Topics in Cognitive Science 2 (2010) 306–319 Copyright  2009 Cognitive Science Society, Inc. All rights reserved. ISSN: 1756-8757 print / 1756-8765 online DOI: 10.1111/j.1756-8765.2009.01052.x

Spontaneous and Training-Induced Visual Learning in Cortical Blindness: Characteristics and Neural Substrates Tim Martin, Krystel R. Huxlin University of Rochester Eye Institute and Center for Visual Science Received 28 February 2009; received in revised form 15 May 2009; accepted 26 May 2009

Abstract Visual learning has been intensively studied in higher mammals, both during development and in adulthood. What is less clear is the extent and properties such plasticity may acquire following permanent damage to the adult visual system. Answering this question is important. Aside from improving our understanding of visual processing in the absence of an intact visual circuitry, such knowledge is essential for the development of effective therapies to rehabilitate the increasing number of people who suffer the functional consequences of damage at different levels of their visual cortical hierarchy. This review summarizes the known characteristics of visual learning after adult visual cortex damage and begins to dissect some of the neural correlates of this process. Keywords: Visual learning; Visual motion; V1 damage; Extrastriate cortex; Plasticity; Blindsight

1. Introduction Learning is tied in the popular imagination to the acquisition of complex skills—the ability to play a musical instrument, speak and understand a new language, and reason in abstract domains such as logic and mathematics. Surely simple perceptual-motor tasks, such as reacting to a flash of light or discriminating the direction of motion or orientation of a line, are so well established during development by exposure to our complex, dynamic environment that further learning in adulthood is unnecessary and even impossible. Yet decades of research have shown that throughout the life span, even the simplest perceptual-motor tasks are subject to improved performance with repetitive practice (Goldstone, 1998; Huxlin, 2008; Sagi & Tanne, 1994), a phenomenon termed ‘‘perceptual learning.’’ The study of perceptual learning in adult systems is important for several reasons. First, it is important in Correspondence should be sent to Krystel R. Huxlin, Department of Ophthalmology, University of Rochester Eye Institute, 601 Elmwood Avenue, Box 314, Rochester, NY 14642. E-mail: [email protected]

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its own right, as a psychological phenomenon to be explained. Second, studies of perceptual learning can provide a window onto its presumptive underlying neural mechanism—neural plasticity. Finally, and most important in the context of the current review, perceptual learning may provide a tool for addressing otherwise intractable sensory losses that often arise in aging or damaged adult organisms.

2. Visual cortex damage: Consequences for perception Unilateral damage to the human primary visual cortex (V1) or its primary inputs causes an inability to consciously perceive most types of visual information in the contralateral visual hemifield, a deficit that has been termed ‘‘cortical blindness’’ (Cowey & Stoerig, 1991, 1995; Holmes, 1918; Teuber, Battersby, & Bender, 1960; Weiskrantz, Warrington, Sanders, & Marshall, 1974). When it affects the majority of the contralateral hemifield, cortical blindness is referred to as a ‘‘homonymous hemianopia’’ or ‘‘hemianopsia.’’ When affecting just a quadrant of the visual field, this deficit is called a ‘‘homonymous quadrantanopia.’’ Although the visual system of humans and other primates is indeed large, complex, and comprised of many different brain centers, there are specific reasons why damage to this single cortical area causes an actual blindness. First, V1 damage destroys an important visual processing center that is involved in the extraction of basic features such as location and orientation (Hubel, 1982; Hubel & Wiesel, 1959), and it may also contribute to higher level perceptual processes and awareness (Lee, Mumford, Romero, & Lamme, 1998; Lee, Yang, Romero, & Mumford, 2002; Rossi, Rittenhouse, & Paradiso, 1996). However, perhaps the most important reason for the dramatic effects of V1 damage are most clearly observed on circuit diagrams of the primate visual system (Fig. 1—see also Felleman & Van Essen, 1991; Van Essen, Anderson, & Felleman, 1992). These clearly show V1 as a major gateway for the transfer of visual information from subcortical centers to the rest of extrastriate visual cortical areas. Therefore, damage to V1 deprives the multiplicity of other visual cortical areas in the brain of a major source of activation and thus information. Finally, V1 damage also affects subcortical stages of visual processing. Indeed, it appears to cause retrograde degeneration of neurons in retinotopically corresponding areas of the dorsal lateral geniculate nucleus (dLGN) and, subsequently, the death of a portion of the parvocellular or Pb retinal ganglion cells in the eye (Cowey & Stoerig, 1991; Cowey, Stoerig, & Perry, 1989). Given the importance of these circuits for acuity, color vision, and form vision, one begins to understand how broad and devastating the effect of V1 damage can be for visual perception and, consequently, visually guided functions in everyday life. Not surprisingly, cortical blindness is an important cause of long-term disability in survivors of stroke and traumatic brain injury (Pambakian, Mannan, Hodgson, & Kennard, 2004; Peli, 2000). Patients with V1 damage are unable to consciously perceive brightness or contrast in their affected hemifield. Most report significant difficulties when reading (Leff et al., 2000; McDonald, Spitsyna, Shillcock, Wise, & Leff, 2006) or navigating in the complex, dynamic visual environments of everyday life (Marigold, Weedersteyn, Patla, & Duysens, 2007; Turano et al., 2004). This can adversely affect their ability to drive, perform most

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Fig. 1. Basic anatomy and connectivity of the primate visual system. (A) Schematic diagram illustrating, in an inferior view of the human brain, the main primary visual projections, which originate in the eyes, travel through the optic nerves and chiasm, synapse in the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the superior colliculus (SC). From the dLGN, most of the visual information travels via the optic radiations to the striate or primary visual cortex (V1). (B) Simplified diagram illustrating some of the more important connections of the standard feed-forward model of visual information processing in the monkey brain (in which these circuits have been much better defined than in humans). These major feed-forward pathways are indicated with black arrows and show the significant divergence of information sent from V1 to different areas making up the rest of extrastriate visual cortex (V2, V4, V3, V3a, V5, etc.). Note that most of these cortico–cortical connections are reciprocal. The alternate pathways found to transmit information from the retina to cortex are indicated with red arrows and appear to effectively bypass V1 in transmitting visual information directly to extrastriate visual areas. These alternate pathways process visual information that is more narrowly tuned in terms of spatial and temporal frequencies, relative to the main retino-geniculo-striate pathway. They are, however, hypothesized to underlie residual visual processing capacities in blindsight and may provide a mechanism for eliciting improvements in visual perception through targeted retraining following V1 damage.

jobs, and enjoy many recreational activities, thus severely affecting their overall quality of life.

3. What the blind can see and why: Neural substrates of residual vision in the blind field Almost surprisingly, given V1’s critical role in vision, V1 damage does not completely eliminate visual processing or sensation within cortically blind portions of the visual field (e.g., Barbur, Harlow, & Weiskrantz, 1994; Morland et al., 1999; Po¨ppel, Held, & Frost, 1973; Riddoch, 1917; Weiskrantz, 1986, 1990, 1996). Evidence from, humans and monkeys demonstrates the existence of basic residual visual motion, form, and wavelength sensitivity in the blind field (e.g., Blythe, Kennard, & Ruddock, 1987; Cowey & Stoerig, 1995; Pasik & Pasik, 1982; Weiskrantz, Harlow, & Barbur, 1991; Zeki & Ffytche, 1998). Such preserved vision was originally termed ‘‘blindsight’’ (Weiskrantz, 1986; Weiskrantz et al., 1974) to denote the fact that it often occurred in the absence of awareness. Residual vision after V1 damage differs significantly from vision with an intact visual system in that it is

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narrowly tuned in the spatio-temporal frequency domain (Barbur et al., 1994; Sahraie et al., 2003; Weiskrantz et al., 1991). Visual stimuli that are sensed tend to be simple (e.g., gratings), containing relatively low spatial frequencies (0.5–2 cycle ⁄ deg), temporal frequencies around 10 Hz, speeds greater than about 5 ⁄ s, and a steep onset and offset (Morland et al., 1999). Residual functions vary considerably among affected individuals, perhaps as a function of the amount and precise location of damage sustained (Blythe et al., 1987; Morland, Le, Carrol, Hoffmann, & Pambakian, 2004). One possible explanation for residual visual capacities after V1 damage is spared islands of tissue within V1 (Fendrich, Wessinger, & Gazzaniga, 1992; Wessinger, Fendrich, & Gazzaniga, 1997). Another possibility is the existence of pathways that bypass V1 to transmit information from the dLGN directly to extrastriate cortical areas, including V2 (Hendry & Reid, 2000), V4 (Cowey & Stoerig, 1989), and V5 or the medial temporal (MT) and medial superior temporal (MST) areas (Sincich, Park, Wohlgemuth, & Horton, 2004). In addition, there are extra-geniculo-calcarine pathways that bypass both the dLGN and V1, and terminate in extrastriate visual cortex (reviewed in Cowey & Stoerig, 1991). The extra-geniculo-calcarine pathway most commonly invoked in residual visual functions after V1 damage is the retinal projection to the superior colliculus (SC), hence to the pulvinar ⁄ LP complex and finally, to extrastriate visual cortex, especially dorsal stream areas such as MT ⁄ MST (Benevento & Rezak, 1976; Cragg, 1969). All these alternate pathways are thought to be relatively small, especially in contrast with the size of the retino-geniculo-calcarine pathway. Consequently, although blindsight is of great interest for what it can reveal about visual processing, it does not appear to play a significant role in conscious perception or visually guided behaviors (Pambakian & Kennard, 1997).

4. Spontaneous plasticity in cortical blindness Oftentimes, the severity of functional deficits induced by a stroke or brain trauma resolves spontaneously over time. With respect to visual cortex damage, a decrease in the extent of the blind field is often reported, but it is usually small and restricted temporally to the first few weeks or months after the insult, and it occurs primarily in the border region between blind and intact portions of the visual field (Zhang, Kedar, Lynn, Newman, & Biousse, 2006). Such improvements are thought to be due to resolving inflammation around the damaged zone and ⁄ or a return of function in neural circuits damaged but not destroyed by the insult (Poggel, Kasten, Mu¨ller-Oehring, Sabel, & Brandt, 2001; Sabel, 1997). With very rare exceptions (e.g., Poggel et al., 2001), perimetric visual improvements are not seen after the second or third month postlesion (Tiel & Kolmel, 1991; Zhang et al., 2006). Electrophysiological studies have shown that in addition to resolving inflammation around the lesion site, spontaneous plasticity following V1 damage may also be mediated by changes in the properties of neural circuits adjoining the lesion (reviewed in Eysel, 1997). Neurons in these perilesional circuits can exhibit significant plasticity, including changes in excitability (Eysel & Schmidt-Kastner, 1991), receptive field size (Eysel &

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Schweigart, 1999), neurochemistry and channel properties (Barmashenko, Eysel, & Mittmann, 2003; Rumpel et al., 2000), and even physical remodeling of synaptic structures such as spines (Keck et al., 2008). Indeed some of the changes in long-term potentiation and ion (especially Ca2+) permeability may underlie the observed changes in field size and excitability around the lesion site (Eysel et al., 1999). Lesions of the postchiasmal afferents to V1 can cause hemianopia ⁄ quadrantanopia while leaving V1 largely intact. Dilks, Serences, Rosenau, Yantis, and McCloskey (2007) reported that in one such patient with an anopic quadrant stimulation of the intact quadrant near the border with the blind quadrant caused distorted object perception in the blind field. Specifically, this person perceived objects near the border of the anopic field to be elongated, extending into the blind portion of the visual field. Although it is not currently possible to establish the exact anatomical and physiological substrates of such perceptual plasticity, these could include disinhibition of preexisting long-range horizontal connections within V1 (Darian-Smith & Gilbert, 1995; Das & Gilbert, 1995), sprouting of new horizontal connections in V1 (Darian-Smith & Gilbert, 1994), or changes in the functional interactions between higher-level visual cortical areas and V1 (De Weerd, Gattass, Desimone, & Ungerleider, 1995; Mendola, Conner, Sharma, Bahekar, & Lemieux, 2006; Mendola, Dale, Fischl, Liu, & Tootell, 1999). Thus, the bulk of experimental evidence suggests that spontaneous plasticity after V1 damage, although present, is quite limited, particularly in terms of regaining lost visual perceptual abilities.

5. Spontaneous behavioral adaptation and compensation after V1 damage A ‘‘ray of hope’’ and an important indication of the potential for perceptual plasticity in damaged, adult visual systems is the observation of spontaneous functional adaptation to and compensation for cortical blindness in both humans and nonhuman species. One of the best-studied and most significant changes in visual behavior following the onset of cortical blindness is a radical alteration in the pattern of eye movements and fixations during performance of visually guided tasks. For example, when presented with point light targets at different, random sites along the horizontal meridian, visually intact humans usually fixate the targets directly, but hemianopes rarely do (Meienberg, Zangemeister, Rosenberg, Hoyt, & Stark, 1981). Instead, when target duration and position are predictable, they perform a series of hypometric saccades that incrementally approach each target until it is found. Once target positions are learned, the saccades become hypermetric, overshooting the target by a few degrees of visual angle, and requiring a short, corrective saccade (Meienberg et al., 1981). Hypometric saccades are also observed when hemianopes are asked to search static images for a small target (Zangemeister, Oechsner, & Freksa, 1995) or when searching for a visual target among distracters (Chedru, Leblanc, & Lhermitte, 1973). Indeed, hemianopes exhibit longer search times, shorter and more frequent fixations, and shorter saccades than visually normal controls (Chedru et al., 1973). Hemianopes also spend more time looking toward their blind than their intact hemifields (Ishiai, Furukawa, & Tsukagoshi, 1987; Pambakian et al., 2000; Riley, Kelly,

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Martin, Hayhoe, & Huxlin, 2007; Zihl, 1995). This is not due to visual or attentional neglect with respect to the intact hemifield (Ishiai et al., 1987) but rather it represents a compensatory strategy. It is not known for certain when these patterns develop following the lesion, but similar patterns emerge within a matter of minutes when neurologically intact observers are confronted with a simulated hemianopic defect (Tant, Cornelissen, Kooijman, & Brouwer, 2002). The sequential gaze patterns exhibited by hemianopes while they perform naturalistic tasks strongly suggest that they also place greater weight on visual memory representations of their visual environment, compared to age-matched, visually intact controls (Martin, Riley, Kelly, Hayhoe, & Huxlin, 2007). All these changes in visual strategy after V1 damage occur spontaneously and in the presence of normal saccade and eye movement dynamics (Martin et al., 2007; Zangemeister et al., 1995), suggesting that they are a true adaptation to the perceptual deficit rather than being due to abnormal oculo-motor control. Because patterns of gaze allocation reflect the quality and quantity of visual information needed and gathered by the organism (Hayhoe & Ballard, 2005; Triesch, Ballard, Hayhoe, & Sullivan, 2003), changes in gaze strategy following visual loss may represent a form of visual plasticity. However, while they provide for a small improvement in visually guided function, people with long-standing cortical blindness, who display all of the adaptive and compensatory eye movement behaviors described above, still complain about the negative impact of their impaired vision on reading, driving, navigation, and life.

6. Training-induced visual relearning in cortical blindness In contrast to cases of motor deficits induced by damage to motor cortex, where rehabilitation is aggressive and relatively successful (Hallett, 2001; Taub, Uswatte, & Elbert, 2002), restoration of vision after postchiasmal brain lesions is highly controversial and rarely attempted clinically (Horton, 2005; Pambakian & Kennard, 1997). Several research groups have asked, given what we know about residual visual pathways after V1 damage and mechanisms of perceptual learning in general, whether directed, visual training could be used to induce visual relearning in cortically blind fields. In adult monkeys with V1 damage, visual training did restore the ability to detect and localize visual stimuli in the blind field (Cowey & Weiskrantz, 1963; Mohler & Wurtz, 1977). These improvements did not occur spontaneously, but required training (Cowey & Weiskrantz, 1963), and they were largely restricted to retrained visual field regions (Mohler & Wurtz, 1977). In humans, several paradigms for visual rehabilitation of cortical blindness have been tested. The only commercially available option is Nova Vision’s Visual Restitution Training or VRT (Kasten, Poggel, & Sabel, 2000; Kasten & Sabel, 1995; Kasten, Wu¨st, BehrensBaumann, & Sabel, 1998; Sabel & Kasten, 2000), who requires clients to fixate a starshaped spot of light while clicking a button every time a bright spot of light is detected on a dark background at one of 500 positions along the border of the sighted and blind hemifields (Kasten et al., 2000). NovaVision reports enlargements of the visible field of an average of about 5 of visual angle (Kasten et al., 1998), as well as improvements in subjective vision

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and activities of daily living (Mueller, Poggel, Kenkel, Kasten, & Sabel, 2003; Sabel, Kenkel, & Kasten, 2004). NovaVision’s claims have recently been challenged by a report that showed visual field improvements to disappear when subjects were tested using a scanning laser ophthalmoscope, a different instrument than that used for training, but one which could tightly control for eye movements (Reinhard et al., 2005). Raninen, Vanni, Hyva¨rinen, and Na¨sa¨nen (2006) trained two cortically blind subjects on a luminance detection task and a letter identification task using flickering stimuli presented at 10 and 30 eccentricity on the horizontal meridian. When compared to performance in their intact hemifield, both participants had regained normal flicker sensitivity in their blind field for 5 and 10 Hz flicker after 1 year of training. Changes in activity of intact visual cortical areas were demonstrated with neuromagnetic recordings (Raninen et al., 2006) and functional magnetic resonance imaging (fMRI; Henriksson, Raninen, Na¨sa¨nen, Hyva¨rinen, & Vanni, 2007). Sahraie et al. (2006) successfully trained cortically blind subjects to discriminate a vertical sinewave grating from a uniform background in their blind field, using stimuli that were optimized to take advantage of the narrow spatiotemporal properties of blind field channels (Sahraie et al., 2003). Results were confirmed by laboratory testing with fixation monitoring. Huxlin et al. (2009) trained adult humans with long-standing stroke-induced V1 damage to perform a global direction discrimination task with random dot stimuli at a single location in their blind field. The patients’ performance progressed from a complete inability to discriminate global motion direction to normal direction integration thresholds following 20–100 training sessions (i.e., 6,000–30,000 trials) in their blind field (Fig. 2). Improvements appeared to be permanent and were retinotopically restricted to retrained blind field locations. Furthermore, contrast sensitivity for direction and the ability to extract motion signals from noise improved at the trained blind-field locations, even though neither had been specifically trained. Interestingly, the spatial and temporal frequencies at which the greatest posttraining improvements in sensitivity were attained hovered around 0.5–1 cycles ⁄ deg and 10 Hz. This matches the known spatio-temporal channels thought to mediate blindsight (Barbur et al., 1994; Sahraie et al., 2003, 2006) and suggests that these channels may well play a role in mediating training-induced recovery of complex motion perception after V1 damage. A point of interest is that just as in the subjects trained by Sahraie et al. (2006), training-induced improvements in global motion discrimination after V1 damage were elicited at least 12, and in some cases 30 or more months after the subjects’ strokes (Huxlin et al., 2009), a time when spontaneous visual improvements in the blind field are no longer thought possible (Zhang et al., 2006). On a final note, although the perceptual learning elicited by Huxlin et al. generalized to other visual motion discriminations, it is not known whether it generalized to other visual functions such as form or color perception. And for all of the studies that have attempted to retrain vision in cortically blind subjects, another major unresolved issue is the functional significance of improvements in vision that are attained—how does improved performance on the relatively artificial stimuli and tasks presented during testing and training of these patients translate to the ability to perform visually guided activities of daily living? Future research is needed to answer this important question.

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Fig. 2. Training-induced recovery of global motion discrimination in the blind field of a human subject with long-standing homonymous hemianopia. (A) Schematic representation of the stimulus size and blind field location where visual training was performed (gray circle). Visual performance was also measured at a control location in the intact hemifield (black circle). Both locations are overlaid on the subject’s Humphrey perimetry data, collected through her right eye 8 months after a stroke that damaged her right occipital lobe (arrowed on MRI insert). (B) Plots of this patient’s visual performance on a left-right, global direction discrimination task using random dot stimuli presented at a single location in her blind field (gray circle in A). The top graph represents % correct performance in consecutive training sessions consisting of 300 trials each, at this location. Chance performance lies at 50% correct for this two-alternative forced-choice task. The bottom graph plots direction range (DR) thresholds measured in these same training sessions. DR thresholds are measured by fitting a Weibull function to the percent correct data at different DR levels and calculating the range of dot directions in the stimulus at which global direction discrimination performance is 75% correct. Note the dramatic improvement first in % correct performance, followed closely by improving thresholds, which reflect increased ability to integrate different motion directions in the random dot stimuli, and extract a global directional vector from them. The gray line and bar represent the mean and SD of thresholds measured at the control location in the intact hemifield. Note the initial period of guessing followed by a rapid increase to stable, near-normal global motion discrimination performance on this task.

7. Neural substrates of training-induced visual relearning after V1 damage The mechanisms of training-induced plasticity following visual cortex damage in adulthood are still poorly understood, and in humans, they could exhibit significant inter-individual variability. Indeed, brain lesions in humans following stroke or trauma are rarely identical and rarely respect functional or regional boundaries. Just as lesions may overlap several functional areas, in many cases, portions of V1 are actually spared. This presents the possibility that some blind portions of the visual field are represented by spared cortex that

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is functionally abnormal due to underperfusion. In support of this hypothesis, there are several case reports of reversal of homonymous hemianopia following arterial bypass to reperfuse occipital cortex (Benzel & Mirfarkhraee, 1987; Holbach, Wassman, Hoheluchter, & Jain, 1977; Roski, Spetzler, & Owen, 1979). Reperfusion has also been observed without surgery, over a longer period of time, in motor-related brain regions following motor therapy (Kononen et al., 2005). Perhaps a similar process takes place in the visual system with targeted, repetitive visual stimulation provided during training. Another possibility is that just like training in an intact brain, intensive visual training after V1 damage activates multiple higher-level visual areas via the extra-geniculo-calcarine pathways mentioned earlier. Such training may act to change responses in these areas in ways that are typical of training-induced changes in intact visual systems—that is, invoking ‘‘normal’’ mechanisms of perceptual learning such as better template matching, channel reweighing, reduction in internal noise, increased external noise filtering (e.g., Dosher & Lu, 1998, 1999, 2006), and changes in cellular and ⁄ or network sensitivities and specificities (e.g., Chowdhury & DeAngelis, 2008; Ghose, Yang, & Maunsell, 2002; Law & Gold, 2008; Schoups, Vogels, Qian, & Orban, 2001; Yang & Maunsell, 2004), also discussed in the article by Rufin Vogels in this volume of topiCS. Finally, it is also possible that visual training might induce visual recovery in the blind field via more significant reactivation and reorganization within and between intact extrastriate visual areas. Following V1 damage, it has been noted using a variety of techniques ranging from electrophysiology to fMRI, that extrastriate visual areas, although not directly damaged, sometimes appear deactivated or at the very least, exhibit abnormal responses to visual stimulation (Girard, Salin, & Bullier, 1992; Nelles et al., 2002). Several factors could contribute to this phenomenon. First, they have lost their primary source of feed-forward input, causing diaschisis (Feeney & Baron, 1986). This may also cause the unmasking of other connections that are normally latent or inhibited, such as occurs in the motor system (Jakobs & Donoghue, 1991). The resolution of these factors may be suboptimal in the normal course of recovery, but targeted retraining may act to improve function in these regions. For example, in a cat model of visual cortex damage, Huxlin, Williams, and Price (2008) found that glutamatergic (AMPA) receptor subunit expression in intact cortical areas interconnected with the lesioned zone was significantly down-regulated, even a year after the lesion. However, if animals were visually retrained to recovery in their impaired visual hemifield, glutamatergic receptor subunit expression returned to normal, although only in regions of cortex corresponding retinotopically to the retrained visual field locations. In humans, visual retraining could induce similar reactivation of intact visual areas, perhaps mediated by increased activity in the extra-geniculo-calcarine pathways that are thought to mediate blindsight.

8. Conclusion Postchiasmal lesions cause a profound, although not absolute, loss of vision. Residual functions are most likely mediated by pathways from retina to cortical and subcortical

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structures that bypass V1. Perceptual learning, both spontaneous and training induced, is possible in such cases and could potentially be harnessed to improve functional outcomes. There are now several reports of promising results using various paradigms in small groups of subjects. A high priority for future research is to definitively establish the efficacy of proposed training paradigms with large, randomized, double-blind clinical trials. Another high priority is to gain better understanding of the mechanisms of recovery, and the extent to which they involve reperfusion of perilesional tissue, retinal connections that bypass V1, and ⁄ or various forms of neural plasticity (dendritic and axonal sprouting, synaptogenesis, long-term potentiation and depression). Only then can we begin to utilize perceptual learning strategies as a tool to formulate more principled visual rehabilitation therapies for those who suffer from cortical blindness.

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