Skip to main content
Log in

Early seizure detection in rats based on vagus nerve activity

  • Original Article
  • Published:
Medical & Biological Engineering & Computing Aims and scope Submit manuscript

Abstract

Continuous, scheduled vagus nerve stimulation (VNS) is used for the treatment of refractory epilepsy. On-demand VNS, started prior to or at the onset of a seizure may improve the effect of the treatment, however, this requires seizures to be predicted or detected early. This study investigates the possibility of early seizure detection based on the cervical vagus electroneurogram (VENG). Fourteen anesthetized rats received an intravenous infusion (IV) of either saline (control, n = 6) or pentylenetetrazol (PTZ) diluted in saline (PTZ-treated, n = 8). A cardiac-related VENG profile (CrVENG) was derived by using R-peak triggered averaging of the VENG energy. Following, changes in this profile were evaluated as a seizure predictor. Using left nerve VENG, seizures were detected in all PTZ-treated rats 103 ± 51 s (mean ± SD) before they developed tonic seizures. Control rats did not develop seizures and our method did also not detected seizures in these rats. Seizures can be early detecting based on left nerve VENG in anesthetized rats. Preictal CrVENG changes may reflect central-mediated changes and/or changes in the relation between the respiration and the cardiac cycle. Further research is needed to evaluate the method in awake and freely moving animals and eventually in humans.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. Aldes LD (1988) Thalamic connectivity of rat somatic motor cortex. Brain Res Bull 20:333–348

    Article  CAS  PubMed  Google Scholar 

  2. Baldi P, Brunak S, Chauvin Y, Andersen CA, Nielsen H (2000) Assessing the accuracy of prediction algorithms for classification: an overview. Bioinformatics 16:412–424

    Article  CAS  PubMed  Google Scholar 

  3. Ben-Menachem E (2001) Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol 18:415–418

    Article  CAS  PubMed  Google Scholar 

  4. Boon P, Vonck K, Van Walleghem P, D’Have M, Goossens L, Vandekerckhove T et al (2001) Programmed and magnet-induced vagus nerve stimulation for refractory epilepsy. J Clin Neurophysiol 18:402–407

    Article  CAS  PubMed  Google Scholar 

  5. Cao WH, Morrison SF (2003) Disinhibition of rostral raphe pallidus neurons increases cardiac sympathetic nerve activity and heart rate. Brain Res 980:1–10

    Article  CAS  PubMed  Google Scholar 

  6. Coleridge HM, Coleridge JC, Kidd C (1964) Cardiac receptors in the dog, with particular reference to two types of afferent ending in the ventricular wall. J Physiol 174:323–339

    CAS  PubMed  Google Scholar 

  7. De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B et al (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269

    Article  PubMed  Google Scholar 

  8. DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman B et al (2000) Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41:1195–1200

    Article  CAS  PubMed  Google Scholar 

  9. Einthoven W, Flohil A, Battaerd PJTA (1908) On vagus currents examined with the string galvanometer. Exp Physiol; Q J Exp Physiol 1:243–245

    Google Scholar 

  10. Fisher RS (1989) Animal models of the epilepsies. Brain Res Rev 14:245–278

    Article  CAS  PubMed  Google Scholar 

  11. Green JH, Neil E (1955) The respiratory function of the laryngeal muscles. J Physiol 129:134–141

    CAS  PubMed  Google Scholar 

  12. Hamlin RL, Smith CR (1968) Effects of vagal stimulation on S-A and A-V nodes. Am J Physiol 215:560–568

    CAS  PubMed  Google Scholar 

  13. Hammond EJ, Uthman BM, Reid SA, Wilder BJ (1992) Electrophysiological studies of cervical vagus nerve stimulation in humans. I. EEG effects. Epilepsia 33:1013–1020

    Article  CAS  PubMed  Google Scholar 

  14. Hoffer JA, Kallesøe K (2001) How to use nerve cuffs to stimulate, record or modulate neural activity. In: Moxon KA, Chapin JK, Moxon KA (eds) Neural prostheses for restoration of sensory and motor function. CRC Press, USA, pp 139–175

    Google Scholar 

  15. Katona PG, Poitras JW, Barnett GO, Terry BS (1970) Cardiac vagal efferent activity and heart period in the carotid sinus reflex. Am J Physiol 218:1030–1037

    CAS  PubMed  Google Scholar 

  16. Kerem DH, Geva AB (2005) Forecasting epilepsy from the heart rate signal. Med Biol Eng Comput 43:230–239

    Article  CAS  PubMed  Google Scholar 

  17. Lathers CM, Schraeder PL (1982) Autonomic dysfunction in epilepsy: characterization of autonomic cardiac neural discharge associated with pentylenetetrazol-induced epileptogenic activity. Epilepsia 23:633

    Article  CAS  PubMed  Google Scholar 

  18. Leung H, Schindler K, Kwan P, Elger C (2007) Asystole induced by electrical stimulation of the left cingulate gyrus. Epilept Disord 9:77–81

    Google Scholar 

  19. Loewy AD, Spyer KM (1990) Vagal preganglionic neurons. In: Loewy AD, Spyer KM (eds) Central Regulation of autonomic functions. Oxford University Press, New York, pp 68–87

    Google Scholar 

  20. Lüttjohann A, Fabene PF, Van Luijtelaar G (2009) A revised Racine’s scale for PTZ-induced seizures in rats. Physiol Behav 98:579

    Article  PubMed  Google Scholar 

  21. Mameli O, Caria MA, Pintus A, Padua G, Mameli S (2006) Sudden death in epilepsy: an experimental animal model. Seizure 15:275–287

    Article  CAS  PubMed  Google Scholar 

  22. McCloskey DI (1994) Cardiorespiratory integration. In: Levy MN, Schwartz PJ (eds) Vagal control of the heart: experimental basis and clinical implications. Futura Publishing Company Inc., Armonk, New York, p 65

    Google Scholar 

  23. Mormann F, Andrzejak RG, Elger CE, Lehnertz K (2007) Seizure prediction: the long and winding road. Brain 130:314–333

    Article  PubMed  Google Scholar 

  24. Morris GL, III (2003) A retrospective analysis of the effects of magnet-activated stimulation in conjunction with vagus nerve stimulation therapy. Epilepsy Behav 4:740–745

  25. Morris GL, III, Mueller WM (1999) Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01–E05. Neurology 53:1731–1735

  26. Nielsen KR, Sevcencu C, Rasmussen A, Struijk JJ (2008) Prediction of epileptic seizures for on-demand vagus nerve stimulation. In: 14th Nordic-Baltic conference on biomedical engineering and medical physics NBC. Springer, Berlin, Heidelberg

  27. Novak V, Reeves AL, Novak P, Low PA, Sharbrough FW (1999) Time–frequency mapping of R–R interval during complex partial seizures of temporal lobe origin. J Auton Nerv Syst 77:195–202

    Article  CAS  Google Scholar 

  28. Onuma T (1957) Relationships of the predisposition to convulsions with the action potentials of the autonomic nerves and the brain. II. Changes in action potential of the autonomic nerves and the brain under conditions for increasing the predisposition to convulsions. Tohoku J Exp Med 65:121–129

    Article  CAS  PubMed  Google Scholar 

  29. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, Inc., London

    Google Scholar 

  30. Pellmar TC, Wilson WA (1977) Synaptic mechanism of pentylenetetrazole: selectivity for chloride conductance. Science 197:912–914

    Article  CAS  PubMed  Google Scholar 

  31. Ramzan IM, Levy G (1985) Kinetics of drug action in disease states. XIV. Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions. J Pharmacol Exp Ther 234:624–628

    CAS  PubMed  Google Scholar 

  32. Sarkisian MR (2001) Overview of the current animal models for human seizure and epileptic disorders. Epilepsy Behav 2:201–216

    Article  PubMed  Google Scholar 

  33. Sevcencu C, Struijk JJ (2010) Autonomic alterations and cardiac changes in epilepsy. Epilepsia 51:725–737

    Article  PubMed  Google Scholar 

  34. Soltis RP, DiMicco JA (1991) GABAA and excitatory amino acid receptors in dorsomedial hypothalamus and heart rate in rats. Am J Physiol 260:R13–R20

    CAS  PubMed  Google Scholar 

  35. Spyer KM, Brooks PA, Izzo PN (1994) Vagal preganglionic neurons supplying the heart. In: Schwartz PJ, Levy MN (eds) Vagal control of the heart: experimental basis and clinical implications. Futura Publishing Company, Armonk, NY, pp 45–64

    Google Scholar 

  36. Takaya M, Terry WJ, Naritoku DK (1996) Vagus nerve stimulation induces a sustained anticonvulsant effect. Epilepsia 37:1111–1116

    Article  CAS  PubMed  Google Scholar 

  37. Terndrup TE, Darnall R, Knuth SL, Bartlett D, Jr (1999) Effects of experimental cortical seizures on respiratory motor nerve activities in piglets. J Appl Physiol; Exerc Physiol 86:2052

    Google Scholar 

  38. Tinuper P, Bisulli F, Cerullo A, Carcangiu R, Marini C, Pierangeli G et al (2001) Ictal bradycardia in partial epileptic seizures: autonomic investigation in three cases and literature review. Brain 124:2361–2371

    Article  CAS  PubMed  Google Scholar 

  39. Uthman BM, Wilder BJ, Penry JK, Dean C, Ramsay RE, Reid SA et al (1993) Treatment of epilepsy by stimulation of the vagus nerve. Neurology 43:1338–1345

    CAS  PubMed  Google Scholar 

  40. Van De Graaff KM (2002) Human anatomy, 6th edn. McGraw-Hill, New York

    Google Scholar 

  41. Woodbury DM, Woodbury JW (1990) Effects of vagal stimulation on experimentally induced seizures in rats. Epilepsia 31(Suppl 2):S7–S19

    Article  PubMed  Google Scholar 

  42. Zabara J (1992) Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia 33:1005–1012

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Danish National Advanced Technology Foundation. The authors have filled a patent application covering the method described.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kristian R. Harreby.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harreby, K.R., Sevcencu, C. & Struijk, J.J. Early seizure detection in rats based on vagus nerve activity. Med Biol Eng Comput 49, 143–151 (2011). https://doi.org/10.1007/s11517-010-0683-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11517-010-0683-1

Keywords