Silent Verb Generation During fMRI Reveals Post-Radiotherapy Alterations in Cerebellar-Cerebral Language Regions in...

Background/Objectives: 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 functional magnetic resonance imaging (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 fully nested leave-one-subject-out cross-validation, in which the sign-consistency threshold was re-selected within each training fold, and was evaluated against the 50% chance level of the paired forced-choice design. Results: In fully nested leave-one-subject-out evaluation, the pipeline correctly ordered the paired pre- and post-radiotherapy scans for 22 of 31 participants (71.0%; 95% CI, 52.0-85.8%; one-sided permutation p = 0.015). Descriptive cohort-derived mapping at the modal inner-loop sign-consistency threshold implicated 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: In this single-center pilot cohort, silent verb-generation fMRI detected early post-radiotherapy activation changes within cerebellar-cerebral language and control networks. These findings require independent validation, test-retest controls, and longitudinal neurocognitive outcomes before being interpreted as clinical biomarkers.