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Magnetic resonance image-based cerebellar volumetry in healthy Korean adults
Neuroscience Letters 270 (1999) 149±152
Magnetic resonance image-based cerebellar volumetry in healthy Korean adults Im Joo Rhyu a, b, Tai Hyoung Cho c, Nam Joon Lee d, Chang-Sub Uhm a, b, Hyun Kim a, b, Young-Suk Suh a, b,* a
Institute of Human Genetics, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea b Department of Anatomy, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea c Department of Neurosurgery, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea d Department of Diagnostic Radiology, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea Received 11 February 1999; received in revised form 26 April 1999; accepted 5 June 1999
Abstract The effects of age and gender on cerebellar size have not been established yet. To understand these effects, the area of cerebellar vermis and the volume of cerebellum were measured using serial magnetic resonance images of 124 Korean adults free of neurologic symptoms and signs. Cerebellar volume of male was signi®cantly larger than that of female, although the size of vermis did not show signi®cant gender difference. Correlation analysis revealed that cerebellar volume was not affected by aging. Regressional analysis demonstrated that female vermis had a tendency to shrink after age of 50, whereas male vermis and total cerebellar volume in both sexes were not altered with aging. The different response of vermis with aging and maintenance of cerebellum volume need to be more explored. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Aging; Gender; Magnetic resonance imaging; Morphometry
Brain size is one of the useful parameters describing functional characters of the body. Many morphometric studies of the brain have given us new insights in the ®eld of neuroanatomy and neuropsychiatric diseases [2,3,15]. Recent development of medical imaging techniques such as magnetic resonance imaging (MRI) and computerized tomography enables us to estimate size of different brain structures in vivo. The studies of previous investigators on the changes of cerebellar size according to age showed controversial results. Some studies suggested the decrease of cerebellum size with aging [4,17,18], while other studies reported no signi®cant decrease [5,13]. The effect of gender is also in a state of dispute [5,6,8,9,13,18]. Therefore, the authors analyzed the size of vermis and volume of cerebellum of Korean adults to understand the effect of the aging and gender on cerebellum. The subjects were selected from those who visited the Health Screening Center of Korea University Medical * Corresponding author. Tel.: 182-2-920-6160; fax: 182-2-9295696. E-mail address: [email protected] (Y.-S. Suh)
Center for routine medical evaluation. Some volunteers were recruited by advertisement. All procedures were fully explained to the subjects. Through history taking including alcohol consumption and neurologic examination, the individuals with possible neurologic abnormalities were ruled out. We analyzed neurologically intact brain MRIs of 67 females and 57 males. We decided to use the same protocol which was used for the accumulated MRI data for additional healthy volunteers, to take advantage of the already accumulated subject data. A series of T1-weighted sagittal image (TR/TE: 665/20, two excitations), 5-mm thickness with a 0.3 mm gap between slices and 256 £ 196 matrix were taken with a 1.5-Telsa Magnetom vision (Siemens, Erlangen, Germany). The printed images were captured by Sony XC-77 CCD camera using NIH-image v1.60 freeware (developed at the U.S. National Institute of Health and available on the Internet at http://rsb.info.nih.gov/nih-image/). The vermal area was segmented on the mid-sagittal slice and total cerebellar area appeared on each sagittal slice was segmented with free drawing tools and measured (Fig. 1). Two investigators who have suf®cient neuroanatomical
0304-3940/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 9 9) 00 48 7- 5
150
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
Fig. 1. Captured screen of NIH image 1.60 for MRI ®lms analysis: initially, scale was set according to scale grid and NIH image menu (A,B). Segmentation of the region of interest (midsagittal vermis and total cerebellum slice) (C) was done with free drawing tool and the segmented area was measured (D).
knowledge measured the region of interest and average volume from two sample measurements was analyzed. Total cerebellar volume was calculated from summation of cerebellar volume in each slice obtained by the multiplication of area by 0.53 cm (sum of slice thickness and interslice gap). To check validity of this estimation method, cerebellar volume of three cadavers was estimated with this experimental procedure and measured with classical volume replacement method using scaled mass cylinder. The estimated volume of cerebella based on MRI ®lms was slightly larger than the actual size (MRI estimated volume: water replaced volume 1.03:1, data not shown). Statistical analyses were performed with SAS-PC (SAS Institute, Cary, USA). The age distribution and gender of the subjects are listed in Table 1. The average vermal area was 10:87 ^ 1:40 cm 2 in female, and 11:29 ^ 1:63 cm 2 in male. The cerebellar volume was 115:38 ^ 11:29 cm 3 in female and 126:01 ^ 10:38 cm 3 in male, which was slightly larger than the result reported by Escalona et al. [5] (104 ^ 10 cm 3 in female and
122 ^ 16 cm 3 in male), smaller than the result of Filipek et al. [6] (134:6 ^ 6:8 cm 3 in female and 152:2 ^ 10:5 cm 3 in male). It is not clear that this discrepancy means racial difference or is due to the variation resulting from different scanning protocols and measuring methods used. Statistical analysis revealed that cerebellar volume of males was bigger signi®cantly (P , 0:05) than that of females. Our results corroborate most of previous reports [5,6,8,18], except for the result of Luft et al. [13]. Luft et al. [13] reported that there was no gender difference in cerebellar volume when the volume was corrected by intracranial volume. Interestingly the area of vermis of both sexes was not statistically different. This may suggest that the gender difference of cerebellar volume is mainly due to the difference of cerebellar hemisphere. This point needs to be further explored. Correlation analysis of age versus vermal area of cerebellum (Pearson Correlation Coef®cients (R) 20.071, P . 0:05) and volume of cerebellum (R 20:020, P . 0:05) revealed that cerebellar size did not correlate with aging signi®cantly (Figs. 2 and 3). This result agrees with the reports of Escalona et al. [5] and Luft et al. [13] but contradicts some of the previous reports [11,17,18]. Regressional curves with quadratic model of the vermal area versus age showed a tendency to be shrunken after age of 50. Atrophy of female, but not male, vermis with aging was statistically signi®cant (female: R2 0:158, P 0:004 , 0:05; male R2 0:060, P 0:187 . 0:05). However the quadratic curve of male vermis with aging looks quite similar to that of female vermis area, which warrants further investigation (Fig. 2). In case of cerebellar volume in both gender, we could not ®nd reasonable models demonstrating relation between age and cerebellar volume (Fig. 3). This different response of cerebellar volume and vermis area with aging and gender is matched with recent reports of Luft et al. [12] and is in contrast to data of Raz et al. [17], who reported shrinkage of cerebellar hemisphere. This con¯ict might be reconciled in the future, if we can overcome differences in the methods of investigation and the variability in cerebellar shrinkage among the subjects. Although it is not clear why the female vermis showed more pronounced atrophy with aging, there
Table 1 Distribution of vermis area (unit: cm 2) and cerebellar volume (unit: cm 3) according to age and sex Age
Female
Male
Number
Vermis
Volume
Number
Vermis
Volume
20±29 30±39 40±49 50±59 60±69 70±79
11 9 13 10 12 12
12.5 ^ 1.7 11.5 ^ 0.7 11.7 ^ 1.3 12.0 ^ 1.2 10.2 ^ 1.2 10.3 ^ 1.1
116.6 ^ 10.3 112.7 ^ 10.7 111.7 ^ 12.8 117.1 ^ 6.1 114.6 ^ 7.2 120.0 ^ 13.8
9 10 10 10 11 7
11.2 ^ 0.9 10.0 ^ 1.7 11.9 ^ 1.7 11.6 ^ 1.6 11.9 ^ 1.8 9.6 ^ 1.4
132.1 ^ 6.8 123.6 ^ 10.9 123.1 ^ 10.3 124.9 ^ 9.7 130.5 ^ 11.0 120.4 ^ 11.7
Total
67
10.9 ^ 1.4
115.4 ^ 11.3
57
11.3 ^ 1.6
126.0 ^ 10.4
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
151
treated with estrogen replacement after menopause [14], and (ii) estrogen therapy improved the cognitive function in some women suffered from Alzheimer's disease [7]. The precise causes why only female vermis area atrophy significantly at old age needs to be further investigated. This data might be used for a valuable reference for various comparison study of cerebellar size in many physiological [19], pathological conditions [10,16], and in different races.
Fig. 2. Cerebellar vermis area plotted against age: There is no gender difference (Student's t-test: P . 0:05). The solid line (male) and dotted line (female) represent quatratic regression of the vermis on age(female R 2 0:158, P , 0:05; male R 2 0:060, P . 0:05). The dark circle represents male and open circle represents female.
are some supportive reports for explaining this sexual dimorphic phenomenon [1,20], which might be attributed to estrogen change in old age: (i) more vulnerable neurodegenerative change was observed in the female who was not
Fig. 3. Scatterplot demonstrating the relationship between cerebellar volume and aging. The volume of male cerebellum is bigger than that of female (Student's t-test: P , 0:05). The solid line (male) and dotted line (female) represent quatratic regression of the cerebellar volume on age (female R 2 0:037, P . 0:05; male R 2 0:017, P . 0:05). The dark circle represents male and open circle represents female.
[1] Allen, L.S., Richey, M.F., Chai, Y.M. and Gorski, R.A., Sex differences in the corpus callosum of the living human being. J. Neurosci., 11 (1991) 933±942. [2] Aylward, E.H., Reiss, A., Barta, P.E., Tien, A., Han, W., Lee, J. and Pearlson, G.D., Magnetic resonance imaging measurement of posterior fossa structures in schizophrenia. Am. J. Psychiatry, 151 (1994) 1448±1452. [3] Coffey, C.E., Wilkinson, W.E., Parashos, I.A., Soady, S.A., Sullivan, R.J., Patterson, L.J., Figiel, G.S., Webb, M.C., Spritzer, C.E. and Djang, W.T., Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging. Neurology, 42 (1992) 527±536. [4] Ellis, R., Norms for some structural changes in the human cerebellum from birth to old age. J. Comp. Neurol., 32 (1920) 1±35. [5] Escalona, P.R., McDonald, W.M., Doraiswamy, P.M., Boyko, O.B., Husain, M.M., Figiel, S.G., Laskowitz, D., Ellinwood, D.E. and Krishnan, K.R., In vivo stereological assessment of human cerebellar volume: effects of gender and age. Am. J. Neuroradiol., 12 (1991) 927±929. [6] Filipek, P.A., Richelme, C., Kennedy, D.N. and Caviness Jr, V.S., The young adult human brain: an MRI-based morphometric analysis. Cereb. Cortex, 4 (1994) 344±360. [7] Fillit, H., Weinreb, H., Cholst, I., Luine, V., McEwen, B., Amador, R. and Zabriskie, J., Observations in a preliminary open trial of estradiol therapy for senile dementia ± Alzheimer's type. Psychoneuroendocrinology, 11 (1986) 337±345. [8] Hayakawa, K., Konishi, Y., Matsuda, T., Kuriyama, M., Konishi, K., Yamashita, K., Okumura, R. and Hamanaka, D., Development and aging of brain midline structures: assessment with MR imaging. Radiology, 172 (1989) 171± 177. [9] Henery, C.C. and Mayhew, T.M., The cerebrum and cerebellum of the ®xed brain: ef®cient and unbiased estimates of volumes and cortical surface areas. J. Anat., 167 (1989) 167± 180. [10] Jacobsen, L.K., Giedd, J.N., Berquin, P.C., Krain, A.L., Hamburger, S.D., Kumra, S. and Rapoport, J.L., Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia. Am. J. Psychiatry, 154 (1997) 1663±1669. [11] Koller, W.C., Glatt, S.L., Fox, J.H., Kaszniak, A.W., Wilson, R.S. and Huckman, M.S., Cerebellar atrophy: relationship to aging and cerebral atrophy. Neurology, 31 (1981) 1486± 1488. [12] Luft, A.R., Skalej, M., Welte, D., Kolb, R., Burk, K., Schulz, J.B., Klockgether, T. and Voigt, K., A new semiautomated, three-dimensional technique allowing precise quanti®cation of total and regional cerebellar volume using MRI. Magn. Reson. Med., 40 (1998) 143±151. [13] Luft, A.R., Skalej, M., Welte, D., Voigt, K. and Klockgether, T., Age and sex do not affect cerebellar volume in humans. Am. J. Neuroradiol., 18 (1997) 593±596.
152
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
[14] Meyer, J.S., Terayama, Y., Konno, S., Akiyama, H., Margishvili, G.M. and Mortel, K.F., Risk factors for cerebral degenerative changes and dementia. Eur. Neurol., 39 (Suppl. 1) (1998) 7±16. [15] O'Sullivan, R.L., Rauch, S.L., Breiter, H.C., Grachev, I.D., Baer, L., Kennedy, D.N., Keuthen, N.J., Savage, C.R., Manzo, P.A., Caviness, V.S. and Jenike, M.A., Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging. Biol. Psychiatry, 42 (1997) 39±45. [16] Piven, J., Saliba, K., Bailey, J. and Arndt, S., An MRI study of autism: the cerebellum revisited. Neurology, 49 (1997) 546± 551.
[17] Raz, N., Dupuis, J.H., Briggs, S.D., McGavran, C. and Acker, J.D., Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study. Am. J. Neuroradiol., 19 (1998) 65±71. [18] Raz, N., Torres, I.J., Spencer, W.A., White, K. and Acker, J.D., Age-related regional differences in cerebellar vermis observed in vivo. Arch. Neurol., 149 (1992) 414±416. [19] Schlaug, G., Lee, L.H.L., Thangraj, V., Edelman, R.R. and Warach, S., Macrostructural adaptation of the cerebellum in musicians. Soc. Neurosci. Abstr., 24 (1998) 2118 (S842.7). [20] Salat, D., Ward, A., Kaye, J.A. and Janowsky, J.S., Sex differences in the corpus callosum with aging. Neurobiol. Aging, 18 (1997) 191±197.
Magnetic resonance image-based cerebellar volumetry in healthy Korean adults Im Joo Rhyu a, b, Tai Hyoung Cho c, Nam Joon Lee d, Chang-Sub Uhm a, b, Hyun Kim a, b, Young-Suk Suh a, b,* a
Institute of Human Genetics, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea b Department of Anatomy, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea c Department of Neurosurgery, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea d Department of Diagnostic Radiology, Korea University College of Medicine, 126±1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul, 136±705 South Korea Received 11 February 1999; received in revised form 26 April 1999; accepted 5 June 1999
Abstract The effects of age and gender on cerebellar size have not been established yet. To understand these effects, the area of cerebellar vermis and the volume of cerebellum were measured using serial magnetic resonance images of 124 Korean adults free of neurologic symptoms and signs. Cerebellar volume of male was signi®cantly larger than that of female, although the size of vermis did not show signi®cant gender difference. Correlation analysis revealed that cerebellar volume was not affected by aging. Regressional analysis demonstrated that female vermis had a tendency to shrink after age of 50, whereas male vermis and total cerebellar volume in both sexes were not altered with aging. The different response of vermis with aging and maintenance of cerebellum volume need to be more explored. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Aging; Gender; Magnetic resonance imaging; Morphometry
Brain size is one of the useful parameters describing functional characters of the body. Many morphometric studies of the brain have given us new insights in the ®eld of neuroanatomy and neuropsychiatric diseases [2,3,15]. Recent development of medical imaging techniques such as magnetic resonance imaging (MRI) and computerized tomography enables us to estimate size of different brain structures in vivo. The studies of previous investigators on the changes of cerebellar size according to age showed controversial results. Some studies suggested the decrease of cerebellum size with aging [4,17,18], while other studies reported no signi®cant decrease [5,13]. The effect of gender is also in a state of dispute [5,6,8,9,13,18]. Therefore, the authors analyzed the size of vermis and volume of cerebellum of Korean adults to understand the effect of the aging and gender on cerebellum. The subjects were selected from those who visited the Health Screening Center of Korea University Medical * Corresponding author. Tel.: 182-2-920-6160; fax: 182-2-9295696. E-mail address: [email protected] (Y.-S. Suh)
Center for routine medical evaluation. Some volunteers were recruited by advertisement. All procedures were fully explained to the subjects. Through history taking including alcohol consumption and neurologic examination, the individuals with possible neurologic abnormalities were ruled out. We analyzed neurologically intact brain MRIs of 67 females and 57 males. We decided to use the same protocol which was used for the accumulated MRI data for additional healthy volunteers, to take advantage of the already accumulated subject data. A series of T1-weighted sagittal image (TR/TE: 665/20, two excitations), 5-mm thickness with a 0.3 mm gap between slices and 256 £ 196 matrix were taken with a 1.5-Telsa Magnetom vision (Siemens, Erlangen, Germany). The printed images were captured by Sony XC-77 CCD camera using NIH-image v1.60 freeware (developed at the U.S. National Institute of Health and available on the Internet at http://rsb.info.nih.gov/nih-image/). The vermal area was segmented on the mid-sagittal slice and total cerebellar area appeared on each sagittal slice was segmented with free drawing tools and measured (Fig. 1). Two investigators who have suf®cient neuroanatomical
0304-3940/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 9 9) 00 48 7- 5
150
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
Fig. 1. Captured screen of NIH image 1.60 for MRI ®lms analysis: initially, scale was set according to scale grid and NIH image menu (A,B). Segmentation of the region of interest (midsagittal vermis and total cerebellum slice) (C) was done with free drawing tool and the segmented area was measured (D).
knowledge measured the region of interest and average volume from two sample measurements was analyzed. Total cerebellar volume was calculated from summation of cerebellar volume in each slice obtained by the multiplication of area by 0.53 cm (sum of slice thickness and interslice gap). To check validity of this estimation method, cerebellar volume of three cadavers was estimated with this experimental procedure and measured with classical volume replacement method using scaled mass cylinder. The estimated volume of cerebella based on MRI ®lms was slightly larger than the actual size (MRI estimated volume: water replaced volume 1.03:1, data not shown). Statistical analyses were performed with SAS-PC (SAS Institute, Cary, USA). The age distribution and gender of the subjects are listed in Table 1. The average vermal area was 10:87 ^ 1:40 cm 2 in female, and 11:29 ^ 1:63 cm 2 in male. The cerebellar volume was 115:38 ^ 11:29 cm 3 in female and 126:01 ^ 10:38 cm 3 in male, which was slightly larger than the result reported by Escalona et al. [5] (104 ^ 10 cm 3 in female and
122 ^ 16 cm 3 in male), smaller than the result of Filipek et al. [6] (134:6 ^ 6:8 cm 3 in female and 152:2 ^ 10:5 cm 3 in male). It is not clear that this discrepancy means racial difference or is due to the variation resulting from different scanning protocols and measuring methods used. Statistical analysis revealed that cerebellar volume of males was bigger signi®cantly (P , 0:05) than that of females. Our results corroborate most of previous reports [5,6,8,18], except for the result of Luft et al. [13]. Luft et al. [13] reported that there was no gender difference in cerebellar volume when the volume was corrected by intracranial volume. Interestingly the area of vermis of both sexes was not statistically different. This may suggest that the gender difference of cerebellar volume is mainly due to the difference of cerebellar hemisphere. This point needs to be further explored. Correlation analysis of age versus vermal area of cerebellum (Pearson Correlation Coef®cients (R) 20.071, P . 0:05) and volume of cerebellum (R 20:020, P . 0:05) revealed that cerebellar size did not correlate with aging signi®cantly (Figs. 2 and 3). This result agrees with the reports of Escalona et al. [5] and Luft et al. [13] but contradicts some of the previous reports [11,17,18]. Regressional curves with quadratic model of the vermal area versus age showed a tendency to be shrunken after age of 50. Atrophy of female, but not male, vermis with aging was statistically signi®cant (female: R2 0:158, P 0:004 , 0:05; male R2 0:060, P 0:187 . 0:05). However the quadratic curve of male vermis with aging looks quite similar to that of female vermis area, which warrants further investigation (Fig. 2). In case of cerebellar volume in both gender, we could not ®nd reasonable models demonstrating relation between age and cerebellar volume (Fig. 3). This different response of cerebellar volume and vermis area with aging and gender is matched with recent reports of Luft et al. [12] and is in contrast to data of Raz et al. [17], who reported shrinkage of cerebellar hemisphere. This con¯ict might be reconciled in the future, if we can overcome differences in the methods of investigation and the variability in cerebellar shrinkage among the subjects. Although it is not clear why the female vermis showed more pronounced atrophy with aging, there
Table 1 Distribution of vermis area (unit: cm 2) and cerebellar volume (unit: cm 3) according to age and sex Age
Female
Male
Number
Vermis
Volume
Number
Vermis
Volume
20±29 30±39 40±49 50±59 60±69 70±79
11 9 13 10 12 12
12.5 ^ 1.7 11.5 ^ 0.7 11.7 ^ 1.3 12.0 ^ 1.2 10.2 ^ 1.2 10.3 ^ 1.1
116.6 ^ 10.3 112.7 ^ 10.7 111.7 ^ 12.8 117.1 ^ 6.1 114.6 ^ 7.2 120.0 ^ 13.8
9 10 10 10 11 7
11.2 ^ 0.9 10.0 ^ 1.7 11.9 ^ 1.7 11.6 ^ 1.6 11.9 ^ 1.8 9.6 ^ 1.4
132.1 ^ 6.8 123.6 ^ 10.9 123.1 ^ 10.3 124.9 ^ 9.7 130.5 ^ 11.0 120.4 ^ 11.7
Total
67
10.9 ^ 1.4
115.4 ^ 11.3
57
11.3 ^ 1.6
126.0 ^ 10.4
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
151
treated with estrogen replacement after menopause [14], and (ii) estrogen therapy improved the cognitive function in some women suffered from Alzheimer's disease [7]. The precise causes why only female vermis area atrophy significantly at old age needs to be further investigated. This data might be used for a valuable reference for various comparison study of cerebellar size in many physiological [19], pathological conditions [10,16], and in different races.
Fig. 2. Cerebellar vermis area plotted against age: There is no gender difference (Student's t-test: P . 0:05). The solid line (male) and dotted line (female) represent quatratic regression of the vermis on age(female R 2 0:158, P , 0:05; male R 2 0:060, P . 0:05). The dark circle represents male and open circle represents female.
are some supportive reports for explaining this sexual dimorphic phenomenon [1,20], which might be attributed to estrogen change in old age: (i) more vulnerable neurodegenerative change was observed in the female who was not
Fig. 3. Scatterplot demonstrating the relationship between cerebellar volume and aging. The volume of male cerebellum is bigger than that of female (Student's t-test: P , 0:05). The solid line (male) and dotted line (female) represent quatratic regression of the cerebellar volume on age (female R 2 0:037, P . 0:05; male R 2 0:017, P . 0:05). The dark circle represents male and open circle represents female.
[1] Allen, L.S., Richey, M.F., Chai, Y.M. and Gorski, R.A., Sex differences in the corpus callosum of the living human being. J. Neurosci., 11 (1991) 933±942. [2] Aylward, E.H., Reiss, A., Barta, P.E., Tien, A., Han, W., Lee, J. and Pearlson, G.D., Magnetic resonance imaging measurement of posterior fossa structures in schizophrenia. Am. J. Psychiatry, 151 (1994) 1448±1452. [3] Coffey, C.E., Wilkinson, W.E., Parashos, I.A., Soady, S.A., Sullivan, R.J., Patterson, L.J., Figiel, G.S., Webb, M.C., Spritzer, C.E. and Djang, W.T., Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging. Neurology, 42 (1992) 527±536. [4] Ellis, R., Norms for some structural changes in the human cerebellum from birth to old age. J. Comp. Neurol., 32 (1920) 1±35. [5] Escalona, P.R., McDonald, W.M., Doraiswamy, P.M., Boyko, O.B., Husain, M.M., Figiel, S.G., Laskowitz, D., Ellinwood, D.E. and Krishnan, K.R., In vivo stereological assessment of human cerebellar volume: effects of gender and age. Am. J. Neuroradiol., 12 (1991) 927±929. [6] Filipek, P.A., Richelme, C., Kennedy, D.N. and Caviness Jr, V.S., The young adult human brain: an MRI-based morphometric analysis. Cereb. Cortex, 4 (1994) 344±360. [7] Fillit, H., Weinreb, H., Cholst, I., Luine, V., McEwen, B., Amador, R. and Zabriskie, J., Observations in a preliminary open trial of estradiol therapy for senile dementia ± Alzheimer's type. Psychoneuroendocrinology, 11 (1986) 337±345. [8] Hayakawa, K., Konishi, Y., Matsuda, T., Kuriyama, M., Konishi, K., Yamashita, K., Okumura, R. and Hamanaka, D., Development and aging of brain midline structures: assessment with MR imaging. Radiology, 172 (1989) 171± 177. [9] Henery, C.C. and Mayhew, T.M., The cerebrum and cerebellum of the ®xed brain: ef®cient and unbiased estimates of volumes and cortical surface areas. J. Anat., 167 (1989) 167± 180. [10] Jacobsen, L.K., Giedd, J.N., Berquin, P.C., Krain, A.L., Hamburger, S.D., Kumra, S. and Rapoport, J.L., Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia. Am. J. Psychiatry, 154 (1997) 1663±1669. [11] Koller, W.C., Glatt, S.L., Fox, J.H., Kaszniak, A.W., Wilson, R.S. and Huckman, M.S., Cerebellar atrophy: relationship to aging and cerebral atrophy. Neurology, 31 (1981) 1486± 1488. [12] Luft, A.R., Skalej, M., Welte, D., Kolb, R., Burk, K., Schulz, J.B., Klockgether, T. and Voigt, K., A new semiautomated, three-dimensional technique allowing precise quanti®cation of total and regional cerebellar volume using MRI. Magn. Reson. Med., 40 (1998) 143±151. [13] Luft, A.R., Skalej, M., Welte, D., Voigt, K. and Klockgether, T., Age and sex do not affect cerebellar volume in humans. Am. J. Neuroradiol., 18 (1997) 593±596.
152
I.J. Rhyu et al. / Neuroscience Letters 270 (1999) 149±152
[14] Meyer, J.S., Terayama, Y., Konno, S., Akiyama, H., Margishvili, G.M. and Mortel, K.F., Risk factors for cerebral degenerative changes and dementia. Eur. Neurol., 39 (Suppl. 1) (1998) 7±16. [15] O'Sullivan, R.L., Rauch, S.L., Breiter, H.C., Grachev, I.D., Baer, L., Kennedy, D.N., Keuthen, N.J., Savage, C.R., Manzo, P.A., Caviness, V.S. and Jenike, M.A., Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging. Biol. Psychiatry, 42 (1997) 39±45. [16] Piven, J., Saliba, K., Bailey, J. and Arndt, S., An MRI study of autism: the cerebellum revisited. Neurology, 49 (1997) 546± 551.
[17] Raz, N., Dupuis, J.H., Briggs, S.D., McGavran, C. and Acker, J.D., Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study. Am. J. Neuroradiol., 19 (1998) 65±71. [18] Raz, N., Torres, I.J., Spencer, W.A., White, K. and Acker, J.D., Age-related regional differences in cerebellar vermis observed in vivo. Arch. Neurol., 149 (1992) 414±416. [19] Schlaug, G., Lee, L.H.L., Thangraj, V., Edelman, R.R. and Warach, S., Macrostructural adaptation of the cerebellum in musicians. Soc. Neurosci. Abstr., 24 (1998) 2118 (S842.7). [20] Salat, D., Ward, A., Kaye, J.A. and Janowsky, J.S., Sex differences in the corpus callosum with aging. Neurobiol. Aging, 18 (1997) 191±197.