Subcortical and Cerebellar Compensation for Motor Control in Medial Frontal Glioblastoma: A Task-Based Connectivity...

Patients with medial frontal gliomas often retain motor function despite tumor infiltration of canonical planning hubs, a paradox suggesting unmapped compensatory networks. We used task-based connectivity analysis to reveal demand-dependent reorganization invisible to standard mapping, aiming to identify distributed systems critical for surgical preservation. Twenty-five WHO Grade IV left medial frontal glioma patients and 25 controls performed visually-paced finger-tapping (2 Hz) during 3 T fMRI. Generalized psychophysiological interaction (gPPI) analysis mapped task-modulated connectivity within sensorimotor, subcortical, cerebellar, and frontoparietal networks. Brain-behavior correlations assessed functional relevance. Canonical sensorimotor coupling and Putamen-Thalamus integration were silenced in patients. Contrary to traditional plasticity models predicting contralesional recruitment, compensation operated through unexpected pathways: Caudate-dominated subcortical connectivity (F = 42.42, p-FDR < 0.05) emerged exclusively in patients, correlating with motor accuracy (ρ = 0.44, p = 0.028); anterior cerebellar feedback circuits (Lobules III/VIII) were recruited; and enhanced frontoparietal engagement indicated cognitive supervision of movement. Patients who exhibited this canonical reorganization pattern, comprising 68% of the cohort, significantly outperformed those who did not (p = 0.014). Preservation of visual network connectivity supported externally-guided timing as a compensatory scaffold. Medial frontal gliomas induce a shift from automatic to cognitively-supervised motor control, mediated by a Caudate-cerebellar-frontoparietal axis that acquires functional significance specifically under task demand. These compensatory networks undetectable at rest represent critical surgical targets. Approximately one-third of patients did not engage this reorganization and showed corresponding performance deficits, suggesting the value of individualized preoperative connectivity mapping. This represents one of the first task-based gPPI evidence demonstrating Caudate-dominated subcortical compensation specifically replacing canonical Putamen-Thalamus motor circuits in WHO Grade IV medial frontal gliomas.