NeuRA Magazine #19

Feature story


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.”

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Brain and Knee Muscle Weakness Study

Why Does Quadriceps Weakness Persist after Total Knee Replacement? An Exploration of Neurophysiological Mechanisms Total knee replacement is a commonly performed surgery for treating end-staged knee osteoarthritis. Although most people recover well after surgery, weakness of the quadriceps muscles (the front thigh muscles) persists long after the surgery (at least for 12 months), despite intensive physiotherapy and exercise. Quadriceps muscle weakness is known to be associated with more severe pain and greatly affect daily activities. This study aims to investigate the mechanisms underlying weakness of the quadriceps muscles in people with knee osteoarthritis and total knee replacement. We hope to better understand the relationship between the changes of the brain and a loss of quadriceps muscle strength after total knee replacement. The study might be a good fit for you if you: Scheduled to undergo a total knee replacement; The surgery is scheduled within the next 4 weeks; Do not have a previous knee joint replacement in the same knee; Do not have high tibial osteotomy; Do not have neurological disorders, epilepsy, psychiatric conditions, other chronic pain conditions; Do not have metal implants in the skull; Do not have a loss of sensation in the limbs. If you decide to take part you would: Be contacted by the researcher to determine your eligibility for the study Be scheduled for testing if you are eligible and willing to take part in the study Sign the Consent Form when you attend the first testing session Attend 3 testing sessions (approximately 2 hours per session): 1) before total knee replacement, 2) 3 months and 3) 6 months after total knee replacement. The testing will include several non-invasive measures of brain representations of the quadriceps muscles, central pain mechanisms, and motor function and questionnaires. Will I be paid to take part in the research study? You will be reimbursed ($50.00 per session) for travel and parking expenses associated with the research study visits. If you would like more information or are interested in being part of the study, please contact: Name: Dr Wei-Ju Chang Email: Phone: 02 9399 1260 This research is being funded by the Physiotherapy Research Foundation.