Skip to main content
Log in

Stimulation strategies for absence seizures: targeted therapy of the focus in coupled thalamocortical model

  • Original Paper
  • Published:
Nonlinear Dynamics Aims and scope Submit manuscript

Abstract

Motivated by the recent experimental findings that thalamic reticular nucleus (TRN) may be a pacemaker of absence seizures, we explore whether changes in the level of TRN activation can induce absence seizures by using a coupled thalamocortical model. We first simulate different firing states by considering the interaction of pathway between cortical excitatory pyramidal neuronal population (PY)–TRN and specific relay nucleus (SRN)–TRN. By simultaneously increasing the coupling strength of each of these pathways, we can reproduce the absence seizures, which indicates that epileptic seizures may be caused by activating the TRN. We further infer that the TRN may be an epileptogenic focus. Following this, different stimulation strategies, including deep brain stimulation, 1:0 coordinated reset stimulation (CRS) and 3:2 CRS, are applied in TRN. By qualitatively analyzing the efficacy of three different stimulation methods, we find that 3:2 CRS is a more effective and safe method to control absence seizures in the first compartment, for which we then further explore the impact of 3:2 CRS in the second compartment. The results show that the additional stimulation in the second compartment also can lead to a considerable decrease in the spike-and-wave discharges (SWD) oscillation region. Therefore, we conclude that TRN-3:2 CRS is an optimal electrical stimulation method for our modeling and simulation studies. Furthermore, we hope that these numerical simulation results can provide some references for the treatment of real epilepsy patients in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Barad, Z., Grattan, D.R., Leitch, B.: NMDA receptor expression in the thalamus of the stargazer model of absence epilepsy. Sci. Rep. 7, 42926 (2017)

    Article  Google Scholar 

  2. Liu, S., Wang, Q.: Transition dynamics of generalized multiple epileptic seizures associated with thalamic reticular nucleus excitability: a computational study. Commun. Nonlinear Sci. Numer. Simul. 52, 203–213 (2017)

    Article  Google Scholar 

  3. Guerrini, R., Melani, F., Brancati, C., et al.: Dysgraphia as a mild expression of dystonia in children with absence epilepsy. PLoS ONE 10(7), e0130883 (2015)

    Article  Google Scholar 

  4. Polack, P.O., Guillemain, I., Hu, E., et al.: Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures. J. Neurosci. 27(24), 6590–6599 (2007)

    Article  Google Scholar 

  5. Steriade, M., Contreras, D.: Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus. J. Neurophysiol. 80(3), 1439–1455 (1998)

  6. Liu, Z., Vergnes, M., Depaulis, A., et al.: Involvement of intrathalamic \(\text{ GABA }_{{\rm B}}\) neurotransmission in the control of absence seizures in the rat. Neuroscience 48(1), 87–93 (1992)

    Article  Google Scholar 

  7. Liu, Z., Vergnes, M., Depaulis, A., et al.: Evidence for a critical role of GABAergic transmission within the thalamus in the genesis and control of absence seizures in the rat. Brain Res. 545(1–2), 1–7 (1991)

    Article  Google Scholar 

  8. Markram, H., Toledo-Rodriguez, M., Wang, Y., et al.: Interneurons of the neocortical inhibitory system. Nat. Rev. Neurosci. 5(10), 793 (2004)

    Article  Google Scholar 

  9. Adotevi, N.K., Leitch, B.: Alterations in AMPA receptor subunit expression in cortical inhibitory interneurons in the epileptic stargazer mutant mouse. Neuroscience 339, 124–138 (2016)

    Article  Google Scholar 

  10. Mineff, E.M., Weinberg, R.J.: Differential synaptic distribution of AMPA receptor subunits in the ventral posterior and reticular thalamic nuclei of the rat. Neuroscience 101(4), 969–982 (2000)

    Article  Google Scholar 

  11. Trevelyan, A.J., Sussillo, D., Watson, B.O., et al.: Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex. J. Neurosci. 26(48), 12447–12455 (2006)

    Article  Google Scholar 

  12. Cammarota, M., Losi, G., Chiavegato, A., et al.: Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy. J. Physiol. 591(4), 807–822 (2013)

    Article  Google Scholar 

  13. Schevon, C.A., Weiss, S.A., McKhann Jr., G., et al.: Evidence of an inhibitory restraint of seizure activity in humans. Nat. Commun. 3, 1060 (2012)

    Article  Google Scholar 

  14. Shiri, Z., Manseau, F., Lévesque, M., et al.: Interneuron activity leads to initiation of lowvoltage fastonset seizures. Ann. Neurol. 77(3), 541–546 (2015)

    Article  Google Scholar 

  15. Yekhlef, L., Breschi, G.L., Lagostena, L., et al.: Selective activation of parvalbumin-or somatostatin-expressing interneurons triggers epileptic seizurelike activity in mouse medial entorhinal cortex. J. Neurophysiol. 113(5), 1616–1630 (2014)

    Article  Google Scholar 

  16. Sessolo, M., Marcon, I., Bovetti, S., et al.: Parvalbumin-positive inhibitory interneurons oppose propagation but favor generation of focal epileptiform activity. J. Neurosci. 35(26), 9544–9557 (2015)

    Article  Google Scholar 

  17. Kwan, P., Brodie, M.J.: Early identification of refractory epilepsy. N. Engl. J. Med. 342(5), 314–319 (2000)

    Article  Google Scholar 

  18. Engel, J., Wiebe, S., French, J., et al.: Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia 44(6), 741–751 (2003)

    Article  Google Scholar 

  19. Kwan, P., Arzimanoglou, A., Berg, A.T., et al.: Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51(6), 1069–1077 (2010)

    Article  Google Scholar 

  20. Pantoja-Jiménez, C.R., Magdaleno-Madrigal, V.M., Almazán-Alvarado, S., et al.: Anti-epileptogenic effect of high-frequency stimulation in the thalamic reticular nucleus on PTZ-induced seizures. Brain Stimul. 7(4), 587–594 (2014)

    Article  Google Scholar 

  21. Lehtimäki, K., Långsjö, J.W., Ollikainen, J., et al.: Successful management of super-refractory status epilepticus with thalamic deep brain stimulation. Ann. Neurol. 81(1), 142–146 (2017)

    Article  Google Scholar 

  22. Nanobashvili, Z., Chachua, T., Nanobashvili, A., et al.: Suppression of limbic motor seizures by electrical stimulation in thalamic reticular nucleus. Exp. Neurol. 181(2), 224–230 (2003)

    Article  Google Scholar 

  23. Wang, Z., Wang, Q.: Eliminating absence seizures through the deep brain stimulation to thalamus reticular nucleus. Front. Comput. Neurosci. 11, 22 (2017)

    Google Scholar 

  24. Zeitler, M., Tass, P.A.: Anti-kindling induced by two-stage coordinated reset stimulation with weak onset intensity. Front. Comput. Neurosci. 10(154), (2016)

  25. Zeitler, M., Tass, P.A.: Augmented brain function by coordinated reset stimulation with slowly varying sequences. Front. Syst. Neurosci. 9, 49 (2015)

    Article  Google Scholar 

  26. Fan, D., Wang, Q.: Improving desynchronization of parkinsonian neuronal network via triplet-structure coordinated reset stimulation. J. Theor. Biol. 370, 157–170 (2015)

    Article  MathSciNet  MATH  Google Scholar 

  27. Wang, Z.H., Wang, Q.Y.: Effect of the coordinated reset stimulations on controlling absence seizure. Sci. China Technol. Sci. 60(7), 985–994 (2017)

    Article  Google Scholar 

  28. Dow, R.S., Fernández-Guardiola, A., Manni, E.: The influence of the cerebellum on experimental epilepsy. Electroencephalogr. Clin. Neurophysiol. 14(3), 383–398 (1962)

    Article  Google Scholar 

  29. Mirski, M.A., Rossell, L.A., Terry, J.B., et al.: Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res. 28(2), 89–100 (1997)

    Article  Google Scholar 

  30. Berdiev, R.K., Luijtelaar, G.V.: Cholinergic stimulation of the nucleus basalis of Meynert and reticular thalamic nucleus affects spike-and-wave discharges in WAG/Rij rats. Neurosci. Lett. 463(3), 249–253 (2009)

    Article  Google Scholar 

  31. Pantojajiménez, C.R., Magdalenomadrigal, V.M., Almazánalvarado, S., et al.: Anti-epileptogenic effect of high-frequency stimulation in the thalamic reticular nucleus on PTZ-induced seizures. Brain Stimul. 7(4), 587–594 (2014)

    Article  Google Scholar 

  32. Fisher, R., Salanova, V., Witt, T., et al.: Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 51(5), 899–908 (2010)

    Article  Google Scholar 

  33. Taylor, P.N., Baier, G.: A spatially extended model for macroscopic spike-wave discharges. J. Comput. Neurosci. 31(3), 679–684 (2011)

    Article  Google Scholar 

  34. Goodfellow, M., Schindler, K., Baier, G.: Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model. Neuroimage 55(3), 920–932 (2011)

    Article  Google Scholar 

  35. Taylor, P.N., Baier, G., Cash, S.S., et al.: A model of stimulusinduced epileptic spike-wave discharges. In: 2013 IEEE Symposium on Computational Intelligence, Cognitive Algorithms, Mind, and Brain (CCMB), pp. 53–59. IEEE (2013)

  36. Yan, B., Li, P.: An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments. PLoS ONE. 6(7), e22440 (2011)

    Article  Google Scholar 

  37. Taylor, P.N., Wang, Y., Goodfellow, M., et al.: A computational study of stimulus driven epileptic seizure abatement. PLoS ONE 9(12), e114316 (2014)

    Article  Google Scholar 

  38. Evangelista, E., Bénar, C., Bonini, F., et al.: Does the thalamo-cortical synchrony play a role in seizure termination? Front. Neurol. 6, 192 (2015)

    Article  Google Scholar 

  39. Moeller, F., Muthuraman, M., Stephani, U., et al.: Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses. Human Brain Map. 34(8), 1896–1909 (2013)

    Article  Google Scholar 

  40. Neal, T.P., Wang, Y., Marc, G., et al.: A computational study of stimulus driven epileptic seizure abatement. PLoS ONE 9(12), e114316 (2014)

    Article  Google Scholar 

  41. Taylor, P.N., Thomas, J., Sinha, N., et al.: Optimal control based seizure abatement using patient derived connectivity. Front. Neurosci. 9(9), 202 (2015)

    Google Scholar 

  42. Ellis, T.L., Stevens, A.: Deep brain stimulation for medically refractory epilepsy. Neurosurg. Focus 25(3), E11 (2008)

    Article  Google Scholar 

  43. McConnell, G.C., So, R.Q., Hilliard, J.D., et al.: Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns. J. Neurosci. 32(45), 15657–15668 (2012)

    Article  Google Scholar 

  44. Benazzouz, A., Piallat, B., Pollak, P., et al.: Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Neurosci. Lett. 189(2), 77–80 (1995)

    Article  Google Scholar 

  45. Feddersen, B., Vercueil, L., Noachtar, S., et al.: Controlling seizures is not controlling epilepsy: a parametric study of deep brain stimulation for epilepsy. Neurobiol. Dis. 27(3), 292–300 (2007)

    Article  Google Scholar 

  46. Vercueil, L., Benazzouz, A., Deransart, C., et al.: High-frequency stimulation of the sub-thalamic nucleus suppresses absence seizures in the rat: comparison with neurotoxic lesions. Epilepsy Res. 31(1), 39–46 (1998)

    Article  Google Scholar 

  47. Fan, D., Wang, Z., Wang, Q.: Optimal control of directional deep brain stimulation in the parkinsonian neuronal network. Commun. Nonlinear Sci. Numer. Simul. 36, 219–237 (2016)

    Article  MathSciNet  Google Scholar 

  48. Chen, M., Guo, D., Wang, T., et al.: Bidirectional control of absence seizures by the basal ganglia: a computational evidence. PLoS Comput. Biol. 10(3), e1003495 (2014)

    Article  Google Scholar 

  49. Chen, M., Guo, D., Li, M., et al.: Critical roles of the direct GABAergic pallido-cortical pathway in controlling absence seizures. PLoS Comput. Biol. 11(10), e1004539 (2015)

    Article  Google Scholar 

  50. Lewis, L.D., Voigts, J., Flores, F.J., Schmitt, L.I., Wilson, M.A., Halassa, M.M., Brown, E.N.: Thalamic reticular nucleus induces fast and local modulation of arousal state. Elife 13(4), e08760 (2015)

    Article  Google Scholar 

  51. John, Y.J., Zikopoulos, B., Bullock, D., Barbas, H.: The emotional gatekeeper: a computational model of attentional selection and suppression through the pathway from the amygdala to the inhibitory thalamic reticular nucleus. PLoS Comput. Biol. 12(2), e1004722 (2016)

    Article  Google Scholar 

  52. Perry, M.S., Duchowny, M.: Surgical versus medical treatment for refractory epilepsy: outcomes beyond seizure control. Epilepsia 54(12), 2060–2070 (2013)

    Article  Google Scholar 

  53. Irimia, A., Van Horn, J.D.: Epileptogenic focus localization in treatment-resistant post-traumatic epilepsy. J. Clin. Neurosci. 22(4), 627–631 (2015)

    Article  Google Scholar 

  54. Fan, D., Wang, Q.: Improved control effect of absence seizures by autaptic connections to the subthalamic nucleus. Phys. Rev. E 98(5), 052414 (2018)

    Article  MathSciNet  Google Scholar 

  55. Liang, S., Wang, Z.H.: Controlling a neuron by stimulating a coupled neuron. Appl. Math. Mech. Engl. Ed. 40(1), 13–24 (2019)

    Article  MathSciNet  MATH  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 11772019).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qingyun Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animals rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Z., Wang, Q. Stimulation strategies for absence seizures: targeted therapy of the focus in coupled thalamocortical model. Nonlinear Dyn 96, 1649–1663 (2019). https://doi.org/10.1007/s11071-019-04876-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11071-019-04876-z

Keywords

Navigation