Brain Advance Access published online on September 12, 2008
Brain, doi:10.1093/brain/awn213
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Structural and functional correlates of unilateral mesial temporal lobe spatial memory impairment
1Department of Psychology, School of Behavioural Science, The University of Melbourne, 2Department of Neuropsychology, Austin Health and 3Department of Neurosciences, Southern Clinical School, Monash University, Melbourne, Australia
Correspondence to:
Yifat Glikmann-Johnston, Department of Psychology, School of Behavioural Science, The University of Melbourne, Victoria 3010, Australia E-mail: yglikman{at}unimelb.edu.au
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Summary |
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The aim of this study was to explore the effects of preoperative and postoperative lateralized mesial temporal damage on three measures of spatial learning: navigation, object location and plan drawing, and to determine the relationship between volumetry of the hippocampus and memory performance. Fifteen patients with well-characterized unilateral hippocampal sclerosis, 15 patients who had undergone unilateral anterior temporal lobectomy (ATL), and a comparison group consisting of 15 patients with idiopathic generalized epilepsy and 25 neurologically healthy participants explored a novel virtual environment. Volumetric analyses of both hippocampi were conducted on unilateral hippocampal sclerosis and idiopathic generalized epilepsy patients’ T1-weighted magnetic resonance imaging scans. Performance of temporal lobe epilepsy (TLE) patients (either unilateral hippocampal sclerosis or anterior temporal lobectomy) on the different spatial memory variables, namely navigation, object location and plan drawing, was significantly worse relative to the comparison groups (either idiopathic generalized epilepsy or controls). Patients with right TLE did not differ from patients with left TLE on any of the spatial memory measures. An index of absolute hippocampal asymmetry did not correlate with any of the spatial memory measures. Together, our lesion and volumetry findings suggest that the domain of spatial memory is systematically related to the integrity of both right and left mesial temporal lobe, and is unlikely to be a strongly lateralized function. From the standpoint of cerebral organization (lateralization), the notion of material-specificity, which postulates that all components of verbal and spatial memory are lateralized in their entirety to the left and right hemispheres, respectively, requires modification. Instead it would appear that the notion of task-specificity is a more accurate description of patterns of lateralization of spatial memory.
Key Words: spatial memory; hippocampus; material-specificity; epilepsy
Abbreviations: FDG, fluorodeoxyglucose; IGE, idiopathic generalized epilepsy; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single-photon emission computed tomography; TLE, temporal lobe epilepsy; video-EEG, video-electroencephalography.
Received February 19, 2008. Revised July 28, 2008. Accepted August 11, 2008.
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Introduction |
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Milner's notion of material-specificity, in which memory deficits ‘are specifically related to the nature of the stimulus material and vary with the side of the lesion’ (Milner, 1970
, p. 29), was postulated following observations of a milder and less debilitating learning impairment in patients with unilateral temporal resections for the relief of intractable focal seizures, as compared with earlier reports of dense amnesia associated with bilateral mesial temporal pathology (Scoville and Milner, 1957). Material-specificity, in its strongest form (Dobbins et al., 1998), implies a complex double dissociation between the side of the temporal lobe lesion and the material nature (verbal versus visuospatial) of the task. This, however, did not hold in subsequent studies conducted within the verbal domain, and a so-called a ‘weak’ model has emerged (Dobbins et al., 1998). According to this model, lateralization of verbal memory is more complex and differentiated than is implied by the strong material-specificity hypothesis. In particular, the cognitive architecture of verbal memory paradigms has a determining effect on patterns of lateralization (Saling et al., 1993; Baxendale, 1995; Dobbins et al., 1998).
The hemispheric organization of spatial cognition, on the other hand, has yet to be understood. Studies on spatial memory and the right temporal lobe have produced mixed results (e.g. Piguet et al., 1994; Maguire et al., 1998a; Gron et al., 2000; Burgess et al., 2001; Kessels et al., 2002), contradicting prediction of the material-specificity model which expect an association between spatial cognition and the right hemisphere. Equivocal findings have been reported across a wide range of spatial memory tasks in both the pre- and postoperative literature (Table 1), including measures of navigation (Maguire et al., 1996a; Jokeit et al., 2001), maze learning (Milner, 1965; Bohbot et al., 1998; Astur et al., 2002), scene recognition (Maguire and Cipolotti, 1998; Spiers et al., 2001a), plan drawing (Spiers et al., 2001b), abstract design (Piguet et al., 1994; Dige and Wik, 2001) and faces (Hermann et al., 1997; Reminger et al., 2004). Inconsistent findings are evident not only in lesion studies using behavioural or cognitive outcome measures (e.g. Piguet et al., 1994; Spiers et al., 2001b; Astur et al., 2002), but are also a feature of the functional neuroimaging literature of spatial memory (e.g. Aguirre et al., 1996; Maguire et al., 1996b; Jokeit et al., 2001).
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While a bilateral temporal contribution to measures of object location has been documented (Baxendale et al., 1998a
; Incisa della Rocchetta et al., 2004; Kessels et al., 2004; Stepankova et al., 2004), most studies suggest that this ability is right lateralized (Owen et al., 1996; Abrahams et al., 1997, 1999; Bohbot et al., 1998; Johnsrude et al., 1999; Duzel et al., 2003; Piekema et al., 2006). This finding is more robust in studies which include a postoperative sample (Smith and Milner, 1981, 1989; Pigott and Milner, 1993; Nunn et al., 1998; Nunn et al., 1999; Crane and Milner, 2005; Parslow et al., 2005) than in studies with a focus on preoperative cases (Abrahams et al., 1997, 1999; Bohbot et al., 1998), reflecting Milner's initial observation of a ‘heightened’ spatial memory deficit following the removal of the epileptogenic area (Milner, 1958, p. 251). The current literature suggests the following: (i) patterns of lateral specialization in the spatial domain appear to be related to the nature of the task; object location abilities might be more right lateralized than other components of spatial memory investigated to date; (ii) standard anterior temporal lobectomy (ATL), which includes the resection of relatively normal lateral temporal neocortex, appears to heighten the extent of spatial memory impairment relative to that produced by left temporal resection; and (iii) taken together, these findings raise the possibility that lateralization of spatial memory at a mesial temporal level is influenced by task-specific factors, while the addition of neocortical damage worsens right temporal spatial function relative to that mediated by the left temporal lobe.
We studied unoperated and postoperative patients with well-lateralized mesial temporal lobe epilepsy (TLE) with the use of a computerized task that demanded memory function on three levels, navigation through a geometrically conventional environment, acquisition of non-conventional (arbitrary) object-location associations and the ability to transform a remembered egocentric view into an allocentric representation by graphic representation of the learned navigational space. Volumetry of the hippocampus was used to study relationships between mesial temporal asymmetry and components of spatial memory.
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Methods |
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The study was approved by the Human Research Ethics Committee of Austin Health, Melbourne, Australia, and participants were assessed on the basis of informed consent, which was obtained according to the Declaration of Helsinki (BMJ 1991; 302: 1194).
Participants
Thirty TLE patients and a comparison group of 40 participants were studied. The diagnosis of right or left mesial TLE was based on clinical history and ictal semiology on video-electroencephalography (video-EEG) monitoring, magnetic resonance imaging (MRI), interictal positron emission tomography (PET) with fluorodeoxyglucose (FDG), ictal and interictal blood flow single-photon emission computed tomography (SPECT) studies and neuropsychological assessment. Exclusion criteria were a history of cerebral infection or head trauma, extra-temporal MRI abnormalities, Full Scale IQ < 79, and a history of non-epilepsy-related psychiatric disturbance.
The TLE patients consisted of 15 (six with right mesial TLE) who had undergone unilateral ATL 3 months or more prior to the commencement of the study, and 15 presurgical cases (seven with right TLE) who had MRI evidence of unilateral hippocampal atrophy (HIPP). The comparison group consisted of 15 patients with idiopathic generalized epilepsy (IGE) evident on EEG examination, and 25 healthy matched controls with no history of neurological or psychiatric illness. Sample characteristics are shown in Table 2.
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The HIPP and the ATL groups did not differ in terms of general intellectual abilities [t(28) = –0.31, P = 0.76], age [t(28) = 0.26, P = 0.79], gender distribution (Fisher's exact test, P = 1.00) or handedness (Pearson chi-square, P = 0.51). IGE patients were younger than control participants [t(38) = 2.35, P = 0.024], but did not differ on any other matching variables [FSIQ: t(38) = 1.67, P = 0.1; gender: Fisher's exact test, P = 0.53; handedness: Pearson chi-square, P = 0.62]. When comparing each of the TLE groups with each of the comparison groups, there were no significant effects of group (ATL versus controls; ATL versus IGE; HIPP versus controls; HIPP versus IGE) as a function of general intellectual abilities [ATL versus controls: t(38) = –1.63, P = 0.11; ATL versus IGE: t(28) = 0.034, P = 0.97; HIPP versus controls: t(38) = –1.27, P = 0.21; HIPP versus IGE: t(28) = 0.34, P = 0.73], gender distribution (Fisher's exact test: ATL versus controls: P = 0.75; ATL versus IGE: P = 0.47; HIPP versus controls: P = 0.51; HIPP versus IGE: P = 0.3) or handedness (Pearson chi-square: ATL versus controls: P = 0.82; ATL versus IGE: P = 0.59; HIPP versus controls: P = 0.73; HIPP versus IGE: P = 0.54). IGE patients were younger than each of the TLE groups [IGE versus ATL: t(28) = 2.4, P = 0.02; IGE versus HIPP: t(28) = 2.5, P = 0.02], but there were no differences in age between control participants and each of the TLE groups [controls versus ATL: t(38) = 0.33, P = 0.75; controls versus HIPP: t(38) = 0.07, P = 0.94].
Materials
A virtual house provided the environment in which participants were tested. The house was constructed using 3D Studio MAX (Autodesk, Inc.) and Macromedia Director MX version 9.0 (Macromedia Inc.). The house was a square structure comprising eight spaces of varying size (Fig. 2). Each space contained objects located in conventional positions, such as a picture on the wall or a chair at a table. There were also objects positioned in arbitrary locations. These constituted the test objects within the object location memory paradigm. There was a total of 11 test objects. Of these, three were geometric shapes (yellow sphere, pink cylinder and blue rectangle), and eight were common objects (boat, tap, model car, shark, vase, balloon, piano and fire extinguisher). The three shapes appeared a total of 15 times in various locations, and each of the eight common objects appeared in one room only. Window views to the exterior of the house differed according to the cardinal compass points they were oriented towards.
The house was displayed on a PC laptop (Toshiba Tecra S1) with a 15-inch screen. A joystick allowed participants to manoeuvre freely within the house. Manipulation of the joystick included the capacity to start/stop ‘walking’, but not to modify speed of ambulation. Participants were instructed to ‘explore the house until you feel that you are ready to have your memory of the house tested’. In the absence of a ‘ready’ response from the participant, exploration was discontinued after 60 min. Participants were informed that they would be tested on their recall of a route described below and on their memory for object location. Finally, they were asked to draw a floor plan of the house.
Procedure
All participants completed the virtual spatial learning and memory task, and an assessment of FSIQ.
Navigation
At the start of the task, participants were told that there was a dog in the house, and that they were required to find it and remember ‘where’ it was found. A sound of a barking dog was heard during the initial 30 min of exploration, followed by the appearance of the dog under a table in one of the rooms (5 in Fig. 2). Following free exploration, participants were asked to navigate from the entrance of the house to the room in which they found the dog by the ‘most direct route’. The number of spaces traversed to locate the dog was recorded. Time taken to reach the dog was measured.
Object location
To assess memory for object location, participants re-entered the house, traversing a standard examiner prescribed route, but on this occasion the objects positioned in arbitrary locations (test objects) had been removed. A pale-blue three-dimensional transparent box replaced the removed objects (Fig. 1B). All conventionally placed objects (such as tables, chairs and pictures) remained in the house. Prior to re-entry, however, a screen showing the objects appeared. The examiner named the objects on the screen, and then requested participants to recall the missing test objects that had occupied the position now marked by a blue box. One point was allocated for recalling each object in its correct location. The maximum score achievable on this task was 23 points.
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Floor plan drawing
Participants were required to draw a floor plan of the house illustrating its general outline, the spatial relations between the rooms, and their relative dimensions. Scoring was based on qualitative assessment of spatial distortions of the plan. See Fig. 2 for a schematic illustration of the house floor plan and scoring criteria.
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Hippocampal volumetry
Image acquisition
As part of diagnostic process, epilepsy patients had undergone high-resolution three-dimensional T1-weighted MRI scans. Patients consented to incorporate their MRI scan in the study. Overall, 23 MRI scans were obtained: 12 of the HIPP group, and 11 of the IGE group. MRIs were acquired on two 1.5 Tesla clinical scanners: a Signa Horizon Echospeed Superconducting Imaging System and a Signa Excite Echospeed Superconducting Imaging System (General Electric Medical Systems, Milwaukee, WI). The three-dimensional spoiled gradient recalled echo acquisition (3DSPGR) in the Signa Horizon scanner comprised TR 17.7 ms, TE 3.3 ms, TI 300 ms, flip angle 25°, FOV 21 cm, matrix 512 x 512, voxel size = 1.5 mm x 0.4102 mm x 0.4102 mm. The 3DSPGR acquisition in the Signa Excite scanner comprised TR 9.7 ms, TE 4.2 ms, T1 300 ms, flip angle 15°, FOV 25 cm, matrix 256 x 256, voxel size = 1.3 mm x 0.9766 mm x 0.9766 mm.
Image registration
Before image registration, MRIs underwent automated scalp removal using purpose-written software for MATLAB (The Mathworks, Natick, MA). The final scalped image was registered into stereotaxic coordinate space based on the 152-subject T1-weighted average template from the Montreal Neurological Institute, using a nine-parameter linear transformation (rotation, translation and rescaling along the principal axes) and the software package AIR 3.08 (http://bishopw.loni.ucla.edu/AIR3.08/index.html). For three MRIs automated registration produced inaccurate results on visual inspection and manual, landmark-based registration, was performed.
Volumetric analysis
The order of participant images was randomized and identities were unmasked prior to volumetric analysis. Manual segmentation of both hippocampi was performed using interactive mouse-driven software which enabled simultaneous display of coronal, sagittal and axial images. The boundaries of the hippocampus were defined using previously described and validated anatomical landmarks established by Watson et al. (1992). The total volume of each hippocampus was calculated using a voxel-counting algorithm.
Intra-rater reliability of volumetric measurements was determined using three randomly selected MRIs segmented by YG-J on two occasions separated by a 12-month interval. To establish inter-rater reliability, a different rater (KC) measured hippocampal volumes on the same set of three scans. Kappa statistic, given by (2 x intersection volume)/(volume 1 + volume 2) (Zijdenbos et al., 1994), ranged from 0.91 to 0.94 for intra-rater reliability and 0.82–0.88 for inter-rater reliability.
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Results |
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Spatial memory function
Performance of all participants on the different spatial memory variables, namely navigation, object location and floor plan drawing, were significantly correlated. Specifically, efficient navigation was related to an increase in correct recall of arbitrarily related objects and locations (navigation-time versus object location: r = –0.34, P = 0.004; navigation-spaces versus object location: r = –0.27, P = 0.02), and to an accurate floor plan drawing (navigation-time versus plan drawing: r = –0.31, P = 0.008; navigation-spaces versus plan drawing: r = –0.26, P = 0.032). Similarly, a better performance on the object location task was correlated with an increased ability to draw an accurate floor plan of the house (r = 0.63, P = 0.0005).
Group membership had a significant effect on all spatial memory measures [navigation-time: F(3,66) = 4.7, P = 0.005; object location: F(3,66) = 13.04, P = 0.0005; plan drawing: F(3,66) = 4.3, P = 0.008] except on the number of rooms traversed to reach the dog [F(3,66) = 1.8, P = 0.15]. Further analysis revealed that the two TLE groups (namely, HIPP and ATL) did not differ on any of the memory variables [navigation-time: t(28) = –0.92, P = 0.37, F(1,28) = 0.84, P = 0.36; navigation-spaces: t(28) = 0.54, P = 0.59, F(1,28) = 0.29, P = 0.59; object location: t(28) = –1.3, P = 0.21, F(1,28) = 1.68, P = 0.21; plan drawing: t(28) = –0.07, P = 0.95, F(1,28) = 0.005, P = 0.95]. Similarly, no differences were seen between IGE and controls [navigation-time: t(38) = 1.34, P = 0.19, F(1,38) = 1.8, P = 0.19; navigation-spaces: t(38) = –0.71, P = 0.48, F(1,38) = 0.5, P = 0.48; object location: t(38) = 0.38, P = 0.7, F(1,38) = 0.15, P = 0.7; plan drawing: t(38) = –0.25, P = 0.8, F(1,38) = 0.06, P = 0.8]. Each TLE group, however, performed significantly worse relative to each comparison group on the virtual spatial memory tasks. Specifically, HIPP and ATL patients recalled fewer arbitrarily located objects [HIPP versus controls: t(38) = –3.8, P = 0.001, F(1,38) = 14.25, P = 0.001; HIPP versus IGE: t(28) = –2.9, P = 0.008, F(1,28) = 8.27, P = 0.008; ATL versus controls: t(38) = –5.75, P = 0.0005, F(1,38) = 33.03, P = 0.0005; ATL versus IGE: t(28) = –4.5, P = 0.0005, F(1,28) = 20.74, P = 0.0005], and drew a less accurate plan of the house [HIPP versus controls: t(38) = –2.45, P = 0.02, F(1,38) = 5.98, P = 0.02; HIPP versus IGE: t(28) = –2.74, P = 0.01, F(1,28) = 7.5, P = 0.01; ATL versus controls: t(38) = –2.4, P = 0.02, F(1,38) = 5.97, P = 0.02; ATL versus IGE: t(24.3) = –2.7, P = 0.01, F(1,28) = 7.09, P = 0.01] than did the comparison group (see Fig. 3 for examples of floor plan drawings).
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While there were no significant differences between TLE patients and each comparison group on the number of rooms traversed to reach the dog [HIPP versus controls: t(16.1) = 1.4, P = 0.2, F(1,38) = 3.08, P = 0.09; HIPP versus IGE: t(28) = 1.15, P = 0.26, F(1,28) = 1.3, P = 0.26; ATL versus controls: t(14.7) = 1.5, P = 0.16, F(1,38) = 3.6, P = 0.07; ATL versus IGE: t(28) = 1.32, P = 0.2, F(1,28) = 1.74, P = 0.2], TLE patients were less efficient navigators, taking longer to recall the route leading to the dog [HIPP versus controls: t(16.4) = 2.1, P = 0.05, F(1,38) = 6.5, P = 0.01; HIPP versus IGE: t(16.2) = 2.7, P = 0.02, F(1,28) = 7.1, P = 0.01; ATL versus controls: t(38) = 2.08, P = 0.04, F(1,38) = 4.3, P = 0.04; ATL versus IGE: t(21.5) = 2.9, P = 0.009, F(1,28) = 8.3, P = 0.007]. See Table 3 for results summary of TLE and comparison groups.
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Lateralization of spatial memory
One-way analysis of variance (ANOVA) on both TLE groups did not show significant effect of side of the lesion on any of the spatial memory variables [navigation-time: F(3,26) = 0.3, P = 0.83; navigation-spaces: F(3,26) = 0.56, P = 0.65; object location: F(3,26) = 0.63, P = 0.6; plan drawing: F(3,26) = 0.6, P = 0.62]. Further, in each of the TLE groups, patients with a right-sided lesion did not differ from patients with a left-sided lesion on any of the spatial memory measures (Table 4).
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Hippocampal volumetry and spatial memory performance
Right and left hippocampal volumes in cubic millimetres were obtained for the HIPP (n = 12 patients; right TLE = 5) and IGE (n = 11) groups (Table 5). In the HIPP group, reduced hippocampal volume was seen ipsilateral to the seizure focus. The right hippocampus was significantly smaller than the left hippocampus in patients with right TLE [t(4) = –4.8, P = 0.009], and the left hippocampus was significantly smaller than the right hippocampus in patients with left TLE [t(6) = 3.7, P = 0.01]. In the IGE group, right and left hippocampal volumes did not differ significantly [t(10) = 1.3, P = 0.23].
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To explore the relationship between the behavioural measures and hippocampal volumes, an index of absolute volumetric asymmetry given by (|R–L|)/(R + L) x 200 was calculated (Table 5). Spearman's correlations were computed for each of the epilepsy groups separately (HIPP and IGE).
In the HIPP group, hippocampal asymmetry was not associated with any of the spatial memory measures [navigation-time: r = 0.05, P = 0.44; navigation-spaces: r = 0.21, P = 0.25; object location: r = –0.23, P = 0.23; plan drawing: r = –0.07, P = 0.4]. Similarly, in the IGE group, none of the spatial memory variables correlated with hippocampal asymmetry [navigation-time: r = 0.22, P = 0.26; navigation-spaces: r = 0.13, P = 0.35; object location: r = –0.15, P = 0.33; plan drawing: r = –0.2, P = 0.26].
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Discussion |
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Our findings suggest that the ability to navigate, learn and recall arbitrarily related objects and locations, and draw a plan of the environment is systematically related to the integrity of both the right and left mesial temporal lobes in patients with TLE. Temporal lobe damage on either side of the brain reduced the efficiency of navigation by increasing navigation time and impaired performance on the object location and plan drawing tasks. There were no differences in performance between patients with right and left mesial temporal sclerosis, or between these with right or left anterior temporal lobectomies. There was no relationship between hippocampal volume and any aspect of spatial memory. Consistent with the absence of a lateralized lesion effect, hippocampal volume asymmetry did not contribute to spatial memory performances. These findings suggest that spatial memory is dependent on both right and left mesial temporal integrity, and parallel those of previous studies in which patients with unilateral TLE show navigation and plan drawing difficulties, irrespective of the side of the lesion (Maguire et al., 1996a
; Spiers et al., 2001b).
To the best of our knowledge, there are no TLE studies that suggest selective involvement of right temporal structures in navigation or plan drawing. The literature on object location is larger, with some studies showing a right lateralized lesion effect (Smith and Milner, 1981, 1984, 1989; Pigott and Milner, 1993; Abrahams et al., 1997, 1999; Crane and Milner, 2005; Parslow et al., 2005), and others showing no lateralization of the lesion effect on performance (Baxendale et al., 1998a; Incisa della Rocchetta et al., 2004; Kessels et al., 2004; Stepankova et al., 2004).
The present study was based on well-selected patients, with a control for the effects of epilepsy per se in the form of the IGE group, as well as normal controls. The left–right comparison is hampered by small sample sizes, and not surprisingly the probability of type II error is elevated. On the basis of the existing literature, the object location task was the one most expected to reveal a right lateralized effect. It is worth noting that Baxendale et al. (1998a) observed the same pattern of findings as we did, with larger samples. On the basis of the data included in the Baxendale study, power is calculated 0.55. It is also worth noting that the sample sizes in Baxendale's study are larger than those, for example in the study of Abrahams et al. (1999), which reported a lateralized effect on object location memory. This suggests that power is not the sole driver of the null result.
We therefore conclude, with caution, that the case for strong right-sided lateralization of spatial memory at a mesial temporal level is not convincing, although task-specific lateralization cannot be ruled out. When a unilateral lesion effect on spatial memory is found, it is always right sided. In the TLE literature, right lateralized findings apply specifically to the object location paradigm (Smith and Milner, 1981, 1984, 1989; Pigott and Milner, 1993; Abrahams et al., 1997, 1999; Crane and Milner, 2005; Parslow et al., 2005), but not all studies of object location memory show a unilateral effect (Baxendale et al., 1998a; Incisa della Rocchetta et al., 2004; Kessels et al., 2004; Stepankova et al., 2004). This pattern of lateralized and non-lateralized aspects of spatial memory suggests that when lateralization to the right is seen it is determined by task-specific factors, but that the domain as a whole is not a lateralized function. Like findings from the domain of verbal memory, the research on spatial memory suggests that the strong form of material-specificity is not tenable (Dobbins et al., 1998).
It is conceivable that the right and left temporal lobes make different contributions to spatial memory. Some support to this notion comes from Maguire's work on navigation in neurologically healthy participants (Maguire et al., 1998a, 2000a, b). Using PET during navigation-related retrieval tasks in a virtual town, Maguire et al. (1998a) found bilateral hippocampal activation during successful versus unsuccessful trials. Accuracy of navigation, however, was associated with increased blood flow in the right, but not in the left hippocampus. A similar pattern of results was later found in a structural brain imaging study on navigation expertise (Maguire et al., 2000a). Grey matter volumes in right and left hippocampi of London taxi drivers were found to be greater than in age-matched controls, but only right hippocampal volumes were related to the time spent as a taxi driver. While the interpretation of this finding is complex, it raises the question of a relationship between hippocampal cellular organization and navigational abilities, against the background of bi-hippocampal involvement in fundamental spatial function (Maguire et al., 2000b). Maguire (2001) has argued that the left hippocampus might be involved in ‘the processing of particular aspects of the context in which the events, such as navigation, are taking place’ (p. 793).
The absence of an association between the degree of hippocampal atrophy on either side of the brain and measures of spatial memory in our study raises the possibility that this function is not solely dependant on the hippocampus proper, but also reflects the function of other temporal lobe structures affected by TLE. In the neuroimaging literature on navigation, a consistent network of brain regions is found to be active. This extended navigation network includes the hippocampus proper, the parietal lobe, occipitotemporal region, cingulate cortex and parahippocampal cortices (Aguirre et al., 1996, 1998; Maguire, 1997; Maguire et al., 1998b; Jokeit et al., 2001). While entorhinal and perirhinal volume loss is observed in TLE patients ipsilateral to the seizure focus (Bernasconi et al., 2003, 2005), the contribution of these brain regions to human navigation has yet to be explored in patients with mesial temporal sclerosis. Studies of object–place association involving presurgical unilateral TLE patients (Abrahams et al., 1999) and neurologically healthy participants (Owen et al., 1996), reveal a parahippocampal contribution. Our study is the first to explore hippocampal volume loss and the ability to draw a plan of an environment. Although hippocampal volumes did not correlate with plan drawing, the effects of right or left mesial temporal damage implicate this region bilaterally in the task. Considering the complexity of the task, which involves the transformation of a remembered egocentric view to an allocentric representation, it is likely that plan drawing is modulated by the entire hippocampo–parietal system. Support for this view comes from Burgess (2006) who proposed a two-system model in which egocentric representation exists in parallel to allocentric schemata. While the neural underpinnings of this model are not fully understood (Burgess, 2006), a network involving hippocampus, the transentorhinal region, inferior parietal lobule and retrosplenial cortex has been postulated (Byrne et al., 2007).
Spatial memory is fundamental to survival across the phylogenetic spectrum, and has a much longer evolutionary history than does language (Ungerleider et al., 1998). Natural spaces do not have an inherent left–right bias, and symmetrical representation would confer advantages in the spatial domain, which do not apply to abstractly represented and non-spatial systems such as language (Corballis and Beale, 1976, p. 91–93). We suggest that a fundamentally bilateral representation of human spatial memory at a mesial temporal level reflects this long evolutionary trend. This does not preclude the possibility that some components of human spatial memory (such as object location memory) have come to be unilaterally represented such that their integrity is affected by right mesial temporal damage.
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Acknowledgements |
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We thank Associate Professor Bharat Dave’ from the Department of Architecture at The University of Melbourne, Australia for constructing the virtual house.
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References |
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