Discharge patterns of human genioglossus motor units during sleep onset

STUDY OBJECTIVES: Multiunit electromyogram recordings of genioglossus have demonstrated an abrupt reduction in the muscle's activity at sleep onset. Recent evidence from single motor unit recordings indicates that the human genioglossus muscle consists of motor units with a variety of discharge patterns. The aim of the present study was to determine the effect of sleep onset on the activity of individual motor units as a function of their particular discharge pattern. DESIGN: Genioglossus activity was assessed using intramuscular fine-wire electrodes via a percutaneous approach. Sleep onsets (alpha-to-theta transitions) were identified and the genioglossus electromyogram recordings analyzed for single motor unit activity. SETTING: Sleep research laboratory. PARTICIPANTS: Sleep and respiratory data were collected in 8 healthy subjects (6 men). MEASUREMENTS AND RESULTS: One hundred twenty-seven motor units were identified: 23% inspiratory phasic, 45% inspiratory tonic, 4% expiratory phasic, 9% expiratory tonic, 16% tonic, and 3% other. Approximately 50% of inspiratory units (phasic and tonic) ceased activity entirely at sleep onset, whereas those inspiratory units that continued to be active showed a reduction in the proportion of each breath over which they were active. However, the rate of discharge of inspiratory units during the period they did fire was not altered. In contrast, tonic and expiratory units were unaffected by sleep onset, maintaining their discharge pattern over the alpha-to-theta transition. CONCLUSIONS: Central control of inspiratory motoneuron output differs from that of tonic and expiratory units during sleep onset, suggesting that the maintenance of airway patency during sleep may become more reliant on the stiffening properties of tonic and expiratory modulated motor units.     

Activities of human genioglossus motor units

Upper airway muscles play an important role in regulating airway lumen and in increasing the ability of the pharynx to remain patent in the face of subatmospheric intraluminal pressures produced during inspiration. Due to the considerable technical challenges associated with recording from muscles of the upper airway, much of the experimental work conducted in human subjects has centered on recording respiratory-related activities of the extrinsic tongue protudor muscle, the genioglossus (GG). The GG is one of eight muscles that invest the human tongue (Abd-El-Malek, 1939). All eight muscles are innervated by the hypoglossal nerve (cranial nerve XII) the cell bodies of which are located in the hypoglossal motor nucleus (HMN) of the caudal medulla. Much of the earlier work on the respiratory-related activity of XII motoneurons was based on recordings obtained from single motor axons dissected from the whole XII nerve or from whole muscle GG EMG recordings. Detailed information regarding respiratory-related GG motor unit activities was lacking until as recently as 2006. This paper examines key findings that have emerged from the last decade of work conducted in human subjects. Wherever appropriate, these results are compared with results obtained from in vitro and in vivo studies conducted in non-human mammals. The review is written with the objective of facilitating some discussion and some new thoughts regarding future research directions. The material is framed around four topics: (a) motor unit type, (b) rate coding and recruitment, (c) motor unit activity patterns, and (d) a compartment based view of pharyngeal airway control.     

Firing patterns of human genioglossus motor units during voluntary tongue movement

The tongue participates in a range of complex oromotor behaviors, including mastication, swallowing, respiration, and speech. Previous electromyographic studies of the human tongue have focused on respiratory-related tongue muscle activities and their role in maintaining upper airway patency. Remarkably, the activities of human hypoglossal motor units have not been studied during the execution of voluntary maneuvers. We recorded single motor unit activity using tungsten microelectrodes in the genioglossus muscle of 10 healthy human subjects performing both slow tongue protrusions and a static holding maneuver. Displacement of the tongue was detected by an isotonic transducer coupled to the lingual surface through a customized lever arm. For protrusion trials, the firing rate at recruitment was 13.1 +/- 3 Hz and increased steeply to an average of 24 +/- 6 Hz, often with very modest increases in tongue protrusion. For the static holding task, the average firing rate was 16.1 +/- 4 Hz, which is surprisingly high relative to limb motor units. The average coefficient of variation of interspike intervals was approximately 20% (range, 10-28%). These are the first recordings of their type obtained in human subjects and provide an initial glimpse into the voluntary control of hypoglossal motoneurons during tongue movements presumably instigated by activity in the motor cortex.     

Effect of caffeine on self-sustained firing in human motor units

This study examined the effect of caffeine on self-sustained firing (SSF) of human motor units. At physiological doses, caffeine acts as a competitive antagonist to the inhibitory effects of adenosine. This antagonism has many possible effects on the central nervous system. One of these effects is to increase the release of the excitatory neurotransmitters serotonin and noradrenaline. In addition, caffeine increases serotonin concentration in brainstem regions that have excitatory projections to spinal motor neurons. Since plateau potentials, which are responsible for SSF, are facilitated by these neurotransmitters, we hypothesized that caffeine would increase the frequency at which SSF occurs. A double-blind, repeated-measures design using either drug (6 mg kg⁻¹ caffeine) or placebo (flour) was carried out on seven male subjects who reported ingesting less than 200 mg week⁻¹ caffeine. We investigated the occurrence of SSF in tibialis anterior motor units (214 trials) and found a significant (   P < 0.05  ) increase in the occurrence of SSF in the caffeine trial (87.0 ± 5.8 %) compared to the placebo (64.6 ± 9.7 %). These data further verify the presence of SSF in the tibialis anterior motor units of young men and provide indirect evidence of the facilitation of plateau potentials by monoamines in the human neuromuscular system.     

Properties of human motor units after prolonged activity at a constant firing rate

The primary purpose of this study was to examine if there are changes in the intrinsic properties of spinal motoneurons after prolonged submaximal contractions. To do this, we assessed whether or not the synaptic drive to motoneurons needs to increase in order to maintain a constant firing rate of a motor unit. Recruitment of new units and an increase in total electromyographic (EMG) activity of the muscle of interest were taken as estimates of an increase in synaptic drive. Subjects were asked to maintain a constant firing rate of a clearly identifiable (targeted) motor unit from the first dorsal interosseous muscle for approximately 10 min, while surface EMG and force were recorded simultaneously. For the 60 units studied, the duration of the constant-firing-rate period ranged from 73 to 1,140 s (448 ± 227 s; mean ± SD). There was a significant increase (t-test, p<0.001) in the magnitude of mean surface EMG, and DC force while the targeted motoneuron maintained a constant rate suggesting an increase in the net excitatory input to the motoneuron pool. Changes occurring simultaneously in other parameters, namely, variability in interspike interval, magnitude of force fluctuations, the duration of motor unit action potentials, and the median power frequency of surface EMG were also computed. The firing rates of 16 concurrently firing motoneurons, not controlled by the subject, remained constant. The key finding of this study is that after prolonged activity, a motoneuron requires a stronger excitatory input to maintain its firing rate. Additional results are indicative of significant changes in the characteristics of the synaptic inputs, changes at the neuromuscular junction (both pre- and postsynaptic regions) and the sarcolemma.     

Changes in firing rate of human motor units during linearly changing voluntary contractions

1. Human subjects generated approximately linearly increasing or decreasing voluntary, isometric contractions using the first dorsal interosseus muscle of the hand.2. Single motor units began firing at 8.4+/-1.3 impulses/sec (mean +/- S.D. of an observation) and increased their firing rate 1.4+/-0.6 impulses/sec for each change of 100 g in voluntary force. These values were independent of the threshold force for recruiting motor units.3. At intermediate rates of increasing and decreasing voluntary force (one complete cycle every 10 sec) the firing rate of single motor units varied linearly with force over the entire range of forces studied. However, during slow increases in voluntary force, the firing rate tended to reach a plateau, while during rapid increases an initial train of impulses at a roughly constant rate was observed.4. The relative importance of recruitment and increased firing rate, as mechanisms for increasing the force of voluntary contraction, was determined. Only at low levels of force is recuitment the major mechanism. Increased firing rate becomes the more important mechanism at intermediate force levels and contributes the large majority of force if the entire physiological range is considered.     

Responses of constantly firing motor units to afferent stimulation

Constantly firing motor units of the short abductor muscles of the first finger in the human hand and the abdominal wall muscle in immobilized rats responded to afferent stimulation of the median and sciatic nerves respectively with changes in the nature of spike activity. In the first 250 msec of the post-stimulus period, the frequency of motor unit spike activity became unstable and peri-stimulus histograms were individually quite distinct. This was followed by relative stabilization of motor unit discharge frequencies, and the subsequently (750 msec) determined motor unit spike frequency depended on most cases on the background spike frequency. Department of Human and Animal Physiology, State University, Kazan'. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 1, pp. 25–32, January, 1996.     

Ia Afferent input alters the recruitment thresholds and firing rates of single human motor units

Vibration of the patellar tendon recruits motor units in the knee extensors via excitation of muscle spindles and subsequent Ia afferent input to the α-motoneuron pool. Our first purpose was to determine if the recruitment threshold and firing rate of the same motor unit differed when recruited involuntarily via reflex or voluntarily via descending spinal pathways. Although Ia input is excitatory to the α-motoneuron pool, it has also been shown paradoxically to inhibit itself. Our second purpose was to determine if vibration of the patellar tendon during a voluntary knee extension causes a change in the firing rate of already recruited motor units. In the first protocol, 10 subjects voluntarily reproduced the same isometric force profile of the knee extensors that was elicited by vibration of the patellar tendon. Single motor unit recordings from the vastus lateralis (VL) were obtained with tungsten microelectrodes and unitary behaviour was examined during both reflex and voluntary knee extensions. Recordings from 135 single motor units showed that both recruitment thresholds and firing rates were lower during reflex contractions. In the second protocol, 7 subjects maintained a voluntary knee extension at 30 N for approximately 40–45 s. Three bursts of patellar tendon vibration were superimposed at regular intervals throughout the contraction and changes in the firing rate of already recruited motor units were examined. A total of 35 motor units were recorded and each burst of superimposed vibration caused a momentary reduction in the firing rates and recruitment of additional units. Our data provide evidence that Ia input modulates the recruitment thresholds and firing rates of motor units providing more flexibility within the neuromuscular system to grade force at low levels of force production. Electronic Publication     

Bistable firing properties of soleus motor units in unrestrained rats

EMG recordings from single motor units in the soleus muscle were performed in alert unrestrained rats. A cuff electrode around the tibial nerve and subcutaneously placed electrodes in the foot permitted stimulation of afferent fibres. The movements of the rat and the simultaneous EMG activity were displayed together on a video monitor. Most motor units were tonically active for extended periods during quiet standing. During tonic discharge, maintained shifts between stable low (8-12 Hz; quartiles) and high (16-22.8 Hz) frequency ranges were initiated by short-lasting synaptic excitation of the motoneuron pool by stimulation of Ia afferents, or inhibition by stimulation of skin afferents. The shifts were not related to gross limb movements. This phenomenon is referred to as a bistable firing pattern. Bistable firing also occurred spontaneously during quiet standing. Typically the firing frequency shifted between a low (9-12.5 Hz) and a high (20-24.5 Hz) mode. During recordings of simultaneous activity in two units, spontaneous and stimulus-induced frequency jumps causing maintained changes in firing frequency were regularly seen to occur in one unit, while the frequency in the second unit was unchanged or only phasically influenced. These results demonstrate for the first time a bistable firing pattern during postural activity in the intact animal. The firing pattern closely resembles the bistable behaviour described in spinal motoneurons in reduced preparations, where it is due to the presence of a plateau potential. This suggests that the bistable firing is unexplained by plateau potentials also in the intact animal.     

Changes in the probability of firing of motor units following electrical stimulation in human limb muscles

Changes in the probability of motor unit firing was studied in ten different muscles (six muscles in the upper extremity and four muscles in the lower extremity) of eleven healthy human subjects. The responses were elicited by the electrical stimulation of cutaneous or mixed nerves during weak voluntary contraction of the muscle studied, and were recorded by averaging the rectified surface electromyogram. In eight of the ten muscles, well-detectable, short and long latency excitatory phases were observed. The most constant and well-identified excitatory responses were observed in the first interosseus dorsalis muscle in the hand, and in the extensor digitorum brevis muscle in the foot. These two distal muscles seem to be the most useful muscles for routine determination of the short and long latency responses to cutaneous stimulation.     

Activity of single motor units in attention-demanding tasks: firing pattern in the human trapezius muscle

Activity of single motor units in relation to surface electromyography (EMG) was studied in 11 subjects in attention-demanding work tasks with minimal requirement of movement. In 53 verified firing periods, single motor units fired continuously from 30 s to 10 min (duration of the experiment work task) with a stable median firing rate in the range of 8–13 Hz. When the integrated surface EMG were stable, the motor units identified as a rule were continuously active with only small modulations of firing rate corresponding to low-amplitude fluctuations in surface EMG. Marked changes in the surface EMG, either sudden or gradual, were caused by recruitment or derecruitment of motor units, and not by modulations of the motor unit firing rate. Motor unit firing periods (duration 10 s-35 s) in low-level voluntary contractions (approximately 1%–5% EMG_max) performed by the same subjects showed median firing rates (7–12 Hz) similar to the observations in attention-related activation.     

Firing patterns of human flexor carpi radialis motor units during the stretch reflex

Single motor unit and gross surface electromyographic responses to torque motor-produced wrist extensions were studied in human flexor carpi radialis muscle. Surface EMG typically showed two "periods" of reflex activity, at a short and long latency following stretch, but both periods occurring before a subject's voluntary reaction to the stretch. The amplitude of EMG activity in both reflex periods increased monotonically with an increase in the torque load. The amplitude of the short-latency reflex response was very dependent on the motoneuron pool excitability, or preload. The amplitude of the long-latency reflex response also varied with the preload, but could, in addition, be modulated by the subject's preparatory set for a voluntary response to the imposed displacement. When a single motor unit that was not tonically active began to fire during the stretch reflex, it did so primarily during the long-latency period. When caused to fire repetitively by voluntary facilitation of the motoneuron pool, that same unit now showed activity during both periods of the stretch reflex. Further increases in either motoneuron pool facilitation or in perturbation strength resulted in a monotonic increase in response probability of a single motor unit during the short-latency period. However, the response probability of a single unit during the long-latency reflex period did not always vary in a monotonic way with increases in either torque load or motoneuron pool facilitation. For an additional series of experiments, the subject was instructed on how to respond voluntarily to the upcoming wrist perturbation. The three instructions to the subject had no effect on the response probability of a single motor unit during either the background or short-latency periods of the stretch reflex. However, prior instruction clearly affected a unit's response probability during the long-latency reflex period. Changes in the firing rate of motor units, and in the recruitment or derecruitment of nontonic units, contributed to this modulation of reflex activity during the long-latency period.     

The number of active motor units and their firing rates in voluntary contraction of human brachialis muscle

To make clear the control mechanism of force generation in human muscle, the electrical activity of the brachialis muscle was studied at various levels of contraction force by recording single motor unit discharges as well as mass electromyograms (EMGs). The firing rate of motor units increased with force along an S-shaped curve. At low levels of force, motor units increased their firing rates steeply with force. At intermediate levels of force, each motor unit increased its firing rate linearly with force at lower rates. As the maximum of force was approached, the firing rate increased very steeply, reaching as high as 50 Hz or more. By applying a new method of statistical processing to mass EMGs, the number of active motor units and the size of action potential were estimated at each level of force. The number of active motor units increased monotonously with muscle force. Motor units recruited at high levels of force had larger amplitudes of action potentials than those recruited at lower levels. Calculations were made to determine how the relative contribution to an increase in muscle force is varied between recruitment and the increase in firing rate. The contribution of recruitment gradually decreased with the increase in force. Up to about 70% of the maximum force, recruitment is the major mechanism for increasing the force of contraction.     

Validating motor unit firing patterns extracted by EMG signal decomposition

Motor unit (MU) firing pattern information can be used clinically or for physiological investigation. It can also be used to enhance and validate electromyographic (EMG) signal decomposition. However, in all instances the validity of the extracted MU firing patterns must first be determined. Two supervised classifiers that can be used to validate extracted MU firing patterns are proposed. The first classifier, the single/merged classifier (SMC), determines whether a motor unit potential train (MUPT) represents the firings of a single MU or the merged activity of more than one MU. The second classifier, the single/contaminated classifier (SCC), determines whether the estimated number of false-classification errors in a MUPT is acceptable or not. Each classifier was trained using simulated data and tested using simulated and real data. The accuracy of the SMC in categorizing a train correctly is 99% and 96% for simulated and real data, respectively. The accuracy of the SCC is 84% and 81% for simulated and real data, respectively. The composition of these classifiers, their objectives, how they were trained, and the evaluation of their performances using both simulated and real data are presented in detail.     

Synchronous discharges in pairs of steadily firing motor units tend to form clusters

We observed the excitatory effects of thyrotropin-releasing hormone (TRH) on isolated, intraarterially perfused spinal cords of frogs. TRH (10(-7)-10(-3) M) produced a transient depolarization and potentiated the spontaneous activities in both the ventral and dorsal roots. The TRH effects were related to both direct and indirect actions, and Na+ deficiency attenuated the direct actions. Serotonin was the only neurotransmitter candidate with which TRH exhibited an interaction. Iproniazid potentiated the TRH effects, in normal Ringer's solution. These results indicate that the TRH depolarization due to direct actions is Na+ dependent, and that indirect actions involve an interaction with a monoaminergic pathway.