Longitudinal Evaluation of Brain Plasticity in Low-Grade Gliomas: fMRI and Graph-Theory Provide Insights on Language Reorganization

SIMPLE SUMMARY: This longitudinal study demonstrates the development of language plasticity in right-handed patients undergoing surgery for left-hemispheric low-grade glioma, characterized by the gradually increased involvement of the right hemisphere in language function. Two patterns of language reorganization were identified: type 1 changes may in part be treatment-related; type 2 may be tumor-induced, since atypical language organization was already present at baseline. Increased inter-hemispheric connectivity may represent the initial step in the development of plastic phenomena. This change could be partially compensatory towards clinical deficits and show prognostic value. ABSTRACT: Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and standardized language assessment. We hypothesized that functional networks obtained from tb-fMRI would show connectivity changes over time, with increased right-hemispheric participation. We recruited five right-handed patients (4M, mean age 47.6Y) with left-hemispheric LGG. Tb-fMRI and language assessment were conducted pre-operatively (pre-op), and post-operatively: post-op1 (4–8 months), post-op2 (10–14 months) and post-op3 (16–23 months). We computed the individual functional networks applying optimal percolation thresholding. Language dominance and hemispheric connectivity were quantified by laterality indices (LI) on fMRI maps and connectivity matrices. A fixed linear mixed model was used to assess the intra-patient correlation trend of LI values over time and their correlation with language performance. Individual networks showed increased inter-hemispheric and right-sided connectivity involving language areas homologues. Two patterns of language reorganization emerged: Three/five patients demonstrated a left-to-codominant shift from pre-op to post-op3 (type 1). Two/five patients started as atypical dominant at pre-op, and remained unchanged at post-op3 (type 2). LI obtained from tb-fMRI showed a significant left-to-right trend in all patients across timepoints. There were no significant changes in language performance over time. Type 1 language reorganization may be related to the treatment, while type 2 may be tumor-induced, since it was already present at pre-op. Increased inter-hemispheric and right-side connectivity may represent the initial step to develop functional plasticity.