Male/female brain reacts differently to cardiac stress
A new study finds that heart related diseases may need to be diagnosed and treated by gender. The new study from the UCLA School of Nursing, identifies a region of the brain that helps manage stress, heart rate and blood pressure — but, reacts differently between men and women.
Cardiovascular diseases may opperate differently in women and men, ultimately affecting how they should be diagnosed and treated. The study led by Paul Macey, associate professor of nursing, is published in the journal Biology of Sex Differences. Primarily used in research, functional MRI, or fMRI, are scans made using magnetic resonance imaging to measure brain activity by following changes in blood flow. fMRI scans were made of volunteers as they performed hand-grip exercises, capturing the rise in their blood pressure and heart rate by following signals to their brains.
Researchers found the portion of a brain region called the insular cortex (made up of gyri — or folds) shows differences between men and women.
In women, the right side of the front insular gyrus was more activated by hand-grip exercise, men had a greater left-side activation. Women showed a higher resting heart rate than did males, and didn't have as great a heart rate increase when challenged with the hand-grip exercise.
The hand-grip test was a follow-on study to earlier published research by Macey and colleagues of the same brain region using a "Valsalva maneuver." Such a maneuver is performed by attempting to exhale against a closed airway. Participants close their mouths and pinch their noses shut while pressing out as if blowing up a balloon. The Valsalva maneuver leads to changes in blood pressure through "fight or flight" brain responses, controlled by a part of the nervous system called the "sympathetic" nervous system.
By contrast, the hand grip cuts back on the "rest and recovery" brain responses, called the "parasympathetic" nervous system. The sympathetic and parasympathetic nervous systems are part of our autonomic or "involuntary" nervous system.
In general, the right side of the insular cortex is more sympathetic, and the left side more parasympathetic.
"With the hand grip, the differences were in the left side of the brain, while in the Valsalva study, the differences appeared on the right side, which was a surprise at first.
"What both studies show is that healthy men's and women's brains respond differently. So, we may have to re-evaluate separately in men and women what constitutes a disease state — versus a healthy state to see if people are more or less vulnerable to cardiovascular illness according to their sex."
Paul M. Macey PhD, Director of Information Technology and Innovation, Chief Innovation Officer, Associate Professor in Residence, UCLA School of Nursing, University of California Los Angeles, California, USA.
The research also sheds more light on the functions of the insular gyri. This middle area of the brain had been difficult to test until recently through imaging techniques, Macey said. Today, the region is studied for its roles in self-awareness and stress, as well as cardiovascular control.
Macey and colleagues are continuing to map the functions of this area to make connections between changes and risks for a wide range of diseases.
Cardiovascular 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.
We 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.
Females 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.
The 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.
Keywords: Parasympathetic fMRI Cardiovascular Functional neuroanatomy Limbic
Macey's colleagues in the study are Nicholas Rieken, Jennifer Ogren, Katherine Macey, Rajesh Kumar and Ronald Harper, all of UCLA.
The study was funded by a grant from the NIH National Institute of Nursing Research (NR013693).
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