Movement is a central behavior of daily living; thus lost or compromised movement due to disease, injury, or amputation causes enormous loss of productivity and quality of life. While prosthetics have evolved enormously over the years, restoring natural sensorimotor (SM) control via a prosthesis is a difficult problem which neuroengineering has yet to solve. With a focus on upper limb prosthetics, this perspective article discusses the neurophysiology of motor control under healthy conditions and after amputation, the development of upper limb prostheses from early generations to current state-of-the art sensorimotor neuroprostheses, and how postinjury changes could complicate prosthetic control.
View Article and Find Full Text PDF(1) Background: The electroencephalogram (EEG) is frequently corrupted by ocular artifacts such as saccades and blinks. Methods for correcting these artifacts include independent component analysis (ICA) and recursive-least-squares (RLS) adaptive filtering (-AF). Here, we introduce a new method, AFFiNE, that applies Bayesian adaptive regression spline (BARS) fitting to the adaptive filter's reference noise input to address the known limitations of both ICA and RLS-AF, and then compare the performance of all three methods.
View Article and Find Full Text PDFPersistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS.
View Article and Find Full Text PDFMuscle force is modulated by sequential recruitment and firing rates of motor units (MUs). However, discrepancies exist in the literature regarding the relationship between MU firing rates and their recruitment, presenting two contrasting firing-recruitment schemes. The first firing scheme, known as "onion skin," exhibits low-threshold MUs firing faster than high-threshold MUs, forming separate layers akin to an onion.
View Article and Find Full Text PDFIntroduction: Bifurcation analysis allows the examination of steady-state, non-linear dynamics of neurons and their effects on cell firing, yet its usage in neuroscience is limited to single-compartment models of highly reduced states. This is primarily due to the difficulty in developing high-fidelity neuronal models with 3D anatomy and multiple ion channels in XPPAUT, the primary bifurcation analysis software in neuroscience.
Methods: To facilitate bifurcation analysis of high-fidelity neuronal models under normal and disease conditions, we developed a multi-compartment model of a spinal motoneuron (MN) in XPPAUT and verified its firing accuracy against its original experimental data and against an anatomically detailed cell model that incorporates known MN non-linear firing mechanisms.
Fast Blue (FB) and Cholera Toxin-B (CTB) are two retrograde tracers extensively used to label alpha-motoneurons (α-MNs). The overall goals of the present study were to (1) assess the effectiveness of different FB and CTB protocols in labeling α-MNs, (2) compare the labeling quality of these tracers at standard concentrations reported in the literature (FB 2% and CTB 0.1%) versus lower concentrations to overcome tracer leakage, and (3) determine an optimal protocol for labeling α-MNs in young B6SJL and aged C57Bl/J mice (when axonal transport is disrupted by aging).
View Article and Find Full Text PDFIn amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS.
View Article and Find Full Text PDFSpinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive cutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice.
View Article and Find Full Text PDFThe overarching goal was to resolve a major barrier to real-life prosthesis usability-the rapid degradation of prosthesis control systems, which require frequent recalibrations. Specifically, we sought to develop and test a motor decoder that provides (1) highly accurate, real-time movement response, and (2) unprecedented adaptability to dynamic changes in the amputee's biological state, thereby supporting long-term integrity of control performance with few recalibrations. To achieve that, an adaptive motor decoder was designed to auto-switch between algorithms in real-time.
View Article and Find Full Text PDFUp to 50% of amputees abandon their prostheses, partly due to rapid degradation of the control systems, which require frequent recalibration. The goal of this study was to develop a Kalman filter-based approach to decoding motoneuron activity to identify movement kinematics and thereby provide stable, long-term, accurate, real-time decoding. The Kalman filter-based decoder was examined via biologically varied datasets generated from a high-fidelity computational model of the spinal motoneuron pool.
View Article and Find Full Text PDFAlthough slice recordings from spinal motoneurons (MNs) are being widely used, the effects of slicing on the measured MN electrical properties under normal and disease conditions have not been assessed. Using high-fidelity cell models of neonatal wild-type (WT) and superoxide dismutase-1 (SOD) cells, we examined the effects of slice thickness, soma position within the slice, and slice orientation to estimate the error induced in measured MN electrical properties from spinal slices. Our results show that most MN electrical properties are not adversely affected by slicing, except for cell time constant, cell capacitance, and Ca persistent inward current (PIC), which all exhibited large errors, regardless of the slice condition.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2020
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the nervous system causing muscle weakness, paralysis, leading to death. Given that abnormalities in spinal motoneuron (MN) excitability begin long before symptoms manifest, developing an approach that could recognize fluctuations in MN firing could help in early diagnosis of ALS. This paper introduces a machine learning approach to discriminate between ALS and normal MN firing.
View Article and Find Full Text PDFThe posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the "neuronic shutter effect." If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex.
View Article and Find Full Text PDFPersistent inward currents are important to motoneuron excitability and firing behaviors and also have been implicated in excitotoxicity. In particular, L-type Ca channels, usually located on motoneuron dendrites, play a primary role in amplification of synaptic inputs. However, recent experimental findings on L-type Ca channel behaviors challenge some fundamental assumptions that have been used in interpreting experimental and computational modeling data.
View Article and Find Full Text PDFExperimental, methodological, and biological variables must be accounted for statistically to maximize accuracy and comparability of published neuroscience data. However, accounting for all variables is nigh impossible. Thus we aimed to identify particularly influential variables within published neurological data, from cat, rat, and mouse studies, via a robust statistical process.
View Article and Find Full Text PDFElectrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord.
View Article and Find Full Text PDFKey Points: Motoneuron soma size is a largely plastic property that is altered during amyotrophic lateral sclerosis (ALS) progression. We report evidence of systematic spinal motoneuron soma size plasticity in mutant SOD1-G93A mice at various disease stages and across sexes, spinal regions and motoneuron types. We show that disease-vulnerable motoneurons exhibit early increased soma sizes.
View Article and Find Full Text PDFObjective: Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results.
Approach: We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations.
The spinal cord contains specialized groups of cells called pattern generators, which are capable of orchestrating rhythmic firing activity in an isolated preparation. Different patterns of activity could be generated in vitro including right-left alternating bursting and bursting in which both sides are synchronized. The cellular and network mechanisms that enable these behaviors are not fully understood.
View Article and Find Full Text PDFSubthreshold oscillations in combination with large-amplitude oscillations generate mixed-mode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductance-based models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under antiepileptic drug conditions (i.
View Article and Find Full Text PDFBurst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blocker cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane that contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca-activated potassium (SK) channels regulate excitatory inputs and firing output of motoneurons and interneurons and therefore, are a candidate for mediating bursting behavior.
View Article and Find Full Text PDFThe possible presence of pathological changes in cholinergic synaptic inputs [cholinergic boutons (C-boutons)] is a contentious topic within the ALS field. Conflicting data reported on this issue makes it difficult to assess the roles of these synaptic inputs in ALS. Our objective was to determine whether the reported changes are truly statistically and biologically significant and why replication is problematic.
View Article and Find Full Text PDFSynaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord.
View Article and Find Full Text PDFJ Appl Physiol (1985)
December 2014
In large network and single three-dimensional (3-D) neuron simulations, high computing speed dictates using reduced cable models to simulate neuronal firing behaviors. However, these models are unwarranted under active conditions and lack accurate representation of dendritic active conductances that greatly shape neuronal firing. Here, realistic 3-D (R3D) models (which contain full anatomical details of dendrites) of spinal motoneurons were systematically compared with their reduced single unbranched cable (SUC, which reduces the dendrites to a single electrically equivalent cable) counterpart under passive and active conditions.
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