Vision - It Is About the Brain

Editorial Vision: It Is About the Brain Jason J. S. Barton, MD, PhD, FRCPC T his issue of the Journal of Neuro-Ophthalmology contains 2 articles about hallucinations and a review of cerebral visual problems beyond hemianopia, providing us with a welcome respite from our obsession with the optic nerve. Is that a rude comment? Maybe. But, as neuro-ophthalmologists, we do tend to focus a lot on that small bit of string and not on the large piece of jelly behind it. Yet, ultimately it is the brain that takes the constant stream of data from the eye and assembles and organizes a meaningful image of our world. Without it, we would have only a jumble of light and color and motion, perhaps not even a very good version of that. Hence, it is worth thinking about what the brain does for vision and, in particular, what happens when it fails to work properly. In this commentary, I merely add a few of my thoughts to the points raised in each of the 3 articles being highlighted. HALLUCINATIONS Hallucinations have great dramatic value: it is always interesting to see what the cerebral visual system gets up to when no one's watching, and normal inhibitory brakes are released. Often these occur as part of a general cognitive failure, as in dementia, toxic states, or delirium. However, when those states are excluded, hallucinations can be a sign that there is something more visually specific happening. Release hallucinations are rare only in the experience of physicians who fail to ask about them because many patients are reluctant to mention their startling visions (1-3). The deafferentation hypothesis proposes that visual input does not just feed us information, it also suppresses spontaneous background activity in the visual cortex. Without that input, the background activity-demonstrable with functional imaging (4-7)-is "released." The hallucinatory content varies with the cortical region that is currently speaking and does not reflect the site of the problem causing visual loss. This is why content is worthless as a localizing clue. Release hallucinations can occur with any kind of visual loss, from the refractive to the occipital. The report by Beaulieu et al (8) reminds us that deafferentation can even occur with visual deprivation that we physicians impose. Indeed, the most striking effects of sensory deprivation experiments in the 1950s were hallucinations much like those of patients with visual loss, with content ranging from simple patterns to bizarre scenes like marching squirrels or little yellow men with black hats (9). Logically, deafferentation should require binocular pathology, although others have contested this claim (1). Indeed, with ocular disorders, hallucinations often do not start until the second eye loses vision (10,11). The second point of Beaulieu et al (8) is that there are atypical cases with acute unilateral visual deprivation despite good vision in the unpatched eye (12,13) "under-afferentation" rather than deafferentation. Such cases would seem the exception rather than the rule and the question is, why does this happen in a few and not the many? One naturally suspects contributing factors besides visual loss, but what? A starting point might be the factors that increase the likelihood of release hallucinations in general, such as age (3,14), medications (15), social isolation (16), low visual stimulation (3), and mild cognitive impairment (16-19). Although we cannot make inferences confidently from a handful of briefly described cases, all these patients were old and patched in a post-anesthetic state (rather than for diplopia, for example). One might speculate that their hallucinations reflect the conjunction of acute Human Vision and Eye Movement Laboratory, Departments of Medicine (Neurology), Ophthalmology and Visual Science, Psychology, University of British Columbia, Vancouver, British Columbia, Canada. Studies of cerebral visual processing have been supported by operating grants from the National Institute of Mental Health (1R01 MH069898), Canadian Institutes of Health Research (MOP-77615, MOP-85004, MOP-102567, MOP-106511) and Natural Sciences and Engineering Research Council (Discovery Grants RGPIN 355879-08, RGPIN 319129). J. J. S. Barton is supported by a Canada Research Chair (950-228984) and the Marianne Koerner Chair in Brain Diseases. Address correspondence to Jason J. S. Barton, MD, PhD, FRCPC, Human Vision and Eye Movement Laboratory, VGH Eye Care Centre, 2550 Willow Street, Vancouver, BC, Canada V5Z 3N9; E-mail: [e-mail] Barton: J Neuro-Ophthalmol 2018; 38: 271-275 271 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial monocular deprivation, local or general anesthesia, possibly other medications, and vulnerable old brains. Peduncular hallucinations have content that is quite similar to that of release hallucinations, but these are attributed to brainstem lesions. They are usually accompanied by inversion of the sleep-wake cycle (20-24) and may reflect altered function of the substantia nigra pars reticulata (25), ascending reticular activating system (26), or thalamic reticular nuclei (23,26,27). The review by Galetta and Prasad (28) makes 2 important points. First, release hallucinations were not excluded in many reports, most of which involved posterior circulation strokes, because visual fields were not documented in 90% of reported cases. Second, ocular motor signs are not a necessary accompaniment, although they were common in the older literature. This is perhaps not surprising. In the days before neuroimaging, ocular motor signs would have been among the key clues to a brainstem lesion in a hallucinating patient. CEREBRAL VISUAL DYSFUNCTION are looking at a face, they just do not know whose face it is. Haque et al (29) note that premorbid expertise with a particular type of object may be an important factor. This point underlies old reports of prosopagnosic restaurant workers who could not recognize vegetables (31) and prosopagnosic farmers who could not recognize their cows (32,33). Yet, for each of these, there is a contrasting report of a prosopagnosic patient who could still recognize objects of their own personal expertise (34,35). Some of the difficulties with such cases are getting appropriate controls and quantifying that expertise: there are very few object categories like the face for which we can assume a universal, uniform proficiency. To advance on this, we developed a test of verbal knowledge about cars (e.g., is a 911 made by Porsche?) to index a person's car expertise first, before testing their visual car recognition. The verbal and visual scores turned out to be very highly correlated in control subjects (36). When this was applied to prosopagnosic subjects, they recognized fewer cars visually than was predicted by their verbal score (37). The hallucinations above are a curious by-product of the visual brain in response to problems elsewhere, but what about when the visual brain itself does not work? Haque et al (29) present a useful and concise review of the disorders of cerebral visual loss. The fact that these are not common makes them all the more fascinating. In the "state-of-the-art" spirit, I will supplement their review with one-well, no more than 2-fun facts about each disorder that I have learned in researching these problems. (I can only hope that this will not lead to accusations of shameless self-promotion, even if true). Topographic Disorientation Dyschromatopsia Pure alexia may not be as "pure" as we think. Writing a few simple words may be fine, but frequently these patients have a surface dysgraphia, in that they have trouble spelling irregular words (e.g., yacht, colonel) (39-41). You cannot use spelling rules to write these words; you need to look them up in a mental dictionary, and this also seems to be affected by left fusiform damage. It remains to be seen whether surface dysgraphia distinguishes between a disconnection variant of alexia and an agnosic variant from damage to the visual word form area. The key diagnostic feature of pure alexia is the wordlength effect. The more letters in a word, the longer it takes to read it (42). Pure alexia is a perceptual disorder and the number of letters is a perceptual variable, indexing how much perceptual processing is needed for a given word. This differs from parts of speech or the frequency of occurrence in the language, which are linguistic variables. In normal readers, the word-length effect is only about 10- 20 milliseconds per letter. In alexia, it can be several seconds per letter (40,42). The word-length effect also is elevated by a right homonymous hemianopia affecting the central 5° (43), but this should be less than 150 ms/letter (43). As with most deficits, cerebral dyschromatopsia does not have to be complete, so that all hue perception is lost and the world reverts to a television set of the 1950s. When it is partial, it is interesting to ask whether a specific part of color space is typically affected. Our study using Fourier analysis suggested no, there is simply an exaggeration of the normal tritan-like tendencies we all have (29). Also, of note, problems with hue discrimination did not occur with anterior temporal lesions (29), despite recent evidence that color perception activates a string of regions extending into this region (30). It remains to be seen what kind of color-related tasks are impaired by more anterior damage. Prosopagnosia Prosopagnosia may or may not be associated with problems recognizing other types of objects. This is not mistaking one type of object for another (e.g., wives for hats): that indicates general visual agnosia. Rather, there is a question whether prosopagnosic patients can distinguish between types of birds, or flowers, or cars, what used to be called "within-category discrimination." After all, they know they 272 Topographic disorientation can occur for several reasons. Our study of prosopagnosic subjects showed that either occipitotemporal or anterior temporal lesions could be associated with reduced landmark recognition, but only occipitotemporal lesions were associated with impaired ability to form a mental map (38). Testing the latter is challenging, but there are free online video-based tests (www.gettinglost.ca). Pure Alexia Barton: J Neuro-Ophthalmol 2018; 38: 271-275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial Akinetopsia and Astereopsis There is little to add about akinetopsia and astereopsis: the former is extremely rare and the latter rarely studied. Bálint Syndrome Bálint syndrome is uncommon but does not lack for reports. Haque et al (29) suggest that simultanagnosia may be considered a restricted window of attention and, indeed, we have used this analogy to simulate and model simultanagnosia (44,45). However, there are limitations to the analogy (46) and it is probably more accurate to characterize simultanagnosia as a limited attentional capacity. When there is competition for attention, healthy subjects have enough capacity to do more than one task but simultanagnosic subjects do not. For example, with Navon letters (Fig. 1), the small "local" letters compete with the overall "global" letter configuration. Most of us do not have a problem seeing both, but in simultanagnosia, especially if the global form is weak because the local elements are sparse, the local letters win out and the patient fails to see the big letter. This is "local capture" (47). Although "seeing the trees and not the forest" can fit with the concept of a small spatial window, this is not the case with other stimuli that have a strong global configuration. Arcimboldo painted faces made up of local elements such as fruit (Fig. 1B). With these pictures, a simultanagnosic patient reported the (global) face but failed to see the (local) fruit (48). Message: the face is a powerful stimulus. This is "global capture" and a nice demonstration that it is attentional capacity rather than the spatial window that is limited. It is as if the simultanagnosic subject can use either the wide-angle or the telephoto lens, but cannot move between the 2 as effortlessly as the rest of us. The Bigger Picture Finally, there are 2 "bigger picture" issues concerning cerebral visual processing. First, as Haque et al (29) point out, patients can have more than one problem. This is true even of focal lesions such as strokes and tumors, not just diffuse degenerations. Most commonly acquired focal lesions cause multiple problems because of a "neighborhood effect." There are lots of processing networks in the brain, often packed close to each other. Local damage is likely to affect several networks, although the exact damage varies with individual anatomy and the extent of pathology. This creates syndromes where different types of defects cluster together but not invariably so. Bálint syndrome is a good example. This "dorsal visual syndrome" consists of simultanagnosia, optic ataxia, and ocular motor apraxia, but not all patients have all 3, because attention, reaching, and saccadic targeting have closely associated but not identical spatial processing networks. Similarly, there is a "ventral visual syndrome," from right or bilateral damage, consisting of dyschromatopsia, the apperceptive variant of prosopagnosia, and topographagnosia from impaired cognitive map formation, often also with superior hemifield defects or a left homonymous hemianopia. If there is left fusiform damage, patients may also have alexia. More recently, there is evidence for an "anterior temporal agnosia syndrome," also with right-sided or bilateral cerebral damage, in which an associative prosopagnosia can be combined with phonagnosia (impaired voice recognition) (49) and/or acquired amusia (50). Again, this reflects the fact that the anterior temporal lobe is a multimodal convergent point, with components of visual and auditory networks for processing faces, voices, and music. Second, how separate are the processing regions for different types of objects? Figure 1 in the review by Haque et al portrays them as distinct but they may not be. One classic example concerns the contrast between visual words and faces. Functional neuroimaging shows considerable overlap between regions activated by these 2 stimuli (51) FIG. 1. A. A Navon letter of a large global letter "F" made up of small local letters "W." B. Arcimboldo painting shows a face made up of various fruits. Barton: J Neuro-Ophthalmol 2018; 38: 271-275 273 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial not only in the all-important fusiform gyrus, a key node in expert visual perception, (52) but elsewhere too. This has led to the recent "many-to-many hypothesis" (53), which proposes that any cortical region participates in processing more than one object type, and any object type involves multiple regions in its processing. Hence, the specificity of brain processing may emerge at a network level. Although words and faces have networks that emphasize opposite hemispheres, their overlapping activation has led to prediction that left-sided lesions that cause alexia will also cause minor prosopagnosic-like deficits, and conversely right-sided lesions that cause prosopagnosia will also create minor alexic-like deficits (54). However, the few studies to date have not shown this (55-57). Rather, there is some evidence of complementary hemispheric functions. The right fusiform lesions that cause prosopagnosia do not affect reading but do impair the ability to recognize handwriting and font (56), whereas alexic subjects with left fusiform lesions can still recognize people but have trouble decoding facial speech patterns-that is, lip reading (41,58,59). Thus, it is the process and not the stimulus that is lateralized. This last point provides a good ending illustration of the complexities of complex visual processing, and of the strange and wonderfully intricate mysteries of the brain. Clearly, there is more to be learned.and more than meets the eye. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. REFERENCES 1. Lepore F. Spontaneous visual phenomena with visual loss: 104 patients with lesions of retinal and neural afferent pathways. Neurology. 1990;40:444-447. 2. Ffytche DH. 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