NEURAL SITES MEDIATING OBSTRUCTIVE SLEEP APNEA

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The objectives are to determine, using functional magnetic resonance (fMRI) techniques, the location and time course of activation of brain structures activated during obstructive sleep apnea. We hypothesize that particular regions of the orbital frontal cortex, rostral hypothalamus, amygdala, locus coeruleus, midline raphe, and dorsal and ventral pons, which activate to simulated obstructive apnea in waking control subjects, will fail to activate, or respond with reduced activity during sleep apnea events of patients, but will continue to activate during simulated obstructive apnea during sleep in controls. Other regions involved in the suppression of muscle tone may show excessive activation in patients, thereby inducing obstructive apnea. A time series of 30 repetitions of 20 image slices across the entire brain will be obtained in the sagittal plane using blood oxygen level dependent (BOLD) Echo Planar-Imaging pulse sequences, optimal for sensing perfusion alterations, in 20 obstructive apnea patients and 20 age- and sex-matched controls during apnea events of sleep (patients) and during inspiratory loads (20 cM water) applied at the onset of an inspiratory effort during sleep (controls). To partition effects of sleep, both groups will undergo a baseline waking recording, followed by inspiratory loading, and Valsalva pressor challengers, which simulate sensory and autonomic aspects of obstructive apnea. Heart rate, flow, non-invasive blood pressure, arm sweating, and digit oximetry will be measured concurrently with image scans. The MR signal changes will be assessed with software optimized for fMRI processing to gauge regional activation changes during apneic events, inspiratory loading and sympathetic challenges. Cross correlations of regional image changes with respiratory, cardiovascular and sympathetic outflow induces will be calculated. The studies have the potential to identify brain regions involved in mediating upper airway atonia, to provide insights into pharmacologic intervention for obstructive sleep apnea, and to determine the neural sites involved in autonomic concomitants of airway obstruction.