Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnoea (OSA) during daytime wakefulness, leading to hypertension, but the underlying mechanisms are poorly understood. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI) of the brain we aimed to identify the central processes responsible for the sympathoexcitation. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted percutaneously into the common peroneal nerve in 17 OSA patients and 15 healthy controls lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. Fluctuations in BOLD signal intensity covaried with the intensity of the concurrently recorded bursts of MSNA. In both groups there was a positive correlation between MSNA and signal intensity in the left and right insulae, dorsolateral prefrontal cortex (dlPFC), dorsal precuneus, sensorimotor cortex and posterior temporal cortex, and the right mid-cingulate cortex and hypothalamus. In OSA the left and right dlPFC, medial PFC (mPFC), dorsal precuneus, anterior cingulate cortex, retrosplenial cortex and caudate nucleus showed augmented signal changes compared with controls, while the right hippocampus/parahippocampus signal intensity decreased in controls but did not change in the OSA subjects. In addition, there were significant increases in grey matter volume in the left mid-insula, the right insula, left and right primary motor cortices, left premotor cortex, left hippocampus and within the brainstem and cerebellum, and significant decreases in the mPFC, occipital lobe, right posterior cingulate cortex, left cerebellar cortex and the left and right amygdala in OSA, but there was no overlap between these structural changes and the functional changes in OSA. These data suggest that the elevated muscle vasoconstrictor drive in OSA may result from functional changes within these brain regions, which are known to be directly or indirectly involved in the modulation of sympathetic outflow via the brainstem. That there was no overlap in the structural and functional changes suggests that asphyxic damage due to repeated episodes of nocturnal obstructive apnoea is not the main cause of the sympathoexcitation.

Obstructive sleep apnoea (OSA) is associated with an increase in the number of bursts of muscle sympathetic nerve activity (MSNA), leading to neurogenic hypertension. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment for preventing collapse of the upper airway in OSA. In addition to improving sleep, CPAP decreases daytime MSNA towards control levels. It remains unknown how this restoration of MSNA occurs, in particular whether CPAP treatment results in a simple readjustment in activity of those brain regions responsible for the initial increase in MSNA or whether other brain regions are recruited to over-ride aberrant brain activity. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI), we aimed to assess brain activity associated with each individual subject's patterns of MSNA prior to and following 6 months of CPAP treatment. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted into the common peroneal nerve in 13 newly diagnosed patients with OSA before and after 6 months of treatment with CPAP and in 15 healthy control subjects while lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. MSNA was significantly elevated in newly diagnosed OSA patients compared to control subjects (55 ± 4 vs 26 ± 2 bursts/min). Fluctuations in BOLD signal intensity in multiple regions covaried with the intensity of the concurrently recorded bursts of MSNA. There was a significant fall in MSNA after 6 months of CPAP (39 ± 2 bursts/min). The reduction in resting MSNA was coupled with significant falls in signal intensity in precuneus bilaterally, the left and right insula, right medial prefrontal cortex, right anterior cingulate cortex, right parahippocampus and the left and right retrosplenial cortices. These data support our contention that functional changes in these suprabulbar sites are, via projections to the brainstem, driving the augmented sympathetic outflow to the muscle vascular bed in untreated OSA.