title: Brain structure, working memory and response inhibition in childhood leukemia survivors.
abstract: Survival rates for children with acute lymphoblastic leukemia (ALL) approach 95%. At the same time, there is growing concern that chemotherapy causes alterations in brain development and cognitive abilities. We performed MRI measurements of white and gray matter volume to explore how variation in brain structure may be related to cognitive abilities in ALL survivors and healthy controls.
  
  
  
  The sample included 24 male ALL survivors who had completed contemporary treatment 3-11 years prior, and 21 age- and sex-matched controls. Participants were between 8 and 18 years old. Working memory and motor response inhibition were measured with the N-Back and Stop Signal Tasks (SST), respectively. Participants underwent 3T structural MRI to assess white and gray matter volumes overall, lobe-wise, and in cortical and atlas-identified subcortical structures. Mental health was assessed with the Child Behavioral Checklist.
  
  
  
  ALL survivors performed more poorly on measures of working memory and response inhibition than controls. Frontal and parietal white matter, temporal and occipital gray matter volume, and volumes of subcortical white and gray matter structures were significantly reduced in ALL survivors compared with controls. Significant structure-function correlations were observed between working memory performance and volume of the amygdala, thalamus, striatum, and corpus callosum. Response inhibition was correlated with frontal white matter volume. No differences were found in psychopathology.
  
  
  
  Compared with controls, a reduction in volume across brain regions and tissue types, was detectable in ALL survivors years after completion of therapy. These structural alterations were correlated with neurocognitive performance, particularly in working memory. Confirming these observations in a larger, more representative sample of the population is necessary. Additionally, establishing the time course of these changes-and the treatment, genetic, and environmental factors that influence them-may provide opportunities to identify at-risk patients, inform the design of treatment modifications, and minimize adverse cognitive outcomes.
authors.affiliation: Physiology and Experimental Medicine The Hospital for Sick Children Research Institute Toronto ON Canada; Psychiatry Research The Hospital for Sick Children Toronto ON Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: van der Plas
authors.affiliation: Psychiatry Research The Hospital for Sick Children Toronto ON Canada; Department of Psychiatry Faculty of Medicine The University of Toronto Toronto ON Canada.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Schachar
authors.affiliation: Department of Pediatrics Faculty of Medicine The University of Toronto Toronto ON Canada; Department of Haematology/Oncology The Hospital for Sick Children Toronto ON Canada.
authors.forename: Johann
authors.identifier: 0000-0003-1158-186X
authors.initials: J
authors.lastname: Hitzler
authors.affiliation: Psychiatry Research The Hospital for Sick Children Toronto ON Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Crosbie
authors.affiliation: Department of Psychology The Hospital for Sick Children Toronto ON Canada.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Guger
authors.affiliation: Department of Pediatrics Faculty of Medicine The University of Toronto Toronto ON Canada; Department of Psychology The Hospital for Sick Children Toronto ON Canada.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Spiegler
authors.affiliation: Physiology and Experimental Medicine The Hospital for Sick Children Research Institute Toronto ON Canada; Clinical Pharmacology and Toxicology The Hospital for Sick Children Toronto ON Canada; Pharmacology and Pharmacy Faculty of Medicine The University of Toronto Toronto ON Canada.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ito
authors.affiliation: Physiology and Experimental Medicine The Hospital for Sick Children Research Institute Toronto ON Canada; Mouse Imaging Centre (MICe) The Hospital for Sick Children Toronto ON Canada; Ontario Institute for Cancer Research Toronto ON Canada; Department of Medical Biophysics The University of Toronto Toronto ON Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nieman
mesh_terms: D000293:Adolescent; D002648:Child; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D017741:Survivors; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: acute lymphoblastic leukemia; cognitive late effects; magnetic resonance imaging