Alteration of default mode network: association with executive dysfunction in frontal glioma patients

Abstract

OBJECTIVE Patients with frontal gliomas often experience executive dysfunction (EF-D) before surgery, and the changes in brain plasticity underlying this effect remain obscure. In this study, the authors aimed to assess whole-brain structural and functional alterations by using structural MRI and resting-state functional MRI (rs-fMRI) in frontal glioma patients with or without EF-D. METHODS Fifty-seven patients with frontal gliomas were admitted prospectively to the authors’ institution and assigned to one of two groups: 1) the normal executive function (EF-N) group and 2) the EF-D group, based on patient results for the Trail Making Test, Part B and Stroop Color-Word Test, Part C. Twenty-nine baseline-matched healthy controls were also recruited. All participants underwent multimodal MRI examination. Cortical surface thickness, surface-based resting-state activity (fractional amplitude of low-frequency fluctuation [fALFF] and regional homogeneity [ReHo]), and edge-based network functional connectivity (FC) were measured with FreeSurfer and fMRIPrep. The correlation between altered MRI parameters and executive function (EF) was assessed using Pearson correlation and receiver operating characteristic (ROC) analysis. RESULTS Demographic characteristics (sex, age, and education level) and clinical characteristics (location, volume, grade of tumor, and preoperative epilepsy) were not significantly different between the groups, but the Karnofsky Performance Scale score was worse in the EF-D group. There was no significant difference in cortical surface thickness between the EF-D and EF-N groups. In both low-grade and high-grade glioma patients the fALFF value (permutation test + threshold-free cluster enhancement, p value after family-wise error correction < 0.05) and ReHo value (t-test, p < 0.001) of the left precuneus cortex in the EF-D group were greater than those in the EF-N group, which were negatively correlated with EF (p < 0.05) and enabled prediction of EF (area under the ROC curve 0.826 for fALFF and 0.855 for ReHo, p < 0.001). Compared with the EF-N group, the FCs between the default mode network (DMN) from DMN node to DMN node (DMN-DMN) and from the DMN to the central executive network (DMN-CEN) in the EF-D group were increased significantly (network-based statistics corrected p < 0.05) and negatively correlated with EF (Pearson correlation, p < 0.05). CONCLUSIONS Apart from local disruption, the abnormally activated DMN in the resting state is related to EF-D in frontal glioma patients. DMN activity should be considered during preoperative planning and postoperative neurorehabilitation for frontal glioma patients to preserve EF. Clinical trial registration no.: NCT03087838 (ClinicalTrials.gov)