Discharge Patterns of Human Genioglossus Motor Units during Arousal from Sleep

Study Objectives:

Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle''s activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern.

Design:

Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion 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:

138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal.

Conclusions:

Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, ∼20% of units active before arousals stopped firing.

Citation:

Wilkinson V; Malhotra A; Nicholas CL; Worsnop C; Jordan AS; Butler JE; Saboisky JP; Gandevia SC; White DP; Trinder J. Discharge patterns of human genioglossus motor units during arousal from sleep. SLEEP 2010;33(3):379-387.     

Motor unit recruitment in human genioglossus muscle in response to hypercapnia

Study Objectives:

Single motor unit recordings of the genioglossus (GG) muscle indicate that GG motor units have a variety of discharge patterns, including units that have higher discharge rates during inspiration (inspiratory phasic and inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do not modify their rate with respiration (tonic). Previous studies have shown that an increase in GG muscle activity is a consequence of increased activity in inspiratory units. However, there are differences between studies as to whether this increase is primarily due to recruitment of new motor units (motor unit recruitment) or to increased discharge rate of already active units (rate coding). Sleep-wake state studies in humans have suggested the former, while hypercapnia experiments in rats have suggested the latter. In this study, we investigated the effect of hypercapnia on GG motor unit activity in humans during wakefulness.

Setting:

Sleep research laboratory.

Participants:

Sixteen healthy men.

Measurements and Results:

Each participant was administered at least 6 trials with P_etCO₂ being elevated 8.4 (SD = 1.96) mm Hg over 2 min following a 30-s baseline. Subjects were instrumented for GG EMG and respiratory measurements with 4 fine wire electrodes inserted subcutaneously into the muscle. One hundred forty-one motor units were identified during the baseline: 47% were inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory related modulation. Sixty-two new units were recruited during hypercapnia. The distribution of recruited units was significantly different from the baseline distribution, with 84% being inspiratory modulated (P < 0.001). Neither units active during baseline, nor new units recruited during hypercapnia, increased their discharge rate as P_etCO₂ increased (P > 0.05 for all comparisons).

Conclusions:

Increased GG muscle activity in humans occurs because of recruitment of previously inactive inspiratory modulated units.

Citation:

Nicholas CL; Bei B; Worsnop C; Malhotra A; Jordan AS; Saboisky JP; Chan JKM; Duckworth E; White DP; Trinder J. Motor unit recruitment in human genioglossus muscle in response to hypercapnia. SLEEP 2010;33(11):1529-1538.     

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 low-threshold trapezius motor units in feedback-controlled contractions and vocational motor activities

The study aimed to examine firing patterns of low-threshold trapezius motor units, with attention given to motor unit recruitment threshold. Different motor tasks were explored: shoulder elevation, arm movement in typing, and the motor response to mental stress. Contraction amplitudes in the range from 1 to 10% of the surface electromyographic (SEMG) signal at maximal voluntary contraction (1–10% EMG_max) were studied, representing the range of trapezius muscle activity commonly observed in daily living. Single motor unit activity was recorded by a quadrifilar fine-wire electrode. A surface electrode simultaneously recorded the SEMG signal. Low-threshold motor units showed a small increase in mean firing rate, from 10.5 to 12.5 pulses per second (p<0.01), in constant-amplitude contractions when SEMG amplitude increased from <2% to >4% EMG_max. After the first few minutes, firing rates were similar for all motor units in a contraction, despite different recruitment thresholds. Firing rates of motor units with threshold <2% EMG_max were the same in constant-amplitude contractions, contractions with vocational arm movement, and contractions with imposed stress for SEMG amplitude at the same level. High-frequency firing patterns were observed in dynamic contractions, limited to bursts of up to a second duration. We conclude that low-threshold trapezius motor units have similar, stable firing rates in sustained contractions, independent of task and recruitment threshold, but with a small increase for increasing contraction amplitude.     

Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy

Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN) from wake to sleep contributes to this reduced activity. Several awake–active neurotransmitters with inputs to the HMN (e.g. serotonin [5-HT]) inhibit K⁺ leak mediated by TASK-1/3 channels on hypoglossal motoneurons, leading to increased neuronal activity in vitro. We hypothesize that TASK channel inhibition at the HMN will increase tongue muscle activity in vivo and modulate responses to 5-HT. We first microperfused the HMN of anesthetized rats with TASK channel inhibitors: doxapram (75 μM, n = 9), A1899 (25 μM, n = 9), ML365 (25 μM, n = 9), acidified artificial cerebrospinal fluid (ACSF, pH = 6.25, n = 9); and a TASK channel activator terbinafine (50 μM, n = 9); all with and without co-applied 5-HT (10 mM). 5-HT alone at the HMN increased tongue motor activity (202.8% ± 45.9%, p < 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p > 0.716) or responses to 5-HT (p > 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p > 0.05) between ChAT-Cre:TASK^f/f mice (n = 8) lacking TASK-1/3 channels on cholinergic neurons versus controls (n = 10). In freely behaving rats (n = 9), microperfusion of A1899 into the HMN increased within-breath phasic tongue motor activity in wakefulness only (p = 0.005) but not sleep, with no effects on tonic activity across all sleep–wake states. Together, the findings suggest robust maintenance of tongue motor activity despite various strategies for TASK channel manipulation targeting the HMN in vivo, and thus currently do not support this target and direction for potential OSA pharmacotherapy.     

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.     

Changes in excitability of motor units during preparation for movement

Summary Single biceps motor units were recorded in two awake monkeys (Macaca fascicularis) during the preparation for and execution of a forearm flexion movement. The motor sequence was organized as follows: after a control period lasting 500 ms, the animal was informed that a preparatory period (PP) was beginning by a preparatory signal (PS) consisting of diffuse sound and light. One to 1.5 s later, the animal was instructed by a bright light response signal (RS) to perform a rapid forearm flexion movement. Two hundred motor sequences were run during each daily session. The single motor units (MU) were recorded and their discharges analysed. In both monkeys, two extreme groups were found to exist on the basis of their pattern of activity during the preparatory and movement execution phases. 56% of the MUs were silent during the PP and showed a brief burst of discharge after the RS, which was strictly correlated to the movement execution. Their high recruitment threshold and their firing frequency during resting and movement periods suggested that these MUs associated with the movement execution could be called presumed fast or phasic MUs. Among the remaining MUs (44%), 15% were active as early as the beginning of the PP (about 300 ms after the PS) and showed a progressively increasing discharge, which stopped just after the beginning of the movement execution. These MUs associated with the preparatory phase had low recruitment thresholds and firing frequencies, which is compatible with the possibility that they might be slow or tonic MUs. Two functional hypotheses can be proposed on the basis of these results. The first is that the presumed slow MUs associated with the preparatory period might modify the physiological state of the muscle, increasing its stiffness and thus enhancing the efficiency of the fast phasic MUs activated during the triggering of rapid movements. This would shorten the reaction time and make it possible to perform the fast movements required in these experiments. The second hypothesis is that the slow MUs may contribute to building up the nervous activity responsible for the forthcoming movement; and more specifically, to controlling the excitability of central neurons producing a phasic discharge which might activate the presumed fast MUs.     

The length-force relationship of the human genioglossus in patients with obstructive sleep apnea

During sleep, patients with obstructive sleep apnea (OSA) have repetitive episodes of upper airway collapse, which are terminated by increased activity of upper airway dilator muscles. The repetitive activation of the genioglossus (GG) may result in muscle remodeling. We hypothesized that OSA patients have an altered length-force relationship, increased force generation and/or decreased force maintenance as compared with control subjects. The GG length-force relationship was determined in 12 patients with OSA and 12 normal control subjects. The optimum length of the GG (LO) was at a longer muscle length in OSA patients than in control subjects. At longer muscle lengths, OSA patients produced greater percentages of their maximum protrusion force than control subjects. Force maintenance was not significantly different between the two groups. We conclude that in OSA patients relative to normal controls, the length-force relationship of the GG is altered, specifically at longer muscle lengths. We speculate that the GG is remodeled in OSA patients and that this facilitates airway re-opening to terminate obstructive events.     

Synchronization of human leg motor units during co-contraction in man

Cross-correlograms were constructed from the spike trains of pairs of individual motor units recorded from the tibialis anterior (TA) and soleus (Sol) muscles. In most correlograms the synchronization consisted of a central peak with a short duration. When the motor units were recorded from the same muscle this synchronization was seen in almost 100% of the cases (TA 92%, Sol 89%) and the peak of synchronization was large (TA 0.060 extra sample spikes per trigger spike, Sol 0.030). In contrast, clear peaks of short duration synchronization was seen in only 4 out of 30 antagonistic TA and Sol motor unit pairs (0.025 extra sample spikes per trigger spike). In another 4 motor unit pairs central troughs were seen. In approximately 10% of all combinations of motor unit pairs a low-amplitude long-duration synchronization was seen. This type of synchronization was seen either as the only type of synchronization or at the same time as the short-duration synchronization. Finally, secondary peaks on both sides of the central peak were seen in a few cases.The distance between the sites of recording of TA motor unit pairs was systematically varied. The latency of the short-duration synchronization became longer and the amount of synchronization smaller the longer the distance between the recording sites. The amount of synchronization of two motor units recorded from the same muscle was shown to be larger when the muscle was activated in co-contraction rather than in an isolated agonist movement. The results are discussed in relation to the organization of the descending command eliciting co-contraction.