Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea

Abstract

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.

Structural and functional neural adaptations in obstructive sleep apnea: An activation likelihood estimation meta-analysis

“…(Ayalon et al, 2009a, Ayalon et al, 2009b, Li et al, 2015, Peng et al, 2014). It is worthy to note that one study performed both VBM and rs-fMRI measurements (Zhang et al, 2013) and another one applied both VBM and task fMRI (Fatouleh et al, 2014) (Fig. 1).…”

New developments in the pathogenesis of obesity-induced hypertension

“…These data suggest that elevated muscle vasoconstrictor drive in obstructive sleep apnea is a 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. Absence of overlap in the structural and functional changes may suggest that asphyxic damage because of repeated episodes of nocturnal hypoxia is not the main cause of the sympathoexcitation [60].…”

Obstructive sleep apnea is associated with altered midbrain chemical concentrations

“…Functional MRI studies show increased activation of the ventral and dorsal midbrain during inspiratory loading exercises (Macey et al, 2006, 2003) and decreased activity during cold pressor and expiratory loading challenges in OSA (Harper et al, 2003; Macey et al, 2003). Elevated muscle sympathetic nerve activity (MSNA) correlates with altered Blood Oxygen-Level-Dependent (BOLD) signals in the midbrain in OSA, suggesting a midbrain role in eliciting the high sympathetic tone in the sleep disorder (Fatouleh et al, 2014; Lundblad et al, 2014). CBF is decreased in the right midbrain of OSA subjects (Yadav et al, 2013), which may reflect lower perfusion demand, perhaps from an altered functional state (for example, lower tonic activity), or impaired cerebral perfusion.…”