One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movement ....One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. We will address one particular aspect of this problem, namely the organisation of the cortical areas that provide visual control for skilled movements. It is proposed that there are two parallel brain circuits involved in the analysis of motion, one tracking the movement of objects, and the other analysing a person s self-motion. Consider, for example, the task of a tennis player who has to return a serve. In order to achieve this, the brain must precisely integrate information about the ball s motion, as well as information about the player s speed and direction. This requires precise control of eye movements (to keep the eyes on the ball), as well as the ability to control the limb and trunk muscles. The aim of this study will be to map the anatomical framework underlying our ability to process all the relevant visual motion information, and to coordinate the appropriate motor responses. Such work is fundamental for understanding the functional organisation of the brain. It also has the potential to lay the groundwork for developments in areas of applied research, including medicine (e.g. the design of better rehabilitation strategies for people with brain damage), robotics- artificial intelligence (e.g. the improvement of artificial systems capable of vision), and the cognitive sciences (e.g. a better understanding of factors that limit human responses to visual stimuli).Read moreRead less
Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw ....Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw muscles. The AIM 1 study will provide important new information about the functional organisation of the motor cortex in the control of jaw muscles during speech. This information is needed to improve understanding of dysarthria, a common disturbance of speech due to impaired muscular control following unilateral cortical stroke, and less common conditions involving speech motor control such as spasmodic dysphonia (a cranial dystonia) and dysprosody (disturbance of speech articulation and rhythm found in Parkinson s disease). The AIM 2 and 3 studies will provide a comprehensive characterization of cortical inhibitory mechanisms that are an important but poorly understood component of the cortical control of jaw muscles. This information is necessary to understand normal function, and the mechanisms of disturbances to jaw muscle function with neurological disease or injury. The AIM 4 studies will show whether impaired cortical inhibition contributes to the pathophysiology of two poorly understood disorders affecting jaw muscles (bruxism and oromandibular dystonia). Current therapies for these conditions are unsatisfactory, due to a limited understanding of the mechanisms involved. If cortical inhibition is abnormal in these conditions this will lead to novel treatment therapies (e.g., drugs to correct the imbalance, or strategies to induce plastic change in the cortex).Read moreRead less
Is EphA4 The Major Molecular Regulator Of Axonal Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$491,000.00
Summary
Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contri ....Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contribuing to the enormous personal, financial, and community costs of this problem, estimated to cost the Australian community $200 million a year. In recent years advanced anatomical and molecular approaches to the problem of repair of the central nervous system have provided great insights into the neuronal and glial reactions to neural damage that appear to govern the success or failure of neural regeneration. Our preliminary data indicate that a receptor tyrosine kinase, EphA4, which is important for axonal pathfinding in the developing nervous system, is a potent inhibitor of neural regeneration following spinal cord injury. In this project we will determine the mechanisms by which EphA4 exerts its inhibitory effects, and examine the effect of neutralizing EphA4 signalling on neural regeneration. Success in achieving this result will lead to the development of a therapeutic intervention that we will test in mouse models.Read moreRead less
One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. In this project, we will address the organization of a poorly known group of visual areas, which is located deep in a part of the brain called the in ....One of the main trends in the evolution of the primate brain was the huge expansion of the cortical areas devoted to visual processing. However, the exact role of individual areas remains highly controversial, making detailed physiological and anatomical studies in suitable primate models a key step to elucidating their function in the human brain. In this project, we will address the organization of a poorly known group of visual areas, which is located deep in a part of the brain called the interhemispheric fissure (the medial complex of visual areas). Preliminary evidence suggests that these areas may provide anatomical shortcuts linking vision, behavioural reactions, and emotion. Suppose, for example, that you are sitting outside reading. Although deep in concentration, you are still able to detect the sudden movement of an approaching object in your peripheral field of vision. In many cases you can react (e.g., by ducking , or raising your arms to protect the face) long before you register what the object actually is. An adrenaline rush often accompanies these quick motor reactions, implying a parallel activation of the autonomic nervous system. While the mechanism by which the brain promotes these quick reactions remains poorly understood, we believe that the medial complex of visual areas holds the key. The aim of this study is to map the anatomical framework underlying our ability to react to sudden stimuli in our peripheral visual field. Such work is fundamental for understanding the functional organization of the brain. It also has the potential to lay the groundwork for developments in areas of applied research, including medicine (e.g. the design of better rehabilitation strategies for people with brain damage) and the cognitive sciences (e.g. a better understanding of the factors that limit human responses to visual stimuli).Read moreRead less
The Use Of Soluble Antagonists Of EphA4 In Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$622,361.00
Summary
Permanent and limited recovery of function following spinal cord injury is a direct result of the lack of nerve regrowth through the injury. Our preliminary data suggest that antagonising the effects of EphA4, a protein involved in brain development, leads to substantial functional recovery simultaneous with nerve regrowth. In addition to designing new, more effective blockers of EphA4, we will study the signalling pathways that EphA4 activates to inhibit nerve regrowth.
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
Neural Mechanisms Associated With Recovery Of Function Following Motor Cortical Lesions
Funder
National Health and Medical Research Council
Funding Amount
$196,415.00
Summary
Damage to movement control areas in the brain early in life (e.g. cerebral palsy) or in adulthood (e.g. stroke, tumours) results in motor weakness and loss of skill; over a period of many months there is gradual recovery of function. The neural mechanisms that are associated with functional reorganization of the brain and motor recovery are not well understood. This project plans to use animal experiments to identify the location of regions in the brain that undergo neural reorganization and com ....Damage to movement control areas in the brain early in life (e.g. cerebral palsy) or in adulthood (e.g. stroke, tumours) results in motor weakness and loss of skill; over a period of many months there is gradual recovery of function. The neural mechanisms that are associated with functional reorganization of the brain and motor recovery are not well understood. This project plans to use animal experiments to identify the location of regions in the brain that undergo neural reorganization and compensate for lost function. Following brain lesions detailed mapping of the motor areas of the brain and a careful study of movement disabilities will be performed. The study will attempt to identify changes in motor maps that indicate neural reorganization and relate these changes to motor recovery. The results of this study will be used in future projects to test training programs, drugs and neural prosthesis on neural reorganization and recovery of function. Eventually the information may be used to direct pharmacological and physiotherapeutic interventions, and motor rehabilitation programs for optimal recovery of function.Read moreRead less
Efficacy And Mechanisms Of Exercise Training In Diastolic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$385,250.00
Summary
Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrom ....Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrome is most frequently due to ischemic or hypertensive heart disease, and most commonly occurs in the elderly. The optimal management of DHF is not well defined, although some drug trials are currently in progress. A number of studies have shown exercise training to improve functional capacity by 15-20% in typical heart failure. However, training has not so far been trialled in DHF. In this multicenter, multi-disciplinary study, we will study a training and control group to determine whether exercise capacity and DHF symptoms are responsive to exercise training. This work will teach us about the optimum exercise prescription, in terms of the duration and nature of training, as well as the safety and effectiveness of exercise training. By using a number of sensitive measurements of heart and vessel function (in which our group has special expertise), we will identify whether exercise training exerts its effect through improvement in vascular function and myocardial properties. If successful, the clinical implications of this study are that; 1. Exercise training will be adopted to improve functional capacity and symptoms of DHF 2. The merits of aerobic and strength training will be identified in DHF 3. Abnormal blood vessel function will be identified as a major and reversible contributor to DHFRead moreRead less