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Biology subjects

Wimalasena, L. N.

Publications and source records attributed to Wimalasena, L. N..

2 recordsLinked to original sources

Estimating muscle activation from EMG using deep learning-based dynamical systems models

ObjectiveTo study the neural control of movement, it is often necessary to estimate how muscles are activated across a variety of behavioral conditions. However, estimating the latent command signal that underlies muscle activation is challenging due to its complex relation with recorded electromyographic (EMG) signals. Common approaches estimate muscle activation independently for each channel or require manual tuning of model hyperparameters to optimally preserve behaviorally-relevant features. ApproachHere, we adapted AutoLFADS, a large-scale, unsupervised deep learning approach originally designed to de-noise cortical spiking data, to estimate muscle activation from multi-muscle EMG signals. AutoLFADS uses recurrent neural networks (RNNs) to model the spatial and temporal regularities that underlie multi-muscle activation. Main ResultsWe first tested AutoLFADS on muscle activity from the rat hindlimb during locomotion, and found that it dynamically adjusts its frequency response characteristics across different phases of behavior. The model produced single-trial estimates of muscle activation that improved prediction of joint kinematics as compared to low-pass or Bayesian filtering. We also tested the generality of the approach by applying AutoLFADS to monkey forearm muscle activity from an isometric task. AutoLFADS uncovered previously uncharacterized high-frequency oscillations in the EMG that enhanced the correlation with measured force compared to low-pass or Bayesian filtering. The AutoLFADS-inferred estimates of muscle activation were also more closely correlated with simultaneously-recorded motor cortical activity than other tested approaches. SignificanceUltimately, this method leverages both dynamical systems modeling and artificial neural networks to provide estimates of muscle activation for multiple muscles that can be used for further studies of multi-muscle coordination and its control by upstream brain areas.

neuroscience↗

Structural determinants of protocadherin-15 elasticity and function in inner-ear mechanotransduction

Protocadherin-15 (PCDH15), an atypical member of the cadherin superfamily, is essential for vertebrate hearing and its dysfunction has been associated with deafness and progressive blindness. The PCDH15 ectodomain, made of eleven extracellular cadherin (EC1-11) repeats and a membrane adjacent domain (MAD12), assembles as a parallel homodimer that interacts with cadherin-23 (CDH23) to form the tip link, a fine filament necessary for inner-ear mechanotransduction. Here we report X-ray crystal structures of a PCDH15 + CDH23 heterotetrameric complex and ten PCDH15 fragments that were used to build complete high-resolution models of the monomeric PCDH15 ectodomain. Using molecular dynamics (MD) simulations and validated crystal contacts we propose models for complete PCDH15 parallel homodimers and the tip-link bond. Steered MD simulations of these models predict their strength and suggest conditions in which a multimodal PCDH15 ectodomain can act as a stiff or soft gating spring. These results provide a detailed view of the first molecular steps in inner-ear sensory transduction.

biophysics↗