Visual Agnosia I. Biran, MD, and H. B. Coslett, MD Address Department of Neurology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA. E-mail: [email protected] Current Neurology and Neuroscience Reports 2003, 3:508–512 Current Science Inc. ISSN 1528–4042 Copyright © 2003 by Current Science Inc. The visual agnosias are an intriguing class of clinical phenomena that have important implications for current theories of high-level vision. Visual agnosia is defined as impaired object recognition that cannot be attributed to visual loss, language impairment, or a general mental decline. At least in some instances, agnostic patients generate an adequate internal representation of the stimulus but fail to recognize it. In this review, we begin by describing the classic works related to the visual agnosias, followed by a description of the major clinical variants and their occurrence in degenerative disorders. In keeping with the theme of this issue, we then discuss recent contributions to this domain. Finally, we present evidence from functional imaging studies to support the clinical distinction between the various types of visual agnosias. Introduction The term “agnosia” was coined by Freud  in his discussion of aphasia and related disorders. Like subsequent investigators, he described a disruption between objects and their concepts. However, there are earlier descriptions of similar clinical phenomena. Munk  described dogs with parieto-occipital lesions that were able to avoid objects in their surroundings but failed to recognize the objects. He termed this behavior as “Seelenblindheit” (mind-blindness) . An important early theoretical contribution was made by Lissauer , who offered the distinction between two clinical forms of impaired object recognition: “apperceptive” and “associative” agnosias. On Lissauer’s account, the former reflects a failure to generate a fully specified perceptual representation, whereas the latter is attributable to an inability to link an adequate percept to stored knowledge indicating its name, function, size, and so forth  (translated into English by Jackson ). As noted by Teuber , associative visual agnosia may be regarded as a “normal percept stripped of its meaning.” Earlier descriptions of visual agnosia were provided by Finkelnburg’s account  of “asymbolia” and Jackson’s concept  of “imperception.” Clinical Variants Visual agnosia can be specific to certain kinds of objects. Accordingly, there are agnosias for objects, agnosias for faces or “prosopagnosia,” agnosias for words or “pure word blindness,” agnosias for colors, and agnosias for the environment, including landmarks. Finally, the disorder of simultanagnosia—an inability to “see” more than one object at a time—is often regarded as a type of visual agnosia. Agnosia for objects Inability to recognize familiar objects is the most common of the agnostic syndromes. Patients are impaired in naming regular objects and are often unable to describe them or mimic their use. Object agnosias are further classified as either apperceptive (the percept is not fully constructed and, therefore, patients are unable to copy drawings) or associative (the percept is relatively intact and patients are able to copy drawings). As the following text discusses, the agnosia can be specific to a semantic category, usually living or animate objects; agnosias for nonliving or inanimate objects have also been described . Prosopagnosia Prosopagnosic patients are unable to recognize the identity of faces (ie, to whom a face belongs), although they are capable of recognizing that a face is a face and, in some instances, the gender and age of the person. Prosopagnosia is usually secondary to temporo-occipital lesions, affecting the fusiform and lingual gyri. Whether a bilateral or a right unilateral lesion is sufficient to cause the deficit has been an issue of debate . There is also evidence that impaired face recognition could be encountered with frontal lesions. Rapcsak et al.  documented both anterograde and retrograde face memory impairment in subjects with frontal lesions. Agnosia for words This is also known as pure alexia, alexia without agraphia, or pure word blindness. Although this phenomenon is usually discussed in the context of language impairments, it is an agnostic symptom, as subjects who suffer from this deficit show a language impairment limited to visually presented stimuli (eg, reading), but not to auditorily presented stimuli. Accordingly, this deficit could be regarded as a failure in the visual recognition of words, and thus as an agnostic deficit . Visual Agnosia • Biran and Coslett 509 Color agnosia In this rare clinical syndrome, patients fail to name colors. This deficit is not secondary to basic color perception, as demonstrated by tasks requiring color categorization and hue perception. The distinction between this syndrome and color anomia is not clear. Some authors suggest that the two syndromes could be differentiated by tasks probing color information (ie, matching between known objects to colors), which is impaired with agnostic subjects and preserved with anomic subjects [12,13]. Progressive prosopagnosia This is a degenerative disorder presenting with progressive impairment in the recognition of faces. This syndrome is part of the fronto-temporal dementias (FTDs), which may present as focal atrophy in any combination of the right and left frontal or temporal cortices. Although in the semantic dementia variant of the FTDs the atrophy is prominent in the left temporal lobe, in progressive prosopagnosia the atrophy is prominent in the right temporal lobe [20–22]. Landmark agnosia Landmark agnosia is one of the causes for topographic disorientation (the loss of way-finding ability). Patients with landmark agnosia are unable to use environmental features for orientation. This deficit is usually secondary to lesions of the medial aspect of the occipital lobes, either bilaterally or right-sided. Pallis  reported a classic case of this disorder, and the topic has recently been reviewed by Aguirre . Schizophrenia Although not a classic neurodegenerative disorder, schizophrenia is often associated with visual agnosia. In a recent study of 41 patients with schizophrenia, Gabrovska et al.  reported a high incidence of visual processing deficits that were similar to associative agnosia. Schizophrenia patients also demonstrate a specific impairment to memorizing faces. This deficit is highly correlated with a reduction in the volume of the fusiform gyrus . In conjunction with other reports of discrete cognitive impairments in schizophrenia , these contributions help to bridge the gap between schizophrenia and behavioral neurology. Simultanagnosia Simultanagnosia is the inability to perceive simultaneously several items in the visual scene. This piecemeal perception of the visual environment causes severe disability and patients often behave as blind subjects. Simultanagnosia can be part of Balint’s syndrome , which also includes an inability to shift gaze (psychic paralysis of gaze) and difficulties in reaching visualized objects (optic ataxia). This complex syndrome is associated with bilateral lesion of the posterior parietal and occipital lobes . Mechanisms The visual agnosias can teach us about the way we allocate attention to the external world and build an internal mental representation. In the following section, we focus on recent work that explores the cognitive deficits underlying visual agnosia. These reports not only contribute to our understanding of the clinical disorders, but also have implications for our understanding of perception and cognition. Visual Agnosia in Degenerative Disorders The clinical phenomena discussed here were described mainly through lesion studies. However, the agnosias are also prevalent in degenerative disorders, often at a stage of the illness at which general cognitive abilities are at least relatively preserved. The following syndromes have been reported in neurodegenerative disorders. Posterior cortical atrophy This disorder presents with a progressive decline in complex visual processing and relative sparing of other cognitive abilities . It is associated with occipito-parietal atrophy and hypometabolism on single photon emission computed tomography (SPECT) or positron emission tomography (PET) scans. In most instances, the disorder is caused by Alzheimer’s disease. However, posterior cortical atrophy differs from typical Alzheimer’s disease in that the lesions show predilection to the posterior parietal and occipital areas. Patients with this syndrome show a high rate of alexia without oral language difficulty (80%), Balint’s syndrome (68%), and visual agnosia (44%) that is primarily apperceptive [19•]. Attention Simultanagnosia can teach us about the way we allocate and shift attention. According to Posner et al.’s  paradigm, shifting attention from a previous to a novel focus is performed in three steps: 1) disengaging from the previous focus, 2) moving attention between the foci, and 3) engaging attention at the new focus. In a recent report, Pavese et al. [27•] provide compelling evidence that, at least in some instances, simultanagnosia is associated with a deficit in disengaging visual attention. They studied a patient with simultanagnosia whose ability to report both items in an array was greatly facilitated by removing the item that he had initially reported. Performance was not improved by the sudden onset of a second stimulus, suggesting that once he had “locked onto” a stimulus, he was unable to disengage attention and shift to a different object or location [27•]. Mental representations Visual agnosia is generally regarded as a deficit in the processing of information, such that knowledge of the shape, form, and other stored knowledge of the physical attributes 510 Behavior of an object cannot be accessed. In some instances, there is strong reason to believe that the mental representations of that knowledge are preserved. Several investigators have recently reported data from visual imagery tasks that demonstrate that stored visual knowledge may be at least relatively preserved in patients with severe visual agnosia. Simultanagnosic patients can be impaired in the allocation of attention not only in the context of a visual scene, but also in mental imagery. An interesting clinical observation is that of an artist who, following a stroke in the posterior circulation, suffered from simultanagnosia. During her stroke recovery while painting scenes from memory, her drawings revealed selective attention to the left lower quadrant, with important aspects of the whole image “clipped,” as if missing from her internal representation of the scene . Subjects with prosopagnosia can show impaired overt recognition of faces with relative preservation of covert recognition of these stimuli (eg, these patients may fail to match faces, but event-related potentials could demonstrate covert matching) . The covert recognition of faces suggests that internal representations of faces can be relatively preserved in prosopagnostic subjects. Barton and Cherkasova  studied nine prosopagnostic patients and assessed their mental imagery for faces by a questionnaire composed of 37 questions probing facial features (eg, who has a bigger moustache—Stalin or Hitler?) and facial shape (eg, who has a more pear-shaped face—John F. Kennedy or Nixon?). They demonstrated a dissociation between performance on tasks assessing facial features as compared with face shape; deficits in the former were associated with left occipito-temporal damage whereas deficits in the latter were associated with lesions of the right fusiform face area. Covert face recognition (assessed by sorting famous faces by occupation and by pointing out a famous face from two faces) correlated with feature imagery. Finally, impaired mental representation in a visual agnostic-like pattern can also be demonstrated in pure alexic subjects. Bartolomeo et al.  described a patient who was impaired in tasks assessing mental imagery of letters (judging whether an upper-case letter has curved lines), but had a faultless performance when he was allowed to trace the contour of the letters with his finger. This suggests that his impairment was isolated to the visual representation of the letters, but not to their relative motor engrams . Semantics As briefly noted previously, for some patients the ability to recognize visually presented stimuli is significantly influenced by the semantic category of the item. Thus, a number of patients have been reported, for example, who are able to name man-made objects but are severely impaired in naming naturally occurring items such as animals, fruits, and vegetables. A number of competing hypotheses try to explain these category-specific deficits. The modality-specific hypothesis , later named the Sensory-Functional Theory (SFT) , postulates that the animate versus inan- imate dissociation follows from a selective impairment of the sensory or functional attributes that subserve the processing of either of these two categories. On this account, the identification of animate objects relies more on sensory attributes and would be disproportionately impaired by damage to the processing of sensory features associated with these objects. In contrast, inanimate objects may be known primarily by virtue of their function and the manner in which they are used or manipulated. As a consequence, a deficit in the recognition of inanimate objects would be disrupted by loss of information regarding the function of an object or sensory-motor knowledge regarding the manner in which the object is manipulated. A competing hypothesis is that the semantic knowledge is organized categorically in the brain . Clearly, teleologic explanations for this organization can be made. Evolutionary pressures would favor an animal that could easily recognize and distinguish other animals that are potential predator or prey or plants that are potential sources of food. Further, developmental data support the idea that infants as young as 3 months of age can differentiate living from nonliving things . There have been several recent contributions to this debate. Borgo and Shallice  demonstrated that subjects with specific impairment to animate objects are also impaired in the recognition of inanimate materials (eg, liquids) for which sensory-motor knowledge is lacking and that are distinguished by sensory features such as texture. They concluded that these data are not consistent with the proposal that there is a fundamental distinction between items as a function of semantic category . The following case study provides data consistent with the categorical hypothesis. We recently studied a 50-yearold patient who suffered a stroke involving the anteromedial aspect of the right occipital lobe (Coslett and Biran, unpublished data). Following this insult, he suffered from a marked visual recognition deficit and memory loss. Neuropsychologic tests showed normal attention, concentration, and working memory, and impaired immediate and long-term memory. The patient performed normally on the Wisconsin Card Sorting Task. Despite good performance on a variety of tests assessing visual processing, he performed poorly on the Boston Naming Test and the Benton Facial Recognition Test. He was significantly impaired naming animate as compared with inanimate items (42% vs 75%, chi-squared test P value=0.019). We than evaluated the contribution of various knowledge types (sensory, functional, encyclopedic, and taxonomic) to the naming performance and the differential animate/inanimate impairment observed with AD. In a naming to confrontation task, the subject was presented with color pictures of 194 inanimate objects and 150 animate objects; accuracy and reaction time were recorded. For each item, 30 control subjects had listed semantic features that were further classified into the following categories: sensory (eg, “a lantern is bright”); function (eg, “ovens Visual Agnosia • Biran and Coslett are used for broiling”); and encyclopedic/taxonomic (eg, “dove is a symbol of peace”) . Using a stepwise discriminant analysis, we evaluated the predictive value of the various factors such as stimulus frequency, familiarity, animacy, and types of knowledge that defined the object. This subject named the inanimate objects significantly better and faster than the animate objects (69% accuracy for inanimate, 37% accuracy for animate, chi-squared test P value=0.0001; response time of -4633 ms for inanimate objects, response time of -7581 ms for animate objects, t=3.416; P=0.008). In a discriminant function analysis, the only factor contributing to his performance was animacy versus inanimacy. This suggests that in this case, the animate/inanimate distinction cannot be reduced to different features, different knowledge types, and other variables such as frequency or familiarity, and are rather related directly to the category itself. 511 trally than peripherally located faces, and that the place areas responded more to peripherally than centrally located places. They suggested that objects whose recognition and analysis require fine details (eg, faces) will be linked to centrally located activation, whereas large objects (eg, houses) will be linked to peripheral activation. Conclusions In reviewing recent contributions to the understanding of the heterogeneous category of visual agnosias, we have attempted to highlight not only the clinical phenomenology of these disorders, but also their implications for accounts of the manner in which visual information articulates with other brain faculties. Although the agnosias have been investigated for more than 100 years, exploration of these fascinating disorders continues to offer important insights into brain function and organization. Functional Imaging of Object Recognition In the past few years, functional imaging in healthy subjects has helped to elucidate the anatomy of object recognition. Malach et al.  described the lateral occipital cortex (LOC), which is located at the lateral and ventral aspects of the occipito-temporal cortex. This area is activated preferentially by objects compared with scrambled objects or textures, regardless of the nature of the object (eg, faces, cars, common objects, and even unfamiliar abstract objects) [36,37]. Further processing of the visual stimuli occurs in specific brain areas according to stimulus category. For example, faces are processed in the fusiform face area  and in the occipital face area ; the former is more selective for faces than the latter. Places and/or spatial layouts are processed in the parahippocampal place area , whereas objects like animals and tools are processed in specific loci in the fusiform and the superior and middle temporal gyri . Orthographic stimuli are processed in the left inferior occipito-temporal cortex on or near the left fusiform gyrus [42,43], although this localization is highly debated . Thus, the specific perceptual categories of visual stimuli dictate very different ways of their processing in the brain and might give an anatomic basis for the different agnostic syndromes. The allocation of the different brain areas to specific object categories could be explained in part by the eccentricity bias (a preferential response to stimuli based on their location in the visual field, either in the center or in the periphery). This is one of the dimensions of organization of the visual cortex, especially the low-level areas. In a recent study, Levy et al. [45••] demonstrated a relationship between category specificity and retinal eccentricity. They scanned subjects while they viewed either faces or houses; in different trials, both types of stimuli were presented in either the center or periphery of the visual fields. 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A functional magnetic resonance imaging study looking at the association between category specificity and retinotopic organization.