Developmental topographical disorientation in a healthy subject

Neuropsychologia 48 (2010) 1563–1573

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Developmental topographical disorientation in a healthy subject F. Bianchini a,b , C. Incoccia b , L. Palermo a,b , L. Piccardi b,c , L. Zompanti a , U. Sabatini b , Patrice Peran b,d , C. Guariglia a,b,∗ a

Dipartimento Psicologia 39, Sapienza Università di Roma, Rome, Italy I.R.C.C.S. Fondazione Santa Lucia, Rome, Italy c Dipartimento di Scienze della Salute, Università degli Studi di L’Aquila, Coppito 2 (AQ), Italy d INSERM U825, Toulouse, France b

a r t i c l e

i n f o

Article history: Received 12 May 2009 Received in revised form 27 January 2010 Accepted 30 January 2010 Available online 6 February 2010 Keywords: Topographical disorientation Spatial memory Spatial orientation Selective developmental disorders Development of navigational skills Environmental navigation

a b s t r a c t We present the case of F.G., a healthy, normally developed 22-year-old male subject affected by a pervasive disorder in environmental orientation and navigation who presents no history of neurological or psychiatric disease. A neuro-radiological examination showed no evidence of anatomical or structural alterations to the brain. We submitted the subject for a comprehensive neuropsychological assessment of the different cognitive processes involved in topographical orientation to evaluate his ability to navigate the spatial environment. The results confirmed a severe developmental topographical disorder and deficits in a number of specific cognitive processes directly or indirectly involved in navigation. The results are discussed with reference to the sole previously described case of developmental topographical disorientation (Pt1; Iaria et al., 2009). F.G. differs from the former case due to the following: the greater severity of his disorder, his complete lack of navigational skills, the failure to develop compensatory strategies, and the presence of a specific deficit in processing the spatial relationships between the parts of a whole. The present case not only confirms the existence of developmental topographical-skill disorders, but also sheds light on the architecture of topographical processes and their development in human beings. © 2010 Elsevier Ltd. All rights reserved.

1. Introduction The human navigation system includes various subcomponents that contribute independently to a person’s ability to find his way within the environment (Brunsdon, Nickels, & Coltheart, 2007; Wang & Spelke, 2002). In healthy children, these subcomponents develop gradually and at distinct points in time (Siegel & White, 1975); Lehnung et al., 2003). By the age of 6–9 months, children are able to find their bearings in the environment using only egocentric strategies (Acredolo, 1978; Acredolo & Evans, 1980; Bremner, 1978; Piaget & Inhelder, 1948). At 11 months they start to use information pertaining to landmarks and landmark arrays (Acredolo, 1978; Acredolo & Evans, 1980). The relation–place–strategies required for cognitive mapping start to develop at around 7 or 8 years of age and are fully functioning by the age of 10 (Lehnung, Leplow, Friege, Ferstl, & Mehdorn, 1998; Lehnung et al., 2003; Overman, Pate, Moore, & Peuster, 1996).

∗ Corresponding author at: Dipartimento di Psicologia, Sapienza Università di Roma, Via dei Marsi, 78, 00185 Rome, Italy. Tel.: +39 (0) 6 49917527/(0) 651501363; fax: +39 (0) 6 49917711/(0) 651501366. E-mail address: [email protected] (C. Guariglia). 0028-3932/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2010.01.025

Developmental deficits in subjects without either evident cerebral damage or perinatal problems are described in relation to many human cognitive competencies, such as the spoken language (i.e., SLI; Plante, 1998), the written language (i.e., dyslexia and dysorthographia; Hinshelwood, 1985; Morgan, 1986), familiar-face recognition and identification (developmental prosopoagnosia; Duchaine & Nakayama, 2006; Duchaine, Germine, & Nakayama, 2007), and vocal-identity recognition (Garrido et al., 2009). To the best of our knowledge, only one case has very recently been described of developmental disorder affecting the acquisition of navigational skills. Selective disorders of topographical orientation and navigation in humans have been described as acquired deficits affecting otherwise normally developed competences (Aguirre & D’Esposito, 1999; De Renzi, 1982). In adults, topographical disorientation, i.e. the selective loss of the ability to find one’s way in familiar or novel environments (Maguire, Burke, Phillips, & Staunton, 1996), is usually described as a consequence of acquired focal brain damage (Barrash, 1998) or dementia (Pai & Jacobs, 2004). Topographical disorientation has also been reported in children and young adults with congenital brain malformations (Iaria et al., 2005), perinatal injury (Ahmed & Dutton, 1996; Brunsdon, Nickels, Coltheart, & Joy, 2007), genetic syndromes (Fine, Mellstrom, Mani,

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& Timmins, 1980; Griffiths & Hunt, 1984) and retarded intrauterine growth (Leitner, Heldman, Harel, & Pick, 2005). Recently, a case of developmental topographical disorientation was described in a normally developed subject (Iaria et al., 2009). Those authors described a 43-year-old woman (Pt1), who presented no evident brain injuries or psychiatric disorders, affected by persistent difficulties in topographical orientation. When Pt1 followed a path in the company of the examiner she was able to identify landmarks and to use them to reproduce the path taken. She was also able to derive verbal instructions from maps to guide her own navigation in the environment. Nevertheless, she demonstrated a deficit when invited to create mental maps of real and virtual environments. As Pt1 presented no detectable brain injury or general developmental delays or deficits, her case, which has been called “Developmental Topographical Disorientation” (DTD) (Iaria et al., 2008), may be compared to other selective developmental disorders such as dyslexia, developmental prosopoganosia, SLI, etc. The case we describe herein differs from that of Pt1 in several respects. First, F.G.’s disorder is more pervasive and includes almost all of the processes pertaining to topographical knowledge and navigation. Unlike Pt1, F.G. has never been able to learn even the most familiar routes (he loses his way even inside his own home!). Furthermore, in addition to his inability to build cognitive maps, F.G. is clearly unable to identify landmarks and to derive verbal instructions useful for navigation from direct navigational experiences. Finally, he is completely unable to use maps. In this study, F.G. was subjected to an extensive battery of navigational tasks and neuropsychological tests to analyze the nature of his developmental topographical disorientation. 2. Case report F.G. is a 22-year-old right-handed man (Salmaso & Longoni, 1985) who was normal at birth and had no perinatal complications. Moreover, he has no medical history of motor, neurological or cognitive developmental delays or of neurological or psychiatric diseases. F.G. is a competent, intelligent, young man who was awarded a degree in Scriptwriting from Rome’s third-level cinema institute (Scuola del Cinema Cinecittà) during the period of this evaluation. In March 2006, F.G. was referred to the Neuropsychological Unit of the Santa Lucia Foundation in Rome because of his persistent topographical disorder. The patient reported that he was unable to navigate in the environment and explicitly mentioned difficulty in learning new routes and in recognizing landmark configurations. He stated that even the slightest change in a very familiar environment, for example the restoration of the fountain near to his home in his native town, sufficed to make it completely unrecognizable to him. Moreover, he reported that whenever he moved to a new apartment it took him several months to learn the positions of the different rooms and that he had to leave the light on in his bedroom in order to recognize it. F.G. reported that he had become fully aware of this difficulty around the age of 14, when he started to ride a scooter. His sister confirmed that from childhood he has been unable to find his bearings in the environment. In fact, as a boy and adolescent he attended classes at a swimming pool for several years and systematically found it difficult to get back to the dressing room after the lesson. Even in his parents’ home where he grew up, F.G. is unable to decide which direction to take when moving from one room to another (for example from his own bedroom to the kitchen) without looking around him carefully. Required to describe how he coped with these difficulties, F.G. reported being able to orient himself in the environment by rely-

ing only on a verbal strategy; he recently decided to avail of an external electronic aid (a GPS navigator) to guide him even when walking short distances. Before that, he always asked a relative or a friend to accompany him; F.G. still asks someone to do so when going to places he has never visited before or when he has to walk long distances. In fact, every time he came to our laboratory he was accompanied by his sister or by a friend of his. After obtaining informed consent from the patient and the approval of the local ethics committee, we set out to investigate the different cognitive processes involved in topographical orientation by subjecting F.G. to a neuropsychological assessment, a neuroradiological examination and a comprehensive evaluation of his ability to navigate. A group of 11 males (C) matched on the basis of their age and education volunteered as controls for tests lacking standardization data. F.G.’s and the controls’ performances were compared using a computer program (CH) developed by Crawford and Howell (1998) for statistical comparisons between predicted and observed scores. The results for each of the tests administered are provided below and are illustrated in Table 2. 3. Neuro-radiological examination 3.1. Materials and methods MR imaging was performed on a scanner (Allegra, Siemens Medical Solutions, Erlangen, Germany) operating at 3.0 T, with a maximum gradient strength of 40 mT/m, using a standard quadrature birdcage head coil for both the RF transmission and RF reception. Particular care was taken to prevent head movement within the coil on the part of the subject by applying foam and tape. The protocol included axial, coronal and sagittal T2-weighted turbo spin-echo (TSE) sequences (TR = 3500 ms, TE = 354 ms), axial fluid-attenuated inversion recovery (FLAIR) sequences (TR = 8500, TE = 109, inversion time = 200) covering the whole brain. Twenty-two, 5-mm gapless sections and a 256 × 256 matrix were obtained using all of the MR imaging techniques available. The axial and the coronal sections ran, respectively, parallel and perpendicular to a line joining the anterior and posterior commissures (AC–PC line). F.G. and 12 male subjects (18–30 years) underwent the same whole-brain T1weighted imaging protocol. Whole-brain T1-weighted images were obtained on the sagittal plane using a modified driven equilibrium Fourier transform (MDEFT) sequence (TE/TR = 2.4/7.92 ms, flip angle 15◦ , voxel-size 1 mm × 1 mm × 1 mm).

4. Data analysis All the images resulting from these instrumental tests involving F.G. were assessed visually by two radiologists. The whole-brain T1 structural data were analyzed with FSLVBM, a voxel-based morphometry style analysis (Good et al., 2001) carried out with FSL tools (Smith et al., 2004) from FMRIB Software Library (Oxford, UK). First, structural images were brain-extracted with BET (Smith, 2002). Next, a tissue-type segmentation was carried out using FAST4 (Zhang, Brady, & Smith, 2001). The resulting grey-matter partial-volume images were then aligned to obtain the MNI152 standard spacing using the FLIRT affine registration tool (Jenkinson & Smith, 2001; Jenkinson, Bannister, Brady, & Smith, 2002) followed by a non-linear registration using FNIRT (Andersson, Jenkinson, & Smith, 2007a, 2007b). We used the result of the linear transformation as starting point for the non-linear transformation. Voxelwise GLM was later applied using permutation-based non-parametric testing. We compared F.G.’s results with those of the male control group using a two-sample t-test. 5. Results 5.1. The radiologists’ observations F.G.’s Magnetic Resonance Imaging examinations revealed a homogeneous signal intensity of the cerebral parenchyma, with-

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out any focal abnormalities, in either the grey or white matter. The cortex was of normal thickness and had regular sulcation and gyration. The corpus callosum was of normal thickness and presented a regular morphology and a homogeneous signal intensity. The ventricular system was normal in size and symmetrical at the midline. The sub-arachnoid spaces were regular. Both hippocampi were normal in morphology and size, with a regular profile and signal intensity. On the whole, the MRI examination seems to present a completely normal picture (Fig. 1). 5.2. VBM analysis The two-sample t-test did not show differences between F.G. and the control group. 6. Neuropsychological assessment The neuropsychological assessment included standard tests used to evaluate general-intelligence and episodic memory. We did not test autobiographical and prospective memory formally since F.G. was able to recall his personal history in detail (as confirmed by an interview with his sister), his academic history did not suggest any difficulty even in acquiring high-level graphic and pictorial skills and currently he followed complex daily life activity schedules without any problem. The patient was cooperative and motivated, his language was fluent and he presented no deficit as far as verbal comprehension was concerned. F.G.’s general-intelligence level was tested with the WAIS-R battery (Italian Version; Laicardi & Orsini, 1997). His overall performance was within the normal range (total IQ = 92). There was a significant difference (Laicardi & Orsini, 1997) between his Verbal IQ (104) and Performance IQ (79) because of his particularly poor performances with the Picture Completion, Block Design and, in particular, with the Object Assembly subtests (see Table 1). In all the tests administered to assess the executive functions (Capitani, Laiacona, & Barbarotto, 1999; Heaton, Chelune, Talley, Kay, & Curtiss, 1993; Krikorian, Bartok, & Gay, 1994; Novelli, Papagno, Capitani, Laiacona, Cappa, & Vallar, 1986; Novelli, Papagno, Capitani, Laiacona, Vallar, & Cappa, 1986) F.G.’s performances were perfectly comparable to those of the controls (see Table 1).

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Neither his verbal nor his visuo-spatial memory abilities (Carlesimo et al., 1996, 2002; Orsini et al., 1987) proved defective. On the contrary, his short- and long-term abilities were both within the normal range (see Table 1).

7. Navigational skill assessment To assess F.G.’s navigational skills, we used a “Battery of tests for navigational disorders”, derived partially from a battery developed previously to study a case of topographical disorientation caused by congenital brain malformation (Iaria et al., 2005). Because normal topographical orientation is a complex process involving the integration of independent cognitive functions (Brunsdon, Nickels, & Coltheart, 2007), the battery includes three different categories of tasks. The first category assesses specific domains such as visual–spatial perception, visual–spatial memory and visual–spatial imagery (see Table 2). The second and third categories of tests assess specific navigational abilities involving an experimental and an ecological environment, respectively (see Table 3). Most of the tests we selected were devised previously to detect the presence of pathological performances in brain-damaged patients. In some of these tests, non-neurological subjects perform near to ceiling level. Thus, the absence of differences between the performances of F.G. and performances of the controls in the competencies measured by these tests may be interpreted with caution because the possibility still remains that more specific and complex tests might well detect deficits in similar competencies.

7.1. Visual–spatial perception, memory and imagery Basic visual–spatial abilities were evaluated using tests aimed at assessing visual–spatial perception (Visual Object Spatial Perception Battery, Benton’s Facial Recognition Test, Unfamiliar Perspective Objects’ Recognition) and memory (Corsi Span and Supraspan Block Test) (see Table 1), as well as visual–spatial imagery (Memory of buildings, Generation of imagery from longterm memory, Mental assembly of object parts, Reconstructions of complex images and Mental spatial-transformation tests) (see Table 2). From this point forward, the present report will describe in detail only those tests that are not commonly used in clinical practice.

Fig. 1. Coronal, sagittal and horizontal slices from F.G.’s T1-weighted image. Zoom on hippocampi.

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Table 1 Performances below the cut-off are in bold. The neuropsychological assessment included tests standardized for use with Italian-speaking patients. For tests lacking standardization dataa we recruited controls matched for age, gender, and years of education. Test General intelligence Wechsler Adult Intelligence Scale Revised (Laicardi & Orsini, 1997) Verbal IQ Performance IQ Full scale IQ Information Digit span Vocabulary Arithmetic Comprehension Similarities Picture Completion Picture arrangement Block Design Object Assembly Digit Symbol Tower of London (Krikorian et al., 1994) Wisconsin Card Sorting Test (Heaton et al., 1993) Numbers of categories Number of cards Number of persevarative errors Fonemic fluency (Novelli, Papagno, Capitani, Laiacona, Cappa et al., 1986; Novelli, Papagno, Capitani, Laiacona, Vallar et al., 1986) Semantic fluency (Capitani et al., 1999) Memory Verbal memory Short story recall (Carlesimo et al., 2002) Immediate recall 20 min delayed recall Oblivion Rey’s 15 words Learning Task (Carlesimo et al., 1996) Immediate recall 15 min delayed recall Spatial memory Rey complex figure () Copy 30 s delayed recall 20 min delayed recall Oblivion Supraspan (n. cubes)a Supraspan recall (n. cubes)a Visual–perceptual abilities VOSP (Warrington & James, 1991) Object perception Screening test Incomplete letters Silhouettes Object decision Progressive silhouettes Space perception Dot counting Position discrimination Number location Cube analysis Benton’s Facial Recognition Test (Benton et al., 1992) Unfamiliar Perspective Objects’ Recognition (Pizzamiglio et al., 1989)a

7.1.1. Visual–spatial perception and memory testing F.G. is endowed with a normal visuo-spatial span as well as with normal learning (number of correct cubes, F.G.: 131/144; control (C): mean = 118.55, SD = 22.42; CH: t = 0.548, p = not significant (n.s.)) and delayed recall (number of correct cubes, F.G.: 8/8; C: mean = 7.53, SD = 1.09; CH: t = 0.426, p = n.s.) (Corsi Span and Supraspan Block Test; Spinnler & Tognoni, 1987). His performances in object and space perception (Visual Object Spatial Perception Battery; Warrington & James, 1991), face recognition (Benton’s Facial Recognition Test; Benton, Van Allen, Hamsher, & Levin, 1975) and recognition of objects presented from unusual perspectives (Unfamiliar Perspective Object Recognition; Pizzamiglio,

F.G. score

Cut-off

104 79 92 9 13 11 10 11 12 6 8 6 4 12 33/36

<75 <75 <75 4 4 4 4 4 4 4 (−1SD) 4 4 (−1SD) 4 (−2SD) 4 29/36

6/6 93/128 6 48

70th percentile 16

19

9

6.09/8 8/8 −1.91

3.09/8 2.38/8 <2.32

57/75 14/15

39.42/75 7.48/15

36/36 11/36 14.5/36 −3.5 131/144 8/8

23.76/36 6.41/36 6.33/36 >4.24 73.71/144 (mean = 118.55, SD = 22.42, t = 0.548, p = n.s.) 5.35/8 (mean = 7.53, SD = 1.09, t = 0.426, p = n.s.)

20/20 19/20 17/30 17/20 9/20

15/20 17/20 16/30 15/20 >14/20

9/10 20/20 10/10 7/10 49/54 15/16

8/10 18/20 7/10 6/10 40/54 10, 89/16 (mean = 13.29, SD = 1.20, t = 1.385, p = n.s.)

Judica, Razzano, & Zoccolotti, 1989) fell well within the normal range. 7.1.2. Visual imagery testing Visual imagery abilities are involved in many aspects of topographical cognition (Farah, 1989; Riddoch & Humphreys, 1989), such as the recognition of scenes and landmark configurations as well as the description and graphic representation of familiar environments. Based on a recent model of visual mental imagery (Kosslyn, 2005), while assessing the patient we considered different aspects of mental imagery, such as the ability to generate, assemble and

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Table 2 Performances below the cut-off or insufficient are in bold. Test

F.G. score

Controls

Visual imagery testing Memory of buildings (a modified version of Nori & Giusberti, 2006) Mental assembly of object parts Reconstructions of complex images (a modified version of Nori & Giusberti, 2006) Mental folding test (Ekstrom et al., 1976) Mental overlapping test Mental rotation test (Grossi, 1991) Thurstone primary mental ability test cards (Thurstone, 1937)

20/20 60/60 17/20 13/20 28/28 6/10 12/20

Mean = 18.08 Mean = 58.6 Mean = 19 Mean = 17.2

SD = 2.27 SD = 1.51 SD = 1 SD = 1.64

t = 0.81; p = n.s. t = 0.85; p = n.s. t = −1.86; p = n.s. t = −2.34; p = n.s.

Mean = 9.06 Mean = 17.72

SD = 1.3 SD = 1.73

t = −2.29; p < 0.05 t = −3.16; p < 0.01

Generation of imagery from long-term memory O’clock Test (Grossi et al., 1989) Descriptions of common objects Descriptions of familiar squares Descriptions of native neighbourhood Map’s drawing of actual house Map’s drawing of native house

31/32 + Very poor Very poor Implausible Implausible

Mean = 30.18

SD = 1.78

t = 0.448; p = n.s.

In bold performances that are below the cut-off or insufficient.

transform mental images of topographical and non-topographical materials.

7.1.3. Memory of buildings The “Memory of buildings” test (a modified version of Nori & Giusberti, 2006) assesses the ability to generate an image from short-term memory. The subject is asked to identify the picture of a building studied for 10 s and chosen from among three other pictures of similar buildings. F.G. identified 20 out of 20 stimuli correctly (C: mean = 18.08; SD = 2.27; t = 0.81; p = n.s.).

7.1.4. The generation of imagery from long-term memory The subject’s ability to generate an image from long-term memory was assessed by asking him to perform the O’clock Test (Grossi, Modaferri, Pelosi, & Trojano, 1989), to describe common objects, familiar squares in Rome and in his native town (Bisiach & Luzzatti, 1978) from memory, and to draw a map of his current as well as of his childhood home. In the O’Clock Test subjects are required to imagine two different times on two analogical clocks, and decide on which face the clock’s hands form the greater angle. This test includes 16 items for comparison occurring in the left hemi-face of the clock (i.e., 7.30 and 8.00) and 16 items in the right one (i.e., 3.30 and 2.00).

F.G.’ s performance on the O’clock Test was as good as those of the matched controls (F.G.: 31/32 correct answers; C: mean = 30.18, SD = 1.78; CH: t = 0.448, p = n.s.). Despite the accuracy and wealth of details provided in his descriptions of common objects (i.e., a car, a cat, etc.) qualitatively comparable to those of controls, his descriptions of familiar squares in Rome and in his childhood environment were very poor. In each description, he failed to report any but a few elements and was unable to describe their features or provide any information about their location. The fact that while describing familiar environments F.G. simply named the elements without describing them seems to suggest that these descriptions were based not on visualization but on verbal recall of lists of elements. F.G. was unable to draw maps of his childhood (see Fig. 2a) or present homes (see Fig. 2b). In order to judge his performance we asked his mother to draw maps of the same places. Although F.G.’s representations of the two flats were drawn at two different times on different sheets of paper, they were very similar and totally implausible, with glaring errors in spatial relationships.

7.1.5. Mental assembly of object parts In this test, the subject was presented with three parts of a stimulus on a PC screen; each part was presented for 2500 ms (ISI: 500), and the subject was requested to assemble the parts mentally following the presentation order. After 500 ms a set of target

Table 3 F.G.’s and average controls’ results on the navigation test in experimental, virtual (CMT), and ecological environments. Performances below the cut-off are in bold. Test

F.G. score

Controls

5/9 142/144 4/8 27/32 0/5 11/35

Mean = 6.08 Mean = 142.68 Mean = 7.93 Mean = 30.14 Mean = 4.30 Mean = 31.00

SD = 1.25 SD = 15.11 SD = 0.35 SD = 2.74 SD = 0.84 SD = 2.92

t = −0.85 p = n.s t = −0.044 p = n.s t = −11.09 p = 0.00 t = −1.11 p = n.s t = −4.67 p = 0.003 t = −6.25 p = 0.003

Virtual reality test CMT (Iaria et al., 2007) Learning task Retrieval task

1080 s 395.5 s

572 s 298.35 s

SD = 199 s SD = 112.58 s

t = 2.48 p = 0.025 t = 0.84 p = n.s

Navigational abilities in ecological environments Landmarks recognition Postcard Test (short version, Palermo et al., 2008) Route strategy Map strategy Verbal strategy

75/213 − − +

Mean = 100.12

SD = 23.77

t = −1.03 p = n.s.

Navigational abilities in experimental environments Walking Corsi Test (Piccardi et al., 2008) Span (no. squares) Supraspan (no. squares) Supraspan recall (no. squares) Road map test (Money et al., 1965) Semmes test (Semmes et al., 1955)

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uli in the Grossi et al. test (C: mean = 9.06, SD = 1.3; CH: t = −2.29, p < 0.05) and 12 out of 20 on the experimental mental rotation test (C: mean = 17.72; SD = 1.73); CH: t = −3.16; p < 0.01). On the contrary, he showed no deficit when addressing the folding test (scores: F.G. = 13 out of 20; C: mean = 17.2, SD = 1.64; CH: t = −2.34, p = n.s.) or the overlapping test, in which he performed flawlessly (correct responses: 28/28 stimuli). The fact that F.G. failed only in the mental rotation tests confirms the possibility that mental transformation processing is not an unitary process but it includes several segregate processes. It is noteworthy that in F.G. the mental transformation processes are generally intact, meaning that he does not have a general impairment in mental transformation, while his performance is clearly defective in the only imagery transformation process (i.e., mental rotation) that has been demonstrated to be related to the ability to develop cognitive maps (Palermo, Iaria, & Guariglia, 2008). 7.2. Navigational abilities in experimental environments

Fig. 2. Drawings by F.G. of his native (on the left) and present (on the right) flats.

representations, half of them corresponding to the required mental assembly, was presented. The subject’s task was to judge whether the stimulus and target were the same or not. In half of these target assemblies, the three stimuli were presented so as to provide a correct picture of the object depicted (i.e., a tower) and in the other half a picture of an unreal object (for example, the roof of the tower situated between the first and the second floors); half of the targets depicted unreal objects. F.G. had no difficulty in carrying out this task; indeed, his score was 60/60 correct responses (C score: mean = 58.6, SD = 1.51; CH: t = 0.85; p = n.s.). 7.1.6. Reconstructions of complex images In this test (a modified version of Nori & Giusberti, 2006), the subject was asked to look carefully for 20 s at a complex scene depicting an urban view. He was then shown the same scene divided into three to five segments, presented at random. The subject’s task was to indicate, by pointing, the correct order in which to arrange the pieces to reconstruct the scene. F.G. correctly reconstructed 17/20 scenes (C score: mean = 19, SD = 1; CH: t = −1.86, p = n.s.). 7.1.7. Mental spatial-transformation tests We assessed F.G.’s ability to transform mental images using a mental folding test (French, Ekstrom, & Price, 1963), a mental overlapping test (Sassi, 1986) and two mental rotation tests: the Grossi (1991) mental rotation test and an experimental test based on Thurstone’s Primary Mental Ability Test Cards (Thurstone, 1937). F.G. showed a specific impairment when handling the mental rotation test; in fact, he identified only 6 out of 10 target stim-

7.2.1. Walking Corsi Test The recently developed Walking Corsi Test (WalCT) (Piccardi et al., 2008) is based on the Corsi Block-Tapping test (CBT) (Corsi, 1972). It assesses the ability to learn and remember spatial locations during navigation. A carpet serves as an enlarged version (on a 10:1 scale) of the wooden tablet used in the CBT. Nine black square patches are attached to the carpet in the same spatial relationship as the wooden blocks on the tablet. F.G.’s short-term memory in the Walking Corsi span test (span = 5) did not differ significantly from those of controls (C: mean = 6.08, SD = 1.25; CH: t = −0.85, p = n.s.). In the Walking Corsi Supraspan, the ability to learn and recall an eight-square path is evaluated (Piccardi et al., 2008). The experimenter walks on the carpet, stopping for 2 s on each of the eight squares. Soon after, the subject is invited to reproduce the same path. The experimenter continues to demonstrate the sequence until the subject reaches the learning criterion foreseen (three consecutive correct repetitions of the eight-square path), up to a maximum of 18 repetitions. The subject is requested to provide a delayed reproduction of the path 5 min after the end of the learning test (for details on Walking Corsi Test procedures and scoring see Piccardi et al., 2008) F.G.’s immediate learning ability was comparable to those of the controls (F.G.: 142; C: mean = 142.68, SD = 15.11; CH: t = −0.044, p = n.s.), but he was unable to recall the learned sequence after the foreseen 5-min delay (F.G.: 4; C: mean = 7.93, SD = 0.35; CH: t = −11.09, p = 0.00). 7.2.2. Road map test In the Road Map Test (Money, Alexander, & Walzer, 1965), subjects are requested to imagine walking along a path drawn on a city map, and at each intersection they are asked to report verbally whether they are turning left or right. F.G.’ s performance was within the normal range: he judged 27 out of 32 turns of the pathway correctly, whereas the controls correctly judged an average of 30.14 turnings (SD = 2.74; CH: t = −1.11, p = n.s.). 7.2.3. Semmes test F.G.’s ability to use a map was assessed using the Semmes test (Semmes, Weinstein, Ghent, & Teuber, 1955). In this test the subject is given a schematic map representing a 3 × 3 point grid placed on the floor (3 m × 3 m). On the map a route connecting the points is drawn. Subjects are required to walk on the grid reproducing the depicted route; they are not allowed to rotate the map, but they are allowed to correct their performance whenever they want. No feedback about the correctness of the performance is given during the test.

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The test includes maps of five different paths of increasing length and complexity. The score is the total sum of the correct performances. An alternative scoring reported by Semmes et al. (1955) consists in summing the number of correct turns on each path. F.G. was totally incapable of translating the allocentric coordinates provided into egocentric coordinates (F.G.: 0/5 correct answers; C: mean = 4.30, SD = 0.84; CH: t = −4.67, p = 0.003). Indeed, in contrast to controls, he never recognized any of his errors and, as a consequence, he did not try to correct or repeat any of the trials. Instead, the normal controls of comparable age, education and gender, committed sporadic errors, which they corrected spontaneously. The score based on the number of correct turns confirms that F.G. performances were significantly worse than those of the controls (F.G.: 11/35 correct answers; C: mean = 31.00, SD = 292; CH: t = −6.25, p = 0.003). 7.2.4. Virtual reality test The CMT virtual reality test (Iaria, Chen, Guariglia, Ptito, & Petrides, 2007) assesses the ability to generate and use a cognitive map. Participants navigate by using a three-button keypad (forward, left and right) in a virtual city that includes six landmarks: a cinema, a restaurant, a pub, a hotel, a pharmacy and a flower shop. The test includes two experimental tasks. In the learning task, subjects explore the virtual city freely until they demonstrate that they have developed a cognitive map of the city by correctly locating the six landmarks on the city map. In the retrieval task the subject is asked to use the previously created cognitive map to move from one location (e.g. the cinema) to another (e.g. the restaurant) as required by each of the 18 trials administered. In the learning task F.G. needed significantly more time than the controls to generate the map of the city (F.G.: time = 1080 s; C: mean time = 572 s, SD = 199 s; CH: t = 2.48, p = 0.025). In the retrieval task, he solved each trial correctly in an amount of time comparable to those of controls (F.G.: time = 395.5 s; C = 298.35 s, SD = 112.58 s; CH: t = 0.84, p = n.s.). F.G. reported spontaneously that he had employed a verbal strategy during the retrieval task in order to navigate the environment. Although this strategy might be useful in similar simple virtual environments, it loses efficacy in the more complex environments

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full of streets, buildings and shops, such as the real environments used in the third part of the set. 7.3. Navigational abilities in ecological environments This section tested navigational tasks devised to assess specific navigational abilities in real environments and the recognition of real landmarks. 7.3.1. Landmark recognition The ability to recognize landmarks was assessed by using a short version of the Postcard Test (for details see Palermo et al., 2008), which requires subjects to recognize 71 well-known landmarks found in Italian and European cities. The performances are scored as follows: three points are assigned for a correct response (the name of the landmark, for example: “Colosseum”), two points are assigned for an appropriate response identifying the landmark or the area in which it is located (the name of the city in which the landmark is located and some additional information about its location; for example: “It is in Rome, in the center of the city near the Campidoglio”), one point is assigned for a general response that does not allow identification of the landmark (such as the name of the city or the country in which the landmark is located; for example: “It is in Rome” or “It is in Italy”), and zero points are assigned for an incorrect response. F.G.’ s performance did not differ from those of the controls (F.G.: score = 75/213; C: mean = 100.12, SD = 23.77; CH: t = −1.03, p = n.s.). 7.3.2. Route strategy This task assesses a person’s ability to learn a novel route by taking it with the examiner. F.G. was instructed to follow the examiner along a route in the hospital that he would subsequently be invited to reproduce. At the end of the route, he was blindfolded, led back to the starting point by means of a shortcut and asked to reproduce the route. The examiner provided no verbal information or feedback during the test. The patient was unable to reproduce the route correctly. In contrast with the controls that performed this task without errors or hesitation, he omitted the central part of the route (see Fig. 3a). 7.3.3. Map strategy In this task, the patient was given a map of the hospital with a pathway he was asked to follow. While age-and-gender-matched

Fig. 3. (a) Route strategy task. The drawing represents the path followed by the examiner (dotted line) and the reproduction of the same path by F.G. (unbroken line). (b) Map strategy task. The dotted line represents the path F.G. was supposed to follow and the unbroken line the path F.G. actually followed; squares indicate the points where F.G. stopped because he was unable to find his position on the map. The arrow and the target represent respectively his points of departure and arrival.

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Fig. 4. Verbal strategy task. On the left, the dotted line represents the path F.G. was supposed to follow and the unbroken line the path F.G. actually followed; the grey line indicates the path F.G. followed to go back to the previous starting point. The black arrow and the black target represent respectively the departure and arrival for verbal information, while the grey arrow and the grey target represent the departure and arrival to go back to the starting point. The instructions for the subject are on the right.

controls did not show any difficulty in this task, F.G. was unable to follow the pathway. He was disoriented, got lost several times, and was unable to find his location on the map or to decide which direction he was supposed to take (see Fig. 3b). 7.3.4. Verbal strategy The experimenter provided F.G. with written instructions about a novel route in the hospital. The instructions included descriptions of each significant landmark he would meet en route. The descriptions were formulated so the subject could recognize the landmarks, and directions of how to go from one landmark to another (for example: “From the glass door at the entrance go straight ahead to the parking lot” or “Turn left in the direction of the green building”) were also provided. This task posed no problem for the patient who was able to reach the final goal without any trouble, demonstrating that he had no deficit in using navigational language and verbal strategies. The fact that F.G. was perfectly able to find his way by relying on verbal strategies is supported by the observation that he was also able to return to the starting point without receiving any new instructions but by simply following the previous directions in reverse (see Fig. 4). 8. Summary Summing up, F.G. performed poorly in three of the WAIS-R subtests (Picture Completion, Block Design and Object Assembly) and in two mental rotation tasks. He showed difficulties in generating a cognitive map of a virtual city (CMT), in drawing a map of his own home and in describing a familiar square in detail. He was unable to follow a path using a map (Semmes test and pathway in a real environment), to apply a route strategy or to retain a previously learned path (Corsi Walk Supraspan). 9. Discussion To date, it was believed that difficulty in orienting and navigating in the environment affected only patients with acquired brain lesions or brain degenerative diseases. Very recently, however, a case of developmental topographical disorientation (DTD) was described (Iaria, Bogod, Fox, & Barton, 2009) that gave rise

to the supposition that some “normal” individuals (i.e., individuals with normal I.Q. who had never suffered from neurological or psychiatric diseases and who were raised in a non-deprived environment) could be affected by defective development of navigational processes. Here, we describe a subject with serious disorders in topographical knowledge, environmental orientation and navigation but with no proven evidence of an acquired or congenital brain injury. F.G.’s neurological, psychomotor and cognitive development appeared to be normal. Furthermore, his case history showed no evidence of disorder. The two radiologists involved in the experiments identified no abnormalities in F.G.’s brain, in particular the hippocampi. We also carried out a VBM analysis, which did not reveal any difference between F.G. and the male control group tested. We concluded that no abnormality was detected in F.G.’s brain, although it should be kept in mind that the VBM method may not be powerful enough to detect subtle abnormalities in individuals (Ashburner & Friston, 2000; Mehta, Grabowski, Trivedi, & Damasio, 2003). One must also consider the possibility that F.G. suffers from functional alterations in the absence of morphological anomalies. Even if the present data are insufficient to demonstrate the neural bases of developmental topographic disorientation, some hypotheses may be forwarded. The difficulties that F.G. encounters in finding his way, in learning routes, in developing cognitive maps and in navigating in environments, suggest a functional alteration of the medial temporal and parietal areas, whose activity has repeatedly and consistently been associated with topographical skills (see for example, Burgess, Becker, King, & O’Keefe, 2001; Byrne, Becker, & Burgess, 2007). In particular, the observation that F.G. recognizes most landmarks, but is completely unable to exploit them, suggests an altered functioning of the retrosplenial cortex (Vann, Aggleton, & Maguire, 2009). F.G. appears to recognize most landmarks, although he is unable to use them for navigation because he seems unable to derive any directional information from them. He admitted that even if he knows that some landmarks are in the same area he is unable to associate their reciprocal spatial relationships and has no idea how far they are from each other. F.G. also reported that he never uses graphic maps to find his way because he is completely unable to do so. He also described many instances of disorientation in his real life, when he recognized where he was, but was unable to derive any directional information even from maps: “I got lost in a shopping center. I called my sister to ask her for help, and she guided me along the route back home over the phone”.

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The assessment confirmed the presence of defective topographical knowledge and navigational processes in almost all the tests of the battery used to assess navigational disorders. Despite his normal memory skills in visuo-spatial and verbal memory tests, F.G. was unable to encode and memorize a route he had followed with the experimenter and after a 5-min delay he forgot the eightstep path he had just learned during the Walking Corsi Supraspan test. These data clearly suggest that F.G. suffers from a navigational memory deficit. F.G. lacks the ability to create and use cognitive maps, and he is also unable to use graphic maps, to find his position on a map and to translate the path drawn on a map into egocentric directions. He also has difficulty describing familiar environments from memory. Indeed, he reported the few landmarks he recalled in a familiar square very concisely, without providing details of their physical features or relative locations. He is also unable to draw a map of very familiar, over-learned environments. Furthermore, on the CMT, which specifically assesses the ability to create and store a cognitive map by traveling in an oversimplified virtual environment, his performance was significantly slower than that of the matched controls. All told, these deficits are compatible with recent hypotheses of a close link between episodic memory and the capacity to conjure images of the future (Hassabis & Maguire, 2007; Schacter & Addis, 2007). Of particular interest in this sense are the assumptions that memory is the base for imaging future events (including imaging the path to follow in order to reach a given goal) and that scene construction is the core process on which different cognitive functions (including navigation) rely. Referring to this hypothesis, F.G.’s impairments may be attributed to a failure to create images of future events and to construct scenes, which prevents him from knowing which direction to take during navigation. Undoubtedly, F.G. has difficulties in generating mental images of familiar environments, that is, he is unable to construct environmental scenes, as demonstrated by the difficulties he encountered in describing or drawing familiar places. Following the original hypothesis (Hassabis & Maguire, 2007) it may be said that scene construction difficulties may affect not only Navigation, but also Episodic memory recall, Episodic future thinking, Imagination and Viewer replay. However, the neuropsychological assessments carried out show that in F.G.’s case no other cognitive function relying on the common-core process of scene construction is impaired. It is important to recall that F.G. has good problem-solving and planning skills even as far as visuospatial material (i.e., Tower of London) is concerned, and that no other memory impairment was detected during the formal testing of short-term and long-term verbal and visuo-spatial memory. In addition, the fact that F.G. was able to recall his past life in detail suggested that we may consider his autobiographical memory normal, even in the absence of formal testing. Furthermore, the above-reported hypothesis cannot account fully for F.G.’s poor performances during some non-navigational tasks. When F.G. was subjected to an extensive battery of tests, he revealed deficits in different cognitive processes directly or indirectly involved in navigation. In the WAIS-R, F.G. was rated as having a normal total I.Q. but he scored significantly lower in the Performance I.Q. than in the Verbal I.Q. because his scores on the Picture Completion, Block Design and Object Assembly were poor. It is unclear which defective component affects the performance in these three subtests and what it may have to do with navigational skills. In all the three subtests, F.G. was invited to analyze the stimuli provided in order to understand the spatial relationships between the parts of each one and to determine what was lacking or how to arrange the parts to reconstruct a familiar object or an abstract figure. To this regard, F.G. seems to have a selective impairment in

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the processing of spatial relationships between parts that prevents him from detecting what is lacking in the Picture Completion task and from correctly arranging the cubes in the Block Design task. Even in Object Assembly, in which he was required to rearrange the parts of common objects, F.G. recognized and named each part but failed to put the parts in their right spatial order because of his deficit in processing the spatial relationships between the parts of the whole. The subject’s inability to arrange the elements in a complex array was also evident in the navigational tasks he was required to carry out. F.G. recognized the environmental elements but could not integrate them into a route or into an overall representation of the environment which might prove useful to navigation. According to Farrell (1996), “A spatial location of an environmental feature in not extrinsic to its identity. The identity of an environmental feature (“what” it is) is partly determined by its location (“where” it is)”. Because of his inability to process spatial relational information, F.G. knows “what” environmental elements are but not “where” they are. This means that environmental elements never acquire topographical value for him. In other words, they do not act as true landmarks for him and therefore cannot be used to develop an autonomous verbal navigational strategy. This might explain why F.G. identified buildings and monuments on the Postcard Test correctly (in fact, he has no problem with object identification and perception) but he failed to exploit them for navigation. F.G.’s inability to combine several objects to produce a complex pattern prevented him from developing cognitive maps. Indeed, to build and manipulate complex cognitive maps it is necessary to integrate different kinds of objects, and their common feature is that the identity of each one also involves its spatial relationship with/within the environment. A question that arises is how the retrosplenial areas, which process navigational information, may affect the processing of spatial relationships among the parts in tasks such as the Block Design, Object Assembly and Picture Completion. One hypothesis is that the retrosplenial areas are responsible for processing spatial relationships even in non-navigational tasks. A second possibility is that a different neural area processes the spatial relationships among the parts and that retrosplenial areas use this process to develop cognitive maps and direct navigation. Currently, there are no data available that allow us to draw conclusions on this point, though future research should focus on this subject. In the virtual environment (CMT), the subject revealed very slow but effective learning skills. In contrast to the analogous reallife situations, in this task the map of the environment was given to the subject at the onset, and he was told that the objects he would encounter during the navigation were landmarks. Thus, in the acquisition of the cognitive map, CMT proved easier than the analogous tasks in which F.G. was required to derive the geometry of the environment from his own direct navigational experience alone. Moreover, the environment in the CMT test was oversimplified. No environmental objects were present except for the six landmarks included. It is possible that, being unable to generate a cognitive map, F.G. developed a verbal description of the CMT environment. Indeed, F.G. reported spontaneously that in the CMT recall test he solved the task by using a verbal strategy, which was probably easier in such a simplified environment. Developing verbal strategies to compensate for topographical disorientation has already been described as successful (Davis & Coltheart, 1999; Incoccia, Magnotti, Iaria, Piccardi, & Guariglia, 2009). In fact, Iaria et al. (2009) reported that Pt1 was able to navigate in her familiar environments by using verbal strategy. Why then is F.G. unable to adopt a verbal strategy in his everyday life? The first hypothesis is that real environments are too complex, and that segregating a landmark and putting a verbal directional

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label on it is difficult because of the complexity of the environment. Furthermore, in real everyday life, the space to be navigated is very large. Therefore, many verbal navigational “scripts” have to be memorized, which requires a long period of learning. If this hypothesis is true, the difference between Pt1’s and F.G.’s abilities to use verbal navigational strategies may lie in the unlikely fact that Pt1 lives in an environment easier to navigate or that, because she is older than F.G., she has had more time to learn the verbal scripts. A second hypothesis is that the difference between F.G. and Pt1 is that they have different types of deficit. F.G.’s knowledge of environmental features lacks the knowledge of spatial relationships that make them “landmarks”. Therefore, he is unable to select the elements to be labeled with verbal instructions. None of Pt1’s data (Iaria et al., 2009) suggest that she was affected by an analogous defect in processing spatial relational information. Indeed, Pt1 had no problem with the mental rotation test (Grossi, 1991) and no differences were reported between her VIQ and her PIQ (suggesting that she performed in all the subtests with the same level of proficiency). It is therefore possible to hypothesize that Pt1 is endowed with the normal ability to process spatial relational information, which makes it easier for her to select landmarks to be labeled with verbal instructions in order to develop navigational scripts. In any case, Pt1 and F.G. differ in the severity of their topographical disorientation. Unlike F.G., Pt1 learned the path shown by the examiner in the route-based navigation task successfully because she was able to develop verbal scripts by herself, as declared in the end-of-test report she provided explaining the strategies she adopted. Pt1 is also able to follow a path shown on a map, possibly by translating the visual–spatial information of the maps into verbal scripts. Even without making a direct comparison between Pt1 and F.G., it seems likely that the above-reported differences are due to the fact that Pt1 has developed the ability to segregate and identify landmarks in a landscape. She not only recognizes a previously seen landmark, but also knows the directional information linked to this specific environmental object. She has a rough idea at least of the location of the landmarks and of the direction she should take to go from one landmark to another. These salvaged abilities allow her to compensate partially for her developmental disorder by using a verbal strategy. Instead, F.G. is able to utilize the verbal scripts only when someone else provides them. He is unable to segregate and identify a landmark in a landscape, and even when he recognizes a landmark he has no knowledge about its location or about the directional information he can derive from it. In conclusion, the present data support the existence of a developmental topographical disorientation deficit, a selective disorder that affects, at times quite severely, a person’s ability to learn how to navigate the environment autonomously. In the present case, developmental topographical disorientation may be defined as a deficit in segregating landmarks and deriving navigational information from them, together with the absence of any non-verbal navigational process, and the presence of a deficit in generating cognitive maps. A comparison between the present case and the one described previously (Iaria et al., 2009) seems to indicate that developmental topographical disorientation may present different degrees of severity in subjects with otherwise normal cognitive functions who are not affected by detectable psychiatric or neurological diseases or by evident brain malformation. The cognitive and functional basis of this developmental syndrome, as well as those of other developmental neuropsychological disorders (i.e., SLI or developmental prosopoagnosia), is far from being thoroughly understood. Given that to date only two subjects have been described with this syndrome, we cannot even advance the hypothesis that the above definition is comprehensive. Descriptions of new cases are necessary to confirm that developmental

topographical disorientation is not simply a disorder in the generation of cognitive maps in the absence of non-verbal navigational skills, and that there are no different sub-types of this syndrome requiring an exhaustive taxonomy.

Conflicts of interest The authors declare that they have no conflicts of interests and that they have no grants to disclose for this study.

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