{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:52:09Z","timestamp":1791640329592,"version":"4.3.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Promoting Science and Technology"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP20dm0107124"],"award-info":[{"award-number":["JP20dm0107124"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP18dm0207023"],"award-info":[{"award-number":["JP18dm0207023"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP19lm0203007"],"award-info":[{"award-number":["JP19lm0203007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["20H05922"],"award-info":[{"award-number":["20H05922"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["20H00549"],"award-info":[{"award-number":["20H00549"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JP21dm0207072"],"award-info":[{"award-number":["JP21dm0207072"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac023","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T12:23:37Z","timestamp":1643891017000},"source":"Crossref","is-referenced-by-count":8,"title":["Epileptic discharges initiate from brain areas with elevated accumulation of \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors"],"prefix":"10.1093","volume":"4","author":[{"given":"Tomoyuki","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira 187-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira 187-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ikegaya","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Tsuchimoto","sequence":"additional","affiliation":[{"name":"Division of System Neuroscience, National Institute for Physiological Sciences, Okazaki 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-0622","authenticated-orcid":false,"given":"Takuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"2022040908214173200_fcac023-B1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1001\/jamaneurol.2017.3949","article-title":"Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: A 30-year longitudinal cohort study","volume":"75","author":"Chen","year":"2018","journal-title":"JAMA Neurol"},{"key":"2022040908214173200_fcac023-B2","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1093\/brain\/124.9.1683","article-title":"Presurgical evaluation of epilepsy","volume":"124","author":"Rosenow","year":"2001","journal-title":"Brain"},{"key":"2022040908214173200_fcac023-B3","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrn.2016.37","article-title":"Synaptic AMPA receptor composition in development, plasticity and disease","volume":"17","author":"Henley","year":"2016","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"2022040908214173200_fcac023-B4","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.neuron.2013.10.025","article-title":"AMPARs and synaptic plasticity: The last 25 years","volume":"80","author":"Huganir","year":"2013","journal-title":"Neuron"},{"key":"2022040908214173200_fcac023-B5","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.neuron.2009.01.015","article-title":"Synaptic AMPA receptor plasticity and behavior","volume":"61","author":"Kessels","year":"2009","journal-title":"Neuron"},{"key":"2022040908214173200_fcac023-B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2183\/pjab.97.001","article-title":"Translational medicine of the glutamate AMPA receptor","volume":"97","author":"Miyazaki","year":"2021","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"},{"key":"2022040908214173200_fcac023-B7","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1126\/science.1079886","article-title":"Experience strengthening transmission by driving AMPA receptors into synapses","volume":"299","author":"Takahashi","year":"2003","journal-title":"Science"},{"key":"2022040908214173200_fcac023-B8","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.neuron.2011.01.016","article-title":"Serotonin mediates cross-modal reorganization of cortical circuits","volume":"69","author":"Jitsuki","year":"2011","journal-title":"Neuron"},{"key":"2022040908214173200_fcac023-B9","doi-asserted-by":"crossref","first-page":"12503","DOI":"10.1073\/pnas.1104558108","article-title":"Contextual learning requires synaptic AMPA receptor delivery in the hippocampus","volume":"108","author":"Mitsushima","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022040908214173200_fcac023-B10","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1038\/ncomms3760","article-title":"A cholinergic trigger drives learning-induced plasticity at hippocampal synapses","volume":"4","author":"Mitsushima","year":"2013","journal-title":"Nat Commun"},{"key":"2022040908214173200_fcac023-B11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nbt.3710","article-title":"Optical inactivation of synaptic AMPA receptors erases fear memory","volume":"35","author":"Takemoto","year":"2017","journal-title":"Nat Biotechnol"},{"key":"2022040908214173200_fcac023-B12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1126\/science.aao2300","article-title":"CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage","volume":"360","author":"Abe","year":"2018","journal-title":"Science"},{"key":"2022040908214173200_fcac023-B13","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0306-4522(99)00392-9","article-title":"Ionotropic glutamate and GABA receptors in human epileptic neocortical tissue: Quantitative in vitro receptor autoradiography","volume":"94","author":"Zilles","year":"1999","journal-title":"Neuroscience"},{"key":"2022040908214173200_fcac023-B14","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1212\/WNL.0000000000001930","article-title":"Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: A randomized trial","volume":"85","author":"French","year":"2015","journal-title":"Neurology"},{"key":"2022040908214173200_fcac023-B15","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1212\/WNL.0b013e318254473a","article-title":"Randomized phase III study 306: Adjunctive perampanel for refractory partial-onset seizures","volume":"78","author":"Krauss","year":"2012","journal-title":"Neurology"},{"key":"2022040908214173200_fcac023-B16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41591-019-0723-9","article-title":"Visualization of AMPA receptors in living human brain with positron emission tomography","volume":"26","author":"Miyazaki","year":"2020","journal-title":"Nat Med"},{"key":"2022040908214173200_fcac023-B17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.neures.2021.05.009","article-title":"[11C]K-2 image with positron emission tomography represents cell surface AMPA receptors","volume":"173","author":"Arisawa","year":"2021","journal-title":"Neurosci Res"},{"key":"2022040908214173200_fcac023-B18","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1038\/s41598-021-81002-3","article-title":"Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [(11)C]K-2, in healthy human subjects","volume":"11","author":"Hatano","year":"2021","journal-title":"Sci Rep"},{"key":"2022040908214173200_fcac023-B19","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/978-3-030-00087-5_39","volume-title":"Magnetoencephalography","author":"Iwasaki","year":"2019"},{"key":"2022040908214173200_fcac023-B20","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.neuron.2013.10.017","article-title":"EEG and MEG: Relevance to neuroscience","volume":"80","author":"da Silva","year":"2013","journal-title":"Neuron"},{"key":"2022040908214173200_fcac023-B21","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1016\/j.clinph.2018.03.042","article-title":"IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)","volume":"129","author":"Hari","year":"2018","journal-title":"Clin Neurophysiol"},{"key":"2022040908214173200_fcac023-B22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1046\/j.1528-1157.2002.30801.x","article-title":"Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy","volume":"43","author":"Iwasaki","year":"2002","journal-title":"Epilepsia"},{"key":"2022040908214173200_fcac023-B23","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1152\/jn.00530.2020","article-title":"Magnetoencephalography: Physics, techniques, and applications in the basic and clinical neurosciences","volume":"125","author":"Kim","year":"2021","journal-title":"J Neurophysiol"},{"key":"2022040908214173200_fcac023-B24","doi-asserted-by":"crossref","first-page":"e576","DOI":"10.1212\/WNL.0000000000006877","article-title":"Electromagnetic source imaging in presurgical workup of patients with epilepsy: A prospective study","volume":"92","author":"Duez","year":"2019","journal-title":"Neurology."},{"key":"2022040908214173200_fcac023-B25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.eplepsyres.2016.05.002","article-title":"Preoperative evaluation using magnetoencephalography: Experience in 382 epilepsy patients","volume":"124","author":"Nissen","year":"2016","journal-title":"Epilepsy Res"},{"key":"2022040908214173200_fcac023-B26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/brain\/awt299","article-title":"Intracranial electroencephalographic seizure-onset patterns: Effect of underlying pathology","volume":"137","author":"Perucca","year":"2014","journal-title":"Brain"},{"key":"2022040908214173200_fcac023-B27","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1097\/00004647-199609000-00008","article-title":"Distribution volume ratios without blood sampling from graphical analysis of PET data","volume":"16","author":"Logan","year":"1996","journal-title":"J Cereb Blood Flow Metab"},{"key":"2022040908214173200_fcac023-B28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.5698\/1535-7597.18.1.12","article-title":"The epileptogenic zone: Concept and definition","volume":"18","author":"Jehi","year":"2018","journal-title":"Epilepsy Curr"},{"key":"2022040908214173200_fcac023-B29","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1684\/j.1950-6945.2006.tb00204.x","article-title":"The epileptogenic zone: General principles","volume":"8","author":"L\u00fcders","year":"2006","journal-title":"Epileptic Disord"},{"key":"2022040908214173200_fcac023-B30","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1212\/WNL.57.2.184","article-title":"Volumetric MRI, pathological, and neuropsychological progression in hippocampal sclerosis","volume":"57","author":"Fuerst","year":"2001","journal-title":"Neurology"},{"key":"2022040908214173200_fcac023-B31","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1111\/epi.17025","article-title":"Dynamic tractography-based localization of spike sources and animation of spike propagations","volume":"62","author":"Mitsuhashi","year":"2021","journal-title":"Epilepsia"},{"key":"2022040908214173200_fcac023-B32","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1212\/WNL.0b013e3182904f82","article-title":"Systematic review and meta-analysis of standard vs. selective temporal lobe epilepsy surgery","volume":"80","author":"Josephson","year":"2013","journal-title":"Neurology"},{"key":"2022040908214173200_fcac023-B33","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/epi.16846","article-title":"Comparison of minimally invasive and traditional surgical approaches for refractory mesial temporal lobe epilepsy: A systematic review and meta-analysis of outcomes","volume":"62","author":"Kohlhase","year":"2021","journal-title":"Epilepsia"},{"key":"2022040908214173200_fcac023-B34","doi-asserted-by":"crossref","first-page":"e0149068","DOI":"10.1371\/journal.pone.0149068","article-title":"Sustained enhancement of lateral inhibitory circuit maintains cross modal cortical reorganization","volume":"11","author":"Nakajima","year":"2016","journal-title":"PLoS One"},{"key":"2022040908214173200_fcac023-B35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/ana.24293","article-title":"Cellular plasticity induced by anti-\u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis antibodies","volume":"77","author":"Peng","year":"2015","journal-title":"Ann Neurol"},{"key":"2022040908214173200_fcac023-B36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrn1327","article-title":"Homeostatic plasticity in the developing nervous system","volume":"5","author":"Turrigiano","year":"2004","journal-title":"Nat Rev Neurosci"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcac023\/42418964\/fcac023.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/4\/2\/fcac023\/43348924\/fcac023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/4\/2\/fcac023\/43348924\/fcac023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T20:47:10Z","timestamp":1726606030000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcac023\/6523721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcac023","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2022,2,7]]},"article-number":"fcac023"}}