Occipito-parietal cortex activation during visuo-spatial imagery in early blind humans

NeuroImage 19 (2003) 698 –709

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Occipito-parietal cortex activation during visuo-spatial imagery in early blind humans Annick Vanlierde,a Anne G. De Volder,b Marie-Chantal Wanet-Defalque,a and Claude Veraarta,* a

Neural Rehabilitation Engineering Laboratory, Universite´ Catholique de Louvain, Brussels, Belgium b Positron Tomography Unit, Universite´ Catholique de Louvain, Brussels, Belgium Received 17 September 2002; revised 14 February 2003; accepted 3 March 2003

Abstract Using positron emission tomography, regional cerebral blood flow was studied in five early blind and five control volunteers during visuo-spatial imagery. Subjects were instructed to generate a mental representation of verbally provided bidimensional patterns that were placed in a grid and to assess pattern symmetry in relation to a grid axis. This condition was contrasted with a verbal memory task. Cerebral activation in both groups was similar during the visuo-spatial imagery task. It involved the precuneus (BA 7), superior parietal lobule (BA 7), and occipital gyrus (BA 19). These results are in accordance with previous studies conducted in sighted subjects that indicated that the same occipito-parietal areas are involved in visual perception as well as in mental imagery dealing with spatial components. The dorsal pathway seems to be involved in visuo-spatial imagery in early blind subjects, indicating that this pathway undergoes development in the absence of vision. © 2003 Elsevier Science (USA). All rights reserved. Keywords: Human blindness; Positron emission tomography; Visuo-spatial processing; Brain plasticity

Introduction As investigated in many behavioral studies, since the 1970s, mental imagery seems to involve functional properties close to visual perception. Mental imagery and perception could share a same internal representation. There is a close relationship between visual mental imagery and visual perception since they exert an influence on each other. For instance, visual imagery is used to complete fragmented perceptual inputs or to match shapes during recognition tasks (Kosslyn and Sussman, 1995). There is also evidence that visual imagery can facilitate perception (Neisser, 1976; Farah, 1985; Ishai and Sagi, 1995, 1997b) or may interfere with perception (Craver-Lemley and Reeves, 1992; Ishai and Sagi, 1997a). Moreover, reaction times taken to men* Corresponding author. Neural Rehabilitation Engineering Laboratory, Universite´ Catholique de Louvain, 54, Av Hippocrate, Box UCL 54-46, Brussels B-1200, Belgium. Fax: ⫹32-2-764-9422. E-mail address: [email protected] (C. Veraart).

tally rotate two shapes, to judge whether they are identical or in mirror, increase with the angular disparity between the stimuli (Shepard and Metzler, 1971; Cooper and Shepard, 1973). The mental visual images respect also the metric spatial information (Kosslyn et al., 1978; Pinker, 1980). In spite of this close relationship between imagery and visual perception, early blind (EB) subjects are able to perform mental imagery tasks with the same efficiency as sighted subjects (Vanlierde et al., 2001). However, these subjects did not have any visual experience and access their environment using nonvisual modalities. EB subjects are able to mentally rotate tactually perceived shapes. They show an increase of reaction time that is heavily correlated with the angular disparity between two shapes in the same way as sighted subjects (Marmor and Zaback, 1976; Carpenter and Eisenberg, 1978). The metric spatial information is also preserved in their mental images. For instance, a linear relationship is observed between scanning time and distance between two objects in an imaged scene (Kerr, 1983). However, behavioral differences exist between EB

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A. Vanlierde et al. / NeuroImage 19 (2003) 698 –709

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Table 1 Characteristics of the early blind (EB) subjects Subjects

Age (yr)

Onset of blindness

Diagnosis

Handedness

1 2 3 4 5

49 61 35 20 45

18 months 1–2 yra Birth Birthb Birth–3 yra

Bilateral retinoblastoma Bilateral retinoblastoma (enucleated) Prematurity Leber optic neuropathy Congenital cataract (enucleated)

R R R R R

a b

These subjects were classified as early blind, as they suffered from very low vision since birth and became completely blind before the age of 3 years. This subject has a perception of night and day.

and sighted subjects in those visuo-spatial imagery tasks. It is difficult for EB subjects to perform tasks requiring a large load in visuo-spatial working memory (Cornoldi et al., 1991, 1993) or requiring an active manipulation (Vecchi et al., 1995; Vecchi, 1998). In these specific tasks, EB’s performance is worse than the one of blindfolded sighted controls. Neuroimaging studies indicate that perception and mental imagery could share the common processing networks in the brain (Parsons et al., 1995; Roland and Gulyas, 1995; O’Craven and Kanwisher, 2000). The reported neuroanatomical dichotomy between spatial and object information processing (Mishkin et al., 1983; Haxby et al., 1991) also appears in mental imagery, leading to the concept of “double dissociation” between object discrimination and spatial localization both in visual perception and mental imagery. This concept is supported by neuropsychological studies in brain-damaged patients (Levine et al., 1985; Farah et al., 1988; Luzzatti et al., 1998) and in healthy humans (Tresch et al., 1993; Hecker and Mapperson, 1997) and further supported by neuroimaging studies in sighted subjects (Faillenot et al., 1997). On the one hand, Mellet et al. (1995, 1996, 2000) show that the dorsal pathway is activated during mental imagery dealing with visuo-spatial information. Furthermore, this activation is independent of the way, visual or verbal, the spatial information is conveyed to the subject but it depends on the spatiality of the information. On the other hand, the ventral pathway is activated during generation of mental images of objects (Kosslyn et al., 1993; D’Esposito et al., 1997; Mellet et al., 1998). Whether early perception areas (V1) are involved in visual imagery is still debated (see, e.g., Kosslyn et al., 1999; Mellet et al., 2000; Thompson et al., 2001). Different brain networks are involved depending on the nature of the material used for mental imagery and depending on the characteristics of the task to be performed (O’Craven and Kanwisher, 2000). The primary visual cortex is claimed to be especially involved in mental imagery tasks requiring a detailed object image (Thompson et al., 2001) or a short-term visual recall (Chen et al., 1998). By contrast, mental imagery tasks related to visuo-spatial material would fail to activate the primary visual cortex (Mellet et al., 1996; Ghae¨m et al., 1997). According to a previous study, mental imagery of object shape activated the ventral pathway in EB subjects in a

similar way as in blindfolded controls (De Volder et al., 2001). This finding indicated a developmental crossmodal reorganization of this cortex to allow perceptual representation in the absence of vision. The present study aims at investigating further the neural bases of mental imagery in EB humans and to determine whether the dorsal pathway would be involved in visuo-spatial imagery in these subjects.

Materials and methods Subjects The positron emission tomography (PET) studies were carried out on 5 male volunteers, with a mean age ⫾ SD of 42.3 ⫾ 14.1 years, who were affected by early blindness as the result of bilateral ocular or optic nerve lesions. The volunteers were otherwise neurologically normal. They were recruited on a voluntary basis with the help of associations for blind people. A summary of their medical history is provided in Table 1. PET measurements in EB subjects were compared with those obtained in 5 blindfolded male sighted controls (SC), with a mean age ⫾ SD of 43.5 ⫾ 16.2 years, whose age was matched with the EB (P ⫽ 0.920) and who present similar metabolic patterns as subjects with late-onset blindness according to previous studies (Veraart et al., 1990). All subjects were right-handed and gave their written informed consent for the study. They were included in a previous behavioral experiment related to visuo-spatial imagery (Vanlierde et al., 2001). The protocol was approved by the Biomedical Ethics Committee of the School of Medicine of the Universite´ Catholique de Louvain. Experimental design The subjects were studied under the following five conditions, each repeated twice in counterbalanced order across the subjects: (1) resting state condition (REST), (2) passive listening of words (PASSIVE), (3) target detection during listening of words (ACTIVE), (4) verbal memory condition using words (MEMORY), and (5) visuo-spatial mental im-

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Fig. 1. Matrix examples used in the study. Left: meaningless pattern; right: meaningful pattern (V). The two symmetry axes are represented by thick lines. The meaningless pattern (left) is slightly symmetric according to the vertical grid axis since one filled-in square is mirrored on another one according to this axis. This pattern is moderately symmetric according to the horizontal axis since two filled in squares are mirrored on two other ones. By contrast, the meaningful pattern (right) is not at all symmetric according to the horizontal axis but it is entirely symmetric according to the vertical axis.

agery (MATRIX). The first and the last scans in each subject were always acquired during REST. Stimuli MATRIX. In this task, subjects were required to mentally generate a 6 ⫻ 6 matrix organized like a crossword grid. This matrix might be parted according to two symmetry axes. One vertical line might part the grid into two equal components, with three columns on the left side and three on the right side (Fig. 1). One horizontal line might part the grid into two equal components, with three lines at the top and three lines at the bottom. In MATRIX, six squares were indicated to the subject as blackened (or filled-in) squares, to create a pattern in the grid. There were eight different matrices, including four meaningful patterns (i.e., T, L, V, and †) and four meaningless patterns. The following four levels of symmetry were considered in the present study: (1) patterns that were not at all symmetric (when no filled-in square was mirrored according to a given symmetry axis, see Fig. 1), (2) patterns that were slightly symmetric (when only one filled-in square in a half matrix was mirrored in the other half according to a given symmetry axis), (3) patterns that were moderately symmetric (when two filled-in squares were mirrored according to a given symmetry axis), (4) patterns that were completely symmetric (when all three filled-in squares of one-half were mirrored on the three others according to a given symmetry axis). These eight matrices were verbally described to the subjects in French, using audio recording. A total of nine words were used for matrix description, as follows: the French translation of first, second, third, fourth, fifth, sixth, line, white, and black. “White” was used for each empty square (30 times/grid) whereas “Black” was used for every filled-in square (n ⫽ 6). After each matrix, subjects had to answer a question about the symmetry level of the pattern in relation to a given symmetry axis (see Appendix for more details). It is worth noting that, until this time, they were not aware about which axis the symmetry would had to be evaluated. The full description of a matrix requested thus a total of 48 words in a sequence.

MEMORY. Four lists of words were used for the MEMORY control condition. They were obtained by replacing each word used during the MATRIX condition by an abstract word with low imagery (n ⫽ 9). These abstract words rated ⬍3.5 on a imagery scale of 7 (Desrochers and Bergeron, 2000). In the four lists, a specific abstract word was matched with a given MATRIX word for the numbers of letters and syllabes (e.g., “avantage” was one of the four abstract words matched with “premiere”). In a sequence, the French word corresponding to “white” in the MATRIX condition was repeated 30 times, the two words corresponding to “black” and “line” were repeated six times each, whereas the other words were presented only once. Special care was taken to organize each sequence with the nine words having an homogeneous occurrence frequency in French (see Appendix for more details). PASSIVE and ACTIVE. Four lists of words were used for the listening conditions and consisted of 52 abstract words that rated ⬍3.5 on a imagery scale of 7 (Desrochers and Bergeron, 2000). A different list was used for each (PASSIVE and ACTIVE) condition. For the ACTIVE condition, one word was randomly chosen as the target and presented as such to the subjects. All sequences were previously prepared using the Corel Edit 96 software on PC and the stored stimuli were provided through earphones connected to the PC. Experimental procedure A familiarization session occurred before the PET study to instruct subjects with all conditions, to verify that they understood the tasks, and to help them to relax during the PET study. Afterward, they underwent the 10 scans of the PET session. REST. During these scans, the subjects were instructed to relax without moving, speaking, or focusing their attention

A. Vanlierde et al. / NeuroImage 19 (2003) 698 –709

on anything in particular. SC subjects were blindfolded in this task as in all other tasks. PASSIVE. In this first control condition, subjects had to listen attentively to the words of one sequence during the scans. This condition aimed at subtracting away from the MATRIX condition the cerebral activity related to verbal auditory stimulation. ACTIVE. During these scans, subjects were instructed to listen to one sequence and to hit the left key of a PC mouse when they heard the target word. The target appeared only once during the scan even if the subjects were aware that it could appear several times. The task complexity was increased by using some words in the sequence that had a phonological similarity with the first or with the last syllable of the target (e.g., gouvernement/gouverneur). This attentional detection task aimed at subtracting away from the MATRIX condition the brain activity related to verbal auditory stimulation and attentional load. MEMORY. During each of these two scans, subjects had to listen to two sequences of words and to memorize the nine presented words. After the first sequence, subjects were asked if a given word was or was not presented during this sequence. The answer was provided by mouse clicking (left key ⫽ yes; right key ⫽ no). Then, the second sequence was generated and lasted beyond the end of data acquisition. Thereafter, subjects were asked if four different words had been presented during this second sequence. One of those four words was occurring 30 times, another one, one of the two occurring six times, yet another, one of the six occurring only once, and finally an outlying word with a phonological similarity with a word in the sequence. Answers were provided as after the first sequence. The purpose of this condition was to subtract away from the MATRIX condition the brain activity related to verbal memory processing, with a similar attentional load as in the MATRIX condition. MATRIX. During each scan in this condition, subjects were presented with two matrix descriptions. They heard a verbal description of the matrix that was organized line by line and square by square to delimitate a pattern as described. Subjects had to memorize this pattern and to maintain it mentally in the grid. After the presentation, they were asked if a given symmetry level, according to one of the two symmetry axes, was present or not. Answers were provided by key pressing as for MEMORY condition. Here again, as in all the other conditions, no verbal answer was requested to avoid activation of language areas. Two additional matrix descriptions were presented after each MATRIX scan to enlarge the behavioral database. At the end of the PET session, subjects had to describe how they kept the information in memory.

701

Positron emission tomography Data acquisition Measurements of local radioactivity uptake were made by using an ECAT EXACT-HR PET tomograph (CTI/Siemens, Knoxville, TN, USA), which allows simultaneous imaging of 47 transaxial slices in three-dimensional (3D, septa rectracted) mode, with an effective resolution of 8-mm full-width at half-maximum (FWHM) (Wienhard et al., 1994) and a slice thickness of 3.125 mm. All images were reconstructed, using a standard ECAT software (3DRP algorithm) including scatter correction, with both transaxial Hanning filters (cutoff frequency of 0.30) and axial Hanning filter (cutoff frequency of 0.50, i.e., Nyquist frequency). Correct positioning of the subject in the gantry was ascertained by aligning two sets of low-power laser beams with the canthomeatal line and the sagittal line, respectively. Head-restraining adhesive bands were used to help maintaining the head in good position throughout all the study. For radiotracer injection, a 22-gauge catheter was placed in the antecubital vein of the left or right arm. Prior to tracer administration, each subject underwent a 15-min transmission scan performed with retractable germanium-68 rotating rod sources, allowing the subsequent correction of emission images for attenuation. Transmission scans were acquired with a rod-windowing technique (Jones et al., 1995) producing scatter-free attenuation correction. Cerebral blood flow measurement was then performed by using a 20-s bolus of oxygen-15-labeled water (8 mCi, 2.96 ⫻ 102 MBq). Stimulation sequences and PET acquisition were started 10 s after the initiation of tracer injection. Integrated counts accumulated during 90-s scans were used as an index of regional cerebral blood flow (rCBF) (Mazziotta et al., 1985). Time interval between successive emission scans was 13 min, which allowed decay of residual radioactivity. For each subject, 3D magnetic resonance imaging (MRI) anatomical data were also obtained on a 1.5-T unit (General Electric Signa) using the spoiled grass technique. T1weighted images (TR ⫽ 25 ms, TE ⫽ 6 ms, flip angle 25°, slice thickness 1.5 mm) were obtained in the bicommissural (AC-PC) orientation. Data analysis PET images were aligned to correct for possible interscan movements and coregistered to the subject’s MRI using AIR 3.0 (Woods et al., 1998a, 1998b). The resulting matching brain images (MRI and coregistered PET) were spatially normalized with statistical parametric mapping (SPM) (Wellcome Department of Cognitive Neurology), in the referential defined by the atlas of Talairach and Tournoux (1988) and the MRI template supplied by the Montreal Neurological Institute (MNI) to allow group analysis (voxel size, 2 ⫻ 2 ⫻ 2 mm). The accuracy of realignment and normalization procedure was assessed with an interactive home made image display software (Michel et al., 1995)

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implemented in IDL language (IDL Research Systems, Inc, Boulder, CO, USA). PET images were further smoothed with an isotropic Gaussian filter (15-mm FWHM) and were corrected for differences in global activity by proportional scaling (Fox et al., 1988). To identify the regions showing significant rCBF changes, statistics were computed on a voxel-by-voxel basis, using the general linear model (Friston et al., 1995). The resulting voxel sets of each contrast constitute a statistical parametric map of the t statistic, SPM{t}, which was then transformed to the unit normal distribution SPM{Z}. This allowed the overlay of the obtained t maps on each spatially normalized MRI. Statistical analysis was performed for each group separately, using a multisubject design (with replication) (SPM 99, Wellcome Department of Cognitive Neurology). Since a hierarchical design was used, the MATRIX condition could be contrasted with three control conditions, each one involving an additional cognitive function. Accordingly, (MATRIX ⫺ PASSIVE) allowed to subtract away from the experimental condition brain activity related to verbal auditory stimulation, while (MATRIX ⫺ ACTIVE) further subtracted the attentional processing. The last contrast (MATRIX ⫺ MEMORY) subtracted brain activity related to verbal memory processing used in encoding the matrix. This last contrast should display neural networks involved in visuo-spatial imagery in case of blindness. Besides, all contrasts were additionally masked by (MATRIX ⫺ REST), used as inclusive mask (thresholded at P ⬍ 0.001, uncorrected), to take account of the high brain activity already observed at rest in EB occipital cortex (Wanet-Defalque et al., 1988; Veraart et al., 1990). Therefore, all activation foci detected with the contrasts were related to activation well above the basal resting state. Differences related to blindness were similarly assessed using a group ⫻ condition interaction analysis. Common activation irrespective of subject group (EB or SC) was assessed by conjunction analysis (Price and Friston, 1997). Only regions significantly activated at P ⬍ 0.001 (uncorrected for multiple comparisons) or P ⬍ 0.05 (corrected for multiple comparisons) were considered.

Results Behavioral results The percentage of correct responses in the MATRIX task was 65.0 ⫾ 15.5% (mean ⫾ standard error of the mean) in EB subjects. Although the performance in SC group was better and slightly less variable (80.0 ⫾ 10.2%), this difference was not significant (t ⫽ 0.809, P ⫽ 0.44). The percentage of correct responses in the MEMORY task was 88.0 ⫾ 5.8% (mean ⫾ standard error of the mean) in EB subjects and 84.0 ⫾ 5.1% in sighted controls (t ⫽ ⫺0.516, P ⫽ 0.62). In addition, there was also no significant difference between the two groups when the four types of

words were tested separately (t ⫽ ⫺0.849, P ⬎ 0.05, for words occurring only once; t ⫽ 1.633 P ⬎ 0.05, for outlying words; both groups had 100% correct answers for words occurring 30 times as well as for those occurring six times). Between the MATRIX task and the MEMORY task the percentage of correct responses did not differ significantly within each group (t ⫽ 1.525, P ⫽ 0.20 in EB; and t ⫽ 0.397, P ⫽ 0.71 in SC group). All subjects gave 100% correct answers for target detection during the ACTIVE condition. As for the way the subjects kept matrix information in memory, strategies reported by EB and SC subjects were identical to those obtained in a previous behavioral experiment (Vanlierde et al., 2001). Briefly, EB subjects used an X–Y coordinate strategy to perform the visuo-spatial task. They encoded each square of the grid by its location (X/Y). By contrast, the SC subjects constructed mentally a visual image of the grid. PET results Main effect of visuo-spatial imagery versus verbal memory EB subjects. The brain regions involved in visuo-spatial imagery (MATRIX ⫺ MEMORY masked by MATRIX ⫺ REST) in the EB group are disclosed in Fig. 2 and listed in Table 2. Visuo-spatial mental imagery by EB subjects activated a large strip of brain areas encompassing the precuneus (BA 7) bilaterally, the right superior parietal lobule (BA 7), and the right superior occipital gyrus (BA 19). There was no activation in the primary visual cortex (BA 17). SC subjects. During visuo-spatial imagery (MATRIX ⫺ MEMORY masked by MATRIX ⫺ REST), SC subjects activated four brain regions (Table 2), as follows: the superior parietal lobule (BA 7, Fig. 2) was bilaterally activated, as well as the left superior occipital gyrus (BA 19) and precuneus (BA 7). There was no activation in the primary visual cortex (BA 17). Visuo-spatial imagery compared to passive and active listening EB subjects. Visuo-spatial imagery, compared to passive listening (MATRIX ⫺ PASSIVE masked by MATRIX ⫺ REST), strongly activated the superior parietal lobule (BA 7) and, to a lesser extent, the inferior parietal lobule (BA 40) bilaterally (Table 3). When compared to active listening (MATRIX ⫺ ACTIVE masked by MATRIX ⫺ REST), visuo-spatial imagery also activated the superior parietal lobule bilaterally, with similar spatial coordinates. Besides, the right precuneus (BA 7) was also activated in this last contrast. SC subjects. In SC subjects, visuo-spatial imagery compared to passive or active listening also activated similar

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Fig. 2. Activation foci observed in visuo-spatial imagery contrasted to verbal memory processing in early blind (EB) subjects (left side) and in blindfolded sighted control (SC) subjects (right side). The statistical parametric map for this comparison is superimposed on the axial, coronal, and sagittal sections of an individual normalized brain magnetic resonance imaging scan. Only positive difference exceeding a threshold of P ⬍ 0.001 (uncorrected) is shown, according to the color scale that codes the T values. In EB subjects, the lines intersect on a voxel in the right precuneus (BA 7) with a Z value of 4.26 (P ⫽ 0.05, corrected for multiple comparisons). In SC subjects, similar brain areas were activated. The lines intersect on a voxel in the left superior parietal lobule (BA 7) with a Z value of 3.81 (see, also, Table 2). Coordinates refer to the referential defined by the atlas of Talairach and Tournoux (1988) and the Montreal Neurological Institute (MNI) template (see materials and methods section).

brain areas. In both contrasts, the right superior parietal lobule (BA 7) and the left superior occipital gyrus (BA 19) were similarly activated. A large activation area was also observed in the right middle frontal gyrus (BA 6, premotor cortex; see Table 3). In the contrast (MATRIX ⫺ PASSIVE masked by MATRIX ⫺ REST), additional activation foci were observed in the left precuneus (BA 7) and in the right superior frontal gyrus (BA 6). In the contrast (MATRIX ⫺ ACTIVE masked by MATRIX ⫺ REST), the right inferior

parietal lobule (BA 40) and the left superior frontal gyrus (BA 6, premotor cortex) were also activated. Comparison of the two groups The differences in visuo-spatial imagery activation, as contrasted to memory processing, between EB and SC groups (Fig. 3) were studied. As shown in Table 2, activation patterns in both groups were very close. There was no significantly higher activation in either group compared to

Table 2 Activations during mental visuo-spatial imagery (MATRIX) contrasted by memory task (MEMORY) masked by (MATRIX ⫺ REST)a Anatomical region

EB subjects Precuneus (BA 7) Superior parietal lobule (BA 7) Precuneus (BA 7) Superior occipital gyrus (BA 19) SC subjects Superior occipital gyrus (BA 19) Superior parietal lobule (BA 7) Precuneus (BA 7) a

Coordinates (mm) Side

X

Y

Z

Z score

R R L R

4 20 ⫺12 30

⫺68 ⫺66 ⫺70 ⫺80

58 56 56 38

4.26 4.00 3.72 3.71

L R L L

⫺32 20 ⫺12 ⫺6

⫺78 ⫺64 ⫺62 ⫺82

30 58 64 46

3.94 3.85 3.81 3.42

Region size (number of voxels)

736 NS b NS b NS b

104 185 67 40

NS NS NS NS

BA, Brodmann area; coordinates refer to the voxel with the highest Z score within each area in the referential defined by the atlas of Talairach and Tournoux (1988) and the Montreal Neurological Institute template (see materials and methods section). EB, early blind; SC, sighted control. b Belongs to the same voxels cluster. NS means that the level is significant only at a P value uncorrected for multiple comparisons.

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Table 3 Activations comparing visuo-spatial imagery (MATRIX) with passive listening (PASSIVE) and comparing visuo-spatial imagery (MATRIX) with active listening (ACTIVE) masked by (MATRIX ⫺ REST)a Contrast

EB subjects (MATRIX ⫺ PASSIVE)

Region size (number of voxels)

Anatomical region

Side

1737

Superior parietal lobule (BA 7)

b

(MATRIX ⫺ ACTIVE)

88 NS 67 NS 1820 b b

SC subjects (MATRIX ⫺ PASSIVE)

2403 b

1780 b

(MATRIX ⫺ ACTIVE)

174 2212 b

212 180 1119 NS

Inferior parietal lobule (BA 40) Precuneus (BA 7) Superior parietal lobule (BA 7) Superior parietal lobule (BA 7) Superior parietal lobule (BA 7) Precuneus (BA 7) Middle frontal gyrus (BA 6) Superior frontal gyrus (BA6) Superior occipital gyrus (BA19) Superior parietal lobule (BA 7) Inferior parietal lobule (BA 40) Superior occipital gyrus (BA 19) Superior frontal gyrus (BA 6) Middle frontal gyrus (BA 6)

Coordinates

Z score

X

Y

Z

R L R L R L R

18 ⫺16 46 ⫺46 4 ⫺10 26

⫺66 ⫺70 ⫺48 ⫺48 ⫺68 ⫺68 ⫺66

54 54 52 52 56 56 52

5.58 5.02 3.50 3.49 5.27 4.93 4.69

R L R R L

22 ⫺6 42 32 ⫺32

⫺68 ⫺66 14 ⫺2 ⫺76

54 58 48 60 38

5.34 4.83 4.87 4.60 4.52

R R L

18 40 ⫺32

⫺68 ⫺46 ⫺78

56 52 32

5.35 4.66 5.20

L R

⫺26 30

6 ⫺6

60 58

4.71 4.38

R

26

2

50

4.12

b

NS a

BA, Brodmann area; coordinates refer to the voxel with the highest Z score within each area in the referential defined by the atlas of Talairach and Tournoux (1988) and the Montreal Neurological Institute template (see materials and methods section). EB, early blind; SC, sighted control. b Belongs to the same voxels cluster. NS means that the level is significant only at a P value uncorrected for multiple comparisons.

the other; there was only a very little trend for higher activation in the superior occipital gyrus on the right side in EB subjects (x,y,z ⫽ 26, ⫺74, 38; Z score ⫽ 2.14; Fig. 3). For other contrasts (MATRIX ⫺ PASSIVE or ACTIVE masked by MATRIX ⫺ REST), there was no difference in activation between groups (uncorrected P ⬍ 0.001). In conclusion, there was a thoroughly similar activation pattern in both groups during visuo-spatial imagery as also assessed by conjunction analysis. This activation pattern extended from the precuneus toward the superior parietal lobule bilaterally (Fig. 3). These cerebral regions were similarly activated in the visuo-spatial imagery task when contrasted with the three control conditions in both groups (conjunction analysis).

Discussion The present study shows a selective activation of occipito-parietal areas during visuo-spatial imagery in early blind as well as in sighted humans. The visuo-spatial imagery task used here was identical to the one performed in a previous experiment (Vanlierde et al., 2001). This task required the subjects to build up a pattern that was verbally described and to mentally maintain the precise location of filled-in squares inside a grid. At the

end of the verbal description, a symmetry axis of the grid was provided to the subject. The subject had then to compare the location of each filled-in square in relation to this axis and to evaluate the symmetry level of the pattern. Although both groups had a similar task performance, they differed in their strategy. Indeed, SC subjects created a visual image in their mind while EB subjects described an X–Y coordinate and encoded the spatial location of each square, further comparing the coordinates of the relevant squares to evaluate the symmetry level. This different strategy was not reflected by differences in neural activation and the dorsal visual pathway was activated during the task in both groups. In sighted subjects, the superior occipital and parietal areas are to be involved in spatial processing of visual stimuli (Mishkin et al., 1983; Haxby et al., 1991). Furthermore, the same brain areas are also activated in mental imagery tasks including nonperceptual spatial information (Mellet et al., 1995, 1996; Faillenot et al., 1997; Knauff et al., 2000). On the one hand, the parietal regions are involved in spatial coordinates computing during mental rotation tasks (Cohen et al., 1996; Trojano et al., 2000; Jordan et al., 2001). These brain areas are recruited during tasks such as building-up of spatial patterns generated by verbal instruction (Mellet et al., 1996) or spatial working memory tasks (Jonides et al., 1993). On the other hand, the precuneus

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would be involved in exploration of mental images (Ghae¨m et al., 1997) and in conscious memory recall of imageable verbal paired associates (Fletcher et al., 1995). In EB subjects, activation of parieto-occipital regions has been previously reported during tasks involving spatial features or spatial analyses. In both the EB and SC, the precuneus as well as the superior parietal lobule were also activated during a visual pattern recognition task using sensory substitution of vision by audition and involving visuo-spatial working memory (Arno et al., 2001). These areas were also activated in spatial auditory localization (Weeks et al., 2000), in distance estimation using an ultrasonic device (De Volder et al., 1999), in Braille reading (Sadato et al., 1996, 1998; Bu¨chel et al., 1998), and in tactile imagery (Uhl et al., 1994). Since visual memories are normally nonexistent in the EB participants to the aforementioned studies, these subjects would use spatial imagery rather than visual mental imagery during these tasks. If spatial imagery was involved, it is not surprising that parieto-occipital regions were recurrently recruited. The present study, using a complex spatial imagery task, confirms that the dorsal visual pathway is involved in visuo-spatial imagery in EB subjects in a similar way as in sighted controls. These results indicate further that this pathway can develop efficiently and remain functional in the absence of vision. The neural network involved in visuo-spatial imagery was activated the same way in both groups. However, although the difference between groups did not reach the level of significance, the superior occipital gyrus was activated in the right hemisphere in EB subjects and in the left hemisphere in sighted controls. The interpretation of this observation is limited by the small number of subjects. Notwithstanding this reservation, this slight difference of lateralization could reveal subtle differences in encoding spatial information related to different behavioral strategies in EB and SC groups. The EB subjects used a (X, Y) coded grid as the relevant information; i.e., they encoded each filled-in square of the matrix by its location coordinates. Then, they assessed the symmetry level of the pattern by comparing each (X, Y) coordinates from one side of the axis to the corresponding coordinates on the other side. This strategy appears to be slightly different from the “coordinate strategies” described in relevant articles. Usually, coordinate strategies refer to precise and quantitative spatial metric information in a visual mental image (Kosslyn et al., 1995a) and are known to activate preferentially the right hemisphere whereas the left hemisphere is involved in the encoding of categorial spatial relations (Kosslyn et al., 1993, 1995a). In the present study, the encoding strategy used by EB subjects could hypothetically recruit the right hemisphere preferentially. However, the strategy used by EB subjects looks more abstract than a haptic or visual representation of metric information. It could be also more difficult than the visual strategy used by SC subjects, and this is in accordance with the slightly lower performance

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level in EB compared to SC, although the difference was not significant (see results section). These two aspects could hypothetically favor a preferential activation of the right hemisphere (Parrot et al., 1999). By contrast, sighted controls memorized a visual image of the arrangement of the various squares of the pattern in the grid, encoding categorial spatial relations. This would recruit preferentially occipital areas in the left hemisphere, in accordance with previous studies about image generation (for review, see Farah, 1995). In some brain imaging studies dealing with mental imagery, the control condition required passive listening to the same auditory stimuli as the ones used in the experimental condition but with the instruction that no mental images would be produced (Kosslyn et al., 1995b; D’Esposito et al., 1997). In other studies, the control condition used lists of abstract words (Charlot et al., 1992; Mellet et al., 1996). Our control conditions also included lists of abstract words, in addition to the verbal memory task, to further compare the present work with these latter studies. In the present SC group, similar activation foci were observed as in previous studies (Mellet et al., 1996, 2000), i.e., in superior occipital gyri, superior parietal lobule, and precuneus and premotor cortex. In particular, several studies provided strong and consistent evidence that premotor cortex and parietal areas were coactivated in dynamic visuo-spatial imagery (Mellet et al., 1996; Lamm et al., 2001). Also the middle and superior frontal gyri (BA 6) were found to be activated in working memory tasks requiring to maintain a large load in memory. This activation of BA 6 was attributed to a recruitment of executive processes, whatever the material (verbal or visual) used for the task (Rypma et al., 1999). Surprisingly, this premotor activation was not observed in EB subjects. This unexpected difference with SC subjects remains largely unexplained. Since this difference did only appear in the (MATRIX ⫺ PASSIVE) and (MATRIX ⫺ ACTIVE) contrasts and did not appear when the MEMORY condition was subtracted from the MATRIX task, it could conjecturally be related to differences in working memory abilities, reflected by changes in the neural networks for spatial imagery and spatial working memory. An alternative hypothesis could stand on a lack of dynamic visuo-spatial imagery in EB subjects during the MATRIX task, compared to SC controls, since consistent evidence exists that the human premotor cortex is involved in such processes (Lamm et al., 2001). However, in the absence of specific studies on that topic, both hypotheses remain highly speculative and additional behavioral and functional data are obviously needed before drawing definite conclusions. In the present study, none of the subjects declared to use a verbal strategy to perform the task and accordingly no activation was found in any verbal processing area in the (MATRIX ⫺ MEMORY) contrast. Besides, no verbal processing area was activated when visuo-spatial imagery was compared to either control condition. Therefore, we can conclude that mental spatial processing, rather than verbal

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Fig. 3. Statistical parametric map (SPM{t}) for group comparisons. Left: Interaction (EB ⬎ SC) analysis for the visuo-spatial imagery task relative to verbal memory processing. Brain areas with a larger activation in EB than in SC group are superimposed on the axial, coronal, and sagittal sections of an individual normalized magnetic resonance imaging scan, according to the color scale that codes the T values. This comparison disclosed only a trend (P ⬍ 0.0025, uncorrected) for higher activation in a small region inside the right superior occipital gyrus (BA 19) in EB subjects. Right: Commonly activated brain areas in EB and SC groups, according to conjunction analysis (P ⬍ 0.001, uncorrected). In both groups, visuo-spatial imagery contrasted to verbal memory processing activated a large strip of brain regions encompassing the precuneus and superior parietal lobule bilaterally. EB, early blind subjects; SC, sighted control subjects.

strategies, was used in both groups of subjects and that the observed brain activation was not related to verbal encoding. In the present study, there was no activation observed in the primary visual cortex (BA 17) during the visuo-spatial imagery task in either group. This negative finding must be interpreted with caution, given the low number of subjects in the present study and the high anatomical variability of the calcarine fissure in the human brain. The activation of this brain region in visual mental imagery is debated in neuroimaging studies conducted with sighted subjects. On the one hand, extraction of high resolution details from a pattern in a visual image strongly activates BA 17, especially when involving “object properties” such as shape and texture (Thompson et al., 2001). On the other hand, tasks involving spatial components (i.e., mental imagery of spatial relations between elements) did not recruit primary visual areas (Cohen et al., 1996; Roland and Gulyas, 1994, 1995; Mellet et al., 1995, 1996, 2000; Ghae¨m et al., 1997; Knauff et al., 2000). In accordance with these works, provided confirmation in a larger group, the lack of BA 17 activation in the present study could be attributed to the specificity of the task that included a strong spatial component.

These results suggest that the input from auditory and tactile modalities are capable of promoting efficient functional development of the dorsal visual pathway in the absence of vision. This view receives support from crossmodal plasticity experiments in animal models of early blindness, in whom a reorganization of sensory representations with crossmodal expansion of nonvisual modalities into normally visual brain areas has been demonstrated (Rauschecker, 1995). According to this view, the brain functional organization is considered to be predetermined and reinforced during learning and to be based on appropriate selection of available afferent stimuli. Since our subjects were congenitally deprived of adequate visual stimulation, reciprocal interactions between the other senses, the mental activity, and the association visual cortex must have contributed to the self-organization of these neuroanatomical structures engaged in spatial imagery. In conclusion, the results reported here support our initial hypothesis that visuo-spatial imagery recruits the dorsal route in EB subjects. Indeed, our findings indicate a similar involvement of the precuneus, superior parietal lobule, and superior occipital cortex in both EB and SC subjects. This indicates further a critical role of the dorsal visual pathway in spatial imagery in the early visually deprived subjects.

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Acknowledgments The authors are grateful to the volunteers and to the Oeuvre Nationale des Aveugles (ONA) for their essential collaboration in this study. Thanks are also due to the cyclotron staff, D. Labar and C. Semal for isotope preparation, A. Bol, C. Michel, M. Sibomana, and B. Gerard for informatic assistance, E. Constant and E. Romero for their medical aid, and R. Bausart for technical assistance. A.D.V. is research associate at the Belgian National Funds for Scientific Research. This work was supported by FRSM grant 3.4547.00 to C.V.

Appendix Details of the experimental design are as follows: During the MATRIX task, the subjects mentally built the stimulus from verbal instruction (see materials and methods section). They heard a verbal description of the matrix that was organized line by line and square by square to delimitate a pattern (for the first example displayed on the left side of Fig. 1, the following words were provided to the subject at a regular rhythm of one word each second: first, line–white–white–white–white–white–white, second, line– white– black–white–white–white–white, third, line–white– black– black–white–white–white, fourth, line–white– black– black– black–white–white, fifth, line–white–white– white–white–white–white, sixth, line–white–white–white– white–white–white). Subjects had to memorize this pattern and to maintain it mentally in the grid. After the presentation, they were asked if a given symmetry level (among four possibilities) was present or not, according to one of the two possible symmetry axes. They were requested to answer by yes or no. In the present example, the question was: “Is there a slight symmetry in the pattern, according to the horizontal axis?” In this case the correct answer was “no,” since the pattern was moderately (not slightly) symmetric according to the horizontal axis. However in the same case, the pattern was slightly symmetric according to the vertical axis. Therefore, chance level for correct answer is 25%. During the MEMORY task, subjects had to listen to a sequence of words and to memorize the 9 uttered words (which could be considered as requiring a large attentional and verbal memory load, since the mean working memory span is 7 ⫾ 2, according to main neuropsychology works). For example, in the MEMORY sequence related to the MATRIX example displayed in Fig. 1 and listed above, the following words (actually in French) were provided to the subject at a regular rhythm of one word each second: advantage– duration–thirst–thirst–thirst–thirst–thirst–thirst– discipline– duration–thirst–sense–thirst–thirst–thirst–thirst– injustice – duration–thirst–sense–sense–thirst–thirst–thirst– reasoning– duration–thirst–sense–sense–sense–thirst– thirst– economy– duration–thirst–thirst–thirst–thirst–thirst–

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thirst– guiltlessness– duration–thirst–thirst–thirst–thirst– thirst–thirst. After the sequence, subjects were asked if four different words (for instance, “economy,” “duration,” “sense,” and “ability”) had been presented during this sequence. The answer was provided for each of these four words by mouse clicking (left key ⫽ yes; right key ⫽ no, four trials). Chance level for each correct answer is 50%.

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