Sex differences in insular cortex gyri responses to a brief static handgrip challenge

Abstract

BackgroundCardiovascular disease varies between sexes, suggesting male-female autonomic control differences. Insular gyri help coordinate autonomic regulation and show a sex-dependent response to a sympathetic challenge.MethodsWe examined sex-related insular gyral responses to a short static handgrip exercise challenge eliciting parasympathetic withdrawal with functional magnetic resonance imaging (fMRI) during four 16-s challenges (80% maximum strength) in 23 healthy females (age; mean ± std 50 ± 8 years) and 40 males (46 ± 9 years). Heart rate (HR) and fMRI signals were compared with repeated measures ANOVA (P < 0.05). Additional analyses were performed with age and age interactions, as well as right-handed only subjects.ResultsFemales showed higher resting HR than males, but smaller percent HR change increases to the challenges. All gyri showed fMRI patterns concurrent with an HR peak and decline to baseline. fMRI signals followed an anterior-posterior organization in both sexes, but lateralization varied by gyri and sex. All subjects showed greater signals in the anterior vs. posterior gyri (females 0.3%, males 0.15%). The middle gyri showed no lateralization in females but left-sided dominance in males (0.1%). The posterior gyri showed greater left than right activation in both sexes. The anterior-most gyri exhibited a prominent sex difference, with females showing a greater right-sided activation (0.2%) vs. males displaying a greater left-sided activation (0.15%). Age and handedness affected a minority of findings but did not alter the overall pattern of results.ConclusionsThe anterior insula plays a greater role in cardiovascular regulation than posterior areas during a predominantly parasympathetic withdrawal challenge, with opposite lateralization between sexes. In females, the left anterior-most gyrus responded distinctly from other regions than males. Those sex-specific structural and functional brain patterns may contribute over time to variations in cardiovascular disease between the sexes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0135-9) contains supplementary material, which is available to authorized users.

Regional cortical thickness changes accompanying generalized tonic-clonic seizures

“…A significant factor in determining neural influences on breathing and cardiovascular control in disease conditions is sex; such conditions, including obstructive sleep apnea, heart failure, and congenital central hypoventilation syndrome can show significant injury in cardiovascular and respiratory regulatory brain sites ( Kumar et al, 2012 ; Kumar et al, 2015 ; Macey et al, 2008 ; Macey et al, 2012b ; Ogren et al, 2014 ), but that injury frequently differs substantially between males and females, especially in limbic areas ( Macey et al, 2012a ). Moreover, responsiveness of affected brain sites to evoked pain or blood pressure challenges significantly differs between sexes ( Henderson et al, 2008 ; Macey et al, 2016 ; Macey et al, 2017 ). The mechanisms underlying these pattern differences between males and females are unclear, but there is a potential for sex-related protective mechanisms and consequent injury differences to exist in GTCS, where analogous exposure to hypoxic and extreme blood pressure changes are common in the condition.…”

Gender Differences in Hemodynamic Regulation and Cardiovascular Adaptations to Dynamic Exercise

“…Very few studies have dealt with gender-related differences in the three main neural reflexes which adjust the cardiovascular system during exercise. To the best of our knowledge, there is only one study addressing the potential differences between males and females in central command activation [ 74 ]. In this research conducted during static handgrip, authors found sex-related different patterns of activation in insular gyral responses.…”

Insular functional organization during handgrip in females and males with obstructive sleep apnea

“…In healthy adults, we showed the functional organization of the insular cortex is gyri-specific for the handgrip, a challenge that combines autonomic perturbation and an intentional motor activity [ 46 , 47 ]. Specifically, the anterior insula is more activated during the early, predominantly parasympathetic withdrawal phase [ 48 , 49 ].…”

“…In contrast, the strain phase of the handgrip challenge, which is associated with a moderate HR and sympathetic increase, elicited the greatest responses in the middle insular gyri. These sex-specific neural patterns co-occur with sex-specific peripheral differences, with females displaying HR smaller increases [ 3 , 47 ]. The data are consistent with a recent human study showing tachycardic responses elicited by stimulating the posterior insula and bradycardic responses from stimulating the more anterior insular cortex [ 50 ].…”