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Deep brain stimulation: current challenges and future directions

Abstract

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.

Key points

  • Deep brain stimulation (DBS) is opening new therapeutic possibilities for neurological and psychiatric disorders.

  • DBS is enabling neuroscientists to obtain direct measures of cellular activity and to probe the function of neural circuits.

  • The delivery of DBS at precise locations and the wide range of stimulation parameters available enable unprecedented temporal and spatial control of brain circuits.

  • The mechanisms of action of DBS at the cell, molecular and systems level are poorly understood and much work remains to be done.

  • The ethical issues presented by the application of DBS in new patient populations and for new indications require careful consideration.

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Fig. 1: Deep brain stimulation mechanisms.

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Acknowledgements

This work was supported by a grant from the World Society for Stereotactic and Functional Neurosurgery. It was coordinated together with the Research Committee of the World Society for Stereotactic and Functional Neurosurgery.

Review criteria

With the growing interest in deep brain stimulation (DBS) and its worldwide use, the leadership of the World Society for Stereotactic and Functional Neurosurgery (WSSFN) decided to address the manifold unanswered questions and unmet needs in this rapidly expanding field. To achieve this goal, the WSSFN produced this Review to outline the contemporary discussions, the challenges and the future directions in this area on the basis of a dedicated workshop, which was held 9–11 March 2017. The objective of the workshop was to identify the most pressing current and emerging challenges and unmet needs in the DBS field. Participants from different disciplines were chosen on the basis of their special expertise in neuroscience, neurology, neurosurgery or psychiatry. Specific sections were assigned to two experts, respectively, and the assembled text was then discussed by the whole group during an intensive 2.5-day workshop. Discussion centred around several key topics, including the current clinical status of DBS, the role of preclinical models, emerging science surrounding DBS mechanisms and the role of DBS in motor and non-motor conditions. Additional topics included the ethical challenges surrounding the application of DBS in neurology and psychiatry as well as emerging trends and future directions of the field. The manuscript then underwent several modifications over the next few months until consensus with regard to both relevance and content was reached among the authors.

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All authors researched data for the article, contributed substantially to discussion of content, contributed to writing of the manuscript and undertook review and/or editing of the manuscript before submission. A.M.L., N.L. and J.K.K. provided overall guidance and oversight of the group writing and review process.

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Correspondence to Andres M. Lozano.

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Competing interests

A.M.L. is a consultant to Medtronic, Abbott (formerly St. Jude) and Boston Scientific and is Scientific Director of Functional Neuromodulation. H.B. has received honoraria for speaking from AlphaOmega, Medtronic and Boston Scientific and research support from the Magnet Program of the Israel Ministry of Economics. P.B. has received honoraria for speaking from Medtronic and Boston Scientific. S.C. is a consultant for Boston Scientific and for Medtronic and has received financial support from Medtronic for preclinical research purposes in the field of deep brain stimulation (DBS). K.M. has chaired advisory boards for studies of DBS for obsessive–compulsive disorder sponsored by Medtronic and has received travel and accommodation support to attend meetings from Medtronic and Abbott. C.C.M. is a paid consultant for Boston Scientific Neuromodulation and Kernel as well as a shareholder in the following companies: Surgical Information Sciences, Inc.; Autonomic Technologies, Inc.; Cardionomic, Inc.; Enspire DBS, Inc.; and Neuros Medical, Inc. T.S. has received limited research support for three investigator-initiated studies from Medtronic. M.S. owns stock in General Electric. J.V. receives grants and personal fees from Boston Scientific and is a consultant and paid speaker for Medtronic. J.K.K. is a consultant to Medtronic and Boston Scientific; has received fees for speaking from Abbott; is a past and honorary president of the European Society for Stereotactic and Functional Neurosurgery; and is a past president of the World Society for Stereotactic and Functional Neurosurgery. The other authors have no competing interests.

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Lozano, A.M., Lipsman, N., Bergman, H. et al. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol 15, 148–160 (2019). https://doi.org/10.1038/s41582-018-0128-2

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