Cortical Manifolds in Cognitive Recovery following Supratentorial Neurosurgery

Abstract 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, 59 unique scans), 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 long-term deficits were associated with decreases in gradient dispersion; longitudinal analyses revealed month 3 (not month 12) as the crucial window for gradient reconstitution. Overall, diffuse gliomas minimally disrupt the assembly of cortical manifolds, but the ability to reorganize the cortical manifold within 3 months post-surgery is predictive of long-term cognitive outcomes. By investigating neurosurgical patients with atypical neuroanatomy, this study contributes to the expanding literature on how aging, disease, and pharmacological interventions impact cortical gradients. Future studies are warranted to assess the utility of mapping cortical manifolds in neurosurgical patients. Competing Interest Statement MES is the co-founder of Omniscient Neurotechnology. Funding Statement 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. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Cambridge Central Research Ethics Committee (Reference number 16/EE/0151) and all patients provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Spelling/grammatical issues corrected, Figure 1 updated, gradient maximization/minimization Data Availability All data produced in the present study are available upon reasonable request to the authors