Impact of Pediatric Posterior Fossa Tumor Treatments on Working Memory Tracts Using Resting‐State fMRI and Tractography

Abstract

BACKGROUND AND PURPOSE: Working memory, a primary cognitive domain, is often impaired in pediatric brain tumor survivors, affecting their attention and processing speed. This study investigated the long-term effects of treatments, including surgery, radiotherapy (RT), and chemotherapy (CT), on working memory tracts in children with posterior fossa tumors (PFTs) using resting-state functional MRI (rs-fMRI) and diffusion MRI tractography. METHODS: This study included 16 medulloblastoma (MB) survivors treated with postoperative RT and CT, 14 pilocytic astrocytoma (PA) survivors treated with surgery alone, and 16 healthy controls from the Imaging Memory after Pediatric Cancer in children, adolescents, and young adults study (NCT04324450). Working memory tracts were identified by combining seed masks from rs-fMRI maps and whole-brain tractography from diffusion MRI. Connectivity alterations were assessed qualitatively and quantitatively, alongside neuropsychological evaluations and correlations with behavioral outcomes and mean supratentorial dose. RESULTS: Compared to controls, MB survivors exhibited significant impairments in the working memory network, including reductions in tract volume (TV), fiber density, fiber cross-section (FC), mean streamline length (MLS), and fractional anisotropy (FA) (all p = 0.04). Lower working memory scores were correlated with reduced TV and FA in MB survivors. Higher mean supratentorial doses were associated with lower TV, FC, and FA values across multiple tracts, particularly in the arcuate and superior longitudinal fasciculi. CONCLUSIONS: Tractography-derived features highlighted white matter damage as a biomarker of treatment-related neurotoxicity in PFTs survivors. These findings underscore the detrimental impact of RT and CT on working memory networks and emphasize the importance of preserving cognitive function during treatment planning.