Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short‐term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2‐3, dentate gyrus (DG)‐CA4, stratum radiatum—lacunosum—moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short‐term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale—third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG‐CA4, CA1, CA2‐3, and stratum radiatum‐lacunosum‐moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG‐CA4, CA1, and stratum radiatum‐lacunosum‐moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.

[1]  H. Duvernoy The Human Hippocampus , 1988, J.F. Bergmann-Verlag.

[2]  D. Amaral,et al.  The three-dimensional organization of the hippocampal formation: A review of anatomical data , 1989, Neuroscience.

[3]  F. Benes,et al.  Myelination of cortical-hippocampal relays during late adolescence. , 1989, Schizophrenia bulletin.

[4]  Nancy C. Andreasen,et al.  Problems with ratio and proportion measures of imaged cerebral structures , 1991, Psychiatry Research: Neuroimaging.

[5]  S. Berkovic,et al.  Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects. , 1993, Journal of clinical and experimental neuropsychology.

[6]  F. Benes,et al.  Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. , 1994, Archives of general psychiatry.

[7]  D R Fish,et al.  Methods for normalization of hippocampal volumes measured with MR. , 1995, AJNR. American journal of neuroradiology.

[8]  O. Abayomi,et al.  Pathogenesis of irradiation-induced cognitive dysfunction. , 1996, Acta oncologica.

[9]  M. Bobinski,et al.  The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease , 1999, Neuroscience.

[10]  Alan Lucas,et al.  Hippocampal Volume and Everyday Memory in Children of Very Low Birth Weight , 2000, Pediatric Research.

[11]  D A Bennett,et al.  Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease , 2000, Hippocampus.

[12]  I. McKeith,et al.  A Comparison of Medial and Lateral Temporal Lobe Atrophy in Dementia with Lewy Bodies and Alzheimer’s Disease: Magnetic Resonance Imaging Volumetric Study , 2001, Dementia and Geriatric Cognitive Disorders.

[13]  Paul E. Gilbert,et al.  Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1 , 2001, Hippocampus.

[14]  M. Monje,et al.  Irradiation induces neural precursor-cell dysfunction , 2002, Nature Medicine.

[15]  C. Elger,et al.  Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy , 2002, Epilepsy Research.

[16]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[17]  S. Engel,et al.  Dynamics of the Hippocampus During Encoding and Retrieval of Face-Name Pairs , 2003, Science.

[18]  T. Madsen,et al.  Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat , 2003, Neuroscience.

[19]  Paul E. Gilbert,et al.  Localization of function within the dorsal hippocampus: the role of the CA3 subregion in paired-associate learning. , 2003, Behavioral neuroscience.

[20]  P. Lucassen,et al.  Neuronal number, volume, and apoptosis of the left dentate gyrus of chronically stressed pigs correlate negatively with basal saliva cortisol levels , 2004, Hippocampus.

[21]  W. Reddick,et al.  Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation. , 2004, AJNR. American journal of neuroradiology.

[22]  Jacob Raber,et al.  Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis , 2004, Radiation research.

[23]  Mónica Giménez,et al.  Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity , 2004, NeuroImage.

[24]  C. Van Petten,et al.  Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: review and meta-analysis. , 2004, Neuropsychologia.

[25]  B. Knowlton,et al.  A Dissociation of Encoding and Retrieval Processes in the Human Hippocampus , 2005, The Journal of Neuroscience.

[26]  Kiralee M. Hayashi,et al.  Dynamic mapping of normal human hippocampal development , 2006, Hippocampus.

[27]  Laurenz Wiskott,et al.  A functional hypothesis for adult hippocampal neurogenesis: Avoidance of catastrophic interference in the dentate gyrus , 2006, Hippocampus.

[28]  D. Delis,et al.  Early patterns of verbal memory impairment in children treated for medulloblastoma. , 2006, Neuropsychology.

[29]  R. Kesner Behavioral functions of the CA3 subregion of the hippocampus. , 2007, Learning & memory.

[30]  Derek K. Jones,et al.  Symmetries in human brain language pathways correlate with verbal recall , 2007, Proceedings of the National Academy of Sciences.

[31]  D. Amaral,et al.  The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). , 2007, Progress in brain research.

[32]  K. Ligon,et al.  Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies , 2007, Annals of neurology.

[33]  Changlian Zhu,et al.  Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain , 2008, Proceedings of the National Academy of Sciences.

[34]  Philip R. Szeszko,et al.  Amygdala and Hippocampal Volumes in Familial Early Onset Major Depressive Disorder , 2008, Biological Psychiatry.

[35]  Deanne K. Thompson,et al.  Preterm infant hippocampal volumes correlate with later working memory deficits. , 2008, Brain : a journal of neurology.

[36]  Xavier Caroff,et al.  Verbal and spatial learning after temporal lobe excisions in children: An adaptation of the Grober and Buschke procedure , 2009, Epilepsy & Behavior.

[37]  K. Blomgren,et al.  Differential Recovery of Neural Stem Cells in the Subventricular Zone and Dentate Gyrus After Ionizing Radiation , 2009, Stem cells.

[38]  L. Saksida,et al.  A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation , 2009, Science.

[39]  M. Saling,et al.  Verbal memory in mesial temporal lobe epilepsy: beyond material specificity. , 2009, Brain : a journal of neurology.

[40]  Polina Golland,et al.  Automated segmentation of hippocampal subfields from ultra‐high resolution in vivo MRI , 2009, Hippocampus.

[41]  N. Koutsouleris,et al.  Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression. , 2010, Journal of psychiatric research.

[42]  Ching-Hsing Yu,et al.  SciNet: Lessons Learned from Building a Power-efficient Top-20 System and Data Centre , 2010 .

[43]  Pierre Lavenex,et al.  Postnatal development of the hippocampal formation: A stereological study in macaque monkeys , 2011, The Journal of comparative neurology.

[44]  C. Stark,et al.  Pattern separation in the hippocampus , 2011, Trends in Neurosciences.

[45]  Michael Weiner,et al.  Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4T , 2011, NeuroImage.

[46]  U. Bartels,et al.  Longitudinal evaluation of neurocognitive function after treatment for central nervous system germ cell tumors in childhood , 2011, Cancer.

[47]  Shauna M. Stark,et al.  Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults , 2010, Hippocampus.

[48]  C. Limoli,et al.  Impaired Cognitive Function and Hippocampal Neurogenesis following Cancer Chemotherapy , 2012, Clinical Cancer Research.

[49]  A. Khundakar,et al.  Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias , 2012, Stroke.

[50]  A. Leemans,et al.  Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  T. Shors,et al.  Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain , 2012, The European journal of neuroscience.

[52]  Manojkumar Saranathan,et al.  Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease , 2012, NeuroImage.

[53]  J. Fike,et al.  Cranial Irradiation Alters Dendritic Spine Density and Morphology in the Hippocampus , 2012, PloS one.

[54]  A. Golby,et al.  Hemispheric Lateralization Interrupted: Material-Specific Memory Deficits in Temporal Lobe Epilepsy , 2013, Front. Hum. Neurosci..

[55]  D. Collins,et al.  Performing label‐fusion‐based segmentation using multiple automatically generated templates , 2013, Human brain mapping.

[56]  Jason P. Lerch,et al.  Hippocampal volumes differ across the mouse estrous cycle, can change within 24hours, and associate with cognitive strategies , 2013, NeuroImage.

[57]  Oxana Palesh,et al.  Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors , 2013, Brain, Behavior, and Immunity.

[58]  H. Scharfman,et al.  Hilar mossy cells of the dentate gyrus: a historical perspective , 2013, Front. Neural Circuits.

[59]  Yalin Wang,et al.  Functional and structural differences in the hippocampus associated with memory deficits in adult survivors of acute lymphoblastic leukemia , 2013, Pediatric blood & cancer.

[60]  E. Tolosa,et al.  Regional vulnerability of hippocampal subfields and memory deficits in Parkinson's disease , 2013, Hippocampus.

[61]  C. Limoli,et al.  Cranial irradiation compromises neuronal architecture in the hippocampus , 2013, Proceedings of the National Academy of Sciences.

[62]  Pierre Lavenex,et al.  Building hippocampal circuits to learn and remember: Insights into the development of human memory , 2013, Behavioural Brain Research.

[63]  D. Fair,et al.  Hemispheric lateralization of verbal and spatial working memory during adolescence , 2013, Brain and Cognition.

[64]  M. Mallar Chakravarty,et al.  A novel in vivo atlas of human hippocampal subfields using high-resolution 3T magnetic resonance imaging , 2013, NeuroImage.

[65]  Qiong Xia,et al.  X-ray irradiation promotes apoptosis of hippocampal neurons through up-regulation of Cdk5 and p25 , 2013, Cancer Cell International.

[66]  Tracy Riggins,et al.  Longitudinal investigation of source memory reveals different developmental trajectories for item memory and binding. , 2014, Developmental Psychology.

[67]  Stine K. Krogsrud,et al.  Development of hippocampal subfield volumes from 4 to 22 years , 2014, Human brain mapping.

[68]  E. Westman,et al.  Regional vulnerability of hippocampal subfields to aging measured by structural and diffusion MRI , 2014, Hippocampus.

[69]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[70]  Anders M. Dale,et al.  Regional Hippocampal Volumes and Development Predict Learning and Memory , 2014, Developmental Neuroscience.

[71]  Arne D. Ekstrom,et al.  Volume of hippocampal subfields and episodic memory in childhood and adolescence , 2014, NeuroImage.

[72]  Simona Ghetti,et al.  Structural development of the hippocampus and episodic memory: developmental differences along the anterior/posterior axis. , 2014, Cerebral cortex.

[73]  Brigitte Landeau,et al.  EFFECTS OF AGE AND ALZHEIMER'S DISEASE ON HIPPOCAMPAL SUBFIELDS: COMPARISON BETWEEN MANUAL AND FREESURFER VOLUMETRY , 2014, Alzheimer's & Dementia.

[74]  M. Mallar Chakravarty,et al.  Multi-atlas segmentation of the whole hippocampus and subfields using multiple automatically generated templates , 2014, NeuroImage.

[75]  Hippocampal sclerosis in dementia, epilepsy, and ischemic injury: differential vulnerability of hippocampal subfields. , 2014, Journal of neuropathology and experimental neurology.

[76]  Neal J. Cohen,et al.  Short-term retention of relational memory in amnesia revisited: accurate performance depends on hippocampal integrity , 2014, Front. Hum. Neurosci..

[77]  Fang Liu,et al.  Changes to Memory Structures in Children Treated for Posterior Fossa Tumors , 2014, Journal of the International Neuropsychological Society.

[78]  Geert Jan Biessels,et al.  A Critical Appraisal of the Hippocampal Subfield Segmentation Package in FreeSurfer , 2014, Front. Aging Neurosci..

[79]  Tracy Riggins,et al.  Developmental Differences in Relations Between Episodic Memory and Hippocampal Subregion Volume During Early Childhood. , 2015, Child development.

[80]  C. Nelson,et al.  20 years after “The ontogeny of human memory: A cognitive neuroscience perspective,” where are we? , 2015 .

[81]  J. Ávila,et al.  Novel connection between newborn granule neurons and the hippocampal CA2 field , 2015, Experimental Neurology.

[82]  P. Yushkevich,et al.  Automated volumetry and regional thickness analysis of hippocampal subfields and medial temporal cortical structures in mild cognitive impairment , 2015, Human brain mapping.

[83]  David A. Jaffray,et al.  Treatment Age, Dose and Sex Determine Neuroanatomical Outcome in Irradiated Juvenile Mice , 2015, Radiation research.

[84]  Michael L. Mack,et al.  Comparison of semi-automated hippocampal subfield segmentation methods in a pediatric sample , 2016 .

[85]  J. Zwanenburg,et al.  Automated Hippocampal Subfield Segmentation at 7T MRI , 2016, American Journal of Neuroradiology.

[86]  M. Sharpe,et al.  Vulnerability of white matter to insult during childhood: evidence from patients treated for medulloblastoma. , 2016, Journal of neurosurgery. Pediatrics.

[87]  Andrew R. Bender,et al.  Age differences in hippocampal subfield volumes from childhood to late adulthood , 2016, Hippocampus.

[88]  Michael Fisher,et al.  Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1 , 2016, Pediatric blood & cancer.

[89]  Fang Liu,et al.  Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training , 2016, Neuro-oncology.

[90]  D. Veltman,et al.  Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study , 2018, Brain Imaging and Behavior.

[91]  Wen Li,et al.  Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors , 2017, Scientific Reports.

[92]  Michael L. Mack,et al.  Performance of semi-automated hippocampal subfield segmentation methods across ages in a pediatric sample , 2018, bioRxiv.