The cerebral cortex is topographically organized to integrate and segregate unimodal (e.g. sensorimotor) and transmodal brain networks to scaffold cognition. Cortical gradient mapping provides a framework to examine the relationship between connectivity patterns of macroscale functional brain networks within a low-dimensional (manifold) space. Using this technique, we longitudinally examine how diffuse gliomas, their neurosurgical resection, and subsequent cognitive rehabilitation impact the topographic organization of brain networks. First, using UKBioBank data (n=4000), we validate the general assembly of cortical gradients in healthy individuals. Next, using CamCan data (n=620), we found that gradient dispersion relates to executive functions (EFs) across the lifespan. Finally, in diffuse glioma patients undergoing neurosurgery (n=17), we observed that gliomas integrate into the cortical manifold by reducing gradient dispersion compared to healthy controls. This finding was replicated in an independent cohort and contrasted with meningioma patients. Finally, long-term cognitive improvement after surgery was linked to increases in gradient dispersion, while deficits were associated with decreases. Overall, diffuse gliomas minimally disrupt the cortical manifold, but the ability to reorganize the cortical manifold post-surgery is predictive of long-term cognitive outcomes. Future studies are warranted to further assess the utility of mapping cortical manifolds in neurosurgical patients.

MES is the co-founder of Omniscient Neurotechnology.

This research was supported by the Alan Turing Institute, NSERC, Guarantors of Brain, Cancer Research UK Cambridge Centre, The Brain Tumour Charity and the EMERGIA Junta de Andalucia program. Y.E. is funded by a Royal Society Dorothy Hodgkin Research Fellowship (DHF130100). This research was also supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). SJP (NIHR Career Development Fellowship, CDF-2018-11-ST2-003) is funded by the National Institute for Health Research (NIHR) for this research project. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

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The study was approved by the Cambridge Central Research Ethics Committee (Reference number 16/EE/0151) and all patients provided written informed consent.

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