Epileptogenesis and the piriform cortex: Understanding temporal lobe epilepsy beyond the hippocampus
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Rolandic Epilepsy
Piriform Cortex
Temporal Lobe
Epileptogenic Zone


Introduction: With the experience of invasive EEG recordings and surgical failure after surgery, it has become clear that temporal lobe epilepsy is much more complex than previously thought, and currently, is conceptualized as a disease of anatomical networks instead of structural lesions.

Content: The current neurophysiological and imaging information allows us to conclude that several temporal and extratemporal anatomical networks are involved in this type of epilepsy. One way of understanding the concept of the epileptic network in temporal lobe epilepsy is from the knowledge of the piriform cortex. Several clinical studies have shown that in patients with temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that is more significant compared to patients with focal extra-hippocampal epilepsy and healthy controls. This alteration is probably the consequence of a dysfunctional neural network that extends beyond the hippocampus and affects other nearby structures, including the piriform cortex.

Conclusion: In this article, we carry out a narrative review of the literature with the aim of establishing a link between the piriform cortex and temporal lobe epileptogenesis, demonstrating that this disease is the consequence of a dysfunctional network that does not depend exclusively of a hippocampal structural abnormality.

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Ioannou P, Foster DL, Sander JW, Dupont S, Gil-Nagel A, Drogon O'Flaherty E, et al. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022;12: e2589. https://doi.org/10.1002/brb3.2589

González Otárula KA, Schuele S. Networks in temporal lobe epilepsy. Neurosurg Clin N Am. 2020; 31:309-17. https://doi.org/10.1016/j.nec.2020.02.001

Bartolomei F, Lagarde S, Wendling F, McGonigal A, Jirsa V, Guye M, et al. Defining epileptogenic networks: Contribution of SEEG and signal analysis. Epilepsia. 2017;58: 1131-47. https://doi.org/10.1111/epi.13791

Bonilha L, Martz GU, Glazier SS, Edwards JC. Subtypes of medial temporal lobe epilepsy: influence on temporal lobectomy outcomes? Epilepsia. 2012;53:1-6. https://doi.org/10.1111/j.1528-1167.2011.03298.x

Spencer SS. Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia. 2002;43:219-27. https://doi.org/10.1046/j.1528-1157.2002.26901.x

Sala-Padro J, Miró J, Rodriguez-Fornells A, Rifa-Ros X, Plans G, Santurino M, et al. Mapping connectivity fingerprints for presurgical evaluation of temporal lobe epilepsy. BMC Neurol. 2021;21:442. https://doi.org/10.1186/s12883-021-02469-1

Vismer MS, Forcelli PA, Skopin MD, Gale K, Koubeissi MZ. The piriform, perirhinal, and entorhinal cortex in seizure generation. Front Neural Circuits. 2015;9:27. https://doi.org/10.3389/fncir.2015.00027

de Curtis M, Librizzi L, Uva L. Limbic and olfactory cortical circuits in focal seizures. Neurobiol Dis. 2023;178:106007. https://doi.org/10.1016/j.nbd.2023.106007

Cheng H, Wang Y, Chen J, Chen Z. The piriform cortex in epilepsy: What we learn from the kindling model. Exp Neurol. 2020;324:113137. https://doi.org/10.1016/j.expneurol.2019.113137

Espinosa-Jovel C, Toledano R, Jiménez-Huete A, Aledo-Serrano Á, García-Morales I, Campo P, et al. Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus. Epilepsia Open. 2019;4:487-92. https://doi.org/10.1002/epi4.12343

Vaughan DN, Jackson GD. The piriform cortex and human focal epilepsy. Front Neurol. 2014;5:259. https://doi.org/10.3389/fneur.2014.00259

Young JC, Vaughan DN, Nasser HM, Jackson GD. Anatomical imaging of the piriform cortex in epilepsy. Exp Neurol. 2019;320:113013. https://doi.org/10.1016/j.expneurol.2019.113013

Löscher W, Ebert U. The role of the piriform cortex in kindling. Prog Neurobiol. 1996;50: 427-81. https://doi.org/10.1016/S0301-0082(96)00036-6

Klingler E. Development and organization of the evolutionarily conserved three-layered olfactory cortex. eNeuro. 2017;4:ENEURO.0193-16.2016. https://doi.org/10.1523/ENEURO.0193-16.2016

Li D, Luo D, Wang J, Wang W, Yuan Z, Xing Y, et al. Electrical stimulation of the endopiriform nucleus attenuates epilepsy in rats by network modulation. Ann Clin Transl Neurol. 2020;7:2356-69. https://doi.org/10.1002/acn3.51214

Suzuki N, Bekkers JM. Neural coding by two classes of principal cells in the mouse piriform cortex. J Neurosci. 2006;26:11938-47. https://doi.org/10.1523/JNEUROSCI.3473-06.2006

Ekstrand JJ, Domroese ME, Johnson DM, Feig SL, Knodel SM, Behan M, Haberly LB. A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy. J Comp Neurol. 2001;434:289-307. https://doi.org/10.1002/cne.1178

Bensafi M. The role of the piriform cortex in human olfactory perception: Insights from functional neuroimaging studies. Chemosens Percept. 2012;5:4-10. https://doi.org/10.1007/s12078-011-9110-8

Zhou G, Lane G, Cooper SL, Kahnt T, Zelano C. Characterizing functional pathways of the human olfactory system. Elife. 2019;8:e47177. https://doi.org/10.7554/eLife.47177

Koepp M, Galovic M. Functional imaging of the piriform cortex in focal epilepsy. Exp Neurol. 2020;330:113305. https://doi.org/10.1016/j.expneurol.2020.113305

McIntyre DC, Kelly ME, Dufresne C. FAST and SLOW amygdala kindling rat strains: comparison of amygdala, hippocampal, piriform and perirhinal cortex kindling. Epilepsy Res. 1999;35:197-209. https://doi.org/10.1016/S0920-1211(99)00012-1

Löscher W, Ebert U, Wahnschaffe U, Rundfeldt C. Susceptibility of different cell layers of the anterior and posterior part of the piriform cortex to electrical stimulation and kindling: comparison with the basolateral amygdala and “area tempestas”. Neuroscience. 1995;66:265-76. https://doi.org/10.1016/0306-4522(94)00614-B

Skopin MD, Bayat A, Kurada L, Siddu M, Joshi S, Zelano CM, et al. Epileptogenesis-induced changes of hippocampal-piriform connectivity. Seizure. 2020;81:1-7. https://doi.org/10.1016/j.seizure.2020.07.008

Haneef Z, Lenartowicz A, Yeh HJ, Levin HS, Engel J Jr, Stern JM. Functional connectivity of hippocampal networks in temporal lobe epilepsy. Epilepsia. 2014;55:137-45. https://doi.org/10.1111/epi.12476

Fahoum F, Lopes R, Pittau F, Dubeau F, Gotman J. Widespread epileptic networks in focal epilepsies: EEG-fMRI study. Epilepsia. 2012;53:1618-27. https://doi.org/10.1111/j.1528-1167.2012.03533.x

Mirandola L, Ballotta D, Talami F, Giovannini G, Pavesi G, Vaudano AE, Meletti S. Temporal lobe spikes affect distant intrinsic connectivity networks. Front Neurol. 2021;12:746468. https://doi.org/10.3389/fneur.2021.746468

Flanagan D, Badawy RA, Jackson GD. EEG-fMRI in focal epilepsy: local activation and regional networks. Clin Neurophysiol. 2014;125:21-31. https://doi.org/10.1016/j.clinph.2013.06.182

Türk BG, Metin B, Tekeli H, Sayman ÖA, K?z?lk?l?ç O, Uzan M, et al. Evaluation of olfactory and gustatory changes in patients with mesial temporal lobe epilepsy. Seizure. 2020;75:110-4. https://doi.org/10.1016/j.seizure.2020.01.001

Galovic M, Baudracco I, Wright-Goff E, Pillajo G, Nachev P, Wandschneider B, et al. Association of piriform cortex resection with surgical outcomes in patients with temporal lobe epilepsy. JAMA Neurol. 2019;76:690-700. https://doi.org/10.1001/jamaneurol.2019.0204

Leon-Rojas JE, Iqbal S, Vos SB, Rodionov R, Miserocchi A, McEvoy AW, et al. Resection of the piriform cortex for temporal lobe epilepsy: a Novel approach on imaging segmentation and surgical application. Br J Neurosurg. 2021,18:1-6. https://doi.org/10.1080/02688697.2021.1966385

Borger V, Hamed M, Bahna M, Rácz Á, Ilic I, Potthoff AL, et al. Temporal lobe epilepsy surgery: Piriform cortex resection impacts seizure control in the long-term. Ann Clin Transl Neurol. 2022; 9:1206-11. https://doi.org/10.1002/acn3.51620

Laufs H, Richardson MP, Salek-Haddadi A, Vollmar C, Duncan JS, Gale K, et al. Converging PET and fMRI evidence for a common area involved in human focal epilepsies. Neurology. 2011;77:904-10. https://doi.org/10.1212/WNL.0b013e31822c90f2

Kang JY, Yenokyan G, Hwang BY, Chen M, Penn R, Mampre D, Sperling MR, Kamath V. Odor identification predicts postoperative seizure control following magnetic resonance-guided laser interstitial thermal therapy. Epilepsia. 2020;61:1949-57. https://doi.org/10.1111/epi.16645

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