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Large walls and other typical boundaries strongly influence neural activity related to navigation and the representations of spatial layouts. They are also major aids to reliable navigation behavior in young children and nonhuman animals. Is this because they are physical boundaries (barriers to movement), or because they present certain visual features, such as visually extended 3D surfaces? Here, these 2 factors were dissociated by using immersive virtual reality and real boundaries. Eighty adults recalled target locations in 1 of 4 environments: plywood, where a virtual wall coincided with a large piece of real plywood; pass through, where the virtual wall coincided with empty space and participants could pass through it; pass over, where the virtual wall was projected downward to be visible underneath a transparent floor; and cones, where the walls were replaced with traffic cones. One condition had features that were boundaries and looked like boundaries (plywood); 2 had features that were not boundaries but looked like boundaries (pass over/through); and 1 had features that were not boundaries and did not look like boundaries (cones). The precision and bias of responses changed only as a function of looking like a boundary. This suggests that variations in spatial coding are more closely linked to the visual properties of environmental layouts than to whether they contain physical boundaries (barriers to movement).

BackgroundMutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited.MethodsWe performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings.ResultsImprovements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG.ConclusionsGene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

Using landmarks and other scene features to recall locations from new viewpoints is a critical skill in spatial cognition. In an immersive virtual reality task, we asked children 3.5-4.5 years old to remember the location of a target using various cues. On some trials they could use information from their own self-motion. On some trials they could use a view match. In the very hardest kind of trial, they were "teleported" to a new viewpoint and could only use an allocentric spatial representation. This approach provides a strict test for allocentric coding (without either a matching viewpoint or self-motion information) while avoiding additional task demands in previous studies (it does not require them to deal with a small table-top environment or to manage stronger cue conflicts). Both the younger and older groups were able to point back at the target location better than chance when they could use view matching and/or self-motion, but allocentric recall was only seen in the older group (4.0-4.5). In addition, we only obtained evidence for a specific kind of allocentric recall in the older group: they tracked one major axis of the space significantly above chance, r(158) = 0.28, but not the other, r(158) = -0.01. We conclude that there is a major qualitative change in coding for spatial recall around the fourth birthday, potentially followed by further development towards fully flexible recall from new viewpoints.

PurposeTo longitudinally characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical gene therapy trials.MethodsThirty-eight molecularly confirmed ACHM subjects underwent serial assessments, including spectral domain optical coherence tomography (SD-OCT), microperimetry, and fundus autofluorescence (FAF). Foveal structure on SD-OCT was graded and compared for evidence of progression, along with serial measurements of foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness. Fundus autofluorescence patterns were characterized and compared over time.ResultsMean follow-up was 19.5 months (age range at baseline, 6-52 years). Only 2 (5%) of 37 subjects demonstrated change in serial foveal SD-OCT scans. There was no statistically significant change over time in FTRT (P = 0.83), ONL thickness (P = 0.27), hyporeflective zone diameter (P = 0.42), visual acuity (P = 0.89), contrast sensitivity (P = 0.22), mean retinal sensitivity (P = 0.84), and fixation stability (P = 0.58). Three distinct FAF patterns were observed (n = 30): central increased FAF (n = 4), normal FAF (n = 11), and well-demarcated reduced FAF (n = 15); with the latter group displaying a slow increase in the area of reduced FAF of 0.03 mm(2) over 19.3 months (P = 0.002).ConclusionsPreviously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.

PurposeTo characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy.DesignCross-sectional study.ParticipantsForty subjects with ACHM.MethodsAll subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined.Main outcome measuresPhotoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype.ResultsForty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P = 0.77), mean retinal sensitivity (P = 0.21), or fixation stability (P = 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P = 0.84) or between age and foveal ONL thickness (P = 0.12).ConclusionsThe lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring the trials' impact.

Background: Sensory substitution and augmentation systems (SSASy) seek to either replace or enhance existing sensory skills by providing a new route to access information about the world. Tests of such systems have largely been limited to untimed, unisensory tasks. Objective: To test the use of a SSASy for rapid, ballistic motor actions in a multisensory environment. Methods: Participants played a stripped-down version of air hockey in virtual reality with motion controls (Oculus Touch). They were trained to use a simple SASSy (novel audio cue) for the puck's location. They were tested on ability to strike an oncoming puck with the SASSy, degraded vision, or both. Results: Participants coordinated vision and the SSASy to strike the target with their hand more consistently than with the best single cue alone, t(13) = 9.16, p <.001, Cohen's d = 2.448. Conclusions: People can adapt flexibly to using a SSASy in tasks that require tightly timed, precise, and rapid body movements. SSASys can augment and coordinate with existing sensorimotor skills rather than being limited to replacement use cases – in particular, there is potential scope for treating moderate vision loss. These findings point to the potential for augmenting human abilities, not only for static perceptual judgments, but in rapid and demanding perceptual-motor tasks. [ABSTRACT FROM AUTHOR]

Adults can integrate multiple sensory estimates to reduce their uncertainty in perceptual and motor tasks. In recent studies, children did not show this ability until after 8 years. Here we investigated development of the ability to integrate vision with proprioception to localize the hand. We tested 109 4- to 12-year-olds and adults on a simple pointing task. Participants used an unseen hand beneath a table to point to targets presented on top of the table to vision alone, proprioception alone, or both together. Overall, 7- to 9-year-olds' and adults' points were significantly less variable given vision and proprioception together compared with either alone. However, this variance reduction was present at all ages in the subset of participants whose proprioceptive estimates were less than two times more variable than their visual. These results, together with analyses of cue weighting, indicate that all groups integrated vision and proprioception, but only 7- to 9-year-olds and adults consistently selected cue weights that were appropriate to their own single-cue reliabilities. Cue weights used at 4-6 and 10-12 years still allowed over half of participants at these ages to reduce their pointing variability. One explanation for poorer group-level cue weighting at 10-12 years is that this ages represents a period of relatively rapid physical growth. An existing Bayesian model of hand localization did not describe either adults' or children's data well, but the results suggest future improvements to the model. (Contains 3 tables and 4 figures.)

It has been suggested that learning an object's location relative to (1) intramaze landmarks and (2) local boundaries is supported by parallel striatal and hippocampal systems, both of which rely upon input from a third system for orientation. However, little is known about the developmental trajectories of these systems' contributions to spatial learning. The present study tested 5- and 7-year-old children and adults on a water maze-like task in which all three types of cue were available. Participants had to remember the location of an object hidden in a circular bounded environment containing a moveable intramaze landmark and surrounded by distal cues. Children performed less accurately than adults, and showed a different pattern of error. While adults relied most on the stable cue provided by the boundary, children relied on both landmark and boundary cues similarly, suggesting a developmental increase in the weighting given to boundary cues. Further, adults were most accurate in coding angular information (dependent on distal cues), whereas children were most accurate in coding distance, suggesting a developing ability to use distal cues to orient. These results indicate that children as young as 5 years use boundary, intramaze landmark, and distal visual cues in parallel, but that the basic accuracy and relative weighting of these cues changes during subsequent development.

Reorientation tasks, in which disoriented participants attempt to relocate objects using different visual cues, have previously been understood to depend on representing aspects of the global organisation of the space, for example its major axis for judgements based on geometry. Careful analysis of the visual information available for these tasks shows that successful performance could be based on the much simpler process of storing a visual "snapshot" at the target location, and subsequently moving in order to match it. We tested 4-8-year olds on a new spatial reorientation task that could not be solved based on information directly contained in any retinal projection that they had been exposed to, but required participants to infer how the space is structured. Only 6-8-year olds showed flexible recall from novel viewpoints. Five-year olds were able to recall locations given movement information or a unique proximal landmark, but without these they could not do so, even when they were not disoriented or when the landmark was a familiar object. These results indicate that early developing spatial abilities based on view matching and self motion are supplemented by a later-developing process that takes into account the structure of spatial layouts and so enables flexible recall from arbitrary viewpoints. (Contains 1 table and 2 figures.)

Williams syndrome (WS) is a genetic disorder associated with severe visuocognitive impairment. Individuals with WS also report difficulties with everyday wayfinding. To study the development of body-, environment-, and object-based spatial frames of reference in WS, we tested 45 children and adults with WS on a search task in which the participant and a spatial array are moved with respect to each other. Although individuals with WS showed a marked delay, like young controls they demonstrated independent, additive use of body- and environment-based frames of reference. Crucially, object-based (intrinsic) representations based on local landmarks within the array were only marginally used even by adults with WS, whereas in typical development these emerge at 5 years. Deficits in landmark use are consistent with wayfinding difficulties in WS, and may also contribute to problems with basic localization, since in typical development landmark-based representations supplement those based on the body and on self-motion. Difficulties with inhibition or mental rotation may be further components in the impaired ability to use the correct reference frame in WS.

In previous studies, children disoriented in small enclosures used room shape, but not wall colors, to find hidden objects. Their reorientation was said to depend solely on a "geometric module" informationally encapsulated with respect to color. We argue that previous studies did not fully evaluate children's use of color owing to a bias in the enclosures' design. In this study, disoriented 18-24 month olds searched for toys in small square enclosures with two blue and two white walls. Children successfully reoriented using wall color. This shows that they can make location judgments based on the left/right sense of the colors of adjoining landmarks. Performance was no different when symmetric colorful shapes were added to walls, but improved with asymmetric shapes which could be used without left/right judgments. The relatively poor use of color in previous studies may be explained partly by a bias in their design, and partly by children's limited ability to discriminate the left/right sense of nongeometric features.

We studied the development of spatial frames of reference in children aged 3-6 years, who retrieved hidden toys from an array of identical containers bordered by landmarks under four conditions. By moving the child and/or the array between presentation and test, we varied the consistency of the hidden toy with (1) the body, and (2) the testing room. The toy's position always remained consistent with (3) the array and bordering landmarks. We found separate, additive performance advantages for consistency with body and room. These effects were already present at 3 years. A striking finding was that the room effect, which implies allocentric representations of the room and/or egocentric representations updated by self-motion, was much stronger in the youngest children than the body effect, which implies purely egocentric representations. Children as young as 3 years therefore had, and greatly favoured, spatial representations that were not purely egocentric. Viewpoint-independent recall based only on the array and bordering landmarks emerged at 5 years. There was no evidence that this later-developing ability, which implies object-referenced (intrinsic) representations, depended on verbal encodings. These findings indicate that core components of adult spatial competence, including parallel egocentric and nonegocentric representations of space, are present as early as 3 years. These are supplemented by later-developing object-referenced representations.

When the illumination falling on a surface change, so does the reflected light. Despite this, adult observers are good at perceiving surfaces as relatively unchanging—an ability termed colour constancy. Very few studies have investigated colour constancy in infants, and even fewer in children. Here we asked whether there is a difference in colour constancy between children and adults; what the developmental trajectory is between six and 11 years; and whether the pattern of constancy across illuminations and reflectances differs between adults and children. To this end, we developed a novel, child‐friendly computer‐based object selection task. In this, observers saw a dragon's favourite sweet under a neutral illumination and picked the matching sweet from an array of eight seen under a different illumination (blue, yellow, red, or green). This set contained a reflectance match (colour constant; perfect performance) and a tristimulus match (colour inconstant). We ran two experiments, with two‐dimensional scenes in one and three‐dimensional renderings in the other. Twenty‐six adults and 33 children took part in the first experiment; 26 adults and 40 children took part in the second. Children performed better than adults on this task, and their performance decreased with age in both experiments. We found differences across illuminations and sweets, but a similar pattern across both age groups. This unexpected finding might reflect a real decrease in colour constancy from childhood to adulthood, explained by developmental changes in the perceptual and cognitive mechanisms underpinning colour constancy, or differences in task strategies between children and adults. Highlights: Six‐ to 11‐year‐old children demonstrated better performance than adults on a colour constancy object selection task.Performance decreased with age over childhood.These findings may indicate development of cognitive strategies used to overcome automatic colour constancy mechanisms. [ABSTRACT FROM AUTHOR]