Neural effects of breathing training in obstructive sleep apnea - PROJECT SUMMARY This proposal aims to investigate the neural mechanisms by which inspiratory muscle training (IMT) reduces blood pressure (BP) in patients with obstructive sleep apnea (OSA). OSA affects over 10% of the population and is a major risk factor for hypertension and cardiovascular disease. Traditional treatments like continuous positive airway pressure (CPAP) have limited efficacy in lowering BP, creating a need for alternative approaches. Several studies show that IMT, which involves breathing in against resistance, can meaningfully reduce systolic BP. The training typically involves performing a daily set of 30 inhalations through a device that provides a fixed resistance (a breathing trainer). The IMT practice only takes 5 minutes a day, and while it does not replace CPAP or other treatments, it is popular with our patients. However, the mechanisms by which IMT lowers BP in OSA are unknown. The hypothesis being tested in this proposal is that IMT lowers BP by reducing centrally-driven sympathetic nervous system activity, which is often elevated in OSA patients. This proposal focuses on the role of the insula, a brain region involved in autonomic regulation and sensory integration, factors likely impacted by IMT. The project will assess whether IMT alters insula function and connectivity within the central autonomic network brain structures, which could underlie a reduction in sympathetic tone and BP. We will use resting-state functional magnetic resonance imaging (rsfMRI) connectivity to measure changes in insula connectivity, and magnetic resonance spectroscopy (MRS) to measure insula levels of glutamate, a key excitatory neurotransmitter. Since high sympathetic drive in OSA is likely being driven by high activity in the anterior insula especially, we hypothesize a reduction in brain activity in this region, reflected as lower connectivity and lower glutamate levels. The study will involve two groups of untreated, moderate or severe OSA patients with elevated BP or stage 1 hypertension (bp ≥120/80 mmHg to <140/90 mmHg). Our target sample is 45 participants who complete each arm, balanced for age and sex. One group will undergo 10 weeks of IMT at resistance 65% of maximum, while a control group will train at resistance 15% of maximum. The specific aims are to assess: 1) changes in insula connectivity with other brain regions involved in autonomic control, and 2) changes in insula glutamate levels. We will consider potential confounds such as anti-hypertensive medication usage. The hypothesis is that IMT will induce lower connectivity and lower glutamate levels compared to the control group. We will monitor and control for potential confounds such as antihypertensive medications, drop-out, and adherence. Overall, the findings will elucidate a potential neural basis of IMT’s impact on BP, offering insights into both breathing training and other potential new interventions for hypertension in OSA patients.
