the magnitude of the shift in the concentration of glutamine/glutamate was correlated with the boost in perceptual plasticity after dark exposure. Surprisingly, the increase in the concentration of glutamine/glutamate was not correlated with the perceptual boost after dark exposure, suggesting that the physiological mechanism of how E/I balance regulates plasticity is not deterministic. In other words, an increased excitation did not unilaterally promote plasticity.

Characteristics and predictive factors of visual function improvements after monocular perceptual learning in amblyopia.

Monocular perceptual learning has shown promising performance in restoring visual function in amblyopes beyond the critical period in the laboratory. However, the treatment outcome is variable and indeterminate in actual clinical and neuroscientific practice. We aimed to explore the efficacy of monocular perceptual learning in the clinical setting. By combining continuous monitoring of perceptual learning and clinical measurements, we evaluated the efficacy and characteristics of visual acuity and contrast sensitivity function improvement and further explored the individualized effect after perceptual learning. Amblyopes (average age:17 ± 7 years old) were trained in a monocular two-alternative forced choice identification task at the 50% contrast threshold of the amblyopic eye for 10-15 days. We found that monocular perceptual learning improves both visual acuity and contrast sensitivity function in amblyopia. The broader activation of spatial contrast sensitivity, with a significant improvement in lower spatial frequencies, contributed to improving visual acuity. Visual acuity changes in the early stage can predict the endpoint treatment outcomes. Our results confirm the efficacy of monocular perceptual learning and suggest potential predictors of training outcomes to assist in the future management of clinical intervention and vision neuroscience research in amblyopia beyond the critical period of visual plasticity.

Thalamic regulation of a visual critical period and motor behavior.

During the visual critical period (CP), sensory experience refines the structure and function of visual circuits. The basis of this plasticity was long thought to be limited to cortical circuits, but recently described thalamic plasticity challenges this dogma and demonstrates greater complexity underlying visual plasticity. Yet how visual experience modulates thalamic neurons or how the thalamus modulates CP timing is incompletely understood. Using a larval zebrafish, thalamus-centric ocular dominance model, we show functional changes in the thalamus and a role of inhibitory signaling to establish CP timing using a combination of functional imaging, optogenetics, and pharmacology. Hemisphere-specific changes in genetically defined thalamic neurons correlate with changes in visuomotor behavior, establishing a role of thalamic plasticity in modulating motor performance. Our work demonstrates that visual plasticity is broadly conserved and that visual experience leads to neuron-level functional changes in the thalamus that require inhibitory signaling to establish critical period timing.

Low frequency repetitive transcranial magnetic stimulation promotes plasticity of the visual cortex in adult amblyopic rats.

The decline of visual plasticity restricts the recovery of visual functions in adult amblyopia. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in treating adult amblyopia. However, the underlying mechanisms of rTMS on visual cortex plasticity remain unclear. In this study, we found that low-frequency rTMS reinstated the amplitude of visual evoked potentials, but did not influence the impaired depth perception of amblyopic rats. Furthermore, the expression of synaptic plasticity genes and the number of dendritic spines were significantly higher in amblyopic rats which received rTMS when compared with amblyopic rats which received sham stimulation, with reduced level of inhibition and perineuronal nets in visual cortex, as observed via molecular and histological investigations. The results provide further evidence that rTMS enhances functional recovery and visual plasticity in an adult amblyopic animal model.

Exercise does not enhance short-term deprivation-induced ocular dominance plasticity: evidence from dichoptic surround suppression.

The input from the two eyes is combined in the brain. In this combination, the relative strength of the input from each eye is determined by the ocular dominance. Recent work has shown that this dominance can be temporarily shifted. Covering one eye with an eye patch for a few hours makes its contribution stronger. It has been proposed that this shift can be enhanced by exercise. Here, we test this hypothesis using a dichoptic surround suppression task, and with exercise performed according to American College of Sport Medicine guidelines. We measured detection thresholds for patches of sinusoidal grating shown to one eye. When an annular mask grating was shown simultaneously to the other eye, thresholds were elevated. The difference in the elevation found in each eye is our measure of relative eye dominance. We made these measurements before and after 120 min of monocular deprivation (with an eye patch). In the control condition, subjects rested during this time. For the exercise condition, 30 min of exercise were performed at the beginning of the patching period. This was followed by 90 min of rest. We find that patching results in a shift in ocular dominance that can be measured using dichoptic surround suppression. However, we find no effect of exercise on the magnitude of this shift. We further performed a meta-analysis on the four studies that have examined the effects of exercise on the dominance shift. Looking across these studies, we find no evidence for such an effect.

The shift in sensory eye dominance from short-term monocular deprivation exhibits no dependence on test spatial frequency.

BACKGROUND: Studies have shown that short-term monocular deprivation induces a shift in sensory eye dominance in favor of the deprived eye. Yet, how short-term monocular deprivation modulates sensory eye dominance across spatial frequency is not clear. To address this issue, we conducted a study to investigate the dependence of short-term monocular deprivation effect on test spatial frequency. METHODS: Ten healthy young adults (age: 24.7 ± 1.7 years, four males) with normal vision participated. We deprived their dominant eye with a translucent patch for 2.5 h. The interocular contrast ratio (dominant eye/non-dominant eye, i.e., the balance point [BP]), which indicates the contribution that the two eyes make to binocular combination, was measured using a binocular orientation combination task. We assessed if BPs at 0.5, 4 or 6 cycles/degree (c/d) change as a result of monocular deprivation. Different test spatial frequency conditions were conducted on three separate days in a random fashion. RESULTS: We compared the BPs at 0.5, 4 and 6 c/d before and after monocular deprivation. The BPs were found to be significantly affected by deprivation, where sensory eye dominance shift to the deprived eye (F1.86, 16.76 = 33.09, P < 0.001). The changes of BP were consistent at 0.5, 4, and 6 c/d spatial frequencies (F2,18 = 0.15, P = 0.57). CONCLUSION: The sensory eye dominance plasticity induced by short-term deprivation is not dependent on test spatial frequency, suggesting it could provide a practical solution for amblyopic therapy that was concerned with the binocular outcome.

Mutual interaction between visual homeostatic plasticity and sleep in adult humans.

Sleep and plasticity are highly interrelated, as sleep slow oscillations and sleep spindles are associated with consolidation of Hebbian-based processes. However, in adult humans, visual cortical plasticity is mainly sustained by homeostatic mechanisms, for which the role of sleep is still largely unknown. Here, we demonstrate that non-REM sleep stabilizes homeostatic plasticity of ocular dominance induced in adult humans by short-term monocular deprivation: the counterintuitive and otherwise transient boost of the deprived eye was preserved at the morning awakening (>6 hr after deprivation). Subjects exhibiting a stronger boost of the deprived eye after sleep had increased sleep spindle density in frontopolar electrodes, suggesting the involvement of distributed processes. Crucially, the individual susceptibility to visual homeostatic plasticity soon after deprivation correlated with the changes in sleep slow oscillations and spindle power in occipital sites, consistent with a modulation in early occipital visual cortex.

Transcriptomic evidence for visual adaptation during the aquatic to terrestrial metamorphosis in leopard frogs.

BACKGROUND: Differences in morphology, ecology, and behavior through ontogeny can result in opposing selective pressures at different life stages. Most animals, however, transition through two or more distinct phenotypic phases, which is hypothesized to allow each life stage to adapt more freely to its ecological niche. How this applies to sensory systems, and in particular how sensory systems adapt across life stages at the molecular level, is not well understood. Here, we used whole-eye transcriptomes to investigate differences in gene expression between tadpole and juvenile southern leopard frogs (Lithobates sphenocephalus), which rely on vision in aquatic and terrestrial light environments, respectively. Because visual physiology changes with light levels, we also tested the effect of light and dark exposure. RESULTS: We found 42% of genes were differentially expressed in the eyes of tadpoles versus juveniles and 5% for light/dark exposure. Analyses targeting a curated subset of visual genes revealed significant differential expression of genes that control aspects of visual function and development, including spectral sensitivity and lens composition. Finally, microspectrophotometry of photoreceptors confirmed shifts in spectral sensitivity predicted by the expression results, consistent with adaptation to distinct light environments. CONCLUSIONS: Overall, we identified extensive expression-level differences in the eyes of tadpoles and juveniles related to observed morphological and physiological changes through metamorphosis and corresponding adaptive shifts to improve vision in the distinct aquatic and terrestrial light environments these frogs inhabit during their life cycle. More broadly, these results suggest that decoupling of gene expression can mediate the opposing selection pressures experienced by organisms with complex life cycles that inhabit different environmental conditions throughout ontogeny.

Rapid alternate monocular deprivation does not affect binocular balance and correlation in human adults.

Recent studies show that the human adult visual system exhibits neural plasticity. For instance, short-term monocular deprivation shifts the eye dominance in favor of the deprived eye. This phenomenon is believed to occur in the primary visual cortex by reinstating neural plasticity. However, it is unknown whether the changes in eye dominance after monocularly depriving the visual input can also be induced by alternately depriving both eyes. In this study, we found no changes in binocular balance and interocular correlation sensitivity after a rapid (7 Hz), alternate and monocular deprivation for one hour in adults. Therefore, the effect of short-term monocular deprivation cannot seem to be emulated by alternately and rapidly depriving both eyes.Significance statementPrevious work has shown that short-term binocular function disruption, which its most extreme form is monocular deprivation, could induce neural plasticity in adult visual system. In this study, we found a balanced deprivation of binocular function could not induce a neuroplastic change in human adults. It appears that ocular dominance plasticity in human adults is unique in so far as it is only driven by an input imbalance not balanced deprivation of binocular function.

Boosting visual perceptual learning by transcranial alternating current stimulation over the visual cortex at alpha frequency.

BACKGROUND: Transcranial alternating current stimulation (tACS) has been widely used to alter ongoing brain rhythms in a frequency-specific manner to modulate relevant cognitive functions, including visual functions. Therefore, it is a useful tool for exploring the causal role of neural oscillations in cognition. Visual functions can be improved substantially by training, which is called visual perceptual learning (VPL). However, whether and how tACS can modulate VPL is still unclear. OBJECTIVE: This work aims to explore how tACS modulates VPL and the role of neural oscillations in VPL. METHODS: A between-subjects design was adopted. Subjects were assigned to six groups and undertook five daily training sessions to execute an orientation discrimination task. During training, five groups received occipital tACS stimulation at 6, 10, 20, 40, and sham 10 Hz respectively, and one group was stimulated at the sensorimotor regions by 10 Hz tACS. RESULTS: Compared with the sham stimulation, occipital tACS at 10 Hz, but not at other frequencies, accelerated perceptual learning and increased the performance improvement. However, these modulatory effects were absent when 10 Hz tACS was delivered to the sensorimotor areas. Moreover, the tACS-induced performance improvement lasted at least two months after the end of training. CONCLUSION: TACS can facilitate orientation discrimination learning in a frequency- and location-specific manner. Our findings provide strong evidence for a pivotal role of alpha oscillations in boosting VPL and shed new light on the design of effective neuromodulation protocols that can facilitate rehabilitation for patients with neuro-ophthalmological disorders.

Normal Retinotopy in Primary Visual Cortex in a Congenital Complete Unilateral Lesion of Lateral Geniculate Nucleus in Human: A Case Study.

Impairment of the geniculostriate pathway results in scotomas in the corresponding part of the visual field. Here, we present a case of patient IB with left eye microphthalmia and with lesions in most of the left geniculostriate pathway, including the Lateral Geniculate Nucleus (LGN). Despite the severe lesions, the patient has a very narrow scotoma in the peripheral part of the lower-right-hemifield only (beyond 15° of eccentricity) and complete visual field representation in the primary visual cortex. Population receptive field mapping (pRF) of the patient's visual field reveals orderly eccentricity maps together with contralateral activation in both hemispheres. With diffusion tractography, we revealed connections between superior colliculus (SC) and cortical structures in the hemisphere affected by the lesions, which could mediate the retinotopic reorganization at the cortical level. Our results indicate an astonishing case for the flexibility of the developing retinotopic maps where the contralateral thalamus receives fibers from both the nasal and temporal retinae.

Impact of Temporal Visual Flicker on Spatial Contrast Sensitivity in Myopia.

PURPOSE: To investigate whether short-term exposure to high temporal frequency full-field flicker has an impact on spatial visual acuity in individuals with varying degrees of myopia. METHODS: Thirty subjects (evenly divided between control and experimental groups) underwent a 5-min exposure to full-field flicker. The flicker rate was lower than critical flicker frequency (CFF) for the experimental group (12.5 Hz) and significantly higher than CFF for the controls (60 Hz). Spatial contrast sensitivity function (CSF) was measured before and immediately after flicker exposure. We examined whether the post flicker CSF parameters were different from the pre-exposure CSF values in either of the subject groups. Additionally, we examined the relationship between the amount of CSF change from pre to post timepoints and the degree of subjects' myopia. The CSF parameters included peak frequency, peak sensitivity, bandwidth, truncation, and area under log CSF (AULCSF). RESULTS: There was no significant difference of all five pre-exposure CSF parameters between the two groups at baseline (P = 0.333 ∼ 0.424). Experimental group subjects exhibited significant (P < 0.005) increases in peak sensitivity and AULCSF, when comparing post-exposure results to pre-exposure ones. Controls showed no such enhancements. Furthermore, the extent of these changes in the experimental group was correlated significantly with the participants' refractive error (P = 0.005 and 0.018, respectively). CONCLUSION: Our data suggest that exposure to perceivable high-frequency flicker (but, not to supra-CFF frequencies) enhances important aspects of spatial contrast sensitivity, and these enhancements are correlated to the degree of myopia. This finding has implications for potential interventions for cases of modest myopia.

Multimodal Neuroimaging Study of Visual Plasticity in Schizophrenia.

Schizophrenia is a severe mental illness with visual learning and memory deficits, and reduced long term potentiation (LTP) may underlie these impairments. Recent human fMRI and EEG studies have assessed visual plasticity that was induced with high frequency visual stimulation, which is thought to mimic an LTP-like phenomenon. This study investigated the differences in visual plasticity in participants with schizophrenia and healthy controls. An fMRI visual plasticity paradigm was implemented, and proton magnetic resonance spectroscopy data were acquired to determine whether baseline resting levels of glutamatergic and GABA metabolites were related to visual plasticity response. Adults with schizophrenia did not demonstrate visual plasticity after family-wise error correction; whereas, the healthy control group did. There was a significant regional difference in visual plasticity in the left visual cortical area V2 when assessing group differences, and baseline GABA levels were associated with this specific ROI in the SZ group only. Overall, this study suggests that visual plasticity is altered in schizophrenia and related to basal GABA levels.

Vitamin A1/A2 chromophore exchange: Its role in spectral tuning and visual plasticity.

Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known as visual pigments that consist of a G-protein-coupled, seven-transmembrane protein known as opsin, and a chromophore prosthetic group, either 11-cis retinal ('A1') or 11-cis 3,4-didehydroretinal ('A2'). The enzyme cyp27c1 converts A1 into A2 in the retinal pigment epithelium. Replacing A1 with A2 in a visual pigment red-shifts its spectral sensitivity and broadens its bandwidth of absorption at the expense of decreased photosensitivity and increased thermal noise. The use of vitamin A2-based visual pigments is strongly associated with the occupation of aquatic habitats in which the ambient light is red-shifted. By modulating the A1/A2 ratio in the retina, an organism can dynamically tune the spectral sensitivity of the visual system to better match the predominant wavelengths of light in its environment. As many as a quarter of all vertebrate species utilize A2, at least during a part of their life cycle or under certain environmental conditions. A2 utilization therefore represents an important and widespread mechanism of sensory plasticity. This review provides an up-to-date account of the A1/A2 chromophore exchange system.

How Learning to Read Changes the Listening Brain.

Reading acquisition reorganizes existing brain networks for speech and visual processing to form novel audio-visual language representations. This requires substantial cortical plasticity that is reflected in changes in brain activation and functional as well as structural connectivity between brain areas. The extent to which a child's brain can accommodate these changes may underlie the high variability in reading outcome in both typical and dyslexic readers. In this review, we focus on reading-induced functional changes of the dorsal speech network in particular and discuss how its reciprocal interactions with the ventral reading network contributes to reading outcome. We discuss how the dynamic and intertwined development of both reading networks may be best captured by approaching reading from a skill learning perspective, using audio-visual learning paradigms and longitudinal designs to follow neuro-behavioral changes while children's reading skills unfold.

Current status and directions of vision rehabilitation in glaucoma / 中华实验眼科杂志

Glaucoma, the leading cause of irreversible visual impairment in the world, leads to visual function damage that seriously affects the daily life activities and psychosocial function of patients, resulting in a significant decline in the quality of life.The life quality of patients can be efficiently improved through vision rehabilitation based on the residual visual function, but there is not enough attention paid to the visual impairment and vision rehabilitation of glaucoma.From a perspective of the epidemiological status of visual impairment in glaucoma at home and abroad, the universality and severity of the glaucomatous visual impairment was revealed.The characteristics of visual changes and corresponding rehabilitation needs of patients, the current situation of rehabilitation service supply, new devices that can expand visual field and the latest proven effective rehabilitation methods in light of the recent development of these fields were reviewed in order to provide certain inspiration and reference for the research of vision rehabilitation of glaucoma.

Effects of Transcranial Direct Current Stimulation on Visual Neuroplasticity in Schizophrenia.

People with schizophrenia (SZ) exhibit visual processing abnormalities that affect their daily functioning and remediating these deficits might help to improve functioning. Transcranial direct current stimulation (tDCS) is a potential tool for perceptual enhancement for this purpose, though there are no reports of tDCS applied to visual cortex in SZ. In a within-subject, crossover design, we evaluated the effects of tDCS on visual processing in 27 SZ. All patients received anodal, cathodal, or sham stimulation over the central occipital region in 3 visits separated by 1 week. In each visit, a backward masking task and an electroencephalography measure of visual neuroplasticity were administered after tDCS. Neuroplasticity was assessed with visual evoked potentials before and after tetanizing visual high-frequency stimulation. Masking performance was significantly poorer in the anodal and cathodal conditions compared with sham. Both anodal and cathodal stimulation increased the amplitude of P1 but did not change the plasticity index. We found significant plasticity effects of tDCS for only one waveform for one stimulation condition (P2 for anodal tDCS) which did not survive correction for multiple comparisons. The reason for the lack of tDCS stimulation effects on plasticity may be because tDCS was not delivered simultaneously with the tetanizing visual stimulus. The present findings emphasize the need for more research on the relevant parameters for stimulation of visual processing regions in clinical populations.

Short-Term Deprivation Does Not Influence Monocular or Dichoptic Temporal Synchrony at Low Temporal Frequency.

Studies on binocular combination and rivalry show that short-term deprivation strengthens the contribution of the deprived eye in binocular vision. However, whether short-term monocular deprivation affects temporal processing per se is not clear. To address this issue, we conducted a study to investigate the effect of monocular deprivation on dichoptic temporal synchrony. We tested ten adults with normal vision and patched their dominant eye with an opaque patch for 2.5 h. A temporal synchrony paradigm was used to measure if temporal synchrony thresholds change as a result of monocular pattern deprivation. In this paradigm, we displayed two pairs of Gaussian blobs flickering at 1 Hz with either the same or different phased- temporal modulation. In Experiment 1, we obtained the thresholds for detecting temporal asynchrony under dichoptic viewing configurations. We compared the thresholds for temporal synchrony between before and after monocular deprivation and found no significant changes of the interocular synchrony. In Experiment 2, we measured the monocular thresholds for detecting temporal asynchrony. We also found no significant changes of the monocular synchrony of either the patched eye or the unpatched eye. Our findings suggest that short-term monocular deprivation induced-plasticity does not influence monocular or dichoptic temporal synchrony at low temporal frequency.

Shaping the visual system: cortical and subcortical plasticity in the intact and the lesioned brain.

Visual system is endowed with an incredibly complex organization composed of multiple visual pathway affording both hierarchical and parallel processing. Even if most of the visual information is conveyed by the retina to the lateral geniculate nucleus of the thalamus and then to primary visual cortex, a wealth of alternative subcortical pathways is present. This complex organization is experience dependent and retains plastic properties throughout the lifespan enabling the system with a continuous update of its functions in response to variable external needs. Changes can be induced by several factors including learning and experience but can also be promoted by the use non-invasive brain stimulation techniques. Furthermore, besides the astonishing ability of our visual system to spontaneously reorganize after injuries, we now know that the exposure to specific rehabilitative training can produce not only important functional modifications but also long-lasting changes within cortical and subcortical structures. The present review aims to update and address the current state of the art on these topics gathering studies that reported relevant modifications of visual functioning together with plastic changes within cortical and subcortical structures both in the healthy and in the lesioned visual system.