Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Electrical brain stimulation for epilepsy

Key Points

  • Electrical brain stimulation is an increasingly utilized therapy for medication-resistant seizures

  • Randomized controlled trials have demonstrated the efficacy and safety of intermittent (on a clock cycle) thalamic deep brain stimulation, and responsive neurostimulation at the site(s) of seizure origin

  • Stimulation to control seizures has been investigated in brain regions including the cerebellum, centromedian thalamus, hippocampus, anterior nucleus of the thalamus, motor cortex, caudate, subthalamic nucleus, and other seizure foci

  • Despite several laboratory studies, the mechanisms by which electrical brain stimulation ameliorates epilepsy remain poorly understood

  • Additional experience will be needed to individualize neurostimulation therapy for patients with drug-resistant seizures, determine which type of neurostimulation to first employ, and decide when to intervene

Abstract

Neurostimulation enables adjustable and reversible modulation of disease symptoms, including those of epilepsy. Two types of brain neuromodulation, comprising anterior thalamic deep brain stimulation and responsive neurostimulation at seizure foci, are supported by Class I evidence of effectiveness, and many other sites in the brain have been targeted in small trials of neurostimulation therapy for seizures. Animal studies have mainly assisted in the identification of potential neurostimulation sites and parameters, but much of the clinical work is only loosely based on fundamental principles derived from the laboratory, and the mechanisms by which brain neurostimulation reduces seizures remain poorly understood. The benefits of stimulation tend to increase over time, with maximal effect seen typically 1–2 years after implantation. Typical reductions of seizure frequency are approximately 40% acutely, and 50–69% after several years. Seizure intensity might also be reduced. Complications from brain neurostimulation are mainly associated with the implantation procedure and hardware, including stimulation-related paraesthesias, stimulation-site infections, electrode mistargeting and, in some patients, triggered seizures or even status epilepticus. Further preclinical and clinical experience with brain stimulation surgery should lead to improved outcomes by increasing our understanding of the optimal surgical candidates, sites and parameters.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sites in the human nervous system where stimulation has been attempted as a method of controlling seizures.
Figure 2: Seizure frequency in active-treatment and control groups of patients undergoing bilateral stimulation of the anterior nucleus of the thalamus.
Figure 3: Four stages of neurostimulation planning in one patient.

References

  1. Heath, R. G. Electrical self-stimulation of the brain in man. Am. J. Psychiatry 120, 571–577 (1963).

    Article  CAS  PubMed  Google Scholar 

  2. Delgado, J. M., Hamlin, H. & Chapman, W. P. Technique of intracranial electrode implacement for recording and stimulation and its possible therapeutic value in psychotic patients. Confin. Neurol. 12, 315–319 (1952).

    Article  CAS  PubMed  Google Scholar 

  3. Cooper, I. S., Amin, I. & Gilman, S. The effect of chronic cerebellar stimulation upon epilepsy in man. Trans. Am. Neurol. Assoc. 98, 192–196 (1973).

    CAS  PubMed  Google Scholar 

  4. Cooper, I. S. & Upton, A. R. Therapeutic implications of modulation of metabolism and functional activity of cerebral cortex by chronic stimulation of cerebellum and thalamus. Biol. Psychiatry 20, 811–813 (1985).

    Article  CAS  PubMed  Google Scholar 

  5. Cooper, I. S., Upton, A. R. & Amin, I. Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man. Appl. Neurophysiol. 43, 244–258 (1980).

    CAS  PubMed  Google Scholar 

  6. Upton, A. R., Cooper, I. S., Springman, M. & Amin, I. Suppression of seizures and psychosis of limbic system origin by chronic stimulation of anterior nucleus of the thalamus. Int. J. Neurol. 19–20, 223–230 (1985–1986).

    PubMed  Google Scholar 

  7. Wright, G. D., McLellan, D. L. & Brice, J. G. A double-blind trial of chronic cerebellar stimulation in twelve patients with severe epilepsy. J. Neurol. Neurosurg. Psychiatry 47, 769–774 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Van Buren, J. M., Wood, J. H., Oakley, J. & Hambrecht, F. Preliminary evaluation of cerebellar stimulation by double-blind stimulation and biological criteria in the treatment of epilepsy. J. Neurosurg. 48, 407–416 (1978).

    Article  CAS  PubMed  Google Scholar 

  9. Limousin, P. et al. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345, 91–95 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Morris, G. L. 3rd & Mueller, W. M. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01–E05. Neurology 53, 1731–1735 (1999).

    Article  PubMed  Google Scholar 

  11. Durand, D. M. Control of seizure activity by electrical stimulation: effect of frequency. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 2375 (2009).

    Google Scholar 

  12. Oakley, J. C. & Ojemann, G. A. Effects of chronic stimulation of the caudate nucleus on a preexisting alumina seizure focus. Exp. Neurol. 75, 360–367 (1982).

    Article  CAS  PubMed  Google Scholar 

  13. Morris, G. L. 3rd et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 81, 1453–1459 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  14. DeGiorgio, C. M. et al. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology 80, 786–791 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rossi, S., Hallett, M., Rossini, P. M. & Pascual-Leone, A. & Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin. Neurophysiol. 120, 2008–2039 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lesser, R. P., Crone, N. E. & Webber, W. R. Using subdural electrodes to assess the safety of resections. Epilepsy Behav. 20, 223–229 (2011).

    Article  PubMed  Google Scholar 

  17. Graber, K. & Fisher, R. in Jasper's Basic Mechanisms Of The Epilepsies 4th edn (eds Noebels, J. L. et al.) (Oxford University Press, 2012).

    Google Scholar 

  18. Wyckhuys, T. et al. Deep brain stimulation for epilepsy: knowledge gained from experimental animal models. Acta Neurol. Belg. 109, 63–80 (2009).

    CAS  PubMed  Google Scholar 

  19. Fisher, R. S. Deep brain stimulation for epilepsy. Handb. Clin. Neurol. 116, 217–234 (2013).

    Article  PubMed  Google Scholar 

  20. Cooke, P. M. & Snider, R. S. Some cerebellar influences on electrically-induced cerebral seizures. Epilepsia 4, 19–28 (1955).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Babb, T. L., Mitchell, A. G. Jr & Crandall, P. H. Fastigiobulbar and dentatothalamic influences on hippocampal cobalt epilepsy in the cat. Electroencephalogr. Clin. Neurophysiol. 36, 141–154 (1974).

    Article  CAS  PubMed  Google Scholar 

  23. Lockard, J. S., Ojemann, G. A., Congdon, W. C. & DuCharme, L. L. Cerebellar stimulation in alumina-gel monkey model: inverse relationship between clinical seizures and EEG interictal bursts. Epilepsia 20, 223–234 (1979).

    Article  CAS  PubMed  Google Scholar 

  24. Laxer, K. D., Robertson, L. T., Julien, R. M. & Dow, R. S. Phenytoin: relationship between cerebellar function and epileptic discharges. Adv. Neurol. 27, 415–427 (1980).

    CAS  PubMed  Google Scholar 

  25. Rosenow, J., Das, K., Rovit, R. L. & Couldwell, W. T. Irving S. Cooper and his role in intracranial stimulation for movement disorders and epilepsy. Stereotact. Funct. Neurosurg. 78, 95–112 (2002).

    Article  PubMed  Google Scholar 

  26. Cooper, I. S. et al. Safety and efficacy of chronic cerebellar stimulation. Appl. Neurophysiol. 40, 124–134 (1977).

    PubMed  Google Scholar 

  27. Cooper, I. S. & Upton, A. R. Effects of cerebellar stimulation on epilepsy, the EEG and cerebral palsy in man. Electroencephalogr. Clin. Neurophysiol. Suppl. 34, 349–354 (1978).

    Google Scholar 

  28. Krauss, G. L. & Fisher, R. S. Cerebellar and thalamic stimulation for epilepsy. Adv. Neurol. 63, 231–245 (1993).

    CAS  PubMed  Google Scholar 

  29. Velasco, F. et al. Double-blind, randomized controlled pilot study of bilateral cerebellar stimulation for treatment of intractable motor seizures. Epilepsia 46, 1071–1081 (2005).

    Article  PubMed  Google Scholar 

  30. Fountas, K. N., Kapsalaki, E. & Hadjigeorgiou, G. Cerebellar stimulation in the management of medically intractable epilepsy: a systematic and critical review. Neurosurg. Focus 29, E8 (2010).

    Article  PubMed  Google Scholar 

  31. Starzl, T., Taylor, C. & Magoun, H. Ascending conduction in reticular activating system, with special reference to the diencephalon. J. Neurophysiol. 14, 479–496 (1951).

    Article  CAS  PubMed  Google Scholar 

  32. Eckert, U. et al. Preferential networks of the mediodorsal nucleus and centromedian-parafascicular complex of the thalamus—a DTI tractography study. Hum. Brain Mapp. 33, 2627–2637 (2012).

    Article  PubMed  Google Scholar 

  33. Velasco, F., Velasco, M., Ogarrio, C. & Fanghanel, G. Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia 28, 421–430 (1987).

    Article  CAS  PubMed  Google Scholar 

  34. Fisher, R. S. et al. Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. Epilepsia 33, 841–851 (1992).

    Article  CAS  PubMed  Google Scholar 

  35. Velasco, F. et al. Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies. Epilepsia 36, 63–71 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Valentin, A. et al. Centromedian thalamic nuclei deep brain stimulation in refractory status epilepticus. Brain Stimul. 5, 594–598 (2012).

    Article  PubMed  Google Scholar 

  37. Pasnicu, A., Denoyer, Y., Haegelen, C., Pasqualini, E. & Biraben, A. Modulation of paroxysmal activity in focal cortical dysplasia by centromedian thalamic nucleus stimulation. Epilepsy Res. 104, 264–268 (2013).

    Article  PubMed  Google Scholar 

  38. Valentin, A. et al. Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies. Epilepsia 54, 1823–1833 (2013).

    Article  PubMed  Google Scholar 

  39. Albensi, B. C., Ata, G., Schmidt, E., Waterman, J. D. & Janigro, D. Activation of long-term synaptic plasticity causes suppression of epileptiform activity in rat hippocampal slices. Brain Res. 998, 56–64 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Akman, T. et al. Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin-induced epilepsy model in rats. Turk. Neurosurg. 21, 1–5 (2011).

    PubMed  Google Scholar 

  41. Bragin, A., Wilson, C. L. & Engel, J. Jr. Increased afterdischarge threshold during kindling in epileptic rats. Exp. Brain Res. 144, 30–37 (2002).

    Article  PubMed  Google Scholar 

  42. Bragin, A., Wilson, C. L. & Engel, J. Jr. Rate of interictal events and spontaneous seizures in epileptic rats after electrical stimulation of hippocampus and its afferents. Epilepsia 43 (Suppl. 5), 81–85 (2002).

    Article  PubMed  Google Scholar 

  43. Sramka, M., Fritz, G., Galanda, M. & Nadvornik, P. Some observations in treatment stimulation of epilepsy. Acta Neurochir. (Wien) 23, 257–262 (1976).

    Google Scholar 

  44. Velasco, M. et al. Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities. Epilepsia 41, 158–169 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Velasco, A. L. et al. Electrical stimulation of the hippocampal epileptic foci for seizure control: a double-blind, long-term follow-up study. Epilepsia 48, 1895–1903 (2007).

    Article  PubMed  Google Scholar 

  46. Boex, C. et al. Chronic deep brain stimulation in mesial temporal lobe epilepsy. Seizure 20, 485–490 (2011).

    Article  PubMed  Google Scholar 

  47. Cukiert, A., Cukiert, C. M., Burattini, J. A. & Lima, A. M. Seizure outcome after hippocampal deep brain stimulation in a prospective cohort of patients with refractory temporal lobe epilepsy. Seizure 23, 6–9 (2014).

    Article  PubMed  Google Scholar 

  48. Vonck, K. et al. A decade of experience with deep brain stimulation for patients with refractory medial temporal lobe epilepsy. Int. J. Neural Syst. 23, 1250034 (2013).

    Article  PubMed  Google Scholar 

  49. Koubeissi, M. Z., Kahriman, E., Syed, T. U., Miller, J. & Durand, D. M. Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy. Ann. Neurol. 74, 223–231 (2013).

    PubMed  Google Scholar 

  50. MacLean, P. D. Psychosomatic disease and the visceral brain; recent developments bearing on the Papez theory of emotion. Psychosom. Med. 11, 338–353 (1949).

    Article  CAS  PubMed  Google Scholar 

  51. Mirski, M. A. & Ferrendelli, J. A. Selective metabolic activation of the mammillary bodies and their connections during ethosuximide-induced suppression of pentylenetetrazol seizures. Epilepsia 27, 194–203 (1986).

    Article  CAS  PubMed  Google Scholar 

  52. Mirski, M. A. & Ferrendelli, J. A. Interruption of the mammillothalamic tract prevents seizures in guinea pigs. Science 226, 72–74 (1984).

    Article  CAS  PubMed  Google Scholar 

  53. Mirski, M. A. & Fisher, R. S. Electrical stimulation of the mammillary nuclei increases seizure threshold to pentylenetetrazol in rats. Epilepsia 35, 1309–1316 (1994).

    Article  CAS  PubMed  Google Scholar 

  54. Khan, S. et al. High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma. Epilepsia 50, 1608–1611 (2009).

    Article  PubMed  Google Scholar 

  55. van Rijckevorsel, K., Abu Serieh, B., de Tourtchaninoff, M. & Raftopoulos, C. Deep EEG recordings of the mammillary body in epilepsy patients. Epilepsia 46, 781–785 (2005).

    Article  PubMed  Google Scholar 

  56. Mirski, M. A., Rossell, L. A., Terry, J. B. & Fisher, R. S. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res. 28, 89–100 (1997).

    Article  CAS  PubMed  Google Scholar 

  57. Bittencourt, S. et al. Microinjection of GABAergic agents into the anterior nucleus of the thalamus modulates pilocarpine-induced seizures and status epilepticus. Seizure 19, 242–246 (2010).

    Article  PubMed  Google Scholar 

  58. Zhong, X. L. et al. Low-frequency stimulation of bilateral anterior nucleus of thalamus inhibits amygdale-kindled seizures in rats. Brain Res. Bull. 86, 422–427 (2011).

    Article  PubMed  Google Scholar 

  59. Jou, S. B., Kao, I. F., Yi, P. L. & Chang, F. C. Electrical stimulation of left anterior thalamic nucleus with high-frequency and low-intensity currents reduces the rate of pilocarpine-induced epilepsy in rats. Seizure 22, 221–229 (2013).

    Article  PubMed  Google Scholar 

  60. Lado, F. A. Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats increases seizure frequency. Epilepsia 47, 27–32 (2006).

    Article  PubMed  Google Scholar 

  61. Cooper, I. S. et al. Evoked metabolic responses in the limbic-striate system produced by stimulation of anterior thalamic nucleus in man. Int. J. Neurol. 18, 179–187 (1984).

    CAS  PubMed  Google Scholar 

  62. Upton, A. R. et al. Evoked metabolic responses in the limbic-striate system produced by stimulation of anterior thalamic nucleus in man. Pacing Clin. Electrophysiol. 10, 217–225 (1987).

    Article  CAS  PubMed  Google Scholar 

  63. Sussman, N. et al. Anterior thalamic stimulation in medically intractable epilepsy. Part II. preliminary clinical results. Epilepsia 29, 677 (1988).

    Google Scholar 

  64. Hodaie, M., Wennberg, R. A., Dostrovsky, J. O. & Lozano, A. M. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia 43, 603–608 (2002).

    Article  PubMed  Google Scholar 

  65. Osorio, I., Overman, J., Giftakis, J. & Wilkinson, S. B. High frequency thalamic stimulation for inoperable mesial temporal epilepsy. Epilepsia 48, 1561–1571 (2007).

    Article  PubMed  Google Scholar 

  66. Graves, N. M. & Fisher, R. S. Neurostimulation for epilepsy, including a pilot study of anterior nucleus stimulation. Clin. Neurosurg. 52, 127–134 (2005).

    PubMed  Google Scholar 

  67. Lee, K. J., Shon, Y. M. & Cho, C. B. Long-term outcome of anterior thalamic nucleus stimulation for intractable epilepsy. Stereotact. Funct. Neurosurg. 90, 379–385 (2012).

    Article  PubMed  Google Scholar 

  68. Fisher, R. et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 51, 899–908 (2010).

    Article  PubMed  Google Scholar 

  69. Salanova, V. et al. Long term efficacy of the SANTE trial (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy). Epilepsy Curr. 13 (Suppl. 1), 123 (2012).

    Google Scholar 

  70. Stypulkowski, P. H., Giftakis, J. E. & Billstrom, T. M. Development of a large animal model for investigation of deep brain stimulation for epilepsy. Stereotact. Funct. Neurosurg. 89, 111–122 (2011).

    Article  PubMed  Google Scholar 

  71. Elisevich, K., Jenrow, K., Schuh, L. & Smith, B. Long-term electrical stimulation-induced inhibition of partial epilepsy. Case report. J. Neurosurg. 105, 894–897 (2006).

    Article  PubMed  Google Scholar 

  72. Velasco, A. L. et al. Neuromodulation of epileptic foci in patients with non-lesional refractory motor epilepsy. Int. J. Neural Syst. 19, 139–147 (2009).

    Article  PubMed  Google Scholar 

  73. Velasco, A., Vazquez, D. & Velasco, F. Open-loop chronic electrical stimulation (CHES) of epileptic foci localized in primary and supplementary motor cortices with nonlesional MRI. Epilepsia 54 (Suppl. 6), 112 (2013).

    Google Scholar 

  74. Sun, F. T., Morrell, M. J. & Wharen, R. E. Jr. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics 5, 68–74 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kossoff, E. H. et al. Effect of an external responsive neurostimulator on seizures and electrographic discharges during subdural electrode monitoring. Epilepsia 45, 1560–1567 (2004).

    Article  PubMed  Google Scholar 

  76. Fountas, K. N. et al. Implantation of a closed-loop stimulation in the management of medically refractory focal epilepsy: a technical note. Stereotact. Funct. Neurosurg. 83, 153–158 (2005).

    Article  PubMed  Google Scholar 

  77. Fountas, K. N. & Smith, J. R. A novel closed-loop stimulation system in the control of focal, medically refractory epilepsy. Acta Neurochir. Suppl. 97, 357–362 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Osorio, I. et al. Automated seizure abatement in humans using electrical stimulation. Ann. Neurol. 57, 258–268 (2005).

    Article  PubMed  Google Scholar 

  79. Morrell, M. J. & RNS System Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77, 1295–1304 (2011).

    Article  PubMed  Google Scholar 

  80. Morrell, M. et al. Long-term safety and efficacy of responsive brain stimulation in adults with medically intractable partial onset seizures. Epilepsy Curr. 14 (Suppl. 1), 467–468 (2013).

    Google Scholar 

  81. Rektor, I., Kuba, R., Brazdil, M. & Chrastina, J. Do the basal ganglia inhibit seizure activity in temporal lobe epilepsy? Epilepsy Behav. 25, 56–59 (2012).

    Article  PubMed  Google Scholar 

  82. La Grutta, V. et al. A study of caudate inhibition on an epileptic focus in the cat hippocampus. Arch. Int. Physiol. Biochim. 96, 113–120 (1988).

    CAS  PubMed  Google Scholar 

  83. Psatta, D. M. Control of chronic experimental focal epilepsy by feedback caudatum stimulations. Epilepsia 24, 444–454 (1983).

    Article  CAS  PubMed  Google Scholar 

  84. Rakic, L., Buchwald, N. A. & Wyers, E. J. Effects of chronic stimulation of the caudate nucleus on a preexisting alumina seizure focus. Electroencephalogr. Clin. Neurophysiol. 14, 809–823 (1962).

    Article  CAS  PubMed  Google Scholar 

  85. Sramka, M. & Chkhenkeli, S. A. Clinical experience in intraoperational determination of brain inhibitory structures and application of implanted neurostimulators in epilepsy. Stereotact. Funct. Neurosurg. 54–55, 56–59 (1990).

    Article  PubMed  Google Scholar 

  86. Gabasvili, V., Chkhenkeli, S. & Sramka, M. The treatment of status epilepticus by electrostimulation of deep brain structures. Presented at the 1st European Congress of Neurology (1988).

  87. Chkhenkeli, S. A. et al. Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy. Clin. Neurol. Neurosurg. 106, 318–329 (2004).

    Article  PubMed  Google Scholar 

  88. Vercueil, L. et al. High-frequency stimulation of the subthalamic nucleus suppresses absence seizures in the rat: comparison with neurotoxic lesions. Epilepsy Res. 31, 39–46 (1998).

    Article  CAS  PubMed  Google Scholar 

  89. Dybdal, D. & Gale, K. Postural and anticonvulsant effects of inhibition of the rat subthalamic nucleus. J. Neurosci. 20, 6728–6733 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Veliskova, J., Velísek, L. & Moshé, S. L. Subthalamic nucleus: a new anticonvulsant site in the brain. Neuroreport 7, 1786–1788 (1996).

    Article  CAS  PubMed  Google Scholar 

  91. Lado, F. A., Velísek, L. & Moshé, S. The effect of electrical stimulation of the subthalamic nucleus on seizures is frequency dependent. Epilepsia 47, 27–32 (2003).

    Article  Google Scholar 

  92. Chabardes, S. et al. Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus. Epileptic Disord. 4 (Suppl. 3), S83–S93 (2002).

    PubMed  Google Scholar 

  93. Capecci, M. et al. Chronic bilateral subthalamic stimulation after anterior callosotomy in drug-resistant epilepsy: long-term clinical and functional outcome of two cases. Epilepsy Res. 98, 135–139 (2012).

    Article  PubMed  Google Scholar 

  94. Handforth, A., DeSalles, A. A. & Krahl, S. E. Deep brain stimulation of the subthalamic nucleus as adjunct treatment for refractory epilepsy. Epilepsia 47, 1239–1241 (2006).

    Article  PubMed  Google Scholar 

  95. Faber, J. & Vladyka, V. Antiepileptic effect of electric stimulation of the locus coeruleus in man. Act. Nerv. Super. (Praha) 25, 304–308 (1983).

    CAS  Google Scholar 

  96. Feinstein, B., Gleason, C. A. & Libet, B. Stimulation of locus coeruleus in man. Preliminary trials for spasticity and epilepsy. Stereotact. Funct. Neurosurg. 52, 26–41 (1989).

    Article  CAS  PubMed  Google Scholar 

  97. Wille, C. et al. Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood—report of five cases. Epilepsia 52, 489–496 (2011).

    Article  PubMed  Google Scholar 

  98. Marino Júnior, R. & Gronich, G. Corpus callosum stimulation and stereotactic callosotomy in the management of refractory generalized epilepsy. Preliminary communication. Arq. Neuropsiquiatr. 47, 320–325 (1989).

    Article  PubMed  Google Scholar 

  99. Franzini, A. et al. Deep brain stimulation of two unconventional targets in refractory non-resectable epilepsy. Stereotact. Funct. Neurosurg. 86, 373–381 (2008).

    Article  PubMed  Google Scholar 

  100. Cif, L. et al. Deep brain stimulation in myoclonus-dystonia syndrome. Mov. Disord. 19, 724–727 (2004).

    Article  PubMed  Google Scholar 

  101. McGovern, R. A. et al. Unchanged safety outcomes in deep brain stimulation surgery for Parkinson disease despite a decentralization of care. J. Neurosurg. 119, 1546–1555 (2013).

    Article  PubMed  Google Scholar 

  102. Blomstedt, P. & Hariz, M. I. Hardware-related complications of deep brain stimulation: a ten year experience. Acta Neurochir. (Wien) 147, 1061–1064 (2005).

    Article  CAS  Google Scholar 

  103. Oh, M. Y., Abosch, A., Kim, S. H., Lang, A. E. & Lozano, A. M. Long-term hardware-related complications of deep brain stimulation. Neurosurgery 50, 1268–1276 (2002).

    PubMed  Google Scholar 

  104. Boviatsis, E. J., Stavrinou, L. C., Themistocleous, M., Kouyialis, A. T. & Sakas, D. E. Surgical and hardware complications of deep brain stimulation. A seven-year experience and review of the literature. Acta Neurochir. (Wien) 152, 2053–2062 (2010).

    Article  Google Scholar 

  105. Sharma, A., Szeto, K. & Desilets, A. R. Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. Ann. Pharmacother. 46, 248–254 (2012).

    Article  PubMed  Google Scholar 

  106. Sansur, C. A. et al. Incidence of symptomatic hemorrhage after stereotactic electrode placement. J. Neurosurg. 107, 998–1003 (2007).

    Article  PubMed  Google Scholar 

  107. Bhatia, S., Zhang, K., Oh, M., Angle, C. & Whiting, D. Infections and hardware salvage after deep brain stimulation surgery: a single-center study and review of the literature. Stereotact. Funct. Neurosurg. 88, 147–155 (2010).

    Article  PubMed  Google Scholar 

  108. Kulisevsky, J. et al. Mania following deep brain stimulation for Parkinson's disease. Neurology 59, 1421–1424 (2002).

    Article  CAS  PubMed  Google Scholar 

  109. Nazzaro, J. M., Lyons, K. E., Wetzel, L. H. & Pahwa, R. Use of brain MRI after deep brain stimulation hardware implantation. Int. J. Neurosci. 120, 176–183 (2010).

    Article  PubMed  Google Scholar 

  110. Gupte, A. A., Shrivastava, D., Spaniol, M. A. & Abosch, A. MRI-related heating near deep brain stimulation electrodes: more data are needed. Stereotact. Funct. Neurosurg. 89, 131–140 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ullman, M. et al. A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). Neuroimage 54 (Suppl. 1), S233–S237 (2011).

    Article  PubMed  Google Scholar 

  112. Rolston, J. D., Englot, D. J., Wang, D. D., Shih, T. & Chang, E. F. Comparison of seizure control outcomes and the safety of vagus nerve, thalamic deep brain, and responsive neurostimulation: evidence from randomized controlled trials. Neurosurg. Focus 32, E14 (2012).

    Article  PubMed  Google Scholar 

  113. Oh, Y. S. et al. Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients. Seizure 21, 183–187 (2012).

    Article  PubMed  Google Scholar 

  114. Miatton, M. et al. The cognitive effects of amygdalohippocampal deep brain stimulation in patients with temporal lobe epilepsy. Epilepsy Behav. 22, 759–764 (2011).

    Article  PubMed  Google Scholar 

  115. Coley, E., Farhadi, R., Lewis, S. & Whittle, I. R. The incidence of seizures following deep brain stimulating electrode implantation for movement disorders, pain and psychiatric conditions. Br. J. Neurosurg. 23, 179–183 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. McIntyre, D. C. & Gilby, K. L. Kindling as a model of human epilepsy. Can. J. Neurol Sci. 36, S33–S35 (2009).

    PubMed  Google Scholar 

  117. Šramka, M., Sedlák, P. & Nádvorník, P. in Neurosurgical Treatment in Psychiatry, Pain and Epilepsy (eds Sweet, W. H. et al.) 651–654 (University Park Press, 1977).

    Google Scholar 

  118. Handforth, A. et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51, 48–55 (1998).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

R.S.F.'s research work is supported by the James and Carrie Anderson fund for epilepsy research, the Susan Horngren Fund, and grant NINCDS NS44601-01.

Author information

Authors and Affiliations

Authors

Contributions

R.S.F. researched the data for the article. Both authors contributed substantially to discussion of content, writing the article, and review or editing of the manuscript before submission.

Corresponding author

Correspondence to Robert S. Fisher.

Ethics declarations

Competing interests

Stanford University received research funding from Medtronic to participate in the multicentre trial, but R.S.F. receives no personal support from either Medtronic or NeuroPace. R.S.F. has acted as a consultant for, or holds stock options in, ICVRx (cerebrospinal fluid perfusion of drugs), Cyberonics (vagus nerve stimulation), and Intelli-vision (seizure alert). A.L.V. declares no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fisher, R., Velasco, A. Electrical brain stimulation for epilepsy. Nat Rev Neurol 10, 261–270 (2014). https://doi.org/10.1038/nrneurol.2014.59

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2014.59

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing