The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy

Survivors of childhood brain tumors (BTs) treated with CNS-directed therapy show changes in cerebral white matter that are related to neurocognitive late effects. We examined the association between white matter volume and working memory ability in survivors treated with conformal radiation therapy (CRT). Fifty survivors (25 males, age at assessment = 13.14 ± 2.88, age at CRT = 7.41 ± 3.41 years) completed Digit Span from the Wechsler Intelligence Scales for Children, 4th Edition and experimental Self-Ordered Search (SOS) tasks as measures of working memory. Caregiver ratings were obtained using the Behavior Rating Inventory of Executive Function. MRI exams were acquired on a 1.5 T scanner. Volumes of normal appearing white matter (NAWM) were quantified using a well-validated automated segmentation and classification program. Correlational analyses demonstrated that NAWM volumes were significantly larger in males and participants with tumors located in the infratentorial space. Correlations between NAWM volume and Digit Span Backward were distributed across anterior and posterior regions, with evidence for greater right hemisphere involvement (r = .32–.34, p ≤ .05). Correlations between NAWM volume with Digit Span Backward (r = .44–.52; p ≤ .05) and NAWM volume with SOS-Object Total (r = .45–.52, p ≤ .05) were of greater magnitude in females. No relationship was found between NAWM volume and caregiver report. Working memory performance in survivors of pediatric BTs treated with CRT are related to regionally specific NAWM volume. Developmental differences in cerebral myelination may explain findings of greater risk for neurocognitive late effects in female survivors. Future studies are needed to better isolate vulnerable white matter pathways, thus facilitating the development of neuroprotective interventions.