It has been hypothesized that interactions between state of consciousness and respiratory control variables may be significant in the etiology of periodic breathing (PB) under such conditions as; sleep onset, prematurity, hypoxia, and occlusive sleep apnea (OSA). Because current clinical methods of sleep staging are inadequate to investigate these interactions, a new method, based on spectrum analysis of the electroencephalogram (EEG), is presented for quantifying graded state changes which may occur in conjunction with periodic breathing. Two state indexes are described; Sia, a measure of EEG amplitude and Slf, a measure of the EEG frequency distribution. Broadly speaking, the objective of the proposed work is to is to develop a system by which to study the mechanisms of interaction between state of consciousness and respiration. A related long range goal is to quantitatively evaluate the role of fluctuating state of consciousness in the mechanisms of sleep related apneas. The proposed work is directly related the pathophysiology of OSA and may have implications for the diagnosis and evaluation of therapeutic interventions in this, and other respiratory disorders. The first specific aim of these studies is to critically evaluate the nature and consistency of the relationships between sleep onset and the development of apnea and between relative arousal and the restoration of ventilation in habitual snorers with PB, patients with Cheyne-Stokes respiration (CSR) and patients with OSA. The second specific aim is to assess the role of state of consciousness, and transient changes in state of consciousness, in determining the type and duration of apnea in PB, CSR and OSA. The third specific aim is to quantitatively evaluate potential mechanisms by which changing state of consciousness affects genesis and resolution of sleep-related upper airway occlusion through its influence on respiratory and upper airway muscles activities, inspiratory pressure generation, thoraco-abdominal configuration and arterial blood gases. Subjects for these studies will be patients with OSA , patients with Cheyne-Stokes respiration, and habitual snorers.
The specific aims will be met by performing nocturnal polysomnography in all subjects, with standard clinical monitoring augmented to include; a naso-gastric catheter instrumented for diaphragmatic pressure and EMG (EMGdi), fine wire electrodes inserted per-orally to record genioglossus EMG (EMGge), calibrated compartmental ventilation, expired gases and arterial oxygen saturation (SaO2)- For each study Sla and Slf will be computer scored to identify all """"""""transient state changes"""""""" (TSC); and airflow, thoraco-abdominal motion and PETCO(2) will be computer-scored to identify and classify all apneas as central, mixed or obstructive. Hypotheses related to the first aim will be tested by computing the concordance between TA's and apneas, stratified by apnea type; and by numerically correlating the relative timing of TA's with apneas as well as the variability of this timing. Hypotheses related to the second and third aims will be tested by performing coherence analysis between the state indexes and each respiratory variable and by multiple regression analysis of respiratory and state variables on apnea type and timing. In addition, interventions including transient closed-system rebreathing and mechanical airway occlusion will be employed to stimulate the effects of occlusive apnea in an attempt to differentiate the importance of various afferent pathways in the stimulation of arousal and of apnea resolution.
