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The powerful short-latency, loading-mediated, inhibitory reflex of human inspiratory muscles is driven by proprioceptive muscle afferents of the chest wall and diaphragm, but the sites of afferent integration and the reflex circuit remain unclear. The inhibition is prolonged in asthma and obstructive sleep apnoea (OSA). This thesis investigates the reflex circuits, and also explores some factors that may unify the causation of the changes in the two diseases, such as airway and systemic inflammation or the chronic resistive loading of breathing.Chapter One summarises the functionality anatomy of the ventilatory muscles and their neural control and the previous studies of the inhibitory reflexes of breathing muscles. The common features of asthma and OSA, including inflammation, abnormal respiratory tract sensation and the chronic resistive loading of breathing muscles, are detailed. The reproducibility of measurement of this inhibitory reflex in human scalene muscles is validated in Chapter Two. In Chapter Three, the involvement of the carbon dioxide-sensitive inspiratory pattern-generating centres of the medulla in the integration of the reflex is investigated with matched volitional and automatic hyperpnoea. As considerable evidence suggests that voluntary inspiratory drive bypasses medullary centres, the absence of variation in the reflex between these conditions argues that the medullary pattern-generators are not involved in the integration of this inhibitory reflex. Chapter Four describes the use of a human model of acute upper airway inflammation to exclude a short-term role of inflammation in changing the reflex. Chapter Five assesses the effect of continuous positive airway pressure (CPAP) therapy on reflex abnormalities in OSA and confirms that the reflex abnormalities persist despite the correction of resistive loading of breathing in sleep. Chapter Six collates these findings and introduces the application of promising single motor unit techniques to thi

This thesis addresses the neural control of the human inspiratory muscles. Single motor unit and multiunit electromyographic recordings are made from inspiratory and limb muscles to investigate the organisation of inspiratory motoneurone output and strategies by which motoneurone output is optimised. In the first two chapters, the output of parasternal intercostal motor units in respiratory and non-respiratory ‘tasks’ are described. The results show that across parasternal intercostal spaces, there is a decreasing rostrocaudal gradient of motor unit output in targeted voluntary breaths, such that inspiratory activity is greatest and earliest in cranial interspaces. This topographic recruitment is similar to quiet breaths and the majority of motor units are active in both voluntary and quiet breaths. In a non-respiratory voluntary task, rotation of the trunk (Chapter 3), common motor units are also active, but inspiratory motor unit output on both sides of the chest wall is altered by unilateral rotation. Multiple descending drives to the respiratory muscles may be organised and integrated at the spinal cord such that the same motoneurones are depolarised but their output depends on the task(s) performed. The strategy of motor unit recruitment in two inspiratory muscles is examined in Chapter 4. The profiles of activation of an obligatory inspiratory muscle, scalenes, and an accessory muscle, sternocleidomastoid, are not altered by lung volume or task (isovolumetric ‘static’ versus ‘dynamic’ task). Rather than the activation of these muscles being dependent on afferent signals of lung volume, they are recruited according to their relative mechanical advantage for inspiration. These results suggest that neural drive to these muscles has an element that is ‘preset’. The final study investigates neural and mechanical behaviour in the first dorsal interosseous muscle. The results show that there is coupling between neural drive and

This thesis addresses the organisation of drive to human upper airway and inspiratory pump muscles. The characterisation of single motor unit activity is important as the discharge frequency or timing of discharge of each motor unit directly reflects the output of single motoneurones. Thus, the firing properties of a population of motor units is indicative of the neural drive to the motoneurone pool. The experiments presented in Chapter 2 measured the recruitment time of five inspiratory pump muscles (diaphragm, scalene, second parasternal intercostal, and third and fifth dorsal external intercostal muscles) during normal quiet breathing and quantified the timing and magnitude of drive reaching each muscle. Chapter 3 examined the EMG activity of a major upper airway muscle (the genioglossus). The single motor units of the genioglossus display activity that can be grouped into six types based on its association or lack of association with respiration. The types of activity are termed: Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic, and Tonic Other. A new method is presented in Chapter 4 to illustrate large amounts of data from single motor units recorded from respiratory muscles in a concise manner. This single figure displays for each motor unit, the recruitment time and firing frequency, the peak discharge frequency and its time, and the derecruitment time and its frequency. This method, termed the time-and-frequency plot, is used to demonstrate differences in behaviour between populations of diaphragm (Chapter 2) and genioglossus (Chapter 3) motoneurones. In Chapter 5, genioglossus activity during quiet breathing is compared between a group of patients with severe OSA and healthy control subjects. The distribution of central drive is identical between the OSA and control subjects with the same proportion of the six types of motor unit activity in both groups. However, there are alterations in the onset time of Inspiratory Phasic