{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T05:57:41Z","timestamp":1763445461852},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Canadian League Against Epilepsy"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In mesial temporal lobe epilepsy (mTLE), the correlation between disease duration, seizure laterality, and rostro-caudal location of hippocampal sclerosis has not been examined in the context of seizure severity and global cortical thinning. In this retrospective study, we analyzed structural 3\u00a0T MRI from 35 mTLE subjects. Regions of FLAIR hyperintensity (as an indicator of sclerosis)\u2014based on 2D coronal FLAIR sequences\u2014in the hippocampus were manually segmented, independently and in duplicate; degree of segmentation agreement was confirmed using the DICE index. Segmented lesions were used for separate analyses. First, the correlation of cortical thickness with disease duration and seizure focus laterality was explored using linear model regression. Then, the relationship between the rostro-caudal location of the FLAIR hyperintense signal and seizure severity, based on the Cleveland Clinic seizure freedom score (ccSFS), was explored using probabilistic voxel-wise mapping and functional connectivity analysis from normative data. The mean DICE Index was 0.71 (range 0.60\u20130.81). A significant correlation between duration of epilepsy and decreased mean whole brain cortical thickness was identified, regardless of seizure laterality<jats:bold>(<\/jats:bold>p\u2009&lt;\u20090.05). The slope of cortical volume loss over time, however, was greater in subjects with right seizure focus. Based on probabilistic voxel-wise mapping, FLAIR hyperintensity in the posterior hippocampus was significantly associated with lower ccSFS scores (greater seizure severity). Finally, the right hippocampus was found to have greater brain-wide connectivity, compared to the left side, based on normative connectomic data. We have demonstrated a significant correlation between duration of epilepsy and right-sided seizure focus with global cortical thinning, potentially due to greater brain-wide connectivity. Sclerosis along the posterior hippocampus was associated with greater seizure severity, potentially serving as an important biomarker of seizure outcome after surgery.<\/jats:p>","DOI":"10.1038\/s41598-021-84281-y","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T11:04:11Z","timestamp":1614251051000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An exploratory study into the influence of laterality and location of hippocampal sclerosis on seizure prognosis and global cortical thinning"],"prefix":"10.1038","volume":"11","author":[{"given":"Alireza","family":"Mansouri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Germann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Boutet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin J. B.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brij","family":"Karmur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Neudorfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Loh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Pat","family":"McAndrews","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George M.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres M.","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taufik A.","family":"Valiante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"84281_CR1","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1212\/WNL.0000000000003289","volume":"87","author":"DN Vaughan","year":"2016","unstructured":"Vaughan, D. N., Rayner, G., Tailby, C. & Jackson, G. D. MRI-negative temporal lobe epilepsy. Neurology 87, 1934\u20131942 (2016).","journal-title":"Neurology"},{"key":"84281_CR2","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/ana.10463","volume":"53","author":"RSN Liu","year":"2003","unstructured":"Liu, R. S. N. et al. Progressive neocortical damage in epilepsy. Ann. Neurol. 53, 312\u2013324 (2003).","journal-title":"Ann. Neurol."},{"key":"84281_CR3","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1001\/jamaneurol.2019.0204","volume":"76","author":"MJ Koepp","year":"2019","unstructured":"Koepp, M. J. et al. Association of piriform cortex resection with surgical outcomes in patients with temporal lobe epilepsy. JAMA Neurol. 76, 690\u2013700 (2019).","journal-title":"JAMA Neurol."},{"key":"84281_CR4","doi-asserted-by":"publisher","first-page":"920","DOI":"10.3389\/fneur.2019.00920","volume":"10","author":"AJ Barnett","year":"2019","unstructured":"Barnett, A. J., Man, V. & McAndrews, M. P. Parcellation of the hippocampus using resting functional connectivity in temporal lobe epilepsy [internet]. Front. Neurol. 10, 920 (2019).","journal-title":"Front. Neurol."},{"key":"84281_CR5","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1002\/ana.25547","volume":"86","author":"VL Boerwinkle","year":"2019","unstructured":"Boerwinkle, V. L. et al. Network-targeted approach and postoperative resting-state functional magnetic resonance imaging are associated with seizure outcome. Ann. Neurol. 86, 344\u2013356 (2019).","journal-title":"Ann. Neurol."},{"key":"84281_CR6","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1148\/radiology.199.2.8668780","volume":"199","author":"CR Jack","year":"1996","unstructured":"Jack, C. R. et al. Mesial temporal sclerosis: Diagnosis with fluid-attenuated inversion-recovery versus spin-echo MR imaging. Radiology 199, 367\u2013373 (1996).","journal-title":"Radiology"},{"key":"84281_CR7","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.yebeh.2015.04.001","volume":"46","author":"BY Kubota","year":"2015","unstructured":"Kubota, B. Y., Coan, A. C., Yasuda, C. L. & Cendes, F. T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI. Epilepsy Behav. 46, 103\u2013108 (2015).","journal-title":"Epilepsy Behav."},{"key":"84281_CR8","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.tics.2013.03.005","volume":"17","author":"J Poppenk","year":"2013","unstructured":"Poppenk, J., Evensmoen, H. R., Moscovitch, M. & Nadel, L. Long-axis specialization of the human hippocampus. Trends Cogn. Sci. 17, 230\u2013240 (2013).","journal-title":"Trends Cogn. Sci."},{"key":"84281_CR9","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.nicl.2016.11.020","volume":"13","author":"C Egger","year":"2017","unstructured":"Egger, C. et al. MRI FLAIR lesion segmentation in multiple sclerosis: Does automated segmentation hold up with manual annotation?. NeuroImage 13, 264\u2013270. https:\/\/doi.org\/10.1016\/j.nicl.2016.11.020 (2017).","journal-title":"NeuroImage"},{"key":"84281_CR10","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.3174\/ajnr.A6138","volume":"40","author":"MT Duong","year":"2019","unstructured":"Duong, M. T. et al. Convolutional neural network for automated FLAIR lesion segmentation on clinical brain MR imaging. Am. J. Neuroradiol. 40, 1282\u20131290. https:\/\/doi.org\/10.3174\/ajnr.A6138 (2019).","journal-title":"Am. J. Neuroradiol."},{"issue":"4","key":"84281_CR11","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/cercor\/10.4.433","volume":"10","author":"JC Pruessner","year":"2000","unstructured":"Pruessner, J. C. Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: Minimizing the discrepancies between laboratories. Cereb Cortex. 10(4), 433\u2013442. https:\/\/doi.org\/10.1093\/cercor\/10.4.433 (2000).","journal-title":"Cereb Cortex."},{"key":"84281_CR12","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1097\/00004728-199403000-00005","volume":"18","author":"DL Collins","year":"1994","unstructured":"Collins, D. L., Neelin, P., Peters, T. M. & Evans, A. C. Automatic 3d intersubject registration of mr volumetric data in standardized talairach space. J. Comput. Assist. Tomogr. 18, 192\u2013205 (1994).","journal-title":"J. Comput. Assist. Tomogr."},{"key":"84281_CR13","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1109\/42.668698","volume":"17","author":"JG Sied","year":"1998","unstructured":"Sied, J. G., Zijdenbos, A. P. & Evans, A. C. A nonparametric method for automatic correction of intensity nonuniformity in mri data. IEEE Trans. Med. Imaging 17, 87\u201397 (1998).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"84281_CR14","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.neuroimage.2004.07.045","volume":"24","author":"JP Lerch","year":"2005","unstructured":"Lerch, J. P. & Evans, A. C. Cortical thickness analysis examined through power analysis and a population simulation. Neuroimage 24, 163\u2013173 (2005).","journal-title":"Neuroimage"},{"key":"84281_CR15","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/epi.12892","volume":"56","author":"C Garcia Gracia","year":"2015","unstructured":"Garcia Gracia, C. et al. Seizure freedom score: A new simple method to predict success of epilepsy surgery. Epilepsia 56, 359\u2013365 (2015).","journal-title":"Epilepsia"},{"key":"84281_CR16","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","volume":"62","author":"M Jenkinson","year":"2012","unstructured":"Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W. & Smith, S. M. FSL. Neuroimage 62, 782\u2013790 (2012).","journal-title":"Neuroimage"},{"key":"84281_CR17","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.nicl.2016.11.019","volume":"13","author":"TA Dembek","year":"2017","unstructured":"Dembek, T. A. et al. Probabilistic mapping of deep brain stimulation effects in essential tremor. NeuroImage Clin. 13, 164\u2013173 (2017).","journal-title":"NeuroImage Clin."},{"key":"84281_CR18","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.wneu.2019.08.094","volume":"132","author":"A Boutet","year":"2019","unstructured":"Boutet, A. et al. Network basis of seizures induced by deep brain stimulation: literature review and connectivity analysis. World Neurosurg. 132, 314\u2013320 (2019).","journal-title":"World Neurosurg."},{"key":"84281_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25975","author":"GJB Elias","year":"2020","unstructured":"Elias, G. J. B. et al. Probabilistic mapping of deep brain stimulation: Insights from 15 years of therapy. Ann. Neurol. https:\/\/doi.org\/10.1002\/ana.25975 (2020).","journal-title":"Ann. Neurol."},{"issue":"2","key":"84281_CR20","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.brs.2019.10.023","volume":"13","author":"H Yan","year":"2020","unstructured":"Yan, H. et al. Aggressiveness after centromedian nucleus stimulation engages prefrontal thalamocortical circuitry. Brain Stimul. 13(2), 357\u2013359. https:\/\/doi.org\/10.1016\/j.brs.2019.10.023 (2020).","journal-title":"Brain Stimul."},{"issue":"1","key":"84281_CR21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/ana.24974","volume":"82","author":"A Horn","year":"2017","unstructured":"Horn, A. et al. Connectivity predicts deep brain stimulation outcome in Parkinson disease. Ann. Neurol. 82(1), 67\u201378. https:\/\/doi.org\/10.1002\/ana.24974 (2017).","journal-title":"Ann. Neurol."},{"issue":"23","key":"84281_CR22","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1056\/NEJMra1706158","volume":"379","author":"MD Fox","year":"2018","unstructured":"Fox, M. D. Mapping symptoms to brain networks with the human connectome. N. Engl. J. Med. 379(23), 2237\u20132245. https:\/\/doi.org\/10.1056\/NEJMra1706158 (2018).","journal-title":"N. Engl. J. Med."},{"issue":"12","key":"84281_CR23","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1097\/j.pain.0000000000001998","volume":"161","author":"GJB Elias","year":"2020","unstructured":"Elias, G. J. B. et al. Mapping the network underpinnings of central poststroke pain and analgesic neuromodulation. Pain 161(12), 2805\u20132819. https:\/\/doi.org\/10.1097\/j.pain.0000000000001998 (2020).","journal-title":"Pain"},{"key":"84281_CR24","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1152\/jn.00338.2011","volume":"106","author":"BT Thomas Yeo","year":"2011","unstructured":"Thomas Yeo, B. T. et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J. Neurophysiol. 106, 1125\u20131165 (2011).","journal-title":"J. Neurophysiol."},{"key":"84281_CR25","doi-asserted-by":"publisher","first-page":"5686","DOI":"10.1002\/hbm.22580","volume":"35","author":"GM Ibrahim","year":"2014","unstructured":"Ibrahim, G. M. et al. Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy. Hum. Brain Mapp. 35, 5686\u20135700 (2014).","journal-title":"Hum. Brain Mapp."},{"key":"84281_CR26","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.biopsych.2019.07.023","volume":"86","author":"JL Padmanabhan","year":"2019","unstructured":"Padmanabhan, J. L. et al. A human depression circuit derived from focal brain lesions. Biol. Psychiatry 86, 749\u2013758 (2019).","journal-title":"Biol. Psychiatry"},{"key":"84281_CR27","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1109\/TMI.2002.806283","volume":"21","author":"AP Zijdenbos","year":"2002","unstructured":"Zijdenbos, A. P., Forghani, R. & Evans, A. C. Automatic \u2018pipeline\u2019 analysis of 3-D MRI data for clinical trials: Application to multiple sclerosis. IEEE Trans. Med. Imaging 21, 1280\u20131291 (2002).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"84281_CR28","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/brain\/awx341","volume":"141","author":"CD Whelan","year":"2018","unstructured":"Whelan, C. D. et al. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain 141, 391\u2013408 (2018).","journal-title":"Brain"},{"key":"84281_CR29","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1111\/j.1468-1331.2006.01188.x","volume":"13","author":"SG Mueller","year":"2006","unstructured":"Mueller, S. G., Laxer, K. D., Cashdollar, N., Lopez, R. C. & Weiner, M. W. Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy. Eur. J. Neurol. 13, 256\u2013260 (2006).","journal-title":"Eur. J. Neurol."},{"key":"84281_CR30","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1111\/j.1528-1167.2008.01604.x","volume":"49","author":"J Schramm","year":"2008","unstructured":"Schramm, J. Temporal lobe epilepsy surgery and the quest for optimal extent of resection: A review. Epilepsia 49, 1296\u20131307 (2008).","journal-title":"Epilepsia"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84281-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84281-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84281-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T23:24:03Z","timestamp":1697930643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84281-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["84281"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-84281-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"assertion":[{"value":"4 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"4686"}}