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Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson’s disease patients

View ORCID ProfileAnders Christian Meidahl, Christian K.E. Moll, View ORCID ProfileBernadette van Wijk, Alessandro Gulberti, View ORCID ProfileGerd Tinkhauser, Manfred Westphal, Andreas K. Engel, Wolfgang Hamel, View ORCID ProfilePeter Brown, Andrew Sharott
doi: https://doi.org/10.1101/433334
Anders Christian Meidahl
1MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom
2Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
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Christian K.E. Moll
3Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Bernadette van Wijk
4Integrative Model-based Cognitive Neuroscience Research Unit, Department of Psychology, University of Amsterdam, 1001NK Amsterdam, the Netherlands
5Department of Neurology, Charité-University Medicine, 10117 Berlin, Germany
6Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, London WC1N 3BG, UK
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Alessandro Gulberti
3Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Gerd Tinkhauser
1MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom
2Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
7Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland
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Manfred Westphal
8Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Andreas K. Engel
3Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Wolfgang Hamel
8Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Peter Brown
1MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom
2Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
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Andrew Sharott
1MRC Brain Network Dynamics Unit, University of Oxford, Oxford OX1 3TH, United Kingdom
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Abstract

Both phase-amplitude coupling (PAC) and beta-bursts in the subthalamic nucleus have been significantly linked to symptom severity in Parkinson’s disease (PD) in humans and emerged independently as competing biomarkers for closed-loop deep brain stimulation (DBS). However, the underlying nature of subthalamic PAC is poorly understood and its relationship with transient beta burst-events has not been investigated. To address this, we studied macro- and micro electrode recordings of local field potentials (LFPs) and single unit activity from 15 hemispheres in 10 PD patients undergoing DBS surgery. PAC between beta phase and high frequency oscillation (HFO) amplitude was compared to single unit firing rates, spike triggered averages, power spectral densities and phase-spike locking, and was studied in periods of beta-bursting. We found a significant synchronisation of spiking to HFOs and correlation of mean firing rates with HFO-amplitude when the latter was coupled to beta phase (i.e. in the presence of PAC). In the presence of PAC, single unit power spectra displayed peaks in the beta and HFO frequency range and the HFO frequency was correlated with that in the LFP. Finally, PAC significantly increased with beta burst-duration. Our findings offer new insight in the pathology of Parkinson’s disease by providing evidence that subthalamic PAC reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with beta-burst duration. These findings suggest that beta-bursts capture periods of increased subthalamic input/output synchronisation in the beta frequency range and have important implications for therapeutic closed-loop DBS.

Significance statement Identifying biomarkers for closed-loop deep brain stimulation (DBS) has become an increasingly important issue in Parkinson’s Disease (PD) research. Two such biomarkers, phase–amplitude coupling (PAC) and beta-bursts, recorded from the implanted electrodes in subthalamic nucleus in PD patients, correlate with motor impairment. However, the physiological basis of PAC, and it relationship to beta bursts, is unclear. We provide multiple lines of evidence that PAC in the human STN reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with the duration of beta-bursts. This suggests that beta-bursts capture increased subthalamic input/output synchronisation and provides new insights in PD pathology with direct implications for closed-loop DBS therapy strategies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 03, 2018.
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Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson’s disease patients
Anders Christian Meidahl, Christian K.E. Moll, Bernadette van Wijk, Alessandro Gulberti, Gerd Tinkhauser, Manfred Westphal, Andreas K. Engel, Wolfgang Hamel, Peter Brown, Andrew Sharott
bioRxiv 433334; doi: https://doi.org/10.1101/433334
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Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson’s disease patients
Anders Christian Meidahl, Christian K.E. Moll, Bernadette van Wijk, Alessandro Gulberti, Gerd Tinkhauser, Manfred Westphal, Andreas K. Engel, Wolfgang Hamel, Peter Brown, Andrew Sharott
bioRxiv 433334; doi: https://doi.org/10.1101/433334

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