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Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinson’s disease

Victor M. Saenger, Joshua Kahan, Tom Foltynie, Karl Friston, Tipu Z. Aziz, Alexander L. Green, Tim J. van Hartevelt, Angus B. A. Stevner, Henrique M. Fernandes, Laura Mancini, John Thornton, Tarek Yousry, Patricia Limousin, Ludvic Zrinzo, Marwan Hariz, Morten L. Kringelbach, Gustavo Deco
doi: https://doi.org/10.1101/083162
Victor M. Saenger
1Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, 08018, Spain
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Joshua Kahan
2Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
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Tom Foltynie
2Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
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Karl Friston
3Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
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Tipu Z. Aziz
4Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom.
5Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, United Kingdom.
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Alexander L. Green
4Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom.
5Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, United Kingdom.
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Tim J. van Hartevelt
6Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom.
7Center for Music in the Brain, Aarhus University, Aarhus, 8000 Aarhus C, Denmark.
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Angus B. A. Stevner
6Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom.
7Center for Music in the Brain, Aarhus University, Aarhus, 8000 Aarhus C, Denmark.
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Henrique M. Fernandes
6Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom.
7Center for Music in the Brain, Aarhus University, Aarhus, 8000 Aarhus C, Denmark.
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Laura Mancini
8Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, WC1N 3BG, United Kingdom.
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John Thornton
8Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, WC1N 3BG, United Kingdom.
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Tarek Yousry
8Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, WC1N 3BG, United Kingdom.
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Patricia Limousin
2Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
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Ludvic Zrinzo
2Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
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Marwan Hariz
2Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
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Morten L. Kringelbach
6Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom.
7Center for Music in the Brain, Aarhus University, Aarhus, 8000 Aarhus C, Denmark.
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  • For correspondence: morten.kringelbach@queens.ox.ac.uk
Gustavo Deco
1Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, 08018, Spain
9Instituci Catalana de la Recerca i Estudis Avanats (ICREA), Universitat Pompeu Fabra, Barcelona, 08010, Spain.
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  • For correspondence: morten.kringelbach@queens.ox.ac.uk
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Abstract

Deep brain stimulation (DBS) for Parkinson’s disease is a highly effective treatment in controlling otherwise debilitating symptoms yet the underlying brain mechanisms are currently not well understood. We used whole-brain computational modeling to disclose the effects of DBS ON and OFF during collection of resting state fMRI in ten Parkinson’s Disease patients. Specifically, we explored the local and global impact of DBS in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts the global brain dynamics of patients nearer to that of healthy people by significantly changing the bifurcation parameters in brain regions implicated in Parkinson’s Disease. We also found higher communicability and coherence brain measures during DBS ON compared to DBS OFF. Finally, by modeling stimulation we identified possible novel DBS targets. These results offer important insights into the underlying effects of DBS, which may in time offer a route to more efficacious treatments.

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Posted October 25, 2016.
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Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinson’s disease
Victor M. Saenger, Joshua Kahan, Tom Foltynie, Karl Friston, Tipu Z. Aziz, Alexander L. Green, Tim J. van Hartevelt, Angus B. A. Stevner, Henrique M. Fernandes, Laura Mancini, John Thornton, Tarek Yousry, Patricia Limousin, Ludvic Zrinzo, Marwan Hariz, Morten L. Kringelbach, Gustavo Deco
bioRxiv 083162; doi: https://doi.org/10.1101/083162
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Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinson’s disease
Victor M. Saenger, Joshua Kahan, Tom Foltynie, Karl Friston, Tipu Z. Aziz, Alexander L. Green, Tim J. van Hartevelt, Angus B. A. Stevner, Henrique M. Fernandes, Laura Mancini, John Thornton, Tarek Yousry, Patricia Limousin, Ludvic Zrinzo, Marwan Hariz, Morten L. Kringelbach, Gustavo Deco
bioRxiv 083162; doi: https://doi.org/10.1101/083162

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