Tracking motion kinematics and tremor with intrinsic oscillatory property of instrumental mechanics

Abstract

Tracking kinematic details of motor behaviors is a foundation to study the neuronal mechanism and biology of motor control. However, most of the physiological motor behaviors and movement disorders, such as gait, balance, tremor, dystonia, and myoclonus, are highly dependent on the overall momentum of the whole-body movements. Therefore, tracking the targeted movement and overall momentum simultaneously is critical for motor control research, but it remains an unmet need.Here, we introduce the intrinsic oscillatory property (IOP), a fundamental mechanical principle of physics, as a method for motion tracking in a force plate. The overall kinetic energy of animal motions can be transformed into the oscillatory amplitudes at the designed IOP frequency of the force plate, while the target movement has its own frequency features and can be tracked simultaneously. Using action tremor as an example, we reported that force plate-based IOP approach has superior performance and reliability in detecting both tremor severity and tremor frequency, showing a lower level of coefficient of variation (CV) compared with video-and accelerometer-based motion tracking methods and their combination. Under the locomotor suppression effect of medications, therapeutic effects on tremor severity can still be quantified by dynamically adjusting the overall locomotor activity detected by IOP. We further validated IOP method in optogenetic-induced movements and natural movements, confirming that IOP can represent the intensity of general Chun-Lun Ni and Yi-Ting Lin contributed equally to this work.

The cerebellum computes frequency dynamics for motions with numerical precision and cross-individual uniformity

“…Based on this initial observation, we trained the mice with a protocol including multiple vibratory frequencies (Fig. 1g), covering the physiological frequency range of spontaneous motor behaviors 18 .…”

“…Cerebellar dysfunctions lead to the breakdown of motor kinematic control in a unique feature linked to motor frequencies. Essential tremor, the most common movement disorder, is characterized by involuntary rhythmic movements with a consistent motor 5 frequency, linked to excessive cerebellar oscillations [13][14][15] . Conversely, cerebellar ataxia features arrhythmic involuntary movements, that are associated with Purkinje cell loss 16,17 .…”

Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients

“…These results suggest that tremor frequencies and amplitudes are regulated by different mechanisms. The intensity of cerebellar oscillations in both mice and humans has been linked to tremor amplitudes ( 20 , 22 , 41 ), potentially reflecting the synchrony of PC complex spikes and DCN neurons ( 33 , 35 , 48 – 51 ). Amplitude-based analysis also revealed that cerebellar tACS at the tremor frequency can bidirectionally modulate tremor amplitudes in patients with ET ( 52 ).…”

“…Grid2 dupE3 mice were used as a mouse model of ET with pathological and electrophysiological characteristics similar to the human disease ( 20 ). Electrophysiology was incorporated with force plate–based motion tracking ( 41 ) in freely moving mice. Viral-based optogenetic tools and transgenic mice were applied to validate tremor-generating mechanisms in nontremulous mice or modulate tremor frequencies in Grid2 dupE3 mice.…”

“…We first assessed whether oscillatory activity could be detected in the cerebro-olivocerebello-thalamo-cortical circuit, as suggested by stroke-related lesioning or functional magnetic resonance imaging studies in patients (37)(38)(39)(40). Using in vivo electrophysiology with implanted deep or surface electrodes (see Supplementary Methods) in conjunction with simultaneous motor kinematic recordings on a force plate (41), we detected 20-Hz tremors and associated oscillatory activity in the primary motor cortex, inferior olive (IO), cerebellar cortex, interposed nucleus of deep cerebellar nuclei (DCN), and thalamus in Grid2 dupE3 tremor mice (Fig. 1, A to F).…”