Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood

Children surviving treatment for malignant brain tumors commonly have problems maintaining their premorbid levels of intellectual development and academic achievement. Our group has been especially interested in the effects of treatment on normal appearing white matter (NAWM) on MRI and the influence of NAWM volumes on neurocognitive functioning. The present study assessed NAWM and attentional abilities among 37 long-term survivors of malignant brain tumors, ranging in age from 1.7 to 14.8 (Mdn = 6.5) years at diagnosis, who had been treated with cranial radiation therapy with or without chemotherapy 2.6 to 15.3 (Mdn = 5.7) years earlier. On the Conners' Continuous Performance Test, the Overall Index and 7 of the other 10 indices were significantly deficient compared to age- and gender-corrected normative values. After statistically controlling for the effects of age at diagnosis and time elapsed from treatment, 5 of the 8 indices were significantly associated with cerebral white matter volumes and/or specific regional white matter volumes of the prefrontal/frontal lobe and cingulate gyrus. No gender effects were observed. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood. (JINS, 2004, 10, 180–189.)

[1]  Qing Ji,et al.  Prediction of total cerebral tissue volumes in normal appearing brain from sub-sampled segmentation volumes. , 2003, Magnetic resonance imaging.

[2]  Amar Gajjar,et al.  Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors , 2003, Cancer.

[3]  Alan C. Evans,et al.  Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. , 2002, JAMA.

[4]  C. Carlson,et al.  Sluggish Cognitive Tempo Predicts a Different Pattern of Impairment in the Attention Deficit Hyperactivity Disorder, Predominantly Inattentive Type , 2002, Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53.

[5]  R. Butler,et al.  Attentional processes and their remediation in children treated for cancer: A literature review and the development of a therapeutic approach , 2002, Journal of the International Neuropsychological Society.

[6]  R. Packer,et al.  Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  W E Reddick,et al.  Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  W E Reddick,et al.  Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  W E Reddick,et al.  Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  B. J. Casey,et al.  Structural and functional brain development and its relation to cognitive development , 2000, Biological Psychology.

[11]  W E Reddick,et al.  Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation. , 2000, Magnetic resonance imaging.

[12]  N. Cohen,et al.  Prefrontal regions play a predominant role in imposing an attentional 'set': evidence from fMRI. , 2000, Brain research. Cognitive brain research.

[13]  Faith M. Gunning-Dixon,et al.  The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. , 2000, Neuropsychology.

[14]  J. Kramer,et al.  Processing speed, working memory, and IQ: a developmental model of cognitive deficits following cranial radiation therapy. , 2000, Neuropsychology.

[15]  D. Inzitari Age‐related white matter changes and cognitive impairment , 2000, Annals of neurology.

[16]  X Xiong,et al.  Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children's Research Hospital. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Amar Gajjar,et al.  Neurocognitive deficits in medulloblastoma survivors and white matter loss , 1999, Annals of neurology.

[18]  J. Hopewell,et al.  Pathophysiological mechanisms leading to the development of late radiation-induced damage to the central nervous system. , 1999, Frontiers of radiation therapy and oncology.

[19]  P. Britton,et al.  Attentional ability among survivors of leukaemia , 1999, Archives of disease in childhood.

[20]  R. Colegrove,et al.  Long-term effects of cranial radiation therapy on attention functioning in survivors of childhood leukemia , 1999 .

[21]  W. Kaiser,et al.  Challenging the anterior attentional system with a continuous performance task: a functional magnetic resonance imaging approach , 1998, European Archives of Psychiatry and Clinical Neuroscience.

[22]  J L Kepner,et al.  Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  W. Reddick,et al.  A hybrid neural network analysis of subtle brain volume differences in children surviving brain tumors. , 1998, Magnetic resonance imaging.

[24]  J. Fletcher Attention in Children: Conceptual and Methodological Issues , 1998 .

[25]  R. Kikinis,et al.  White matter changes with normal aging , 1998, Neurology.

[26]  Edwin N. Cook,et al.  Automated segmentation and classification of multispectral magnetic resonance images of brain using artificial neural networks , 1997, IEEE Transactions on Medical Imaging.

[27]  Jonathan D. Cohen,et al.  A Developmental Functional MRI Study of Prefrontal Activation during Performance of a Go-No-Go Task , 1997, Journal of Cognitive Neuroscience.

[28]  P. Renshaw,et al.  Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls , 1997, Neurology.

[29]  A. Reiss,et al.  Brain development, gender and IQ in children. A volumetric imaging study. , 1996, Brain : a journal of neurology.

[30]  J. Rapoport,et al.  Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. , 1996, Archives of general psychiatry.

[31]  A. Baddeley Exploring the Central Executive , 1996 .

[32]  D. Roman,et al.  Neuropsychological effects of cranial radiation: current knowledge and future directions. , 1995, International journal of radiation oncology, biology, physics.

[33]  R. Noll,et al.  Long-term neurobehavioral outcome in pediatric brain-tumor patients: review and methodological critique. , 1994, Journal of clinical and experimental neuropsychology.

[34]  R. Connelly,et al.  Quality of life in long-term survivors of CNS tumors of childhood and adolescence. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  P. Fedio,et al.  Attentional deficits in long-term survivors of childhood acute lymphoblastic leukemia (ALL). , 1984, Journal of clinical neuropsychology.

[36]  J. Kramer,et al.  Chemotherapeutic CNS prophylaxis and neuropsychologic change in children with acute lymphoblastic leukemia: a prospective study. , 2001, Journal of pediatric psychology.

[37]  C. Filley,et al.  Toxic leukoencephalopathy. , 2001, The New England journal of medicine.

[38]  Bonnie L. Huxford Relationships between the California Verbal Learning Test - Children's Version and the Wechsler Intelligence Test for Children - Third Edition , 2000 .

[39]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[40]  M. Posner,et al.  Executive attention: Conflict, target detection, and cognitive control. , 1998 .

[41]  J. Ehrhardt,et al.  Intelligence and brain structure in normal individuals. , 1993, The American journal of psychiatry.

[42]  R. Mulhern,et al.  Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis. , 1992, Medical and pediatric oncology.

[43]  M. Posner,et al.  The attention system of the human brain. , 1990, Annual review of neuroscience.

[44]  Wiley Mittenberg,et al.  Memory Indices of LD Readers Using the California Verbal Learning Test for Children , 1990 .