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Changes to Memory Structures in Children Treated for Posterior Fossa Tumors

  • Lily Riggs (a1) (a2), Eric Bouffet (a3) (a4), Suzanne Laughlin (a5), Normand Laperriere (a6), Fang Liu (a1), Jovanka Skocic (a1), Nadia Scantlebury (a1), Frank Wang (a5), Nicholas J. Schoenhoff (a1), Douglas Strother (a7), Juliette Hukin (a8), Christopher Fryer (a8), Dina McConnell (a9) and Donald J. Mabbott (a1) (a2) (a3) (a10)...

Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma. (JINS, 2014, 1, 1–13)

Corresponding author
Correspondence and reprint requests to: Donald J. Mabbott, Psychology Department, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. E-mail:
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M. Andres-Mach , R. Rola , J.R. Fike (2008). Radiation effects on neural precursor cells in the dentate gyrus. Cell and Tissue Research, 331(1), 251262. doi:10.1007/s00441-007-0480-9

C. Beaulieu (2002). The basis of anisotropic water diffusion in the nervous system – A technical review. NMR in Biomedicine, 15(7–8), 435455. doi:10.1002/nbm.782

T.E. Behrens , H.J. Berg , S. Jbabdi , M.F. Rushworth , M.W. Woolrich (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage, 34(1), 144155. doi:10.1016/j.neuroimage.2006.09.018

N.M. Ben Abdallah , R.K. Filipkowski , M. Pruschy , P. Jaholkowski , J. Winkler , L. Kaczmarek , H.P. Lipp (2013). Impaired long-term memory retention: Common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice. Behavioural Brain Research. doi:10.1016/j.bbr.2013.05.034

M. Catani , R.J. Howard , S. Pajevic , D.K. Jones (2002). Virtual in vivo interactive dissection of white matter fasciculi in the human brain. Neuroimage, 17(1), 7794.

M. Catani , M. Thiebaut de Schotten (2008). A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex, 44(8), 11051132. doi:10.1016/j.cortex.2008.05.004

D.M. Demaster , S. Ghetti (2012). Developmental differences in hippocampal and cortical contributions to episodic retrieval. Cortex, 49(6), 14821493. doi:10.1016/j.cortex.2012.08.004

K. Edelstein , B.J. Spiegler , S. Fung , T. Panzarella , D.J. Mabbott , N. Jewitt , D.C. Hodgson (2011). Early aging in adult survivors of childhood medulloblastoma: Long-term neurocognitive, functional, and physical outcomes. Neuro-Oncology, 13(5), 536545. doi:10.1093/neuonc/nor015

H. Eichenbaum (2013). What H.M. taught us. Journal of Cognitive Neuroscience, 25(1), 1421. doi:10.1162/jocn_a_00285

M. Eijkenboom , F.J. Van Der Staay (1999). Spatial learning deficits in rats after injection of vincristine into the dorsal hippocampus. Neuroscience, 91(4), 12991313.

A. Gajjar , M. Chintagumpala , D. Ashley , S. Kellie , L.E. Kun , T.E. Merchant , R.J. Gilbertson (2006). Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): Long-term results from a prospective, multicentre trial. The Lancet Oncology, 7(10), 813820. doi:10.1016/S1470-2045(06)70867-1

A.P. George , S.M. Kuehn , M. Vassilyadi , P.M. Richards , S.E. Parlow , D.L. Keene , E.C. Ventureyra (2003). Cognitive sequelae in children with posterior fossa tumors. Pediatric Neurology, 28(1), 4247.

S. Ghetti , S.A. Bunge (2012). Neural changes underlying the development of episodic memory during middle childhood. Developmental Cognitive Neuroscience, 2(4), 381395. doi:10.1016/j.dcn.2012.05.002

S. Ghetti , D.M. DeMaster , A.P. Yonelinas , S.A. Bunge (2010). Developmental differences in medial temporal lobe function during memory encoding. The Journal of Neuroscience, 30(28), 95489556. doi:10.1523/JNEUROSCI.3500-09.2010

N. Gogtay , T.F. Nugent III, D.H. Herman , A. Ordonez , D. Greenstein , K.M. Hayashi , P.M. Thompson (2006). Dynamic mapping of normal human hippocampal development. Hippocampus, 16(8), 664672. doi:10.1002/hipo.20193

N.G. Gottardo , A. Gajjar (2006). Current therapy for medulloblastoma. Current Treatment Options in Neurology, 8(4), 319334.

R. Insausti , S. Cebada-Sanchez , P. Marcos (2010). Postnatal development of the human hippocampal formation. Advances in Anatomy, Embryology and Cell Biology, 206, 186.

E.B. Isaacs , F. Vargha-Khadem , K.E. Watkins , A. Lucas , M. Mishkin , D.G. Gadian (2003). Developmental amnesia and its relationship to degree of hippocampal atrophy. Proceedings of the National Academy of Sciences of the United States of America, 100(22), 1306013063. doi:10.1073/pnas.1233825100

P.L. Khong , L.H. Leung , A.S. Fung , D.Y. Fong , D. Qiu , D.L. Kwong , G.C. Chan (2006). White matter anisotropy in post-treatment childhood cancer survivors: Preliminary evidence of association with neurocognitive function. Journal of Clinical Oncology, 24(6), 884890. doi:10.1200/JCO.2005.02.4505

V. Kieffer-Renaux , C. Bulteau , J. Grill , C. Kalifa , D. Viguier , I. Jambaque (2000). Patterns of neuropsychological deficits in children with medulloblastoma according to craniospatial irradiation doses. Developmental Medicine and Child Neurology, 42(11), 741745.

L. Lafay-Cousin , E. Bouffet , C. Hawkins , A. Amid , A. Huang , D.J. Mabbott (2009). Impact of radiation avoidance on survival and neurocognitive outcome in infant medulloblastoma. Current Oncology, 16(6), 2128.

N. Law , E. Bouffet , S. Laughlin , N. Laperriere , M.E. Briere , D. Strother , D. Mabbott (2011). Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: Impact on working memory. Neuroimage, 56(4), 22382248. doi:10.1016/j.neuroimage.2011.03.065

C. Lebel , C. Beaulieu (2011). Longitudinal development of human brain wiring continues from childhood into adulthood. The Journal of Neuroscience, 31(30), 1093710947. doi:10.1523/JNEUROSCI.5302-10.2011

C. Lebel , L. Walker , A. Leemans , L. Phillips , C. Beaulieu (2008). Microstructural maturation of the human brain from childhood to adulthood. Neuroimage, 40(3), 10441055. doi:10.1016/j.neuroimage.2007.12.053

M.B. Luskin (1993). Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron, 11(1), 173189.

D.J. Mabbott , M.D. Noseworthy , E. Bouffet , C. Rockel , S. Laughlin (2006). Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: Correlation with IQ. Neuro-Oncology, 8(3), 244252. doi:10.1215/15228517-2006-002

D.J. Mabbott , J. Rovet , M.D. Noseworthy , M.L. Smith , C. Rockel (2009). The relations between white matter and declarative memory in older children and adolescents. Brain Research, 1294, 8090. doi:10.1016/j.brainres.2009.07.046

M.L. Monje , T. Palmer (2003). Radiation injury and neurogenesis. Current Opinion in Neurology, 16(2), 129134. doi:10.1097/01.wco.0000063772.81810.b7

R.K. Mulhern , T.E. Merchant , A. Gajjar , W.E. Reddick , L.E. Kun (2004). Late neurocognitive sequelae in survivors of brain tumours in childhood. The Lancet Oncology, 5(7), 399408. doi:10.1016/S1470-2045(04)01507-4

B.J. Nagel , D.C. Delis , S.L. Palmer , C. Reeves , A. Gajjar , R.K. Mulhern (2006). Early patterns of verbal memory impairment in children treated for medulloblastoma. Neuropsychology, 20(1), 105112. doi:10.1037/0894-4105.20.1.105

Z. Nagy , H. Westerberg , T. Klingberg (2004). Maturation of white matter is associated with the development of cognitive functions during childhood. Journal of Cognitive Neuroscience, 16(7), 12271233. doi:10.1162/0898929041920441

N. Ofen , X.J. Chai , K.D. Schuil , S. Whitfield-Gabrieli , J.D. Gabrieli (2012). The development of brain systems associated with successful memory retrieval of scenes. The Journal of Neuroscience, 32(29), 1001210020. doi:10.1523/JNEUROSCI.1082-11.2012

R.K. Olsen , D.J. Palombo , J.S. Rabin , B. Levine , J.D. Ryan , R.S. Rosenbaum (2013). Volumetric analysis of medial temporal lobe subregions in developmental amnesia using high-resolution magnetic resonance imaging. Hippocampus, doi:10.1002/hipo.22153

L. Padovani , N. Andre , L.S. Constine , X. Muracciole (2012). Neurocognitive function after radiotherapy for paediatric brain tumours. Nature Reviews. Neurology, 8(10), 578588. doi:10.1038/nrneurol.2012.182

S.L. Palmer (2008). Neurodevelopmental impact on children treated for medulloblastoma: A review and proposed conceptual model. Developmental Disabilities Research Reviews, 14(3), 203210. doi:10.1002/ddrr.32

S.L. Palmer , W.E. Reddick , A. Gajjar (2007). Understanding the cognitive impact on children who are treated for medulloblastoma. Journal of Pediatric Psychology, 32(9), 10401049. doi:10.1093/jpepsy/jsl056

J.B. Pereira , C. Junque , D. Bartres-Faz , B. Ramirez-Ruiz , M.J. Marti , E. Tolosa (2013). Regional vulnerability of hippocampal subfields and memory deficits in Parkinson's disease. Hippocampus, 23(8), 720728. doi:10.1002/hipo.22131

A. Pfefferbaum , D.H. Mathalon , E.V. Sullivan , J.M. Rawles , R.B. Zipursky , K.O. Lim (1994). A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Archives of Neurology, 51(9), 874887.

T. Pfluger , S. Weil , S. Weis , C. Vollmar , D. Heiss , J. Egger , K. Hahn (1999). Normative volumetric data of the developing hippocampus in children based on magnetic resonance imaging. Epilepsia, 40(4), 414423.

D. Qiu , L.H. Leung , D.L. Kwong , G.C. Chan , P.L. Khong (2006). Mapping radiation dose distribution on the fractional anisotropy map: Applications in the assessment of treatment-induced white matter injury. Neuroimage, 31(1), 109115. doi:10.1016/j.neuroimage.2005.12.007

J. Raber , Y. Fan , Y. Matsumori , Z. Liu , P.R. Weinstein , J.R. Fike , J. Liu (2004). Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Annals of Neurology, 55(3), 381389doi:10.1002/ana.10853

W.E. Reddick , J.O. Glass , S.L. Palmer , S. Wu , A. Gajjar , J.W. Langston , R.K. Mulhern (2005). Atypical white matter volume development in children following craniospinal irradiation. Neuro-Oncology, 7(1), 1219. doi:10.1215/S1152851704000079

W.E. Reddick , H.A. White , J.O. Glass , G.C. Wheeler , S.J. Thompson , A. Gajjar , R.K. Mulhern (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer, 97(10), 25122519. doi:10.1002/cncr.11355

M.D. Saxe , F. Battaglia , J.W. Wang , G. Malleret , D.J. David , J.E. Monckton , M.R. Drew (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 1750117506. doi:10.1073/pnas.0607207103

M. Shabani , M.H. Larizadeh , S. Parsania , M. Asadi Shekaari , N. Shahrokhi (2012). Profound destructive effects of adolescent exposure to vincristine accompanied with some sex differences in motor and memory performance. Canadian Journal of Physiology and Pharmacology, 90(4), 379386. doi:10.1139/Y11-132

Z.Y. Shan , J.Z. Liu , J.O. Glass , A. Gajjar , C.S. Li , W.E. Reddick (2006). Quantitative morphologic evaluation of white matter in survivors of childhood medulloblastoma. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. Magn Reson Imaging, 24(8), 10151022. doi:10.1016/j.mri.2006.04.015

T.J. Shors , D.A. Townsend , M. Zhao , Y. Kozorovitskiy , E. Gould (2002). Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus, 12(5), 578584. doi:10.1002/hipo.10103

B.J. Spiegler , E. Bouffet , M.L. Greenberg , J.T. Rutka , D.J. Mabbott (2004). Change in neurocognitive functioning after treatment with cranial radiation in childhood. Journal of Clinical Oncology, 22(4), 706713. doi:10.1200/JCO.2004.05.186

L.R. Squire (1992). Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychological Review, 99(2), 195231.

R.W. Thatcher , R.A. Walker , S. Giudice (1987). Human cerebral hemispheres develop at different rates and ages. Science, 236(4805), 11101113.

G. Winocur , J.M. Wojtowicz , M. Sekeres , J.S. Snyder , S. Wang (2006). Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus, 16(3), 296304. doi:10.1002/hipo.20163

S.J. Wong-Goodrich , M.L. Pfau , C.T. Flores , J.A. Fraser , C.L. Williams , L.W. Jones (2010). Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer Research, 70(22), 93299338. doi:10.1158/0008-5472.CAN-10-1854

J.C. Pruessner , L.M. Li , W. Serles , M. Pruessner , D.L. Collins , N. Kabani , A.C. Evans (2000). Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cerebral cortex, 10(4), 433442.

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