The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism

  1. Christoph Wiest
  2. Flavie Torrecillos
  3. Alek Pogosyan
  4. Manuel Bange
  5. Muthuraman Muthuraman
  6. Sergiu Groppa
  7. Natasha Hulse
  8. Harutomo Hasegawa
  9. Keyoumars Ashkan
  10. Fahd Baig
  11. Francesca Morgante
  12. Erlick A Pereira
  13. Nicolas Mallet
  14. Peter J Magill
  15. Peter Brown
  16. Andrew Sharott
  17. Huiling Tan  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University Medical Center of the Johannes Gutenberg University Mainz, Germany
  3. King's College London, United Kingdom
  4. St. George's University, United Kingdom
  5. CNRS UMR5293, Université de Bordeaux, France

Abstract

Periodic features of neural time series data, such as local field potentials (LFP), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically-relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal populations. Here, we used a cross-species in vivo electrophysiological approach to test the E/I hypothesis in the context of experimental and idiopathic Parkinsonism. We demonstrate in dopamine-depleted rats that aperiodic exponents and power at 30-100 Hz in subthalamic nucleus (STN) LFPs reflect defined changes in basal ganglia network activity; higher aperiodic exponents tally with lower levels of STN neuron firing and a balance tipped towards inhibition. Using STN-LFPs recorded from awake Parkinson's patients, we show that higher exponents accompany dopaminergic medication and deep brain stimulation (DBS) of STN, consistent with untreated Parkinson's manifesting as reduced inhibition and hyperactivity of STN. These results suggest that the aperiodic exponent of STN-LFPs in Parkinsonism reflects E/I balance, and might be a candidate biomarker for adaptive DBS.

Data availability

The code was uploaded directly to eLife and in addition can be found here https://doi.org/10.5287/bodleian:rJ7jyjX97. The animal data (Mallet et al., 2022) used for this project is available at the Medical Research Council Brain Networks Dynamics Unit (MRC BNDU) Data Sharing Platform at the University of Oxford https://data.mrc.ox.ac.uk/stn-rat and DOI: https://doi.org/10.5287/bodleian:wx6D7oenk. The human data (Wiest et al., 2022) is also available at the MRC BNDU Data Sharing Platform https://data.mrc.ox.ac.uk/stn-lfp-on-off-and-dbs and DOI: https://doi.org/10.5287/bodleian:mzJ7YwXvo.

The following data sets were generated

Article and author information

Author details

  1. Christoph Wiest

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  2. Flavie Torrecillos

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Alek Pogosyan

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Manuel Bange

    Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    Manuel Bange, received grants from the German Research Council (DFG) grant number DFG CRC-TR-128. The author has no other competing interests to declare..
  5. Muthuraman Muthuraman

    Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6158-2663
  6. Sergiu Groppa

    Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    Sergiu Groppa, has received funding from BMBF, UM Mainz, Boehringer Foundation, Precisis, DFG, Abbott, Magventure and Innovationsfond GBA. The author received consulting fees from Abbott and Boston Scientific, and received payment or honoraria for lectures from Abbott, Bial, IPSEN, Abbvie, BVDN, BVDN and UCB. The author has no other competing interests to declare..
  7. Natasha Hulse

    Department of Neurosurgery, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  8. Harutomo Hasegawa

    Department of Neurosurgery, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Keyoumars Ashkan

    Department of Neurosurgery, King's College London, London, United Kingdom
    Competing interests
    Keyoumars Ashkan, received funding from Medtronic and Abbott, and received support for attending meetings and/or travel from Medtronic and Abbott. The author has no other competing interests to declare..
  10. Fahd Baig

    Molecular and Clinical Sciences Institute, St. George's University, London, United Kingdom
    Competing interests
    No competing interests declared.
  11. Francesca Morgante

    Molecular and Clinical Sciences Institute, St. George's University, London, United Kingdom
    Competing interests
    Francesca Morgante, has received research support from NIHR, consulting fees from Boston Scientific and royalties from Springer for the book Disorders of Movement. The author has received speaking honoraria from Abbvie.
  12. Erlick A Pereira

    Molecular and Clinical Sciences Institute, St. George's University, London, United Kingdom
    Competing interests
    Erlick A Pereira, has received grants from Life after Paralysis, and royalties and licenses from Elsevier. The author has received consulting fees from Boston Scientific. The author has no other competing interests to declare..
  13. Nicolas Mallet

    Institut des Maladies Neurodégénératives, CNRS UMR5293, Université de Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
  14. Peter J Magill

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    Peter J Magill, has received funding from the MRC Programme Grant MC_UU_00003/5 and Parkinson's UK (grant G-0806). The author has no other competing interests to declare..
  15. Peter Brown

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    Peter Brown, has been issued the following patents: Fischer P He S Tan H Brown P Patent Application: Treatment of gait impairment using deep brain stimulation 2021. WO/2021/250398; Debarros J Brown P Tan H Denison T Patent Application: Emulation of electrophysiological signals derived by stimulation of a body 2020. WO/2020/165591; Debarros J Brown P Tan H Patent Application: Measurement of electrophysiological signals during stimulation of a target area of a body 2020. WO/2020/070492. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5201-3044
  16. Andrew Sharott

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    Andrew Sharott, has received funding from the MRC Programme Grant MC_UU_00003/6. The author has been issued Patent WO/2020/183152. The author participates on the Grant Advisory Panel for Aligning Science Across Parkinson's (ASAP). The author has no other competing interests to declare..
  17. Huiling Tan

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    For correspondence
    huiling.tan@ndcn.ox.ac.uk
    Competing interests
    Huiling Tan, has received funding from the MRC Programme Grant MC_UU_00003/2, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and Rosetrees Trust. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8038-3029

Funding

Medical Research Council (MC_UU_00003/2)

  • Huiling Tan

Medical Research Council (MC_UU_00003/5)

  • Peter J Magill

Medical Research Council (MC_UU_00003/6)

  • Andrew Sharott

National Institute for Health Research Oxford Biomedical Research Centre

  • Huiling Tan

Rosetrees Trust

  • Huiling Tan

Parkinson's UK (G-0806)

  • Peter J Magill

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nicole C Swann, University of Oregon, United States

Ethics

Animal experimentation: Experiments were performed on adult male Sprague Dawley rats (Charles River), and were conducted in accordance with the Animals (Scientific Procedures) Act, 1986 (UK) and the provisions of the Society for Neuroscience Policies on the Use of Animals in Neuroscience Research. Animal data that was analysed in this paper has been generated under the project licence numbers 30/2131 and 30/2629. All details on the 6-OHDA lesion and electrophysiological recordings were published before (Mallet et al., 2008a).

Human subjects: This protocol was approved by the Health Research Authority UK, the National Research Ethics Service local Research Ethics Committee (IRAS: 46576) and the local ethics committee at the University of Mainz (837.208.17(11042)). Patients were recruited at St. George's University Hospital NHS Foundation Trust, London, King's College Hospital NHS Foundation Trust, London, and the University Medical Center Mainz. Written informed consent, and consent to publish, was obtained before surgery in line with the Declaration of the Principles of Helsinki. We analysed data from 24 patients from these 3 centres.

Version history

  1. Received: August 4, 2022
  2. Preprint posted: August 23, 2022 (view preprint)
  3. Accepted: February 22, 2023
  4. Accepted Manuscript published: February 22, 2023 (version 1)
  5. Version of Record published: March 10, 2023 (version 2)

Copyright

© 2023, Wiest et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Christoph Wiest
  2. Flavie Torrecillos
  3. Alek Pogosyan
  4. Manuel Bange
  5. Muthuraman Muthuraman
  6. Sergiu Groppa
  7. Natasha Hulse
  8. Harutomo Hasegawa
  9. Keyoumars Ashkan
  10. Fahd Baig
  11. Francesca Morgante
  12. Erlick A Pereira
  13. Nicolas Mallet
  14. Peter J Magill
  15. Peter Brown
  16. Andrew Sharott
  17. Huiling Tan
(2023)
The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism
eLife 12:e82467.
https://doi.org/10.7554/eLife.82467

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https://doi.org/10.7554/eLife.82467