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.

Fast Oscillatory Commands from the Motor Cortex Can Be Decoded by the Spinal Cord for Force Control

“…This lowfrequency input is the most commonly used in previous simulation studies (Farina et al, 2014;Gallego et al, 2015) of muscle force control.…”

“…Due to unsurmountable experimental difficulties to measure the inputs to MN pools in humans (Heckman and Enoka, 2012), the study of how the CSIs influence the MN spike trains was approached previously by means of computer model simulations (Williams and Baker, 2009a,b;Stegeman et al, 2010;Negro andFarina, 2011a,b, 2012;Watanabe et al, 2013;Farina et al, 2014;Gallego et al, 2015). This approach was also used to study oscillatory CSIs in general neuron populations (Knight, 1972;Fourcaud-trocme et al, 2003) (MNs and MUs).…”

New Perspectives for Computer-Aided Discrimination of Parkinson’s Disease and Essential Tremor

“…These interactions between muscles are also yet not fully understood. For example, it has been recently demonstrated that not all the muscles are equally affected by ET [20] and that the interaction between antagonist muscles is different across conditions and patients, and intrinsically nonstationary [21].…”

“…However, not all of these algorithms are applicable to hdEMG data in pathological tremor; in pathological tremor, motor unit firings tend to be significantly more synchronized than in healthy conditions [21,23], causing bursts of EMG activity ( Figure 2) that are very difficult to decompose into the contributions of individual motor units. The Convolution Kernel Compensation (CKC) technique has been recently demonstrated to successfully solve this problem [23], providing a solid ground for fully automatic and highly accurate assessment of the tremulous neural drive to muscles.…”

One central oscillatory drive is compatible with experimental motor unit behaviour in essential and Parkinsonian tremor

“…As in previous studies of motor unit activity in tremor [32], only identified spike trains with pulse-to-noise ratio ^26 dB (metric describing the decomposition accuracy; see [33] for details) was included in the analysis. For each muscle pair, a period of 30 s of the complete recording was selected for further analysis.…”