White matter network topology relates to cognitive flexibility and cumulative neurological risk in adult survivors of pediatric brain tumors

Abstract

Adult survivors of pediatric brain tumors exhibit deficits in executive functioning. Given that brain tumors and medical treatments for brain tumors result in disruptions to white matter, a network analysis was used to explore the topological properties of white matter networks. This study used diffusion tensor imaging and deterministic tractography in 38 adult survivors of pediatric brain tumors (mean age in years = 23.11 (SD = 4.96), 54% female, mean years post diagnosis = 14.09 (SD = 6.19)) and 38 healthy peers matched by age, gender, handedness, and socioeconomic status. Nodes were defined using the Automated Anatomical Labeling (AAL) parcellation scheme, and edges were defined as the mean fractional anisotropy of streamlines that connected each node pair. Global efficiency and average clustering coefficient were reduced in survivors compared to healthy peers with preferential impact to hub regions. Global efficiency mediated differences in cognitive flexibility between survivors and healthy peers, as well as the relationship between cumulative neurological risk and cognitive flexibility. These results suggest that adult survivors of pediatric brain tumors, on average one and a half decades post brain tumor diagnosis and treatment, exhibit altered white matter topology in the form of suboptimal integration and segregation of large scale networks, and that disrupted topology may underlie executive functioning impairments. Network based studies provided important topographic insights on network organization in long-term survivors of pediatric brain tumor.

The Neurological Predictor Scale Predicts Adaptive Functioning via Executive Dysfunction in Young Adult Survivors of Childhood Brain Tumor

“…The NPS is associated with cognitive outcomes over and above individual risk factors, suggesting that the cumulative examination of risk factors can better characterize the heterogeneity in survivors' long-term outcomes (Kautiainen, Na, & King, 2019;King & Na, 2016;Micklewright et al, 2008;Papazoglou, King, Morris, & Krawiecki, 2008;Taiwo, Na, & King, 2017). Prior research has demonstrated that the NPS is related to core cognitive abilities, executive function, and functional outcomes in pediatric brain tumor survivors (King & Na, 2016;McCurdy, Rane, Daly, & Jacobson, 2016;Na et al, 2018).…”

Neuropsychological functioning in survivors of childhood medulloblastoma/CNS-PNET: The role of secondary medical complications

“…The neural mechanism for this association is not well known (Bells et al, 2017;Glass et al, 2017), but an association between altered white matter microstructure, in the form of reduced neural synchronization, and functioning has been found in brain tumor patients (Bells et al, 2017). Furthermore, suboptimal integration and segregation of white matter networks correlate with executive functioning impairments (Na et al, 2018).…”

“…In line with this, focus has shifted from survival only to also include quality of life post-treatment. This shift has brought with it an increased focus on the late effects survivors may experience (Na et al, 2018), as survival comes at a cost for children with MB and CNS-PNET. They experience cognitive impairments, academic and social challenges, hearing loss, epileptic seizures, endocrine insufficiency, secondary neoplasm, stroke, and problems with balance and coordination (Benesch et al, 2009;Chevignard et al, 2017;Doger de Sp eville et al, 2018;Edelstein et al, 2011;King et al, 2017).…”

Impact of non‐CNS childhood cancer on resting‐state connectivity and its association with cognition

“…Disturbances to the development of networks not only occur in survivors of pediatric brain tumors (Chen et al, 2016;Na et al, 2018) but also affect children with cancers outside the CNS such as leukemia and lymphoma (Kesler et al, 2014(Kesler et al, , 2016. Leukemia and its potentially neurotoxic therapy might disrupt the functional and structural development of the brain (Hearps et al, 2017).…”