Zhengge Wang1, Sara Larivière1, Qiang Xu1, Reinder Vos de Wael1, Seok-Jun Hong1, Zhongyuan Wang1, Yun Xu1, Bin Zhu1, Neda Bernasconi1, Andrea Bernasconi1, Bing Zhang1, Zhiqiang Zhang1, Boris C Bernhardt2. 1. From the Departments of Radiology (Z.W., B.Z., B.Z.) and Neurology (Z.W., Y.X.), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China; Multimodal Imaging and Connectome Analysis Laboratory (Z.W., S.L., R.V.d.W., S.-J.H., B.C.B.) and Neuroimaging of Epilepsy Laboratory (S.-J.H., N.B., A.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Quebec, Canada; and Department of Medical Imaging (Q.X., Z.Z.), Jinling Hospital, Nanjing University School of Medicine, China. 2. From the Departments of Radiology (Z.W., B.Z., B.Z.) and Neurology (Z.W., Y.X.), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China; Multimodal Imaging and Connectome Analysis Laboratory (Z.W., S.L., R.V.d.W., S.-J.H., B.C.B.) and Neuroimaging of Epilepsy Laboratory (S.-J.H., N.B., A.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Quebec, Canada; and Department of Medical Imaging (Q.X., Z.Z.), Jinling Hospital, Nanjing University School of Medicine, China. boris.bernhardt@mcgill.ca.
Abstract
OBJECTIVE: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. METHODS: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. RESULTS: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. CONCLUSIONS: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.
OBJECTIVE: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. METHODS: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. RESULTS: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. CONCLUSIONS: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.
Authors: Bo-Yong Park; Seok-Jun Hong; Sofie L Valk; Casey Paquola; Oualid Benkarim; Richard A I Bethlehem; Adriana Di Martino; Michael P Milham; Alessandro Gozzi; B T Thomas Yeo; Jonathan Smallwood; Boris C Bernhardt Journal: Nat Commun Date: 2021-04-13 Impact factor: 14.919
Authors: Sara Larivière; Raúl Rodríguez-Cruces; Jessica Royer; Maria Eugenia Caligiuri; Antonio Gambardella; Luis Concha; Simon S Keller; Fernando Cendes; Clarissa Yasuda; Leonardo Bonilha; Ezequiel Gleichgerrcht; Niels K Focke; Martin Domin; Felix von Podewills; Soenke Langner; Christian Rummel; Roland Wiest; Pascal Martin; Raviteja Kotikalapudi; Terence J O'Brien; Benjamin Sinclair; Lucy Vivash; Patricia M Desmond; Saud Alhusaini; Colin P Doherty; Gianpiero L Cavalleri; Norman Delanty; Reetta Kälviäinen; Graeme D Jackson; Magdalena Kowalczyk; Mario Mascalchi; Mira Semmelroch; Rhys H Thomas; Hamid Soltanian-Zadeh; Esmaeil Davoodi-Bojd; Junsong Zhang; Matteo Lenge; Renzo Guerrini; Emanuele Bartolini; Khalid Hamandi; Sonya Foley; Bernd Weber; Chantal Depondt; Julie Absil; Sarah J A Carr; Eugenio Abela; Mark P Richardson; Orrin Devinsky; Mariasavina Severino; Pasquale Striano; Domenico Tortora; Sean N Hatton; Sjoerd B Vos; John S Duncan; Christopher D Whelan; Paul M Thompson; Sanjay M Sisodiya; Andrea Bernasconi; Angelo Labate; Carrie R McDonald; Neda Bernasconi; Boris C Bernhardt Journal: Sci Adv Date: 2020-11-18 Impact factor: 14.136