Original Paper Received: August 30, 2013 Accepted: January 8, 2014 Published online: May 17, 2014
Eur Neurol 2014;72:38–44 DOI: 10.1159/000358511
The Card Placing Test: A New Test for Evaluating the Function of the Retrosplenial and Posterior Cingulate Cortices Ritsuo Hashimoto a Imaharu Nakano b a b
Department of Neurology, International University of Health and Welfare Hospital, Nasushiobara, and Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
Key Words Card Placing Test · Correlation mapping · Heading disorientation · Retrosplenial and posterior cingulate cortices · Single-photon emission tomography
Abstract Background/Aim: We developed a test named the Card Placing Test (CPT), which is potentially useful for evaluating a function of the retrosplenial and posterior cingulate cortices (RSC/PCC). Part A of the test assesses the ability of a subject to retain information on spatial locations of cards placed on the floor around the subject. Part B examines the subject’s ability to integrate information on the spatial locations of similarly arranged cards and information on changes in body direction. The aim of this study is to identify brain regions involved in the CPT performance. Subjects and Methods: Twenty-five subjects were recruited from our memory clinic. We analyzed the correlation between the CPT scores and resting state regional cerebral blood flow (rCBF) determined by single-photon emission tomography. Results: The scores for part A correlated with rCBF in the right inferior parietal lobule. The scores for part B were associated with rCBF in the RSC/PCC. Conclusions: The right inferior parietal lobule seems to play a pivotal role in performing part A of the CPT, whereas the RSC/PCC appears to be involved in accomplishing part B of the CPT. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0722–0038$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
There is growing evidence that the retrosplenial and posterior cingulate cortices (RSC/PCC) in animals and humans play a pivotal role in spatial memory and navigation [1–5]. Indeed, it has been reported that patients with damage involving the RSC/PCC demonstrate a selective deficit in spatial orientation [5–13]. More specifically, such patients can easily recognize familiar landmarks and do not have apparent deficits in representation of the location of objects with respect to the self (preserved egocentric orientation), but are unable to navigate in the environment suggesting that they cannot derive directional information from landmark cues (lost allocentric orientation). They have difficulty navigating in both new and familiar environments. This symptom is known as a type of topographical disorientation, namely ‘heading disorientation (HD)’ [1]. Understanding the mechanism underlying HD will shed light on the function of the RSC/ PCC. In previous studies, patients with HD were usually evaluated by assessing their ability to recognize familiar landmarks, to draw maps of familiar places, and to describe routes [6–8, 11]. Almost all of them showed preserved ability to recognize familiar places, but had great difficulty drawing maps. Interestingly, there is a report of one patient who could draw detailed maps of familiar Ritsuo Hashimoto, MD Department of Neurology, International University of Health and Welfare Hospital 537-3 Iguchi, Nasushiobara, Tochigi (Japan) E-Mail ritsuo @ iuhw.ac.jp
places, but could not depict routes from those maps [13]. Though these findings are very suggestive, the tests used were qualitative in nature and the subjects’ performance is thought to have depended on how much knowledge they had about the routes or maps of the environment before their illness. Recently, we developed a new test named the Card Placing Test (CPT) [14]. The test was designed to evaluate a subject’s ability to coordinate the egocentric with the allocentric spatial reference frame following rotation of the subject. We found that patients with HD following ischemic stroke involving the right RSC/PCC were specifically deficient as to performance of the test [14]. The advantages of the test seem to be that it does not depend on a subject’s premorbid knowledge of the environment, and that it can evaluate quantitatively and directly a subject’s ability to represent visuospatial information either egocentrically or allocentrically. The present study aimed to determine which brain regions are responsible for successful performance of the test.
Subjects and Methods Subjects Subjects were selected from among those who came to the Memory Clinic at the International University of Health and Welfare Hospital between 2006 and 2009. We excluded subjects whose Mini-Mental State Examination (MMSE) scores were 22 points or lower to avoid the possibility that poor achievement of tasks might be due to the subjects’ misunderstanding or inability to comprehend what was required for the tasks. Also excluded were those who had obvious cerebrovascular disease, chronic subdural hematomas, or other focal brain lesions revealed by CT or MRI. Consequently, 25 subjects were recruited for this study. All subjects underwent the following neuropsychological tests: MMSE, digit and tapping forward spans, Trail Making Test parts A (TMT-A) and B (TMT-B), Rey Auditory Verbal Learning Test, and Rey-Osterrieth Complex Figure Test. As for imaging studies, all subjects underwent brain MRI (1.5 T) or brain CT and technetium-99m-L, L-ethyl cysteinate dimer single-photon emission tomography (99mTc-ECD SPECT). Control data were obtained from 17 age-matched healthy volunteers who had no history of cerebrovascular disease, head trauma, epilepsies, or episodes of topographical disorientation. The study was approved by the local ethical committee. Card Placing Test The CPT consists of two parts – A and B. In part A (CPT-A), a subject stands in the center square of a grid of 9 squares (3 × 3) drawn on the floor. The subject is instructed to remember the spatial locations of 3 different cards (a circle, a triangle, and a cross), each of which is randomly placed in 1 of the 8 squares surrounding the subject. After 10 s, all the cards are taken away and the subject is asked to restore them to their original positions. In part B (CPTB), the subject also has to remember the locations of the 3 cards,
Card Placing Test
the positions of the cards being the same as in part A. Immediately after the cards are removed, the subject is rotated to the right or to the left by 90° or 180°, and then asked to replace the cards. For both CPT-A and CPT-B, the subject undergoes 10 consecutive trials. A subject gets 1 point if the location of a card that he/she has replaced is correct. The maximum score for both the CPT-A and CPT-B is 30 points (fig. 1) [14]. SPECT Image Acquisition Each subject underwent resting state cerebral blood flow (CBF) measurement using a Siemens E-CAM scanner with a two-head rotating gamma-camera fitted with low-energy high-resolution collimators. 600-MBq of 99mTc-ECD was administered intravenously while the subject was lying down in a dimly lit room. Images were obtained starting at 10 min following the injection. The data were acquired in a 128 × 128 matrix with 180° rotation at an angle interval of 4°. The projection data were prefiltered through a Butterworth filter, and then reconstructed using a Ramp backprojection filter. Chang’s attenuation correction, but not scattering correction, was applied to the reconstructed images. Correlation Mapping between CPT Scores and Regional CBF First, proportional scaling of the SPECT data was performed to adjust the mean whole brain activity to 50 ml/100 g/min to avoid interindividual variation in global CBF. The data were then standardized with the Montreal Neurological Institute (MNI) atlas. The dimensions of resulting voxels were 2 × 2 × 2 mm. The standardized data were smoothed with a Gaussian filter (full width at half maximum: 12 mm). We analyzed voxel-by-voxel correlations between the test scores and regional CBF (rCBF) of the subjects using Statistical Parametric Mapping 5. Significance and extent thresholds were set at p < 0.01 and 50 voxels, respectively.
Results
Demographic Data for the Subjects The demographic data for the subjects are presented in table 1. In total, their ages ranged from 43 to 84 years (mean ± SD: 69.12 ± 11.1), CPT-A scores from 19 to 30 (26.2 ± 3.1), CPT-B scores from 12 to 30 (19.2 ± 5.4), MMSE scores from 23 to 30 (28.0 ± 1.9), digit forward spans from 4 to 8 (5.9 ± 0.9), tapping forward spans from 4 to 7 (5.8 ± 0.9), times to accomplish TMT-A from 52 to 287 s (141 ± 63) and TMT-B from 62 to 546 s (209 ± 118), Rey Auditory Verbal Learning Test delayed recall from 1 to 14 words (7.4 ± 3.5), and Rey-Osterrieth Complex Figure Test delayed recall from 0 to 24.5 points (17.1 ± 7.0). Correlations between CPT Scores and Other Neuropsychological Tests We investigated the correlations of both the CPT-A and CPT-B scores with the results of other neuropsychological tests. As the CPT-A and CPT-B test scores were not normally distributed (as assessed by KolEur Neurol 2014;72:38–44 DOI: 10.1159/000358511
39
1
2
3
×
4
×
5
×
× 6
×
7
8
9
10
×
× ×
×
×
Fig. 1. Card Placing Test. The figure shows the positions of the 3 cards that were used. The rotation of the subjects in trials 1–10 of part B was as follows: trial 1, 90° to the right; trial 2, 90° to the left; trial 3, 180° to the right; trial 4, 180° to the left; trial 5, 90° to the right; trial 6, 90° to the left; trial 7, 180° to the right; trial 8, 180° to the left; trial 9, 90° to the right, and trial 10, 90° to the left. The numbers indicate the trial number [14].
Table 1. Demographic data for the 25 subjects
Table 2. Correlations between the CPT-A or CPT-B scores and the
results of other neuropsychological tests1
Age, years MMSE Digit span Tapping span CPT-A CPT-B TMT-A, s TMT-B, s RAVLT delayed recall R-O CFT delayed recall
Subjects (n = 25)
Controls (n = 17)
69.2 ± 11.1 28.0 ± 1.9 5.9 ± 1.0 5.6 ± 0.9 26.2 ± 3.1 19.2 ± 5.4 141 ± 63 209 ± 118 7.4 ± 3.5 17.1 ± 7.0
66.0 ± 4.0 28.4 ± 1.6 7.4 ± 1.6 7.8 ± 2.3 28.3 ± 1.8 22.9 ± 2.9 98 ± 15 135 ± 18 10.0 ± 2.3 20.7 ± 6.9
p
1
CPT-A, ρ n.s. (p = 0.21) n.s. (p = 0.43)
Eur Neurol 2014;72:38–44 DOI: 10.1159/000358511
The Card Placing Test: A New Test for Evaluating the Function of the Retrosplenial and Posterior Cingulate Cortices Ritsuo Hashimoto a Imaharu Nakano b a b
Department of Neurology, International University of Health and Welfare Hospital, Nasushiobara, and Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
Key Words Card Placing Test · Correlation mapping · Heading disorientation · Retrosplenial and posterior cingulate cortices · Single-photon emission tomography
Abstract Background/Aim: We developed a test named the Card Placing Test (CPT), which is potentially useful for evaluating a function of the retrosplenial and posterior cingulate cortices (RSC/PCC). Part A of the test assesses the ability of a subject to retain information on spatial locations of cards placed on the floor around the subject. Part B examines the subject’s ability to integrate information on the spatial locations of similarly arranged cards and information on changes in body direction. The aim of this study is to identify brain regions involved in the CPT performance. Subjects and Methods: Twenty-five subjects were recruited from our memory clinic. We analyzed the correlation between the CPT scores and resting state regional cerebral blood flow (rCBF) determined by single-photon emission tomography. Results: The scores for part A correlated with rCBF in the right inferior parietal lobule. The scores for part B were associated with rCBF in the RSC/PCC. Conclusions: The right inferior parietal lobule seems to play a pivotal role in performing part A of the CPT, whereas the RSC/PCC appears to be involved in accomplishing part B of the CPT. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0722–0038$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
There is growing evidence that the retrosplenial and posterior cingulate cortices (RSC/PCC) in animals and humans play a pivotal role in spatial memory and navigation [1–5]. Indeed, it has been reported that patients with damage involving the RSC/PCC demonstrate a selective deficit in spatial orientation [5–13]. More specifically, such patients can easily recognize familiar landmarks and do not have apparent deficits in representation of the location of objects with respect to the self (preserved egocentric orientation), but are unable to navigate in the environment suggesting that they cannot derive directional information from landmark cues (lost allocentric orientation). They have difficulty navigating in both new and familiar environments. This symptom is known as a type of topographical disorientation, namely ‘heading disorientation (HD)’ [1]. Understanding the mechanism underlying HD will shed light on the function of the RSC/ PCC. In previous studies, patients with HD were usually evaluated by assessing their ability to recognize familiar landmarks, to draw maps of familiar places, and to describe routes [6–8, 11]. Almost all of them showed preserved ability to recognize familiar places, but had great difficulty drawing maps. Interestingly, there is a report of one patient who could draw detailed maps of familiar Ritsuo Hashimoto, MD Department of Neurology, International University of Health and Welfare Hospital 537-3 Iguchi, Nasushiobara, Tochigi (Japan) E-Mail ritsuo @ iuhw.ac.jp
places, but could not depict routes from those maps [13]. Though these findings are very suggestive, the tests used were qualitative in nature and the subjects’ performance is thought to have depended on how much knowledge they had about the routes or maps of the environment before their illness. Recently, we developed a new test named the Card Placing Test (CPT) [14]. The test was designed to evaluate a subject’s ability to coordinate the egocentric with the allocentric spatial reference frame following rotation of the subject. We found that patients with HD following ischemic stroke involving the right RSC/PCC were specifically deficient as to performance of the test [14]. The advantages of the test seem to be that it does not depend on a subject’s premorbid knowledge of the environment, and that it can evaluate quantitatively and directly a subject’s ability to represent visuospatial information either egocentrically or allocentrically. The present study aimed to determine which brain regions are responsible for successful performance of the test.
Subjects and Methods Subjects Subjects were selected from among those who came to the Memory Clinic at the International University of Health and Welfare Hospital between 2006 and 2009. We excluded subjects whose Mini-Mental State Examination (MMSE) scores were 22 points or lower to avoid the possibility that poor achievement of tasks might be due to the subjects’ misunderstanding or inability to comprehend what was required for the tasks. Also excluded were those who had obvious cerebrovascular disease, chronic subdural hematomas, or other focal brain lesions revealed by CT or MRI. Consequently, 25 subjects were recruited for this study. All subjects underwent the following neuropsychological tests: MMSE, digit and tapping forward spans, Trail Making Test parts A (TMT-A) and B (TMT-B), Rey Auditory Verbal Learning Test, and Rey-Osterrieth Complex Figure Test. As for imaging studies, all subjects underwent brain MRI (1.5 T) or brain CT and technetium-99m-L, L-ethyl cysteinate dimer single-photon emission tomography (99mTc-ECD SPECT). Control data were obtained from 17 age-matched healthy volunteers who had no history of cerebrovascular disease, head trauma, epilepsies, or episodes of topographical disorientation. The study was approved by the local ethical committee. Card Placing Test The CPT consists of two parts – A and B. In part A (CPT-A), a subject stands in the center square of a grid of 9 squares (3 × 3) drawn on the floor. The subject is instructed to remember the spatial locations of 3 different cards (a circle, a triangle, and a cross), each of which is randomly placed in 1 of the 8 squares surrounding the subject. After 10 s, all the cards are taken away and the subject is asked to restore them to their original positions. In part B (CPTB), the subject also has to remember the locations of the 3 cards,
Card Placing Test
the positions of the cards being the same as in part A. Immediately after the cards are removed, the subject is rotated to the right or to the left by 90° or 180°, and then asked to replace the cards. For both CPT-A and CPT-B, the subject undergoes 10 consecutive trials. A subject gets 1 point if the location of a card that he/she has replaced is correct. The maximum score for both the CPT-A and CPT-B is 30 points (fig. 1) [14]. SPECT Image Acquisition Each subject underwent resting state cerebral blood flow (CBF) measurement using a Siemens E-CAM scanner with a two-head rotating gamma-camera fitted with low-energy high-resolution collimators. 600-MBq of 99mTc-ECD was administered intravenously while the subject was lying down in a dimly lit room. Images were obtained starting at 10 min following the injection. The data were acquired in a 128 × 128 matrix with 180° rotation at an angle interval of 4°. The projection data were prefiltered through a Butterworth filter, and then reconstructed using a Ramp backprojection filter. Chang’s attenuation correction, but not scattering correction, was applied to the reconstructed images. Correlation Mapping between CPT Scores and Regional CBF First, proportional scaling of the SPECT data was performed to adjust the mean whole brain activity to 50 ml/100 g/min to avoid interindividual variation in global CBF. The data were then standardized with the Montreal Neurological Institute (MNI) atlas. The dimensions of resulting voxels were 2 × 2 × 2 mm. The standardized data were smoothed with a Gaussian filter (full width at half maximum: 12 mm). We analyzed voxel-by-voxel correlations between the test scores and regional CBF (rCBF) of the subjects using Statistical Parametric Mapping 5. Significance and extent thresholds were set at p < 0.01 and 50 voxels, respectively.
Results
Demographic Data for the Subjects The demographic data for the subjects are presented in table 1. In total, their ages ranged from 43 to 84 years (mean ± SD: 69.12 ± 11.1), CPT-A scores from 19 to 30 (26.2 ± 3.1), CPT-B scores from 12 to 30 (19.2 ± 5.4), MMSE scores from 23 to 30 (28.0 ± 1.9), digit forward spans from 4 to 8 (5.9 ± 0.9), tapping forward spans from 4 to 7 (5.8 ± 0.9), times to accomplish TMT-A from 52 to 287 s (141 ± 63) and TMT-B from 62 to 546 s (209 ± 118), Rey Auditory Verbal Learning Test delayed recall from 1 to 14 words (7.4 ± 3.5), and Rey-Osterrieth Complex Figure Test delayed recall from 0 to 24.5 points (17.1 ± 7.0). Correlations between CPT Scores and Other Neuropsychological Tests We investigated the correlations of both the CPT-A and CPT-B scores with the results of other neuropsychological tests. As the CPT-A and CPT-B test scores were not normally distributed (as assessed by KolEur Neurol 2014;72:38–44 DOI: 10.1159/000358511
39
1
2
3
×
4
×
5
×
× 6
×
7
8
9
10
×
× ×
×
×
Fig. 1. Card Placing Test. The figure shows the positions of the 3 cards that were used. The rotation of the subjects in trials 1–10 of part B was as follows: trial 1, 90° to the right; trial 2, 90° to the left; trial 3, 180° to the right; trial 4, 180° to the left; trial 5, 90° to the right; trial 6, 90° to the left; trial 7, 180° to the right; trial 8, 180° to the left; trial 9, 90° to the right, and trial 10, 90° to the left. The numbers indicate the trial number [14].
Table 1. Demographic data for the 25 subjects
Table 2. Correlations between the CPT-A or CPT-B scores and the
results of other neuropsychological tests1
Age, years MMSE Digit span Tapping span CPT-A CPT-B TMT-A, s TMT-B, s RAVLT delayed recall R-O CFT delayed recall
Subjects (n = 25)
Controls (n = 17)
69.2 ± 11.1 28.0 ± 1.9 5.9 ± 1.0 5.6 ± 0.9 26.2 ± 3.1 19.2 ± 5.4 141 ± 63 209 ± 118 7.4 ± 3.5 17.1 ± 7.0
66.0 ± 4.0 28.4 ± 1.6 7.4 ± 1.6 7.8 ± 2.3 28.3 ± 1.8 22.9 ± 2.9 98 ± 15 135 ± 18 10.0 ± 2.3 20.7 ± 6.9
p
1
CPT-A, ρ n.s. (p = 0.21) n.s. (p = 0.43)
