Neurocognitive and resting-state functional MRI changes in patients with diffuse gliomas after chemoradiotherapy.

Abstract

Background: This prospective observational study employed resting-state functional MRI (rs-fMRI) to investigate network-level disturbances associated with neurocognitive function (NCF) changes in patients with gliomas following partial-brain radiation therapy (RT).

Methods: Adult post-operative patients with either IDH-wildtype or IDH-mutant gliomas underwent computerized NCF testing and rs-fMRI at baseline and 6 months post-RT. rs-fMRI data were assessed using seed-based functional connectivity (FC). NCF changes were quantified by the percent change in age-normalized composite scores from baseline (ΔNCF_comp). Connectivity-regression analysis assessed the association between network FC changes and NCF changes, using a split-sample approach with a 26-patient training set and a 6-patient validation set, iterated 200 times. Permutation tests evaluated the significance of network selection.

Results: Between September 2020 and December 2023, 43 patients were enrolled, with 32 completing both baseline and follow-up evaluations. The mean ΔNCF_comp was 2.9% (SD: 13.7%), with 38% experiencing a decline. Patients with IDH-mutant glioma had similar NCF changes compared to those with IDH-wildtype glioma. Intra-hemispheric FC was similar between ipsilateral and contralateral hemispheres for 91% patients at baseline, and 69% had similar intra-hemispheric FC change post-treatment. FC changes accounted for a moderate fraction of variance in NCF changes (mean R²: 0.301, SD: 0.249), with intra-network FC of the Parietal Memory Network (PMN-PMN, p=0.001) and inter-network FC between the PMN and the Visual Network (PMN-VN, p=0.002) as the most significant factors. Similar findings were obtained by sensitivity analyses using only the FC data from the hemisphere contralateral to the tumor.

Conclusions: Post-RT rs-fMRI changes significantly reflected NCF decline, highlighting rs-fMRI as a promising imaging biomarker for neurocognitive decline after RT.