Sub-harmonic entrainment of cortical gamma oscillations to deep brain stimulation in Parkinson's disease: Model based predictions and validation in three human subjects

James J. Sermon; Maria Olaru; Juan Ansó; Stephanie Cernera; Simon Little; Maria Shcherbakova; Rafal Bogacz; Philip A. Starr; Timothy Denison; Benoit Duchet

Brain Stimulation (Sep 2023)

Sub-harmonic entrainment of cortical gamma oscillations to deep brain stimulation in Parkinson's disease: Model based predictions and validation in three human subjects

James J. Sermon,
Maria Olaru,
Juan Ansó,
Stephanie Cernera,
Simon Little,
Maria Shcherbakova,
Rafal Bogacz,
Philip A. Starr,
Timothy Denison,
Benoit Duchet

Affiliations

James J. Sermon: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK; MRC Brain Networks Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
Maria Olaru: Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Juan Ansó: Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Stephanie Cernera: Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Simon Little: Department of Neurology, University of California San Francisco, San Francisco, CA, USA
Maria Shcherbakova: Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Rafal Bogacz: MRC Brain Networks Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
Philip A. Starr: Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA
Timothy Denison: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK; MRC Brain Networks Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
Benoit Duchet: MRC Brain Networks Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Corresponding author at: MRC Brain Network Dynamics Unit, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK.

Journal volume & issue: Vol. 16, no. 5
pp. 1412 – 1424

Abstract

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Objectives: The exact mechanisms of deep brain stimulation (DBS) are still an active area of investigation, in spite of its clinical successes. This is due in part to the lack of understanding of the effects of stimulation on neuronal rhythms. Entrainment of brain oscillations has been hypothesised as a potential mechanism of neuromodulation. A better understanding of entrainment might further inform existing methods of continuous DBS, and help refine algorithms for adaptive methods. The purpose of this study is to develop and test a theoretical framework to predict entrainment of cortical rhythms to DBS across a wide range of stimulation parameters. Materials and Methods: We fit a model of interacting neural populations to selected features characterising PD patients' off-stimulation finely-tuned gamma rhythm recorded through electrocorticography. Using the fitted models, we predict basal ganglia DBS parameters that would result in 1:2 entrainment, a special case of sub-harmonic entrainment observed in patients and predicted by theory. Results: We show that the neural circuit models fitted to patient data exhibit 1:2 entrainment when stimulation is provided across a range of stimulation parameters. Furthermore, we verify key features of the region of 1:2 entrainment in the stimulation frequency/amplitude space with follow-up recordings from the same patients, such as the loss of 1:2 entrainment above certain stimulation amplitudes. Conclusion: Our results reveal that continuous, constant frequency DBS in patients may lead to nonlinear patterns of neuronal entrainment across stimulation parameters, and that these responses can be predicted by modelling. Should entrainment prove to be an important mechanism of therapeutic stimulation, our modelling framework may reduce the parameter space that clinicians must consider when programming devices for optimal benefit.

Published in Brain Stimulation

ISSN: 1935-861X (Print); 1876-4754 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-stimulation

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