Silent Verb Generation During fMRI Reveals Post-Radiotherapy Alterations in Cerebellar–Cerebral Language Regions in Patients Treated for Medulloblastoma

Background: Medulloblastoma is the most common malignant pediatric brain tumor. Although radiotherapy improves survival, it is often associated with neurocognitive impairments affecting language and executive functions in developing brains. We investigated treatment-related changes in task-evoked activation using silent verb generation fMRI. Methods: Thirty-one children and adolescents with medulloblastoma enrolled on SJMB12 (18 males; mean age 14.1 ± 4.7 years) completed visual and auditory noun-cued covert verb generation during fMRI before radiotherapy and again within 6 weeks after completing radiotherapy. A two-stage, nested feature-selection framework coupled with a linear Support Vector Machine differentiated pre- from post-irradiation scans using leave-one-subject-out cross-validation, benchmarked against a paired pre-to-post label-swap permutation test. Results: The classifier distinguished pre- from post-irradiation scans with 80.7% leave-one-subject-out accuracy, exceeding the permutation-derived null distribution (one-sided p = 0.0149). Post-treatment task-related BOLD changes showed reduced activity in bilateral cerebellar hemispheres (Crus I/II, lobules VI-VIII), left inferior frontal gyrus, left insula, left putamen, supragenual anterior cingulate, and left middle temporal gyrus. Reduced task-negative responses were observed in a large cluster overlapping right precuneus, right superior parietal, right paracentral, and right postcentral cortices, alongside increased engagement of the left supramarginal gyrus and left inferior parietal lobule. Conclusions: These findings indicate that radiotherapy is associated with early functional reorganization in cerebellar-cerebral circuits supporting language production and cognitive control, with possible compensatory recruitment of dorsal parietal phonological working memory regions during covert speech. Neuroimaging-based monitoring of these network changes may help guide interventions aimed at minimizing cognitive sequelae in medulloblastoma patients.