Abstract PR006: Mechanisms of Cognitive Impairment in Children Treated for Brain Tumors

Abstract Brain tumors are a leading cause of disability and death among children. Brain tumor treatments are often required for cure, but are damaging to brain tissue – particularly white matter, and is related to cognitive impairments for pediatric brain tumor survivors (PBTS). White matter tracts are critical for neural communication and supports cognition, including information processing speed, which underlies higher-order cognitive processes and is mediated by the brain’s default mode (DMN) and executive control (ECN) networks. It is unknown how white matter damage results in compromised information processing speed in PBTS. Thus, we explore the impact of DMN and ECN structural and functional connectivity on cognition during resting state, a visual-motor task, and through computational modeling. Forty-one healthy children and fifty-two PBTS were scanned at The Hospital for Sick Children. Tractography was conducted to examine DMN and ECN structural connectivity. MEG and measures of neural communication was conducted to examine DMN and ECN functional connectivity. Computational models were built using experimentally acquired structural connectomes to simulate functional connectivity. Partial least-squares path modeling was conducted to describe the relationship among white matter organization, neural communication, and information processing speed. Compared to healthy children, PBTS showed: slower information processing speed, DMN and ECN white matter compromise, and resting state DMN and ECN neural communication compromise that generalized to simulated and task-based neural synchrony compromise. Overall, DMN and ECN structural connectivity significantly influenced network neural communication and information processing speed, and white matter compromise had an indirect adverse impact on reaction time via perturbed neural synchrony. Our findings show an important connection between DMN and ECN connectivity that is essential for information processing speed. Further establishing alterations in DMN and ECN structural and functional connectivity as novel biomarkers of cognitive impairments could facilitate early intervention and monitoring of these deficits following brain tumor treatment. Citation Format: Noor Al Dahhan. Mechanisms of Cognitive Impairment in Children Treated for Brain Tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr PR006.