title: The phase difference between neural drives to antagonist muscles in essential tremor is associated with the relative strength of supraspinal and afferent input.
abstract: The pathophysiology of essential tremor (ET), the most common movement disorder, is not fully understood. We investigated which factors determine the variability in the phase difference between neural drives to antagonist muscles, a long-standing observation yet unexplained. We used a computational model to simulate the effects of different levels of voluntary and tremulous synaptic input to antagonistic motoneuron pools on the tremor. We compared these simulations to data from 11 human ET patients. In both analyses, the neural drive to muscle was represented as the pooled spike trains of several motor units, which provides an accurate representation of the common synaptic input to motoneurons. The simulations showed that, for each voluntary input level, the phase difference between neural drives to antagonist muscles is determined by the relative strength of the supraspinal tremor input to the motoneuron pools. In addition, when the supraspinal tremor input to one muscle was weak or absent, Ia afferents provided significant common tremor input due to passive stretch. The simulations predicted that without a voluntary drive (rest tremor) the neural drives would be more likely in phase, while a concurrent voluntary input (postural tremor) would lead more frequently to an out-of-phase pattern. The experimental results matched these predictions, showing a significant change in phase difference between postural and rest tremor. They also indicated that the common tremor input is always shared by the antagonistic motoneuron pools, in agreement with the simulations. Our results highlight that the interplay between supraspinal input and spinal afferents is relevant for tremor generation.
authors.affiliation: Neural and Cognitive Engineering Group, Centre for Automation and Robotics, Consejo Superior de Investigaciones Científicas, 28500 Arganda del Rey, Spain, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Juan A
authors.identifier: http://orcid.org/0000-0003-2146-0703
authors.initials: JA
authors.lastname: Gallego
authors.affiliation: Department of Neurorehabilitation Engineering, Bernstein Focus Neurotechnology Göttingen, Bernstein Center for Computational Neuroscience, University Medical Center Göttingen, Georg-August University, 37075 Göttingen, Germany, Center for Sensory-Motor Interaction, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark.
authors.forename: Jakob L
authors.initials: JL
authors.lastname: Dideriksen
authors.affiliation: Faculty of Electrical Engineering and Computer Science, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Ales
authors.initials: A
authors.lastname: Holobar
authors.affiliation: Neural Rehabilitation Group, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
authors.forename: Jaime
authors.identifier: http://orcid.org/0000-0001-8439-151X
authors.initials: J
authors.lastname: Ibáñez
authors.affiliation: Faculty of Electrical Engineering and Computer Science, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Vojko
authors.initials: V
authors.lastname: Glaser
authors.affiliation: Department of Neurology, University Hospital 12 de Octubre, 28041 Madrid, Spain, Biosanitary Sciencies School, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarcón, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Romero
authors.affiliation: Department of Neurology, University Hospital 12 de Octubre, 28041 Madrid, Spain, Department of Medicine, Complutense University, 28040 Madrid, Spain, and.
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.affiliation: Neural Rehabilitation Group, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Pons
authors.affiliation: Neural and Cognitive Engineering Group, Centre for Automation and Robotics, Consejo Superior de Investigaciones Científicas, 28500 Arganda del Rey, Spain, Post-Graduate Program, Universidade Federal do Espírito Santo, 29075-910 Vitória, Brazil.
authors.forename: Eduardo
authors.identifier: http://orcid.org/0000-0001-9618-2176
authors.initials: E
authors.lastname: Rocon
authors.affiliation: Department of Neurorehabilitation Engineering, Bernstein Focus Neurotechnology Göttingen, Bernstein Center for Computational Neuroscience, University Medical Center Göttingen, Georg-August University, 37075 Göttingen, Germany, dario.farina@bccn.uni-goettingen.de.
authors.forename: Dario
authors.initials: D
authors.lastname: Farina
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000368:Aged; D000818:Animals; D003198:Computer Simulation; D004576:Electromyography; D020329:Essential Tremor / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D013116:Spinal Cord / Q000473:pathology*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000502:physiology; D014738:Vibrissae / Q000294:innervation
keywords: EMG; Ia afferents; essential tremor; motoneuron; motor unit; tremor