New epilepsy-taxonomy based on the system epilepsy concept – A mini-review and proposal
Main Article Content
Abstract
In this review we propose a new epilepsy-taxonomy, based on recent sleep- and epilepsy research. It has been evidenced that sleep is a “cradle” of human cognitive development, and epileptogenesis – as an inbuilt risk - is underlined by the pathologic increase of the homeostatic NREM sleep regulation and the derailment of synaptic plasticity. Therefore, NREM sleep has an essential role in epileptogenesis and across the course of epilepsies. This approach goes hand in hand with the emerging system-concept abolishing the “Procrustean bed” of the now untenable focal-generalized epilepsy classification.
Based on the system-approach, we briefly reinterpret the most frequent epilepsies each presenting with system-specific features both ictally and interictally while sharing the common mechanism of disfigured epileptic “learning”.
Article Details
How to Cite
HALÁSZ, Péter; SZŰCS, Anna.
New epilepsy-taxonomy based on the system epilepsy concept – A mini-review and proposal.
Medical Research Archives, [S.l.], v. 13, n. 5, may 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6524>. Date accessed: 21 june 2025.
doi: https://doi.org/10.18103/mra.v13i5.6524.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;(3):195-204.
2. Tononi G, Cirelli C. Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003;62 (2):143-50. doi: 10.1016/j.
3. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Medicine Reviews 2006; 10(1): 49-62.
https://doi.org/10.1016/j.smrv.2005.05.002
4. Kattler H, Dijk DJ, Borbély AA. Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans. J Sleep Res 1994;3: 159–64.
5. Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014 Jan 8;81(1):12-34. doi: 10.1016/j.neuron.201 3.12.025
6. Buzsáki Gy, Bayardo F, Miles R, Wong RKS, Gage FH. The grafted hippocampus: An epileptic focus. Experimental Neurology. 1989; 105 (1):10-22. https://doi.org/10.1016/0014-4886(89)90167-2
7. Goddard GV, McIntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol. 1969;25(3): 295-330. doi: 10.1016/0014-4886(69)90128-9.
8. Beenhakker MP, Huguenard JR. Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy? Neuron. 2009;11;62(5):612-32. doi: 10.1016/j.neuron.200 9.05.015.
9. Nobili L, Frauscher B, Eriksson S, Gibbs SA, Halasz P, Lambert I, Manni R, Peter-Derex L, Proserpio P, Provini F, de Weerd A, Parrino L. Sleep and epilepsy: A snapshot of knowledge and future research lines. J Sleep Res. 2022;31(4):e13622. doi: 10.1111/jsr.13622
10. Frauscher B, Gotman J. Sleep, oscillations, interictal discharges, and seizures in human focal epilepsy. Neurobiol Dis. 2019;127:545-53. doi: 10.1016/j.nbd.2019.04.007.
11. Sheybani L, Frauscher B, Bernard C, Walker MC. Mechanistic insights into the interaction between epilepsy and sleep. Nat Rev Neurol. 2025;21(4): 177-92. doi: 10.1038/s41582-025-01064-z.
12. Bernard C, Frauscher B, Gelinas J, Timofeev I. Sleep, oscillations and epilepsy. Epilepsia. 2023;64 Suppl 3(Suppl 3):S3-12. doi: 10.1111/epi.17664
13. Halász P, Szűcs A. Sleep and epilepsy, link with plasticitY Front Neurol. 2020 Aug 28;11:911. doi: 10.3389/fneur.2020.00911.
14. Maglóczky Z, Freund TF. Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield. Neuroscience. 1993;56(2):317–336. doi: 10.1016/0 306-4522(93)90334-c.
15. Avanzini G, Manganotti P, Meletti S, Moshé SL, Panzica F, Wolf P, Capovilla G. The system epilepsies: a pathophysiological hypothesis. Epilepsia. 2012;53(5):771-8. doi: 10.1111/j.1528-1167.2012.0 3462.x.
16. Wolf P, Yacubian EM, Avanzini G, Sander T, Schmitz B, Wandschneider B, Koepp M. Juvenile myoclonic epilepsy: A system disorder of the brain. Epilepsy Res. 2015;114:2-12. doi: 10.1016/j.epilep sy res.2015.04.008.
17. Striano P, Striano S. Reading epilepsy and its variants: a model for system epilepsy. Epilepsy Behav. 2011;20(3):591. doi: 10.1016/j.yebeh.2011.0 1.021
18. Halász P, Kelemen A, Clemens B, Saracz J, Rosdy B, Rásonyi G, Szücs A. The perisylvian epileptic network. A unifying concept. Ideggyogy Sz. 2005; 58(1-2):21-31.
19. Buzsáki G. Hippocampal Sharp Wave-Ripple: A cognitive Biomarker for Episodic Memory and Planning. Hippocampus. 2015;25–8, 10738 10.1093/brain/awaa072.
20. Gulyás A, Freund T. Physiological and pathological high frequency oscillations: The role of perisomatic inhibition in sharp-wave ripple and interictal spike generation10.1126/science.8392750. Current Opinion in Neurobiology. 2015; 31:26–32.
21. von Krosigk M, Bal T, McCormick DA. Cellular mechanisms of a synchronized oscillation in the thalamus. Science. 1993, 16;261(5119):361-4. doi:
22. Crunelli V, Lőrincz ML, McCafferty C, Lambert RC, Leresche N, Di Giovanni G, David F. Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures. Brain. 2020;143(8):2341-2368. doi.
23. Hayman M, Scheffer IE, Chinvarun Y, Berlangieri SU, Berkovic SF. Autosomal dominant nocturnal frontal lobe epilepsy: demonstration of focal frontal onset and intrafamilial variation. Neurology. 1997;49(4):969-75. doi: 10.1212/wnl.4 9.4.969.
24. Halasz P, Simor P,Szűcs A. Fearful arousals in sleep terrors and sleep-related hypermotor epilepticseizures may involve the salience network and the acute stress response of Cannon and Selye Epilepsy Behav Rep. 2024 Feb 1;25:100650. doi:10.1016/j.ebr.2024.100650.
25. Durkin J, Aton SJ. Sleep-Dependent Potentiation in the Visual System Is at Odds with the Synaptic Homeostasis Hypothesis, Sleep, 2016; 19:155– https://doi.org/10.5665/sleep.5338
26. Schomers MR, Garagnani M, Pulvermüller F. Neurocomputational consequences of evolutionary connectivity changes in perisylvian language cortex. J Neuroscience. 2017;37(11):3045–55.
https://doi.org/10.1523/jneurosci.2693-16.2017
27. Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, Guerreiro M, Gwer S, Zuberi SM, Wilmshurst JM, Yozawitz E, Pressler R, Hirsch E, Wiebe S, Cross HJ, Perucca E, Moshé SL, Tinuper P, Auvin S. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63:1398–442. doi: 10.1111/epi.17241
28. Alving, J., Fabricius, M., Rosenzweig, I., & Beniczky, S. (2017). Ictal source imaging and electroclinical correlation in self-limited epilepsy with centrotemporal spikes. Seizure - European
Journal of Epilepsy, 52, 7-10. https://doi.org/10.1016/j.seizure.2017.09.006
29. Tassinari CA, Cantalupo G, Rios-Pohl L, Giustina ED, Rubboli G. Encephalopathy with status epilepticus during slow sleep: "the Penelope syndrome". Epilepsia. 2009;50 Suppl 7:4-8. doi: 10.1111/j.1528-1167.2009.02209.x.
30. Halász P, Szũcs A. Self-limited childhood epilepsies are disorders of the perisylvian communication system, carrying the risk of progress to epileptic encephalopathies-Critical review. Front Neurol. 2023; 1: 1092244. doi: 10.3389/fneur.202 3.1092244.
31. Lu G, Cheng Y, Yang W, Hu J, Zhang F. The Prevalence and Risk Factors of Electrical Status Epilepticus During Slow-Wave Sle Clin EEG Neurosci. 2024; 55(2):265-271. https://doi.org/10.1177/15500594231182758
32. Posar A, Visconti P. Continuous Spike-Waves during Slow Sleep Today: An Update. Children (Basel). 2024;11(2):169. doi: 10.3390/children1102 0169.
33. an den Munckhof B, Zwart AF, Weeke LC, Claessens NHP, Plate JDJ, Leemans A, Kuijf HJ, van Teeseling HC, Leijten FSS, Benders MJN, Braun KPJ, de Vries LS, Jansen FE. Perinatal thalamic injury: MRI predictors of electrical status epilepticus in sleep and long-term neurodevelopment. Neuroimage Clin. 2020;26:102227. doi: 10.1016/j.nicl.2020.102 227
34. Kobayashi K, Yoshinaga H, , Toda Y, Inoue T, Oka M. High-frequency oscillations in idiopathic partial epilepsy of childhood. Epilepsia 2011; 52(10):p. 1812-9; https://doi.org/10.1111/j.1528-1167.2011.03169.x
35. van Klink NE, van 't Klooster MA, Leijten FS, Jacobs J, Braun KP, Zijlmans M. Ripples on rolandic spikes: A marker of epilepsy severity. Epilepsia. 2016; 57:1179–89. 10.1111/epi.13423
36. Overvliet GM, Besseling RM, Vles JS, Hofman PA, Backes WH, van Hall MH, Klinkenberg S, Hendriksen J, Aldenkamp AP. Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature. Epilepsy Behav. 2010;19 (4):550-8. doi: 10.1016/j.yebeh.2010.09.015.
37. Vaudano AE, Avanzini P, Cantalupo G, Filippini M, Ruggieri A, Talami F, Caramaschi E, Bergonzini P, Vignoli A, Veggiotti P, Guerra A, Gessaroli G, Santucci M, Canevini MP, Piccolo B, Pisani F, Gobbi G, Dalla Bernardina B, Meletti S. Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes. Front Neurol. 2019;10:1316. doi: 10.3389/f neur.2019.01316.
38. Wolf P. Reading epilepsy. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, ed. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. London: John Libbey, 1992: 281-98.
39. Puteikis K, Mameniškienė R, Wolf P. Reading epilepsy today: A scoping review and meta-analysis of reports of the last three decades. Epilepsy Behav. 2023;145:109346. doi: 10.1016/j.yebeh.2023.109346.
40. Timofeev I, Bazhenov M, Avramescu S, Nita DA. Posttraumatic epilepsy: the roles of synaptic plasticity. Neuroscientist. 2010;16(1):19-27. doi: 10.1 177/1073858409333545.
41. Houweling AR, Bazhenov M, Timofeev I, Steriade M. Sejnowski TJ. Homeostatic Synaptic Plasticity Can Explain Post-traumatic Epileptogenesis in Chronically Isolated Neocortex Cerebral Cortex 2005; 15(6): 83-45
https://doi.org/10.1093/cercor/bhh184
42. Bagshaw AP, Rollings DT, Khalsa S, Cavanna AE. Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep. Epilepsy Behav. 2014;30:33-7. doi:0.1016/j.yebeh.2013.0 9.027
43. Suntsova N, Kumar S, Guzman-Marin R, Alam MN, Szymusiak R, McGinty D. A role for the preoptic sleep-promoting system in absence epilepsy. Neurobiol Dis. 2009 Oct;36(1):126-41. doi: 10.101 6/j.nbd.2009.07.005.
44. Massimini M, Corbetta M, Sanchez-Vives MV, Andrillon T, Deco G, Rosanova M, Sarasso S. Sleep-like cortical dynamics during wakefulness and their network effects following brain injury. Nat Commun. 2024;15(1):7207. doi: 10.1038/s41467-024-1586-1
2. Tononi G, Cirelli C. Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003;62 (2):143-50. doi: 10.1016/j.
3. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Medicine Reviews 2006; 10(1): 49-62.
https://doi.org/10.1016/j.smrv.2005.05.002
4. Kattler H, Dijk DJ, Borbély AA. Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans. J Sleep Res 1994;3: 159–64.
5. Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014 Jan 8;81(1):12-34. doi: 10.1016/j.neuron.201 3.12.025
6. Buzsáki Gy, Bayardo F, Miles R, Wong RKS, Gage FH. The grafted hippocampus: An epileptic focus. Experimental Neurology. 1989; 105 (1):10-22. https://doi.org/10.1016/0014-4886(89)90167-2
7. Goddard GV, McIntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol. 1969;25(3): 295-330. doi: 10.1016/0014-4886(69)90128-9.
8. Beenhakker MP, Huguenard JR. Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy? Neuron. 2009;11;62(5):612-32. doi: 10.1016/j.neuron.200 9.05.015.
9. Nobili L, Frauscher B, Eriksson S, Gibbs SA, Halasz P, Lambert I, Manni R, Peter-Derex L, Proserpio P, Provini F, de Weerd A, Parrino L. Sleep and epilepsy: A snapshot of knowledge and future research lines. J Sleep Res. 2022;31(4):e13622. doi: 10.1111/jsr.13622
10. Frauscher B, Gotman J. Sleep, oscillations, interictal discharges, and seizures in human focal epilepsy. Neurobiol Dis. 2019;127:545-53. doi: 10.1016/j.nbd.2019.04.007.
11. Sheybani L, Frauscher B, Bernard C, Walker MC. Mechanistic insights into the interaction between epilepsy and sleep. Nat Rev Neurol. 2025;21(4): 177-92. doi: 10.1038/s41582-025-01064-z.
12. Bernard C, Frauscher B, Gelinas J, Timofeev I. Sleep, oscillations and epilepsy. Epilepsia. 2023;64 Suppl 3(Suppl 3):S3-12. doi: 10.1111/epi.17664
13. Halász P, Szűcs A. Sleep and epilepsy, link with plasticitY Front Neurol. 2020 Aug 28;11:911. doi: 10.3389/fneur.2020.00911.
14. Maglóczky Z, Freund TF. Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield. Neuroscience. 1993;56(2):317–336. doi: 10.1016/0 306-4522(93)90334-c.
15. Avanzini G, Manganotti P, Meletti S, Moshé SL, Panzica F, Wolf P, Capovilla G. The system epilepsies: a pathophysiological hypothesis. Epilepsia. 2012;53(5):771-8. doi: 10.1111/j.1528-1167.2012.0 3462.x.
16. Wolf P, Yacubian EM, Avanzini G, Sander T, Schmitz B, Wandschneider B, Koepp M. Juvenile myoclonic epilepsy: A system disorder of the brain. Epilepsy Res. 2015;114:2-12. doi: 10.1016/j.epilep sy res.2015.04.008.
17. Striano P, Striano S. Reading epilepsy and its variants: a model for system epilepsy. Epilepsy Behav. 2011;20(3):591. doi: 10.1016/j.yebeh.2011.0 1.021
18. Halász P, Kelemen A, Clemens B, Saracz J, Rosdy B, Rásonyi G, Szücs A. The perisylvian epileptic network. A unifying concept. Ideggyogy Sz. 2005; 58(1-2):21-31.
19. Buzsáki G. Hippocampal Sharp Wave-Ripple: A cognitive Biomarker for Episodic Memory and Planning. Hippocampus. 2015;25–8, 10738 10.1093/brain/awaa072.
20. Gulyás A, Freund T. Physiological and pathological high frequency oscillations: The role of perisomatic inhibition in sharp-wave ripple and interictal spike generation10.1126/science.8392750. Current Opinion in Neurobiology. 2015; 31:26–32.
21. von Krosigk M, Bal T, McCormick DA. Cellular mechanisms of a synchronized oscillation in the thalamus. Science. 1993, 16;261(5119):361-4. doi:
22. Crunelli V, Lőrincz ML, McCafferty C, Lambert RC, Leresche N, Di Giovanni G, David F. Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures. Brain. 2020;143(8):2341-2368. doi.
23. Hayman M, Scheffer IE, Chinvarun Y, Berlangieri SU, Berkovic SF. Autosomal dominant nocturnal frontal lobe epilepsy: demonstration of focal frontal onset and intrafamilial variation. Neurology. 1997;49(4):969-75. doi: 10.1212/wnl.4 9.4.969.
24. Halasz P, Simor P,Szűcs A. Fearful arousals in sleep terrors and sleep-related hypermotor epilepticseizures may involve the salience network and the acute stress response of Cannon and Selye Epilepsy Behav Rep. 2024 Feb 1;25:100650. doi:10.1016/j.ebr.2024.100650.
25. Durkin J, Aton SJ. Sleep-Dependent Potentiation in the Visual System Is at Odds with the Synaptic Homeostasis Hypothesis, Sleep, 2016; 19:155– https://doi.org/10.5665/sleep.5338
26. Schomers MR, Garagnani M, Pulvermüller F. Neurocomputational consequences of evolutionary connectivity changes in perisylvian language cortex. J Neuroscience. 2017;37(11):3045–55.
https://doi.org/10.1523/jneurosci.2693-16.2017
27. Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, Guerreiro M, Gwer S, Zuberi SM, Wilmshurst JM, Yozawitz E, Pressler R, Hirsch E, Wiebe S, Cross HJ, Perucca E, Moshé SL, Tinuper P, Auvin S. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63:1398–442. doi: 10.1111/epi.17241
28. Alving, J., Fabricius, M., Rosenzweig, I., & Beniczky, S. (2017). Ictal source imaging and electroclinical correlation in self-limited epilepsy with centrotemporal spikes. Seizure - European
Journal of Epilepsy, 52, 7-10. https://doi.org/10.1016/j.seizure.2017.09.006
29. Tassinari CA, Cantalupo G, Rios-Pohl L, Giustina ED, Rubboli G. Encephalopathy with status epilepticus during slow sleep: "the Penelope syndrome". Epilepsia. 2009;50 Suppl 7:4-8. doi: 10.1111/j.1528-1167.2009.02209.x.
30. Halász P, Szũcs A. Self-limited childhood epilepsies are disorders of the perisylvian communication system, carrying the risk of progress to epileptic encephalopathies-Critical review. Front Neurol. 2023; 1: 1092244. doi: 10.3389/fneur.202 3.1092244.
31. Lu G, Cheng Y, Yang W, Hu J, Zhang F. The Prevalence and Risk Factors of Electrical Status Epilepticus During Slow-Wave Sle Clin EEG Neurosci. 2024; 55(2):265-271. https://doi.org/10.1177/15500594231182758
32. Posar A, Visconti P. Continuous Spike-Waves during Slow Sleep Today: An Update. Children (Basel). 2024;11(2):169. doi: 10.3390/children1102 0169.
33. an den Munckhof B, Zwart AF, Weeke LC, Claessens NHP, Plate JDJ, Leemans A, Kuijf HJ, van Teeseling HC, Leijten FSS, Benders MJN, Braun KPJ, de Vries LS, Jansen FE. Perinatal thalamic injury: MRI predictors of electrical status epilepticus in sleep and long-term neurodevelopment. Neuroimage Clin. 2020;26:102227. doi: 10.1016/j.nicl.2020.102 227
34. Kobayashi K, Yoshinaga H, , Toda Y, Inoue T, Oka M. High-frequency oscillations in idiopathic partial epilepsy of childhood. Epilepsia 2011; 52(10):p. 1812-9; https://doi.org/10.1111/j.1528-1167.2011.03169.x
35. van Klink NE, van 't Klooster MA, Leijten FS, Jacobs J, Braun KP, Zijlmans M. Ripples on rolandic spikes: A marker of epilepsy severity. Epilepsia. 2016; 57:1179–89. 10.1111/epi.13423
36. Overvliet GM, Besseling RM, Vles JS, Hofman PA, Backes WH, van Hall MH, Klinkenberg S, Hendriksen J, Aldenkamp AP. Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature. Epilepsy Behav. 2010;19 (4):550-8. doi: 10.1016/j.yebeh.2010.09.015.
37. Vaudano AE, Avanzini P, Cantalupo G, Filippini M, Ruggieri A, Talami F, Caramaschi E, Bergonzini P, Vignoli A, Veggiotti P, Guerra A, Gessaroli G, Santucci M, Canevini MP, Piccolo B, Pisani F, Gobbi G, Dalla Bernardina B, Meletti S. Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes. Front Neurol. 2019;10:1316. doi: 10.3389/f neur.2019.01316.
38. Wolf P. Reading epilepsy. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, ed. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. London: John Libbey, 1992: 281-98.
39. Puteikis K, Mameniškienė R, Wolf P. Reading epilepsy today: A scoping review and meta-analysis of reports of the last three decades. Epilepsy Behav. 2023;145:109346. doi: 10.1016/j.yebeh.2023.109346.
40. Timofeev I, Bazhenov M, Avramescu S, Nita DA. Posttraumatic epilepsy: the roles of synaptic plasticity. Neuroscientist. 2010;16(1):19-27. doi: 10.1 177/1073858409333545.
41. Houweling AR, Bazhenov M, Timofeev I, Steriade M. Sejnowski TJ. Homeostatic Synaptic Plasticity Can Explain Post-traumatic Epileptogenesis in Chronically Isolated Neocortex Cerebral Cortex 2005; 15(6): 83-45
https://doi.org/10.1093/cercor/bhh184
42. Bagshaw AP, Rollings DT, Khalsa S, Cavanna AE. Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep. Epilepsy Behav. 2014;30:33-7. doi:0.1016/j.yebeh.2013.0 9.027
43. Suntsova N, Kumar S, Guzman-Marin R, Alam MN, Szymusiak R, McGinty D. A role for the preoptic sleep-promoting system in absence epilepsy. Neurobiol Dis. 2009 Oct;36(1):126-41. doi: 10.101 6/j.nbd.2009.07.005.
44. Massimini M, Corbetta M, Sanchez-Vives MV, Andrillon T, Deco G, Rosanova M, Sarasso S. Sleep-like cortical dynamics during wakefulness and their network effects following brain injury. Nat Commun. 2024;15(1):7207. doi: 10.1038/s41467-024-1586-1