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

Abstract

Objective. Pathological tremors are symptomatic to several neurological disorders that are difficult to differentiate and the way by which central oscillatory networks entrain tremorogenic contractions is unknown. We considered the alternative hypotheses that tremor arises from one oscillator (at the tremor frequency) or, as suggested by recent findings from the superimposition of two separate inputs (at the tremor frequency and twice that frequency). Approach. Assuming one central oscillatory network we estimated analytically the relative amplitude of the harmonics of the tremor frequency in the motor neuron output for different temporal behaviors of the oscillator. Next, we analyzed the bias in the relative harmonics amplitude introduced by superimposing oscillations at twice the tremor frequency. These findings were validated using experimental measurements of wrist angular velocity and surface electromyography (EMG) from 22 patients (11 essential tremor, 11 Parkinson's disease). The ensemble motor unit action potential trains identified from the EMG represented the neural drive to the muscles. Main results. The analytical results showed that the relative power of the tremor harmonics in the analytical models of the neural drive was determined by the variability and duration of the tremor bursts and the presence of the second oscillator biased this power towards higher values. The experimental findings accurately matched the analytical model assuming one oscillator, indicating a negligible functional role of secondary oscillatory inputs. Furthermore, a significant difference in the relative power of harmonics in the neural drive was found across the patient groups, suggesting a diagnostic value of this measure (classification accuracy: 86%). This diagnostic power decreased substantially when estimated from limb acceleration or the EMG. Signficance. The results indicate that the neural drive in pathological tremor is compatible with one central network providing neural oscillations at the tremor frequency. Moreover, the regularity of this neural oscillation varies across tremor pathologies, making the relative amplitude of tremor harmonics a potential biomarker for diagnostic use.

An OpenSim-Based Closed-Loop Biomechanical Wrist Model for Subject-Specific Pathological Tremor Simulation

“…According to Dideriksen et al [15], one CPG representing CNS oscillatory activity can reproduce most syndromes with PT manifestations. A Matsuoka's CPG oscillator (eq.…”

“…We used a "simple and robust rule" (eq. 15) proposed by Freedman and Diaconis [34] for choosing bin width (w) based on the data's interquartile range function (IQR). N is the data vector length.…”

“…We linked these tools to create a framework with realistic neuromechanical components embedded within OpenSim, such as muscle geometry and dynamics. The model is disturbed by an endogenous nonlinear central pattern generator (CPG), mimicking the central nervous circuitry that generates basal ganglia-originated tremors [11,15]. Closed-loop gains and physiological relationships are implemented in Matlab, which allows tuning the model for subject-specific tremor characteristics.…”

Motor Unit-Driven Identification of Pathological Tremor in Electroencephalograms

“…The amplitude B was set equal to 1, whereas the amplitude of the first harmonic, H 1 , was varied across simulations and was set to 0, 0.2, 0.4, 0.6, 0.8, and 1. This way we simulated the experimentally observed ratios between the basic tremor frequency and its first harmonic ( 9 , 13 , 32 ). The frequency f j of the oscillatory inputs was set to 5+ j /2 Hz with j = 1, 2 … 10, and the phase ϕ j was randomly selected from the interval [0, 2π].…”

Identifying and modulating distinct tremor states through peripheral nerve stimulation in Parkinsonian rest tremor

“…Studies of the coherence between microelectrode recordings within the globus pallidus or subthalamic nucleus (STN) and electromyography (EMG) in people with Parkinson’s disease provide evidence for the former [ 34 , 35 ]. A recent modelling study has also highlighted that one central tremor drive is sufficient to capture features derived from experimental recordings [ 36 ]. On the other hand, the presence of spatially distinct pockets of coherence with tremor within the STN and ventral thalamus raises the possibility of multiple competing central oscillators [ 37 , 38 ].…”