Resection of highly functionally connected glioma regions predicts long-term cognitive preservation
- 1Amsterdam UMC, Vrije Universiteit Amsterdam
Abstract
BackgroundGlioma surgery requires balancing maximal tumor resection against preservation of neurological and cognitive function. Intraoperative direct electrical stimulation guides this balance but is invasive and not always feasible. Preoperative magnetoencephalography (MEG) can identify tumor regions with high functional connectivity (HFC) to the rest of the brain. These HFC areas contain more malignant glioma cells and relate to poorer short-term outcome when resected. We aimed to determine whether HFC voxel resection relates to postoperative neurological and cognitive outcomes.
MethodsIn this preregistered analysis, 54 adults with diffuse glioma underwent resting-state MEG before resection. Imaginary coherence identified voxels with significantly higher connectivity against their contralateral controls, and these HFC voxels within the resection cavity were counted. Neurological status was assessed at short-term ([~]1 week) and long-term ([~]1 year) follow-up, and neuropsychological assessment took place at baseline and long-term follow-up. Logistic regressions related resected HFC voxels to decline at each timepoint, adjusting for Karnofsky performance status, sex and resectability index.
ResultsResected HFC voxels were not associated with neurological decline at short-term (48% declined; odds ratio [OR] 0.98, P = .50) or long-term follow-up (27% declined; OR 0.99). For cognition, more resected HFC voxels were associated with less long-term decline (48% declined; OR 0.85, P = .02); a binarized analysis was consistent (OR 0.076, P = .01), indicating that tumor volume did not drive this result.
ConclusionsResecting more HFC voxels associates with preserved long-term cognition, without apparent neurological cost. Non-invasive MEG connectivity mapping may help optimize the onco-functional balance in glioma surgery.
Key pointsO_LIResecting more highly functionally connected tumor voxels relates to preserved long-term cognition in glioma. C_LIO_LIConnectivity did not predict postsurgical neurological outcome. C_LIO_LIPreoperative MEG connectivity mapping may help inform the onco-functional balance. C_LI
Importance of the StudyAchieving the optimal onco-functional balance in glioma surgery means resecting as much tumor as possible, while preserving neurological and cognitive function over the long term. Intraoperative direct electrical stimulation helps guide this balance but is invasive, time-consuming, and not always feasible. This study extends preoperative, non-invasive MEG functional connectivity mapping to neurological and cognitive outcomes up to one year after surgery, using a different MEG system, cohort, and center than used in prior work. We show that resecting more high functionally connected voxels associates with preserved long-term cognition, at no neurological cost. Preoperative MEG connectivity could therefore complement stimulation mapping to guide safer, more effective resections, particularly in IDH-mutant glioma, whose longer survival makes long-term cognitive preservation especially important.
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BibTeX
@misc{lingen2026resection,
title = {{Resection of highly functionally connected glioma regions predicts long-term cognitive preservation}},
author = {M. R. van Lingen and A. Jaiswal and S. Nagarajan and V. Jayabal and M. Klein and N. Verburg and P. de Witt Hamer and A. Hillebrand and L. Douw},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26363885},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26363885v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Resection of highly functionally connected glioma regions predicts long-term cognitive preservation
AU - M. R. van Lingen
AU - A. Jaiswal
AU - S. Nagarajan
AU - V. Jayabal
AU - M. Klein
AU - N. Verburg
AU - P. de Witt Hamer
AU - A. Hillebrand
AU - L. Douw
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26363885
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26363885v1
AB - BackgroundGlioma surgery requires balancing maximal tumor resection against preservation of neurological and cognitive function. Intraoperative direct electrical stimulation guides this balance but is invasive and not always feasible. Preoperative magnetoencephalography (MEG) can identify tumor regions with high functional connectivity (HFC) to the rest of the brain. These HFC areas contain more malignant glioma cells and relate to poorer short-term outcome when resected. We aimed to determine whether HFC voxel resection relates to postoperative neurological and cognitive outcomes. MethodsIn this preregistered analysis, 54 adults with diffuse glioma underwent resting-state MEG before resection. Imaginary coherence identified voxels with significantly higher connectivity against their contralateral controls, and these HFC voxels within the resection cavity were counted. Neurological status was assessed at short-term ([~]1 week) and long-term ([~]1 year) follow-up, and neuropsychological assessment took place at baseline and long-term follow-up. Logistic regressions related resected HFC voxels to decline at each timepoint, adjusting for Karnofsky performance status, sex and resectability index. ResultsResected HFC voxels were not associated with neurological decline at short-term (48% declined; odds ratio [OR] 0.98, P = .50) or long-term follow-up (27% declined; OR 0.99). For cognition, more resected HFC voxels were associated with less long-term decline (48% declined; OR 0.85, P = .02); a binarized analysis was consistent (OR 0.076, P = .01), indicating that tumor volume did not drive this result. ConclusionsResecting more HFC voxels associates with preserved long-term cognition, without apparent neurological cost. Non-invasive MEG connectivity mapping may help optimize the onco-functional balance in glioma surgery. Key pointsO_LIResecting more highly functionally connected tumor voxels relates to preserved long-term cognition in glioma. C_LIO_LIConnectivity did not predict postsurgical neurological outcome. C_LIO_LIPreoperative MEG connectivity mapping may help inform the onco-functional balance. C_LI Importance of the StudyAchieving the optimal onco-functional balance in glioma surgery means resecting as much tumor as possible, while preserving neurological and cognitive function over the long term. Intraoperative direct electrical stimulation helps guide this balance but is invasive, time-consuming, and not always feasible. This study extends preoperative, non-invasive MEG functional connectivity mapping to neurological and cognitive outcomes up to one year after surgery, using a different MEG system, cohort, and center than used in prior work. We show that resecting more high functionally connected voxels associates with preserved long-term cognition, at no neurological cost. Preoperative MEG connectivity could therefore complement stimulation mapping to guide safer, more effective resections, particularly in IDH-mutant glioma, whose longer survival makes long-term cognitive preservation especially important.
ER -