{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:22:41Z","timestamp":1789525361208,"version":"build-2803163510"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.953356","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T10:47:21Z","timestamp":1658486841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Reconfiguration of static and dynamic thalamo-cortical network functional connectivity of epileptic children with generalized tonic-clonic seizures"],"prefix":"10.3389","volume":"16","author":[{"given":"Yongxin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1093\/cercor\/bhs352","article-title":"Tracking whole-brain connectivity dynamics in the resting state.","volume":"24","author":"Allen","year":"2014","journal-title":"Cereb. cortex"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1016\/j.clinph.2020.04.164","article-title":"Thalamic and cortical hyperexcitability in juvenile myoclonic epilepsy.","volume":"131","author":"Assenza","year":"2020","journal-title":"Clin. Neurophys."},{"key":"B3","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/j.1528-1167.2010.02522.x","article-title":"Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE commission on classification and terminology, 2005\u20132009.","volume":"51","author":"Berg","year":"2010","journal-title":"Epilepsia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.neuroimage.2009.01.055","article-title":"Thalamo\u2013cortical network pathology in idiopathic generalized epilepsy: insights from MRI-based morphometric correlation analysis.","volume":"46","author":"Bernhardt","year":"2009","journal-title":"NeuroImage"},{"key":"B5","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/mrm.1910340409","article-title":"Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.","volume":"34","author":"Biswal","year":"1995","journal-title":"Magn. Reson. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/epi.14614","article-title":"Alterations in the hippocampal-thalamic pathway underlying secondarily generalized tonic\u2013clonic seizures in mesial temporal lobe epilepsy: a diffusion tensor imaging study.","volume":"60","author":"Chen","year":"2019","journal-title":"Epilepsia"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5648","DOI":"10.1002\/hbm.25644","article-title":"Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy.","volume":"42","author":"Chen","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1093\/cercor\/bhaa334","article-title":"Reconfiguration of Directed Functional Connectivity Among Neurocognitive Networks with Aging: Considering the Role of Thalamo-Cortical Interactions.","volume":"31","author":"Das","year":"2021","journal-title":"Cereb. cortex"},{"key":"B9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s10548-014-0366-6","article-title":"Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy.","volume":"28","author":"Doucet","year":"2015","journal-title":"Brain Topogr."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23175-z","article-title":"The genetic architecture of the human thalamus and its overlap with ten common brain disorders.","volume":"12","author":"Elvs\u00e5shagen","year":"2021","journal-title":"Nat. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1111\/epi.17094","article-title":"Experience and consensus on stimulation of the anterior nucleus of thalamus for epilepsy.","volume":"62","author":"Fasano","year":"2021","journal-title":"Epilepsia"},{"key":"B12","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/epi.13671","article-title":"Instruction manual for the ILAE 2017 operational classification of seizure types.","volume":"58","author":"Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"B13","doi-asserted-by":"publisher","first-page":"9673","DOI":"10.1073\/pnas.0504136102","article-title":"The human brain is intrinsically organized into dynamic, anticorrelated functional networks.","volume":"102","author":"Fox","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1002\/hbm.25444","article-title":"Distinct effects of the basal ganglia and cerebellum on the thalamocortical pathway in idiopathic generalized epilepsy.","volume":"42","author":"Gong","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"B15","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s13311-021-01049-y","article-title":"Recent advances in neuroimaging of epilepsy.","volume":"18","author":"Goodman","year":"2021","journal-title":"Neurotherapeutics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/hbm.24812","article-title":"Altered inter- and intrahemispheric functional connectivity dynamics in autistic children.","volume":"41","author":"Guo","year":"2020","journal-title":"Hum. Brain Mapp."},{"key":"B17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.neubiorev.2005.06.004","article-title":"Idiopathic epileptic syndromes and cognition.","volume":"30","author":"Hommet","year":"2006","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11061612","article-title":"Distinct functional cortico-striato-thalamo-cerebellar networks in genetic generalized and focal epilepsies with generalized tonic-clonic seizures.","volume":"11","author":"Hsieh","year":"2022","journal-title":"J. Clin. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5594","DOI":"10.1523\/JNEUROSCI.0067-17.2017","article-title":"The human thalamus is an integrative hub for functional brain networks.","volume":"37","author":"Hwang","year":"2017","journal-title":"J. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.3174\/ajnr.A4308","article-title":"Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy.","volume":"36","author":"Ji","year":"2015","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1148\/radiol.13131638","article-title":"Generalized tonic-clonic seizures: aberrant interhemispheric functional and anatomical connectivity.","volume":"271","author":"Ji","year":"2014","journal-title":"Radiology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063183","article-title":"Disrupted causal connectivity in mesial temporal lobe epilepsy.","volume":"8","author":"Ji","year":"2013","journal-title":"PLos One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/hbm.24787","article-title":"Reconfiguration of dynamic large-scale brain network functional connectivity in generalized tonic-clonic seizures.","volume":"41","author":"Jia","year":"2020","journal-title":"Hum. Brain Mapp."},{"key":"B24","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1111\/epi.12580","article-title":"Altered thalamocortical functional connectivity in idiopathic generalized epilepsy.","volume":"55","author":"Kim","year":"2014","journal-title":"Epilepsia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1002\/hbm.24519","article-title":"Brain network dynamics in schizophrenia: Reduced dynamism of the default mode network.","volume":"40","author":"Kottaram","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1111\/epi.16695","article-title":"Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin.","volume":"61","author":"Kowalczyk","year":"2020","journal-title":"Epilepsia"},{"key":"B27","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1111\/ane.12257","article-title":"Diffusional kurtosis imaging reveals a distinctive pattern of microstructural alternations in idiopathic generalized epilepsy.","volume":"130","author":"Lee","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.833837","article-title":"impaired functional homotopy and topological properties within the default mode network of children with generalized tonic-clonic seizures: a resting-state fMRI study.","volume":"16","author":"Li","year":"","journal-title":"Front. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1002\/hbm.25763","article-title":"Dynamic functional connectivity in modular organization of the hippocampal network marks memory phenotypes in temporal lobe epilepsy.","volume":"43","author":"Li","year":"","journal-title":"Hum. Brain Mapp."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2022.106969","article-title":"Altered dynamic functional network connectivity within default mode network of epileptic children with generalized tonic-clonic seizures.","volume":"184","author":"Li","year":"","journal-title":"Epilepsy Res."},{"key":"B31","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1002\/hbm.23323","article-title":"Disrupted structural and functional rich club organization of the brain connectome in patients with generalized tonic-clonic seizure.","volume":"37","author":"Li","year":"2016","journal-title":"Hum. Brain Mapp."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00374","article-title":"Alterations in spontaneous brain activity and functional network reorganization following surgery in children with medically refractory epilepsy: a resting-state functional magnetic resonance imaging study.","volume":"8","author":"Li","year":"","journal-title":"Front. Neurol."},{"key":"B33","article-title":"Disrupted architecture of large-scale brain functional connectivity networks in patients with generalized tonic\u2013clonic seizure.","volume":"4","author":"Li","year":"","journal-title":"Appl. Inf."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1890","article-title":"Disrupted topological properties of functional networks in epileptic children with generalized tonic-clonic seizures.","volume":"10","author":"Li","year":"","journal-title":"Brain Behav."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00253","article-title":"Impaired topological properties of gray matter structural covariance network in epilepsy children with generalized tonic-clonic seizures: a graph theoretical analysis.","volume":"11","author":"Li","year":"","journal-title":"Front. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4105","DOI":"10.1002\/hbm.24235","article-title":"Static and dynamic connectomics differentiate between depressed patients with and without suicidal ideation.","volume":"39","author":"Liao","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"B37","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1089\/brain.2014.0253","article-title":"DynamicBC: a MATLAB toolbox for dynamic brain connectome analysis.","volume":"4","author":"Liao","year":"2014","journal-title":"Brain Connect"},{"key":"B38","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1002\/hbm.23430","article-title":"Dynamic functional network connectivity in idiopathic generalized epilepsy with generalized tonic\u2013clonic seizure.","volume":"38","author":"Liu","year":"2017","journal-title":"Hum. Brain Mapp."},{"key":"B39","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1006\/nimg.1997.0315","article-title":"Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations.","volume":"7","author":"Lowe","year":"1998","journal-title":"NeuroImage"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1002\/hbm.21286","article-title":"Resting state basal ganglia network in idiopathic generalized epilepsy.","volume":"33","author":"Luo","year":"2012","journal-title":"Hum. Brain Mapp."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2022.106918","article-title":"The role of thalamic nuclei in genetic generalized epilepsies.","volume":"182","author":"L\u00fcttjohann","year":"2022","journal-title":"Epilepsy Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.nicl.2014.10.008","article-title":"Functional neuroimaging abnormalities in idiopathic generalized epilepsy.","volume":"6","author":"McGill","year":"2014","journal-title":"NeuroImage Clin."},{"key":"B43","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1002\/hbm.23836","article-title":"Development of short-range white matter in healthy children and adolescents.","volume":"39","author":"Oyefiade","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2019.106254","article-title":"Default mode network dysfunction in idiopathic generalised epilepsy.","volume":"159","author":"Parsons","year":"2020","journal-title":"Epilepsy Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.neuroimage.2016.12.061","article-title":"The dynamic functional connectome: State-of-the-art and perspectives.","volume":"160","author":"Preti","year":"2017","journal-title":"NeuroImage"},{"key":"B46","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1073\/pnas.98.2.676","article-title":"A default mode of brain function.","volume":"98","author":"Raichle","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1002\/hbm.25404","article-title":"Brain dynamics: synchronous peaks, functional connectivity, and its temporal variability.","volume":"42","author":"Rolls","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"B48","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/epi.17171","article-title":"Epilepsy and brain network hubs.","volume":"63","author":"Royer","year":"2022","journal-title":"Epilepsia"},{"key":"B49","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1007\/s10548-019-00744-6","article-title":"Towards a universal taxonomy of macro-scale functional human brain networks.","volume":"32","author":"Uddin","year":"2019","journal-title":"Brain Topogr."},{"key":"B50","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.euroneuro.2010.03.008","article-title":"Exploring the brain network: a review on resting-state fMRI functional connectivity.","volume":"20","author":"van den Heuvel","year":"2010","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1111\/epi.17157","article-title":"Deep brain stimulation targets in epilepsy: systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus.","volume":"63","author":"Vetkas","year":"2022","journal-title":"Epilepsia"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01038","article-title":"Multimodal data and machine learning for detecting specific biomarkers in pediatric epilepsy patients with generalized tonic-clonic seizures.","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1212\/WNL.0000000000008096","article-title":"Community-informed connectomics of the thalamocortical system in generalized epilepsy.","volume":"93","author":"Wang","year":"","journal-title":"Neurology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1097\/WNR.0000000000001262","article-title":"Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.","volume":"30","author":"Wang","year":"","journal-title":"Neuroreport"},{"key":"B55","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.brainres.2010.12.034","article-title":"Altered resting state networks in epileptic patients with generalized tonic\u2013clonic seizures.","volume":"1374","author":"Wang","year":"2011","journal-title":"Brain Res."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039701","article-title":"Impairments of thalamic nuclei in idiopathic generalized epilepsy revealed by a study combining morphological and functional connectivity MRI.","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"B57","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.yebeh.2015.03.031","article-title":"Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy.","volume":"46","author":"Wei","year":"2015","journal-title":"Epilepsy Behav."},{"key":"B58","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/brain\/awx341","article-title":"Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.","volume":"141","author":"Whelan","year":"2018","journal-title":"Brain"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134361I","article-title":"Local activity and causal connectivity in children with benign epilepsy with centrotemporal spikes.","volume":"10","author":"Wu","year":"2015","journal-title":"PLoS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1002\/hbm.25279","article-title":"Cortico-striato-thalamo-cerebellar networks of structural covariance underlying different epilepsy syndromes associated with generalized tonic-clonic seizures.","volume":"42","author":"Xu","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"B61","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s12021-016-9299-4","article-title":"DPABI: data processing & analysis for (resting-state) brain imaging.","volume":"14","author":"Yan","year":"2016","journal-title":"Neuroinformatics"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.953356\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T10:47:23Z","timestamp":1658486843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.953356\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":61,"alternative-id":["10.3389\/fnins.2022.953356"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.953356","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"953356"}}