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  • Adaptive deep brain stimulation for Parkinson's disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting

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Adaptive deep brain stimulation for Parkinson's disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting
  1. Simon Little1,
  2. Elina Tripoliti1,
  3. Martijn Beudel2,
  4. Alek Pogosyan3,
  5. Hayriye Cagnan3,
  6. Damian Herz3,
  7. Sven Bestmann1,
  8. Tipu Aziz4,
  9. Binith Cheeran4,
  10. Ludvic Zrinzo1,
  11. Marwan Hariz1,
  12. Jonathan Hyam1,
  13. Patricia Limousin1,
  14. Tom Foltynie1,
  15. Peter Brown3
  1. 1 Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, UK
  2. 2 Department of Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  3. 3 MRC Brain Network Dynamics Unit (BNDU), Department of Pharmacology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  4. 4 Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
  1. Correspondence to Professor Peter Brown, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK; peter.brown{at}ndcn.ox.ac.uk

https://doi.org/10.1136/jnnp-2016-313518

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    Introduction

    Deep brain stimulation (DBS) for Parkinson's disease (PD) is currently limited by costs, partial efficacy and surgical and stimulation-related side effects. This has motivated the development of adaptive DBS (aDBS) whereby stimulation is automatically adjusted according to a neurophysiological biomarker of clinical state, such as β oscillatory activity (12–30 Hz). aDBS has been studied in parkinsonian primates and patients and has been reported to be more energy efficient and effective in alleviating motor symptoms than conventional DBS (cDBS) at matched amplitudes.1 ,2

    However, these studies have not considered whether side effects can also be avoided with clinically effective stimulation. In PD, it is well recognised that a significant proportion of patients develop speech deterioration following DBS of the subthalamic nucleus (STN), which may be reversible.3

    Here we test bilateral stimulation, optimising parameters for aDBS, and evaluate speech intelligibility. We hypothesised that acute aDBS would be more effective and more efficient than cDBS at matched stimulation parameters while causing less speech impairment.

    Methods

    We recruited 10 patients with advanced idiopathic PD following implantation of DBS electrodes into the STN.2 Recordings took place 3–6 days following electrode placement during a temporary period of externalisation. All participants gave informed written consent, and were tested following overnight withdrawal of dopaminergic medication (see online supplementary material). Two patients were excluded due to external stimulator failure leading to no voltage delivery under aDBS and cDBS conditions.

    supplementary data

    [jnnp-2016-313518supp.pdf]

    aDBS stimulation was delivered bilaterally, only when β amplitude exceeded a threshold as previously described.2 aDBS contacts, voltages and trigger thresholds were independently set for the two sides according to motor benefit versus induced paraesthesiae, with the same contacts/voltages used for cDBS.

    Stimulation in each block continued for 15 min prior to evaluation. Participants were assessed …

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    Footnotes

    • Twitter Follow Martijn Beudel at @mbeudel

    • Contributors SL designed the study, collected and analysed the data and wrote the manuscript. ET helped with the design of the study, speech ratings and writing of the manuscript. MB, HC, DH and SB helped with data collection, analysis and review and improvement of the manuscript. AP helped with design of the study and technical aspects of aDBS that facilitated its implementation, guidance and discussion of results, as well as review and improvement of the manuscript. TA provided help with trial facilitation and review and improvement of the manuscript. BC helped with UPDRS-III ratings, analysis and review and improvement of the manuscript. LZ, MH, JH and PL helped with design and ongoing trial facilitation, review and improvement of the manuscript. TF helped with design and ongoing trial facilitation, MDS-UPDRS-III blinded ratings, review and improvement of the manuscript. PB designed the study, collected and analysed the data and wrote the manuscript.

    • Funding This study was funded by clinical research training grants (SL—093929/Z/10/Z and 105804/Z/14/Z) from the Wellcome Trust and supported by the Medical Research Council (MC_UU_12024/1), National Institute for Health Research Oxford Biomedical Research Centre and Rosetrees Trust. The Unit of Functional Neurosurgery is supported by the Parkinson Appeal UK and Monument trust.

    • Competing interests SL has been a participant in a DBS teaching course funded by Medtronic, the manufacturer of the electrodes used in this study. TA has performed consultancy for and received speaking fees from Medtronic. BC has received travel support and unrestricted educational grants for organising CPD events from Medtronic, St Judes and Boston scientific (manufacturers of DBS electrodes), and some of which were used in this study. LZ, MH, TF and PL have received speaking fees and travel support from Medtronic and St Judes, and some of which were used in this study. PB has received fees and non-financial support from Medtronic and personal fees from Boston Scientific, and some of which were used in this study.

    • Ethics approval NRES Committee South Central—Oxford A.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement This study resulted in a small volume of clinical scoring data which we would be happy to share on request by email to the corresponding author.