title: Distinguishing the central drive to tremor in Parkinson's disease and essential tremor.
abstract: Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N = 24) and ET (N = 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.
authors.affiliation: Experimental Neurology Group, Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom, and.
authors.forename: John-Stuart
authors.initials: JS
authors.lastname: Brittain
authors.affiliation: Experimental Neurology Group, Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom, and.
authors.forename: Hayriye
authors.initials: H
authors.lastname: Cagnan
authors.affiliation: Experimental Neurology Group, Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom, and.
authors.forename: Arpan R
authors.initials: AR
authors.lastname: Mehta
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.
authors.forename: Tabish A
authors.initials: TA
authors.lastname: Saifee
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
authors.affiliation: Experimental Neurology Group, Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom, and peter.brown@ndcn.ox.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002531:Cerebellum / Q000503:physiopathology; D020329:Essential Tremor / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000503:physiopathology*; D014202:Tremor / Q000503:physiopathology*
keywords: Parkinson's disease; accelerometery; cerebellum; essential tremor; transcranial alternating current stimulation; tremor