NeuRA Magazine #19

Feature story

TAKE THE PRESSURE DOWN

A new experimental technique using functional magnetic resonance imaging has improved our understanding of how the brain controls blood pressure.

Vaughan Macefield blood pressure MSNA

Prof Vaughan Macefield

People with high blood pressure caused by chronic pain, obstructive sleep apnoea, anxiety or kidney disease all stand to benefit from the new studies coming out of Prof Vaughan Macefield’s lab.

One of the central questions that Prof Macefield and his team (PhD student Sophie Kobuch, Dr Rachael Brown and Assoc Prof Luke Henderson) hope to address is how the brain is involved in increasing or decreasing blood pressure. Until now, it hasn’t been clear which particular areas of the brain are involved in this process. Macefield’s team suspect that “higher centres” of the brain are involved – that is, the centres that process sensory information, analyse information and experience emotion.

New sets of studies hope to answer how these areas bring about changes to blood pressure. “It’s important to know this when you consider that chronic mental stress and anxiety can lead to high blood pressure,” Prof Macefield explains.

Currently, we know that blood pressure is altered when blood vessels that serve our skeletal muscles are constricted, and that this is controlled by muscle sympathetic nerve activity (MSNA). Studies emerging from Prof Macefield’s lab are looking at how the brain is involved in this process by using fine microelectrodes, inserted through the skin into a nerve at the side of the knee, to record bursts of MSNA going to the blood vessels.

“MSNA originates in the brain then travels down the spinal cord and out to all the nerves in the body, supplying all the muscles,” he explains. “We’re recording that signal using a needle in a nerve cluster at the side of the knee. While we’re doing that, we’re also recording brain activity, via functional magnetic resonance imaging (fMRI), so that we can identify where in the brain these bursts of nerve activity are occurring.”

The fMRI studies have shown that areas of the brain such as the insula, the dorsolateral prefrontal cortex, the dorsomedial and ventromedial hypothalamus, the precuneus, and structures in the cerebellum all contribute to the generation of MSNA. Some of these areas, such as the prefrontal cortex, are involved in higher-order emotional and cognitive functions, including reasoning, problem solving, planning, some aspects of memory and controlling emotional responses.

These are also areas that are involved in modulating chronic pain or anxiety. “Many people who experience chronic pain often go on to develop hypertension,” Prof Macefield explains, “but we haven’t yet been able to use physiological or psychological factors to predict who is likely to do so. Understanding the underlying neural cause of these different responses to pain opens up a whole new avenue of research to explore.”

More recently, the lab published a study that looked at the parts of the brain that regulate blood pressure to see how they behave during pain.

“For this we used two groups; one who show an increase in MSNA and blood pressure during pain and the other who show a decrease. We measured their brain activity and MSNA while infusing sterile, salty water into their leg muscle for an hour to simulate long-term pain.”

Initially, it was thought that these different reactions may have been caused by differences in pain tolerance, attitudes to pain, resting MSNA levels, or levels of anxiety. However, none of these were shown to have a significant correlation with MSNA levels. Instead, it had to do with a part of the brain – the dorsomedial hypothalamus – that plays a key role in creating physiological responses to stress.

“We also found the executive areas of the brain were involved, which are responsible for our higher order processing. So the fact that they were upregulated supports our conclusions from our earlier work, that these higher-order structures of the brain are indeed involved in blood pressure regulation.

“It also explains why anxiety and blood pressure are related. Australia was the first country to recognise anxiety as a cause of hypertension. So there are all these executives and various people who have work-related stresses that end up with high blood pressure.”

The team will go on to further explore the link between anxiety, chronic pain and blood pressure in future studies to understand how to better treat hypertension. These studies will also improve our understanding of the neural factors that increase blood pressure in people with renovascular hypertension, and extending the work they have recently published on changes in the brains of people with obstructive sleep apnoea.

“Now that we have these experimental tools where we can look at the generation of MSNA using fMRI in real time we can address these various questions, which will ultimately increase our understanding of how the brain controls blood pressure.”

To access to the NeuRA Magazine #19 Dr Julie Brown: 5 minutes with story click here

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This project aims to deliver the most comprehensive, detailed and stereotaxically accurate MRI atlas of the canonical human brain. In human neuroscience, researchers and clinicians almost always investigate images obtained from living individuals. Yet, there is no satisfactory MRI atlas of the human brain in vivo or post-mortem. There are some population-based atlases, which valiantly solve a number of problems, but they fail to address major needs. Most problematically, they segment only a small number of brain structures, typically about 50, and they are of limited value for the interpretation of a single subject/patient. In contrast to population-based approaches, the present project will investigate normal, living subjects in detail. We aim to define approximately 800 structures, as in the histological atlas of Mai, Majtanik and Paxinos (2016), and, thus, provide a “gold standard” for science and clinical practice. We will do this by obtaining high-resolution MRI at 3T and 7T of twelve subjects through a collaboration with Markus Barth from the Centre for Advanced Imaging at the University of Queensland (UQ). The limited number of subjects will allow us to image each for longer periods, obtaining higher resolution and contrast, and to invest the required time to produce unprecedented detail in segmentation. We will produce an electronic atlas for interpreting MR images, both as a tablet application and as an online web service. The tablet application will provide a convenient and powerful exegesis of brain anatomy for researchers and clinicians. The open access web service will additionally provide images, segmentation and anatomical templates to be used with most common MR-analysis packages (e.g., SPM, FSL, MINC, BrainVoyager). This will be hosted in collaboration with UQ, supporting and complementing their population-based atlas.
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