Estimates of persistent inward currents are reduced in upper limb motor units of older adults.

Ageing is a natural process causing alterations in the neuromuscular system, which contributes to reduced quality of life. Motor unit (MU) contributes to weakness, but the mechanisms underlying reduced firing rates are unclear. Persistent inward currents (PICs) are crucial for initiation, gain control and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since concentrations of monoamines (i.e. serotonin and noradrenaline) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (ΔFrequency; or simply ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ∼1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ∼1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ∼1 pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in the upper limbs of older adults during submaximal isometric contractions. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and function in older individuals, but further work is required to understand the implications in other muscles and during a variety of motor tasks. KEY POINTS: Persistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. During ageing, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults. Estimates of persistent inward currents have a negative relationship with age in the older adults, but not in the young. This novel mechanism may play a role in the alteration of motor firing rates that occurs with ageing, which may have consequences for motor control.

Robust and accurate decoding of motoneuron behaviour and prediction of the resulting force output.

KEY POINTS: The spinal alpha motoneuron is the only cell in the human CNS whose discharge can be routinely recorded in humans. We have reengineered motor unit collection and decomposition approaches, originally developed in humans, to measure the neural drive to muscle and estimate muscle force generation in the in vivo cat model. Experimental, computational, and predictive approaches are used to demonstrate the validity of this approach across a wide range of modes to activate the motor pool. The utility of this approach is shown through the ability to track individual motor units across trials, allowing for better predictions of muscle force than the electromyography signal, and providing insights in to the stereotypical discharge characteristics in response to synaptic activation of the motor pool. This approach now allows for a direct link between the intracellular data of single motoneurons, the discharge properties of motoneuron populations, and muscle force generation in the same preparation. ABSTRACT: The discharge of a spinal alpha motoneuron and the resulting contraction of its muscle fibres represents the functional quantum of the motor system. Recent advances in the recording and decomposition of the electromyographic signal allow for the identification of several tens of concurrently active motor units. These detailed population data provide the potential to achieve deep insights into the synaptic organization of motor commands. Yet most of our understanding of the synaptic input to motoneurons is derived from intracellular recordings in animal preparations. Thus, it is necessary to extend the new electrode and decomposition methods to recording of motor unit populations in these same preparations. To achieve this goal, we use high-density electrode arrays and decomposition techniques, analogous to those developed for humans, to record and decompose the activity of tens of concurrently active motor units in a hindlimb muscle in the in vivo cat. Our results showed that the decomposition method in this animal preparation was highly accurate, with conventional two-source validation providing rates of agreement equal to or superior to those found in humans. Multidimensional reconstruction of the motor unit action potential provides the ability to accurately track the same motor unit across multiple contractions. Additionally, correlational analyses demonstrate that the composite spike train provides better estimates of whole muscle force than conventional estimates obtained from the electromyographic signal. Lastly, stark differences are observed between the modes of activation, in particular tendon vibration produced quantal interspike intervals at integer multiples of the vibration period.

Motor Unit Discharge Variability Is Increased in Mild-To-Moderate Parkinson's Disease.

Individuals with Parkinson's disease (PD) demonstrate deficits in muscle activation such as decreased amplitude and inappropriate bursting. There is evidence that some of these disturbances are more pronounced in extensor vs. flexor muscles. Surface EMG has been used widely to quantify muscle activation deficits in PD, but analysis of discharge of the underlying motor units may provide greater insight and be more sensitive to changes early in the disease. Of the few studies that have examined motor unit discharge in PD, the majority were conducted in the first dorsal interosseous, and no studies have measured motor units from extensor and flexor muscles within the same cohort. The objective of this study was to characterize the firing behavior of single motor units in the elbow flexor and extensor muscles during isometric contractions in people with mild-to-moderate PD. Ten individuals with PD (off-medication) and nine healthy controls were tested. Motor unit spike times were recorded via intramuscular EMG from the biceps and triceps brachii muscles during 30-s isometric contractions at 10% maximum voluntary elbow flexion and elbow extension torque, respectively. We selected variables of mean motor unit discharge rate, discharge variability, and torque variability to evaluate motor abnormalities in the PD group. The effects of group, muscle, and group-by-muscle on each variable were determined using separate linear mixed models. Discharge rate and torque variability were not different between groups, but discharge variability was significantly higher in the PD group for both muscles combined (p < 0.0001). We also evaluated the asymmetry in these motor variables between the triceps and biceps for each individual participant with PD to evaluate whether there was an association with disease severity. The difference in torque variability between elbow flexion and extension was significantly correlated with both the Hoehn and Yahr scale (rho = 0.71) and UPDRS (rho = 0.62). Our findings demonstrate that variability in motor output, rather than decreased discharge rates, may contribute to motor dysfunction in people with mild-to-moderate PD. Our findings provide insight into altered neural control of movement in PD and demonstrate the importance of measuring from multiple muscles within the same cohort.

Impact of parameter selection on estimates of motoneuron excitability using paired motor unit analysis.

OBJECTIVE: Noninvasive estimation of motoneuron excitability in human motoneurons is achieved through a paired motor unit analysis (ΔF) that quantifies hysteresis in the instantaneous firing rates at motor unit recruitment and de-recruitment. The ΔF technique provides insight into the magnitude of neuromodulatory synaptic input and persistent inward currents (PICs). While the ΔF technique is commonly used for estimating motoneuron excitability during voluntary contractions, computational parameters used for the technique vary across studies. A systematic investigation into the relationship between these parameters and ΔF values is necessary. APPROACH: We assessed the sensitivity of the ΔF technique with several criteria commonly used in selecting motor unit pairs for analysis and methods used for smoothing the instantaneous motor unit firing rates. Using high-density surface EMG and convolutive blind source separation, we obtained a large number of motor unit pairs (5409) from the triceps brachii of ten healthy individuals during triangular isometric contractions. MAIN RESULTS: We found an exponential plateau relationship between ΔF and the recruitment time difference between the motor unit pairs and an exponential decay relationship between ΔF and the de-recruitment time difference between the motor unit pairs, with the plateaus occurring at approximately 1 s and 1.5 s, respectively. Reduction or removal of the minimum threshold for rate-rate correlation of the two units did not affect ΔF values or variance. Removing motor unit pairs in which the firing rate of the control unit was saturated had no significant effect on ΔF. Smoothing the filter selection had no substantial effect on ΔF values and ΔF variance; however, filter selection affected the minimum recruitment and de-recruitment time differences. SIGNIFICANCE: Our results offer recommendations for standardized parameters for the ΔF approach and facilitate the interpretation of findings from studies that implement the ΔF analysis but use different computational parameters.

Differences between flexion and extension synergy-driven coupling at the elbow, wrist, and fingers of individuals with chronic hemiparetic stroke.

OBJECTIVE: The flexion and extension synergies were quantified at the paretic elbow, forearm, wrist, and finger joints within the same group of participants for the first time. Differences in synergy expression at each of the four joints were examined, as were the ways these differences varied across the joints. METHODS: Twelve post-stroke individuals with chronic moderate-to-severe hemiparesis and six age-matched controls participated. Participants generated isometric shoulder abduction (SABD) and shoulder adduction (SADD) at four submaximal levels to progressively elicit the flexion and extension synergies, respectively. Isometric joint torques and EMG were recorded from shoulder, elbow, forearm (radio-ulnar), wrist, and finger joints and muscles. RESULTS: SABD elicited strong wrist and finger flexion torque that increased with shoulder torque level. SADD produced primarily wrist and finger flexion torque, but magnitudes at the wrist were less than during SABD. Findings contrasted with those at the elbow and forearm, where torques and EMG generated due to SABD and SADD were opposite in direction. CONCLUSIONS: Flexion and extension synergy expression are more similar at the hand than at the shoulder and elbow. Specific bulbospinal pathways that may underlie flexion and extension synergy expression are discussed. SIGNIFICANCE: Whole-limb behavior must be considered when examining paretic hand function in moderately-to-severely impaired individuals.

Exogenous neuromodulation of spinal neurons induces beta-band coherence during self-sustained discharge of hind limb motor unit populations.

The spontaneous or self-sustained discharge of spinal motoneurons can be observed in both animals and humans. Although the origins of this self-sustained discharge are not fully known, it can be generated by activation of persistent inward currents intrinsic to the motoneuron. If self-sustained discharge is generated exclusively through this intrinsic mechanism, the discharge of individual motor units will be relatively independent of one another. Alternatively, if increased activation of premotor circuits underlies this prolonged discharge of spinal motoneurons, we would expect correlated activity among motoneurons. Our aim is to assess potential synaptic drive by quantifying coherence during self-sustained discharge of spinal motoneurons. Electromyographic activity was collected from 20 decerebrate animals using a 64-channel electrode grid placed on the isolated soleus muscle before and following intrathecal administration of methoxamine, a selective α1-noradrenergic agonist. Sustained muscle activity was recorded and decomposed into the discharge times of ~10-30 concurrently active individual motor units. Consistent with previous reports, the self-sustained discharge of motor units occurred at low mean discharge rates with low-interspike variability. Before methoxamine administration, significant low-frequency coherence (<2 Hz) was observed, while minimal coherence was observed within higher frequency bands. Following intrathecal administration of methoxamine, increases in motor unit discharge rates and strong coherence in both the low-frequency and 15- to 30-Hz beta bands were observed. These data demonstrate beta-band coherence among motor units can be observed through noncortical mechanisms and that neuromodulation of spinal/brainstem neurons greatly influences coherent discharge within spinal motor pools.NEW & NOTEWORTHY The correlated discharge of spinal motoneurons is often used to describe the input to the motor pool. We demonstrate spinal/brainstem neurons devoid of cortical input can generate correlated motor unit discharge in the 15- to 30-Hz beta band, which is amplified through neuromodulation. Activity in the beta band is often ascribed to cortical drive in humans; however, these data demonstrate the capability of the mammalian segmental motor system to generate and modulate this coherent state of motor unit discharge.

Properties of the motor unit action potential shape in proximal and distal muscles of the upper limb in healthy and post-stroke individuals.

Spectral analysis of surface electromyograms (sEMG) is often used to estimate central and peripheral characteristics of a motor unit (MU) population, such as average conduction velocity, proportion of muscle fiber types, and pattern of MU recruitment. This estimation is based on the assumption that the sEMG adequately reflects the frequency characteristics of the underlying MU action potentials (MUAP). However, sEMG has limitations in this respect, based on physiological and non-physiological factors that influence its frequency content. We present a method to examine characteristics of a MU population more reliably by assessing the distributions of frequency content and amplitude for a collection of individual MUAPs, identified using high-density sEMG decomposition. We demonstrate the use of this approach to examine how MU characteristics differ across muscles and in the post-stroke state by presenting preliminary data from deltoid (DELT), biceps (BIC), and finger flexor (FF) MU populations from 12 post-stroke individuals and 8 able-bodied controls. The results show differences in the magnitude and range of MUAP median frequencies across muscles in both groups. The group median values were higher in the stroke group for the DELT and FF and lower in the stroke group for the BIC. The range of frequencies was larger in the stroke group for all muscles. The distribution of MUAP RMS amplitude in both stroke and control groups had a substantially larger range in FF than in DELT and BIC. The group median values for the FF were twice as large in the stroke group. In addition, there were differences in the frequency and amplitude results between MUAP and global sEMG analyses. The implications of these findings and possible applications of the approach are discussed.