Impact of High-Grade Glioma Lesion Location on Preoperative Neuropsychological Deficits

<b>Background</b>: Glioblastoma (GBM) is an aggressive brain tumor, with surgery being an integral part of treatment. Aggressive resections improve clinical outcomes but need to be balanced against potential functional impairment. Neuropsychological (NP) testing is an important tool neurosurgeons use to assess cognitive functioning. Importantly, associations between NP test scores and imaging biomarkers could enable a testable baseline by which to track patient outcomes over time and aid in presurgical counseling. <b>Methods</b>: We identified 44 patients diagnosed with primary GBM and who had detailed NP testing and presurgical imaging. Regression models for NP indices were created with tumor size, hemisphere, and lobar location as predictors. Lesion-symptom mapping (LSM) analyses were used to identify more detailed structure-function relationships. <b>Results</b>: Larger tumor volumes predicted worse attention, immediate memory, language, visuospatial, and overall NP performance (<i>p</i> < 0.05 for all). Left hemisphere involvement predicted worse attention, language, and immediate memory NP performance (<i>p</i> < 0.01 for all). Only visuospatial testing had lobar location significantly associated with worse scores (occipital lobe; <i>p</i> < 0.05). The LSM analyses identified areas around the left sagittal stratum as significantly associated with language performance (<i>p</i> < 0.05), with no other structure-function relationships being identified. <b>Conclusions</b>: These findings support the growing evidence that outside of a small number of truly critical regions, high-grade gliomas impair cognition generally, likely due to progressive tumor infiltration-associated neuroplasticity of complex parallel and interconnected networks. To investigate this, future studies should incorporate larger cohort sizes and should examine the relationship of glioma-induced network-level perturbations on cognitive decline.