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Memory Performance and Normalized Regional Brain Volumes in Patients with Pediatric-Onset Multiple Sclerosis

  • Amanda Fuentes (a1), Donald Louis Collins (a2), Daniel Garcia-Lorenzo (a2), John G. Sled (a3), Sridar Narayanan (a2), Douglas L. Arnold (a2), Brenda L. Banwell (a3) (a4) and Christine Till (a1) (a3)...


Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls. Memory performance was correlated with volumetric measures of the whole brain, hippocampus, amygdala, and thalamus. Brain volumes were normalized for age and sex using magnetic resonance imaging (MRI) data from the National Institutes of Health MRI Study of Normal Brain development. With the exception of story recall, performance on memory tests was similar to that of the control group. Relative to controls, patient with MS showed reduced volume in the whole brain (p < .001), amygdala (p < .005), and thalamus (p < .001), but not the hippocampus. In the patient group, word-list learning correlated with whole brain volume (r = .53) and hippocampal volume (r = .43), whereas visual recognition memory correlated with thalamic volume (r = .48). Findings are consistent with the well-established role of the hippocampus in learning and consolidation and also highlight the importance of diffuse brain pathology on memory function. (JINS, 2012, 18, 471–480)


Corresponding author

Correspondence and reprint requests to: Christine Till, Department of Psychology, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3. E-mail:


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Amato, M.P., Goretti, B., Ghezzi, A., Lori, S., Zipoli, V., Portaccio, E., Trojano, M. (2008). Cognitive and psychosocial features of childhood and juvenile MS. Neurology, 70, 18911897.
Anderson, V.M., Fisniku, L.K., Khaleeli, Z., Summers, M.M., Penny, S.A., Altman, D.R., Miller, D.H. (2010). Hippocampal atrophy in relapsing-remitting and primary progressive MS: A comparative study. Multiple Sclerosis, 16, 10831090.
Aubert-Broche, B., Fonov, V., Ghassemi, R., Narayanan, S., Arnold, D.L., Banwell, B., Collins, D.L. (2011). Regional brain atrophy in children with multiple sclerosis. Neuroimage, 58(2), 409415.
Banwell, B.L., Anderson, P.E. (2005). The cognitive burden of multiple sclerosis in children. Neurology, 64, 891894.
Benedict, R.H.B., Ramsamy, D., Munshauer, F., Weinstock-Guttman, B., Zivadinov, R. (2009). Memory impairment in multiple sclerosis: Correlation with deep grey matter and mesial temporal atrophy. Journal of Neurology, Neurosurgery, and Psychiatry, 80, 201206.
Collins, D.L., Holmes, T.M., Peters, T.M., Evans, A.C. (1995). Automatic 3D model-based neuroanatomical segmentation. Human Brain Mapping, 3(3), 190208.
Collins, D.L., Neelin, P., Peters, T.M., Evans, A.C. (1994). Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. Journal of Computer Assisted Tomography, 18(2), 192205.
Collins, D.L., Pruessner, J.C. (2010). Towards accurate, automatic segmentation of the hippocampus and amygdala from MRI by augmenting ANIMAL with a template library and label fusion. Neuroimage, 52, 1355.
Cowan, N., Wood, N., Keller, T., Nugent, L.D., Keller, C.V. (1998). Two separate verbal processing rates contributing to short-term memory span. Journal of Experimental Psychology: General, 127, 141160.
de Haan, M., Mishkin, M., Baldeweg, T., Vargha-Khadem, F. (2006). Human memory development and its dysfunction after early hippocampal injury. Trends in Neurosciences, 29, 374381.
Fonov, V., Evans, A.C., Botteron, K., Almli, C.R., McKinstry, R.C., Collins, L. (2011). Unbiased average age-appropriate atlases for pediatric studies. Neuroimage, 54(1), 313327.
Fritsch, T., Larsen, J.D., Smyth, K.A. (2007). The role of adolescent IQ and gender in the use of cognitive support for remembering in aging. Aging, Neuropsychology, and Cognition, 14, 394416.
Geurts, J.J., Bo, L., Roosendaal, S.D., Hazes, T., Daniels, R., Barkhof, F., van der Valk, P. (2007). Extensive hippocampal demyelination in multiple sclerosis. Journal of Neuropathology and Experimental Neurology, 66(9), 819827.
Geurts, J.J., Reuling, I.E., Vrenken, H., Uitdehaag, B.M., Polman, C.H., Castelijns, J.A., Pouwels, P.J. (2006). MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magnetic Resonance in Medicine, 55(3), 478483.
Greenstein, Y., Blachstein, H., Vakil, E. (2010). Interrelations between attention and verbal memory is affected by developmental age. Child Neuropsychology, 16, 4259.
Haist, F., Shimamura, A.P., Squire, L.R. (1992). On the relationship between recall and recognition memory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 18, 691702.
Holm, S. (1977). A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics, 6, 6570.
Janowsky, J.S., Shimamura, A.P., Kritchevsky, M., Squire, L.R. (1989). Cognitive impairment following frontal lobe damage and its relevance to human amnesia. Behavioral Neuroscience, 103, 548560.
Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology, 33, 14441452.
MacAllister, W.S., Belman, A.L., Milazzo, M., Weisbrot, D.M., Christodoulou, C., Scherl, W.F., Krupp, L.B. (2005). Cognitive functioning in children and adolescents with multiple sclerosis. Neurology, 64, 14221425.
Nocentini, U., Pasqualetti, P., Bonavita, S., Buccafusca, M., De Caro, M.F., Farina, D., Caltagirone, C. (2006). Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis. Multiple Sclerosis, 12, 7787.
Olivares, T., Sanchez, M.P., Wollmann, T., Hernandez, M.A., Barroso, J. (2005). Pattern of neuropsychological impairment in early phases of relapsing-remitting multiple sclerosis. Multiple Sclerosis, 11, 191197.
Papadopoulos, D., Sumayya, D., Patel, R., Nicholas, R., Vora, A., Reynolds, R. (2009). Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis. Brain Pathology, 19, 238253.
Paulesu, E., Perani, D., Fazio, F., Comi, G., Pozzilli, C., Martinelli, V., Fieschi, C. (1996). Functional basis of memory impairment in multiple sclerosis: A[18F]FDG PET study. Neuroimage, 4, 8796.
Polman, C.H., Reingold, S.C., Edan, G., Filippi, M., Hartung, H., Kappos, L., Wolinsky, J.S. (2005). Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald criteria.”. Annals of Neurology, 58, 840846.
Ramasamy, D.P., Benedict, R.H.B., Cox, J.L., Fritz, D., Abdelrahman, N., Hussein, S., Zivadinov, R. (2009). Extent of cerebellum, subcortical and cortical atrophy in patients with MS: A case-control study. Journal of the Neurological Sciences, 282, 4754.
Rao, S.M., Leo, G.J., St. Aubin-Faubert, P. (1989). On the nature of memory disturbance in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology, 11(5), 699712.
Reynolds, C.R., Kamphaus, R.W. (2004). In Assessments P. (Ed.), Behavior assessment system for children, second edition (BASC-2). Bloomington, MN: AGS Publishing.
Reynolds, C.R., Voress, J.K. (2007). Test of memory and learning–second edition (TOMAL-2). Texas: Pro-Ed.
Roosendaal, S.D., Hulst, H.E., Vrenken, H., Feenstra, H.E., Castellins, J.A., Pouwels, P.J., Geurts, J.J. (2010). Structural and functional hippocampal changes in multiple sclerosis patients with intact memory function. Radiology, 225, 595604.
Sicotte, N.L., Kern, K.C., Giesser, B.S., Arshanapalli, A., Schultz, M., Montag, M., Boohheimer, S.Y. (2008). Regional hippocampal atrophy in multiple sclerosis. Brain, 131, 11341141.
Sled, J.G., Zijdenbos, A.P., Evans, A.C. (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imaging, 17, 8797.
Smith, S.M., Zhang, Y., Jenkinson, M., Chen, J., Matthews, P.M., Federico, A., De Stefano, N. (2002). Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage, 17, 479489.
Squire, L.R., Stark, C.E., Clark, R.E. (2004). The medial temporal lobe. Annual Review of Neuroscience, 27, 279306.
Till, C., Ghassemi, R., Aubert-Broche, B., Narayanan, S., Arnold, D.L., Desrocher, M., Banwell, B. (2011). MRI correlates of cognitive impairment in childhood onset multiple sclerosis. Neuropsychology, 25(3), 319332.
Van Der Werf, Y.D., Jolles, J., Witter, M.P., Uylings, H.B. (2003). Contributions of thalamic nuclei to declarative memory functioning. Cortex, 39, 10471062.
Wechsler, D. (1999). Wechsler abbreviated scale of intelligence (WASI). San Antonio, TX: The Psychological Corporation.
Zola-Morgan, S., Squire, L.R. (1993). Neuroanatomy of memory. Annual Review of Neuroscience, 16, 547563.



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