Ryan Wier1, Holly A Aleksonis1, Matthew M Pearson2, Christopher J Cannistraci3, Adam W Anderson4, John F Kuttesch5, Bruce E Compas6, Kristen R Hoskinson7,8. 1. Center for Biobehavioral Health, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, USA. 2. Institute for Neurology and Neurosurgery, Sacred Heart Medical Group, 5153 N. Ninth Avenue, Pensacola, FL, USA. 3. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, USA. 4. Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Nashville, TN, USA. 5. Pediatric Hematology and Oncology, University of New Mexico, 1 University of New Mexico, MSC10 5590, Albuquerque, NM, USA. 6. Psychology and Human Development, Peabody College, Vanderbilt University, #552, 230 Appleton Place, Nashville, TN, USA. 7. Center for Biobehavioral Health, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, USA. Kristen.hoskinson@nationwidechildrens.org. 8. Department of Pediatrics, The Ohio State University College of Medicine, 370 W. Ninth Avenue, Columbus, OH, USA. Kristen.hoskinson@nationwidechildrens.org.
Abstract
PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.
PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.
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