Seeing in the dark: High-order visual functions under scotopic conditions.

It is unknown how and to what degree people function visually in almost complete darkness, where only rod photoreceptors are active (scotopic conditions). To explore this, we first tested scotopic acuity and crowding. We demonstrated the ∼1° foveal scotoma and found that crowding increases with eccentricity, resulting in optimal scotopic discrimination 2° into the periphery. We then investigated whether these limitations affect high-level foveal tasks. We recorded eye movements while testing reading and upright/inverted face matching under photopic and scotopic conditions. Under scotopic conditions, participants read accurately and showed a face inversion effect. Temporally, fixation durations were longer. Spatially, surprisingly, participants did not avert their gaze 2° into the periphery. Instead, they fixated on similar locations as under photopic conditions, locations that were shown to correlate with global perception. We propose that this result suggests global perception governs under scotopic conditions, and we discuss how receptive-field properties support this conclusion.

Abnormal network connections to early visual cortex in posterior cortical atrophy.

INTRODUCTION: Posterior Cortical Atrophy (PCA), a visual variant of Alzheimer's disease, initially manifests with higher-order visual disorders and parieto/temporo-occipital atrophy. Recent studies have shown remote functional impairment in both distant brain networks and along the calcarine sulcus (V1). Functional alteration in the calcarine differs along its length, reflecting center to periphery visual space differences. Herein, we aim to connect between these two sets of findings by looking at the retinotopic patterns of functional connectivity between large-scale brain networks and V1, comparing patients with normally sighted subjects. METHODS: Resting state functional magnetic resonance imaging (fMRI) and T1 anatomical scans were obtained from 11 PCA patients and 17 age-matched healthy volunteers. Default mode network (DMN) and fronto parietal network (FPN) were defined and differences between the networks in patients and healthy controls were evaluated at the whole brain level, specifically their connectivity to V1. RESULTS: Connectivity patterns within the DMN and the FPN were similar between the groups, although differences were found in regions within and beyond the networks. Focusing on V1, in the control group we identified the expected pattern of a distributed connectivity along eccentricity, with foveal regions showing stronger connectivity to the FPN and peripheral regions showing stronger connectivity to the DMN. However, in PCA patients we could not identify a clear difference in connectivity along the eccentricities. CONCLUSION: Lost specialization of function along the calcarine in PCA patients may have further implications on large-scale networks or vice versa. This impairment, distant from the core pathology, might explain patients' visual disabilities.

Seeing color following gene augmentation therapy in achromatopsia.

How will people who spent their visual lives with only rods respond to cone function restoration? Will they be able suddenly see the colors of the rainbow? CNGA3-achromatopsia is a congenital hereditary disease in which cone dysfunction leads patients to have rod photoreceptor-driven vision only in daylight,1,2,3,4 seeing the world in blurry shades of gray.5,6 We studied color perception in four CNGA3-achromatopsia patients following monocular retinal gene augmentation therapy.7,8,9 Following treatment, although some cortical changes were reported,3,4 patients did not report a dramatic change in their vision.3,9 However, in accordance with the fact that sensitivity of rods and cones is most different at long wavelengths, they consistently reported seeing red objects on dark backgrounds differently than they did before surgery.3 Because clinical color assessments failed to find any indication of color vision, we conducted a gamut of tailored tests to better define patients' descriptions. We evaluated patients' perceived lightness of different colors, color detection, and saliency, comparing their treated with their untreated eyes. Although the perceived lightness of different colors was generally similar between the eyes and matched a rod-input model, patients could detect a colored stimulus only in their treated eyes. In a search task, long response times, which were further extended with array size, suggested low saliency. We suggest that treated CNGA3-achromatopsia patients can perceive a stimulus's color attribute, although in a manner that is different and very limited compared with sighted individuals. We discuss the retinal and cortical obstacles that might explain this perceptual gap.

Gaze following requires early visual experience.

Gaze understanding­a suggested precursor for understanding others' intentions­requires recovery of gaze direction from the observed person's head and eye position. This challenging computation is naturally acquired at infancy without explicit external guidance, but can it be learned later if vision is extremely poor throughout early childhood? We addressed this question by studying gaze following in Ethiopian patients with early bilateral congenital cataracts diagnosed and treated by us only at late childhood. This sight restoration provided a unique opportunity to directly address basic issues on the roles of "nature" and "nurture" in development, as it caused a selective perturbation to the natural process, eliminating some gaze-direction cues while leaving others still available. Following surgery, the patients' visual acuity typically improved substantially, allowing discrimination of pupil position in the eye. Yet, the patients failed to show eye gaze-following effects and fixated less than controls on the eyes­two spontaneous behaviors typically seen in controls. Our model for unsupervised learning of gaze direction explains how head-based gaze following can develop under severe image blur, resembling preoperative conditions. It also suggests why, despite acquiring sufficient resolution to extract eye position, automatic eye gaze following is not established after surgery due to lack of detailed early visual experience. We suggest that visual skills acquired in infancy in an unsupervised manner will be difficult or impossible to acquire when internal guidance is no longer available, even when sufficient image resolution for the task is restored. This creates fundamental barriers to spontaneous vision recovery following prolonged deprivation in early age.

Development of multisensory integration following prolonged early-onset visual deprivation.

Adult humans make effortless use of multisensory signals and typically integrate them in an optimal fashion.1 This remarkable ability takes many years for normally sighted children to develop.2,3 Would individuals born blind or with extremely low vision still be able to develop multisensory integration later in life when surgically treated for sight restoration? Late acquisition of such capability would be a vivid example of the brain's ability to retain high levels of plasticity. We studied the development of multisensory integration in individuals suffering from congenital dense bilateral cataract, surgically treated years after birth. We assessed cataract-treated individuals' reliance on their restored visual abilities when estimating the size of an object simultaneously explored by touch. Within weeks to months after surgery, when combining information from vision and touch, they developed a multisensory weighting behavior similar to matched typically sighted controls. Next, we tested whether cataract-treated individuals benefited from integrating vision with touch by increasing the precision of size estimates, as it occurs when integrating signals in a statistically optimal fashion.1 For participants retested multiple times, such a benefit developed within months after surgery to levels of precision indistinguishable from optimal behavior. To summarize, the development of multisensory integration does not merely depend on age, but requires extensive multisensory experience with the world, rendered possible by the improved post-surgical visual acuity. We conclude that early exposure to multisensory signals is not essential for the development of multisensory integration, which can still be acquired even after many years of visual deprivation.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception.SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3-achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.

Learning to perceive shape from temporal integration following late emergence from blindness.

Visual perception requires massive use of inference because the 3D structure of the world is not directly provided by the sensory input.1 Particularly challenging is anorthoscopic vision-when an object moves behind a narrow slit such that only a tiny fraction of it is visible at any instant. Impressively, human observers correctly recognize objects in slit-viewing conditions by early childhood,2,3 via temporal integration of the contours available in each sliver.4,5 But can this capability be acquired if one has been effectively blind throughout childhood? We studied 23 Ethiopian children which had bilateral early-onset cataracts-resulting in extremely poor vision in infancy-and surgically treated only years later. We tested their anorthoscopic vision, precisely because it requires a cascade of demanding visual inference processes to perceive veridical shape. Failure to perform the task may allow mapping specific bottlenecks for late visual recovery. The patients' visual acuity typically improved substantially within 6 months post-surgery. Still, at this stage many were unable to recover shape under slit-viewing conditions, although they could infer the direction of global motion. However, when retested later, almost all patients could judge shape in slit-conditions necessitating temporal integration. This acquired capability often transferred to novel stimuli, in similar slit-viewing conditions. Thus, learning was not limited to the specific visual features of the original shapes. These results indicate that plasticity of sophisticated visual inference routines is preserved well into adolescence, and vision restoration after prolonged early-onset blindness is feasible to a greater extent than previously thought.

Convergence Along the Visual Hierarchy Is Altered in Posterior Cortical Atrophy.

Purpose: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome manifesting with visuospatial processing impairment. We recently suggested that abnormal population receptive field properties are associated with the symptoms of PCA patients. Specifically, simultanagnosia, the inability to perceive multiple items simultaneously, can be explained by smaller peripheral population receptive fields, and foveal crowding, in which nearby distractors interfere with object perception, may result from larger foveal population receptive fields. These effects occurred predominantly in V1, even though atrophy mainly involves high-order areas. In this study, we used connective field modeling to better understand these inter-area interactions. Methods: We used functional magnetic resonance imaging to scan six PCA patients and eight controls while they viewed drifting bar stimuli. Resting-state data were also collected. Connective field modeling was applied for both conditions: once when the source was V1 and the targets were extrastriate areas and once for the opposite direction. The difference between the two was defined as convergence magnitude. Results: With stimulus, the convergence magnitude of the controls increased along the visual pathway, suggesting that spatial integration from V1 becomes larger up the visual hierarchy. No such slope was found in the PCA patients. The difference between the groups originated mainly from the dorsal pathway. Without stimulus, the convergence magnitude was negative, slightly more so for the PCA patients, with no slope, suggesting constant divergence along the visual hierarchy. Conclusions: Atrophy in one part of the visual system can affect other areas within the network through complex intervisual area interactions, resulting in modulation of population receptive field properties and an ensemble of visuocognitive function impairments.

Lack of Automatic Imitation in Newly Sighted Individuals.

Viewing a hand action performed by another person facilitates a response-compatible action and slows a response-incompatible one, even when the viewed action is irrelevant to the task. This automatic imitation effect is taken as the clearest evidence for a direct mapping between action viewing and motor performance. But there is an ongoing debate whether this effect is innate or experience dependent. We tackled this issue by studying a unique group of newly sighted children who suffered from dense bilateral cataracts from early infancy and were surgically treated only years later. The newly sighted children were less affected by viewing task-irrelevant actions than were control children, even 2 years after the cataract-removal surgery. This strongly suggests that visually guided motor experience is necessary for the development of automatic imitation. At the very least, our results indicate that if imitation is based on innate mechanisms, these are clearly susceptible to long periods of visual deprivation.

Size constancy following long-term visual deprivation.

We can estimate the veridical size of nearby objects reasonably well irrespective of their viewing distance. This perceptual capability, termed size constancy, is accomplished by combining information about retinal image size together with the viewing distance, or using the relational information available in the scene, via direct perception [1]. A previous study [2] showed that children typically underestimate the size of a distant object. This underestimation is reduced with time, suggesting that years of visual experience may be essential for attaining true size constancy. But what if you have had very limited vision during the early years of life? We studied 23 Ethiopian children suffering from bilateral, early-onset cataract, who were surgically treated only years after birth. Surprisingly, most children were able to estimate object size reasonably well irrespective of distance; in fact, they usually tended to overestimate the far-object size. Closer examination indicated that, although before surgery the patients were diagnosed as having a full, mature bilateral cataract, they nevertheless had some residual form of vision, typically limited to very close range. Gandhi et al.[3] earlier reported immediate susceptibility to geometric visual illusions in a similar group of newly-sighted children, concluding that size constancy was probably innate. We suggest that their immediate ability to judge physical size irrespective of distance is more likely to result from their previous visual experience.

The Limits of Shape Recognition following Late Emergence from Blindness.

Visual object recognition develops during the first years of life. But what if one is deprived of vision during early post-natal development? Shape information is extracted using both low-level cues (e.g., intensity- or color-based contours) and more complex algorithms that are largely based on inference assumptions (e.g., illumination is from above, objects are often partially occluded). Previous studies, testing visual acuity using a 2D shape-identification task (Lea symbols), indicate that contour-based shape recognition can improve with visual experience, even after years of visual deprivation from birth. We hypothesized that this may generalize to other low-level cues (shape, size, and color), but not to mid-level functions (e.g., 3D shape from shading) that might require prior visual knowledge. To that end, we studied a unique group of subjects in Ethiopia that suffered from an early manifestation of dense bilateral cataracts and were surgically treated only years later. Our results suggest that the newly sighted rapidly acquire the ability to recognize an odd element within an array, on the basis of color, size, or shape differences. However, they are generally unable to find the odd shape on the basis of illusory contours, shading, or occlusion relationships. Little recovery of these mid-level functions is seen within 1 year post-operation. We find that visual performance using low-level cues is relatively robust to prolonged deprivation from birth. However, the use of pictorial depth cues to infer 3D structure from the 2D retinal image is highly susceptible to early and prolonged visual deprivation.

Motion adaptation reveals that the motion vector is represented in multiple coordinate frames.

Accurately perceiving the velocity of an object during smooth pursuit is a complex challenge: although the object is moving in the world, it is almost still on the retina. Yet we can perceive the veridical motion of a visual stimulus in such conditions, suggesting a nonretinal representation of the motion vector. To explore this issue, we studied the frames of representation of the motion vector by evoking the well known motion aftereffect during smooth-pursuit eye movements (SPEM). In the retinotopic configuration, due to an accompanying smooth pursuit, a stationary adapting random-dot stimulus was actually moving on the retina. Motion adaptation could therefore only result from motion in retinal coordinates. In contrast, in the spatiotopic configuration, the adapting stimulus moved on the screen but was practically stationary on the retina due to a matched SPEM. Hence, adaptation here would suggest a representation of the motion vector in spatiotopic coordinates. We found that exposure to spatiotopic motion led to significant adaptation. Moreover, the degree of adaptation in that condition was greater than the adaptation induced by viewing a random-dot stimulus that moved only on the retina. Finally, pursuit of the same target, without a random-dot array background, yielded no adaptation. Thus, in our experimental conditions, adaptation is not induced by the SPEM per se. Our results suggest that motion computation is likely to occur in parallel in two distinct representations: a low-level, retinal-motion dependent mechanism and a high-level representation, in which the veridical motion is computed through integration of information from other sources.

Tactile interactions activate mirror system regions in the human brain.

Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.

Pattern matching is assessed in retinotopic coordinates.

We typically examine scenes by performing multiple saccades to different objects of interest within the image. Therefore, an extra-retinotopic representation, invariant to the changes in the retinal image caused by eye movements, might be useful for high-level visual processing. We investigate here, using a matching task, whether the representation of complex natural images is retinotopic or screen-based. Subjects observed two simultaneously presented images, made a saccadic eye movement to a new fixation point, and viewed a third image. Their task was to judge whether the third image was identical to one of the two earlier images or different. Identical images could appear either in the same retinotopic position, in the same screen position, or in totally different locations. Performance was best when the identical images appeared in the same retinotopic position and worst when they appeared in the opposite hemifield. Counter to commonplace intuition, no advantage was conferred from presenting the identical images in the same screen position. This, together with performance sensitivity for image translation of a few degrees, suggests that image matching, which can often be judged without overall recognition of the scene, is mostly determined by neuronal activity in earlier brain areas containing a strictly retinotopic representation and small receptive fields.

The coordinate frame of pop-out learning.

Saccades are ubiquitous in natural vision. One way to generate a coherent representation of a scene across saccades is to produce an extra-retinal coordinate frame (such as a head-based representation). We investigate this issue by behavioral means: Participants learned to detect a 3D-pop-out target in a fixed position. Next, target was relocated in one coordinate frame while maintaining it fixed in the others. Performance was severely affected only when the change in target position occurred in a retinotopic coordinate frame. This further suggests that perceptual learning occurs in retinotopic regions having receptive fields restricted within a hemifield.

Beyond retinotopic mapping: the spatial representation of objects in the human lateral occipital complex.

The spatial representation in the human ventral object-related areas (i.e., the lateral occipital complex [LOC]) is currently unknown. It seems plausible, however, that it would diverge from the strict retinotopic mapping (characteristic of V1) to a more invariant coordinate frame, thereby allowing for reliable object recognition in the face of eye, head, or body movement. To study this, we compared the fMRI activation in LOC when object displacement was limited to either the retina or the screen by manipulating eye position and object locations. We found clear adaptation in LOC when the object's screen position was fixed, regardless of the object's retinal position. Furthermore, we found significantly greater activation in LOC in the hemisphere contralateral to the object's screen position, although the visual task was constructed in a way that the objects were present equally often on each of the 2 retinal hemifields. Together, these results indicate that a sizeable fraction of the neurons in LOC may have head-based receptive fields. Such an extraretinal representation may be useful for maintenance of object coherence across saccadic eye movements, which are an integral part of natural vision.