Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males

During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative-pressure reflex that may be diminished in sleep. Previous studies have assessed the negative-pressure reflex using multi-unit, rectified, moving-time-average EMG recordings during brief pulses of negative upper-airway pressure. However, moving-time averaging probably obscures the true time-related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re-examine the genioglossus negative-pressure reflex in detail, without moving-time averaging. Bipolar fine-wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative-pressure stimuli (∼−10 cmH₂O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble-averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26 ± 1 ms; peak amplitude 231 ± 29% of baseline) followed by a previously unreported suppression (peak latency 71 ± 4 ms; 67 ± 8% of baseline). Single-motor-unit activity, clearly identifiable in ∼10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26 ± 9 ms, P = 0.01). Genioglossus negative-pressure reflex morphology and amplitude of the initial peak were maintained in non-rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative-pressure reflex which are differentially affected by state.     

Modulation of Genioglossus Muscle Activity Across Sleep-Wake States by Histamine at the Hypoglossal Motor Pool

Study Objectives:

Histamine neurons comprise a major component of the aminergic arousal system and significantly influence sleep-wake states, with antihistamines widely used as sedative hypnotics. Unlike the serotonergic and noradrenergic components of this arousal system, however, the role of histamine in the central control of respiratory motor activity has not been determined. The aims of this study were to characterize the effects of histamine receptor agonists and antagonists at the hypoglossal motor pool on genioglossus muscle activity across sleep and awake states, and also determine if histamine contributes an endogenous excitatory drive to modulate hypoglossal motor outflow to genioglossus muscle.

Design, Participants, and Interventions:

Thirty-three rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states, and genioglossus and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the hypoglossal motor nucleus.

Measurements and Results:

Histamine at the hypoglossal motor nucleus significantly increased tonic genioglossus muscle activity in wakefulness, non-REM sleep and REM sleep. The activating effects of histamine on genioglossus muscle activity also occurred with a histamine type-1 (H₁) but not H₂ receptor agonist. However, H₁ receptor antagonism at the hypoglossal motor nucleus did not decrease genioglossus muscle activity in wakefulness or sleep.

Conclusions:

The results suggest that histamine at the hypoglossal motor pool increases genioglossus muscle activity in freely behaving rats in wakefulness, non-REM, and REM sleep via an H₁ receptor mechanism.

Citation:

Bastedo T; Chan E; Park E; Liu H; Horner RL. Modulation of genioglossus muscle activity across sleep-wake states by histamine at the hypoglossal motor pool. SLEEP 2009;32(10):1313-1324.     

Brief airway occlusion produces prolonged reflex inhibition of inspiratory muscles in obstructive sleep apnea

STUDY OBJECTIVES: The human inspiratory muscles respond to a brief occlusion of the upper airway during inspiration with a profound short-latency reflex inhibition. This inhibition contrasts with the excitatory stretch reflex of limb muscles and may protect the airway from aspiration. It was postulated that this reflex would be altered in subjects with obstructive sleep apnea (OSA) who have repetitive upper airway occlusion. DESIGN: Subjects underwent overnight polysomnography, as well as muscle reflex studies. For the reflex studies (performed during wakefulness), occlusions lasting 250 milliseconds were delivered during inspiration. Surface electromyogram was recorded over the scalenes, parasternal intercostals, and chest wall (overlying diaphragm). SETTING: Research and sleep laboratories. PARTICIPANTS: Nineteen subjects with untreated OSA (9 moderate and 10 severe) and 9 healthy control subjects. MEASUREMENTS AND RESULTS: In the subjects with severe OSA, the duration of the inhibition was prolonged by at least 25% compared with control subjects. The peak of the inhibitory response for scalenes occurred significantly later for subjects with severe OSA than for control subjects (by 76 +/- 5 ms vs 60 +/- 3 ms [mean +/- SEM], respectively). Onset latencies of the later excitatory response were delayed for scalenes, parasternal intercostals, and chest wall recordings (eg, scalenes: 105 +/- 9 ms for subjects with severe OSA vs 83 +/- 5 ms for control subjects). CONCLUSIONS: The latency of peak inhibition and duration of inhibition were positively correlated with the respiratory disturbance index for all muscle groups. These changes may reflect adaptation in central respiratory paths due to repetitive loading during sleep.     

The human genioglossus response to negative airway pressure: stimulus timing and route of delivery

The genioglossus reflex response to sudden onset pulses of negative airway pressure (NAP) in humans is reported to occur more commonly at end rather than onset of expiration when delivered via a mouthpiece. We examined whether this response was modulated by the route of stimulus delivery throughout the respiratory cycle. The genioglossus surface EMG (GGsEMG) response to NAP delivered randomly throughout the respiratory cycle was measured in a set of experiments: (i) 40 stimuli of NAP at -5, -7.5 and -10 cmH2O applied to eight healthy, awake, supine males via nose-mask; and (ii) 60 stimuli of -7.5 cmH2O NAP applied to 15 subjects via both nose-mask and mouthpiece in random order. Despite similar pressure changes being detected in the epiglottis during both routes of stimulus delivery, far lower pressure changes were measured at the nasal choanae during mouthpiece compared with nose-mask delivery. There were no significant differences between the responses during any phase of respiration, nor when NAP was delivered via nose-mask or mouthpiece. We conclude that the sensitivity of the GGsEMG response to NAP in humans does not vary significantly with phase of respiration or route of breathing.     

Genioglossal muscle response to CO2 stimulation during NREM sleep

STUDY OBJECTIVES: The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness. DESIGN: We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position. SETTING: Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital. PATIENTS OR PARTICIPANTS: Eleven normal healthy subjects. INTERVENTIONS: During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level. MEASUREMENTS AND RESULTS: We observed that CO2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs. 10.2 +/- 3.1% of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP). CONCLUSIONS: We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep.     

Inspiratory muscle responses to airway occlusion during learned breathing movements

Respiratory muscle responses to sudden obstruction of learned breathing movements were studied in seven normal adults. Subjects were trained to inspire at a constant rate (0.4 liters/s), or maintain a static inspiratory effort(-10 cmH2O). On each trial these efforts were loaded unpredictably by occluding the airway or applying an opposing negative pressure at the mouth. Surface EMGs were recorded from the neck, parasternal intercostal, pectoral, diaphragmatic, and abdominal muscles. The latency and pattern of the responses to occlusion or to negative pressure were obtained from 10-trial computer-averaged records. When subjects were trained to relax in response to loading, inhibitory responses (mean latency: 32 ms) were recorded from the neck (16 out of 21 10-trial averages), diaphragm (9 out of 21), and parasternal (3 out of 21) locations. Excitatory responses (mean latency: 69 ms) were also recorded from the neck (11 out of 21 10-trial averages), diaphragm (8 out of 21), and parasternal (1 out of 21) sites. These responses were also observed in many single trial records. When subjects were trained to make an additional inspiratory effort as quickly as possible after loading, the reaction was a high-amplitude EMG burst, sometimes preceded by a brief inhibitory response. The mean reaction times for the large bursts were: 70 ms for the neck, 86 ms for the diaphragm, and 91 ms for the parasternal intercostals. Latencies in the 60- to 70-ms range were found on many 10-trial averages. Because the latencies of the excitatory responses evoked when subjects were trained to relax in response to loading were similar to those of the EMG bursts recorded when subjects were trained to react quickly in response to loading, it is not possible to distinguish long-latency reflex and learned response components on the basis of latency alone. Previous work, which has assumed that responses in the 50- to 70-ms latency range must be reflexive rather than learned, may need to be reexamined.     

Effects of sleep on the tonic drive to respiratory muscle and the threshold for rhythm generation in the dog.

1. The present study was designed to determine the effect of sleep on the tonic output to respiratory muscle and on the level of chemical respiratory stimulation required to produce rhythmic respiratory output. 2. Chronically implanted electrodes recorded expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic (EMG) activities in three trained dogs during wakefulness and sleep. The dogs were mechanically hyperventilated via an endotracheal tube inserted into a permanent tracheostomy. During the studies, a cold block of the cervical vagus nerves was maintained to avoid the complicating effects of vagal inputs on respiratory drive and rhythm. 3. During wakefulness, steady-state hypocapnia (partial pressure of CO2, PCO2 = 30 mmHg) abolished inspiratory EMG activity, resulting in apnoea, but the expiratory muscle became tonically active. Compared to wakefulness, the level of the tonic expiratory EMG activity was decreased in non-REM (non-rapid eye movement) sleep (median decrease = 34%, P = 0.005) and was further decreased in REM sleep (median decrease = 78%, P < 0.0001). During REM sleep, the tonic expiratory EMG activity was highly variable (mean coefficient of variation = 39% compared to 7% awake, P < 0.0001) and in some periods of REM, bursts of inspiratory EMG activity and active breathing movements were observed despite the presence of hypocapnia. 4. During constant mechanical hyperventilation, progressive increases in arterial PCO2 (in hyperoxia) were produced by rebreathing. Measurement of the CO2 threshold for the onset of spontaneous breathing showed that this threshold was not different between wakefulness and non-REM sleep (mean difference = 0.1 mmHg from paired observations, 95% confidence interval for the difference = -1.0 to +1.1 mmHg, P = 0.898). 5. The results show that sleep reduces the tonic output to respiratory muscles but does not increase the CO2 threshold for the generation of rhythmic respiratory output. These observations suggest that changes in the tonic drives to the respiratory motoneurones may be a principal mechanism by which changes in sleep-wake states produce changes in respiratory output.     

Pentobarbital sedation increases genioglossus respiratory activity in sleeping rats

OBJECTIVE: To determine whether certain sedatives may, by increasing arousal threshold, allow pharyngeal dilator muscle activity to increase more in response to chemical stimuli before arousal occurs. DESIGN, PARTICIPANTS AND INTERVENTIONS: Thirteen chronically instrumented rats were studied during sleep following injections of placebo or sedating doses of pentobarbital (10 mg/kg). Intermittently, inspired CO2 was increased gradually until arousal occurred. MEASUREMENTS AND RESULTS: Maximum genioglossus activity reached before arousal was higher with pentobarbital than placebo (34.5 +/- 24.3 vs 3.7 +/- 2.9mV; P < 0.001) for 2 reasons. First, genioglossus activity was greater during undisturbed sleep before CO2 was applied (23.3 +/- 15.3 vs 2.5 +/- 1.5 mV, P < 0.001). When sleep periods were long, a ramp-like increase in genioglossus activity (GG-Ramp) began and progressed until arousal. GG-Ramps developed with both placebo and pentobarbital but reached higher levels with pentobarbital due to longer sleep periods and faster increase in genioglossus activity during the ramp. GG-Ramps began when diaphragm activity was lowest and progressed despite unchanged diaphragm activity. Second, as hypothesized, the increase in genioglossus activity with CO2 before arousal was greater than with placebo (11.2 +/- 2.5 vs 1.2 +/- 2.5mV; P < 0.05) due to increased arousal threshold. In 27 of 126 CO2 challenges delivered while GG-Ramps were in progress, genioglossus activity paradoxically decreased despite increased diaphragmatic activity. These negative responses occurred randomly in 7 of 13 rats. CONCLUSIONS: In rats: 1) Sedatives may allow genioglossus activity to reach higher levels during sleep. 2) A time-dependent increase in genioglossus activity occurs during undisturbed sleep that is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of genioglossus activity under currently unidentified circumstances.     

Respiratory-related evoked potentials during the transition from alpha to theta EEG activity in Stage 1 NREM sleep

It has been argued previously that evoked potential components during Stage 1 sleep in response to both auditory and respiratory stimuli are intermediate between those of wakefulness and Stage 2 sleep. However, state fluctuations in the ECG between alpha and theta during Stage 1 sleep have been linked to changes in a number of respiratory functions including ventilation, upper airway resistance and chemical drive. It was therefore hypothesized that if respiratory related evoked potentials (RREP) were averaged separately for alpha and theta EEG periods during Stage 1 sleep, the alpha RREP would resemble wakefulness and the theta RREP would resemble Stage 2 sleep. RREPs were produced by 250 ms occlusions in 10 subjects. EEG was recorded from 29 scalp sites, referenced to linked ears, together with EOG and EMG. The N1 component was not specifically associated with alpha vs. theta activity, but appeared to be sensitive to any decrease in arousal level, suggesting that it was more related to attention than to changes in the EEG. The late N2 and P300 components were present during wake and Stage 1 alpha. However, in Stage 1 theta, different late components emerged (N300 and P450) that differed in latency, amplitude or topographical distribution from those seen in wakefulness. The P2 proved difficult to interpret, whereas the N550 did not appear until Stage 2 sleep, and as such, was not dependent on alpha/theta state. The results indicate that RREP components are differentially affected by the transition into sleep.     

The cardiorespiratory activation response at an arousal from sleep is independent of the level of CO(2)

Arousal from sleep is associated with transient cardiorespiratory activation. Traditionally, this response has been understood to be a consequence of state-dependent changes in the homeostatic control of ventilation. The hypothesis predicts that the magnitude of ventilatory and cardiac responses at an arousal will be a function of the intensity of concurrent respiratory stimuli (primarily PCO(2)). Alternatively, it has been proposed that increased cardiorespiratory activity is due to reflex activation. This hypothesis predicts that the magnitude of the cardiorespiratory response will be independent of respiratory stimuli. To compare these hypotheses we measured minute ventilation (V(i)), heart rate (HR) and blood pressure (BP) during wakefulness and stage 2 sleep, while manipulating P(et)CO(2). Further, we assessed the magnitude of the response of these variables to an arousal from sleep at the various levels of P(et)CO(2). The subjects were male aged 18-25 years. P(et)CO(2) was manipulated by clamping it at four levels during wakefulness [wake eucapnic, sleep eucapnic (Low), and sleep eucapnic +3 mmHg (Medium) and +6 mmHg (High)] and three levels during sleep (Low, Medium and High). The average number of determinations for each subject at each level was 14 during wakefulness and 25 during sleep. Arousals were required to meet American Sleep Disorders Association criteria and were without body movement. The results indicated that average increases in V(i), HR and BP at arousal from sleep did not significantly differ as a function of the level of P(et)CO(2) present at the time of the arousal (all P > 0.05). Further, the magnitude of the ventilatory response to an arousal was significantly less than the values predicted by the homeostatic hypothesis (P < 0.05). We conclude that, in normal subjects, the cardiorespiratory response to an arousal from sleep is not because of a homeostatic response, but of a reflex activation.     

Usefulness of phrenic nerve stimulation to measure upper airway collapsibility in normal awake subjects

Upper airway (UA) collapsibility can be characterized during sleep by looking at the changes in inspiratory flow limitation (IFL) with changing nasal pressure. IFL can be induced during wakefulness using phrenic nerve stimulation (PNS) applied during exclusive nasal breathing. The aim of the study was to evaluate the possibility of measuring UA critical pressure (Pcrit) in normal awaked subjects using electrical PNS (EPNS) or bilateral anterior magnetic phrenic stimulation (BAMPS). Instantaneous flow, esophageal (Peso) and mask pressures (Pmask), and genioglossal (GG) end-expiratory EMG activity were recorded in 13 normal subjects (4F, 9M) with randomly changing Pmask (0 to -20 cmH2O). For each trial, we examined the relationship between maximal inspiratory flow (Vtmax) of IFL twitches and the corresponding Pmask. Pcrit could be determined in 12 subjects (mean -33.5 +/- 16.3 cmH2O). No difference in Pcrit values was found between the EPNS and BAMPS methods but the strength of the Vtmax/Pmask relationship was higher with BAMPS. GG end-expiratory EMG activity increased with decreasing Pmask but no significant relationship was found between the slope of the GG end-expiratory EMG activity/Pmask relationship and Pcrit. We conclude that: (1) Pcrit can be measured during wakefulness in normal using PNS: (2) Pcrit measurements may be easier and more reliable with BAMPS than EPNS: and (3) Pcrit does not seem to be influenced by the pressure-related changes in GG end-expiratory EMG.     

Sleep/wake firing patterns of human genioglossus motor units

Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the "wakefulness" input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (eta(2)) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.     

Electromyographic responses to constant position errors imposed during voluntary elbow joint movement in human

The role of reflexes in the control of stiffness during human elbow joint movement was investigated for a wide range of movement speeds (1.5–6 rad/s). The electromyographic (EMG) responses of the elbow joint muscles to step position errors (step amplitude 0.15 rad; rise time 100 ms) imposed at the onset of targeted flexion movements (1.0 rad amplitude) were recorded. For all speeds of movement, the step position disturbance produced large modulations of the usual triphasic EMG activity, both excitatory and inhibitory, with an onset latency of 25 ms. In the muscles stretched by the perturbation, the early EMG response (25–60 ms latency) magnitude was greater than 50% of the activity during the unperturbed movements (background activity). In all muscles the EMG responses integrated over the entire movement were greater than 25% of the background activity. The responses were relatively greater for slower movements. Perturbations assisting the movement caused a short-latency (25–60 ms) reflex response (in the antagonist muscle) that increased with movement speed and was constant as a percentage of the background EMG activity. In contrast, perturbations resisting the movement caused a reflex response (in the agonist muscle) that was of the same absolute magnitude at all movement speeds, and thus decreased with movement speed as a percentage of the background EMG activity. There was a directional asymmetry in the reflex response, which produced an asymmetry in the mechanical response during slow movements. When the step perturbation occurred in a direction assisting the flexion movement, the antagonist muscle activity increased, but the main component of this response was delayed until the normal time of onset of the antagonist burst. When the step perturbation resisted the movement the agonist muscles responded briskly at short latency (25 ms). A reflex reversal occurred in two of six subjects. A fixed reflex response occurred in the antagonist muscle, regardless of the perturbation direction. For the extension direction perturbations (resisting movement), this response represented a reflex reversal (50 ms onset latency) and it caused the torque resisting the imposed step (stiffness) to drop markedly (below zero for one subject). Reflex responses were larger when the subject was prevented from reaching the target. That is, when the perturbation remained on until after the normal time of reaching the target, the EMG activity increased, with a parallel increase in stiffness. Similarly, when the perturbations prevented the subject from reaching the target during a 1-rad voluntary cyclic movement, the EMG and stiffness increased markedly. Coactivation of the antagonist muscle with the agonist muscle was not prominent (<30% of antagonist activity) during unperturbed movements. The perturbations were resisted with reciprocal activity, and thus reflex action did not increase the coactivation. However, as a result of the low-pass properties of muscle, substantial cocontraction of the agonist and antagonists muscle forces may have occurred during rapid movements, thus leading to increased stiffness. As the relative changes in normal EMG activity produced by the perturbation were often comparable with the changes in mean muscle torque (stiffness) reported in the first paper of this series, we conclude that the action of reflexes produced a significant portion of the resistance to perturbations. This reflexive portion was greater for slower movements, it was greater when the subject neared the target, and it was variable according to the perturbation direction and the particular subject. Given that the perturbations were of similar frequency content to the movement itself (though of smaller amplitude) and that the reflexes contributed substantially to the resistance to these perturbations, we suggest that in normal unperturbed movements the observed EMG is likewise substantially determined by the reflex activity.     

Electromyographic activity at the base and tip of the tongue across sleep–wake states in rats

Obstructive sleep apnea (OSA) patients have elevated tonic and phasic inspiratory activity in the genioglossus and other upper airway muscles during wakefulness; this protects their upper airway from collapse. In this group, sleep-related decrements of upper airway motor tone result in sleep-related upper airway obstructions. We previously reported that in the rat, a species widely used to study the neural mechanisms of both sleep and breathing, lingual electromyographic activity (EMG) is minimal or absent during slow-wave sleep (SWS) and then gradually increases after the onset of rapid eye movement sleep (REMS) due to the appearance of large phasic bursts. Here, we investigated whether sleep–wake patterns and respiratory modulation of lingual EMG depend on the site of EMG recording within the tongue. In nine chronically instrumented rats, we recorded from 17 sites within the tongue and from the diaphragm across sleep–wake states. We quantified lingual EMG in successive 10 s intervals of continuous 2 h recordings (1–3 p.m.). We found that sleep–wake patterns of lingual EMG did not differ between the base and tip of the tongue, and that respiratory modulation was extremely rare regardless of the recording site. We also determined that the often rhythmic lingual bursts during REMS do not occur with respiratory rhythmicity. This pattern differs from that in OSA subjects who, unlike rats, have collapsible upper airway, exhibit prominent respiratory modulation of upper airway motor tone during quiet wakefulness, retain considerable tonic and inspiratory phasic activity during SWS, and show nadirs of activity during REMS.     

Lip muscle reflex and intentional response levels in a simple speech task

Summary Sensorimotor integration in human lip muscle was studied by recording muscle activity while subjects produced simple speech utterances in response to mechanical stimulation. On each trial subjects were instructed either to produce the syllable pa or not respond when they detected movement of a small paddle held between the lips. Mechanical stimuli were adequate to elicit reflexes over poststimulus intervals of 15–30 ms (R1) and 30–50 ms (R2). EMG recordings were obtained from upper and lower lip muscles, and EMG levels were calculated for individual trials over several poststimulus time intervals. The independent effects of stimulus magnitude, prestimulus EMG, and reaction time on poststimulus response levels were assessed using multiple regression analysis. R1 and R2 levels were positively correlated with stimulus magnitude, but stimulus magnitude had little modulating effect on intentional lip muscle responses. Both reflex and intentional response levels showed positive associations with prestimulus EMG level. Instructional set had significant modulating effects on reflex responses in 9 of 10 subjects, but the nature of these effects varied among subjects. These various findings are discussed in relation to similar studies on limb motor systems and lip motor control for speech.     

Postural effects on pharyngeal protective reflex mechanisms

STUDY OBJECTIVES: Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion. DESIGN: We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses. SETTING: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. SUBJECTS/PARTICIPANTS: 17 normal subjects. MEASUREMENTS AND RESULTS: We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness. CONCLUSION: We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.     

Effects of local and remote muscle pain on human jaw reflexes evoked by fast stretches at different clenching levels

Muscle pain imposes significant changes on natural motor tasks, but the consequences for stretch reflexes are still disputed. The present study examined the jaw reflexes to fast (10 ms) stretches of the mandible in an experimental model with local pain in the masseter muscle and remote pain in the tibialis anterior muscle. The stretch reflexes were elicited in healthy volunteers (n=13) before, during, and after periods with constant levels of experimental pain and while the subjects clenched at 0%, 15%, 30%, and 45% of the maximal voluntary contraction (MVC) levels. Surface electromyography (EMG) was used to record the reflex responses. Pain in the masseter muscle (mean ± SEM, 3.8±0.4 on a 10-cm visual analogue scale), but not in the tibialis anterior muscle (3.4±0.3; paired t-test, P=0.318) was associated with significant changes in both prestimulus EMG activity (ANOVA, P=0.002) and in peak-to-peak amplitudes of the stretch reflex (ANOVA, P=0.022). However, when the changes in prestimulus EMG activity were taken into consideration a significant increase in the stretch reflex persisted in the painful muscle at 15% and 30% MVC. Local circuits at the trigeminal level involving the fusimotor system are proposed to mediate a significant part of this modulatory effect. Electronic Publication     

Chemosensory induced arousals during sleep in premenopausal women

Only a limited number of studies is available addressing chemosensory stimulation during sleep. Recent work indicates that stimulation with a nasal irritant produces an increase in arousal frequency in non-REM sleep, whereas a selective olfactory stimulant does not. The present study focused on arousal reactions in REM sleep. Five young healthy volunteers were investigated during 27 nights. Using air-dilution olfactometry CO(2) was used for nasal irritation and H(2)S was used as a specific olfactory stimulant. Both stimuli were presented at four concentrations, odorless stimuli served as control. Other than in previous studies arousal latency was used as a dependent measure. Even the strongest olfactory stimulus did not produce an increase in arousal frequency in REM sleep whereas for irritation such an increase was clearly present. Latencies of arousal responses to CO(2) shortened with increasing stimulus concentrations. Olfactory stimulation does not lead to arousal reactions. In contrast, trigeminal stimulation produces a concentration-dependent increase in arousal frequency and decrease in arousal latency across all sleep stages. The present data shows for the first time that arousals are not present during REM sleep in response to selective olfactory stimuli. However, such changes are easily evoked by irritants activating the trigeminal nerve.     

Reproducibility of the short-latency reflex inhibition to loading of human inspiratory muscles

Loading of inspiratory muscles produces a profound short-latency inhibitory response (IR) of the electromyogram (EMG), followed by an excitatory response (ER). Duration of IR correlates positively with the apnoea hypopnoea index in obstructive sleep apnoea (OSA) patients, for whom measurement of this reflex may allow the assessment of a physiological response to therapy. To test the reliability of reflex measurement, we studied 11 human subjects on 4 separate days. Inspiration was transiently occluded during 2 sets of 30 trials on each day. Scalene muscle EMG was rectified and averaged. Ten parameters (4 latencies and 6 EMG sizes) were measured. Reproducibility was analysed by ANOVA, intraclass correlation coefficient (ICC) and coefficient of variation (CV). The mean ICC was 0.56 (range 0.30-0.76) and the mean CV was 25% (range 6.7-48%). These results show good measurement reliability. The abnormalities seen in disease are significantly larger than these CVs. The reflex response to airway occlusion may be assessed reliably using our method.     

Differential effect of sleep-wake states on lingual and dorsal neck muscle activity in rats

Postural tone is reduced during slow-wave sleep (SWS) and absent during rapid eye movement sleep (REMS). In obstructive sleep apnea subjects, upper airway dilating muscles, including those of the tongue, show a similar pattern; this contributes to sleep-related airway obstructions. However, in healthy subjects, state-dependent changes in the activity of pharyngeal muscles are variable. In seven chronically instrumented Sprague-Dawley rats, an animal model used to study sleep and sleep-disordered breathing, we quantified lingual and postural muscle activity across the sleep-wake states by measuring the root mean square levels of the electromyograms (EMG) in successive 10s intervals collected during 2h of recording at a constant circadian time (1-3p.m.). The nuchal EMG was low and steady during SWS and further reduced with occasional twitches during REMS. In contrast, the mean lingual EMG during SWS was only 5.9+/-1.6% (S.E.) of its mean in wakefulness, and during REMS, it increased to 46+/-15% (S.E.) (p<0.03) due to the appearance of phasic bursts, the intensity of which progressively increased. The lingual and nuchal activities also had different time courses during state transitions. In obstructive sleep apnea subjects, the sleep-wake changes in the activity of pharyngeal muscles may become similar to those in postural muscles as a result of pharyngeal tone adaptations to the disorder.