{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:23:41Z","timestamp":1788967421051,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Brain tumours impose complex, spatially heterogeneous disturbances on neural circuits that extend far beyond the immediate lesion site. While gross anatomical displacement of the cortico-spinal tract (CST) has been extensively studied, the topological reorganization of the functionally informed structural connectome\u2014and its dependence on tumour molecular phenotype\u2014remains incompletely understood. Objectives: This study aimed to characterize upper-limb functionally informed network topology in brain tumour patients, identify histological and molecular patterns of structural reorganization at the cortical and subcortical level, and determine the impact on neurophysiological parameters. Methods: Forty-eight patients with supratentorial motor-eloquent tumours (MET\u2019s) underwent diffusion-weighted imaging (DWI) as part of their preoperative motor mapping. Connectivity matrices based on streamline passing counts were extracted from 426 nodes of the HCPex atlas using DSI Studio\u00ae upon seeding the structural connectome in the motor hotspot (best motor response) for the functional area of the upper limb identified using preoperative navigated transcranial magnetic stimulation (nTMS). Paired-sample t-tests compared tumour versus healthy hemispheres across network topology metrics. The impact of nTMS-derived excitability metrics\u2014interhemispheric resting motor threshold ratio (iRMTr) and cortical silent period (CSP)\u2014and tumour histological and molecular characteristics on the connectome was assessed. Results: The global network topology of the tumour hemisphere was preserved when compared to the healthy baseline hemisphere across all tumour types (p &gt; 0.05). Subcortical analysis revealed significant hyper-connectivity in the tumour hemisphere, with elevated degree, strength, clustering coefficient, local efficiency, and eigenvector centrality (p &lt; 0.05). Basal ganglia motor loop degree was increased in the tumour hemisphere (mean 7.37 versus 5.19; p = 0.0009). IDH-mutant tumours generated significantly more topologically organized compensatory networks than IDH-wildtype tumours (Clustering Coefficient 0.345 versus 0.273; p = 0.018). Of the cortical nodes on the side of the tumour, significant hyper-connectivity was seen in the supplementary motor area (p = 0.0011), premotor cortex (Area 6), with increased connection seen in 6 mp (medial premotor at p =0.0033) and 6 d (dorsal premotor at p = 0.025) and primary somatosensory cortex (p = 0.027). The presence of the tumour induced significant changes across all three domains: loss of CST volume (p &lt; 0.001), prolongation of the cortical silent period indicative of intracortical inhibition (p &lt; 0.0001), with significant prolongation in glioblastoma versus an oligodendroglioma. Conclusions: Brain tumours significantly impact the upper limb-centred structural connectome. While global network topology is preserved, tumours induce substantial subcortical and basal ganglia network reorganization by inducing compensatory hyper-connectivity. These findings suggest that structural connectomics offers a novel framework for non-invasive tumour characterization and surgical planning.<\/jats:p>","DOI":"10.3390\/cancers18182925","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:01:56Z","timestamp":1788966116000},"page":"2925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functionally Informed Hand Knob Reveals Structural Connectome Differences in Motor-Eloquent Tumours"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0579-2425","authenticated-orcid":false,"given":"Sankhya","family":"Prakashvel","sequence":"first","affiliation":[{"name":"Queens\u2019 Hospital Romford, London RM7 0AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Sinosi","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-218X","authenticated-orcid":false,"given":"Laura","family":"Ferrari","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0103-9500","authenticated-orcid":false,"given":"Feras","family":"Fayez","sequence":"additional","affiliation":[{"name":"University College London Hospital, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Patel","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-0289","authenticated-orcid":false,"given":"Yasir A.","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Perera","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1408-1396","authenticated-orcid":false,"given":"Nida","family":"Kalyal","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Awan","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-516X","authenticated-orcid":false,"given":"Alba","family":"Diaz-Baamonde","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-898X","authenticated-orcid":false,"given":"Ana","family":"Mirallave-Pescador","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyoumars","family":"Ashkan","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjeev","family":"Bhangoo","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Vergani","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-111X","authenticated-orcid":false,"given":"Jose Pedro","family":"Lavrador","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brown, N.F., Ottaviani, D., Tazare, J., Gregson, J., Kitchen, N., Brandner, S., Fersht, N., and Mulholland, P. (2022). Survival Outcomes and Prognostic Factors in Glioblastoma. Cancers, 14.","DOI":"10.3390\/cancers14133161"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-211-72283-1_1","article-title":"Brain plasticity and tumors","volume":"33","author":"Duffau","year":"2008","journal-title":"Adv. Tech. Stand. Neurosurg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104398","DOI":"10.1016\/j.bas.2025.104398","article-title":"Structural versus Functionally-informed Supratotal Resection: Where do we stand?","volume":"5","author":"Chowdhury","year":"2025","journal-title":"Brain Spine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.neuroimage.2009.10.003","article-title":"Complex network measures of brain connectivity: Uses and interpretations","volume":"52","author":"Rubinov","year":"2010","journal-title":"Neuroimage"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1038\/s41467-024-47185-9","article-title":"Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging","volume":"15","author":"Watson","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"bhad493","DOI":"10.1093\/cercor\/bhad493","article-title":"Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability","volume":"34","author":"Pescador","year":"2024","journal-title":"Cereb. Cortex"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15158","DOI":"10.1038\/s41598-021-94494-w","article-title":"Cortical silent period reflects individual differences in action stopping performance","volume":"11","author":"Paci","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3171\/2016.4.JNS152896","article-title":"Risk stratification in motor area-related glioma surgery based on navigated transcranial magnetic stimulation data","volume":"126","author":"Rosenstock","year":"2017","journal-title":"J. Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/2023.11.FOCUS23648","article-title":"Radiographic growth rate as a predictor of aggressiveness of diffuse gliomas without 1p19q codeletion","volume":"56","author":"Leclerc","year":"2024","journal-title":"Neurosurg. Focus."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1093\/brain\/aww194","article-title":"Brain networks under attack: Robustness properties and the impact of lesions","volume":"139","author":"Aerts","year":"2016","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Martinez Lozada, P.S., Neira, J.P., and Leon-Rojas, J.E. (2025). From Tumor to Network: Functional Connectome Heterogeneity and Alterations in Brain Tumors-A Multimodal Neuroimaging Narrative Review. Cancers, 17.","DOI":"10.3390\/cancers17132174"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.wneu.2018.09.198","article-title":"Navigated Transcranial Magnetic Stimulation in Patient with Cranioplasty in Situ: Safe and Accurate Procedure","volume":"122","author":"Lavrador","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00701-017-3187-z","article-title":"Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report","volume":"159","author":"Krieg","year":"2017","journal-title":"Acta Neurochir."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.nicl.2017.08.010","article-title":"Specific DTI seeding and diffusivity-analysis improve the quality and prognostic value of TMS-based deterministic DTI of the pyramidal tract","volume":"16","author":"Rosenstock","year":"2017","journal-title":"Neuroimage Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E3435","DOI":"10.1073\/pnas.1302581110","article-title":"Two distinct forms of functional lateralization in the human brain","volume":"110","author":"Gotts","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s42003-022-03190-6","article-title":"Network analysis shows decreased ipsilesional structural connectivity in glioma patients","volume":"5","author":"Fekonja","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lohmann, G., Margulies, D.S., Horstmann, A., Pleger, B., Lepsien, J., Goldhahn, D., Schloegl, H., Stumvoll, M., Villringer, A., and Turner, R. (2010). Eigenvector centrality mapping for analyzing connectivity patterns in fMRI data of the human brain. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010232"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Joyce, K.E., Laurienti, P.J., Burdette, J.H., and Hayasaka, S. (2010). A new measure of centrality for brain networks. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012200"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e26723","DOI":"10.1002\/hbm.26723","article-title":"Structural changes in eloquent cortex secondary to glioma in sensorimotor area","volume":"45","author":"Guo","year":"2024","journal-title":"Hum. Brain Mapp."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fang, S., Li, L., Weng, S., Guo, Y., Zhong, Z., Fan, X., Jiang, T., and Wang, Y. (2022). Contralesional Sensorimotor Network Participates in Motor Functional Compensation in Glioma Patients. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.882313"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.cortex.2013.08.005","article-title":"The huge plastic potential of adult brain and the role of connectomics: New insights provided by serial mappings in glioma surgery","volume":"58","author":"Duffau","year":"2014","journal-title":"Cortex"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s42003-024-06119-3","article-title":"Functional and structural reorganization in brain tumors: A machine learning approach using desynchronized functional oscillations","volume":"7","author":"Cacciola","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12943-025-02246-5","article-title":"Hijacking of the nervous system in cancer: Mechanism and therapeutic targets","volume":"24","author":"Zhang","year":"2025","journal-title":"Mol. Cancer."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1093\/brain\/awac360","article-title":"Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients","volume":"146","author":"Wei","year":"2023","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Choate, K.A., Pratt, E.P.S., Jennings, M.J., Winn, R.J., and Mann, P.B. (2024). IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications. Biology, 13.","DOI":"10.20944\/preprints202410.0393.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1016\/j.cell.2022.06.054","article-title":"Glioblastoma hijacks neuronal mechanisms for brain invasion","volume":"185","author":"Venkataramani","year":"2022","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hosseini, S.A., Hosseini, E., Hajianfar, G., Shiri, I., Servaes, S., Rosa-Neto, P., Godoy, L., Nasrallah, M.P., O\u2019Rourke, D.M., and Mohan, S. (2023). MRI-Based Radiomics Combined with Deep Learning for Distinguishing IDH-Mutant WHO Grade 4 Astrocytomas from IDH-Wild-Type Glioblastomas. Cancers, 15.","DOI":"10.3390\/cancers15030951"},{"key":"ref_28","first-page":"102377","article-title":"Preoperative prediction of IDH1 mutation status Ki-67 expression in glioma using apparent diffusion coefficient parameters","volume":"19","author":"Han","year":"2026","journal-title":"J. Radiat. Res. Appl. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/s41467-017-01285-x","article-title":"The challenge of mapping the human connectome based on diffusion tractography","volume":"8","author":"Neher","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18719","DOI":"10.1038\/s41598-022-23444-x","article-title":"Assessing the feasibility of mapping the tibialis anterior muscle with navigated transcranial magnetic stimulation in neuro-oncologic patients","volume":"12","author":"Eibl","year":"2022","journal-title":"Sci. Rep."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2925\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:05:29Z","timestamp":1788966329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":30,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18182925"],"URL":"https:\/\/doi.org\/10.3390\/cancers18182925","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}