Abstract
Brain regulation of autonomic function in obstructive sleep apnea (OSA) is disrupted in a sex-specific manner, including in the insula, which may contribute to several comorbidities. The insular gyri have anatomically distinct functions with respect to autonomic nervous system regulation; yet, OSA exerts little effect on the organization of insular gyral responses to sympathetic components of an autonomic challenge, the Valsalva. We further assessed neural responses of insular gyri in people with OSA to a static handgrip task, which principally involves parasympathetic withdrawal. We measured insular function with blood oxygen level dependent functional MRI. We studied 48 newly-diagnosed OSA (age mean±std:46.5±9 years; AHI±std:32.6±21.1 events/hour; 36 male) and 63 healthy (47.2±8.8 years;40 male) participants. Subjects performed four 16s handgrips (1 min intervals, 80% subjective maximum strength) during scanning. fMRI time trends from five insular gyri-anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)-were assessed for within-group responses and between-group differences with repeated measures ANOVA (p<0.05) in combined and separate female-male models; age and resting heart-rate (HR) influences were also assessed. Females showed greater right anterior dominance at the ASG, but no differences emerged between OSA and controls in relation to functional organization of the insula in response to handgrip. Males showed greater left anterior dominance at the ASG, but there were also no differences between OSA and controls. The males showed a group difference between OSA and controls only in the ALG. OSA males had lower left activation at the ALG compared to control males. Responses were mostly influenced by HR and age; however, age did not impact the response for right anterior dominance in females. Insular gyri functional responses to handgrip differ in OSA vs controls in a sex-based manner, but only in laterality of one gyrus, suggesting anterior and right-side insular dominance during sympathetic activation but parasympathetic withdrawal is largely intact, despite morphologic injury to the overall structure.
Highlights
Cardiovascular disease (CVD) in obstructive sleep apnea (OSA) is difficult to treat [1, 2], possibly due to long-term changes in the autonomic nervous system (ANS) that underpin high sympathetic tone and disrupt blood pressure regulation [3]
Females showed greater right anterior dominance at the anterior short gyrus (ASG), but no differences emerged between OSA and controls in relation to functional organization of the insula in response to handgrip
Insular gyri functional responses to handgrip differ in OSA vs controls in a sex-based manner, but only in laterality of one gyrus, suggesting anterior and right-side insular dominance during sympathetic activation but parasympathetic withdrawal is largely intact, despite morphologic injury to the overall structure
Summary
Cardiovascular disease (CVD) in obstructive sleep apnea (OSA) is difficult to treat [1, 2], possibly due to long-term changes in the autonomic nervous system (ANS) that underpin high sympathetic tone and disrupt blood pressure regulation [3]. Most studies exploring the comorbidities associated with OSA include both male and female participants, and evidence of whether these links are affected by sex remain under investigation [5]. There is evidence of a female predominance of OSA-related stoke as well as more severe detrimental changes in endothelial function, peak blood flow, systemic inflammation, and digital vascular function [7, 8]. Other clinical cardiovascular characteristics, such as morning BP patterns and responses to acute BP challenges in OSA vary by sex [3, 9]. These differences in physiologic responses between sexes in OSA presumably have an underlying neural basis
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