Functional imaging of the brainstem and cortical sites of blood pressure control in subjects with obstructive sleep apnoea

  • Rania H. Fatouleh

Western Sydney University thesis: Doctoral thesis

Abstract

Obstructive sleep apnoea (OSA) is a common sleep disorder associated with repeated bouts of nocturnal hypoxaemia during collapse of the upper airways during sleep. The hypoxaemia leads to a physiologically appropriate increase in total peripheral resistance, brought about by an increase in sympathetically-mediated vasoconstriction in the muscle vascular bed. The increase in muscle sympathetic nerve activity (MSNA) persists in the awake state, leading to neurogenic hypertension and an elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the elevated MSNA in OSA are poorly understood. This thesis composes a series of studies I conducted in healthy subjects and OSA patients, before and after treatment with continuous positive airway pressure (CPAP), to improve our understanding of the disturbances in autonomic control that manifests in OSA. In Studies I-IV, I recorded MSNA in healthy controls and in OSA subjects before and after treatment with CPAP. I confirmed that MSNA was significantly elevated in newly diagnosed OSA patients compared to control subjects and that there was a significant fall in MSNA after 6 months of CPAP, with no further change after 12 months. In Study I, I tested the hypothesis that respiratory-sympathetic coupling, postulated to be the underlying cause of neurogenic hypertension, is increased in OSA. In 21 OSA patients and 21 control subjects, cross-correlation analysis revealed no significant difference in the magnitude of respiratory modulation of MSNA between the OSA patients and controls, but the temporal coupling of MSNA to respiration was tighter in OSA, with more activity occurring in post-inspiration and less in inspiration and expiration. This was largely reversed following long-term treatment with CPAP. In Study II-IV, I concurrently recorded MSNA and fMRI to identify regions within the brain that are functionally coupled to the generation of the elevated. I also measured regional grey matter volume using voxel-based morphometry. In Study II, in 17 OSA patients, the elevated MSNA drive was associated with significant changes in Blood Oxygen Level Dependent signal intensity within dorsolateral and medial prefrontal cortices (dlPFC, mPFC), dorsal precuneus, anterior cingulate (ACC) and retrosplenial cortices, caudate nucleus, as well as the right hippocampus/parahippocampus, compared to 17 healthy controls. Surprisingly, none of the regions displayed significant anatomical changes. In addition, in Study III, elevated MSNA in OSA was correlated to altered changes in signal intensity in the dorsolateral pons, rostral ventrolateral medulla (RVLM), medullary raphe and midbrain in comparison to the healthy controls. Except for the midbrain, those regions had significantly increased grey matter volumes in OSA compared with controls. Furthermore, OSA was also associated with grey matter volume increases in the region of the hypoglossal nucleus. Finally, in Study IV, I aimed to assess the changes to brain activity following 6 months of CPAP treatment in 13 OSA patients before and after 6 months of treatment with CPAP and in 15 healthy control subjects. The reduction in resting MSNA after 6 months of CPAP described earlier was coupled with significant changes in signal intensity in precuneus bilaterally, as well as in the insula, retrosplenial cortex bilaterally, right mPFC, right ACC, and right parahippocampus. In addition, CPAP treatment had no significant effect on grey matter volume in any of those brain regions. These data suggest that the elevated muscle vasoconstrictor drive that occurs in individuals with OSA may be driven by activity changes in these suprabulbar sites through influences on brainstem regulatory nuclei.
Date of Award2014
Original languageEnglish

Keywords

  • sleep apnea syndromes
  • obstructive sleep apnoea
  • treatment
  • blood pressure
  • blood vessels
  • brain stem
  • neuroimaging

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