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.

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).
CONCLUSIONS: 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.

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.

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.

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.

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.

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).
CONCLUSIONS: 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.

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.

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.
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.
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.

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.