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
Investigating The Clinical And Research Applications Of Whole-genome Sequencing In Parkinson Disease And Other Movement Disorders
Funder
National Health and Medical Research Council
Funding Amount
$266,623.00
Summary
There are many ‘movement disorders’ including Parkinson disease, dystonia, and hereditary spastic paraplegia. These disorders can be caused by mutations (errors in the genetic code) in different genes. The discovery of these genes has improved our understanding of the underlying disease mechanisms. We will use ‘whole genome sequencing’ to read a person’s entire genetic material in a single experiment, allowing us to identify a genetic diagnosis and to discover entirely new disease-causing genes.
Tremor is the rhythmic shaking of a body part and is a common and disabling problem seen in diseases such as Parkinson’s disease and Essential Tremor. At present there is no single diagnostic test to determine the cause of a person’s tremor. This project aims to combine the use of sensors that measure tremor and muscle activity with clinical assessment to develop new tests for reliably diagnosing and monitoring tremor, a key step to treating patients correctly and conducting future drug trials.
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
Investigating The Interaction Of Precursor Inner Membrane Proteins With Translocase Components
Funder
National Health and Medical Research Council
Funding Amount
$585,274.00
Summary
Proteins are synthesised on ribosomes located in the cellular plasm, and then moved to their site of action by specialised transport systems. Import of proteins to the mitochondria involves translocase pores, which come equipped with receptors and chaperones. We are investigating the targeting and transfer of newly synthesised proteins of the MCF carrier family from the ribosomal machinery to the inner mitochondrial membrane, focusing on interaction with chaperones in the intermembrane space.
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
TorsinA Mediated Dystonia, Functional Analysis And Molecular Models
Funder
National Health and Medical Research Council
Funding Amount
$479,817.00
Summary
The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years se ....The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause dystonia. The overall aim of this proposal is to characterise a gene that causes dystonia when disrupted. Understanding the function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model dystonia in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in dystonia and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less