Prevention of epileptogenesis as a future strategy for the treatment of epilepsy
- Authors: Bragin A.G.1
-
Affiliations:
- David Geffen Medical School at University of California
- Issue: Vol 47, No 7 (2019)
- Pages: 614-622
- Section: INVITED ARTICLE
- URL: https://almclinmed.ru/jour/article/view/1060
- DOI: https://doi.org/10.18786/2072-0505-2019-47-028
- ID: 1060
Cite item
Full Text
Abstract
Epilepsy affects more than 70 million people worldwide. From 30 to 40% of the patients are resistant to existing medication. This paper describes the current state of the treatment of epilepsy and proposes a future approach to preventative treatment at earlier stages of epileptogenesis. For preventative treatment biomarkers are needed that predict the development of epilepsy at its earlier stages. Pathological high frequency oscillations are the only acceptable biomarker of epileptogenesis. However, the main limitation of this biomarker is the necessity of implanting of recording electrodes. The search for noninvasive biomarkers of epileptogenesis is one of the hot topics in epilepsy research. There are two potentially interesting directions in this area: search for inflammatory biomarkers in the peripheral blood and analysis of different parameters of imaging methods. In this paper we present approaches for identification of potential epileptogenesis biomarkers by magnetic resonance imaging. Some of magnetic resonance imaging parameters correlate with the existence of pathological high frequency oscillations, may indirectly reflect ongoing inflammation process in the brain and be potential biomarkers of epileptogenesis.
About the authors
A. G. Bragin
David Geffen Medical School at University of California
Author for correspondence.
Email: abragin@mednet.ucla.edu
ORCID iD: 0000-0003-1207-8481
Anatol Bragin – PhD, DSci, Department of Neurology.
710 Westwood Plaza, Los Angeles, CA, 90095
СШАReferences
- Kaiboriboon K, Bakaki PM, Lhatoo SD, Koroukian S. Incidence and prevalence of treated epilepsy among poor health and low-income Americans. Neurology. 2013;80(21):1942–9. doi: 10.1212/WNL.0b013e318293e1b4.
- Tang DH, Malone DC, Warholak TL, Chong J, Armstrong EP, Slack MK, Hsu CH, Labiner DM. Prevalence and Incidence of Epilepsy in an Elderly and Low-Income Population in the United States. J Clin Neurol. 2015;11(3):252–61. doi: 10.3988/jcn.2015.11.3.252.
- Kim H, Thurman DJ, Durgin T, Faught E, Helmers S. Estimating epilepsy incidence and prevalence in the US pediatric population using nationwide health insurance claims data. J Child Neurol. 2016;31(6):743–9. doi: 10.1177/0883073815620676.
- Elger CE. Pharmacoresistance: modern concept and basic data derived from human brain tissue. Epilepsia. 2003;44 Suppl 5:9–15. doi: 10.1046/j.1528-1157.44.s6.2.x.
- Jamali S, Bartolomei F, Robaglia-Schlupp A, Massacrier A, Peragut JC, Régis J, Dufour H, Ravid R, Roll P, Pereira S, Royer B, Roeckel-Trevisiol N, Fontaine M, Guye M, Boucraut J, Chauvel P, Cau P, Szepetowski P. Large-scale expression study of human mesial temporal lobe epilepsy: evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex. Brain. 2006;129(Pt 3): 625–41. doi: 10.1093/brain/awl001.
- Badawy RA, Macdonell RA, Berkovic SF, Newton MR, Jackson GD. Predicting seizure control: cortical excitability and antiepileptic medication. Ann Neurol. 2010;67(1):64–73. doi: 10.1002/ana.21806.
- Doeser A, Dickhof G, Reitze M, Uebachs M, Schaub C, Pires NM, Bonifácio MJ, Soares-daSilva P, Beck H. Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug. Brain. 2015;138(Pt 2): 371–87. doi: 10.1093/brain/awu339.
- Begley CE, Famulari M, Annegers JF, Lairson DR, Reynolds TF, Coan S, Dubinsky S, Newmark ME, Leibson C, So EL, Rocca WA. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia. 2000;41(3):342–51. doi: 10.1111/j.1528-1157.2000.tb00166.x.
- Kobau R, Zahran H, Thurman DJ, Zack MM, Henry TR, Schachter SC, Price PH; Centers for Disease Control and Prevention (CDC). Epilepsy surveillance among adults – 19 States, Behavioral Risk Factor Surveillance System, 2005. MMWR Surveill Summ. 2008;57(6):1–20.
- French JA, Gazzola DM. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety? Ther Adv Drug Saf. 2011;2(4):141–58. doi: 10.1177/2042098611411127.
- Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011;52(4):657–78. doi: 10.1111/j.1528-1167.2011.03024.x.
- Simonato M, Löscher W, Cole AJ, Dudek FE, Engel J Jr, Kaminski RM, Loeb JA, Scharfman H, Staley KJ, Velíšek L, Klitgaard H. Finding a better drug for epilepsy: preclinical screening strategies and experimental trial design. Epilepsia. 2012;53(11):1860–7. doi: 10.1111/j.1528-1167.2012.03541.x.
- Androsova G, Krause R, Borghei M, Wassenaar M, Auce P, Avbersek A, Becker F, Berghuis B, Campbell E, Coppola A, Francis B, Wolking S, Cavalleri GL, Craig J, Delanty N, Koeleman BPC, Kunz WS, Lerche H, Marson AG, Sander JW, Sills GJ, Striano P, Zara F, Sisodiya SM, Depondt C; EpiPGX Consortium. Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2017;58(10):1734–41. doi: 10.1111/epi.13871.
- Bragin A, Wilson CL, Engel J Jr. Chronic epileptogenesis requires development of a network of pathologically interconnected neuron clusters: a hypothesis. Epilepsia. 2000;41 Suppl 6:S144–52. doi: 10.1111/j.1528-1157.2000.tb01573.x.
- Blumenfeld H. From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy. Epilepsia. 2003;44 Suppl 2:7–15. doi: 10.1046/j.1528-1157.44.s11.3.x.
- Feldt Muldoon S, Soltesz I, Cossart R. Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks. Proc Natl Acad Sci U S A. 2013;110(9): 3567–72. doi: 10.1073/pnas.1216958110.
- Blumenfeld H. What is a seizure network? Long-range network consequences of focal seizures. Adv Exp Med Biol. 2014;813:63–70. doi: 10.1007/978-94-017-8914-1_5.
- Aronica E, Crino PB. Inflammation in epilepsy: clinical observations. Epilepsia. 2011;52 Suppl 3:26–32. doi: 10.1111/j.1528-1167.2011.03033.x.
- Friedman A, Dingledine R. Molecular cascades that mediate the influence of inflammation on epilepsy. Epilepsia. 2011;52 Suppl 3:33–9. doi: 10.1111/j.1528-1167.2011.03034.x.
- Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 2013;36(3):174–84. doi: 10.1016/j.tins.2012.11.008.
- Holtman L, van Vliet EA, Aronica E, Wouters D, Wadman WJ, Gorter JA. Blood plasma inflammation markers during epileptogenesis in post-status epilepticus rat model for temporal lobe epilepsy. Epilepsia. 2013;54(4):589–95. doi: 10.1111/epi.12112.
- Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017;58(6): 973–82. doi: 10.1111/epi.13769.
- Euston DR, Gruber AJ, McNaughton BL. The role of medial prefrontal cortex in memory and decision making. Neuron. 2012;76(6):1057–70. doi: 10.1016/j.neuron.2012.12.002.
- Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C, Deisseroth K. Projections from neocortex mediate top-down control of memory retrieval. Nature. 2015;526(7575):653–9. doi: 10.1038/nature15389.
- Khodagholy D, Gelinas JN, Buzsáki G. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science. 2017;358(6361):369–72. doi: 10.1126/science.aan6203.
- Morgane PJ, Galler JR, Mokler DJ. A review of systems and networks of the limbic forebrain/ limbic midbrain. Prog Neurobiol. 2005;75(2): 143–60. doi: 10.1016/j.pneurobio.2005.01.001.
- Kobow K, Auvin S, Jensen F, Löscher W, Mody I, Potschka H, Prince D, Sierra A, Simonato M, Pitkänen A, Nehlig A, Rho JM. Finding a better drug for epilepsy: antiepileptogenesis targets. Epilepsia. 2012;53(11):1868–76. doi: 10.1111/j.1528-1167.2012.03716.x.
- van Vliet EA, Dedeurwaerdere S, Cole AJ, Friedman A, Koepp MJ, Potschka H, Immonen R, Pitkänen A, Federico P. WONOEP appraisal: Imaging biomarkers in epilepsy. Epilepsia. 2017;58(3):315–30. doi: 10.1111/epi.13621.
- Laitinen T, Sierra A, Pitkänen A, Gröhn O. Diffusion tensor MRI of axonal plasticity in the rat hippocampus. Neuroimage. 2010;51(2):521– 30. doi: 10.1016/j.neuroimage.2010.02.077.
- Coras R, Milesi G, Zucca I, Mastropietro A, Scotti A, Figini M, Mühlebner A, Hess A, Graf W, Tringali G, Blümcke I, Villani F, Didato G, Frassoni C, Spreafico R, Garbelli R. 7T MRI features in control human hippocampus and hippocampal sclerosis: an ex vivo study with histologic correlations. Epilepsia. 2014;55(12):2003–16. doi: 10.1111/epi.12828.
- Sierra A, Laitinen T, Gröhn O, Pitkänen A. Diffusion tensor imaging of hippocampal network plasticity. Brain Struct Funct. 2015;220(2):781– 801. doi: 10.1007/s00429-013-0683-7.
- Modo M, Hitchens TK, Liu JR, Richardson RM. Detection of aberrant hippocampal mossy fiber connections: Ex vivo mesoscale diffusion MRI and microtractography with histological validation in a patient with uncontrolled temporal lobe epilepsy. Hum Brain Mapp. 2016;37(2):780–95. doi: 10.1002/hbm.23066.
- Khoo HM, Hao Y, von Ellenrieder N, Zazubovits N, Hall J, Olivier A, Dubeau F, Gotman J. The hemodynamic response to interictal epileptic discharges localizes the seizure-onset zone. Epilepsia. 2017;58(5):811–23. doi: 10.1111/epi.13717.
- Khoo HM, von Ellenrieder N, Zazubovits N, Dubeau F, Gotman J. Epileptic networks in action: Synchrony between distant hemodynamic responses. Ann Neurol. 2017;82(1):57–66. doi: 10.1002/ana.24973.
- Pittau F, Ferri L, Fahoum F, Dubeau F, Gotman J. Contributions of EEG-fMRI to assessing the epileptogenicity of focal cortical dysplasia. Front Comput Neurosci. 2017;11:8. doi: 10.3389/fncom.2017.00008.
- Dev SI, Moore RC, Soontornniyomkij B, Achim CL, Jeste DV, Eyler LT. Peripheral inflammation related to lower fMRI activation during a working memory task and resting functional connectivity among older adults: a preliminary study. Int J Geriatr Psychiatry. 2017;32(3): 341–9. doi: 10.1002/gps.4482.
- Budde MD, Janes L, Gold E, Turtzo LC, Frank JA. The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. Brain. 2011;134(Pt 8):2248–60. doi: 10.1093/brain/awr161.
- Mihai PG, Otto M, Domin M, Platz T, Hamdy S, Lotze M. Brain imaging correlates of recovered swallowing after dysphagic stroke: A fMRI and DWI study. Neuroimage Clin. 2016;12:1013–21. doi: 10.1016/j.nicl.2016.05.006.
- Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, Miller AH. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry. 2016;21(10):1358–65. doi: 10.1038/mp.2015.168.
- Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4(3):316–29. doi: 10.1016/j.nurt.2007.05.011.
- MacKenzie-Graham AJ, Rinek GA, Avedisian A, Morales LB, Umeda E, Boulat B, Jacobs RE, Toga AW, Voskuhl RR. Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. J Neurosci Res. 2012;90(7):1310–23. doi: 10.1002/jnr.23019.
- Hemanth Kumar BS, Mishra SK, Trivedi R, Singh S, Rana P, Khushu S. Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T. Neuroscience. 2014;275:12–21. doi: 10.1016/j.neuroscience.2014.05.037.
- Begonia MT, Prabhu R, Liao J, Whittington WR, Claude A, Willeford B, Wardlaw J, Wu R, Zhang S, Williams LN. Quantitative analysis of brain microstructure following mild blunt and blast trauma. J Biomech. 2014;47(15):3704–11. doi: 10.1016/j.jbiomech.2014.09.026.
- Harris NG, Verley DR, Gutman BA, Sutton RL. Bi-directional changes in fractional anisotropy after experiment TBI: Disorganization and reorganization? Neuroimage. 2016;133:129–43. doi: 10.1016/j.neuroimage.2016.03.012.
- Kikinis Z, Muehlmann M, Pasternak O, Peled S, Kulkarni P, Ferris C, Bouix S, Rathi Y, Koerte IK, Pieper S, Yarmarkovich A, Porter CL, Kristal BS, Shenton ME. Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study. Brain Inj. 2017;31(10):1376–81. doi: 10.1080/02699052.2017.1318450.
- Koyama T, Domen K. Diffusion Tensor Fractional Anisotropy in the Superior Longitudinal Fasciculus Correlates with Functional Independence Measure Cognition Scores in Patients with Cerebral Infarction. J Stroke Cerebrovasc Dis. 2017;26(8):1704–11. doi: 10.1016/j.jstrokecerebrovasdis.2017.03.034.
- Thomalla G, Glauche V, Koch MA, Beaulieu C, Weiller C, Röther J. Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke. Neuroimage. 2004;22(4):1767–74. doi: 10.1016/j.neuroimage.2004.03.041.
- Gotman J. Epileptic networks studied with EEG-fMRI. Epilepsia. 2008;49 Suppl 3:42–51. doi: 10.1111/j.1528-1167.2008.01509.x.
- Bettus G, Ranjeva JP, Wendling F, Bénar CG, Confort-Gouny S, Régis J, Chauvel P, Cozzone PJ, Lemieux L, Bartolomei F, Guye M. Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations. PLoS One. 2011;6(5):e20071. doi: 10.1371/journal.pone.0020071.
- Bertoglio D, Jonckers E, Ali I, Verhoye M, Van der Linden A, Dedeurwaerdere S. In vivo measurement of brain network connectivity reflects progression and intrinsic disease severity in a model of temporal lobe epilepsy. Neurobiol Dis. 2019;127:45–52. doi: 10.1016/j.nbd.2019.02.012.
- Jozwiak S, Becker A, Cepeda C, Engel J Jr, Gnatkovsky V, Huberfeld G, Kaya M, Kobow K, Simonato M, Loeb JA. WONOEP appraisal: Development of epilepsy biomarkers – What we can learn from our patients? Epilepsia. 2017;58(6): 951–61. doi: 10.1111/epi.13728.
- Mirsattari SM, Wang Z, Ives JR, Bihari F, Leung LS, Bartha R, Menon RS. Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy. Neuroimage. 2006;30(4):1133–48. doi: 10.1016/j.neuroimage.2005.11.006.
- Dubé CM, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci. 2010;30(22):7484–94. doi: 10.1523/JNEUROSCI.0551-10.2010.
- Parekh MB, Carney PR, Sepulveda H, Norman W, King M, Mareci TH. Early MR diffusion and relaxation changes in the parahippocampal gyrus precede the onset of spontaneous seizures in an animal model of chronic limbic epilepsy. Exp Neurol. 2010;224(1):258–70. doi: 10.1016/j.expneurol.2010.03.031.
- Dedeurwaerdere S, Shultz SR, Federico P, Engel J Jr. Workshop on Neurobiology of Epilepsy appraisal: new systemic imaging technologies to study the brain in experimental models of epilepsy. Epilepsia. 2014;55(6):819–28. doi: 10.1111/epi.12642.
- Gupta PK, Sayed N, Ding K, Agostini MA, Van Ness PC, Yablon S, Madden C, Mickey B, D'Ambrosio R, Diaz-Arrastia R. Subtypes of post-traumatic epilepsy: clinical, electrophysiological, and imaging features. J Neurotrauma. 2014;31(16):1439–43. doi: 10.1089/neu.2013.3221.
- Salo RA, Miettinen T, Laitinen T, Gröhn O, Sierra A. Diffusion tensor MRI shows progressive changes in the hippocampus and dentate gyrus after status epilepticus in rat – histological validation with Fourier-based analysis. Neuroimage. 2017;152:221–36. doi: 10.1016/j. neuroimage.2017.03.003.
- Shultz SR, Cardamone L, Liu YR, Hogan RE, Maccotta L, Wright DK, Zheng P, Koe A, Gregoire MC, Williams JP, Hicks RJ, Jones NC, Myers DE, O'Brien TJ, Bouilleret V. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome? Epilepsia. 2013;54(7):1240–50. doi: 10.1111/epi.12223.
- Mishra AM, Bai X, Sanganahalli BG, Waxman SG, Shatillo O, Grohn O, Hyder F, Pitkänen A, Blumenfeld H. Decreased resting functional connectivity after traumatic brain injury in the rat. PLoS One. 2014;9(4):e95280. doi: 10.1371/journal.pone.0095280.
- Liao W, Zhang Z, Pan Z, Mantini D, Ding J, Duan X, Luo C, Wang Z, Tan Q, Lu G, Chen H. Default mode network abnormalities in mesial temporal lobe epilepsy: a study combining fMRI and DTI. Hum Brain Mapp. 2011;32(6): 883–95. doi: 10.1002/hbm.21076.
- Miller KJ. Broadband spectral change: evidence for a macroscale correlate of population firing rate? J Neurosci. 2010;30(19):6477–9. doi: 10.1523/JNEUROSCI.6401-09.2010.
- Miller KJ, Honey CJ, Hermes D, Rao RP, denNijs M, Ojemann JG. Broadband changes in the cortical surface potential track activation of functionally diverse neuronal populations. Neuroimage. 2014;85 Pt 2:711–20. doi: 10.1016/j.neuroimage.2013.08.070.
- Foster BL, Rangarajan V, Shirer WR, Parvizi J. Intrinsic and task-dependent coupling of neuronal population activity in human parietal cortex. Neuron. 2015;86(2):578–90. doi: 10.1016/j.neuron.2015.03.018.
- Scott RC, Menendez de la Prida L, Mahoney JM, Kobow K, Sankar R, de Curtis M. WONOEP APPRAISAL: The many facets of epilepsy networks. Epilepsia. 2018;59(8):1475–83. doi: 10.1111/epi.14503.
- Bragin A, Engel J Jr, Wilson CL, Fried I, Buzsáki G. High-frequency oscillations in human brain. Hippocampus. 1999;9(2):137–42. doi: 10.1002/(SICI)1098-1063(1999)9:23.0.CO;2-0.
- Bragin A, Engel J Jr, Wilson CL, Fried I, Mathern GW. Hippocampal and entorhinal cortex high-frequency oscillations (100–500 Hz) in human epileptic brain and in kainic acid-treated rats with chronic seizures. Epilepsia. 1999;40(2):127–37. doi: 10.1111/j.1528-1157.1999.tb02065.x.
- Bragin A, Engel J Jr, Wilson CL, Vizentin E, Mathern GW. Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection. Epilepsia. 1999;40(9):1210–21. doi: 10.1111/j.1528-1157.1999.tb00849.x.
- Bragin A, Mody I, Wilson CL, Engel J Jr. Local generation of fast ripples in epileptic brain. J Neurosci. 2002;22(5):2012–21. doi: 10.1523/JNEUROSCI.22-05-02012.2002.
- Bragin A, Wilson CL, Engel J. Voltage Depth Profiles of High-frequency Oscillations after Kainic Acid-induced Status Epilepticus. Epilepsia. 2007;48:35–40.
- Ponomarenko AA, Korotkova TM, Haas HL. High frequency (200 Hz) oscillations and firing patterns in the basolateral amygdala and dorsal endopiriform nucleus of the behaving rat. Behav Brain Res. 2003;141(2):123–9. doi: 10.1016/S0166-4328(02)00327-3.
- Dzhala VI, Staley KJ. Mechanisms of fast ripples in the hippocampus. J Neurosci. 2004;24(40):8896–906. doi: 10.1523/JNEUROSCI.3112-04.2004.
- Akiyama T, Otsubo H, Ochi A, Ishiguro T, Kadokura G, Ramachandrannair R, Weiss SK, Rutka JT, Carter Snead O 3rd. Focal cortical high-frequency oscillations trigger epileptic spasms: confirmation by digital video subdural EEG. Clin Neurophysiol. 2005;116(12):2819–25. doi: 10.1016/j.clinph.2005.08.029.
- Jirsch JD, Dubeau F, Urrestarazu E, LeVan P, Gotman J. High frequency activity (100 to 500 hz) in areas of ictal onset and propagation in patients with focal seizures. Epilepsia. 2005;46 Suppl 8:267.
- Foffani G, Uzcategui YG, Gal B, Menendez de la Prida L. Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus. Neuron. 2007;55(6): 930–41. doi: 10.1016/j.neuron.2007.07.040.
- Ochi A, Otsubo H, Donner EJ, Elliott I, Iwata R, Funaki T, Akizuki Y, Akiyama T, Imai K, Rutka JT, Snead OC 3rd. Dynamic changes of ictal high-frequency oscillations in neocortical epilepsy: using multiple band frequency analysis. Epilepsia. 2007;48(2):286–96.
- Jacobs J, Zijlmans M, Zelmann R, Chatillon CE, Hall J, Olivier A, Dubeau F, Gotman J. High-frequency electroencephalographic oscillations correlate with outcome of epilepsy surgery. Ann Neurol. 2010;67(2):209–20. doi: 10.1002/ana.21847.
- Brázdil M, Halámek J, Jurák P, Daniel P, Kuba R, Chrastina J, Novák Z, Rektor I. Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia. Epilepsy Res. 2010;90(1–2):28–32. doi: 10.1016/j.eplepsyres.2010.03.003.
- Melani F, Zelmann R, Mari F, Gotman J. Continuous High Frequency Activity: a peculiar SEEG pattern related to specific brain regions. Clin Neurophysiol. 2013;124(8):1507–16. doi: 10.1016/j.clinph.2012.11.016.
- Bragin A, Wilson CL, Engel J. Spatial stability over time of brain areas generating fast ripples in the epileptic rat. Epilepsia. 2003;44(9): 1233–7.
- Bragin A, Li L, Almajano J, Alvarado-Rojas C, Reid AY, Staba RJ, Engel J Jr. Pathologic electrographic changes after experimental traumatic brain injury. Epilepsia. 2016;57(5):735–45. doi: 10.1111/epi.13359.
- Bragin A, Wilson CL, Almajano J, Mody I, Engel J Jr. High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis. Epilepsia. 2004;45(9):1017–23. doi: 10.1111/j.0013-9580.2004.17004.x.