Associative Visual Agnosia and Alexia Without Prosopagnosia

ASSOCIATIVE VISUAL AGNOSIA AND ALEXIA WITHOUT PROSOPAGNOSIA * Todd E. Feinberg., Rachel J. Schindler:!, Elizabeth Ochoa 2, Peter C. Kwan 1 and Martha J. Farah4 (Neurobehavior and Alzheimer's Disease Center, Beth Israel Medical Center; Departments of INeurology and Psychiatry, and 2Psychology, Beth Israel Medical Center and Mount Sinai School of Mecidine; 3Department of Neurology, SUNY at Stony Brook; and 4Department of Psychology, University of Pennsylvania)

INTRODUCTION

Associative visual agnosia refers to an impairment in visual object recognition that is not attributable to elementary perceptual deficit, nor to general decline or linguistic or communicative difficulties. Associative visual agnosics can see objects well enough to draw them. They can also name objects from verbal definitions, suggesting that they have retained the conceptual and linguistic abilities needed to demonstrate recognition. Nevertheless, they are impaired at recognizing objects by vision alone. The scope of the agnostic impairment varies from case to case. Face recognition is frequently, but not invariably, compromised along with objects recognition in associative visual agnosia. Similarly, the ability to recognize printed words mayor may not be impaired. The critical lesion sites and neuropathological mechanisms of associative visual agnosia remain controversial. Despite many decades of case studies, at least three separate issues are still unresolved: the necessity for bilateral lesions, the intrahemispheric locus of damage, and the roles of disconnection versus cortical damage. Regarding the necessity for bilateral lesions, Nielsen (1937) surveyed the literature from the early decades of this century and concluded that unilateral dominant hemisphere damage was sufficient to cause associative visual agnosia. On the basis of her own more recent observations, Warrington (1985) proposed that unilateral dominant hemisphere damage is the usual cause of associative visual agnosia. However, this represents a minority view, with most writers emphasizing the overwhelming frequency with which bilateral lesions accompany associative visual agnosia (Benson, Segarra and Albert, 1974; Albert, Soffer, Silverberg et aI., 1979; Alexander and Albert, 1983; Damasio and Damasio, 1983) and arguing that the nondominant lesions in these cases cannot plausibly be viewed as coincidental. Within the visual areas of each hemisphere, most authors have concluded that ventral (Benson et aI., 1974; AI* Presented in 1992.

part at the 44th annual meeting of the American Academic of Neurology, San Diego, California, April

Cortex, (1994) 30, 395-412

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T.E. Feinberg and Others

bert et aI., 1979; Alexander et aI., 1983; Potzl, 1928; Levine, 1982) rather than dorsal, areas are critical, although even this point is not unanimously held. As to the lateral versus medial locus of the critical lesion for associative visual agnosia, Neilson (1937) argued for a lateral locus, whereas Albert and co-workers (1979) emphasized the importance of medial structures. Finally, the mechanism by which brain lesions cause associative visual agnosia is also unresolved. Geschwind (1965) proposed a disconnection account according to which the outflow of visual areas was cut off from multimodal association areas and language areas. This provided a parsimonious account of the preservation of vision, conceptual knowledge and language in the face of impaired visual object recognition. A related account was put forth by Albert et ai. (1979) according to which visual areas were disconnected from medial temporal memory areas. In both cases, the critical lesion would be those affecting the white matter connecting visual areas with more anterior brain regions. Other authors have argued that a disconnection account cannot explain associative visual agnosia, neither on the basis of anatomical findings (Cambier, Masson, Elghozi et aI., 1980) nor behavioral considerations (Ross, 1980; Farah, 1990). These authors conceptualize associative visual agnosia as a loss of visual memory representation and therefore emphasize the role of cortical damage to visual association areas in the neuropathogenesis of associative visual agnosia. It is surprising that consensus has not been reached on such basic and straight forward empirical issues. One reason for the lack of consensus might be that associative visual agnosia is not a homogeneous syndrome and that different authors were studying different types of patients (Alexander et aI., 1983). Farah (1990, 1991) has argued for the existence of two models of visual object recognition, which when damaged separately or together will produce associative visual agnosia. According to this analysis, one of the pure forms of associative visual agnosia resulting from damage to a single form of visual recognition, is associative visual agnosia for objects and printed words (pure alexia), with preserved face recognition. In the present paper we confine ourselves to this one, purportedly pure, sUbtype of associative visual agnosia. Our goal is to obtain a more consistent localization for one sUbtype of associative visual agnosia by selecting patients who are behaviorally homogeneous. We had the opportunity to examine three patients with associative visual agnosia for objects and pure alexia with no prosopagnosia. On the basis of a previous review of visual agnosic patients (Farah, 1990), we obtained the CAT scans of four additional patients with the same profile of impaired and spared visual recognition abilities (Pillon, Signoret and Lhermitte, 1981; Feinberg, Gonzalez-Rothi and Heilman, 1986; McCarthy and Warrington, 1986; Gallois, Ovelacq, Hautecoeur et aI., 1988). The anatomy of these seven cases shows considerable uniformity and enables us to address the three issues raised in the introduction. In addition, one patient underwent extensive serial neuropsychological investigations.

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TABLE I

Patients with Associative Visual Agnosia (Groups 1 and 2)

Age/Sex

Handedness

Visual acuity

Group 1 PI. 1 56/M

RH

20/200U

PI. 2

68IM

RH

201700U

PI. 3

711F

RH

20/200U

RH

8110 OS 7I100D

RH

20/300U

RH

NR

RH

10110 OU

Group 2 Pillon et al. (1981) 66IM Feinberg et al. (1986) 64IM McCarthy et al. (1986) 77IM Gallois et al. (1988) 621F

Vascular lesion

Visual fields RHH macular sparing RHH macula largely spared RH macular sparing

L posterior cerebral artery occlusion L posterior cerebral artery occlusion

RHH non-macular sparing RHH macular sparing RHH

L

RHH non-macular sparing

posterior cerebral artery occlusion

L

posterior cerebral artery occlusion posterior cerebral artery occlusion L posterior cerebral artery occlusion L posterior cerebral artery occlusion

L

RH - Right handed. RHH - Right homonymous hemianopia. NR - Not reported. THREE PATIENTS WITH VISUAL AGNOSIA

Three patients with severe object recognition disorders were identified (Group 1; Table

I). All had acute posterior hemispheric strokes. Patients were tested on a series of object TABLE II

Results of Agnosia on 3 Patients (Group 1)

Stimulus mode

Response mode

Patient #1

Patient #2

Patient #3**

Visual object*

Name or describe use Pantomime use Visual match*

1110 1110 10/10

3110 6110 6110

0110 0/10 10/10

Tactile object

Name Pantomime use Tactile match*

5/10 6/10 10110

7110 7110 9/10

10/10 10/10 10110

10/10 10/10

10/10 10110

10/10 10110

Verbal description of object Name Pantomime

* Correct object selected from among 5 choices. ** Tested during stage 3 of recovery (see text). recognition tasks (Table II). Ten objects were presented visually and patients were first requested to provide names, or describe the objects' use. Errors were not corrected. The same 10 objects, in different order, were presented in a second series in which the patient was requested to gesture the objects' use without verbalizing. Finally, as a test of visual per-

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b.

c.

Fig. I - Examples of figure copy and writing of patients with object agnosia and alexia. (a) copy of flower (below) and (b) copy of elephant (below) both by patient 2. Neither object was recognized. (c) copy of flower and sample of writing by patient 3. The flower could not be idenfied; after a delay her own handwriting could not be read.

ception and immediate memory, the objects were presented visually and then with the patient's eyes closed, placed in a group with four other objects. The patient had to then, with eyes open, retrieve the object first presented. A second series of tests assessed tactile object recognition and perception. The same objects were presented tactually and the patient was allowed to manipulate the target object with eyes closed. The patient was then given a series of 5 objects, including the target, and required to select the target again using tactile manipulation (with eyes closed). A third series of tests assessed the patient's ability to name and pantomime, independent of object recognition. The same objects were verbally described and the patient was required to either name or pantomime the objects' use. As shown in Table II, these patients could not demonstrate visual object recognition by verbal or nonverbal means. The impairment in both verbal and nonverbal tests of object recognition implies that these patient are agnosic rather than optic aphasic. Patient 1 could name or describe the use of only 1/10, patient 2-3/10 and patient 3-0/10 visually presented objects. Patient 1 and 3 had a near total failure of performance when required to pantomime the use of objects presented visually (patient 1-1/10, patient 3-0/10). Patient 3 improved on this condition of performance, but was still impaired with only 6/10 correct. When shown and object and then asked to retrieve it from a group of five different objects, patients 1 and 3 demonstred good perception of and immediate memory for objects' visual appearance. Only patient 2 had some impairment on this task, scoring 6/1 0 correct. All patients were able to copy figures, as indicated by Figure 1, although in all cases the performance was slower than normal. All patients easily supplied the correct names for verbally defined objects (10/10 for all patients). Patients were also tested in their abilities to identify objects tactually. As sometimes observed in case of visual object agnosia (Morin, Riurain, Eustache et aI., 1984; Feinberg et aI., 1986), tactile object identification was mildly to moderately impaired, but less severely; Patient 1 named 5/10 objects, patient 2 named 7/10, and patient 3 named 10/10

Associative visual agnosia and alexia

399

tactually presemed objects. Pantomime of tactually explored objects was tested with the patients' eyes closed, palpating the object and then after the object was taken away, demonstrating the use. Performance on this task was nearly indentical to that obtained with naming to tactually presented objects. In addition to their object agnosia, the patients were all similar in their abilities to recognize printed words and faces. All patients were completely unable to read any words aloud. Given the severity of their visual object agnosia, the absence of prosopagnosia was striking. At no time did these patients evince any difficulty in recognizing the fac~s· of examiners, family members or friends. Patients recognized family members in persan'before they spoke and recognized family members from photographs. They were all able to pick out the examiner from a group of other doctors even when other clues (clothes, glasses etc.) were concealed. In summary, all 3 patients had a severe disorder of visual object recpgnition. They were unable to identify visually presented objects by name, description or gesture, in spite of normal naming and gesturing to verbal definitions. Perception appeared,ooequate to sustain object recognition beyond that displayed by all patients. Visual matching was imperfect in patient 2 and this patient had some mixed apperceptive agnosic features. Reading was uniformly impaired and face recognition uniformly spared.

Neuropsychological Assessment Premorbid intellectual abilities of all cases were estimated to be at least average on the basis of their educational and occupational histories. A comparison of the results of the evaluations is shown in Table III. Assessment of language only showed abnormalities of visual naming (Kertesz, 1982; Kaplan, Goodglass and Weintraub, 1983). Results of visuospatial testing revealed a differential performance by the three patients, with patients 2 and 3 having substantially greater deficits in visual perception and reasoning across tests than patient 1. Patient 1 performed in the average range on structured multiple choice tests requiring the matching of unfamiliar faces (Benton, Hamsher and Varney, 1983) and geometric figures (Benton, Hamsher and Varney, 1983). Visual logic and reasoning were above average (Raven, 1956). Performance was in the bordeline range on judgement of line orientation (Benton, Hamsher and Varney, 1983). In contrast, the ability of patient 2 to perform these same tasks was generally quite deficient. He either missed all but the easiest items or he said he could not do the task after trying the first few items. However, he correctly: (1) matched simple and complex geometric patterns from an array on several informal tests (9/10 correct) and from an adapted visual matching task (Mattis, 1988: 4/4 correct); (2) identified similarities and differences among geometric shapes (Mattis, 1988, Identities and Oddities items, 12/16 correct) and, (3) accurately counted 20 3 mm dots on a page. Visual searching was intact in that he accurately identified all of the letters "A" from among other letters on a page (Mattis, 1988, Distraction· 1: 6/6 correct; Distraction 2: 5/5 correct). The most striking confirmation of the perceptual abilities of patients 2 and 3 was found in their drawings of familiar objects (Figure 1) despite their inability of name them. While execution was at times slow and laborious, these results suggest that these patients had the capacity to make fine visual discriminations. As mentioned earlier none of these patients had prosopagnosia and this provides further evidence of preserved visual perception. This was judged by

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400

TABLE IJJ

Results of Neuropsychological Testing on 3 Patients

Western Aphasia Battery Naming Auditory comprehension Repetition Color naming Boston Naming Test Benton Form Discrimination Wechsler Memory Scale Information and Orientation Digit span forward Digit span backward Logical memory I Logical Memory II Verbal paired associates I Verbal paired associates II Mental control

Patient # 1

Patient # 2

Patient # 3

0/10 57/60 821100 4/6 28/60 27/32

9/20 54/60 1001100 4/6 3/60 20/32

0120

8 6 7/50 0/50 6/24 0/8 5/6 (5/6 untimed)

5 7 2 2150 0/50 0/24 0/8 2/6 (3/6 untimed)

8 12 8 8/50 0/50 6/24 0/8 2/6 (4/6 un timed)

Raven Part A Part B Part C Part D Part E Total

44/60 correct

Facial recognition Judgement of line

45 19

-

-0 -2 -4 -2

60/60 100/100 0/6 1/60 25/32

-7 -9

-8

16/30 correct (short form) 41 13

Not administered.

the ability of all patients to identify verbally family members and examiners both in person and from pictures. Patient 3 correctly identified 20120 pictures of family members and friends either by name (10/20) or description of relationship to the patient (10/20); all were confirmed as correct by the spouse. All patients demonstrated adequate attention skills when asked to repeat digits forward. However, verbal memory deficits foraB patients were identified on Wechsler Memory Scale-Revised subtests (Wechsler, 1987) (Table III), presumably attributable to damage to medial temporal limbic structures including the left hippocampal region. Patient 3 underwent a series of additional perceptual and cognitive tests in order to better understand the nature of her impairment. Progressive improvement in her perceptual and amnestic abilities was noted and her progress will be described in stages. Longitudinal Study of Agnosia in Case 3 Stage 1 (weeks 1-9): Impaired Shape Discrimination The first tasks assessed the ability to perform non-delayed shape and position matching to sample. The patient was shown a single drawing of a complex

Associative visual agnosia and alexia

401

geometric pattern and was required to match it to an identical shape from among a variable number of choices. The shapes were selected on the basis that they had been shown previously not to be easily described in verbal terms (Vanderplas and Garvin, 1959). There were 4 blocks consisting of 25 trials each. Patterns were presented in pseudo-random order in which the patient made the se1ctions from among 6, 9, 12 or 15 choices, only one of which matched the target stimulus. In order to determine if the deficit was selective for shapes, in the second part of this experiment her performance was assessed with an analogous task testing position matching. In the position test, the patient was shown a board divided into 6, 9, 12 or 15 alternate positions randomly distributed across the apparatus. The target position was indicated with a star and the patient was asked to mark on another board the position identical to the target position. There were 25 trials presented in 4 blocks in pseudo-random order, in which the patient had to choose between 6, 9, 12, or 15 possible locations. In order to eliminate memory as a variable, all responses were made in the presence of the target. The patient's performance on all tasks was compared with several control patients with amnestic syndromes of differing etiologies (CI-C3). Cl is a 38 year-old man with an amnestic syndrome due to a ruptured anterior cerebral artery aneurysm and an extensive right mediofrontal and basal forebrain infarction (WMS-R; verbal memory index=88; visual memory index =91). C2 is a 83 year-old man with a confirmed diagnosis of Alzheimer's Disease (WMSR: verbal memory index = 58; visual memory index = 79). C3 is a 78 year-old man with a diagnosis of multi-infarct dementia (WMS-R; verbal memory index = 78; visual memory index = 90). A fourth control (C4) is a normal 73 year old woman without neurological illness and normal memory abilities.

Results On the shape discrimination task for blocks of 6, 9, 12, or 15 shape choices, the patient made 9 (36%), 12 (48%), 11 (44%), 16 (64%) errors. In contrast, the patient made no errors in the 6, 9, 12, or 15 position matching task, thus demonstrating a clear dissociation between the ability to discriminate alternate shapes versus alternate positions. No controls made any errors on either task, demonstrating no shape or position discrimination deficits.

Stage 2 (weeks 10-15): Dissociated 1mpairment of Visual Memory for Shapes During this period the patient improved to a normal score on the previously described shape discrimination task. Visual memory for shapes versus position was then assessed with a test of a delayed shape and position match to sample patterned after experiments performed in monkeys with inferotemporal lesions (Mishkin, 1982; Mishkin, Ungerleider and Macho, 1983; Ungerleider and Mishkin, 1982). The experiment consisted of two parts. In the first part the patient was shown 6 distinguishable geometric shapes (Vanderplas and Garvin, 1959) which previous experience had shown she could now discriminate and match

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402

TABLE IV

Results of Shape and Position Discrimination Matching in Patient 3 with a Medial Occipitotemporal Lesion, and Control Patients Seconds Subjects

0

5

10

30

60

Patient 3

Shape Position

0(0%) 0(0%)

9 (36%) 0(0%)

14 (56%) 0(0%)

17(68%) 0(0%)

18 (72%) 1(4%)

Control I

Shape Position

Q(O%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

3 (12%) 2 (8%)

Control 2

Shape Position

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

1(4%) 1(4%)

Control 3

Shape Position

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

2 (8%) 2 (8%)

Control 4

Shape Position

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

0(0%) 0(0%)

Control I '" right mediofrontal lesion. Control 2", Alzheimer's Disease. Control 3"" multi-infarct dementia. Control 4 = normal control. Increasing delay in second appears on the right. Numbers represent errors and % incorrect (in parenthesis).

to sample without interposed delay from among 6 choices on 100% of trials. The patient was exposed to the stimulus for 5 seconds and a screen was then interposed between the subject and the choices. On successive blocks of 25 trials each, a delay of 0, 5, 10, 30, or 60 seconds was interposed before the subject was allowed to respond, at which point the board was removed and the subject pointed to the stimulus just seen from among 6 choices. In part two, a delayed position match to sample task was developed in which the patient was shown a random display of 6 eAually randomly placed circles. The examiner indicated the target circle from among the 6 choice array. A screen was then interposed and after delays of 0, 5, 10, 30, and 60 seconds (25 trials each), the patient was asked to indicate the target. Results

°

On the shape matching task, after interposed delays on 0, 5, 10, 30 and 60 seconds, the patient made (0%), 9 (36%), 14 (56%), 17 (68%), and 18 (72%) errors. In contrast, a normal performance was achieved on position matching after 0, 5, 10, 30 or 60 seconds and did not differ from the control patients (Table IV). These data demonstrated a discussion between visual memory for shape versus position. Stage 3 (weeks 16-48): Associative Visual Agnosia During this final assessment period, the patient improved to 100% performance on those tests of shaped and position discrimination and memory administered in stages 1 and 2. Visual perceptual and memory abilities had thus dra-

Associative visual agnosia and alexia

403

TABLE V

Results of Agnosia Testing on 4 Patients (Group 2) Pillon et al. (1981)

Feinberg et al. McCarthy et al. Gallois et al. (1986) (1986) (1988)

Stimulus mode

Response mode

Visual objects of pictures

Name or describe Pantomime use Visual matching

Impaired Preserved Preserved

Impaired Impaired Perserved

Impaired

Impaired Impaired Preserved

Tactile object

Name or describe

Relatively preserved

Impaired

Relatively preserved

Preserved

Pantomime use Tactile matching Verbal description of object

Name

Impaired Normal Preserved

Preserved Preserved

Pantomime use

Reading

Impaired

Impaired

Impaired

Impaired

Face recognition

Relatively preserved

Relatively preserved

Relatively preserved

Relatively preserved

Blank boxes indicate functions which were not adequately described to infer degree of function.

matically improved, while object recognition remained quite impaired. I During this stage she displayed many of the elements of associative visual object agnosia in addition to some residual apperceptive features. The data listed in Tables II and III were collected during this stage.

NEUROANATOMICAL ASSESSMENT OF

7 CASES OF VISUAL AGNOSIA

In addition to the 3 index cases, additional cases that met the following criterial were selected from the literature: (1) Associative visual agnosia defined as a clinical syndrome of impaired object recognition with adequate vision as judged by visual acuity, object matching and figure copying, (2) syndrome of alexia without agraphia, (3) preserved face recognition, (4) presence of a unilateral lesion in either hemisphere, (5) adequate documentation of deficit. 11 cases were identified which met this criteria, 6 of which had CAT or MRI scans. Authors of these 6 reports were contacted and 4 additional scans were made available for analysis (Pillon, Signoret and Lhermitte, 1981; Feinberg, Gonzalez-Rothi and Heilman, 1986; McCarthy and Warrington, 1986; Gallois, Ovelacq, Hautecoeur et aI., 1988). These cases comprise Group 2 (Tables I and V).

Materials and Method From the CAT scans of our cases (Group 1) and the 4 additional cases (Group 2), individual lesions were mapped onto templates adapted from neuroanatomic I Although this patient was impaired on standard overt tests of object recognition, she did come to manifest considerable (but non perfect) covert recognition of objects (Taylor and Warrington, 1971; Albert, Yamadori and Gardner, 1973). This will be subject of a separate article.

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404

TABLE VI

Lesion Localization in Patient with Associative Object Agnosia, Alexia, without Prosopagnosia Medial occipito-temporal

Medial occipito-parietal

Lateral occipital

fus

cun

inf

mid

0 2 2

0 I 0

ling parah

pcun cing

White matter twm

scc

fm

pvm

3 2 3

I 3 0

2

I 0 1

8

4

4

2

3

0

3

2

Group I Case # I Case # 2 Case # 3

2 3 3

2 3 3

2 3 3

0 2 2

0 0 0

Total

8

8

8

4

0

3

3

3

3

3

3

3

2

2

3

3

2

2

0

0

2

0

2

0

0

0

2

2

2

3

3

2

2

8

7

5

11

6

7

6

9

11

6

19

10

11

8

Group 2 Pillon et al. (1981) Feinberg et al. (1986) McCarthy et aI. (1986) Gallois et al. (1988) Total Total Group 1 and 2

2 3

3

3

3

3

3

3

3

3

3

11

10

12

10

7

19

18

20

14

7

fus = fusiform gyrus ling = lingual gyrus parah = parahippocampal gyrus cun = cuneus pcun = precuneus cing = cingulate gyrus Numbers represent 0 = spared; I = mildly; 2 = moderately;

0 I 0

4

inf = inferior mid = middle twm = temporal white matter scc = splenium corpus callosum fm = fornix major pvm = paraventricular white matter 3 = severely involved.

atlases (Damasio and Damasio, 1989; Matsui and Hirano, 1978). The templates represented 10 horizontal sections at various levels at a 0 degree angle relative to the canthomeatal line. A series of composite templates that included all individual templates at each level were constructed as shown in Figure 2A and 2B. The templates were divided into 12 anatomic regions, and reach region was rated to be spared (0), mildly (1), moderately (2), or severely involved (3). The results of this analysis are shown in Table VI. Results

Of the additional cases analyzed in Group 2, all were the result of left hemisphere infarction (Table I). The index cases and all additional cases included in the analysis had infarction in the distribution of the left posterior cerebral artery. When cortical regions are considered, dominant parahippocampal, lingual and fusiform gyri were the regions with the most extensive involvement in Group 1 (8/9 all cases). In Group 2, parahippocampal gyrus was severely involved in all cases (12112), and lingual and fusiform gyri were also severely and universally involved. When both groups are considered, other cortical regions were spared in at least one instance, including lateral occipital gyri which

Associative visual agnosia and alexia

405

were not extensively or consistently damaged. Splenium of corpus callosum was spared or minimally involved in two instances in Group 1 and in half the cases in Group 2. Temporal white matter including the inferior longitudinal fasciculus of the left hemisphere, which connects the ipsilateral primary visual area with the dominant medial occipitotemporal cortex, showed the greatest degree of involvement of white matter tracts surveyed (19/21 ' overall). The primary visual area of the contralateral visual cortex, via the splenium, also makes connections which utilize this white matter tract to reach contralateral medial occipito-temporal cortex. A lesion of inferior longitudinal fasciculus in the dominant hemisphere thus disconnects both primary visual areas from medial occipito-temporal cortex of the dominant hemisphere. All other white matter tracts were minimally involved or entirely spared in four instances overall. DISCUSSION

In seven cases of associative visual agnosia with pure alexia, sparing face recognition, a high degree of consistency in lesion location was observed. On the basis of this finding, we can offer a tentative answer to the questions posed earlier concerning the localization and mechanisms of associative visual agnosia. The critical lesion for producing associative visual agnosia with pure alexia, sparing face recognition, appears to be destruction of the dominant parahippocampal gyrus, adjacent fusiform and lingual gyri along with damage to the dominant inferior longitudinal fasciculus. In the cases studied, it is these medial occipito-temporal areas that are critical, with or without callosal damage. Thus, for one form of associative visual agnosia, a unilateral lesion of the dominant hemisphere is sufficient for at least some right-handed individuals, and the intrahemispheric locus of the lesion is clearly ventral and medial. The most parsimonious explanation for the pattern of impaired and preserved abilities seen in our patients is the destruction or disconnection of a dominant visual association region necessary for visual identification of objects but not faces with sparing of right hemisphere visual representations, perhaps also ventromedial in location, which is normally dominant for faces but not objects. Support for this hypothesis comes from several lines of evidence: (1) the consistent left hemisphere locus of lesions producing associative visual agnosia without prosopagnosia suggests this region supports a critical role in these functions; (2) the fact that the splenium need not be involved also suggests that some critical regions in the left hemisphere are destroyed and even if cerebral disconnection is not present, these regions must be preserved and accessed if normal object recognition is to occur; (3) recent independent PET scan evidence which indicates that the left hemisphere has a prominent role in object processing while the right hemisphere plays a predominant role in face perception (Horwitz et aI., 1992; Sergent, Ohta and MacDonald, 1992). These dominant-nondominant differences may be conceptualized along several lines. A purely verbal-nonverbal dichotomy seems unlikely as a sole ex-

406

T.E. Feinberg and Others

lateral occipital

] convolution

Group 2

Group 1

A

Group 2

Group 1

Group 1

Group 1

Group 2

middle

temporal gyrus Iflteriof temPOral gyrus

, cioQulale gyrus calcarine

~>.<:"'.-"'.\ = gyrus

supramargNl gyrus

prewneos

.."'"

liogUllgyrus t*arine

B Fig. 2 - Overlap of CAT or MRI scans of present three cases (Group J) and 4 additional cases (Group 2). All lesions are outlined. Areas involved in any case are stippled. Areas involved in all cases within each group are shown with dark stippling. (A) lateral (top) and medial (bottom), (B) horizontal asects of left hemisphere are shown.

Associative visual agnosia and alexia

407

planation since the failure in gesturing cannot be the result of a vi suo-verbal disconnection. Another possibility is that the dichotomy is based on differing perceptual abilities of the two hemispheres, with the left hemisphere showing a superiority for the visual analysis of stimuli with mUltiple parts (complex objects and words) and a right hemisphere superiority for visual analysis of stimuli which do not require visual decomposition into parts for recognition to occur (Farah, 1991). On this basis, complex objects and words require the greatest amount of visual decomposition and also require the ability to rapidly encode multiple parts, and thus associative visual agnosia and alexia would tend to occur together. Faces, which undergo little or no decomposition (Tanaka and Farah, 1993), would not be involved by a lesion of this system. If the right hemisphere were better at recognizing objects which are processed with little or no visual decomposition, faces would be involved to a greater extent with a lesion of the non-dominant hemisphere. Although the disorder demonstrated in these cases is primarily a disorder of visual recognition, our cases, and other cases of associative visual agnosia described in the literature (Morin et aI., 1986; Feinberg et aI., 1986; De Renzi et aI., 1987) frequently have some impairment in tactile recognition as well. Critchley (1953) pointed out the importance of visual associations in stereognosis, and visualizing aspects to tactually explored objects may be necessary for tactile identification in some cases (Feinberg et aI., 1986; Farah, 1990). There appears to be considerable clinical heterogenicity in the outcome of patients with temporal lesions secondary to posterior cerebral occlusions (De Renzi, Zambolin and Crisi, 1987; Iorio, Falanga and Fragassi, 1992). The clinical picture these patients demonstrate is variable and may include hemianopia alone, pure alexia, optic aphasia or object agnosia. The clinical differences between patients have been only partially explained by anatomical differences in lesions. It is also likely that individual differences in right hemisphere visual and semantic abilities contribute to clinical outcome. The evolution of the deficits in patient 3 offers further clues to the functional significance of this region and the mechanism of associative visual agnosia, by correspondence with findings in visual neurophysiology. There is considerable evidence that in the monkey (Mishkin, 1982; Mishkin and Ungerleider, 1983; Ungerleider and Mishkin, 1982) and human (Newcombe and Russell, 1969; Newcombe, Ratcliff and Damasio, 1987; Haxby, Grady, Horwitz et aI., 1991; Grady, Haxby and Horwitz, 1992; Horwitz, Grady and Haxby, 1992) there are two major dissociable pathways subserving higher order visual processes. Both paths originate in primary visual cortex OC and project to visual association cortical areas OB and OA from which two major projections emerge. A dorsal pathway traverses superior longitudinal fasciculus, projects to parietal lobe, and subserves the spatial localization of objects ("Where is it?"). A ventral or occipito-temporal pathway traverses inferior longitudinal fasciculus, projects to von Bonin and Bailey (1947) areas TEO and TE, and subserves visual object perception and identification ("What is it?") (Ungerleider and Mishkin, 1982). Evidence suggests TEO, located at the occipito-temporal junction between areas V4 and TE, plays a major role in shape and pattern perception and discrimination (Boussaoud, Desimone and Ungerleider, 1991; Iwai and Mishkin, 1969,

408

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1980; Kikuchi and Iway, 1980; Mishkin, 1982; Mishkin and Ungerleider, 1983; Ungerleider and Mishkin, 1982; Plaut and Farah, 1990). Area TE, located within the inferior temporal cortex (Mishkin, 1982), is the hypothesized highest order region subserving visual object recognition and the presumed locus for their central representation (Mishkin, 1982; Mishkin and Ungerleider, 1983). Animals with lesions in TE do not have prominent visual discrimination deficits, but rather show a memory dependent visual recognition defect (Mishkin, 1982). The performance of patient 3 on tests of visual perception and memory can be interpreted in terms of these distinctions initially developed in the context of the monkey brain. This patient initially (stage 1) showed a non-memory dependent disturbance in visual perception as judged by the ability to match complex shapes, similar to monkeys with lesions in TEO. However, our patients demonstrated visual perception adequate to perform visual matches and figure copying, which suggests a visual perceptual disturbance alone does not adequately explain their severe object recognition defects. Therefore, our patients may also suffer from some disturbance in the high-level representations of objects, akin to the hypothesized disturbance in animals with lesions in TE. Consistent with this idea, the visual memory impairment of patient 3 showed a disturbance in visual discrimination akin to animals with lesions in TEO. Subsequently during recovery the patient showed the classical dissociation between visual object identification versus object localization memory described in monkeys with lesions in TE (Mishkin, 1982; Mishkin and Ungerleider, 1983; Ungerleider and Mishkin, 1982). A combination of TEO and TE type impairments would explain the evolution of case 3 from an apperceptive to an associative type agnosia; a pattern previously described in agnosic patients (Bauer and Rubens, 1985). A point of divergence between results from monkeys and humans is that object perception and recognition disorders in monkeys require bilateral lesions for their occurrence, whereas our results confirm earlier suggestions (Nielsen, 1937; Warrington, 1985; Levine, 1982) that for humans, a unilateral dominant hemisphere lesion will suffice. This suggests a greater specialization of dominant ventral medial cortex in human for object perception. Perhaps with the increasing specialization of the dominant hemisphere for language, a comparable dominance in visual perception for written words and objects also occurred. Although areas TEO and TE in the monkey occupy the dorsolateral cortical suface, they also extend medially as far as parahippocampal gyrus. Typical TEOI TE ablations in the monkey include these medial regions. The occurrence of severe object recognition disorders in our patients with medial occipitotemporal lesions suggests in humans the areas critical for object perception and recognition occupy a more ventral medial position when compared with the monkey. It is probable that the increased development and size of temporal lobe language cortices caused a shift in these areas to a more ventromedial locus. Our results also suggest that in at least one of our cases, spatial perception ("Where is it"?) was spared. This spatial perceptual function could have been spared because it was sub served by a dorsal pathway projecting to parietal lobe in either or both hemispheres. It is possible that, consistent with the greater

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spatial capacities of the non-dominant hemisphere in humans, the bilateral but dichotomous visual pathways described in monkeys for object perception versus spatial perception are lateralized in humans, with a ventral dominant pathway somewhat specialized for object perception and a non-dominant dorsal pathway specialized for spatial perception. ABSTRACT

Disagreement over the neuroanatomical substrate of associative visual agnosia encompasses such basic issues as: (1) the necessity for bilateral lesions; (2) the intrahemispheric locus of damage; and (3) the roles of disconnection versus cortical damage. We examined three patients whose associative visual agnosia encompassed objects and printed words but spared faces. CAT scans revealed unilateral dominant occipitotemporal strokes. CAT scans of four previously reported cases with this same profile of associative agnosia were obtained. Dominant parahippocampal, fusiform and lingual gyri were the most extensively damaged cortical regions surveyed and were involved in all cases. Of white matter tracts surveyed, only temporal white matter including inferior longitudinal fasciculus was severely and universally involved. Splenium of the corpus callosum was frequently but not always involved. We conclude there is a form of associative visual agnosia with agnosia for objects and printed words but sparing face recognition which has a characteristic unilateral neuropathology. Damage or disconnection of dominant parahippocampal, fusiform and lingual gyri is the necessary and sufficient lesion. Acknowledgements. The authors thank Drs. R. McCarthy, E.K. Warrington, B. Pillon, and Ph. Gallois for allowing us to examine the CAT scans of their patients. Dr. Leslie Ungerleider for helpful discussion during the preparation of this paper; Dr. David Levine for translation of a paper by Potzl; Lynne Cooper and Michael Grimaldi for help with photographic and illustrative materials; and N. Kamen for manuscript preparation. This research was partially supported by the following grants (Dr. Farah): ONT grant NSOOI4-89-B016, NIMH grant ROI MH48274, NIH career development award K04-NS01405, McDonnellPew Program in Cognitive Neuroscience grant 90-36. REFERENCES ALBERT, M.L., SOFFER, D., SILVERBERG, R., and RECHES, A. The anatomic basis of visual agnosia. Neurology, 29: 876-879, 1979. ALBERT, M.L., YAMADORI, A., GARDNER, H., and HOWES, D. Comprehension in alexia. Brain, 96: 317-328, 1973. ALEXANDER, M.P., and ALBERT, M.L. The anatomical basis of visual agnosia. In A. Kertesz (Ed.), Localization in Neuropsychology. New York: Academic Press, 1983, pp. 393-415. BAUER, R.M., and RUBENS, A.B. Agnosia. In K.M. Heilman and E. Valenstein (Eds.), Clinical Neuropsychology. New York: Oxford University Press, 1985, pp. 187-241. BENSON, D.F., SEGARRA, 1., and ALBERT, M.L. Visual agnosia-prosopagnosia. Neurology, 30: 307-310, 1974. BENTON, A.L., HAMSHER, K. de S., V ARNEY, N.R., and SPREEN, O. Facial Recognition Test. New York: Oxford University Press, 1983. BENTON, A.L., HAMSHER, K. de S., V ARNEY, N.R., and SPREEN, O. Visual Form Discrimination Test. New York: Oxford University Press, 1983. BENTON, A.L., HAMSHER, K. de S., V ARNEY, N.R., and SPREEN, O. Judgement of Line Orientation. New York: Oxford University Press, 1983. BONIN, G., and BALEY, P. The Neocortex of Macaca Mulatta. Urbana: University of Illinois Press, 1947. BOUSSAOUD, D., DESIMONE, R., and UNGERLEIDER, L.G. Visual topography of area TEO in the macaque. Contemporary Neurology, 306: 554-575, 1991. CAMBlER, 1., MASSON, M., ELGHOZI, D., HENIN, D., and VIADER, F. Visual agnosia without right hemianopia in a right-handed patient. Revue Neurologique, 136: 727-740, 1980. COSLETT, H.B., and SAFFRAN, E.M. Preserved object recognition and reading comprehension in optic

T.E. Feinberg and Others

410

aphasia. Brain, 112: 1091-1110, 1989. CRITCHLEY, M. Tactile thought, with special reference to the blind. Brain, 76: 19-35, 1953. DAMASIO, A.R., and DAMASIO, H. The anatomic basis of pure alexia. Neurology, 33: 1573-83, 1983. DAMASIO, H., and DAMASIO, A. Lesion Analysis in Neuropsychology. New York: Oxford University Press, 1989, pp. 184-194. DE RENZI, E., ZAMBOLIN, A., and CRISI, G. The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain, 110: 1099-1116, 1987. FARAH, M.J. Visual Agnosia. Disorders of Object Recognition and What They Tell Us aboul Normal Vision. Cambridge: MIT Press, 1990. FARAH, MJ. Patterns of co-occurrence among the associative agnosias: Implications for visual object representation. Cognitive Neuropsychology, 8: 1-19, 1991. FEINBERG, T .E., GONZALEZ-RoTHI, LJ., and HEILMAN, K.M. Multimodal agnosia after unilateral left hemisphere lesion. Neurology, 36: 864-867, 1986. GALLOIS, P.H., OVELACQ, E., HAUTECOEUR, P., and DEREUX, J.F. Disconnection and recognition of faces. One case with left visual cortex and splenium lesions. Revue Neurologique (Paris), 144:

113-119,1988.

GESCHWIND, N. Disconnexion syndromes in animals and man. Brain, 88: 237-294, 585-644, 1965. GRADY, CL, HAXBY, J.V ., HORWITZ, B., UNGERLEIDER, L.G., SCHAPIRO, M.B., CARSON, R.E., HERSCOVITCH, P., MISHKIN, M., and RAPOPORT, S.L Dissociation of object and spatial vision in human extrastriate cortex: age-related changes in activation of regional cerebral blood flow measured with 15 0 water and positron emission tomography. lournal of Cognitive Neuroscience, 4: 23-34, 1992. GROSSI, D., FRAGASSI, N.A., ORSINI, A., DE FALCO, F.A., and SEPE, O. Residual reading capability in a patient with alexia without agraphia. Brain and Language, 23: 337-348, 1984. HAXBY, J.V., GRADY, c.L., HORWITZ, B., UNGERLEIDER, L.G., MISHKIN, M., CARSON, RE., HERSCOVITCH, P., SCHAPIRO, M .B., and RAPOPORT, S.l. Dissociation of object and spatial visual processing pathways in human extrastriate cortex. Proceedings of the National Academy of Science

USA, 88: 1621-1625, 1991.

HORWITZ, B., GRADY, C.L. , HAXBY, J.V., SCHAPIRO, M.B. , RAPOPORT, S.1., UNGERLEIDER, L.G., and MISHKIN, M . Functional associations among. human posterior extrastriate brain regions during object and spatial vision. lournal of Cognitive Neuroscience, 4: 311-322, 1992. IORIO, L., FALANGA, A., FRAGASSI, N.A., and GROSSI, D. Visual associative agnosia and optic aphasia. A single case study and a review of the syndromes. Cortex, 28: 23-37, 1992. IWAI, E., and MISHKIN, M. Two visual foci in the temporal lobe of monkeys. In N. Yoshii and N.A. Buchwald (Eds.), Neuropsychological Basis of Learning alld Behavior. Osaka: Osaka University Press, 1969, pp. 1-8. IWAI, E., and MISHKIN, M. Further evidence on the locus of the visual area in the temporal lobe of the monkey. Experimental Neurology, 25: 583-594, 1980. KAPLAN, E., GOODGLASS, H., and WEINTRAB, S. Boston Naming Test. Philadelphia: Lea and Febiger,

1983.

KERTESZ, A. Weslern Aphasia Battery. New York: Harcourt Brace Janovich, 1982. KIKUCHI, R., and IWAI, E. The locus of the posterior subdivision of the inferotemporal visual learning area in the monkey. Brain, 198: 347-360, 1980. LEVINE, D N . . Visual agnosia in monkey and in man. In DJ. Ingle, M.A. Goodale and RJ.W. Mansfield (Eds.), Analysis of Visual Behavior. Cambridge, Mass: MIT Press, 1982, pp. 629-670. MATSUI, T., and HIRANO, A. An Atlas of the Human Brain for Computerized Tomography. Tokyo: Igaku-Shoin, 1978, pp. 138-167. MATTIS, S. Mattis Dementia Rating Scale. Odessa, FL: Psychological Assessment Resources, 1988. MCCARTHY, RA., and WARRINGTON, E.K. Visual associative agnosia: a clinico-anatomical study of a single case. lournal of Neurology, Neurosurgery and Psychiatry, 49: 1233-1240, 1986. MISHKIN, M. A memory system in the monkey. Philosophical Transactions Royal Society of London,

Series B, 298: 83-95, 1982.

MISHKIN, M., UNGERLEIDER, L.G., and MACHO, K.A. Object vision and spatial vision: Two cortical pathways. Trends ill Neurosciellce, 6: 414-417, 1983. MORIN, P., RIVRAIN, Y., EUSTACHE, F ., LAMBERT, J., and COURTHEOUX, P. Agnosie visuelle et agnosie tactile. Revue Neurologique, 140: 271-277, 1984. NEWCOMBE, F., RATCLIFF, G., and DAMASIO, H. Dissociable visual and spatial impairments following right posterior cerebral lesions: clinical, neuropsychological and anatomical evidence. Neuropsy-

chologia,25: 149-161 , 1987.

NIELSEN, I.M. Unilateral cerebral dominance as related to mind blindness. Archives of Neurology alld

Psychiatry, 38: 108-135, 1937.

PILLON, B., SIGNORET, 1.L., and LHERMITTE, F. Agnosie visuelle associative: Role de I' hemisphere gauche dans la perception visuelle. Revue Neurologique, 137: 831-842, 1981. POTZL, O. Die Aphasielehre yom Standpunkte der klinischen Psychialrie. Leipzig: Franz Deuticke, 1928, vol. 1, pp. 183-188.

Associative visual agnosia and alexia

411

PLAUT, D.e., and FARAH, M.J. Visual object representation: Interpreting neurophysiological data within a computational framework. Journal of Cognitive Neuroscience, 2: 320-343, 1990. RAVEN, J.e. Standard Progressive Matrices Test - Revised. New York: Harcourt Brace Jovanovich, 1956. Ross, E.D. Sensory-specific and fractional disorders of recent memory in man. Archives of Neurology, 37: 193-200, 1980. SERGENT, J., OHTA, S., and MACDONALD, B. Functional neuroanatomy of face and object processing. A positron emission tomography study. Brain, 115: 15-36, 1992. SHALLICE, T., and SAFFRAN, E. Lexical processing in the absence of explicit word identification: Evidence from a letter-by-letter reader. Cognitive Neuropsychology, 4: 429-458, 1986. TAYLOR, A., and WARRINGTON, E.K. Visual agnosia: A single case report. Cortex, 1: 152-164, 1971. TANAKA, J.W., and FARAH, M.J. Parts and wholes in face recognition. Quarterly Journal of Experimental Psychology, 46A: 225-245, 1993. UNGERLEIDER, L.G., and MISHKIN, M. Two cortical visual systems. In DJ. Ingle, M.A. Goodale and RJ.W. Mansfield (Eds.), Analysis of Visual Behavior. Cambridge: MIT Press, 1982, pp. 549-580. V ANDERPLAS, J.M., and GARVIN, E.A. The association value of random shapes. Journal of Experimental Psychology, 57: 147-154, 1959. WARRINGTON, E.K. Agnosia: The impairment of object recognition. In PJ. Vinken, W. Bruyn and H.L. Klawans (Eds.), Handbook of Clinical Neurology. Amsterdam: Elsevier, 1985, pp. 333-349. WECHSLER, D. Wechsler Memory Scale - Revised. New York: Harcourt Brace Jovanovich, 1987. Todd E. Feinberg, M.D .. Neurobehavior and Alzheimer's Disease Center, Beth Israel Medical Center. 317 East New York 10003. U.S.A.

17th

Street, New York,