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Accumulating evidence recognizes the following importance of grey matter networks: they only require high-resolution anatomical scans for their extraction, they capture changes beyond detectable atrophy and their alteration is associated with disability progression and cognitive impairment. Therefore, it is crucial to understand their behaviours over the initial years of the disease. This observational longitudinal study aimed to investigate changes in grey matter networks after the first demyelinating attack, and how they correlate with brain damage, disability, and conversion to multiple sclerosis over 3\u20135 years. So far, in multiple sclerosis, network construction has only been based on cortical grey matter, neglecting a possible role for deep grey matter. We applied a radiomics-based network methodology incorporating both deep and cortical grey matter. Patients recruited within 3 months of disease onset and healthy controls attended study visits at 6 months, 1 year, 3 years and 5 years. Study visits included physical and cognitive scales and brain MRI scans. Individual grey matter networks were constructed by computing the correlations between T1w-based radiomic features extracted from any pair of regions of the Brainnetome atlas and characterized with measures of network integration (global efficiency and characteristic path length), segregation (clustering coefficient and modularity), resilience (assortativity) and smallworldness. Additionally, eigenvector centrality was computed for all brain regions as a measure of nodal influence. We enrolled 89 patients (median follow-up 7 months, range 0\u201375) and 31 healthy controls. Patients showed higher global efficiency, lower shortest characteristic path length and higher smallworldness than controls suggesting a reorganization that prioritize more efficient global communication over local processing. Over time, patients\u2019 networks converged towards healthy controls\u2019 values by increasing the shortest characteristic path length and decreasing the smallworldness. Assortativity, and the eigenvector centrality in the right ventromedial putamen decreased compared with controls. All the observed changes were driven by non-converters to multiple sclerosis. This study shows that grey matter networks adopt a biphasic behaviour. They respond to the demyelinating event with an increase in nodal integration and then converge to healthy control values. In the process, however, their network resilience is compromised. This suggests that a single demyelinating event has longer-lasting effects on grey matter networks, even in non-converters, and that studying these networks may reveal relevant changes that are not captured by conventional MRI in the early years of the disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf367","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T16:25:12Z","timestamp":1758644712000},"source":"Crossref","is-referenced-by-count":1,"title":["The bi-phasic behaviour of grey matter networks after the first demyelinating attack"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-8983","authenticated-orcid":false,"given":"Sara","family":"Collorone","sequence":"first","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pontillo","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]},{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Vrije Universiteit , Amsterdam 1081 BT ,","place":["Netherlands"]},{"name":"Department of Advanced Biomedical Sciences, University \u2018Federico II\u2019 , Naples 80138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Foster","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-0142","authenticated-orcid":false,"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]},{"name":"Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London , London WC1B 6BT ,","place":["UK"]},{"name":"eHealth Center, Universitat Oberta de Catalunya , Barcelona 08018 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-8800","authenticated-orcid":false,"given":"Baris","family":"Kanber","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]},{"name":"Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London , London WC1B 6BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios C","family":"Yiannakas","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailbhe","family":"Burke","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital , London EC1V 2PD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Ogunbowale","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital , London EC1V 2PD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indran","family":"Davagnanam","sequence":"additional","affiliation":[{"name":"Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, Faculty of Brain Sciences, UCL , London WC1N 3AZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-1300","authenticated-orcid":false,"given":"Claudia A M","family":"Gandini Wheeler-Kingshott","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London , London WC1B 5EH ,","place":["UK"]},{"name":"Department of Brain and Behavioural Sciences, University of Pavia , Pavia 27100 ,","place":["Italy"]},{"name":"Brain MRI 3T Research Centre, IRCCS Mondino Foundation , Pavia 27100 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