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.

  • Review Article
  • Published:

Emerging technologies for improved deep brain stimulation

Nature Biotechnology volume 37, pages 1024–1033 (2019)Cite this article

Subjects

A Publisher Correction to this article was published on 09 September 2019

This article has been updated

Abstract

Deep brain stimulation (DBS) is an effective treatment for common movement disorders and has been used to modulate neural activity through delivery of electrical stimulation to key brain structures. The long-term efficacy of stimulation in treating disorders, such as Parkinson’s disease and essential tremor, has encouraged its application to a wide range of neurological and psychiatric conditions. Nevertheless, adoption of DBS remains limited, even in Parkinson’s disease. Recent failed clinical trials of DBS in major depression, and modest treatment outcomes in dementia and epilepsy, are spurring further development. These improvements focus on interaction with disease circuits through complementary, spatially and temporally specific approaches. Spatial specificity is promoted by the use of segmented electrodes and field steering, and temporal specificity involves the delivery of patterned stimulation, mostly controlled through disease-related feedback. Underpinning these developments are new insights into brain structure–function relationships and aberrant circuit dynamics, including new methods with which to assess and refine the clinical effects of stimulation.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Deep brain stimulation.
Fig. 2: Field steering.
Fig. 3: A comparison of different stimulation strategies.

Similar content being viewed by others

Change history

  • 09 September 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. Obeso, J. A. et al. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N. Engl. J. Med. 345, 956–963 (2001).

    CAS  PubMed  Google Scholar 

  2. Deuschl, G. et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N. Engl. J. Med. 355, 896–908 (2006).

    CAS  PubMed  Google Scholar 

  3. Benabid, A. L., Chabardes, S., Mitrofanis, J. & Pollak, P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. 8, 67–81 (2009).

    PubMed  Google Scholar 

  4. Rodriguez-Oroz, M. C. et al. Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up. Brain 128, 2240–2249 (2005).

    CAS  PubMed  Google Scholar 

  5. Koller, W. C., Lyons, K. E., Wilkinson, S. B., Troster, A. I. & Pahwa, R. Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Mov. Disord. 16, 464–468 (2001).

    CAS  PubMed  Google Scholar 

  6. Benabid, A. L. et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337, 403–406 (1991).

    CAS  PubMed  Google Scholar 

  7. Kupsch, A. et al. Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N. Engl. J. Med. 355, 1978–1990 (2006).

    CAS  PubMed  Google Scholar 

  8. Vidailhet, M. et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N. Engl. J. Med. 352, 459–467 (2005).

    CAS  PubMed  Google Scholar 

  9. Kiss, Z. H. Bilateral pallidal neurostimulation—long-term motor and cognitive effects in primary generalized dystonia. Nat. Clin. Pract. Neurol. 3, 482–483 (2007).

    PubMed  Google Scholar 

  10. Kiss, Z. H. T. et al. The Canadian multicentre study of deep brain stimulation for cervical dystonia. Brain 130, 2879–2886 (2007).

    PubMed  Google Scholar 

  11. Bergman, H., Wichmann, T. & DeLong, M. R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249, 1436–1438 (1990).

    CAS  PubMed  Google Scholar 

  12. Jankovic, J., Cardoso, F., Grossman, R. G. & Hamilton, W. J. Outcome after stereotactic thalamotomy for parkinsonian, essential, and other types of tremor. Neurosurgery 37, 680–686 (1995). discussion 686–687.

    CAS  PubMed  Google Scholar 

  13. Limousin, P. et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N. Engl. J. Med. 339, 1105–1111 (1998).

    CAS  PubMed  Google Scholar 

  14. Volkmann, J. et al. Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson’s disease. Mov. Disord. 24, 1154–1161 (2009).

    PubMed  Google Scholar 

  15. Kestenbaum, M., Ford, B. & Louis, E. D. Estimating the proportion of essential tremor and Parkinson’s disease patients undergoing deep brain stimulation surgery: five-year data from Columbia University Medical Center (2009–2014). Mov. Disord. Clin. Pract. (Hoboken) 2, 384–387 (2015).

    Google Scholar 

  16. Hariz, M. I. Complications of deep brain stimulation surgery. Mov. Disord. 17, S162–S166 (2002). (Suppl. 3).

    PubMed  Google Scholar 

  17. Hariz, M. I. et al. Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency: a case study. Mov. Disord. 15, 136–139 (2000).

    CAS  PubMed  Google Scholar 

  18. Mink, J. W. et al. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov. Disord. 21, 1831–1838 (2006).

    PubMed  Google Scholar 

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

    CAS  Google Scholar 

  20. Benazzouz, A. et al. Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat. Neuroscience 99, 289–295 (2000).

    CAS  PubMed  Google Scholar 

  21. Dostrovsky, J. O. et al. Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J. Neurophysiol. 84, 570–574 (2000).

    CAS  PubMed  Google Scholar 

  22. Welter, M.-L. et al. Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients. Arch. Neurol. 61, 89–96 (2004).

    PubMed  Google Scholar 

  23. Meissner, W. et al. Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations. Brain 128, 2372–2382 (2005).

    PubMed  Google Scholar 

  24. Hashimoto, T., Elder, C. M., Okun, M. S., Patrick, S. K. & Vitek, J. L. Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J. Neurosci. 23, 1916–1923 (2003).

    CAS  PubMed  Google Scholar 

  25. Anderson, M. E., Postupna, N. & Ruffo, M. Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J. Neurophysiol. 89, 1150–1160 (2003).

    PubMed  Google Scholar 

  26. Montgomery, E. B. Jr. Effects of GPi stimulation on human thalamic neuronal activity. Clin. Neurophysiol. 117, 2691–2702 (2006).

    PubMed  Google Scholar 

  27. Vitek, J. L., Zhang, J., Hashimoto, T., Russo, G. S. & Baker, K. B. External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network. Exp. Neurol. 233, 581–586 (2012).

    PubMed  Google Scholar 

  28. Hershey, T. et al. Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology 61, 816–821 (2003).

    CAS  PubMed  Google Scholar 

  29. Perlmutter, J. S. et al. Blood flow responses to deep brain stimulation of thalamus. Neurology 58, 1388–1394 (2002).

    CAS  PubMed  Google Scholar 

  30. Li, S., Arbuthnott, G. W., Jutras, M. J., Goldberg, J. A. & Jaeger, D. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. J. Neurophysiol. 98, 3525–3537 (2007).

    CAS  PubMed  Google Scholar 

  31. Miocinovic, S. et al. Cortical potentials evoked by subthalamic stimulation demonstrate a short latency hyperdirect pathway in humans. J. Neurosci. 38, 9129–9141 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. McIntyre, C. C., Grill, W. M., Sherman, D. L. & Thakor, N. V. Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J. Neurophysiol. 91, 1457–1469 (2004).

    PubMed  Google Scholar 

  33. Xu, W., Russo, G. S., Hashimoto, T., Zhang, J. & Vitek, J. L. Subthalamic nucleus stimulation modulates thalamic neuronal activity. J. Neurosci. 28, 11916–11924 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Johnson, M. D., Vitek, J. L. & McIntyre, C. C. Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey. Exp. Neurol. 219, 359–362 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Rubin, J. E. & Terman, D. High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model. J. Comput. Neurosci. 16, 211–235 (2004).

    PubMed  Google Scholar 

  36. Kühn, A. A. et al. Pathological synchronisation in the subthalamic nucleus of patients with Parkinson’s disease relates to both bradykinesia and rigidity. Exp. Neurol. 215, 380–387 (2009).

    PubMed  Google Scholar 

  37. Schnitzler, A., Münks, C., Butz, M., Timmermann, L. & Gross, J. Synchronized brain network associated with essential tremor as revealed by magnetoencephalography. Mov. Disord. 24, 1629–1635 (2009).

    PubMed  Google Scholar 

  38. Barow, E. et al. Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements. Brain 137, 3012–3024 (2014).

    PubMed  PubMed Central  Google Scholar 

  39. Eusebio, A. et al. Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients. J. Neurol. Neurosurg. Psychiatry jnnp. 2010, 217489 (2010).

    Google Scholar 

  40. Yu, T. et al. High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans. Brain 141, 2631–2643 (2018).

    PubMed  Google Scholar 

  41. Medeiros, D., de, C. & Moraes, M. F. D. Focus on desynchronization rather than excitability: a new strategy for intraencephalic electrical stimulation. Epilepsy Behav. 38, 32–36 (2014).

    Google Scholar 

  42. Stypulkowski, P. H., Stanslaski, S. R., Jensen, R. M., Denison, T. J. & Giftakis, J. E. Brain stimulation for epilepsy—local and remote modulation of network excitability. Brain Stimul. 7, 350–358 (2014).

    PubMed  Google Scholar 

  43. Kim, H. Y. et al. Modification of electrophysiological activity pattern after anterior thalamic deep brain stimulation for intractable epilepsy: report of 3 cases. J. Neurosurg. 126, 2028–2035 (2017).

    PubMed  Google Scholar 

  44. Rappel, P. et al. Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder. Transl. Psychiatry 8, 118 (2018).

    PubMed  PubMed Central  Google Scholar 

  45. Wojtecki, L. et al. Oscillatory coupling of the subthalamic nucleus in obsessive compulsive disorder. Brain 140, e56 (2017).

    PubMed  Google Scholar 

  46. Neumann, W.-J. et al. Pallidal and thalamic neural oscillatory patterns in Tourette syndrome. Ann. Neurol. 84, 505–514 (2018).

    PubMed  Google Scholar 

  47. Servello, D., Porta, M., Sassi, M., Brambilla, A. & Robertson, M. M. Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J. Neurol. Neurosurg. Psychiatry 79, 136–142 (2008).

    CAS  PubMed  Google Scholar 

  48. Kohl, S. et al. Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review. BMC Psychiatry 14, 214 (2014).

    PubMed  PubMed Central  Google Scholar 

  49. Figee, M. et al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat. Neurosci. 16, 386–387 (2013).

    CAS  PubMed  Google Scholar 

  50. Graat, I., Figee, M. & Denys, D. The application of deep brain stimulation in the treatment of psychiatric disorders. Int. Rev. Psychiatry 29, 178–190 (2017).

    PubMed  Google Scholar 

  51. Morishita, T., Fayad, S. M., Higuchi, M. A., Nestor, K. A. & Foote, K. D. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics 11, 475–484 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Riva-Posse, P. et al. A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol. Psychiatry 23, 843–849 (2018).

    CAS  PubMed  Google Scholar 

  53. Dougherty, D. D. et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression. Biol. Psychiatry 78, 240–248 (2015).

    PubMed  Google Scholar 

  54. Lozano, A. M. et al. A phase II study of fornix deep brain stimulation in mild Alzheimer’s disease. J. Alzheimers Dis. 54, 777–787 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sankar, T. et al. Deep brain stimulation influences brain structure in Alzheimer’s disease. Brain Stimul. 8, 645–654 (2015).

    PubMed  Google Scholar 

  56. Holtzheimer, P. E. et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry 4, 839–849 (2017).

    PubMed  Google Scholar 

  57. Rehncrona, S. et al. Long-term efficacy of thalamic deep brain stimulation for tremor: double-blind assessments. Mov. Disord. 18, 163–170 (2003).

    PubMed  Google Scholar 

  58. Goodfellow, M. et al. Estimation of brain network ictogenicity predicts outcome from epilepsy surgery. Sci. Rep. 6, 29215 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Lopes, M. A. et al. An optimal strategy for epilepsy surgery: disruption of the rich-club? PLOS Comput. Biol. 13, e1005637 (2017).

    PubMed  PubMed Central  Google Scholar 

  60. Dayal, V. et al. The effect of short pulse width settings on the therapeutic window in subthalamic nucleus deep brain stimulation for Parkinson’s disease. J. Parkinsons Dis. 8, 273–279 (2018).

    PubMed  Google Scholar 

  61. Choe, C.-U. et al. Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients. Neurology 91, e704–e713 (2018).

    PubMed  Google Scholar 

  62. Bouthour, W. et al. Short pulse width in subthalamic stimulation in Parkinson’s disease: a randomized, double-blind study. Mov. Disord. 33, 169–173 (2018).

    PubMed  Google Scholar 

  63. McIntyre, C. C., Savasta, M., Kerkerian-Le Goff, L. & Vitek, J. L. Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin. Neurophysiol. 115, 1239–1248 (2004).

    PubMed  Google Scholar 

  64. Butson, C. R. & McIntyre, C. C. Role of electrode design on the volume of tissue activated during deep brain stimulation. J. Neural Eng. 3, 1–8 (2006).

    PubMed  Google Scholar 

  65. McIntyre, C. C., Mori, S., Sherman, D. L., Thakor, N. V. & Vitek, J. L. Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus. Clin. Neurophysiol. 115, 589–595 (2004).

    PubMed  Google Scholar 

  66. Butson, C. R. & McIntyre, C. C. Current steering to control the volume of tissue activated during deep brain stimulation. Brain Stimul. 1, 7–15 (2008).

    PubMed  PubMed Central  Google Scholar 

  67. Steigerwald, F., Müller, L., Johannes, S., Matthies, C. & Volkmann, J. Directional deep brain stimulation of the subthalamic nucleus: a pilot study using a novel neurostimulation device. Mov. Disord. 31, 1240–1243 (2016).

    PubMed  PubMed Central  Google Scholar 

  68. Dembek, T. A. et al. Directional DBS increases side-effect thresholds-A prospective, double-blind trial. Mov. Disord. 32, 1380–1388 (2017).

    PubMed  Google Scholar 

  69. Pollo, C. et al. Directional deep brain stimulation: an intraoperative double-blind pilot study. Brain 137, 2015–2026 (2014).

    PubMed  Google Scholar 

  70. Reker, P., Dembek, T. A., Becker, J., Visser-Vandewalle, V. & Timmermann, L. Directional deep brain stimulation: a case of avoiding dysarthria with bipolar directional current steering. Parkinsonism Relat. Disord. 31, 156–158 (2016).

    PubMed  Google Scholar 

  71. Fernández-García, C. et al. Directional local field potential recordings for symptom-specific optimization of deep brain stimulation. Mov. Disord. 32, 626–628 (2017).

    PubMed  Google Scholar 

  72. Tinkhauser, G. et al. Directional local field potentials: a tool to optimize deep brain stimulation. Mov. Disord. 33, 159–164 (2018).

    PubMed  Google Scholar 

  73. Timmermann, L. et al. Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson’s disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study. Lancet Neurol. 14, 693–701 (2015).

    PubMed  Google Scholar 

  74. Connolly, A. T. et al. A novel lead design for modulation and sensing of deep brain structures. IEEE Trans. Biomed. Eng. 63, 148–157 (2016).

    PubMed  Google Scholar 

  75. Sinclair, N. C. et al. Subthalamic nucleus deep brain stimulation evokes resonant neural activity. Ann. Neurol. 83, 1027–1031 (2018).

    PubMed  PubMed Central  Google Scholar 

  76. Butson, C. R., Cooper, S. E., Henderson, J. M. & McIntyre, C. C. Patient-specific analysis of the volume of tissue activated during deep brain stimulation. Neuroimage 34, 661–670 (2007).

    PubMed  Google Scholar 

  77. Frankemolle, A. M. M. et al. Reversing cognitive-motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming. Brain 133, 746–761 (2010).

    PubMed  PubMed Central  Google Scholar 

  78. Horn, A. et al. Connectivity predicts deep brain stimulation outcome in Parkinson disease. Ann. Neurol. 82, 67–78 (2017).

    PubMed  PubMed Central  Google Scholar 

  79. Little, S. et al. Adaptive deep brain stimulation for Parkinson’s disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting. J. Neurol. Neurosurg. Psychiatry 87, 1388–1389 (2016).

    PubMed  PubMed Central  Google Scholar 

  80. Herz, D. M. et al. Mechanisms underlying decision-making as revealed by deep-brain stimulation in patients with Parkinson’s disease. Curr. Biol. 28, 1169–1178.e6 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Voges, B. R. et al. Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients. Epilepsia 56, e99–e103 (2015).

    PubMed  Google Scholar 

  82. Swann, N. C. et al. Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing. J. Neural Eng. 15, 046006 (2018).

    PubMed  PubMed Central  Google Scholar 

  83. Arlotti, M. et al. Eight-hours adaptive deep brain stimulation in patients with Parkinson disease. Neurology 90, e971–e976 (2018).

    PubMed  PubMed Central  Google Scholar 

  84. Almeida, L. et al. Chasing tics in the human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for Tourette syndrome. J. Clin. Neurol. 11, 122–131 (2015).

    PubMed  PubMed Central  Google Scholar 

  85. Molina, R. et al. Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept. J. Neurosurg. 129, 308–314 (2018).

    PubMed  Google Scholar 

  86. Morrell, M. J. et al. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77, 1295–1304 (2011).

    PubMed  Google Scholar 

  87. Rouse, A. G. et al. A chronic generalized bi-directional brain-machine interface. J. Neural Eng. 8, 036018 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Little, S. et al. Adaptive deep brain stimulation in advanced Parkinson disease. Ann. Neurol. 74, 449–457 (2013).

    PubMed  PubMed Central  Google Scholar 

  89. Little, S. et al. Bilateral adaptive deep brain stimulation is effective in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry jnnp-2015-310972 (2015).

  90. Rosa, M. et al. Adaptive deep brain stimulation in a freely moving Parkinsonian patient. Mov. Disord. 30, 1003–1005 (2015).

    PubMed  PubMed Central  Google Scholar 

  91. Cagnan, H. et al. Stimulating at the right time: phase-specific deep brain stimulation. Brain 140, 132–145 (2017).

    PubMed  Google Scholar 

  92. Cagnan, H., Brown, P., Bourget, D. & Denison, T. Inertial-based control system concepts for the treatment of movement disorders. in 2015 Transducers—2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS) 70–73 (IEEE, 2015); https://doi.org/10.1109/TRANSDUCERS.2015.7180863

  93. Kühn, A. A., Kupsch, A., Schneider, G.-H. & Brown, P. Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. Eur. J. Neurosci. 23, 1956–1960 (2006).

    PubMed  Google Scholar 

  94. de Hemptinne, C. et al. Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc. Natl Acad. Sci. USA 110, 4780–4785 (2013).

    PubMed  Google Scholar 

  95. de Hemptinne, C. et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat. Neurosci. 18, 779–786 (2015).

    PubMed  PubMed Central  Google Scholar 

  96. Neumann, W.-J. et al. A localized pallidal physiomarker in cervical dystonia. Ann. Neurol. 82, 912–924 (2017).

    CAS  PubMed  Google Scholar 

  97. Sani, O. G. et al. Mood variations decoded from multi-site intracranial human brain activity. Nat. Biotechnol. 36, 954–961 (2018).

    CAS  PubMed  Google Scholar 

  98. Herron, J. A. et al. Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient. J. Neurosurg. 127, 580–587 (2017).

    PubMed  Google Scholar 

  99. Herron, J. & Chizeck, H.J. Prototype closed-loop deep brain stimulation systems inspired by Norbert Wiener. in 2014 IEEE Conference on Norbert Wiener in the 21st Century (21CW) 1–6 (IEEE, 2014); https://doi.org/10.1109/NORBERT.2014.6893922

  100. Yamamoto, T. et al. On-demand control system for deep brain stimulation for treatment of intention tremor. Neuromodulation 16, 230–235 (2013). discussion 235.

    PubMed  Google Scholar 

  101. Basu, I. et al. Pathological tremor prediction using surface electromyogram and acceleration: potential use in ‘ON-OFF’ demand driven deep brain stimulator design. J. Neural Eng. 10, 036019 (2013).

    PubMed  PubMed Central  Google Scholar 

  102. Graupe, D., Basu, I., Tuninetti, D., Vannemreddy, P. & Slavin, K. V. Adaptively controlling deep brain stimulation in essential tremor patient via surface electromyography. Neurol. Res. 32, 899–904 (2010).

    PubMed  Google Scholar 

  103. Tan, H. et al. Decoding voluntary movements and postural tremor based on thalamic LFPs for closed-loop stimulation for essential tremor. Preprint at bioRxiv https://doi.org/10.1101/436709 (2018).

  104. Tan, H. et al. Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans. Elife 5, e19089 (2016).

    PubMed  PubMed Central  Google Scholar 

  105. Kremen, V. et al. Integrating brain implants with local and distributed computing devices: a next generation epilepsy management system. IEEE J. Transl. Eng. Health Med. 6, 2500112 (2018).

    PubMed  Google Scholar 

  106. Tinkhauser, G. et al. Beta burst coupling across the motor circuit in Parkinson’s disease. Neurobiol. Dis. 117, 217–225 (2018).

    PubMed  PubMed Central  Google Scholar 

  107. Cagnan, H., Duff, E. P. & Brown, P. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson’s disease. Brain 138, 1667–1678 (2015).

    PubMed  PubMed Central  Google Scholar 

  108. Cagnan, H. et al. Temporal evolution of beta bursts in the parkinsonian cortico-basal ganglia network. Preprint at bioRxiv https://doi.org/10.1101/458414 (2018).

  109. Rosin, B. et al. Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron 72, 370–384 (2011).

    CAS  PubMed  Google Scholar 

  110. Tass, P. A. A model of desynchronizing deep brain stimulation with a demand-controlled coordinated reset of neural subpopulations. Biol. Cybern. 89, 81–88 (2003).

    PubMed  Google Scholar 

  111. Tass, P. A. et al. Coordinated reset has sustained aftereffects in Parkinsonian monkeys. Ann. Neurol. 72, 816–820 (2012).

    PubMed  Google Scholar 

  112. Adamchic, I. et al. Coordinated reset neuromodulation for Parkinson’s disease: proof-of-concept study. Mov. Disord. 29, 1679–1684 (2014).

    PubMed  PubMed Central  Google Scholar 

  113. Tass, P. A. Desynchronizing double-pulse phase resetting and application to deep brain stimulation. Biol. Cybern. 85, 343–354 (2001).

    CAS  PubMed  Google Scholar 

  114. Holt, A. B., Wilson, D., Shinn, M., Moehlis, J. & Netoff, T. I. Phasic burst stimulation: a closed-loop approach to tuning deep brain stimulation parameters for Parkinson’s disease. PLOS Comput. Biol. 12, e1005011 (2016).

    PubMed  PubMed Central  Google Scholar 

  115. Wilson, D. & Moehlis, J. Locally optimal extracellular stimulation for chaotic desynchronization of neural populations. J. Comput. Neurosci. 37, 243–257 (2014).

    PubMed  PubMed Central  Google Scholar 

  116. Ghahremani, A. et al. Event-related deep brain stimulation of the subthalamic nucleus affects conflict processing. Ann. Neurol. 84, 515–526 (2018).

    PubMed  PubMed Central  Google Scholar 

  117. Patel, S. R. et al. Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive behavior in human subjects. Elife 7, e36460 (2018).

    PubMed  PubMed Central  Google Scholar 

  118. Fischer, P. et al. Alternating modulation of subthalamic nucleus beta oscillations during stepping. J. Neurosci. 38, 5111–5121 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Sharma, V. D., Sengupta, S., Chitnis, S. & Amara, A. W. Deep brain stimulation and sleep-wake disturbances in Parkinson disease: a review. Front. Neurol. 9, 697 (2018).

    PubMed  PubMed Central  Google Scholar 

  120. Afshar, P. et al. A translational platform for prototyping closed-loop neuromodulation systems. Front. Neural Circuits 6, 117 (2013).

    PubMed  PubMed Central  Google Scholar 

  121. Grossman, N. et al. Noninvasive deep brain stimulation via temporally interfering electric fields. Cell 169, 1029–1041.e16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Brittain, J.-S., Probert-Smith, P., Aziz, T. Z. & Brown, P. Tremor suppression by rhythmic transcranial current stimulation. Curr. Biol. 23, 436–440 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Elias, W. J. et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N. Engl. J. Med. 369, 640–648 (2013).

    CAS  PubMed  Google Scholar 

  124. Lipsman, N. et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 12, 462–468 (2013).

    PubMed  Google Scholar 

  125. Khanna, P. et al. Enabling closed-loop neurostimulation research with downloadable firmware upgrades. in 2015 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1–6 (IEEE, 2015); https://doi.org/10.1109/BioCAS.2015.7348348

  126. US Food and Drug Administration. Cybersecurity. https://www.fda.gov/MedicalDevices/DigitalHealth/ucm373213.htm (accessed 2 October 2018)

  127. Ritter, P. et al. Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study. Eur. Heart J. 36, 2510–2519 (2015).

    PubMed  PubMed Central  Google Scholar 

  128. Oxley, T. J. et al. Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. Nat. Biotechnol. 34, 320–327 (2016).

    CAS  PubMed  Google Scholar 

  129. Wiegert, J. S., Mahn, M., Prigge, M., Printz, Y. & Yizhar, O. Silencing neurons: tools, applications, and experimental constraints. Neuron 95, 504–529 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Dunbar, C. E. et al. Gene therapy comes of age. Science 359, eaan4672 (2018).

    PubMed  Google Scholar 

  131. Williams, J. C. & Denison, T. From optogenetic technologies to neuromodulation therapies. Sci. Transl. Med. 5, 177ps6 (2013).

    PubMed  Google Scholar 

  132. Legon, W., Bansal, P., Tyshynsky, R., Ai, L. & Mueller, J. K. Transcranial focused ultrasound neuromodulation of the human primary motor cortex. Sci. Rep. 8, 10007 (2018).

    PubMed  PubMed Central  Google Scholar 

  133. Legon, W., Ai, L., Bansal, P. & Mueller, J. K. Neuromodulation with single-element transcranial focused ultrasound in human thalamus. Hum. Brain Mapp. 39, 1995–2006 (2018).

    PubMed  Google Scholar 

  134. Ai, L., Bansal, P., Mueller, J. K. & Legon, W. Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study. BMC Neurosci. 19, 56 (2018).

    PubMed  PubMed Central  Google Scholar 

  135. Bertrand, A. et al. Beamforming approaches for untethered, ultrasonic neural dust motes for cortical recording: a simulation study. Conf. Proc. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 2014, 2625–2628 (2014).

    Google Scholar 

  136. Neely, R. M., Piech, D. K., Santacruz, S. R., Maharbiz, M. M. & Carmena, J. M. Recent advances in neural dust: towards a neural interface platform. Curr. Opin. Neurobiol. 50, 64–71 (2018).

    CAS  PubMed  Google Scholar 

  137. Seo, D. et al. Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91, 529–539 (2016).

    CAS  PubMed  Google Scholar 

  138. Jermakowicz, W. J. et al. Laser thermal ablation for mesiotemporal epilepsy: analysis of ablation volumes and trajectories. Epilepsia 58, 801–810 (2017).

    PubMed  PubMed Central  Google Scholar 

  139. McClelland, S. III & Jaboin, J. J. Treatment of the ventral intermediate nucleus for medically refractory tremor: a cost-analysis of stereotactic radiosurgery versus deep brain stimulation. Radiother. Oncol. 125, 136–139 (2017).

    PubMed  Google Scholar 

  140. Harris, M. et al. MRI-guided laser interstitial thermal thalamotomy for medically intractable tremor disorders. Mov. Disord. 34, 124–129 (2019).

    PubMed  Google Scholar 

  141. Hawkes, C. H., Del Tredici, K. & Braak, H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol. Appl. Neurobiol. 33, 599–614 (2007).

    CAS  PubMed  Google Scholar 

  142. Svensson, E. et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann. Neurol. 78, 522–529 (2015).

    PubMed  Google Scholar 

  143. McIntyre, C. C. & Hahn, P. J. Network perspectives on the mechanisms of deep brain stimulation. Neurobiol. Dis. 38, 329–337 (2010).

    PubMed  Google Scholar 

  144. Contarino, M. F. et al. Directional steering: a novel approach to deep brain stimulation. Neurology 83, 1163–1169 (2014).

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  146. Heck, C. N. et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia 55, 432–441 (2014).

    PubMed  PubMed Central  Google Scholar 

  147. Bittar, R. G. et al. Deep brain stimulation for pain relief: a meta-analysis. J. Clin. Neurosci. 12, 515–519 (2005).

    PubMed  Google Scholar 

  148. Schultz, D. M. et al. Sensor-driven position-adaptive spinal cord stimulation for chronic pain. Pain Physician 15, 1–12 (2012).

    PubMed  Google Scholar 

  149. Schade, C. M., Schultz, D. M., Tamayo, N., Iyer, S. & Panken, E. Automatic adaptation of neurostimulation therapy in response to changes in patient position: results of the Posture Responsive Spinal Cord Stimulation (PRS) Research Study. Pain Physician 14, 407–417 (2011).

    PubMed  Google Scholar 

  150. Russo, M. et al. Effective relief of pain and associated symptoms with closed-loop spinal cord stimulation system: preliminary results of the Avalon Study. Neuromodulation 21, 38–47 (2018).

    PubMed  Google Scholar 

  151. Cameron, T. & Alo, K. M. Effects of posture on stimulation parameters in spinal cord stimulation. Neuromodulation 1, 177–183 (1998).

    CAS  PubMed  Google Scholar 

  152. Olin, J. C., Kidd, D. H. & North, R. B. Postural changes in spinal cord stimulation perceptual thresholds. Neuromodulation 1, 171–175 (1998).

    CAS  PubMed  Google Scholar 

  153. Lesser, R. P. et al. Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation. Neurology 53, 2073–2081 (1999).

    CAS  PubMed  Google Scholar 

  154. Sun, F. T. & Morrell, M. J. Closed-loop neurostimulation: the clinical experience. Neurotherapeutics 11, 553–563 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Gotman, J. Automatic recognition of epileptic seizures in the EEG. Electroencephalogr. Clin. Neurophysiol. 54, 530–540 (1982).

    CAS  PubMed  Google Scholar 

  156. Esteller, R., Echauz, J., Tcheng, T., Litt, B. & Pless, B. Line length: an efficient feature for seizure onset detection. in 2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2, 1707–1710 Vol. 2 (IEEE, 2001).

  157. Litt, B. et al. Evolution of accumulated energy predicts seizures in mesial temporal lobe epilepsy. in Proceedings of the First Joint BMES/EMBS Conference. 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Annual Fall Meeting of the Biomedical Engineering Society 1, 440 (1999).

  158. Maling, N., Lempka, S. F., Blumenfeld, Z., Bronte-Stewart, H. & McIntyre, C. C. Biophysical basis of subthalamic local field potentials recorded from deep brain stimulation electrodes. J. Neurophysiol. 120, 1932–1944 (2018).

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Medical Research Council UK (MC_UU_12024/1 1188 to P.B. and MR/R020418/1 to H.C.). T.D. is supported by the Royal Academy of Engineering through a chair in emerging technology. C.M. is supported by NIH R01 NS086100.

Author information

Authors and Affiliations

  1. MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK

    Hayriye Cagnan, Timothy Denison & Peter Brown

  2. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Hayriye Cagnan, Timothy Denison & Peter Brown

  3. Department of Engineering Sciences, University of Oxford, Oxford, UK

    Timothy Denison

  4. School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Cameron McIntyre

Authors
  1. Hayriye Cagnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy Denison
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cameron McIntyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hayriye Cagnan.

Ethics declarations

Competing interests

C.M. is a shareholder in Surgical Information Sciences, Hologram Consultants, Cortics, Autonomic Technologies, Cardionomic and Enspire DBS, as well as a paid consultant to Boston Scientific Neuromodulation. C.M. has intellectual property directly related to the areas we discuss and receives royalties from Neuros Medical, Boston Scientific, Hologram Consultants and Qr8 Health. T.D. is a shareholder in Medtronic, is a consultant for Inspire Medical and Cortec Neurotechnologies, is an advisor for Nia therapeutics, and has intellectual property directly related to the areas we discuss. P.B. has intellectual property directly related to the areas we discuss. H.C. has intellectual property directly related to the areas we discuss.

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

Cagnan, H., Denison, T., McIntyre, C. et al. Emerging technologies for improved deep brain stimulation. Nat Biotechnol 37, 1024–1033 (2019). https://doi.org/10.1038/s41587-019-0244-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41587-019-0244-6

This article is cited by

Search

Advanced 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