Contralesional grey matter volume as an index of macrostructural plasticity in patients with brain tumors

Abstract This research challenges the traditional localizationist view that brain tumors affect only regions directly associated with the lesion, by examining whether they also induce macrostructural alterations in the contralesional hemisphere. We applied Voxel-Based Morphometry, linear regression, and Principal Component Analysis (PCA) to a cohort of 107 adults, including patients with gliomas in the language-dominant left hemisphere and healthy participants. Unlike previous studies, a subset of the clinical population was followed longitudinally for up to four months after oncological treatment, allowing us to describe the temporal progression of structural grey matter changes. Interestingly, a principal component model based on anomaly detection enabled robust differentiation between patients and controls. Patients exhibited significantly greater grey matter volume in the contralesional hemisphere compared to healthy participants, and these structural differences evolved over time, improving the model’s AUC-ROC metrics. Although exploratory, a correlation analysis revealed that these structural changes were negatively associated with postsurgical cognitive performance. Together with the PCA findings, these results suggest that brain tumors induce extensive and dynamic adaptive mechanisms in the contralateral, unaffected hemisphere, likely reflecting altered patterns of structural covariance rather than simple regional volume increases. Understanding whether these changes could represent potential predictors of postoperative cognitive recovery is crucial for developing comprehensive clinical strategies. Key Points Left-hemisphere tumors induce contralesional grey matter increases pre- and post-sugery PCA detects altered structural covariance and distinguishes patients from healthy participants Contralesional grey matter volume changes correlate with postoperative cognitive performance Importance of the Study This study challenges the traditional view that brain tumors cause only localized effects by demonstrating widespread macrostructural alterations in the contralesional hemisphere. We reveal increased grey matter volume and altered patterns of structural covariance outside the tumor region. Longitudinal follow-up after surgery shows these changes are dynamic and evolve over time. Further, we identify moderate associations between contralesional grey matter alterations and cognitive performance, suggesting a link between large-scale neuroplastic responses and functional outcomes. These findings offer new insights into tumor-related neuroplasticity and position structural covariance as a promising marker for tracking brain-wide adaptation in this population. The study has translational relevance for developing predictive tools to monitor recovery and guide personalized rehabilitation.