Epicardial Mapping Of Persistent Atrial Fibrillation. Identifying AF Mechanisms In Different Atrial Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$654,341.00
Summary
Atrial fibrillation (AF) is a very common heart rhythm disturbance (arrhythmia) which carries with it an increased risk of having a stroke and a twofold risk of dying. At present, we still have only a limited understanding of the mechanism of AF when it becomes persistent. The aim of this study is to determine the critical mechanism of persistent AF in patients with different types of heart conditions. This knowledge is fundamental to the development of more successful curative approaches.
Changes In Motoneurone And Motor Axon Properties Distal To The Lesion In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$367,530.00
Summary
Following a stroke, adaptive changes occur in spinal cord motoneurones below the level of the stroke, but these are poorly understood. Apart from the exaggeration of spinal reflexes, distal changes have largely been neglected by clinicians. Even the mechanisms responsible for the exaggeration of spinal reflexes are still debated, in part because no single process can account for it. Using novel experimental techniques originally developed to study biophysical properties of human peripheral nerve ....Following a stroke, adaptive changes occur in spinal cord motoneurones below the level of the stroke, but these are poorly understood. Apart from the exaggeration of spinal reflexes, distal changes have largely been neglected by clinicians. Even the mechanisms responsible for the exaggeration of spinal reflexes are still debated, in part because no single process can account for it. Using novel experimental techniques originally developed to study biophysical properties of human peripheral nerves, this project will quantify the changes in excitability that occur in motoneurones and their peripheral extension, the motor axon, and compare these with the findings on the non-paralysed side of the same patients and with healthy matched control subjects. The changes that occur over time will be documented in longitudinal studies. The findings will be correlated with the patient's clinical status, providing insight into the extent to which changes in motoneurone properties drive clinical manifestations such as spasticity. In addition, control studies will provide further insight into whether disturbed transmission in some specific spinal reflex pathways contributes significantly to spasticity. The project is important for understanding the nature of adaptive changes (plasticity) in neural structures following lesions in the central nervous system and will shed light on the remote changes that occur in stroke. The studies are relevant not only for understanding current deficits but also for understanding and perhaps altering outcomes using rehabilitation procedures.Read moreRead less
Cardiac Arrhythmias And Cardiac Contractility During Stress: Regulation By Brainstem Medullary Raph Neurons
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
Life is stressful, and in subjects with predisposed hearts stressful events may provoke sudden life-threatening or fatal disturbances of the heart rhythm (arrhythmias). Activity in nerves that control the heart is the main trigger of arrhythmias. This activity is initiated in the brain, when, for example, we have a sudden emotional shock. At present, the neurochemistry and connections of the brain neurons responsible for arrhythmias, have not been identified. Our project is designed to find answ ....Life is stressful, and in subjects with predisposed hearts stressful events may provoke sudden life-threatening or fatal disturbances of the heart rhythm (arrhythmias). Activity in nerves that control the heart is the main trigger of arrhythmias. This activity is initiated in the brain, when, for example, we have a sudden emotional shock. At present, the neurochemistry and connections of the brain neurons responsible for arrhythmias, have not been identified. Our project is designed to find answers to these questions. Our hypothesis is that the responsible neurons are located in the midline portion of the medulla oblongata (the lower part of the brain); that activation of these neurons will increase cardiac function in a manner that may provoke arrhythmias; and, conversely, that their inhibition will protect the heart during stressful events by suppressing potentially arrhythmogenic neural signals. We hypothesise that cardiac-controlling neurons possess receptors for serotonin (one of the brain neurotransmitters), and that the neurons can be inhibited by drugs that selectively activate a specific subtype of these receptors. Our results will increase our understanding of the causes of cardiac arrhythmias by elucidating the link between emotional-psychological events in the brain and stress-induced cardiac events. Our findings could contribute to the identification of new drugs that will protect the heart during stress.Read moreRead less
Rapid, Cost-effective, Diagnosis And Monitoring Of Multiple Sclerosis By Novel Multifocal Evoked Potential Methods
Funder
National Health and Medical Research Council
Funding Amount
$152,463.00
Summary
A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increas ....A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increasing disability of MS. MS only affects about 0.04% of Australians but the early onset of MS, the high cost of medication, and the prolonged period of disability, mean that the cost to Australia is about $2 billion pa. MRI quantifies the inflammatory phase well but is poorly correlated with the debilitating secondary progression. The common treatments for MS target the inflammatory phase but not the causes of secondary progression, which are unknown. Current diagnostic methods mean diagnosis can take years, meaning that patients can be denied treatment for some time. The applicants have published experiments on 50 MS patients and 27 normal subjects using a variant of the new method. Not only has it shown high diagnostic accuracy, but the new method seems to provide data on the progressive phase, suggesting strongly that it is complementary to MRI. The new method is also much cheaper to set up and run than MRI and so could provide cost-effective means for monitoring patient condition and testing new drugs that are effective against the progressive phase. The applicants have considerable experience commercialising diagnostic technologies, and are currently working with an Australian company developing new diagnostic hardware. That hardware has been adapted to perform the presently proposed experiments. Overall it is reasonable to assume that positive outcomes will be translated into economic and health benefits for Australians.Read moreRead less
Saving Sight Through Novel BioTech Innovations For Inherited Retinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,534,523.00
Summary
Inherited retinal diseases (IRDs) are the leading cause of blindness in working-aged adults. My work focuses on learning more about IRDs, including the correlation between genes and the degenerative changes in the eye. I am developing new outcome measures to predict who might lose vision faster, and to use in clinical trials. I will then use this knowledge in two clinical trials for new IRD treatments - a gene therapy and an electronic device that is implanted into the eye.
Predicting Treatment Response To Onabotulinumtoxin-a In MS-related Tremor: A Combined Clinical, Electrophysiological And Neuroimaging Approach.
Funder
National Health and Medical Research Council
Funding Amount
$546,359.00
Summary
Shaking (tremor) of the upper limbs occur in many people with multiple sclerosis (MS). We have previously shown that botulinum toxin (Botox) injections could help reduce tremor. This study aims to study the effect of Botox in a larger group of people with MS and will include detailed MRI scans and electrical tremor monitoring tests to define the underlying changes in the brain that causes tremor. The results will help make Botox available as a tremor treatment for people with MS.