Biology subjects

Beauchamp, J. A.

Publications and source records attributed to Beauchamp, J. A..

5 recordsLinked to original sources

bioRxiv2022

Supercomputers and Reverse Engineering of Motoneuron Firing Patterns

In this study, we develop new reverse engineering (RE) techniques to identify the organization of the synaptic inputs generating firing patterns of populations of neurons. We tested these techniques in silico to allow rigorous evaluation of their effectiveness, using remarkably extensive parameter searches enabled by massively-parallel computation on supercomputers. We chose spinal motoneurons as our target neural system, since motoneurons process all motor commands and have well established input-output properties. One set of simulated motoneurons was driven by 300,000+ simulated combinations of excitatory, inhibitory, and neuromodulatory inputs. Our goal was to determine if these firing patterns had sufficient information to allow RE identification of the input combinations. Like other neural systems, the motoneuron input-output system is likely non-unique. This non-uniqueness could potentially limit this RE approach, as many input combinations can produce similar outputs. However, our simulations revealed that firing patterns contained sufficient information to sharply restrict the solution space. Thus, our RE approach successfully generated estimates of the actual simulated patterns of excitation, inhibition, and neuromodulation, with variances accounted for ranging from 75% to 90%. It was striking that nonlinearities induced in firing patterns by the neuromodulation inputs did not impede RE, but instead generated distinctive features in firing patterns that aided RE. These simulations demonstrate the potential of this form of RE analysis. It is likely that the ever-increasing capacity of supercomputers will allow increasingly accurate RE of neuron inputs from their firing patterns from many neural systems.

neuroscience↗

bioRxiv2022

The effects of biological sex on estimates of persistent inward currents in the human lower limb

Non-invasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of study participants in human and non-human animal physiology studies are male, and it is assumed mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes by quantifying {Delta}F. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed effects models to determine if peak discharge rate and {Delta}F were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of significant sex-differences in peak discharge rates across all muscles, {Delta}F was larger ({chi}2(1) = 6.26, p = 0.012) in females (4.73 {+/-} 0.242 pps) than males (3.81 {+/-} 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns. KEY POINTS- Sex differences in motor unit studies have been revealed with greater inclusion of female participants, however, mechanisms for these differences remain unclear. - Estimates of persistent inward currents (i.e., {Delta}F) were greater in females than males in the tibialis anterior, medial gastrocnemius, and soleus muscles. - This suggests that neuromodulatory drive, monoaminergic signaling, or descending control may differ between the sexes. - Therefore, sex differences in estimates of PICs may provide a mechanism behind previously reported sex differences in motoneuron discharge patterns..

neuroscience↗

bioRxiv2022

A geometric approach to quantifying the neuromodulatory effects of persistent inward currents on single motor unit discharge patterns

ObjectiveAll motor commands flow through motoneurons, which entrain control of their innervated muscle fibers, forming a motor unit (MU). Owing to the high fidelity of action potentials within MUs, their discharge profiles detail the organization of ionotropic excitatory/inhibitory as well as metabotropic neuromodulatory commands to motoneurons. Neuromodulatory inputs (e.g., norepinephrine, serotonin) enhance motoneuron excitability and facilitate persistent inward currents (PICs). PICs introduce quantifiable properties in MU discharge profiles by augmenting depolarizing currents upon activation (i.e., PIC amplification) and facilitating discharge at lower levels of excitatory input than required for recruitment (i.e., PIC prolongation). Approach: Here, we introduce a novel geometric approach to estimate neuromodulatory and inhibitory contributions to MU discharge through exploiting discharge non-linearities introduced by PIC amplification during time-varying linear tasks. In specific, we quantify the deviation from linear discharge ("brace height") and the rate of change in discharge (i.e., acceleration slope, attenuation slope, angle). We further characterize these metrics on a simulated motoneuron pool with known excitatory, inhibitory, and neuromodulatory inputs and on human MUs (Tibialis Anterior: 1448, Medial Gastrocnemius: 2100, Soleus: 1062, First Dorsal Interosseus: 2296). Main ResultIn the simulated motor pool, we found brace height and attenuation slope to consistently indicate changes in neuromodulation and the pattern of inhibition (excitation-inhibition coupling), respectively, whereas the paired MU analysis ({Delta}F) was dependent on both neuromodulation and inhibition pattern. Furthermore, we provide estimates of these metrics in human MUs and show comparable variability in {Delta}F and brace height measures in MUs matched across multiple trials. SignificanceSpanning both datasets, we found brace height quantification to provide an intuitive method for achieving graded estimates of neuromodulatory and inhibitory drive to MUs on a single unit level. This complements common techniques and provides an avenue for decoupling changes in the level of neuromodulatory and pattern of inhibitory motor commands.

bioengineering↗

bioRxiv2022

Antagonist tendon vibration dampens estimates of persistent inward currents in motor units of the human lower limb

We can readily measure motoneuron discharge patterns in humans due to the one-to-one spike relation between motoneuron and muscle fiber action potentials, which allows us to make inferences about motor commands. Persistent inward currents (PICs), which provide gain control of motoneuronal output, are facilitated by monoaminergic input from the brainstem. This monoaminergic input is greatly diffuse, but resulting PICs are highly sensitive to inhibitory inputs. Antagonist muscle stretch, and thus Ia input from the antagonist decreases PIC magnitudes in the decerebrate cat. In the present study, we explored whether estimates of PICs are altered with vibratory input to antagonist muscles in humans. MUs of the tibialis anterior (TA), soleus (SOL), and medial gastrocnemius (MG) were discriminated using high-density surface electromyography and convolutive blind source separation. We estimated PICs using the paired MU analysis technique, which quantifies discharge rate hysteresis ({Delta}F) by comparing the discharge rate of a lower-threshold MU at the onset and offset of a higher-threshold MU. Participants performed isometric plantarflexion and dorsiflexion contractions to a peak of 30% of maximal voluntary contraction, with 10 s ascending and descending phases. In half of the trials, we applied vibration to the antagonist tendon and found that {Delta}F in agonist MUs decreased in the presence of vibration. These findings suggest that inhibition from the antagonist muscle, most likely Ia reciprocal inhibition, can reduce discharge rate hysteresis. This provides insights about non-invasive methods potentially capable of dampening PICs in hyperexcitable motoneurons, which are manifest in some neurological impairments. KEY POINTSO_LIPersistent inward currents in motoneurons amplify synaptic inputs and thus have a major impact on motor unit firing patterns. C_LIO_LIWe show that sustained vibration to the antagonist tendon reduces estimates of persistent inward currents ({Delta}F) of the contracting muscle in both the plantarflexors and dorsiflexors. C_LIO_LIThese findings provide evidence for the important role of sensory input in the control of persistent inward currents in the human. C_LIO_LIReciprocal inhibition may help refine neuromodulatory commands to tailor motor unit activation to diverse movement patterns and specific tasks, and loss of inhibition may exacerbate symptoms of neurological impairment. C_LI

physiology↗

bioRxiv2021

A computational approach for generating smooth estimates of motor unit discharge rates and visualizing population discharge characteristics

ObjectiveSuccessive improvements in high density surface electromyography and decomposition techniques have facilitated an increasing yield in decomposed motor unit (MU) spike times. Though these advancements enhance the generalizability of findings and promote the application of MU discharge characteristics to inform the neural control of motor output, limitations remain. Specifically, 1) common approaches for generating smooth estimates of MU discharge rates introduce artifacts in quantification, which may bias findings, and 2) discharge characteristics of large MU populations are often difficult to visualize. ApproachIn the present study, we propose support vector regression (SVR) as an improved approach for generating continuous estimates of discharge rate and compare the fit characteristics of SVR to traditionally used methods, including Hanning window filtering and polynomial regression. Furthermore, we introduce ensembles as a method to visualize the discharge characteristics of large MU populations. We define ensembles as the average discharge profile of a subpopulation of MUs, composed of a time normalized ensemble average of all units within this subpopulation. Analysis was conducted with MUs decomposed from the tibialis anterior (N = 2128), medial gastrocnemius (N = 2673), and soleus (N = 1190) during isometric plantarflexion and dorsiflexion contractions. Main ResultCompared to traditional approaches, we found SVR to alleviate commonly observed inaccuracies and produce significantly less absolute fit error in the initial phase of MU discharge and throughout the entire duration of discharge. Additionally, we found the visualization of MU populations as ensembles to intuitively represent population discharge characteristics with appropriate accuracy for visualization. SignificanceThe results and methods outlined here provide an improved method for generating smooth estimates of MU discharge rate with SVR and present a unique approach to visualizing MU populations with ensembles. In combination, the use of SVR and generation of ensembles represent an efficient method for rendering population discharge characteristics.

bioengineering↗