High-resolution Brain Imaging Of Basal Ganglia Function
Funder
National Health and Medical Research Council
Funding Amount
$589,083.00
Summary
This project will develop new methods for high resolution MRI imaging of the human brain. We will assess functions of deep brain areas known as the basal ganglia that play a critical role in movement planning and co-ordination. Dysfunction within the basal ganglia is responsible for the motor impairments seen in people with Parkinson’s disease. In this project, we will examine changes in basal ganglia function and structure that lead to individual differences in movement control and learning.
Experience drives changes in the connections between neurons in the brain. This neuroplasticity is a fundamental property of the nervous system, critical for learning and memory, but also important for recovery from injury and development of some nervous system disorders. This study will improve understanding of how, with practice, the human brain adapts to functional demands in the development of motor skill. Musicians are used as exemplars of fine motor skill who show long-term experience-driv ....Experience drives changes in the connections between neurons in the brain. This neuroplasticity is a fundamental property of the nervous system, critical for learning and memory, but also important for recovery from injury and development of some nervous system disorders. This study will improve understanding of how, with practice, the human brain adapts to functional demands in the development of motor skill. Musicians are used as exemplars of fine motor skill who show long-term experience-driven plasticity in the brain. This study will provide specific and detailed quantitative information about how motor cortex circuits important for control of the hand are altered in musicians. The study will also improve understanding of basic mechanisms involved in short-term neuroplasticity associated with motor learning in musicians and non-musicians, and hemispheric or training-related differences in these properties which may contribute to different abilities to use the hand for fine motor tasks.Read moreRead less
The Role Of Afferent Input In The Development Of Focal Task Specific Dystonia
Funder
National Health and Medical Research Council
Funding Amount
$213,000.00
Summary
The term dystonia is used to describe a condition that is characterised by abnormal muscle activation patterns. This leads to impaired control of voluntary movements. Depending upon which part of the body is affected, dystonia may be classified as generalised (affecting two or more body segments), hemi (involving one side), segmental (involving adjacent body parts or a segment), or focal (affecting one part of the body). Many of the focal dystonias are also task specific and the aim of this prop ....The term dystonia is used to describe a condition that is characterised by abnormal muscle activation patterns. This leads to impaired control of voluntary movements. Depending upon which part of the body is affected, dystonia may be classified as generalised (affecting two or more body segments), hemi (involving one side), segmental (involving adjacent body parts or a segment), or focal (affecting one part of the body). Many of the focal dystonias are also task specific and the aim of this proposal is to investigate these task-specific focal dystonias. Task-specific focal dystonia is common in the community and causes considerable suffering and loss of productivity. For example, writer's cramp (a common form of task specific focal dystonia) is probably the commonest cause of writing difficulty in patients in whom this is the sole complaint. No treatment regimen has been shown to be effective in alleviating it's often debilitating symptoms. The aim of these studies is to further define the pathophysiological changes seen in task-specific dystonia and investigate the mechanisms responsible for their generation. Using the techniques of transcranial magnetic stimulation and peripheral nerve stimulation we will investigate the organisation of the motor cortex in this condition and examine the influence of afferent input on intrinsic cortical circuitry. We hypothesise that the motor regions of the brain are more sensitive to the particular repeated patterns of sensory information reaching the brain during repetitive movement and this results in abnormal alterations in organisation that may be responsible for the symptoms of dystonia. Additionally, we predict that it may be possible to reverse these organisational changes by applying novel patterns of nerve stimulationRead moreRead less
Bilateral Movement Therapy In Post-stroke Hemiparesis
Funder
National Health and Medical Research Council
Funding Amount
$265,993.00
Summary
Stroke is the leading cause of long-term disability in adults in Australia, accounting for approximately 25% of all disability. A common motor disability resulting from stroke is hemiparesis, weakness or paralysis on one side of the body. This disability severely impairs an individual's capacity to perform activities of daily living, making them dependent on relatives and health professionals for daily care. By developing effective interventions to treat stroke-induced hemiparesis both the disab ....Stroke is the leading cause of long-term disability in adults in Australia, accounting for approximately 25% of all disability. A common motor disability resulting from stroke is hemiparesis, weakness or paralysis on one side of the body. This disability severely impairs an individual's capacity to perform activities of daily living, making them dependent on relatives and health professionals for daily care. By developing effective interventions to treat stroke-induced hemiparesis both the disability caused by stroke and the associated personal and financial costs will be lessened. A number of interventions focusing on the affected side (unilateral), including active movements and muscle stimulation are being investigated as possible treatments for stroke-induced hemiparesis. Recent evidence suggests that involving the unaffected side simultaneously (bilateral therapies) could be effective, and may provide addtional benefits over unilateral therapies. The aim of this research is to thoroughly examine the effectiveness of bilateral therapies by incorporating them into established interventions. The findings from these studies will aid in the development and refinement of movement therapies aimed at promoting recovery from stroke-induced hemiparesis.Read moreRead less
Pathologies Of Action Control: Amygdala-striatal Interactions And The Development Of Habits.
Funder
National Health and Medical Research Council
Funding Amount
$431,867.00
Summary
Changes in basal ganglia function, whether produced by neurodegenerative disorders, stroke, injury or disease, can produce pathological changes in action control. This proposal will assess the role of amygdala afferents on basal ganglia structures, most notably the dorsal striatum, in this process. Using an animal model we will compare the role of central and basolateral amygdala inputs to striatum in decision-making, choice and the transition of actions to reflexive, habitual responses.
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
Novel Assessments Of The Central And Peripheral Control Of The Human Hand
Funder
National Health and Medical Research Council
Funding Amount
$365,105.00
Summary
This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the t ....This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the thumb is flexed by a single muscle, a muscle only present in humans. We want to determine how this muscle works, and how the force it produces affects the whole hand. We will use specialised neurophysiological techniques to do this in human volunteers. There is no comparable animal model for this type of work due to significant differences at both the level of the brain and the level of the muscle. Second, we want to understand better how the cells in the spinal cord which control the hand (and other) muscles work. We have two new ways to do this, including a novel technique which can activate these cells with a form of stimulation that may help us improve functional electrical stimulation. Finally, with 27 bones and more than 25 muscles which operate it, the hand is not simple to control. We will use a new apparatus to measure how well it is controlled, and we will directly stimulate the motor areas of the brain to evaluate the control. From this, we will come up with new understanding, as well as new stimulus and measurement techniques that can be applied to patients with impaired hand function, as occurs all too often after stroke.Read moreRead less
Volitional And Non-volitional Control Of Human Balance: Normal Physiology And Changes With Ageing
Funder
National Health and Medical Research Council
Funding Amount
$383,066.00
Summary
How does the brain control balance when we stand? Our research shows that two very distinct processes operate to produce distinct postural, perceptual and cardiovascular outcomes. These experiments investigate the neurophysiology that coordinates these systems and what happens with age. The results will fundamentally change views on balance control. Balance problems are common in neurological disorders and old age. Knowing how balance works will improve diagnosis, treatment and rehabilitation.
Influence Of Cortical Stroke And Experimental Brain Stimulation On Excitability Of Human Corticobulbar Motor Projections And Swallowing Function
Funder
National Health and Medical Research Council
Funding Amount
$130,183.00
Summary
Swallowing disorders often result from damage to the brain. They have profound consequences on patient health and quality of life and result in significant medical and socioeconomic costs. This project firstly investigates how motor networks in the brain control the muscles involved in swallowing and how this control is affected by stroke. Secondly, it evaluates the potential of novel interventions to improve impaired swallowing function following stroke by reorganising motor networks.
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.