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How Can Computer Modelling Help in Understanding the Dynamics of Absence Epilepsy?

  • Piotr SuffczynskiEmail author
  • Stiliyan Kalitzin
  • Fernando H. Lopes da Silva
Chapter
Part of the Springer Series in Cognitive and Neural Systems book series (SSCNS, volume 13)

Abstract

An overview of the pathophysiology of absence seizures is given, focusing on computational modelling where recent neurophysiological experimental evidence is incorporated. The main question addressed is what is the dynamical process by which the same brain can produce sustained bursts of synchronous spike-and-wave discharges (SWDs) and normal, largely desynchronized brain activity, i.e. to display bistability. This generic concept, tested on an updated neural mass computational model of absence seizures, predicts certain properties of the probability distributions of inter-ictal intervals and of the durations of ictal events. A critical analysis of the distributions predicted by the model and those found in reality led to adjustments of the model with respect to the control of the duration of ictal events. Another prediction derived from the bistable dynamics, the possibility of aborting absence seizures by means of counter-controlled electrical stimulation, is also discussed in the light of current experimental studies. Finally the most recent update of the model was carried out to account for the particular properties of the cortical “driver” of SWDs, and the underlying putative role of the persistent Na+ current of cortical neurons in this process.

Keywords

Generalized epilepsies Absence seizures Neural mass models Dynamical neural systems Bistability Inter-ictal and ictal distributions Counter-stimulation Ih current Na-persistent current 

References

  1. 1.
    Avoli M (2012) A brief history on the oscillating roles of thalamus and cortex in absence seizures. Epilepsia 53(5):779–789CrossRefGoogle Scholar
  2. 2.
    Berényi A, Belluscio M, Mao D, Buzsáki G (2012) Closed-loop control of epilepsy by transcranial electrical stimulation. Science 337:735–737CrossRefGoogle Scholar
  3. 3.
    Blumenfeld H, Klein JK, Schridde U, Vestal M, Rice T, Khera DS, Bashyal C, Giblin K, Paul-Laughinghouse C, Wang F, Phadke A, Mission J, Agarwal RK, Englot DJ, Motelow J, Nerseyan H, Waxman SG, Levin AR (2008) Early treatment suppresses the development of spike-wave epilepsy in a rat model. Epilepsia 49(3):400–409CrossRefGoogle Scholar
  4. 4.
    Bouwman BM, Suffczynski P, Midzyanovskaya IS, Matis E, van den Broek PLC, van Rijn CM (2007) The effects of vigabatrin on spike and wave discharges in WAG/Rij rats. Epilepsy Res 76:34–40CrossRefGoogle Scholar
  5. 5.
    Breakspear M, Roberts JA, Terry JR, Rodrigues S, Mahant N, Robinson PA (2006) A unifying explanation of primary generalized seizures through nonlinear brain modeling and bifurcation analysis. Cereb Cortex 16:1296–1313CrossRefGoogle Scholar
  6. 6.
    Chipaux M, Charpier S, Polack PO (2011) Chloride-mediated inhibition of the ictogenic neurons initiating genetically-determined absence seizures. Neuroscience 192:642–651CrossRefGoogle Scholar
  7. 7.
    Destexhe A, Contreras D, Steriade M (1998) Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. J Neurophysiol 79:999–1016. [PubMed: 9463458]CrossRefGoogle Scholar
  8. 8.
    Destexhe A, Sejnowski TJ (2003) Interactions between membrane conductances underlying thalamocortical slow-wave oscillations. Physiol Rev 83:1401–1453CrossRefGoogle Scholar
  9. 9.
    Dezsi G, Ozturk E, Stanic D, Powell KL, Blumenfeld H, O’Brien TJ, Jones NC (2013) Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia 54(4):635–643CrossRefGoogle Scholar
  10. 10.
    Feynman, R WikiquoteGoogle Scholar
  11. 11.
    Gerstein GL, Mandelbrot B (1964) Random walk models for the spike activity of a single neurons. Biophys J 4:41–68CrossRefGoogle Scholar
  12. 12.
    Goodfellow M, Schindler K, Baier G (2011) Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model. NeuroImage 55(3):920–932CrossRefGoogle Scholar
  13. 13.
    Johnston D, Wu SMS (1995) Foundations of cellular neurophysiology. The MIT Press, Cambridge, MAGoogle Scholar
  14. 14.
    Klein JP, Khera DS, Nersesyan H, Kimchi EY, Waxman SG, Blumenfeld H (2004) Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy. Brain Res 1000:102–109CrossRefGoogle Scholar
  15. 15.
    Koppert MMJ, Kalitzin SN, Lopes da Silva FH, Viergever MA (2011) Plasticity-modulated seizure dynamics for seizure termination in realistic neuronal models. J Neural Eng 8:1–11CrossRefGoogle Scholar
  16. 16.
    Koppert MMJ, Kalitzin SN, Velis D, Lopes da Silva FH, Viergever MA (2013) Reactive control of epileptiform discharges in realistic computational neuronal models with bistability. Int J Neural Syst 23(1). (No 1230032)):1–10CrossRefGoogle Scholar
  17. 17.
    Kozák G, Berenyi A (2017) Sustained efficacy of closed loop electrical stimulation for long-term treatment of absence epilepsy in rats. Sci Rep 7(6300):1–9Google Scholar
  18. 18.
    Leresche N, Parri HR, Erdemli G, Guyon A, Turner JP, Williams SR, Asprodini E, Crunelli V (1998) On the action of the anti-absence drug ethosuximide in the rat and cat thalamus. J Neurosci 18:4842–4853CrossRefGoogle Scholar
  19. 19.
    Lopes da Silva FH, Blanes W, Kalitzin SN, Parra J, Suffczynski P, Velis DN (2003) Dynamical diseases of brain systems: different routes to epileptic seizures. IEEE Trans Biomed Eng 50(5):540–548CrossRefGoogle Scholar
  20. 20.
    Lopes da Silva FH et al (2003) Epilepsies as dynamical diseases of brain systems: basic models of the transition between normal and epileptic activity. Epilepsia 44(Suppl. 12):72–83CrossRefGoogle Scholar
  21. 21.
    Lüttjohann A, van Luijtelaar G (2013) Thalamic stimulation in absence epilepsy. Epilepsy Res 106:136–145CrossRefGoogle Scholar
  22. 22.
    Lytton WW (2008) Computer modeling of epilepsy. Nat Rev Neurosci 9:626–637CrossRefGoogle Scholar
  23. 23.
    Lytton WW, Contreras D, Destexhe A, Steriade M (1997) Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. J Neurophysiol 77:1676–1696Google Scholar
  24. 24.
    Mackey MC, Glass L (1977) Oscillation and chaos in physiological control systems. Sci New Ser 197(4300):287–289Google Scholar
  25. 25.
    Mackey MC, Milton JM (1987) Dynamical diseases. Ann N Y Acad Sci 504:16–32CrossRefGoogle Scholar
  26. 26.
    Manning JPA, Richards DA, Leresche N, Crunelli V, Bowery NG (2004) Cortical-area-specific block of genetically determined absence seizures by ethosuximide. Neuroscience 123:5–9CrossRefGoogle Scholar
  27. 27.
    Marten F, Rodrigues S, Suffczynski P, Richardson MP, Terry JR (2009) Derivation and analysis of an ordinary differential equation mean-field model for studying clinically recorded epilepsy dynamics. Phys Rev E 79(2 Pt 1):021911CrossRefGoogle Scholar
  28. 28.
    Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH (2002) Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 22:1480–1495CrossRefGoogle Scholar
  29. 29.
    Meeren H, van Luijtelaar G, Lopes da Silva F, Coenen A (2005) Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory. Arch Neurol 62:371–376CrossRefGoogle Scholar
  30. 30.
    Milton J, Jianhong W, Campbell SA, Bélair J (2017) Outgrowing neurological diseases: microcircuits, conduction delay and childhood absence epilepsy. In: Érdi P, Sen Bhattacharya B, Cochran AL (eds) Computational neurology and psychiatry. Springer International Publishing, Cham, pp 11–47CrossRefGoogle Scholar
  31. 31.
    Osorio I, Frei MG (2009) Seizure abatement with single dc pulses: is phase resetting at play? Int J Neural Syst 19(3):149–156CrossRefGoogle Scholar
  32. 32.
    Paz JT, Huguenard JR (2015) Microcircuits and their interactions in epilepsy: is the focus out of focus? Nat Neurosci 18:351–359.Google Scholar
  33. 33.
    Robinson PA, Rennie CJ, Rowe DL (2002) Dynamics of large-scale brain activity in normal arousal states and epileptic seizures. Phys Rev E 65:041924CrossRefGoogle Scholar
  34. 34.
    Polack PO, Guillemain I, Hu E, Deransart C, Depaulis A, Charpier S (2007) Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures. J Neurosci 27:6590–6599CrossRefGoogle Scholar
  35. 35.
    Rajna P, Lona C (1989) Sensory stimulation for inhibition of epileptic seizures. Epilepsia 30:168–174CrossRefGoogle Scholar
  36. 36.
    Sorokin JM, Davidson TJ, Frechette E, Abramian AM, Deisseroth K, Huguenard JR, Paz JT (2017) Bidirectionsl control of generalized epilepsy networks via rapid real-time switching of firing mode. Neuron 93:149–210CrossRefGoogle Scholar
  37. 37.
    Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685CrossRefGoogle Scholar
  38. 38.
    Suffczynski P, Kalitzin SN, Lopes da Silva FH (2004) Dynamics of nonconvulsive epileptic phenomena modeled by a bistable neuronal network. Neuroscience 126:467–484CrossRefGoogle Scholar
  39. 39.
    Suffczynski P, Lopes da Silva FH, Parra J, Velis DN, Bouwman BM, van Rijn CM, van Hese P, Boon P, Khosravani H, Derchansky M, Carlen P, Kalitzin SN (2006) Dynamics of epileptic phenomena determined from statistics of ictal transitions. IEEE Trans Bio Med Eng 53(3):524–532CrossRefGoogle Scholar
  40. 40.
    Van Heukelum S, Kelderhuis J, Janssen P, van Luijtelaar G, Lüttjohann A (2016) Timing of high-frequency stimulation in a genetic absence model. Neuroscience 324:191–201CrossRefGoogle Scholar
  41. 41.
    Wang XJ (1994) Multiple dynamical modes of thalamic relay neurons: rhythmic bursting and intermittent phase-locking. Neuroscience 59:21–31CrossRefGoogle Scholar
  42. 42.
    Williams MS, Altwegg-Boussac T, Chavez M, Lecas S, Mahon S, Charpier S (2016) Integrative properties and transfer function of cortical neurons initiating s=absence seizures in a rat genetic model. J Physiol 594(22):6733–6751CrossRefGoogle Scholar
  43. 43.
    Wilson HR, Cowan JD (1972) Excitatory and inhibitory interactions in localized populations of model neurons. Biophys J 12:121–124Google Scholar
  44. 44.
    Wendling F, Bartolomei F, Bellanger JJ, Chauvel P (2002) Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition. Eur J Neurosci 15:1499–1508CrossRefGoogle Scholar
  45. 45.
    Wendling F, Hernandez A, Bellanger JJ, Chauvel P, Bartolomei F (2005) Interictal to ictal transition in human temporal lobe epilepsy; insights from a computational model of intracerebral EEG. J Clin Neurophysiol 22:343–356PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Piotr Suffczynski
    • 1
    Email author
  • Stiliyan Kalitzin
    • 2
    • 3
  • Fernando H. Lopes da Silva
    • 4
    • 5
  1. 1.Department of Biomedical Physics, Institute of Experimental PhysicsUniversity of WarsawWarsawPoland
  2. 2.Foundation Epilepsy Institute in The Netherlands (SEIN)HeemstedeThe Netherlands
  3. 3.Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Swammerdam Institute for Life Sciences, Center of NeuroscienceUniversity of AmsterdamAmsterdamThe Netherlands
  5. 5.Department of Bioengineering, Instituto Superior TécnicoLisbon Technical UniversityLisbonPortugal

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