한빛사논문
인하대학교, 기초과학연구원, McGill University
Bo-yong Park,1,2,3,* Sara Larivière,1 Raul Rodríguez-Cruces,1 JessicaRoyer,1 Shahin Tavakol,1 Yezhou Wang,1 Lorenzo Caciagli,4,5,6 Maria Eugenia Caligiuri,7 Antonio Gambardella,7,8 Luis Concha,9 Simon S. Keller,10,11 Fernando Cendes,12 Marina K. M. Alvim,12 Clarissa Yasuda,12 Leonardo Bonilha,13 Ezequiel Gleichgerrcht,13 Niels K. Focke,14 Barbara A. K. Kreilkamp,14 Martin Domin,15 Felix von Podewils,16 Soenke Langner,17 Christian Rummel,18 Michael Rebsamen,18 Roland Wiest,18 Pascal Martin,19 Raviteja Kotikalapudi,19,20 Benjamin Bender,20 Terence J. O’Brien,21,22 Meng Law,21 Benjamin Sinclair,21,22 Lucy Vivash,21,22 Patrick Kwan,21,22 Patricia M. Desmond,22 Charles B. Malpas,22 Elaine Lui,22 Saud Alhusaini,23,24 Colin P. Doherty,25,26 Gianpiero L. Cavalleri,23,26 Norman Delanty,23,26 Reetta Kälviäinen,27,28 Graeme D. Jackson,29 Magdalena Kowalczyk,29 Mario Mascalchi,30 Mira Semmelroch,29 Rhys H. Thomas,31 Hamid Soltanian-Zadeh,32,33 Esmaeil Davoodi-Bojd,34 Junsong Zhang,35 Matteo Lenge,36,37 Renzo Guerrini,36 Emanuele Bartolini,38 Khalid Hamandi,39,40 Sonya Foley,39 Bernd Weber,41 Chantal Depondt,42 Julie Absil,43 Sarah J. A. Carr,44 Eugenio Abela,44 Mark P. Richardson,44 Orrin Devinsky,45 Mariasavina Severino,46 Pasquale Striano,46 Costanza Parodi,46 Domenico Tortora,46 Sean N. Hatton,47 Sjoerd B. Vos,4,5,48 John S. Duncan,4,5 Marian Galovic,4,5,49 Christopher D. Whelan,50 Núria Bargalló,51,52 Jose Pariente,51 Estefania Conde-Blanco,53 Anna Elisabetta Vaudano,54,55 Manuela Tondelli,54,55 Stefano Meletti,54,55 Xiang‐Zhen Kong,56,57 Clyde Francks,56,58 Simon E. Fisher,56,58 Benoit Caldairou,59 Mina Ryten,60,61,62 Angelo Labate,7,8 Sanjay M. Sisodiya,4,5 Paul M. Thompson,63 Carrie R. McDonald,64 Andrea Bernasconi,59 Neda Bernasconi59 and Boris C. Bernhardt1,*
1Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
2Department of Data Science, Inha University, Incheon, Republic of Korea
3Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea
4Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK
5MRI Unit, Epilepsy Society, Chalfont St Peter, Bucks, UK
6Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
7Neuroscience Research Center, University Magna Græcia, Catanzaro, CZ, Italy
8Institute of Neurology, University Magna Græcia, Catanzaro, CZ, Italy
9Institute of Neurobiology, Universidad Nacional Autónoma de México, Querétaro, México
10Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
11Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
12Department of Neurology, University of Campinas–UNICAMP, Campinas, São Paulo, Brazil
13Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
14Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
15Institute of Diagnostic Radiology and Neuroradiology, Functional Imaging Unit,
University Medicine Greifswald, Greifswald, Germany
16Department of Neurology, University Medicine Greifswald, Greifswald, Germany
17Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
18Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland
19Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
20Department of Radiology, Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany
21Department of Neuroscience, Central Clinical School, Alfred Hospital, Monash University, Melbourne, Victoria, Australia
22Departments of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
23Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland
24Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
25Department of Neurology, St James’ Hospital, Dublin, Ireland
26FutureNeuro SFI Research Centre, Dublin, Ireland
27Epilepsy Center, Neuro Center, Kuopio University Hospital, Member of the European Reference Network for Rare and Complex Epilepsies EpiCARE, Kuopio, Finland
28Faculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
29Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne VIC 3010, Australia
30Neuroradiology Research Program, Meyer Children Hospital of Florence, University of Florence, Florence, Italy
31Transitional and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
32Control and Intelligent Processing Center of Excellence (CIPCE), School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran
33Departments of Research Administration and Radiology, Henry Ford Health System, Detroit, MI, USA
34Department of Neurology, Henry Ford Health System, Detroit, MI, USA
35Department of Artificial Intelligence, Xiamen University, Xiamen, China
36Child Neurology Unit and Laboratories, Neuroscience Department, Children’s Hospital A. Meyer-University of Florence, Italy
37Functional and Epilepsy Neurosurgery Unit, Neurosurgery Department, Children’s Hospital A. Meyer-University of Florence, Italy
38USL Centro Toscana, Neurology Unit, Nuovo Ospedale Santo Stefano, Prato, Italy
39Cardiff University Brain Research Imaging Centre (CUBRIC), College of Biomedical Sciences, Cardiff University, Cardiff, UK
40The Welsh Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff, UK
41Institute of Experimental Epileptology and Cognition Research, University Hospital Bonn, Bonn, Germany
42Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
43Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
44Division of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK
45Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA
46IRCCS Istituto Giannina Gaslini, Genova, Italy and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova,
Genova, Italy
47Department of Neurosciences, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA
48Centre for Medical Image Computing, University College London, London, UK
49Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
50Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland
51Magnetic Resonance Image Core Facility., Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
52Department of Radiology CDIC, Hospital Clinic Barcelona, Spain
53Epilepsy Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain
54Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, OCB Hospital, Modena, Italy
55Department of Biomedical, Metabolic, and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy
56Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands
57Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China
58Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
59Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
60Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, UK
61NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, UK
62Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, UK
63Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging and Informatics, USC Keck School of Medicine, Los Angeles, CA, USA
64Department of Psychiatry, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA
*Correspondence to: Bo-yong Park
*Correspondence may also be addressed to: Boris C. Bernhardt, PhD
Abstract
Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated.
Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 TLE patients and 53 healthy controls, and examined clinical associations using machine learning.
We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables.
Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.
Keywords : temporal lobe epilepsy, asymmetry, cortical thickness, multi-site, gradients
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