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BackgroundAmblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children.MethodsThe AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n = 30, 6-35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n = 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before and after each treatment with 8-week follow-up.DiscussionThe VR-based games used in this study have been conceived to deliver binocular visual stimulation tailored to the individual visual needs of the patient, which will potentially result in improved basic and functional vision skills as well as visual attention and motor control skills.Trial registrationThis protocol is registered on ClinicalTrials.gov (identifier: NCT05114252) and in the Swiss National Clinical Trials Portal (identifier: SNCTP000005024).

In cognitive neurosciences, fundamental principles of mental processes and functional brain organization have been established with highly controlled tasks and testing environments. Recent technical advances allowed the investigation of these functions and their brain mechanisms in naturalistic settings. The diversity in those approaches have been recently (Matusz, P. J., Dikker, S., Huth, A. G., & Perrodin, C. (2019). Are we ready for real-world neuroscience? "Journal of Cognitive Neuroscience," 31(3), 327-338. doi:10.1162/jocn_e_01276) classified via a three-category cycle, including "controlled laboratory," "partially naturalistic laboratory," and "naturalistic real-world research." Based on this model, we developed the Multidimensional Assessment of Research in Context (MARC) tool to easily delineate the approach researchers have taken in their study. MARC provides means to describe the degree of ecological validity for each component of a study (e.g., sample, stimuli, measures, etc.), and the study's location on the cycle. The tool comprises seven questions concerning a study's characteristics. It outputs a summary of those and a compass plot, which can be used for presentations, preregistration, grant proposals, and papers. It aims to improve drawing conclusions across studies and raise awareness about the generalizability of research findings.

Schooling may shape children's abilities to control their attention, but it is unclear if this impact extends from control over visual objects to encompass multisensory objects, which are more typical of everyday environments. We compared children across three primary school grades (Swiss first, third, and fifth grades) on their performance on a game-like audiovisual attentional control task, while recording their electroencephalogram (EEG). Behavioral markers of "visual" attentional control were present from third grade (after 2 years of schooling), whereas multisensory attentional control was not detected in any group. However, multivariate whole-brain EEG analyses ("electrical neuroimaging") revealed stable patterns of brain activity that indexed both types of attentional control--visual control in all age groups, and multisensory attentional control from third grade onward. Multivariate EEG approaches can uncover otherwise undetectable mechanisms of attentional control over visual and multisensory objects, and characterize how these mechanisms differ across educational stages.