Annual Review of Vision Science - Volume 2, 2016

The author relates his intellectual journey from eye-testing clinician to experimental vision scientist. Starting with the quest for underpinning in physics and physiology of vague clinical propositions and of psychology's acceptance of thresholds as “fuzzy-edged,” and a long career pursuing a reductionist agenda in empirical vision science, his journey led to the realization that the full understanding of human vision cannot proceed without factoring in an observer's awareness, with its attendant uncertainty and open-endedness. He finds support in the loss of completeness, finality, and certainty revealed in fundamental twentieth-century formulations of mathematics and physics. Just as biology prospered with the introduction of the emergent, nonreductionist concepts of evolution, vision science has to become comfortable accepting data and receiving guidance from human observers’ conscious visual experience.

During development, the environment exerts a profound influence on the wiring of brain circuits. Due to the limited resolution of studies in fixed tissue, this experience-dependent structural plasticity was once thought to be restricted to a specific developmental time window. The recent introduction of two-photon microscopy for in vivo imaging has opened the door to repeated monitoring of individual neurons and the study of structural plasticity mechanisms at a very fine scale. In this review, we focus on recent work showing that synaptic structural rearrangements are a key mechanism mediating neural circuit adaptation and behavioral plasticity in the adult brain. We examine this work in the context of classic studies in the visual systems of model organisms, which have laid much of the groundwork for our understanding of activity-dependent synaptic remodeling and its role in brain plasticity.

Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system.

A classic problem in psychology is understanding how the brain creates a stable and accurate representation of space for perception and action despite a constantly moving eye. Two mechanisms have been proposed to solve this problem: Herman von Helmholtz's idea that the brain uses a corollary discharge of the motor command that moves the eye to adjust the visual representation, and Sir Charles Sherrington's idea that the brain measures eye position to calculate a spatial representation. Here, we discuss the cognitive, neuropsychological, and physiological mechanisms that support each of these ideas. We propose that both are correct: A rapid corollary discharge signal remaps the visual representation before an impending saccade, computing accurate movement vectors; and an oculomotor proprioceptive signal enables the brain to construct a more accurate craniotopic representation of space that develops slowly after the saccade.

The mechanisms underlying the emergence of orientation selectivity in the visual cortex have been, and continue to be, the subjects of intense scrutiny. Orientation selectivity reflects a dramatic change in the representation of the visual world: Whereas afferent thalamic neurons are generally orientation insensitive, neurons in the primary visual cortex (V1) are extremely sensitive to stimulus orientation. This profound change in the receptive field structure along the visual pathway has positioned V1 as a model system for studying the circuitry that underlies neural computations across the neocortex. The neocortex is characterized anatomically by the relative uniformity of its circuitry despite its role in processing distinct signals from region to region. A combination of physiological, anatomical, and theoretical studies has shed some light on the circuitry components necessary for generating orientation selectivity in V1. This targeted effort has led to critical insights, as well as controversies, concerning how neural circuits in the neocortex perform computations.

Our perceptual abilities significantly improve with practice. This phenomenon, known as perceptual learning, offers an ideal window for understanding use-dependent changes in the adult brain. Different experimental approaches have revealed a diversity of behavioral and cortical changes associated with perceptual learning, and different interpretations have been given with respect to the cortical loci and neural processes responsible for the learning. Accumulated evidence has begun to put together a coherent picture of the neural substrates underlying perceptual learning. The emerging view is that perceptual learning results from a complex interplay between bottom-up and top-down processes, causing a global reorganization across cortical areas specialized for sensory processing, engaged in top-down attentional control, and involved in perceptual decision making. Future studies should focus on the interactions among cortical areas for a better understanding of the general rules and mechanisms underlying various forms of skill learning.

Neurons in early visual cortical areas not only represent incoming visual information but are also engaged by higher level cognitive processes, including attention, working memory, imagery, and decision-making. Are these cognitive effects an epiphenomenon or are they functionally relevant for these mental operations? We review evidence supporting the hypothesis that the modulation of activity in early visual areas has a causal role in cognition. The modulatory influences allow the early visual cortex to act as a multiscale cognitive blackboard for read and write operations by higher visual areas, which can thereby efficiently exchange information. This blackboard architecture explains how the activity of neurons in the early visual cortex contributes to scene segmentation and working memory, and relates to the subject's inferences about the visual world. The architecture also has distinct advantages for the processing of visual routines that rely on a number of sequentially executed processing steps.

Circadian rhythms are self-sustained, approximately 24-h rhythms of physiology and behavior. These rhythms are entrained to an exactly 24-h period by the daily light-dark cycle. Remarkably, mice lacking all rod and cone photoreceptors still demonstrate photic entrainment, an effect mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells utilize melanopsin (OPN4) as their photopigment. Distinct from the ciliary rod and cone opsins, melanopsin appears to function as a stable photopigment utilizing sequential photon absorption for its photocycle; this photocycle, in turn, confers properties on ipRGCs such as sustained signaling and resistance from photic bleaching critical for an irradiance detection system. The retina itself also functions as a circadian pacemaker that can be autonomously entrained to light-dark cycles. Recent experiments have demonstrated that another novel opsin, neuropsin (OPN5), is required for this entrainment, which appears to be mediated by a separate population of ipRGCs. Surprisingly, the circadian clock of the mammalian cornea is also light entrainable and is also neuropsin-dependent for this effect. The retina thus utilizes a surprisingly broad array of opsins for mediation of different light-detection tasks.

Much remains to be understood about visual system malfunction following injury. The resulting deficits range from dense, visual field scotomas to mild dysfunction of visual perception. Despite the predictive value of anatomical localization studies, much patient-to-patient variability remains regarding (a) perceptual abilities following injury and (b) the capacity of individual patients for visual rehabilitation. Visual field perimetry is used to characterize the visual field deficits that result from visual system injury. However, standard perimetry mapping does not always precisely correspond to underlying anatomical or functional deficits. Functional magnetic resonance imaging can be used to probe the function of surviving visual circuits, allowing us to classify better how the pattern of injury relates to residual visual perception. Identifying pathways that are potentially modifiable by training may guide the development of improved strategies for visual rehabilitation. This review discusses primary visual cortex lesions, which cause dense contralateral scotomas.

Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions.

Glaucoma is a complex disorder of aging defined by the death of retinal ganglion cells and remodeling of connective tissues at the optic nerve head. Intraocular pressure-induced axonal injury at the optic nerve head leads to apoptosis. Loss of retinal ganglion cells follows a slowly progressive sequence. Clinical features of the disease have suggested and corroborated pathological events. The death of retinal ganglion cells causes secondary loss of neurons in the brain, but only as a by-product of injury to the retinal ganglion cells. Although therapy to lower intraocular pressure is moderately effective, new treatments are being developed to alter the remodeling of ocular connective tissue, to interrupt the injury signal from axon to soma, and to upregulate a variety of survival mechanisms.

Research on aging and vision has increased dramatically over the past few decades. Changes in our visual capacities in later adulthood have the potential to impact our ability to perform common everyday visual tasks such as recognizing objects, reading, engaging in mobility activities, and driving, thus influencing the quality of our life and well-being. Here, we discuss several common visual problems in older adults that cause performance problems in the visual tasks of everyday living and when exacerbated are related to the development of common eye conditions and diseases of aging.

Retinal prostheses aim to restore vision to blind individuals suffering from retinal diseases such as retinitis pigmentosa and age-related macular degeneration. These devices function by electrically stimulating surviving retinal neurons, whose activation is interpreted by the brain as a visual percept. Many prostheses are currently under development. They are categorized as epiretinal, subretinal, and suprachoroidal prostheses on the basis of the placement of the stimulating microelectrode array. Each can activate ganglion cells through direct or indirect stimulation. The response of retinal neurons to these modes of stimulation are discussed in detail and are placed in context of the visual percept they are likely to evoke. This article further reviews challenges faced by retinal prosthesis and discusses potential solutions to address them.

Ophthalmology was the first medical specialty to adopt lasers right after their invention more than 50 years ago, and they gradually revolutionized ocular imaging, diagnostics, therapy, and surgery. Challenging precision, safety, and selectivity requirements for ocular therapeutic and surgical procedures keep advancing the laser technologies, which in turn continue enabling novel applications for the preservation and restoration of sight. Modern lasers can provide single-cell-layer selectivity in therapy, submicrometer precision in three-dimensional image-guided surgery, and nondamaging retinal therapy under optoacoustic temperature control. This article reviews the evolution of laser technologies; progress in understanding of the laser–tissue interactions; and concepts, misconceptions, and accidental discoveries that led to modern therapeutic and surgical applications of lasers in ophthalmology. It begins with a brief historical overview, followed by a description of the laser–tissue interactions and corresponding ophthalmic applications.

Low vision is any type of visual impairment that affects activities of daily living. In the context of low vision, we define plasticity as changes in brain or perceptual behavior that follow the onset of visual impairment and that are not directly due to the underlying pathology. An important goal of low-vision research is to determine how plasticity affects visual performance of everyday activities. In this review, we consider the levels of the visual system at which plasticity occurs, the impact of age and visual experience on plasticity, and whether plastic changes are spontaneous or require explicit training. We also discuss how plasticity may affect low-vision rehabilitation. Developments in retinal imaging, noninvasive brain imaging, and eye tracking have supplemented traditional clinical and psychophysical methods for assessing how the visual system adapts to visual impairment. Findings from contemporary research are providing tools to guide people with low vision in adopting appropriate rehabilitation strategies.

Human perception is remarkably flexible: We experience vivid three-dimensional (3D) structure under diverse conditions, from the seemingly random magic-eye stereograms to the aesthetically beautiful, but obviously flat, canvases of the Old Masters. How does the brain achieve this apparently effortless robustness? Using brain imaging we are beginning to discover how different parts of the visual cortex support 3D perception by tracing different computations in the dorsal and ventral pathways. This review concentrates on studies of binocular disparity and its combination with other depth cues. This work suggests that the dorsal visual cortex is strongly engaged by 3D information and is involved in integrating signals to represent the structure of viewed surfaces. The ventral cortex may store representations of object configurations and the features required for task performance. These differences can be broadly understood in terms of the different computational demands of reducing estimator variance versus increasing the separation between exemplars.

How do we recognize objects despite changes in their appearance? The past three decades have been witness to intense debates regarding both whether objects are encoded invariantly with respect to viewing conditions and whether specialized, separable mechanisms are used for the recognition of different object categories. We argue that such dichotomous debates ask the wrong question. Much more important is the nature of object representations: What are features that enable invariance or differential processing between categories? Although the nature of object features is still an unanswered question, new methods for connecting data to models show significant potential for helping us to better understand neural codes for objects. Most prominently, new approaches to analyzing data from functional magnetic resonance imaging, including neural decoding and representational similarity analysis, and new computational models of vision, including convolutional neural networks, have enabled a much more nuanced understanding of visual representation. Convolutional neural networks are particularly intriguing as a tool for studying biological vision in that this class of artificial vision systems, based on biologically plausible deep neural networks, exhibits visual recognition capabilities that are approaching those of human observers. As these models improve in their recognition performance, it appears that they also become more effective in predicting and accounting for neural responses in the ventral cortex. Applying these and other deep models to empirical data shows great promise for enabling future progress in the study of visual recognition.

Creating realistic three-dimensional (3D) experiences has been a very active area of research and development, and this article describes progress and what remains to be solved. A very active area of technical development has been to build displays that create the correct relationship between viewing parameters and triangulation depth cues: stereo, motion, and focus. Several disciplines are involved in the design, construction, evaluation, and use of 3D displays, but an understanding of human vision is crucial to this enterprise because in the end, the goal is to provide the desired perceptual experience for the viewer. In this article, we review research and development concerning displays that create 3D experiences. And we highlight areas in which further research and development is needed.

This review discusses several pervasive myths about peripheral vision, as well as what is actually true: Peripheral vision underlies a broad range of visual tasks, in spite of its significant loss of information. New understanding of peripheral vision, including likely mechanisms, has deep implications for our understanding of vision. From peripheral recognition to visual search, from change blindness to getting the gist of a scene, a lossy but relatively fixed peripheral encoding may determine the difficulty of many tasks. This finding suggests that the visual system may be more stable, and less dynamically changing as a function of attention, than previously assumed.

Visual confidence refers to an observer's ability to judge the accuracy of her perceptual decisions. Even though confidence judgments have been recorded since the early days of psychophysics, only recently have they been recognized as essential for a deeper understanding of visual perception. The reluctance to study visual confidence may have come in part from obtaining convincing experimental evidence in favor of metacognitive abilities rather than just perceptual sensitivity. Some effort has thus been dedicated to offer different experimental paradigms to study visual confidence in humans and nonhuman animals. To understand the origins of confidence judgments, investigators have developed two competing frameworks. The approach based on signal decision theory is popular but fails to account for response times. In contrast, the approach based on accumulation of evidence models naturally includes the dynamics of perceptual decisions. These models can explain a range of results, including the apparently paradoxical dissociation between performance and confidence that is sometimes observed.