Introduction

The plasticity of the mammalian brain – that is, its ability to adapt to environmental situations by changing its connectivity – is one of its most outstanding properties, distinguishing it from most other computational devices. This plasticity is perhaps most striking in the sensory systems that provide input to the brain. The plasticity of sensory systems in higher centers of the brain, such as the cerebral cortex, is the basis for its adaptability to the environment. During individual development, neural plasticity is greater than during adulthood, which is necessitated by the growth of the organism and the need of the brain to get programmed. Although sensory plasticity tapers off in adulthood, it does not cease completely. This chapter deals with the behavioral, anatomical, and physiological plasticity in animals and humans that grow up blind. I discuss plasticity in the somatosensory and auditory systems of visually deprived cats, mice, and humans. Evidence for crossmodal plasticity was acquired using single-unit neurophysiology and neuroanatomy in animal models of early blindness and using imaging techniques in humans. The data support a concept of developmental plasticity whereby major sensory processing modules in the cortex are set up without the influence of sensory experience, but the sensory modality that drives them depends on sensory experience.

Expansion of Whisker-Barrel System in Early-Blind Animals

In rodents, the facial vibrissae, or whiskers, provide one of the most important sources of information to the brain. This is underscored by the fact that rodents possess a special representation in their somatosensory cortex known as barrels that can be visualized with various anatomical and histochemical techniques (Van der Loos and Woolsey, 1973). The barrel cortex shows pronounced intramodal plasticity: when one of the whiskers is removed, the corresponding barrel shrinks. However, this plasticity of the whisker-barrel system is apparent even when sensory deprivation is exerted in a different sensory modality, such as the visual: mice that are reared blind from birth with a binocular enucleation develop significantly longer vibrissae and, correspondingly, an expanded barrel field (Rauschecker et al., 1992; Fig. 8.1). This may be interpreted by increased usage of the whiskers, which leads to not only use-dependent expansion of their central representation but also a hypertrophy of the peripheral sense organ itself.

Introduction

Severe visual impairments varying in etiology and intensity, affect more than 280 million people worldwide (World Health Organization [WHO], 2011; Elkhayat, 2012). Although, as described in other chapters in this book, the brain of the blind undergoes massive plastic changes in an effort to compensate for the lack of vision, providing increased support for other senses and abilities, the blind and visually impaired remain significantly limited in their ability to perform tasks ranging from navigation and orientation to object recognition. Thus, the blind are prevented from fully taking part in modern society, constituting a major clinical and scientific challenge to develop effective visual rehabilitation techniques for them. Many attempts have been made to help the blind using a wide variety of different approaches; however, unfortunately, until recent years most have born discouraging results. This chapter discusses if and how the plasticity described in this book can be harnessed for visual rehabilitation in adulthood to enable the blind to use their own brain to process “raw” visual information, despite the discouraging outcome of past attempts. We describe several different approaches to visual rehabilitation and their practical real world and clinical results, focusing on sensory substitution devices and their potential. We then show some examples of what using these devices has taught us about the brain, offering a theoretical basis for their empirical results, and finish with some practical conclusions and recommendations for future visual rehabilitation attempts.

Historical Preamble

When I arrived in Cambridge in the late 1970s to work with the late Fergus Campbell, the notion of critical periods for visual development was already well established through the seminal works of Hubel and Wiesel (1967), Blakemore (1976), and others (see Daw, 1995). The clinical implication of this was also recognized, namely, that visual improvements from the patching treatment of amblyopia were likely to be strongly age dependent and ineffective after the age of 7 to 8 years. At that time, the wisdom of Sir Stewart Duke-Elder held sway: “for patching to work it needs to be total and complete, day and night.” Fergus always felt that the stronger the statement, the more likely it was to be wrong. In fact, at that time, I remember his method for choosing research projects for graduate students. He would go to his bookshelf and choose at random one of Duke-Elder's System of Ophthalmology volumes, open it at random and locate a definitive statement on some visual topic. “Let's show this is wrong,” he would say, and the die was cast for what usually turned out to be another fruitful piece of research.

Fergus felt that some form of active stimulation would be better than the passive viewing that resulted from patching. He was enamored with the idea of the visual cortex as a spatial frequency analyzer, and because my early results suggested amblyopes suffered from severe spatial distortions (Hess et al., 1978), his first suggestion for a new therapy was to show a single spatial frequency at sequential orientations to help their visual cortex “sort out” what we hypothesized were anomalous interactions between these spatial analysers.

Introduction

Amblyopia is a visual impairment of one eye caused by inadequate use during early childhood and cannot be corrected by optical means (American Academy of Ophthalmology, 2007). Clinically, it is usually defined as a visual acuity of 20/30 or worse without any apparent structural abnormality in the affected eye. Amblyopia is a significant public health issue because it is the number one cause of monocular visual loss worldwide, affecting 3 to 5 percent of the population in the Western world (Attebo et al., 1998; Hillis, 1986). Because of its prevalence, the financial burden of amblyopia is enormous. A major U.S. study estimated that untreated amblyopia causes a yearly loss of US$7.4 billion in earning power and a corresponding decrease in the gross domestic product. An estimated US$341 million is spent each year to prevent and treat amblyopia (Membreno et al., 2002). Unfortunately, approximately 50 percent of patients do not respond to therapies (Holmes, Beck, et al., 2003; Holmes, Kraker, et al., 2003; The Pediatric Eye Disease Investigator Group [PEDIG], 2003; Repka et al., 2004, 2008; Scheiman et al., 2005). The personal cost of amblyopia is also substantial. People with amblyopia (including those treated successfully and those whose treatment failed) often have limited career choices and reduced quality of life such as reduced social contact, distance and depth estimation deficits, visual disorientation, and fear of losing vision in the better eye (van de Graaf et al., 2004).

Introduction

The central nervous system (CNS) integrates information from multiple sensory modalities, including visual and proprioceptive information, when planning a reaching movement (Jeannerod, 1988). Although visual and proprioceptive information regarding hand (or end point effector) position are not always consistent, performance is typically better under reaching conditions in which both sources of information are available. Under certain task conditions, visual signals tend to dominate such that one relies more on visual information than proprioception to guide movement. For example, individuals reaching to a target with misaligned visual feedback of the hand, as experienced when reaching in a virtual reality environment or while wearing prism displacement goggles, adjust their movements in order for the visual representation of the hand to achieve the desired end point even when their actual hand is elsewhere in the workspace (Krakauer et al., 1999, 2000; Redding and Wallace, 1996; Simani et al., 2007). This motor adaptation typically occurs rapidly, reaching baseline levels within twenty trials per target, and without participants' awareness (Krakauer et al., 2000). Furthermore, participants reach with these adapted movement patterns following removal of the distortion, and hence show aftereffects (Baraduc and Wolpert, 2002; Buch et al., 2003; Krakauer et al., 1999, 2000; Martin et al., 1996). These aftereffects provide a measure of motor learning referred to as visuomotor adaptation and result from the CNS learning a new visuomotor mapping to guide movement.

In this chapter, we discuss the recently proposed residual vision activation theory that is based on both human and animal studies (Sabel, Henrich-Noack, et al., 2011). The central point of the theory is that partially damaged brain systems have a particularly good potential for restoration of vision. Fortunately, in the clinical world, complete visual system lesions are extremely rare because complete damage is only found in total eye or optic nerve damage or some severe congenital defects. As a consequence, even in patients considered to be legally blind, there is almost always some degree of residual vision and hence restoration potential.

This chapter focuses on human studies and therapeutic applications that build on the “residual vision activation theory.” We discuss work with patients that suffered postretinal lesions to the central visual pathway. Although visual fields may recover spontaneously to some extent, after the first few weeks or months following damage, this recovery no longer continues in most cases. Therefore, we focus on the time after this initial recovery and consider the effects of training procedures and noninvasive alternating current stimulation as an innovative mean to kindle vision restoration long after the lesion has occurred. Both treatment approaches restore visual fields, mainly in areas that were not absolutely blind but have some residual capacities. The nature of residual vision, its measurement, and the role of activating residual vision as a means to promote recovery of vision are discussed.

At birth, infants can see only large objects of high contrast located in the central visual field. Over the next half year, basic visual sensitivity improves dramatically. The infant begins to perceive the direction of moving objects and stereoscopic depth, and to integrate the features of objects and faces. Nevertheless, it takes until about 7 years of age for acuity and contrast sensitivity to become as acute as those of adults and into adolescence for some aspects of motion and face processing to reach adult levels of expertise.

An important developmental question is whether, and to what extent, the improvements in vision during normal development depend on normal visual experience. To find out, we have taken advantage of a natural experiment: children born with dense, central cataracts in both eyes that block all patterned visual input to the retina. The children are treated by surgically removing the cataractous lenses and fitting the eyes with compensatory contact lenses that allow the first focused patterned visual input to reach the retina. In the studies summarized in this chapter, the duration of deprivation – from birth until the fitting of contact lenses after surgery – ranged from just a few weeks to most of the first year of life. In other cases, the child began with apparently normal eyes but developed dense bilateral cataracts postnatally that blocked visual input. As in the congenital cases, the cataractous lenses were removed and the eyes fitted with contact lenses.

When we look at our environment, we immediately detect and recognize they objects, buildings, and people surrounding us. Our perception of fine detail, lines, edges, color, movement, and depth are all important for building up representations of these objects, scenes, and people. This processing occurs rapidly and is achieved effortlessly by the visual system as we take in the world with both eyes. Imagine what it might be like to not have vision through two eyes – to be completely blind. We would have to use our remaining intact sensory systems to their fullest capacity in order to interact with the world. Our senses of touch, taste, smell, and hearing would become significantly more important to allow us to connect with and understand our world.

Now instead, consider what it might be like to lose vision in only one eye. With one completely nonfunctional eye and one intact eye, our visual system would still receive light input through the intact remaining eye. So, one might ask, how could having only one eye affect our ability to see? From a systems point of view, the physical light input to our visual system would be reduced by half compared to the intact binocular visual system.

Introduction

The brain has long been considered as being hard wired in a predetermined manner shaped by evolution. This view has been challenged in the past decades by increasing evidence documenting the impressive capacity of the brain to be modulated through learning and experience, even well into adulthood. Pioneering studies of Hubel and Wiesel (1963; Hubel et al., 1977) on the development of ocular dominance columns have compellingly demonstrated that alterations in visual experience can influence the normal development of the visual cortex.

One of the most striking demonstrations of experience-dependent plasticity comes from studies in congenitally blind individuals (CB) showing dramatic cortical reorganizations as a consequence of visual deprivation. Experiments have documented that cortical sensory maps in the remaining senses of CB can expand with experience. For instance, finger representation in the somatosensory cortex is increased in blind individuals who are proficient Braille readers (Pascual-Leone et al., 1993; Sterr et al., 1999), and the tonotopic map in the auditory cortex is larger in visually deprived individuals (Elbert et al., 2002). Such cortical changes are thought to underlie enhanced reading abilities and auditory processing skills in the blind (Elbert et al., 2002; Sterr et al., 1998).

Aside from these examples of intramodal plasticity, massive crossmodal changes have been reported in the occipital cortex deprived of its natural visual inputs. In people born blind, occipital regions thatwould normally process visual stimuli are “hijacked” by the other senses as these regions become responsive to nonvisual input (Bavelier and Neville, 2002; Pascual-Leone et al., 2005).

When I was 48 years old, my vision improved in ways that most scientists and physicians considered impossible (Barry, 2009; Sacks 2006, 2010). I had developed strabismus, or misaligned eyes, within the first months of life. When I looked at an object, I aimed or fixated one eye at the target and turned the other eye in. In contrast, most infants aim their eyes simultaneously at the same point in space and are able to fuse the two eyes' images into one view of the world. They develop stereopsis, or the ability to use the slightly different viewing perspectives of the two eyes to create the perception of stereoscopic depth. Because I aimed my eyes at different regions of space, I received uncorrelated images that could not be fused. How could I create a single worldview from the conflicting input from my two eyes? Like most children with strabismus, I learned to ignore or suppress the input from the turned eye. This provided me with a single view of the world but one that lacked stereoscopic depth. I did not see with stereopsis: I was stereoblind.

In an attempt to correct this condition, I underwent three eye muscle surgeries at the ages of 2, 3, and 7 years. The operations helped my eyes to look straight but did not change my viewing habits. I continued to fixate with one eye and turn in the other, rapidly alternating between the eye that I used for fixation and the eye that I turned in.