title: Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.
abstract: Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment.
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK Medical Research Council Brain Network Dynamics Unit, University of Oxford, UK Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, 12 Queen Square, London, UK.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Oswal
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK University Medical Centre Groningen, Department of Neurology, University of Groningen, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Beudel
authors.affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Ludvic
authors.initials: L
authors.lastname: Zrinzo
authors.affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Marwan
authors.initials: M
authors.lastname: Hariz
authors.affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Foltynie
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, 12 Queen Square, London, UK.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Litvak
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK Medical Research Council Brain Network Dynamics Unit, University of Oxford, UK peter.brown@ndcn.ox.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D046690:Deep Brain Stimulation; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000502:physiology*
keywords: Parkinson’s disease; deep brain stimulation; local field potential; magnetoencephalography; resting state networks