Brain structure, working memory and response inhibition in childhood leukemia survivors

Ellen van der Plas; Russell J Schachar; Johann Hitzler; Jennifer Crosbie; Sharon L Guger; Brenda J Spiegler; Shinya Ito; Brian J Nieman

doi:10.1002/brb3.621

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Brain structure, working memory and response inhibition in childhood leukemia survivors

Journal article

Open access

Peer reviewed

Brain structure, working memory and response inhibition in childhood leukemia survivors

Ellen van der Plas, Russell J Schachar, Johann Hitzler, Jennifer Crosbie, Sharon L Guger, Brenda J Spiegler, Shinya Ito and Brian J Nieman

Brain and behavior, Vol.7(2), pp.e00621-n/a

02/2017

DOI: 10.1002/brb3.621

PMCID: PMC5318374

PMID: 28239531

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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.

Magnetic Resonance Imaging

Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy

White Matter - diagnostic imaging

Inhibition, Psychological

Humans

Adolescent

Survivors

Male

Memory, Short-Term - physiology

Cognitive Dysfunction - physiopathology

Child

Gray Matter - diagnostic imaging

Details

Title: Subtitle: Brain structure, working memory and response inhibition in childhood leukemia survivors
Creators: Ellen van der Plas - Physiology and Experimental Medicine The Hospital for Sick Children Research Institute Toronto ON Canada; Psychiatry Research The Hospital for Sick Children Toronto ON Canada
Russell J Schachar - Psychiatry Research The Hospital for Sick Children Toronto ON Canada; Department of Psychiatry Faculty of Medicine The University of Toronto Toronto ON Canada
Johann Hitzler - 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
Jennifer Crosbie - Psychiatry Research The Hospital for Sick Children Toronto ON Canada
Sharon L Guger - Department of Psychology The Hospital for Sick Children Toronto ON Canada
Brenda J Spiegler - Department of Pediatrics Faculty of Medicine The University of Toronto Toronto ON Canada; Department of Psychology The Hospital for Sick Children Toronto ON Canada
Shinya Ito - 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
Brian J Nieman - 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
Resource Type: Journal article
Publication Details: Brain and behavior, Vol.7(2), pp.e00621-n/a
DOI: 10.1002/brb3.621
PMID: 28239531
PMCID: PMC5318374
NLM abbreviation: Brain Behav
ISSN: 2162-3279
eISSN: 2162-3279
Publisher: United States
Grant note: CIHR
Language: English
Date published: 02/2017
Academic Unit: Psychiatry
Record Identifier: 9984004076002771

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