Biology subjects

Khurram, O. U.

Publications and source records attributed to Khurram, O. U..

4 recordsLinked to original sources

bioRxiv2023

Intrinsic properties of spinal motoneurons degrade ankle torque control in humans

Motoneurons are the final common pathway for all motor commands and possess intrinsic electrical properties that must be tuned to control muscle across the full range of motor behaviors. Neuromodulatory input from the brainstem is likely essential for adapting motoneuron properties to match this diversity of motor tasks. A primary mechanism of this adaptation, control of dendritic persistent inward currents (PICs) in motoneurons by brainstem monoaminergic systems, generates both amplification and prolongation of synaptic inputs. While essential, there is an inherent tension between this amplification and prolongation. Although amplification by PICs allows for quick recruitment and acceleration of motoneuron discharge during discrete motor tasks, PICs must be deactivated to de-recruit motoneurons upon movement cessation. In contrast, during stabilizing or postural tasks, PIC-induced prolongation of synaptic inputs is likely critical for sustained motoneuron discharge. Here, we designed two motor tasks that show PIC amplification and prolongation may conflict and generate errors that degrade the precision of motor output in humans. This included a paradigm comprised of a discrete motor task superimposed atop a stabilizing task and a paradigm with muscle length-induced changes to the balance of excitatory and inhibitory inputs available for controlling PICs. We show that prolongation from PICs introduces deficits in ankle torque control and that these deficits are further degraded at shorter muscle lengths when PIC prolongation is greatest. These results highlight the necessity for inhibitory control of PICs and showcase issues that are introduced when inhibitory control is perturbed or constrained. Our findings suggest that, like sensory systems, errors are inherent in motor systems. These errors are not due to problems in the perception of movement-related sensory input but are embedded in the final stage of motor output.

physiology↗

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↗