Visuospatial deficits and visual agnosia Masud Husain

Dept Experimental Psychology & Nuffield Dept Clinical Neurosciences, University of Oxford

1 Visuospatial deficits Often associated with right posterior parietal (dorsal visual stream) damage or dysfunction

§ Visual disorientation often with visual mislocalization and gaze apraxia § Constructional apraxia § Spatial working memory deficits § Optic ataxia | associated with right (or left) superior parietal lesions § Visual extinction |associated with right (or left) parietal lesions § Neglect syndrome | more severe and long-lasting with right inferior parietal lesions § Topographical disorientation | of the egocentric variety (see later)

In contrast, left parietal damage is often associated with language dysfunction, verbal working memory deficits, dyscalculia and limb apraxia

2 Visual disorientation

Gordon Holmes (1918)

Visual disorientation

When asked to touch an object in front of him he would grope hopelessly.

He could not count coins set before him. He had difficulty in seeing more than one item at a time and would bump into objects.

Emphasized a disorder of visual space perception Gordon Holmes (1918) Bálint’s syndrome Bálint put greater emphasis on inattention and visually guided misreaching

§ Patient could no longer judge where things were. Felt unsafe to cross roads. § Looked straight ahead, unware of objects on either side (bilateral inattention) § Bálint called it “psychic paralysis of gaze” (effectively a gaze apraxia) § Could only report one object at a time (simultagnosia) § Misreached to visual objects (optic ataxia) § Post-mortem: large bilateral strokes involving parietal lobes

8 Bálint (1917) Balint-Holmes' syndrome 119 shown by Holmes’ patients. They could move their eyes in any direction spontaneously, in response to a sudden sound, or towards a part of their own body that had been named or touched by the examiner (with the exception of patient 5), but failed when requested to search for a visual target or to direct their gaze to a stimulus suddenly appearing in the peripheral field. In such a case eye movements often initiated with the patient staring in the wrong direction and then rolling his eyes about until he found, as if by chance, the target. For instance, asked to look at the ceiling, Holmes’ (1918) patient 1 “pointed correctly to it with his hand, but moved the eyes first to the right, then to the left and finally downwards.” In less severe cases the search was slow and awkward and when the patient’s eyes eventually fell on the target, they easily lost it and could hardly find it again. Not only visually elicited saccades and fixation, but also following movements, convergence upon a near object, and the blinking reflex in reaction to a threatening stimulus were poorly controlled.

Holmes’TABLE 10.1 case series from 1918 RemarkableSymptoms Displayedsimilarity by Holmes’to Bálint’s Patientscase although Holmes emphasized disorder of space perception

Patient Oculomotor Misreaching Disorders Space Run Topographical no. apraxia of perception into disorientation attention disorders things 1 + + + + + + 2 + + Right + + neglect 3 + + + + 4 + + Left neglect + + 5 + + + + + 6 + + + + + 7 + + + + + +

+=presence of symptoms. Patient 7 was reported by Holmes and Horrax (1919). From gunshot injuries through both parietal lobes.

SomeAnother refer symptom, to this constellation which Holmes as emphasised Bálint-Holmes and investigated syndrome much more carefully than Balint, was the inability to appreciate the relative position of objects in space, 9 namely, to say which of them was the nearer or the higher, at what distance did it lie and to discriminate between two lines of different length or two objects of different size. The impairment shown in space perception was held responsible for the patients’ difficulty in reading (they frequently lost the place, skipping some lines, and settling on another column), in counting scattered points (some were neglected and some counted twice or more), in walking (they easily bumped into objects) and in reaching for a target. Optic ataxia was as striking in Holmes’ patients as it had been in Balint’s (1909) patient; it Dot counting Still used as a simple test of visuospatial ability, e.g. in Addenbrooke’s Cognitive Examination

V I S U O S P A T I A L A B I L I T I E S Visuospatial Ask the subject to count the dots without pointing to them [Score 0-4]

10

Updated 20/11/2012

Other tests of spatial localisation Position discrimination | Number location | Both from Warrington’s VOSP battery

11 Optic ataxia Misreaching to peripheral visual targets

12 Constructional apraxia Difficulty in perceiving spatial relationships – tested by asking patient to copy a figure

Rey-Osterreith Figure Patient A’s copy Patient B’s copy

13 Constructional apraxia Difficulty in perceiving spatial relationships – tested by asking patient to copy a block model

Block construction

14 Spatial working memory Traditionally tested using the Corsi blocks task – remember increasing sequences of spatial locations

§ Examiner taps out a sequence of locations

§ Patient has to reproduce this

§ Obtain a measure of spatial span or how many locations can patient maintain

Examiner’s view

15 V I S U O S P A T I A L A B I L I T I E S Visuospatial Ask the subject to count the dots without pointing to them [Score 0-4]

So what underlies visual disorientation?

Egocentric perceptual mislocalization, impaired attention, spatial working memory or visuomotor control?

§ Even simple dot counting requires spatial perceptual localization, attention, memory and eye movement control

§ Would a deficit in egocentric localization be sufficient?

§ Is there a deficit in ‘spatial remapping’ (remapping locations across eye, head and body movements so there is spatial constancy)? Russell et al (2010) Brain

16

Updated 20/11/2012

Proulx et al. Spatial and Social Cognition individual’s interaction with the environment, in particular The concept of a frame of reference has is origins in describing by preventing social and spatial interactions and limiting spatial coordinates and is still used in physics to describe “a perception. In addition, they could have an impact on system of coordinate axes in relation to which size, position, or personality, and thus have an impact on the self in this manner. motion can be defined” (Dictionary, 2015). However, this term Second, personality influences how the external environment has since been broadened in its usage to describe an aspect of a is perceived. Much research and theoretical development has cognizant being, whose frame of reference (or reference frames, noted the role of attention for consciousness (Dehaene et al., frames of mind, and framing) influences behavior. The ways in 2006)[thoughadmittedlycontroversialVan Boxtel et al., 2010], which one can mentally represent the locations of things are such that one is consciously aware of only that to which one called spatial reference frames.Egocentricandallocentricare pays attention, whether with simple visual search task (Joseph two general forms of spatial reference frames (see Figure 2). An et al., 1997), or more complex video displays (Simons and egocentric reference frame is where one denotes the locationof Chabris, 1999). Personality traits influence what one attends to. something else in reference to oneself. In contrast, an allocentric For example, in emotion-induced blindness, there is impairment reference frame is where the location of something else is in in visual processing due to attention to an emotional stimulus. reference to yet another object, independent of oneself (Byrne The degree to which emotional stimuli can alter visual attention et al., 2007). For example, a person in the UK could define the is directly related to a personality trait: harm avoidance (Most location of France compared to himself in an egocentric sense, et al., 2005). Thus, one’s personality creates a reference frame, or instead define the location of France compared to Germany via attentional prioritization, of what is valued, and therefore instead, in an allocentric sense. The reference frame used may attended to, in the environment (Anderson et al., 2011). interact with other, non-spatial domains of cognition, such as The ways in which we sense and perceive the world could social cognition. influence the sense of who we are in personality and social There has been much discussion about how, in practice, space domains. Although there have not been reports of different is actually represented cognitively in humans and other animals, personality dimensions for visually impaired persons, higher and whether one of the frames of reference dominates, or they levels of anxiety have been noted (Donoyama and Takeda, 2007; necessarily work together (Wang and Spelke, 2002)(Burgess, Donoyama and Munakata, 2009), and this has been shown to 2006). These reference frames interact to guide behavior, but influence the expression and character of one’s personality. Thus, can also be preferentially used depending on the conditions although visual impairment does not influence personality per of one’s environment. Different circumstances seem to favor se,itcanaffect the expression and perception of personality egocentric and allocentric approaches differently (discussed in linked behaviors (Zahran, 1965; Coren and Harland, 1995; Reid, Section Environmental Influences on Spatial Reference Frames; 2000), and provides an important method for examining whether Byrne et al., 2007). Byrne and colleagues describe in their visual experience rather than innate mechanisms shape social model how spatial cognition involves separate egocentric and and spatial behavior. Further, sensory abilities influence social allocentric neural pathways working together (discussed in interactions—standard social interaction is multisensory, though Section Social and Spatial Cognitive Neuroscience). Briefly, often driven by visual experiences such as facial, emotional, egocentric reference frames appear to be supported by a number and body expressions. Although, as discussed, personality is of cortical areas, from primary sensory processing such as influenced by several systems, the social system is largely the retinotopic maps from primary visual cortex through to posterior focus, because personality is visible in the social domain. For parietal cortex (PPC), including the precuneus and retroplenial example, according to Furnham, personality comprises the correlated states, traits, and expectations of behavior in social settings (Furnham, 1992). Egocentric localisation Mapping objects with respect to the body | Requires convergence of different types of sensory input

Egocentric or Allocentric: Individual Retinal locus Differences in Spatial Reference Frames Head position Target position with Head position and Personalities with respect respect to body orientation with respect to gravity in gravity to body The terms “egocentric” and “allocentric” are used in both social and spatial domains. Theories of grounded cognition are Eye position built on the notion that mental concepts and representations are not merely semantic, and thus amodal, but instead are grounded in sensorimotor experience and interactions with the environment (Barsalou et al., 2003; Barsalou, 2008). Such grounding implies that there could be a common source for these 17 reference frames in both the social and spatial domains. Here we FIGURE 2 | The location of objects can be represented in egocentric define reference frames in the spatial sense, review evidence for and allocentric spatial reference frames. An egocentric reference frame individual differences in reference frames in cognition, and then represents objects in relation to the location of the self (the observer). An describe how reference frames interact with self-perception and allocentric reference frame represents objects in relationtooneanother. Inspired by Kozhevnikov (2010). personality.

Frontiers in Psychology | www.frontiersin.org 5 February 2016 | Volume 7 | Article 64 Egocentric localisation Mapping objects with respect to the body | Requires convergence of different types of sensory input

If I know: • where an object is with respect to direction of gaze (retinotopic or eye-centred location) • which direction the eye is pointing with respect to the head and • where the head is with respect to the trunk I can calculate the object’s position with respect to the body.

The position of the hand with respect to the body can also be computed from proprioceptive inputs from the arm, so I can reach accurately even to the remembered location of an object.

18 Proulx et al. Spatial and Social Cognition individual’s interaction with the environment, in particular The concept of a frame of reference has is origins in describing by preventing social and spatial interactions and limiting spatial coordinates and is still used in physics to describe “a perception. In addition, they could have an impact on system of coordinate axes in relation to which size, position, or personality, and thus have an impact on the self in this manner. motion can be defined” (Dictionary, 2015). However, this term Second, personality influences how the external environment has since been broadened in its usage to describe an aspect of a is perceived. Much research and theoretical development has cognizant being, whose frame of reference (or reference frames, noted the role of attention for consciousness (Dehaene et al., frames of mind, and framing) influences behavior. The ways in 2006)[thoughadmittedlycontroversialVan Boxtel et al., 2010], which one can mentally represent the locations of things are such that one is consciously aware of only that to which one called spatial reference frames.Egocentricandallocentricare pays attention, whether with simple visual search task (Joseph two general forms of spatial reference frames (see Figure 2). An et al., 1997), or more complex video displays (Simons and egocentric reference frame is where one denotes the locationof Chabris, 1999). Personality traits influence what one attends to. something else in reference to oneself. In contrast, an allocentric For example, in emotion-induced blindness, there is impairment reference frame is where the location of something else is in in visual processing due to attention to an emotional stimulus. reference to yet another object, independent of oneself (Byrne The degree to which emotional stimuli can alter visual attention et al., 2007). For example, a person in the UK could define the is directly related to a personality trait: harm avoidance (Most location of France compared to himself in an egocentric sense, et al., 2005). Thus, one’s personality creates a reference frame, or instead define the location of France compared to Germany via attentional prioritization, of what is valued, and therefore instead, in an allocentric sense. The reference frame used may attended to, in the environment (Anderson et al., 2011). interact with other, non-spatial domains of cognition, such as The ways in which we sense and perceive the world could social cognition. influence the sense of who we are in personality and social There has been much discussion about how, in practice, space domains. Although there have not been reports of different is actually represented cognitively in humans and other animals, personality dimensions for visually impaired persons, higher and whether one of the frames of reference dominates, or they levels of anxiety have been noted (Donoyama and Takeda, 2007; necessarily work together (Wang and Spelke, 2002)(Burgess, Donoyama and Munakata, 2009), and this has been shown to 2006). These reference frames interact to guide behavior, but influence the expression and character of one’s personality. Thus, can also be preferentially used depending on the conditions although visual impairment does not influence personality per of one’s environment. Different circumstances seem to favor se,itcanaffect the expression and perception of personality egocentric and allocentric approaches differently (discussed in linked behaviors (Zahran, 1965; Coren and Harland, 1995; Reid, Section Environmental Influences on Spatial Reference Frames; 2000), and provides an important method for examining whether Byrne et al., 2007). Byrne and colleagues describe in their visual experience rather than innate mechanisms shape social model how spatial cognition involves separate egocentric and and spatial behavior. Further, sensory abilities influence social allocentric neural pathways working together (discussed in interactions—standard social interaction is multisensory, though Section Social and Spatial Cognitive Neuroscience). Briefly, often driven by visual experiences such as facial, emotional, egocentric reference frames appear to be supported by a number and body expressions. Although, as discussed, personality is of cortical areas, from primary sensory processing such as influenced by several systems, the social system is largely the retinotopic maps from primary visual cortex through to posterior focus, because personality is visible in the social domain. For parietal cortex (PPC), including the precuneus and retroplenial example, according to Furnham, personality comprises the correlated states, traits, and expectations of behavior in social settings (Furnham, 1992). Allocentric localisation Mapping objects relative to each other’s location | Requires viewpoint independent representations Egocentric or Allocentric: Individual Differences in Spatial Reference Frames and Personalities The terms “egocentric” and “allocentric” are used in both social and spatial domains. Theories of grounded cognition are built on the notion that mental concepts and representations are not merely semantic, and thus amodal, but instead are grounded in sensorimotor experience and interactions with the environment (Barsalou et al., 2003; Barsalou, 2008). Such grounding implies that there could be a common source for these 19 reference frames in both the social and spatial domains. Here we FIGURE 2 | The location of objects can be represented in egocentric define reference frames in the spatial sense, review evidence for and allocentric spatial reference frames. An egocentric reference frame individual differences in reference frames in cognition, and then represents objects in relation to the location of the self (the observer). An describe how reference frames interact with self-perception and allocentric reference frame represents objects in relationtooneanother. Inspired by Kozhevnikov (2010). personality.

Frontiers in Psychology | www.frontiersin.org 5 February 2016 | Volume 7 | Article 64 Egocentric to allocentric transformation Hypothesized to require lateral parietal to hippocampalREVIEWS inputs, via medial parietal regions REVIEWS ATN Parietal cortex Head direction, Body-oriented information theta

Prefrontal cortex for guidingExecutiv e,the scene action manipula oftion body parts. These neurons are Egocentric also very sensitive to the speed of optic flow57, which is framework 58 useful for updating position during navigation . There are also reports that cIPL neurons code direction during mental navigation of mazes102,103. Differentiation among posterior parietal areas in Retrosplenial cortex humans is difficult, but fMRI signal changes have been Scene translation Medial parietal regions observed in both parietal cortex and hippocampus dur- ing navigation104, and this activity predicts the accuracy Precuneus of chosen heading directions105. One recent study has Posterior cingulate cortex (PCC) also reportedPerirhinal that cothertex response of the posterior par- Retrosplenial cortex (RSC) ietal cortex Object-basedduring navigation information of a virtual environment may be consistent with a representation of absolute dis- 106 Occipital cortex tance . The representation of egocentric depth seems Visual information to involve V3A, the most caudal subregionsHippoc of theampus pos- Parahippocampal Event within a scene, Scene-based terior parietal cortex V6 and V6A, and the IPS.scene There construction is information a large amount of information about depth throughout Allocentric the IPS60,61,107, and this information may contribute to framework the coding of three-dimensional shape62. Posterior par- ietal lesions can also lead to egocentric disorientation15, a form of topographic disorientation typified by striking deficits in navigation, and to impaired memory for land- 108 marks . Patients with suchFigure lesions 3 | Theare keyunable anatomical to ori -and functional relationships of the retrosplenial cortex. Effective episodic ent themselves within real ormemory, imagined navigation environments and future thinking all require the ability to integrate and manipulateNatur differente Reviews frameworks | Neuroscienc ofe and therefore can neither navigateinformation, nor fordescribe example routes egocentric (self-centred) and allocentric (world-centred) frameworks. By virtue of its between familiar locationsprincipal15,109,110. connections,This deficit the sug retrosplenial- cortex is uniquely placed to enable translation within these domains. ATN, anterior thalamic nuclei. gests that posterior parietal cortex is the source of the Figure 3 | Parieto–medial temporal pathway in humans. This figure is based on egocentric information needed for navigation. resting-state MRI functional connectivity of the precuneus in humans. Medial parietal 20 area PGm (also known as 7m) and area V6 (part of parieto-occipital area PO) in the caudal In summary, there is strongkey functionalquestions could evidence be addressed in by assessing patients been the poor relation of cognitive neuroscience. It is part of the medial surface show strong functional connectivity (black lines) with the both monkeys and humans forwith the RSC participation damageVann, on theirof Aggleton the ability to imagine& Maguireficti- our hope (2009) that the RSC Nat will now Rev become Neurosci a major focus angular gyrus, the likely human homologue of the caudal inferior parietal lobule (cIPL). posterior parietal cortex in differenttious and conscious future experiences and non- and on how they process of dedicated research, and our belief that defining its V6 also shows strong connectivity with early visual areas in the region of the calcarine conscious forms of visuospatialscenes, processing. and by using Different fMRI studies with task designs role will prove pivotal in understanding a range of sulcus (cs), reflecting a network that is the presumptive human homologue of the forms of spatial representationthat arespecifically widely targetdistributed the RSC. The RSC has too long crucial cognitive functions. occipito–parietal network observed in monkeys (FIG. 2a). Similarly, the posterior across the posterior parietal cortex, resulting in con- cingulate cortex (PCC, areas 23 and 31) and the retrosplenial cortex (RSC, areas 29 and 1. Brodmann, K. Vergleichende Lokalisationslehre der 9. Vogt, B. A., Vogt, L., Farber, N. B. & Bush, G. 16. Kobayashi, Y. & Amaral, D. G. Macaque monkey siderableGrosshirnrinde overlap among inihren Prinzipien the regions dargestellt that auf Grund are importantArchitecture and neurocytology of monkey retrosplenial cortex: III. Cortical efferents. J. Comp. 30), on the medial surface, show strong functional connectivity (shown by blue lines) with for spatialdes working Zellenbaues (Barth,memory, Leipzig, visually 1909). guided actioncingulate and gyrus. J. Comp. Neurol. 485, 218–239 Neurol. 502, 810–833 (2007). both cIPL and the parahippocampal gyrus in the medial temporal lobe, reflecting a 2. Vogt, B. A., Absher, J. R. & Bush, G. Human (2005). The final paper in a series of three that provide the navigation.retrosplenial This functional cortex: where is overlap it and is it involvedis unsurprising in 10. givenMorris, R., Petrides, M. & Pandya, D. N. Architecture most detailed descriptions to date of the inputs to network that is the presumptive human homologue of the parieto–medial temporal emotion? Tre n d s N e u ro s c i . 23, 195–197 and connections of retrosplenial area 30 in the rhesus the RSC in an Old World monkey brain. the strong(2000). interconnectivity within the occipito–parietalmonkey (Macaca mulatta). Eur. J. Neurosci. 11, 17. Mufson, E. J. & Pandya, D. N. Some observations on pathway observed in monkeys (FIG. 2b). ips, intraparietal sulcus; pos, parieto–occipital circuit.3. Unfortunately,Papez, J. W. A proposed there mechanism has beenof emotion. little Arch. research 2506–2518 that (1999). the course and composition of the cingulum bundle in sulcus; SPL, superior parietal lobule. Figure is modified, with permission, from REF. 51 © Neurol. Psychiatry 38, 725–743 (1937). 11. Vogt, B. A. in Cingulate Neurobiology and Disease (ed. the rhesus monkey. J. Comp. Neurol. 225, 31–43 directly4. comparesMacLean, P. Psychosomatic the relative disease importance and the visceral of these differVogt, B.- A.) 65–93 (Oxford Univ. Press, London, (1984). (2009) National Academy of Sciences. brain; recent developments bearing on the Papez 2009). 18. Morris, R., Pandya, D. N. & Petrides, M. Fiber system ent functionaltheory of propertiesemotion. Psychosom. (for Med.example, 11, 338–353 peripersonal A verchapter- from a recent book devoted to the entire linking the mid-dorsolateral frontal cortex with the (1949). cingulate cortex, of which the RSC is a component retrosplenial/presubicular region in the rhesus sus extrapersonal5. Vogt, B. A., Nimchinsky, coding) E. A.,within Vogt, L. J.the & Hof, same P. R. region. area.Such This is the first book devoted to the monkey. J. Comp. Neurol. 407, 183–192 (1999). Human cingulate cortex: surface features, flat maps, neurobiology of this region since 1993. 19. Jones, B. F. , G ro e n ewe g e n , H . J. & Witter, M. P. of the functional properties of IPL found that many PFG research andis essential cytoarchitecture. if we J. Comp. are toNeurol. determine 359, 490–506 whether 12. funcVogt, B.- A. & Peters, A. Form and distribution of Intrinsic connections of the cingulate cortex in the rat neurons were multimodal, showing sensitivity to both tional biases(1995). exist within the posterior parietal cortexneurons in in rat cingulate cortex: areas 32, 24, and suggest the existence of multiple functionally segregated 6. Cavanna, A. E. & Trimble, M. R. The precuneus: a 29. J. Comp. Neurol. 195, 603–625 (1981). networks. Neuroscience 133, 193–207 (2005). review of its functional anatomy and behavioural 13. Van Groen, T. & Wyss, J. M. Connections of the 20. Vogt, B. A. & Miller, M. W. Cortical connections Optic flow somatosensation, motor activity and visual stimuli in line with the proposed anatomical pathways originating 97 correlates. Brain 129, 564–583 (2006). retrosplenial granular a cortex in the rat. J. Comp. between rat cingulate cortex and visual, motor, and The apparent motion of the peripersonal space . in this7. cortex.Kobayashi, Y. & Amaral, D. G. Macaque monkey Neurol. 300, 593–606 (1990). postsubicular cortices. J. Comp. Neurol. 216, retrosplenial cortex: II. Cortical afferents.FIG. J. 2b Comp. 14. Van Groen, T. & Wyss, J. M. Connections of the 192–210 (1983). environment caused by relative Nonetheless,Neurol. 466 ,as 48–79 indicated (2003). in , the three pathretrosplenial- granular b cortex in the rat. J. Comp. 21. Vogt, B. A. in Cerebral Cortex: Association and motion between the observer Parieto–medial temporal pathway. The same survey97 ways8. clearly Kobayashi, have Y. & differently Amaral, D. G. Macaque weighted monkey parietal inputs,Neurol. 463 , 249–263 (2003). Auditory Cortices Vol. 4 (eds Peters, A. & Jones, E.) and the visual surround. During retrosplenial cortex: I. Three-dimensional and 15. Van Groen, T. & Wyss, J. M. Connections of the 89–149 (Plenum, New York, 1985). reported that a subregion of cIPL (area PG), whose pro- with thecytoarchitectonic parieto–medial organization. temporal J. Comp. Neurol. pathway 426, beingretrosplenial the dysgranular cortex in the rat. J. Comp. 22. Sutherland, R. J. & Hoesing, J. M. in Neurobiology of navigation, it can be a source 339–365 (2000). Neurol. 315, 200–216 (1992). Cingulate Cortex and Limbic Thalamus: A of information about the jections contribute to the parieto–medial temporal path- most dependent on the cIPL. Next, we turn to evaluat- observer’s movement. way (FIG. 2b), contained fewer somatosensory or motor ing the functional properties of the other regions along

neurons than rIPL and was more responsive to changes this complex800 | NOVEMBER pathway. 2009 | VOLUME 10 www.nature.com/reviews/neuro Neglect in eye position towards extrapersonal loci. This is con- Ÿ)''0DXZd`ccXeGlYc`j_\ijC`d`k\[%8cci`^_kji\j\im\[ A deficit resulting from cortical Functional properties of the PCC lesions that causes the sistent with the suggestion that cIPL is specialized for 94,98 observer to ignore part of processing distant space and less involved in guiding The PCC (areas 31 and 23 in FIG. 2b) is often treated visual space. This deficit can be actions of the body. Indeed, one recent study reported no together with the RSC, despite its distinct cytoarchitec- egocentric, as in hemispatial activation in the cIPL (specifically, area Opt) in response ture14. However, the functional properties that are uniquely neglect (in which one half of to observed or executed actions92. Further, some cIPL attributable to the PCC are closely related to those of the the visual field is ignored) or 79 99–101 allocentric (for example, when neurons encode space in world- or object-centred cIPL, which is consistent with the direct interconnectivity the left side of all objects is reference frames, which are potentially useful for naviga- of the two regions. Here, we briefly review the role of the ignored). tion and encoding landmarks but are of limited utility PCC in eye movements, attention and navigation.

222 | APRIL 2011 | VOLUME 12 www.nature.com/reviews/neuro © 2011 Macmillan Publishers Limited. All rights reserved Topographical disorientation There are different ways to get lost!

§ Egocentric disorientation

Associated with right posterior parietal lesions TOPOGRAPHICAL MEMORY DIFFERENTIATES AD FROM FTLD 1159

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Court Hall rstb.royalsocietypublishing.org § scheme, the PPA identifies landmarks, the RSC uses landmarks to determine the current location and facing/heading direction (and mayNorth also encode information about directions toICA Landmark agnosia other locations—not shown) and the MTL encodes a cognitive map that represents landmarks and goals in terms of their coordinates in allocentric space.(Onlineversionincolour.) Franklin Annex

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Associated with parahippocampal place area (PPA) lesions could have used a general-purpose object recognition system to These observations seem to fit well with behavioural data 20120533 : East solve this problem. However, it appears to rely instead on a showing that humansWest and animals use geometric informationAnnenberg Addams Dietrich bookstore School Hall Graduate Van Pelt specialized mechanism for landmark recognition, analogous preferentially (and sometimes exclusively) to reorient after Library Library Annenberg in many ways to the specialized mechanism that is believed disorientation [12,13]. However, results from two recentPPC The Sweeten Blanche P. ARCH to support face recognition. fMRI adaptation studies suggestSouth that coding of geometry is Alumni Levy Park House

The primary neural locus of this mechanism is the par- not the whole story. The first study found that the PPA exhi- B Soc. R. Trans. Phil. ahippocampal place area (PPA)—a region in the collateral bits cross-adaptation between visual stimuli that have similar § Allocentric disorientation sulcus near the parahippocampal/lingualFigure 1. boundaryHypothesized that roles exhi- of the parahippocampalvisual place summary area (PPA), statistics retrosplenia [14].lcomplex(RSC)andmedialtemporallobe(MTL)inlandmark-basedpiloting The second study found that .Intheproposed bits a strong functional magnetic resonancescheme, the PPA imaging identifies landmarks, (fMRI) the RSC usesthe landmarks PPA exhibits to determine cross-adaptation the current location between and facing/heading mirror direction images (and of may also encode information about directions to response when subjects view environmentalother locations—not stimuli, shown) such and as the MTL encodesthe a same cognitive scene, map that which represents contain landmarks the and same goals in visual terms of features, their coordinates but in allocentric space.(Onlineversionincolour.) buildings, streets, rooms and landscapes [3,4]. By contrast, the shown in different spatial arrangements relative to the

Hippocampal damage? PPA only responds weakly when subjects view common every- viewer [15]. Thus, the first study shows sensitivity to non- 369 day objects, such as vehicles, tools and appliances, and it does spatial features, whereas the second study shows insensitivity could have used a general-purpose object recognition system to These observations seem to fit well with behavioural data 20120533 : not respond at all when they view faces. Notably, the PPA exhi- to one kind of spatial information. Taken as a whole, the litera- solve this problem. However, it appears to rely instead on a showing that humans and animals use geometric information bits this strong preference for environmental stimuli even when ture suggests the PPA encodes both spatial and non-spatial specialized mechanism for landmark recognition, analogous preferentially (and sometimes exclusively) to reorient after subjects simply view stimuli passively without performing any aspects of scenes and may use both kinds of features for scene in many ways to the specialized mechanism that is believed disorientation [12,13]. However, results from two recent explicit navigational task. Consistent with these neuroimaging recognition. Further, the relative insensitivity of the PPA to to support face recognition. fMRI adaptation studies suggest that coding of geometry is results, patients with damage to the PPA find it difficult to ident- mirror reversal suggests that it may be more involved in identi- The primary neural locus of this mechanism is the par- not the whole story. The first study found that the PPA exhi- 21 ify their surroundings based on analysis of the visual scene as a fying scenes based on visual features and/or intrinsic spatial ahippocampal place area (PPA)—a region in the collateral bits cross-adaptation between visual stimuli that have similar whole, although they can sometimes figure out where they are geometry than in calculating one’s egocentric orientation relative Epsteinsulcus near the parahippocampal/lingual& Vass (2013) boundary thatBrain exhi- visual summary statistics [14]. The second study found that by focusing on small details, such as a mailbox or a door knocker to that geometry. bits a strong functional magnetic resonance imaging (fMRI) the PPA exhibits cross-adaptation between mirror images of [5,6]. That is, they can recognize objects but they cannot What about landmarks that take the form of individual recognize the scenes within which theresponse objects when are contained. subjects view environmentalpunctate objects stimuli, (such such as as a statue orthe a same mailbox)? scene, Several which find- contain the same visual features, but An especially salient kind of landmarkbuildings, is streets, the geometric rooms and landscapesings suggest [3,4]. By that contrast, the PPA the may supportshown recognition in different of these spatial as arrangements relative to the arrangement (i.e. spatial layout) ofPPA theonly major responds surfaces weakly of the when subjectswell. The view fact common that the every- PPA respondsviewer strongly [15]. Thus, to buildings the first study shows sensitivity to non- local scene. Several lines of evidenceday indicateobjects, such that as the vehicles, PPA toolseven and appliances, when they and are it shown does as discretespatial features, items cut whereas out from the second study shows insensitivity might be concerned with processingnot this respond kind of atinformation. all when they view faces.their Notably, surroundings the PPA has exhi- long beento known one kind [16]. of Recent spatial studies information. Taken as a whole, the litera- The PPA responds strongly tobits images this strong of empty preference rooms for environmentalhave shown stimuli that even the whenPPA also exhibitsture suggests preferential the PPA response encodes both spatial and non-spatial containing little more than baresubjects walls, which simply containview stimuli no passivelyto certain without kinds performing of common any everydayaspects objects of scenes when and presented may use both kinds of features for scene discrete objects but depict a three-dimensionalexplicit navigational space task. as Consistentin thewith same these way. neuroimaging For example, the PPArecognition. responds Further, more strongly the relative insensitivity of the PPA to defined by fixed background elementsresults, [3]. patients It also with responds damage to theto PPA large find objects it difficult compared to ident- with smallmirror objects reversal [17,18], suggests distant that it may be more involved in identi- strongly to ‘scenes’ made out of Legoifyblocks their surroundings that have a simi-based on analysisobjects of compared the visual scene withnearby as a objectsfying [19], scenes objects based with on strong visual features and/or intrinsic spatial lar geometric organization [7] evenwhole, when although they arethey perceived can sometimescontextual figure out associations where they compared are withgeometry objects than with in calculating weak con- one’s egocentric orientation relative haptically rather than visually [8].by Further, focusing multi-voxel on small details, pat- such astextual a mailbox associations or a door knocker [20] and objectsto that that geometry. define the space tern analysis (MVPA) studies have[5,6]. found That is, that they the can PPA recognizearound objects them but compared they cannot with objectsWhat with weak about spatial landmarks defi- that take the form of individual distinguishes between scenes basedrecognize on their the geometric scenes within fea- which thenition objects [21]. are In contained.all four cases, the PPApunctate responds objects more (such strongly as a statue or a mailbox)? Several find- tures, with distinct activity patterns elicitedAn especially by open salient vistas kind ofto landmark objects thatis the are geometric more useful asings landmarks suggestthan that the to PPAobjects may support recognition of these as (e.g. a highway stretching througharrangement an open (i.e. desert) spatial and layout) ofthat the are major less surfaces useful [22]. of the In addition,well. PPAThe fact response that the can PPA be responds strongly to buildings closed-in scenes (e.g. a crowded citylocal street) scene. [9,10]. Several Finally, lines of evidencemodulated indicate by that the the navigational PPA historyeven when of an they object: are objects shown as discrete items cut out from PPA response to scenes is greatermight when be subjects concerned judge with the processinginitially this kind encountered of information. at navigationaltheir surroundings decision points, has long for been known [16]. Recent studies location of a target object relativeThe to the PPA fixed responds architectural strongly toexample images intersections, of empty rooms elicit morehave activity shown when that they the are PPA sub- also exhibits preferential response elements in the scene than when theycontaining judge its little location more rela- than baresequently walls, which observed contain in no isolationtocompared certain kinds with of common objects everyday objects when presented tive to a movable object or the viewer,discrete thus objects demonstrating but depict a a three-dimensionalinitially encountered space at as non-decisionin the same point way. locations For example, [23]. the PPA responds more strongly role for the PPA in the processingdefined of environment-centred by fixed background elementsThese results[3]. It also demonstrate responds that theto PPA large responds objects comparednot only to with small objects [17,18], distant spatial relationships [11]. strongly to ‘scenes’ made out of Legoscenes, blocks but that also have to non-scene a simi- objectsobjects with compared orientational with value, nearby objects [19], objects with strong lar geometric organization [7] even when they are perceived contextual associations compared with objects with weak con- FIGURE 2. Top: Timing and layout of test items. Perceptual images based solelyhaptically on rather the than nonspatial visually [8]. Further, features multi-voxel pat- in thetextual scene; associations cloud [20] and objects that define the space tests used a concurrent match to sample task. Participants had to cover, lighting,tern texture, analysis (MVPA) and studies color haveof found vegetation. that the PPA Thearound them target compared is with objects with weak spatial defi- distinguishes between scenes based on their geometric fea- nition [21]. In all four cases, the PPA responds more strongly choose one picture from four alternatives (on the lower page of shown at the bottomtures, with left distinct of activity the patterns four elicited choices. by open vistas Topographicalto objects that are morefea- useful as landmarks than to objects the test booklet) that matched the sample image (upper page). tures were varied(e.g. between a highway stretching sample through and an opentest desert) images. and Inthat topographi- are less useful [22]. In addition, PPA response can be closed-in scenes (e.g. a crowded city street) [9,10]. Finally, modulated by the navigational history of an object: objects Memory tests used a delayed match to sample task, interposing a cal tasks subjectsPPA had response to to matchscenes is greater images when subjects based judge solely the initially on the encountered topo- at navigational decision points, for 2 s delay (during which a blank page was shown) between sample graphical features;location viewpoint of a target object and relative nonspatial to the fixed architectural featuresexample were intersections, varied elicit more activity when they are sub- elements in the scene than when they judge its location rela- sequently observed in isolation compared with objects and test images. In both cases participants had a maximum of 60 s between sampletive and to a movable test images.object or the viewer, The thus target demonstrating is a showninitially at encountered the top at non-decision point locations [23]. role for the PPA in the processing of environment-centred These results demonstrate that the PPA responds not only to to make a response. Bottom: Examples of nonspatial and topo- left of the four choices.spatial relationships [Color [11]. figure can be viewedscenes, in the but also online to non-scene objects with orientational value, graphical items. In nonspatial tests participants had to match issue, which is available at wileyonlinelibrary.com.]

each task began with three practice items, with feedback from the pants then saw a blank page for approximately 2 s before experimenter that drew their attention to relevant features of the being presented with the four way choice on the next page stimuli. Typed instructions were present throughout testing. (Fig. 2). In both tasks, if the participant had made no response within 30 s they were given a neutral prompt for an answer. If they had made no response within a minute they Topographical Perception and Short-Term were asked to guess. Memory The sample image showed one viewpoint of a landscape at a The participant was presented with a sample image, and a particular time of day and year. The four test scenes showed four-alternative choice of test scenes arranged in a 2 3 2 the target and three foil items. All four test scenes were land- grid. In the perception task, the test scenes were on the facing scapes rendered under the same prevailing conditions as each page of the test booklet (Fig. 2). In the short-term memory other (they showed the same time of day and year), but with task, the sample image was presented in isolation for approxi- different prevailing conditions and viewpoint from the sample mately 8 s. The page of the booklet was turned and partici- image. However, the test scenes showed different topographical

Hippocampus Visual agnosias Often associated with temporal lobe damage or dysfunction

§ Apperceptive visual agnosia § Associative visual agnosia § Prosopagnosia § Topographical disorientation | some types of disorientation § Cerebral achromatopsia § Akinetopsia

22 Visual agnosia Difficulty in recognizing visual objects

Note that a patient with anomia may also respond in a similar way, but they can describe what the object is used for, whereas a patient with agnosia cannot.

23 Lissauer’s (1890) two-stage framework For understanding disorders of object processing

Object

apperception Form stable perceptual representation

association Access stored knowledge

24 Elizabeth Warrington’s view on apperception What it must be like to see the world with apperceptive agnosia

25 Test of early visual processing | apperceptive agnosia Incomplete letters from Warrington’s VOSP battery

26 Lissauer’s (1890) two-stage framework For understanding disorders of object processing

Object

apperception Form stable perceptual representation

association Access stored knowledge

27 Copying in apperceptive agnosia Poor because perception is poor

28 Shape matching in apperceptive agnosia Poor because perception is poor

29 Copying in associative agnosia Can be good although slow because perception is present but stripped of meaning

30 Patient DF Perhaps the most famous visual agnosic

• She was unable to identify shapes but able to recognize objects by colour • Could not identify edges, line orientation or figure from ground – she has visual form agnosia (a type of apperceptive agnosia) • Poor direct copying

31 Preserved ability to “grasp shape” in D.F. Ability to negotiate obstacles

Pebble like objects (Blake’s shapes) used to test robotic grasping abilities Unfamiliar environment with obstacles of different height PatientCurvature DF of different parts of the object to be taken into account But she could shape her hand correctly to grasp different objects

As in controls, D.F. was able to step over the obstacles leaving Just enough clearance to ensure that the foot does not touch the obstacle

D.F. grasping not very different from controls

32

How do we know that D.F. symptoms are not due to general “poor” vision that Matching and posting task Goodale, et al., (1991) makes it impossible for her to process detailed aspects of shape but leaves enough visual processing ability to carry out generalised actions towards objects? Matching turn card to match the orientation of the slot Posting reach out and “post” the card into the slot Double dissociations can be used to rule out the possibility that deficits in a particular task are just related to task difficulty

Need for evidence from another syndrome presenting opposite patterns of impaired and spared functions

D.F. undistinguishable from controls in the posting task only

Optic ataxia as part of “Balint’s syndrome” Symptoms can vary according to the specific damage suffered by different similar patients e.g. in addition to reaching problems Balint (1909) inability to shift gaze patient with bilateral inability to focus attention on more than one part damage to parietal (and of a visual scene dorsal occipital) cortex

Inability to reach for visible objects with right hand Holmes (1918) considered the deficit as mainly spatial deficit could not be purely perceptual since patient could reach i.e. inability to use egocentric co-ordinates to locate objects for objects using left hand Ability to reach for specific body parts on request the deficit cannot be purely motor as reaching can be achieved using tactile or proprioceptive information

Therefore, specific problems in translating vision into action little difficulty in giving perceptual reports of the orientation and location of the very objects they fail to grasp.

On the other side of the equation, an impairment of ventral stream function seems to occur in humans who suffer from the condition known as visual form agnosia. The classic case of this disorder was described by Benson and Greenberg (1969). Their patient was not only unable to recognize faces or objects, he could not even reliably identify geometric shapes visually, nor distinguish reliably between a square and a rectangle with a 2:1 aspect ratio. Yet the patient was certainly not cortically blind. Recently we have described a very similar patient, D.F. (Milner et al., 1991). We have examined her spared abilities to use visual information in a series of experimental studies. We have found that her attempts to make a perceptual report of the orientation of an oriented slot show little relationship to its actual orientation, whether her reports are made verbally or by manual means (see Figure 2). However, when she was asked to insert her Patienthand orDF a hand-held card into the slot, she shows no difficulty, moving her hand or the card towards the slot in the correct orientation and inserting it quite accurately (see Figure 2). Videorecordings have shown that her hand begins to rotate in the appropriate direction as soon as it leaves the start position. In short, although she cannot report the orientation She could alsoof the slot, ‘post’ she can insert her a hand letter or post a card into through it with considerable skill. different slot orientations correctly

Figure 2

The diagram at the top of this figure illustrates the apparatus that was used to test sensitivity to orientation in the patient D.F. The slot could be placed in any one of a number of orientations around the clock. Subjects were required either to rotate a hand-held card to match the orientation of the slot or to 'post' the card into the slot as shown in this figure. The polar plots at the right of the figure illustrate the orientation of the hand-held card on the perceptual matching task and the visuomotor posting task for D.F. and an age-matched control subject. The correct orientation on each trial has

33 Patient DF Bran damage in DF aligns with area LOC (lateral occipital complex)

34 The neural basis of object perception Grill-Spector 161 fMRI studies reveal object, face and place regions Figure 2 In human ventral visual stream (a) (b) LO 2

1 % signal 0 Right FANHST JHT ITG ips 2

Dorsal foci lateral 1 % signal

v7 0 v3a FANHST v3 FFA v2 2 . v1 LO MT 1 % signal

ITG 0 FANHST pFus FFA v4 mFus 2 vp mFus VOT v2 v1 PPA 1 % signal

0 FANHST ventral PPA 2 Objects, places & faces Faces & objects Places & objects 1 Grill-Spector Current Opinion Neurobiology 2003 & Objects Faces Places % signal Grill-Spector & Weiner Nature Reviews Neurosci 2014 0 35 FANHST

Current Opinion in Neurobiology

Object-selective regions in the human brain. (a) The maps shown in Figure 1 were combined into a single map, which is displayed on the flattened, lateral and ventral view of the right hemisphere. (b) Percentage change in the signal from several regions of interests (ROIs) of the same size (200 mm3) centered on each ROI: LO, lateral occipital (Talairach coordinates [x,y,z]: 40, 74, 2); ITG, ROI centered on blue region in the inferior temporal À À gyrus (46, 58, 3); FFA, fusiform face area (40, 50, 15); PPA, parahippocampal place area (25, 35, 9); mFus, region in the mid fusiform that À À À À À À responds to all object categories (33, 38, 15); Pfus, posterior fusiform gyrus. À À

(Figure 1 Legend Continued) patterns. Object-selective regions in the ventral stream consist of the lateral occipital complex (LOC), which can be subdivided to at least three partitions: lateral occipital (LO), which is located posterior to MT, a region in the inferior temporal gyrus and a region in the mid fusiform gyrus (mFus). In the dorsal stream, object-selective areas include v7, which lies anterior to v3a located in the posterior bank of the intra- parietal sulcus and responds both to objects and scenes, and a region in the intraparietal sulcus that has a separate fovea and periphery organization. Abbreviations: CA, calcarine sulcus; COS, collateral sulcus; IPS, intraparietal sulcus; ITS, inferior temporal sulcus; MT, human motion area; OTS, occipito-temporal sulcus; STS, superior temporal sulcus; TOS, transverse occipital sulcus.

www.current-opinion.com Current Opinion in Neurobiology 2003, 13:159–166 One conceptual framework for object recognition And its breakdown in visual agnosias

A hierarchical, bottom-up model

Integrative agnosia

36 Humphreys & Riddoch Cognitive Neuropsychology 2006 ATALEOFTWOAGNOSIAS

Patient HJA A case of ‘integrative’ agnosia

Figure 1. (a)–(d): Functional magnetic resonance imaging (fMRI) showing a dorsal extrastriate lesion (S.A.). (e)–(h): fMRI showing a ventral extrastriate lesion (H.J.A.).

SECTION A: DEFINING THE TYPE including a part-time clerical job. She self- OF AGNOSIA reported with some difficulties in object recog- nition and reading. Her colour naming was Case histories relatively spared. There was some impairment in face recognition. She scored 38/54 on the S.A. S.A., a hospital clerical worker, suffered a Benton Face Recognition Test (Benton, bilateral occipital stroke in 1997 at the age of 50 Hamsher, Varney, & Spreen, 1983), thus falling years. She attended for testing 4 years post- into the “moderately impaired class”. On the lesion, in 2001. Figure 1 presents the results Warrington Recognition Test (Warrington, from a high-resolution (3T) structural scan 1984) she scored 34/50 for faces and 46/50 (1 mm isotropic) performed in February 2006. for words. Age-matched control scores are 42.7 This revealed a sparing of the calcarine cortex

Downloaded by [the Bodleian Libraries of the University Oxford] at 14:49 30 January 2016 (SD 3.8) for faces and 43.2 (SD 4.0) for (although there was some involvement on the ¼ ¼ 37 words (from the Warrington Recognition Test left) and the ventral extrastriate areas (including manual). S.A.’s recognition memory for faces is the lingual and fusiform gyri). The lesion involved therefore impaired relative to that for words. the dorsal extrastriate cortex, including the right intraparietal sulcus. Areas MT, LOC, PEF, and V4 were spared (see Figure 1b). S.A. lived with H.J.A. H.J.A. was aged 82 years at the time of the her husband and had an independent life, present investigations. He had suffered a posterior

COGNITIVE NEUROPSYCHOLOGY, 2008, 25 (1) 59 Agnosia 31

part substantiated this line of theory, with deficits in indentifying real-world objects than still photographs, identifying biological objects following inferior–temporal and have the poorest performance when required to lobe damage. identify line drawings. Such findings suggest that the addition of surface information and depth information appears to increase performance via benefiting the pro- Integrative Agnosia cesses involved in integrating elements of the stimuli into a perceptual whole. Interestingly, when H.J.A. incorrectly While Lissauer’s pioneering work dichotomizing forms of named an object, his errors were visually related to the recognition disorder (apperceptive vs. associative) is still target objects and never seemed to be a result of semantic often cited, we are now fully aware that object recognition association, suggesting a deficit before access of item- is a far more complicated process than Lissauer could specific stored knowledge has been retrieved. This notion have intuited. Rather than simply matching stimuli is furthered by findings that integrative agnosics are coded in terms of primitives (like line orientation) to unable to perform matching tasks that require semantic previously acquired knowledge, the visual system must code the spatial relations between lines and features, the information or, to gesture, the correct use of misidentified object must be parsed from the background, and indivi- objects. In sum, the deficit truly is one of object identifica- dual parts of the object need to be related to one another. tion, rather than object naming. Although the disruption Problems with this intermediate level of vision can result in processing is undoubtedly before higher visual pro- in poor overall perceptual integration of form informa- cesses, such as the attachment of meaning, most tion. Perhaps the best-studied patient was described in integrative agnosics perform quite well on standardized detail by Riddoch and Humphreys, H.J.A., who had bilat- test of early perceptual processing. For example, H.J.A eral occipitotemporal damage following an infarct of the was able to accurately reproduce etchings presented to posterior cerebral artery. Following the lesion, H.J.A. him, as can be seen in Figure 3 (although his order of demonstrated profound impairments in a number of drawing lines was abnormal). higher-level visual tasks, including face recognition, In addition, H.J.A. performed well on a task requiring word recognition, and visual navigation. When attempt- the perceptual discrimination of objects that are matched ing to identify objects, H.J.A.’s descriptions generally for overall area and brightness, which patients suffering consisted of fragmented reports of various form-based from impairments in the encoding of basic visual proper- features, with correct identification of an object seemingly ties could not. In order to account for all features of hinged on either an elongated process of deduction or the performance found in integrative agnosics, basic, local presence of a highly diagnostic feature. For example, visual elements are thought to be processed in a normal when asked to identify a line drawing of a pig, H.J.A. way, but the integration of these elements into unitary began identifying features such as having four short legs wholes is impaired. In more concrete terms, integrative and a powerful body. Once he realized the mystery ani- agnosia appears to be a deficit located between the stage mal possessed a small curly tail, he was quick to correctly of visual processing concerned with shape processing and identify the stimulus. Typically, integrative agnosics the visual access to memory representations. Since the over-segment stimuli, with parts of the same object human visual system is limited recognizing one object at a being classified as separate. For example, while describing time, any deficiencies in the ability to properly segment/ a paintbrush, H.J.A. suspected there may be two objects group the visual field will lead to the deficits observed in Patient HJAclose together, rather than the single paintbrush pre- integrative agnosia by way of perception breaking down sented. These patients typically perform best when into a parts-based analysis of objects. A case of ‘integrative’ agnosia

1438 M. JANE RIDDOCH AND GLYN W. HUMPHREYS

Figure 3 Copy of an etching of St. Paul’s cathedral by patient H.J.A. Reproduced from Humphreys GW (2001) Case Studies in the Neuropsychology of Vision, Figure 3.1 (pg. 45), withDownloaded from permission from Psychology Press. Copy of an etching of St Paul’s cathedral http://brain.oxfordjournals.org/ • Good identification of elementary shapes Owl • Very accurate copy of drawings and objects

Bee

38 by guest on January 30, 2016 FIG. 5. Examples of H.J.A.'s copying of objects he fails to identify. In each example, the original line drawing Riddoch & Humphreys Brain 1987 is shown on the left and H.J.A.'s copy is shown alongside it. He named the eagle as 'a cat sitting up", the guitar as 'some kind of a machine, a press', the owl as 'a pattern', and the bee as "an animal with horns and a tail, a rhino?'

(0.66 x 0.66 x 25) correct on both occasions, the number of stimuli which he names correctly on one occasion and incorrectly on the other should be 5.61 (0.66 x 0.34 x 25), and the number which he fails to name on both occasions should be 2.39 (0.34x25). The observed frequencies (15 correct on both occasions, 2 correct on the first and incorrect on the second, 1 correct on the second and incorrect on the first, and 7 incorrect both times) differ significantly from those expected from complete independence (/><0.05, goodness of fit with 3deg of freedom). The observed frequencies are also close to those expected from complete dependence (16.5, 0, 0, 8.5). Finally, if there was complete independence, per- formance accuracy in the second test should be the same for the items wrong on the first test as for the items right. Out of 9 errors on test 1, only 2 were correct on test 2; out of 16 correct responses on test 1,15 were correct on test 2. Performance on the items wrong on test 1 differed from that on the items correct (y2= 10.46). Patient HJA A case of ‘integrative’ agnosia

• Good identification of elementary shapes • Very accurate copy of drawings and objects • Good semantic memory as indexed by drawing from memory 39 Riddoch & Humphreys Brain 1987 Patient HJA A case of ‘integrative’ agnosia

• Good identification of elementary shapes

• Very accurate copy of drawings and objects

• Good semantic memory as indexed by drawing from memory

• Deficit in integrating single features of a stimulus in a coherent fashion

40 Riddoch & Humphreys Brain 1987 Apperceptive Agnosia Patient HJA •Incomplete silhouette drawings of objects (Street Difficulties with parsing briefly presented overlapping figures 1931, Ghent overlapping figure test, Gollin’s test)

41 Riddoch & Humphreys Brain 1987 ASSOCIATIVE VISUAL AGNOSIA: COPY

ASSOCIATIVEWhereas VISUAL AGNOSIA: associative SEGMENT COMPLEXagnosics DRAWINGScan do this INTO THEIR EvenPARTS though they might not identify each object

42 McCarthy & Warrington J Neurol Neurosurg Psych 1986

7 Framework for understanding object recognition From retinal image to object identity in the ventral visual stream

Image

Local computation of In early visual cortex (V1) - intact in HJA contours

Integration of contours Intermediate visual areas into shapes

Computing object Inferotemporal cortex ‘identity’ 43 One framework for object recognition And its breakdown in visual agnosias

A hierarchical, bottom-up model

Integrative agnosia

Semantic dementia

44 Humphreys & Riddoch Cognitive Neuropsychology 2006 Overview wires.wiley.com/cogsci Behrmann’sOverview classification for visual agnosias wires.wiley.com/cogsci

ButTABLE note 1 thatClassification now degenerative of Types of Visual conditions Agnosia, their are Unde farrlying more Neuropathology, common an causesdClinicalManifestation than strokes TABLE 1 Classification of Types of Visual Agnosia, their Underlying Neuropathology, andClinicalManifestation Neuropathology Clinical Manifestation Neuropathology Clinical Manifestation Apperceptive agnosia ApperceptiveVisual form agnosia Stroke, anoxia, carbon monoxide poisoning Unable to copy, match, or identify visual stimuli Visual form agnosia Stroke,affecting anoxia, occipital, carbon parietal, monoxide or posterior poisoning Unable to copy, match, or identify visual stimuli temporalaffecting occipital, regions bilaterally parietal, or posterior Integrative agnosia Extensivetemporal extrastriate regions bilaterally damage bilaterally or Able to copy and match stimuli, may even be Integrative agnosia Extensivejust to the extrastriate right hemisphere damage bilaterally or Ableable to to copy provide and match verbal stimuli, description may of even aspects be of just to the right hemisphere inputable to but provide still fails verbal to recognize description object of aspects of Associative agnosia input but still fails to recognize object AssociativeImpaired access agnosia to structural Both types: usually bilateral infarction of the Fails to access stored representation of object Impairedknowledge access to structural Bothposterior types: usually cerebral bilateral arteries infarction but unilateral of the Failsstructural to access description stored representation of object knowledge temporo-occpitalposterior cerebral damage arteries butmay unilateral suffice structural description Impaired access to/within temporo-occpital damage may suffice Fails to access or activate stored semantic Impairedsemantic access knowledge to/within Failsknowledge to access of or objects activate either stored just semantic from vision or semantic knowledge fromknowledge all modalities of objects either just from vision or Perceptual categorization Not yet definitively specified Impairedfrom all recognition modalities of objects from unusual Perceptualdeficit categorization Not yet definitively specified Impairedviews or recognition under unusual of objects lighting from conditions unusual 45 deficit views or under unusual lighting conditions Prosopagnosia Acquired form: bilateral infero-mesialBehrmann visual& NishimuraFailure (2010) to Wiley recognize Interdisciplinary faces Review Cognitive Science Prosopagnosia Acquiredassociation form: cortices bilateral (lingual infero-mesial and fusiform visual Failure to recognize faces gyri)association and subjacent cortices white (lingual matter and fusiform Agnosia for words Leftgyri) occipitotemporal and subjacent cortex white matter ‘Pure’ alexia—fails to read words normally Agnosia for words Left occipitotemporal cortex ‘Pure’despite alexia—fails normal language to read words and sensory normally visual functiondespite normal language and sensory visual Agnosia for scenes Bilateral or right posterior artery infarction Failurefunction to recognize landmarks or known scenes Agnosia for scenes Bilateralinvolving or right the fusiform posterior and artery lingual infarction gyri, Failure to recognize landmarks or known scenes extendinginvolving the to the fusiform parahippocampal and lingual gyri, gyrus Developmental agnosia Noextending obvious neural to the concomitant parahippocampal on gyrus Difficulty in acquiring mastery over word or face Developmental agnosia Noconventional obvious neural CT concomitant or MRI scanning on Difficultyrecognition in acquiring (developmental mastery over dyslexia word or or face conventional CT or MRI scanning developmental/congenitalrecognition (developmental prosopagnosia) dyslexia or Posterior cortical agnosia Focal right temporal and/or occipital lobe Progressivedevelopmental/congenital decline in complex prosopagnosia) visual functions Posterior cortical agnosia Focalatrophy right temporal and/or occipital lobe Progressiveand recognition decline in complex visual functions atrophy and recognition

as in associative agnosia). The nomenclature below individuals cannot recognize, copy, match, or dis- proceedsas in associative from the agnosia). most severe The perceptual nomenclature impairment below criminateindividuals simple cannot visual recognize, stimuli, copy, and cannot match, recognize or dis- toproceeds the most from intact the perception. most severe perceptual impairment evencriminate simple simple shapes visual such stimuli, as triangles and cannot or circles. recognize Some to the most intact perception. individualseven simple may shapes also such have as achromatopsia, triangles or circles.19 in which Some individuals may also have achromatopsia,19 in which Apperceptive Agnosia case they cannot match stimuli by color either. These case they cannot match stimuli by color either. These PatientsApperceptive with apperceptive Agnosia agnosia are unable to patients usually do better with real images than with patients usually do better with real images than with constructPatients with a stimulus-specific apperceptive agnosia structural are description. unable to line drawings—for example, one such patient recog- line drawings—for example, one such patient recog- Twoconstruct predominant a stimulus-specific forms exist, structural as detailed description. below.17 nized only 17% of black-and-white line drawings but Two predominant forms exist, as detailed below.17 whennized only the same 17% images of black-a werend-white presented line indrawings color they but when the same images were presented20 in color they Visual Form Agnosia were recognized with 26% accuracy. Performance were recognized with 26% accuracy.20 Performance Visual form Form agnosia, Agnosia a term introduced by Benson also improves when motion accompanies the input, andVisual Greenberg, form agnosia,18 and a synonymous term introduced with severe by Benson form presumablyalso improves because when motion this provides accompanies additional the input, cues andperception, Greenberg, refers18 and to thesynonymous class of with individuals severe form who topresumably assist in shape because perception. this provides Tracing additional the contours cues complainperception, of refers blurred to or the unclear class vision of individuals but, on formal who alsoto assist aids recognition,in shape perception. because the Tracing traced the information contours examination,complain of blurred their acuity or unclear is more vision than but, adequate on formal to canalso aids be represented recognition, because internally the through traced information the hand recognizeexamination, objects. their In acuity addition, is more color, than brightness, adequate and to movements,can be represented perhaps internally by visual through imagery processes,the hand movementrecognize objects. discrimination In addition, are color, typically brightness, preserved, and whichmovements, provides perhaps a compensatory by visual approach imagery to processes, support whilemovement the ability discrimination to perceive are figural typically properties preserved, such recognition.which provides The a compensatorylesions in visual approach form agnosia to support are aswhile size, the orientation, ability to and perceive shape figural is typically properties lost. These such typicallyrecognition. diffuse The and lesions posterior. in visual The form prominence agnosia are of as size, orientation, and shape is typically lost. These typically diffuse and posterior. The prominence of

206 © 2010 John Wiley & Sons, Ltd. Volume 1, March/April 2010 206 © 2010 John Wiley & Sons, Ltd. Volume 1, March/April 2010 Framework for understanding object recognition From retinal image to object identity in the ventral visual stream

Image

Local computation of In early visual cortex (V1) - intact in HJA contours

Integration of contours Intermediate visual areas into shapes

Computing object Temporal Inferotemporal cortex Semantics ‘identity’ pole 46 cortex 44 (2008) 1265–1270 1267 cortex 44 (2008) 1265–1270 1267

In a pilot version of the test, participants were asked to to the ‘‘stethoscope’’, to minimise working memory demands. define the repeated item prior to pointing at its pictorial ref- The experimenter/clinician can provide the target word In a pilotcortex version 44 of (2008) the test, 1265–1270 participants were asked to to the ‘‘1267stethoscope’’, to minimise working memory demands. erent. Adefine four point the repeated system was item adopted prior to for pointing scoring at defini- its pictorialmore ref- than onceThe at experimenter/clinicianany stage of the test if the patientcan provide requests the target word tions accordingerent. A to four the point detailsystem and specificity was adopted of the response for scoringit. defini- In our assessmentmore than study, once all at sessions any stage were of the tape-recorded test if the patient requests In a pilot version of the(from test, 0 participantsincorrect, were or no asked response, to to to the 3 ‘‘stethoscopereferent’’, reliably to minimisefor working scoring memory of repetition demands. attempts, but this is not necessary tions according to the detailcortex and 44 (2008) specificity 1265–1270 of the response it. In our assessment1267 study, all sessions were tape-recorded ¼ ¼ cortex 44 (2008) 1265–1270 1267 define the repeated itemidentifiable prior to(from pointing from 0 at theincorrect, itspictorial verbal descriptionref- or noThe response, given). experimenter/clinician After to 3 a num-referent can reliablyfor provide routine the usefortarget of scoring the wordtest. of repetition attempts, but this is not necessary ¼ ¼ erent. A four point systember was of attemptsidentifiable adopted for to scoringrefine from and the defini- simplifyverbalmore description the thancortex scoring once 44 given). atcriteria (2008) any stage 1265–1270 After it of the a num- test if the patientfor routine requests use of the1267 test. tions according to theIn detail a pilot and version specificity of the test,of the participants response wereit. asked In our to assessmentto the ‘‘stethoscope study,cortex all’’, to sessions minimise 44 (2008) were working 1265–1270 tape-recorded memory demands. 1267 was decidedber of to attempts excludeIn a pilotthis to refine versioncomponent and of the simplifyfrom test, participants the the final scoring weretest. asked criteria2.4.1. to itto Repeat the ‘‘stethoscope’’, to minimise working memory demands. (from 0 incorrect,define or no the response, repeated item to 3 priorreferent to pointing reliably at its pictorialfor scoring ref- ofThe repetition experimenter/clinician attempts, but this can is provide not necessary the target word ¼ Both theIn aPNFA pilot version and¼ define SD of patients the test,repeated participants had item difficulty prior were togenerating pointingasked to at itsto def- pictorial the ‘‘stethoscopeOnly ref- ’’, theThe to minimisefirst experimenter/clinician repetition working memoryattempt can demands. was provide scored, the and target was word given identifiable from theerent. verbal A four description pointwas system decided given). was After to adopted exclude a num- for scoring thisfor component defini- routine usemore of from the than test. once the at final any stage test. of the test2.4.1. if the patient Repeat requests initions,define but the repeated for differenterent. item A prior four reasons.In to a point pointing pilot system versionFor at example, its wasof pictorial the adopted test, a ref- participants PNFA for scoringThe pa- experimenter/clinician were defini-a asked score tomore of 1to than if the correct can ‘‘oncestethoscope provide at and any’’,stage thea to score minimise target of the of testword 0working otherwise. if the memory patient demands.requests ber of attempts totions refine according and simplifyBoth to the the detail scoring PNFA and specificity and criteria SD it of patients the response had difficultyit. In our generatingassessment study, def- all sessionsOnly were the tape-recorded first repetition attempt was scored, and was given erent. A four pointtions system accordingdefine was the adopted to repeated the detail for item scoring and prior specificity defini- to pointing ofmore the at its thanresponse pictorial once atref- anyit. InstageThe our of experimenter/clinician assessment the test if the study, patient all requests cansessions provide were the tape-recorded target word (fromtient 0 incorrect, havinginitions, or difficulty no but response, for expressing different to 3 referent the reasons. reliably meaning Forfor of example, scoring a word, of repetitiona PNFA attempts, pa- buta score this is of not 1 necessaryif correct and a score of 0 otherwise. was decided to exclude this¼ componenttions according from to(from the the detail 0 finalerent.incorrect, and test.¼ A specificity four or point2.4.1. no of response, system the Repeat response was to adopted 3 referentit. for In ourscoring reliably assessment defini-for study, scoringmore all than of sessions repetitiononce at were any attempts, stage tape-recorded of the but test this if the is patient not necessary requests identifiablesuch from as caterpillar the verbal, description might¼ concurrently given). After a demonstrate num- for routine¼ an un- use of the2.4.2. test. Point Both the PNFA and SD patients(from hadtient 0 difficultyincorrect, havingidentifiable generating or difficulty notions response, from def- according the expressing to verbalOnly 3 toreferent the descriptionthe detail first the reliably and repetition meaning given). specificityfor Afterattempt scoring of of the a num- a response of wasword, repetition scored,for routineit. attempts, In and our use was assessment butof thegiven this test. is study, not necessary all sessions were tape-recorded ber of attempts to¼ refine and simplify the scoring criteria¼ it initions, but for differentderstanding reasons.identifiablesuch Forof example,as from thecaterpillar theber concept verbalof a attempts PNFA(from description, might using pa- 0 toincorrect, refine pantomime, concurrently given).a score and or Aftersimplify noof 1 response, a if num- whereas correct the demonstrate scoring to andfor 3 an routinereferent a criteria score useParticipants an reliably of it of0 un- theotherwise. test.for were2.4.2. scoring shown of Pointrepetition an array attempts, of seven but this pictures is not necessary and asked was decided to exclude this component from¼ the final test. 2.4.1. Repeat¼ tient having difficulty expressingSDber patient of attemptsthe failing meaning towas refine to decided of define andidentifiable a word, simplify to caterpillarexclude from the thisthe scoring verbal component accurately criteria description it from would given). the final After test.to a pointnum-2.4.1. tofor the routine Repeat target use item of the named test. by the examiner, which was Both the PNFA andderstanding SD patients had of difficultytheber of concept attempts generating to using refine def- and pantomime, simplifyOnly the the first scoringwhereas repetition criteria attempt an it wasParticipants scored, and was were given shown an array of seven pictures and asked such as caterpillar, might concurrentlywas decided demonstrate to excludeBoth the this PNFA an component un- and SD2.4.2. patientsfrom the Point had final difficulty test. generating2.4.1. Repeat def- Only the first repetition attempt was scored, and was given initions,rarely but for evenSD different patient attempt reasons. tofailing gestureForwas example, decided to its define meaning.to a PNFA exclude caterpillar pa- this As componenta gesture score accurately of was 1from if correct the finalpresented andwould test. a score in ofto a 0 randomotherwise. point to location. the target All sixitem foils named were chosen by the examiner,to be which was Both the PNFA andinitions, SD patients but for had different difficulty reasons. generating For def- example,Only a PNFAthe first pa- repetitiona score2.4.1. attempt of 1 ifRepeat was correct scored, andand a score was of given 0 otherwise. derstanding of thetient concept havingnot using part difficulty pantomime,of the expressing instruction, whereas theBoth meaning the anthis PNFA could ofParticipants and a SDword, not patients ‘count’ were had shown difficulty for or an generating arraysemantically of def-seven picturesOnly close the and first to askedtherepetition target attempt (e.g., wasfor the scored, target and wasitem givenostrich initions,rarely buteven for differenttient attempt having reasons. difficulty to For gesture example, expressing its a PNFA meaning. the pa- meaninga As score of gesture a of word, 1 if correct was and apresented score of 0 otherwise. in a random location. All six foils were chosen to be SD patient failingsuch to define as caterpillar caterpillar, mightaccurately concurrentlyinitions, would demonstrate but forto different point an un- to reasons. the2.4.2. target For itemPoint example, named a PNFA by the pa- examiner,a score of which 1 if correct was and a score of 0 otherwise. againsttientnot a having patient’s part difficulty ofsuch performance. the as expressingcaterpillar instruction, theBecause, might meaning concurrentlythis the of goal could a word, was demonstrate not to pro- ‘count’ anall un- for distractors or2.4.2.semantically Point were large wild close birds), to the and target in some (e.g., cases, for the per- target item ostrich rarely even attempt to gesture its meaning. As gesturetient was having difficultypresented expressing in a random the meaning location. of All a word, six foils were chosen to be derstandingducesuch of a the test as caterpillar concept withderstanding, ausing might simple pantomime, concurrently scoringof the conceptwhereas demonstrate system, using an the an pantomime,Participants un- (otherwise2.4.2. whereas were Point shownceptually an an arrayParticipants similar of seven were pictures(see shownFig. and an 1 asked arrayfor anof seven example). pictures and Participants asked against a patient’ssuch performance. as caterpillar, might Because concurrently thegoal demonstrate was to an pro- un- 2.4.2.all distractors Point were large wild birds), and in some cases, per- not part of the instruction,SD patientderstanding thisfailing could to defineof not theSD ‘count’ conceptcaterpillar patient for using failing accurately or pantomime, tosemantically define would whereas caterpillar closeto anpoint accuratelyto to theParticipants the target target would (e.g., item were for named shownto the pointtarget byan thearray to the examiner,item of target sevenostrich itempictures which named was and by asked the examiner, which was ratherduce fascinating) a test definition withderstanding a simple component of the scoring concept of the system,using test pantomime, wasthe (otherwise whereaswere an not givenParticipantsceptually any were feedback similarshown an on array (see their of sevenFig. performance. pictures1 for and an asked example). Again, Participants against a patient’s performance.rarely evenSD attempt Because patient to failinggesture therarely goal to its was define evenmeaning. to attempt pro- caterpillar As gesture toall gesture accurately distractors was its meaning. wouldpresented were large Asto in pointgesture a wild random to birds), the was location. target andpresented item in All some named six foilsin cases,a by random were the per-examiner, chosen location. to which be All six was foils were chosen to be dropped. SD patient failing to define caterpillar accuratelyonly would first responsesto point to the were target itemscored: named 1 byfor the a examiner, correctly which identified was duce a test with anot simple part of scoringrarely therather instruction, even system, attempt fascinating)not the this to part (otherwisegesture could of the definitionnot its meaning. instruction, ‘count’ceptually for As component gesturethisor similar couldsemantically was not (see ofpresented ‘count’Fig. the close 1 for testfor to in the aor anrandom was target example).semantically location.(e.g.,were for Participants the All close sixnot target foils to given the item were targetostrich chosen any (e.g., feedbackto for be the target on item theirostrich performance. Again, rarely even attempt to gesture its meaning. As gesture was presented in a random location. All six foils were chosen to be against a patient’snot part performance. of the instruction, Because this the goal could was not to ‘count’pro- forall ordistractorssemantically were largeitem, close wild 0 to otherwise. the birds), target and (e.g., in somefor the cases, target per- item ostrich rather fascinating) definition componentdropped. ofagainst the testanot patient’s part was of performance. thewere instruction, not Because given this any the could goal feedback not was ‘count’ toon pro- for their orall performance. distractorssemanticallyonly firstwere closeAgain, large responses to the wild target birds), (e.g., were and for inthe scored: some target cases, item 1 forostrich per- a correctly identified duce a2.4. testagainst with Repeat a a patient’s simple and scoring performance. Point system, test administrationBecause the (otherwise the goal was toceptually pro- all similar distractors (see wereFig. 1 largefor wild an example). birds), and Participants in some cases, per- dropped. duce a testagainst with a patient’s a simpleonly performance. first scoring responses system, Because were the the(otherwise goal scored: was to 1 pro- forceptually a correctlyall distractorsitem, similar identified 0 otherwise. were (see largeFig. 1wildfor birds), an example). and in some Participants cases, per- rather fascinating)duce a test definition with a component simple scoring of thesystem, test the was (otherwisewere notceptually given any similar feedback (see onFig. their 1 for performance. an example). Again, Participants rather fascinating)duce a test definitionwithitem, a simple 0 otherwise. component scoring system, of the the test (otherwise was2.5.were Statisticalceptually not given similar analyses any feedback (see Fig. 1onfor their an example).performance. Participants Again, dropped. rather2.4. fascinating) Repeat definition and Point component test of administration the testonly was firstwere responses not given were any scored: feedback 1 for on a correctly their performance. identified Again, 2.4. Repeat and PointThe test final administration version ofdropped. the Repeatrather andfascinating) Pointtest definition takes component between of 5 the test wasonlywere first notresponses given any were feedback scored: on 1 for their a correctlyperformance. identified Again, dropped. item, 0 otherwise.only first responsesitem, were 0 scored:2.5. otherwise. 1 for Statistical a correctly identified analyses and 10 min to complete.Semantic Eachdropped. word is2.5. read aloud Statistical by the analysesdementia exam- Scores (percentonly first correct) responses were were scored: analysed 1 for a with correctly three identified by two 2.4. RepeatThe and Point final test version2.4. administration Repeat of the and Repeat Point test and administration Point test takesitem, 0 betweenotherwise. 5 item, 0 otherwise. The final version of the Repeatiner2.4. for and each Point Repeat task test and in takes Point turn, between test e.g., administration repeat 5 ‘‘stethoscope2.5.’’ thenStatistical point analysesANOVAs by both subjects (F ) and items (F ), with and 10 min to complete.2.4. Repeat Each and word Point testis read administration aloud by the exam-2.5.Scores Statistical (percent analyses correct)s were analysedi with three by two cortex 44 (2008) 1265–1270 1269 and 10 min to complete. Each word is read aloud by the exam- Scores (percent correct) were analysed with three by two The final version of the RepeatThe and finalProgressive Point version test takes of the between Repeat andloss 5 Point testof takes 2.5.understanding between Statistical 5 analyses2.5. Statistical of analysesmeaning iner for each task in turn, e.g., repeat ‘‘stethoscope’’ then point ANOVAs by both subjects (Fs) and items (Fi), with iner for each task inand turn, 10 min e.g., toThe repeat complete. final ‘‘ versionstethoscope Each ofand word the’’ 10 Repeat then is minThe read to point final and aloud complete. Pointversion by thetestANOVAs Each of exam- takes the word Repeat between by is readScoresand both 5 Point aloud (percent subjectstest bytakes the correct) exam- between (Fs) were and 5Scores analysed items (percent ( withFi), correct) withthree bywere two analysed with three by two iner for eachand task 10 in min turn, to complete. e.g., repeat Each ‘‘stethoscope word is read’’ then aloud point by the exam-ANOVAsScores by both (percent subjects correct) (F were) and analysed items with (F ), three with by two iner for eachand 10 task min in to turn, complete. e.g., repeat Each word ‘‘stethoscope is read aloud’’ then by point the exam-ANOVAsScoress by (percent both correct) subjectsi were (Fs analysed) and items with three (Fi), by with two represented by the Point component reinforces the conclusion iner for each task in turn, e.g., repeat ‘‘stethoscope’’ then point ANOVAs by both subjects (F ) and items (F ), with iner for each task in turn, e.g., repeat ‘‘stethoscope’’ then point ANOVAss by both subjectsi (Fs) and items (Fi), with that single word comprehension is largely preserved in PNFA (Hodges and Patterson, 1996; Grossman et al., 1996; Karbe et al., 1993). This clearly delineates them from SD patients for whom impaired word comprehension is a defining charac- teristic (Hodges et al., 1992; Hodges and Patterson, 1996; Adlam et al., 2006; Rogers et al., 2006). The most striking finding was the discriminant function analysis that resulted in 100% correct patient classification based on a combination of the patients’ Repeat and Point scores. This finding indicates high specificity and sensitivity of the Repeat and Point test in the discrimination of PNFA and SD patients. In addition to its specificity and sensitivity, the Repeat and Point test has a number of practical advan- tages, including: (i) it can be administered in less than 10 min; (ii) the objective nature of the scoring criteria makes this test resistant to interpretation errors; and (iii) for clinical purposes, the cut-off Repeat-to-Point ratio for diagnostic dif- Fig. 2 – The mean percentage correct responses on the ferentiation is approximately 1. Specifically, in the present Repeat and Point test. Standard errors are shown for each sample of patients, this ratio never fell below 1.25 for SD group. patients and never fell above .9 for PNFA patients. One clear limitation is that the PNFA group was rather small (N 6). The test was, however, based on extensive clin- ¼ Semantic4. Discussion dementia patients can icalrepeat experience the and evolved word from an informal test used in the “ostrich” but have difficulty pointingclinic, prior to to formalisationit. as the Repeat and Point, which The simple 10-item Repeat and Point test was remarkably suc- very consistently discriminated SD from PNFA. Despite this cessful in discriminating between patients previously classi- limitation, we propose that the Repeat and Point test lends Theyfied (on existing lack criteria) the as conceptual either SD or PNFA. In knowledge terms of itself to commonof what use in a clinicalan context to aid in accurate di- the group results, a double dissociation was apparent, such agnosis of SD and PNFA. ostrichthat SD patients is. were significantly better at repetition than A recent large clinico-pathological study, using a statistical pointing, with the reverse pattern for the PNFA patients. Using modelling method that made no prior assumptions about the 47 discriminant function analysis, a perfect classification of data structure, demonstrated that patients with primary pro- patients was achieved based upon their performance on the gressive aphasiaHodges can be dividedet al (2008) into two coherent Cortex syndromes Fig. 1 – An example from the pointing task. The participant is required to point to the ostrich (target) amongst the six Fig. 1 – An example from the pointing task. The participant is required to point to the ostrich (target) amongst the six Repeat and Point tasks, in that all SD patients obtained a Re- that closely conform to the clinical descriptions of PNFA and Fig. 1 – An example from theFig. pointing 1 – Ansemantically task.example The from related participant the and, pointing inis somerequired task. cases, toThe pointperceptually participant to the similarostrich is required foils. (target) to amongstpoint to the the ostrich six (target) amongst the six peat-to-Point ratio of more than one (in fact 1.25) and all SD (Knibb et al., 2006). Interestingly, the language variables semanticallysemantically related and, related insemantically some and, cases, in some related perceptually cases, and, perceptually in similar some foils. cases, similar perceptually foils. similar foils. PNFA patients obtained a Repeat-to-Point ratio of less than that best differentiated between the two groups included im- Fig. 1 – An example from the pointing task. The participant is required to point to the ostrich (target) amongst the six one (in fact .9). paired repetition and impaired single word comprehension, semantically related and, in some cases, perceptually similar foils. Fig. 1 – An example from the pointing task. The participant is required to point to the ostrich (target) amongstDespite the six the consistent numerical and statistically reliable i.e., the two components of the Repeat and Point test. It remains superiority of SD > PNFA for the Repeat component, there semantically related and, in some cases, perceptually similar foils. to be seen whether there are patients who conform to the broad Fig. 1 – An example from the pointing task. The participant is required to point to the ostrichwas (target) a slight, amongst but nonetheless the six statistically significant, repeti- clinical criteria for progressive aphasia yet who cannot be clas- tion impairment in the SD group relative to controls. Previous sified, at presentation, using the Repeat and Point test. semantically related and, in some cases, perceptually similar foils. research has suggested that knowledge of the meaning of words supports repetition (Patterson et al., 1994): SD patients showed a clear advantage for repeating short sequences of Acknowledgements familiar words judged as still ‘known’ to them (on the basis of naming and comprehension tests) relative to sequences of We thank the participants and their families for their contin- real words with deteriorated meaning for those specific pa- ued support with our research. We also thank Dr. Jonathan tients. Although this phenomenon has mainly been observed Knibb, Dr. Sharon Davies, Joanna Drake, Robert Arnold, and when there is a fairly substantial ‘‘load’’ on phonological work- Tina Emery for their help with the development of the Repeat ing memory, e.g., repetition of four- or five-word sequences and Point test. This research was funded by the Medical Re- (Jefferies et al., 2004), it is certainly plausible that it might occa- search Council (MRC). sionally extend to the repetition of a single multi-syllabic word. Thus the occasional SD repetition errors observed in the current study might be expected given the SD patients’ references degraded comprehension of the same items (as revealed on the pointing component). Indeed, the SD patients did not accu- rately point to any of the incorrectly repeated items, although Adlam A-LR, Patterson K, Rogers TT, Nestor PJ, Salmond CH, and they had a one in seven likelihood of doing so by chance. Acosta-Cabronero J, et al. Semantic dementia and fluent The finding that the PNFA patients scored within the nor- primary progressive aphasia: two sides of the same coin? mal range on the reasonably difficult comprehension task Brain, 129: 3066–3080, 2006. 2560 | Brain 2009: 132; 2553–2565 M. Mesulam et al.

difficulty in making a choice (P = 0.005, Table 7). Normal controls did not show significant differences (interaction P = 0.04). On an individual basis, this category effect was significant in P2 and P4–P6 (Fig. 3). It is interesting that P6, who did not have a semantic relatedness effect in the overall analysis, did show greater slowing of responses for natural kinds, illustrating the selectivity of disease-related distortions of semantic maps. The category-specific difference of the relatedness effect could not be attributed to differences in accuracy since the patients were no more accurate in trials where both choices were living than Figure 2 Reaction times in the computerized word-to-picture in trials where they both were artefacts. matching task in trials where the two choices on the screen were semantically related or unrelated. Asterisks indicate significant differences at the individual level (Experiment 2). Imaging The cortical thickness maps revealed highly significant cortical thinning (e.g. atrophy) when the PPA group was compared to controls (Fig. 4). The atrophy was much more extensive in the left hemisphere and encompassed all parts of the anterior tempo- ral lobe, including the anterior two thirds of the superior temporal (s), middle temporal (m), inferior temporal, and fusiform gyri as pole which wellis theconsidered anterior parahippocampal gyrusa ‘semantic (ph) and the temporal hub’ pole (p). In the right hemisphere areas of peak atrophy had a much more limited distribution, encompassing mostly the most Downloaded from anterior parts of the inferior temporal gyrus. Perisylvian atrophy, reflecting the thinning of the superior temporal gyrus was prom- inent only on the left. Only outside scans were available for P2 Semantic dementiaand P6 (Fig. 5). Qualitative analysis of their scans revealed nearly by guest on August 22, 2015 Figure 3 Reaction times in trials on the computerized task identical features to the scans of the other five patients, including where both choices were living or non-living objects. Asterisks indicate significant differencesImaging at the demonstrates individual level atrophythe of asymmetrical left temporal left perisylvian pole atrophy, – considered and involvement by ofsome to be a ‘semantic hub’ (Experiment 2). inferomedial temporal areas.

Figure 4 Distribution of cortical thinning in group of five PPA-S patients (P1, P3–P5 and P6) compared to a control group. f = fusiform (occipitotemporal) gyrus; i = inferior temporal gyrus; m = middle temporal gyrus; p = temporal polar cortex; ph = parahippocampal gyrus; 48 s = superior temporal gyrus. Significance is displayed as a log(10) P-value. Mesulam et al (2009) Brain Anatomy of achromatopsia and prosopagnosia Involvement of regions specialized for colour and face processing

Hemiachromatopsia

49 Akinetopsia | Motion blindness Very rare following focal lesions – requires bilateral V5 / MT dysfunction

Poured fluid ‘frozen’ like a glacier, or like viewing the world with strobe lighting

50 Structure from motion Biological motion examples show how sparse motion information can be decoded as an object

51 Structure from motion Sparse motion information can be decoded as an object

52 Case History Middle aged man with visual symptoms

• 59 year old right-handed man with a progressive history • 7 years ago: Frustrated with difficulty reading. “Letters jumbled” • Seen by several opticians & ophthalmologists: no cause found • 5 years ago at daughter’s wedding: Daughter realized he was afraid of treading on her gown • Wouldn’t eat at wedding for fear of making a mess • Prior to admission: Hit by a car moving slowly • No visual hallucinations § Examination | No Parkinsonism. Occasional myoclonic jerks. Optic ataxia – with both arms in both visual fields. Constructional apraxia. Simultagnosia. Bilateral neglect.

53 Copying Revealed severe constructional apraxia

54 Describing a scene Demonstrated simultagnosia

Described parts of the picture piecemeal but had no grasp of what the entire scene depicted

55 Eye movements while asked to view a scene Shows he neglects to inspect left and right sides of space

56 Case History Middle aged man with visual symptoms

• 59 year old right-handed man with a progressive history • 7 years ago: Frustrated with difficulty reading. “Letters jumbled” • Seen by several opticians & ophthalmologists: no cause found • 5 years ago at daughter’s wedding: Daughter realized he was afraid of treading on her gown • Wouldn’t eat at wedding for fear of making a mess • Prior to admission: Hit by a car moving slowly • No visual hallucinations § Examination | No Parkinsonism. Occasional myoclonic jerks. Optic ataxia – with both arms in both visual fields. Simultagnosia § Investigations | MRI brain abnormal

57 MRI brain Bilateral posterior atrophy

58 Diagnosis: Posterior cortical atrophy (PCA) A clinical diagnosis which most commonly is found to be due to Alzheimer’s disease at post mortem

Progressive condition with predilection for occipital, parietal and temporal regions with both dorsal and ventral stream deficits

• Often presents to neurologists many years after symptom-onset • May have been seen by ophthalmologists or psychiatrists previously • Elements of Bálint’s syndrome • Visual agnosia • Memory affected long after visual symptoms • Many cases have Alzheimer pathology

59 Review

Posterior cortical atrophy Associated with progressive atrophy of posterior visual regions

Baseline: October 2005 Repeat 1: October 2006 Repeat 2: November 2007 Repeat 3: October 2008 inconsistent and based on very few cases. Some studies Structural MRI (T1) have shown diff erences in both plaques and neuro- fi brillary tangles between PCA and typical Alzheimer’s disease,10,12,72 whereas others have recorded no diff erences in plaque distribution.15,21 For example, Levine and colleagues10 reported pathological fi ndings of one patient with PCA who showed the greatest density of senile plaques and neurofi brillary tangles in occipito-

L R parietal regions and the lowest density in frontal lobe regions. Hof and co-workers72,73 reported similar Fluid maps fi ndings, with plaques and tangles found predominantly in primary visual and visual association areas around the occipitoparietotemporal junction, whereas frontal regions—such as the prefrontal cortex—had very low densities of pathological changes. By contrast, Tang-Wai and colleagues21 looked at pathological changes in nine patients with PCA versus 30 with typical Alzheimer’s L R disease. The PCA group showed signifi cantly higher densities of neurofi brillary tangles in visual and visual- –20% Contraction 0% Expansion 20% association cortices and fewer tangles and senile plaques in the hippocampus and subiculum. However, Figure 3: Evolution of neurodegeneration in posterior cortical atrophy Registered serial MRIs showing axial views of a woman with posterior cortical atrophy at four timepoints density of senile plaques in other cortical areas was 60 Crutch et al. (2012) Lancet Neurology (age 59–63 years old). Repeat scans were fl uid-registered to the baseline image and colour-coded comparable in both groups.21 Reasons for the discrepant voxel-compression maps were produced. The scale shows the percentage volume change per voxel (–20 to 20%), fi ndings in these autopsy studies could include with green and blue representing contraction and yellow and red representing expansion. diff erences in inclusion criteria and demographic characteristics (such as age and disease severity) and pathology? Do diff erent (as yet unrecognised) genetic diff erences in the methods used to quantify pathological factors underlie PCA compared with so-called typical changes (such as diff erent staining techniques and late-onset Alzheimer’s disease? Studies with large sample discrimination between diff use and neuritic plaques).

sizes, consistent defi nitions of PCA, and post-mortem Studies in which CSF biomarkers (Aβ1–42, T-tau, and

confi rmation of diagnosis are needed to obtain conclusive P-tau181) were assessed have recorded similar fi ndings results. Genome-wide association studies to assess in patients with PCA compared with Alzheimer’s frequencies of other genetic risk factors for sporadic disease,27,56,60,74 lending support to previous reports that Alzheimer’s disease will be useful. PCA is associated typically with underlying Alzheimer’s disease pathology. Pathology Findings of pathological studies all show that Alzheimer’s Diagnostic and research criteria disease is the most common underlying cause of Two sets of diagnostic criteria for PCA have been PCA.13,15,21,65–67 However, some cases are attributable to proposed.17,21 Suggested core features for a diagnosis of other causes, such as corticobasal degeneration,15,68,69 PCA include insidious onset and gradual progression; dementia with Lewy bodies,15,70 prion disease (including presentation of visual defi cits in the absence of ocular CJD and familial fatal insomnia),15,71 and subcortical disease; relatively preserved episodic memory, verbal gliosis.71 In the largest series studied to date, Renner and fl uency, and personal insight; presence of symptoms colleagues15 reported pathological data for 21 patients including visual agnosia, simultanagnosia, optic ataxia, with PCA, of whom 13 had Alzheimer’s disease, two had ocular apraxia, dyspraxia and environmental disorien- pathological features of an Alzheimer’s disease-Lewy tation; and absence of stroke or tumour. Supportive body variant, one had Alzheimer’s disease with coexisting features include alexia, ideomotor apraxia, agraphia, Parkinson’s disease, one had dementia with Lewy bodies acalculia, onset before the age of 65 years, and with coexisting subcortical gliosis, two had corticobasal neuroimaging evidence of PCA or hypoperfusion. degeneration, and two had prion disease (CJD and fatal Although these criteria have proved useful in several familial insomnia). Tang-Wai and colleagues21 reported clinical and research contexts, they are based on clinical that seven of nine patients with PCA had pathological experience at single centres and have not been validated features of Alzheimer’s disease, whereas the other two more widely. Without objective evidence linking clinical had corticobasal degeneration.21 phenotype to underlying pathology, there continues to Although the distribution patterns of pathological be inconsistency, with the term PCA being used as a features diff er between PCA and typical Alzheimer’s descriptive syndromic term and as a diagnostic label. disease, the exact pattern of pathological changes is Such inconsistencies present several diffi culties in

174 www.thelancet.com/neurology Vol 11 February 2012 Case History Middle aged man with visual symptoms

• 55 year old right-handed bus driver • Retired because of accidents while driving • Reported seeing shadowy figures moving beside him • Sometimes well-formed like people, but often vague • Never with auditory hallucinations § Examination | Mild reduction of arm swing bilaterally on walking. Neuropsychological assessment demonstrated profound deficits in executive function and visuospatial abilities, as well as fluctuating attention.

61 Copying Revealed constructional apraxia

62 Diagnosis: Dementia with Lewy bodies (DLB) A clinical diagnosis which most commonly is found to be associated with Lewy body pathology

Progressive condition associated with • Fluctuating attention • Visual hallucinations • Visuospatial deficits • Executive dysfunction Lewy body • May not have signs of Parkinsonism at presentation but these often develop • Probably the same condition as Parkinson’s disease dementia (in the latter motor signs of Parkinsonism precede cognitive changes) • Both conditions can show marked improvements on cholinesterase inhibitors • NB: Hallmark of Parkinson’s disease is Lewy body pathology

63 Reading Core text is available online on SOLO

§ For overviews: parts of Chapters 4, 5 and 14 cover ventral and dorsal visual stream and deficits associated with damage to them

§ See also separate reading list

64