The Phase Difference Between Neural Drives to Antagonist Muscles in Essential Tremor Is Associated with the Relative Strength of Supraspinal and Afferent Input.
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.post-print2260 K
