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Student research project

Supervisors: Professor Vaughan Macefield and Dr Tye Dawood

Project summary

This project will look to identify the cortical and subcortical areas of the human brain responsible for the control of blood pressure in health and cardiovascular disease.

The sympathetic branch of the autonomic nervous system plays a critical role in the control of blood pressure, both through its effects on the heart and, importantly, through the beat-to-beat control of blood flow through systemic blood vessels. Arterioles in the skeletal muscles are particularly important in this regard (the muscle vascular bed has a very high volume), and increases in muscle sympathetic nerve activity (MSNA) feature in many cardiovascular and cardiorespiratory diseases — such as hypertension, heart failure, obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD). MSNA can be recorded directly via metal microelectrodes inserted percutaneously into a peripheral nerve in awake humans (microneurography), and my group has spent the last 30 years using this technique.

Most recently, my group developed the methodology for recording MSNA at the same time as performing functional Magnetic Resonance Imaging (fMRI) of the brain: MSNA-coupled fMRI, combined with functional connectivity analyses, allows us to use the pattern of muscle sympathetic nerve activity to identify regions within the brain that contribute to the generation of MSNA. This gives us unparalleled access to cortical and subcortical regions of the brain involved in the beat-to-beat control of blood pressure, allowing us to explore this control both in health and in disease. Mine is the only group in the world undertaking MSNA-coupled fMRI. We have used this approach to functionally identify sites — including the prefrontal cortex, insula, hypothalamus and medulla — that contribute to the generation of spontaneous bursts of MSNA in healthy normotensive subjects. Moreover, in our recently completed NHMRC grant we identified several functional changes in the brain in hypertensive patients with obstructive sleep apnoea (OSA), following them over 12 months of treatment. We are currently using MSNA-coupled fMRI to investigate the increases in MSNA in different forms of hypertension and during experimentally-induced muscle pain.

The proposed project will extend this line of enquiry to heart failure and chronic obstructive pulmonary disease to address the following questions: what are the functional and structural changes in the brain responsible for generating the pathophysiological increases in MSNA in these two conditions, and how does heart or lung transplant reduce the sympathoexcitation?

This project is suitable for a PhD student.

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