The role of the fusimotor system with respect to the contribution of the diaphragm and the intercostal muscles to the respiratory tidal volume

Summary The efferent electrical activity in the phrenic nerve can be quantified in such a way that it gives a good correlation to tidal volume. After administration of the drug benzoctamine this relationship changes: more phrenic nerve activity is needed for the same tidal volume. No changes were found in the neuro-muscular transmission from the phrenic nerve to the diaphragm. There was no alteration in dynamic compliance of the lungs or in airway resistance. The afferent phrenic nerve activity from proprioceptors in the diaphragm did not change. It seems unlikely that respiratory neurons in the brainstem were affected since the sensitivity of the respiratory system to CO₂ did not change.It is known that the tonic fusimotoneuron activity is suppressed at a supraspinal level by benzoctamine. Since intercostal muscles have muscle spindles and the diaphragm hardly has any, the intercostal muscle activity will be affected more than diaphragmatic activity by benzoctamine. This could actually be shown by quantifying the electromyogram of inspiratory external intercostal muscles.The tidal volume regulation is controlled by the vagal feedback loop. In order to reach a certain tidal volume after administration of benzoctamine, the contribution of the diaphragm has to increase because the activity of the intercostal muscles is diminished.     

Effects of abdominal distension on breathing pattern and respiratory mechanics in rabbits

The effects of acute abdominal distension (AD) on the electromechanical efficiency (Eff) of the inspiratory muscles were investigated in anesthetized rabbits by recording the electrical activity (A), pressure (P) exerted by the diaphragm (di) and parasternal intercostal muscles (ic), and lung volume changes when an abdominal balloon was inflated to various degrees. Eff,ic increased with increasing AD both in supine and upright postures. In upright rabbits Eff,di increased for intermediate but decreased at higher levels of AD, whilst it decreased at all levels of AD in supine rabbits. Tidal volume (VT) response followed that of Eff,di. Tonic Aic and Adi and inspiratory prolongation were elicited by AD. The effects of these neural mechanisms, acting to limit end-expiratory lung volume and VT changes, were however small since vagotomy prevented tonic Adi and inspiratory prolongation and reduced tonic Aic, but changed lung volume responses to AD only little. Hence, reduced respiratory system compliance and changes in inspiratory muscle electromechanical efficiency dominate lung volume responses to acute AD.     

Maximal activation of the human diaphragm but not inspiratory intercostal muscles during static inspiratory efforts

It is widely held that transdiaphragmatic pressure is a reliable index of the extent of central activation of the diaphragm but the maximal voluntary transdiaphragmatic pressure is lower during inspiratory than expulsive efforts. To determine whether the diaphragm is fully activated during the two manoeuvres supramaximal stimuli were delivered to both phrenic nerves during maximal efforts. No discernible twitch was evoked during 30-55% of attempted maximal efforts with either voluntary manoeuvre. Thus the difference in maximal transdiaphragmatic pressure between the manoeuvres must reflect changes in chest-wall geometry or mechanics rather than in the phrenic motor outflow. Inspiratory intercostal muscle activity was consistently submaximal during maximal inspiratory efforts.     

Mechanisms of genioglossus responses to inspiratory resistive load in rabbits

The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were 'bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 +/- 14.7% of control) and its inspiratory duration (to 113 +/- 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 +/- 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (-13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of 'pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations.     

Characteristics of inspiratory inhibition by occlusion of both external carotid and basilar arteries in cats.

Effects of the occlusion of both the external carotid and basilar arteries on the inspiratory activity were studied in anesthetized, vagotomized, paralyzed, and artificially ventilated cats. Integrated phrenic nerve activity was used as an index of the inspiratory activity. Blood pressure in the lingual artery, located downstream from the occluded external carotid arteries, was measured as the arterial pressure of the upper brain stem during occlusion. The basilar artery was occluded at the boundary between the medulla and pons. Occlusions of the external carotid arteries and basilar artery suppressed the phrenic nerve activity to finally disappear within 1 min (phrenic nerve apnea, 45 out of 50 occlusions in 6 cats). The blood pressure in the upper brain stem was 16.6 +/- 5.7 mmHg (mean +/- S.D.) during occlusions. These effects of occlusion on the phrenic nerve activity were also observed during hypercapnia and hypoxia, although they were not so remarkable as those during normocapnia and normoxia. The results indicate that the upper part of the brain stem operates a profound facilitatory mechanism on the medullary inspiratory activity.     

Positive feedback facilitation of external intercostal and phrenic inspiratory activity by pulmonary stretch receptors

Both in lightly pentobarbitone anesthetized and decerebrate cats increments in lung volume (V) during inspiration caused facilitation of inspiratory activity both in phrenic (Phr) and external intercostal (EI) motoneurons. This effect had low volume threshold, well below eupnoeic tidai volumes. It was readily reduced or abolished by small additional doses of pentobarbitone. This facilitatory effect appeared with considerably greater magnitude in El than in Phr. The response magnitude was linearly related to the corresponding increments in V? but not to increments in airflow (V?). Sustained elevation of V at zero V caused sustained facilitation of EI and Phr. This positive feedback facilitation which was similarly obtained in spontaneously breathing and paralysed cats occurred continuously with great regularity in every breath. It was abolished by bilateral vagotomy but could then be elicited by electrical stimulation of the central end of the vagus nerve at the same threshold strengths required to elicit a just detectable shortening of inspiratory duration. The results indicate that the slowly adapting pulmonary stretch receptors are responsible for this positive feedback facilitation prior to the negative feedback effect on the inspiratory ‘off-switch’ elicited by the same receptors. Clear distinctions are described between the reflex characteristics of this ‘low-threshold’ volume dependent facilitatory reflex and the ‘high-threshold’ transient excitatory reflex effects provoked by large and rapid inflations.     

Expiratory activity of the inspiratory muscles during cough.

To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles.     

The output from human inspiratory motoneurone pools

Survival requires adequate pulmonary ventilation which, in turn, depends on adequate contraction of muscles acting on the chest wall in the presence of a patent upper airway. Bulbospinal outputs projecting directly and indirectly to 'obligatory' respiratory motoneurone pools generate the required muscle contractions. Recent studies of the phasic inspiratory output of populations of single motor units to five muscles acting on the chest wall (including the diaphragm) reveal that the time of onset, the progressive recruitment, and the amount of motoneuronal drive (expressed as firing frequency) differ among the muscles. Tonic firing with an inspiratory modulation of firing rate is common in low intercostal spaces of the parasternal and external intercostal muscles but rare in the diaphragm. A new time and frequency plot has been developed to depict the behaviour of the motoneurone populations. The magnitude of inspiratory firing of motor unit populations is linearly correlated to the mechanical advantage of the intercostal muscle region at which the motor unit activity is recorded. This represents a 'neuromechanical' principle by which the CNS controls motoneuronal output according to mechanical advantage, presumably in addition to the Henneman's size principle of motoneurone recruitment. Studies of the genioglossus, an obligatory upper airway muscle that helps maintain airway patency, reveal that it receives simultaneous inspiratory, expiratory and tonic drives even during quiet breathing. There is much to be learned about the neural drive to pools of human inspiratory and expiratory muscles, not only during respiratory tasks but also in automatic and volitional tasks, and in diseases that alter the required drive.     

Bilateral vagotomy differentially alters the magnitude of hypoglossal and phrenic long-term facilitation in anesthetized mechanically ventilated rats

Acute intermittent hypoxia elicits long-term increases in respiratory motor output (long-term facilitation, LTF). Most investigators study LTF in mechanically ventilated, bilaterally vagotomized, and anesthetized animals. Vagotomy blocks inhibitory lung-volume feedback that could diminish the magnitude of LTF. However, the effects of vagotomy on LTF may not be so straight forward. In cats, vagotomy increases LTF of upper airway muscles but may decrease LTF of accessory pump muscles. The effects of vagotomy on LTF in rats are unknown. We hypothesized that the magnitude of hypoglossal and phrenic LTF would be differentially regulated by vagal afferent feedback in anesthetized and mechanically ventilated rats. Hypoglossal and phrenic motor outputs were recorded from vagotomized and vagally intact anesthetized mechanically ventilated adult Sprague-Dawley rats before, during, and up to 60-min after intermittent hypoxia. Ventilator frequency (f), pump volume, and peak tracheal pressure were not different between groups. The effects of vagotomy on the magnitude of LTF depended on the motoneuron population in question. The magnitude of hypoglossal LTF increased after vagotomy (vagi intact, -5+/-10%; vagotomy, 66+/-11% above baseline; p<0.05); whereas, the magnitude of phrenic LTF decreased after vagotomy (vagi intact, 135+/-24%; vagotomy, 40+/-13% above baseline; p<0.05). These data support previous work in anesthetized cats, and suggest that the expression of hypoglossal and phrenic respiratory motor plasticity is differentially regulated by vagal afferent feedback.     

Experimental evaluation of the optimal tidal volume for simultaneous pacing of the diaphragm and respiratory muscles

Because of problems with pacing devices, surgical procedures, and diaphragm fatigue in pacing therapy of the phrenic nerve, we performed simultaneous pacing of the diaphragm alone and of multiple respiratory muscles in dogs and evaluated the optimal tidal volume. After intravenously anesthetizing 20 dogs with an average weight of 11kg, their tidal volume was measured with a spirometer to obtain control values. In the first 4 dogs, electrodes were sutured to the diaphragm and the optimal voltage, pulse width, and output to maximize tidal volume were determined. In the remaining 16 dogs, we stimulated individual canine respiratory muscles, i.e., the diaphragm, the rectus thoracis, and intercostal muscles 3-5 and simultaneously stimulated the diaphragm and the rectus thoracis; the diaphragm and intercostal muscles; the rectus thoracis and the intercostal muscles; or the diaphragm, rectus thoracis, and intercostal muscles. We compared a group in which a counterelectrode was positioned in each muscle group (group A) with a group in which no counterelectrode was used (group B). The best tidal volume was obtained at 10V, 50Hz, and a pulse width of 1.0ms. All the respiratory muscle pacings yielded better tidal volumes in group B than in group A. The greatest tidal volume was obtained with the rectus thoracis and intercostal muscle combination, suggesting the possibility of being able to reduce diaphragm fatigue by alternate pacing of these muscles and the diaphragm.     

Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.     

Effects of exercise and CO2 inhalation on the breathing pattern in man

Conflicting opinions exist concerning the breathing pattern in man during resting and stimulated ventilation. Some but not all investigators have reported the existence of an abrupt change, a 'breakpoint', in the relation between mean tidal volume and mean inspiratory time. Different opinions exist as to whether the slope and the intercept for the relation between mean minute ventilation and mean tidal volume are identical regardless of the mode of stimulating the ventilation. We have studied 10 subjects, at rest and during graded stimulation of ventilation by CO2 inhalation and exercise. No breakpoint was observed in the relations between (1) mean tidal volume and mean inspiratory time and (2) mean tidal volume and mean expiratory time, even if a wide range of tidal volumes was achieved in our subjects. Carbon dioxide inhalation (normoxic or hyperoxic) and exercise gave different regression lines for the relation between mean minute ventilation and mean tidal volume in 8 out of 10 subjects with a larger slope during exercise. At exercise inspiratory time decreased with any increase in tidal volume, while during CO2 breathing no consistent change in inspiratory time was seen. Mean inspiratory flow was linearly related to exercise load and apparently also to arterial carbon dioxide pressure. We conclude that CO2 breathing gives a breathing pattern which is different from that obtained with exercise in the majority of normal subjects. Furthermore, we could not confirm the existence of breakpoints in relations describing the breathing pattern of normal man.     

Effects of hypocapnia on respiratory timing and inspiratory activities of the superior laryngeal, hypoglossal, and phrenic nerves in the vagotomized rat

Effects of acute hypocapnia on respiratory timing (inspiratory and expiratory times (TI, TE) ) and on inspiratory activities of the efferent superior laryngeal (Xs1), hypoglossal (XII), and phrenic (Phr) nerves were studied in artificially ventilated vagotomized, and anesthetized rats. Hyperventilation induced a decrease in respiratory frequency exclusively due to prolongation of TE and resulted in expiratory apnea. Inspiratory activities of three nerves decreased with reduction in CO2 concentration of end-tidal gas (FETCO2), and disappeared simultaneously at a threshold FETCO2 for apnea. The decrease in the peak inspiratory activity by hypocapnia was larger in the XII than in the Phr or Xs1 nerve (XII greater than Phr greater than Xs1). The results suggest that the CO2 stimulus (mainly via a central chemosensor) plays an important role in the process of terminating expiration or of expiratory-inspiratory phase switching and that the responses of the XII or Xs1 motoneurons to variation in CO2 stimulus differ from that of the Phr motoneurons (or of the Phr driving medullary neurons). A possible functional significance of these observations is discussed.     

Synaptic interactions between respiratory neurons during inspiratory on-switching evoked by vagal stimulation in decerebrate cats

To elucidate neuronal mechanisms underlying phase-switching from expiration to inspiration, or inspiratory on-switching (IonS), postsynaptic potentials (PSPs) of bulbar respiratory neurons together with phrenic nerve discharges were recorded during IonS evoked by vagal stimulation in decerebrate and vagotomized cats. A single shock stimulation of the vagus nerve applied at late-expiration developed an inspiratory discharge in the phrenic neurogram after a latency of 79+/-11 ms (n = 11). Preceding this evoked inspiratory discharge, a triphasic response was induced, consisting of an early silence (phase 1 silence), a transient burst discharge (phase 2 discharge) and a late pause (phase 3 pause). During phase 1 silence, IPSPs occurred in augmenting inspiratory (aug-I) and expiratory (E2) neurons, and EPSPs in postinspiratory (PI) neurons. During phase 2 discharge, EPSPs arose in aug-I neurons and IPSPs in PI and E2 neurons. These initial biphasic PSPs were comparable with those during inspiratory off-switching evoked by the same stimulation applied at late-inspiration. In both on- and off-switching, phase-transition in respiratory neuronal activities started to arise concomitantly with the phrenic phase 3 pause. These results suggest that vagal inputs initially produce a non-specific, biphasic response in bulbar respiratory neurons, which consecutively activates a more specific process connected to IonS.     

Effect of posture on inspiratory muscle electromyogram response to hypercapnia

Summary The aim of our study was to examine the effect of posture on inspiratory muscle activity response to hypercapnia. Recent research has revealed that in normal subjects the activation of the rib cage muscles and of the diaphragm is actually greater in the upright than in the supine position during resting tidal breathing. In this study we examined whether the upright position necessarily entails a greater activation of the inspiratory muscles also under conditions of ventilatory stress. For this purpose we compared the responses to CO₂-rebreathing in the supine and sitting positions in five volunteers, by simultaneously recording the electromyogram of the diaphragm (EMG_di) and the intercostal muscles (EMG_int). The electromyogram was recorded by means of surface electrodes to measure the EMG amplitude. While the slopes of ventilatory (V _E) response to increasing arterial CO₂ tension (P _aCO₂) were similar in the two positions, both the EMG_di-V _E and EMG_int-V _E relationship showed steeper slopes in the supine than in the sitting position. In each CO₂ run the increases in EMG_di were linearly related to those in EMG_int. This relationship was not affected by the body position. These results suggested that, in spite of similar ventilatory responses to CO₂-rebreathing in the lying and sitting positions, the supine position, in humans, required a higher activation of the inspiratory muscles.     

The effects of high-frequency inflation and high-frequency deflation on respiration in rabbits

High-frequency inflating and deflating triangular pulses of pressure were applied to air in the trachea of urethane-chloralose-anesthetized rabbits. Expiratory time was increased by high-frequency inflation (HFI) and decreased by high-frequency deflation (HFD). Both had little effect on inspiratory time or tidal phrenic nerve activity. HFD provoked more tonic type phrenic activity, with discharges being evident during the expiratory phase. It was demonstrated that HFI, which probably stimulates pulmonary stretch receptors, inhibits the initiation of inspiration and HFD, which probably stimulates irritant receptors, facilitates inspiration.     

Diaphragmatic and external intercostal muscle control during vomiting: behavior of inspiratory bulbospinal neurons

1. The role of dorsal and ventral respiratory group (DRG and VRG) bulbospinal inspiratory (I) neurons in the control of diaphragmatic and external intercostal (inspiratory) muscle activity during vomiting was examined by recording from these neurons during fictive vomiting in decerebrate, paralyzed cats. Fictive vomiting was defined by a characteristic series of bursts of coactivation of phrenic and abdominal muscle nerves, elicited either by electrical stimulation of abdominal vagal afferents or by emetic drugs, which would be expected to produce vomiting if the animals were not paralyzed. 2. Data were recorded from 22 DRG and 29 VRG I neurons that were antidromically activated from the fourth cervical spinal segment (C4). Only 10% (5/51) of these neurons started to fire near the beginning of phrenic discharge during fictive vomiting and thus had the appropriate discharge pattern to contribute to the initial activation of the diaphragm and coactive external intercostal muscles during vomiting. The frequency of occurrence of these Active neurons was not significantly different in the DRG (3/22) and VRG (2/29) (chi 2 test). Most remaining neurons were either totally silent (n = 7) or had only sporadic, infrequent firing (n = 16) (Silent neurons, 23/51 = 45%), or else fired near the end of phrenic discharge during fictive vomiting (End neurons, 21/51 = 41%). Two neurons were categorized as having miscellaneous (Misc) behavior. 3. No differences were found among neurons having different response patterns during fictive vomiting in regard to the following: the manner in which fictive vomiting was elicited: cell location: conduction velocity; and neuronal firing onset, rate, and pattern during respiration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilation induced apnea and its effect on dorsal brainstem inspiratory neurones in the rat

The purpose of this study was to examine the effect of mechanical ventilation (MV) on inherent breathing and on dorsal brainstem nucleus tractus solitarius (NTS) respiratory cell function. In pentobarbitone-anaesthetised rats, application of MV at combined high frequencies and volumes (representing threshold levels) produced apnea. The apnea persisted as long as MV was maintained at or above the threshold frequency and volume. Following removal of MV, inherent breathing did not resume immediately, with the diaphragm exhibiting post-mechanical ventilation apnea. The fall in arterial P(CO2) (Pa(CO2)) levels evoked by MV-engendered hyperventilation was shown not to be the trigger for initiation of apnea. MV-induced apnea was immediately reversed by bilateral vagotomy. Further, MV-induced apnea could not be evoked in bilaterally vagotomized animals suggesting that vagal feedback is the critical pathway for its initiation. NTS inspiratory neurones were inhibited during both MV-induced apnea and post-mechanical ventilation apnea, implying the involvement of central neural mechanisms in mediating this effect.     

Chest wall volumes during inspiratory loaded breathing in COPD patients

Chest wall volumes and breathing patterns of 13 male COPD patients were evaluated at rest and during inspiratory loaded breathing (ILB). The sternocleidomastoid (SMM) and abdominal muscle activity was also evaluated. The main compartment responsible for the tidal volume at rest and during ILB was the abdomen. During ILB patients exhibited, in addition to increases in the ratio of inspiratory time to total time of the respiratory cycle and minute ventilation, increases (p < 0.05) in the chest wall tidal volume by an increase in abdomen tidal volume as a result of improvement of end chest wall inspiratory volume without changing on end chest wall expiratory volume. The SMM and abdominal muscle activity increased 63.84% and 1.94% during ILB. Overall, to overcome the load imposed by ILB, COPD patients improve the tidal volume by changing the inspiratory chest wall volume without modifying the predominant mobility of the abdomen at rest and without affecting the end chest wall expiratory volume.     

Synchronization of presynaptic input to motor units of tongue, inspiratory intercostal, and diaphragm muscles

The respiratory central pattern generator distributes rhythmic excitatory input to phrenic, intercostal, and hypoglossal premotor neurons. The degree to which this input shapes motor neuron activity can vary across respiratory muscles and motor neuron pools. We evaluated the extent to which respiratory drive synchronizes the activation of motor unit pairs in tongue (genioglossus, hyoglossus) and chest-wall (diaphragm, external intercostals) muscles using coherence analysis. This is a frequency domain technique, which characterizes the frequency and relative strength of neural inputs that are common to each of the recorded motor units. We also examined coherence across the two tongue muscles, as our previous work shows that, despite being antagonists, they are strongly coactivated during the inspiratory phase, suggesting that excitatory input from the premotor neurons is distributed broadly throughout the hypoglossal motoneuron pool. All motor unit pairs showed highly correlated activity in the low-frequency range (1-8 Hz), reflecting the fundamental respiratory frequency and its harmonics. Coherence of motor unit pairs recorded either within or across the tongue muscles was similar, consistent with broadly distributed premotor input to the hypoglossal motoneuron pool. Interestingly, motor units from diaphragm and external intercostal muscles showed significantly higher coherence across the 10-20-Hz bandwidth than tongue-muscle units. We propose that the lower coherence in tongue-muscle motor units over this range reflects a larger constellation of presynaptic inputs, which collectively lead to a reduction in the coherence between hypoglossal motoneurons in this frequency band. This, in turn, may reflect the relative simplicity of the respiratory drive to the diaphragm and intercostal muscles, compared with the greater diversity of functions fulfilled by muscles of the tongue.