The Role Of The Posterior Cingulate Cortex In Verbal Associative Learning
Funder
National Health and Medical Research Council
Funding Amount
$146,500.00
Summary
Functional magnetic resonance imaging (fMRI) is a technique which utilises differences between oxygenated and deoxygenated blood to identify regions which are active when the brain is performing a task. This enables us to determine the regions of the brain which are involved in performing different functions. The brain regions supporting memory and learning functions include the hippocampus, the posterior cingulate cortex (PCC), and the frontal lobes. Research has already established the importa ....Functional magnetic resonance imaging (fMRI) is a technique which utilises differences between oxygenated and deoxygenated blood to identify regions which are active when the brain is performing a task. This enables us to determine the regions of the brain which are involved in performing different functions. The brain regions supporting memory and learning functions include the hippocampus, the posterior cingulate cortex (PCC), and the frontal lobes. Research has already established the importance of the hippocampus in memory and learning. However, the exact role of the PCC and the interaction between the PCC and other memory regions remains unclear. This study will use fMRI to investigate the role of the PCC in memory and learning. Specifically, we will compare the activity associated with performance of a difficult memory task and an easier memory task in healthy subjects. The study will then be repeated in patients sustaining damage to the hippocampus. This part of the study will allow us to see how the PCC adapts to disease in the memory system. The results of this study will further clarify the role of the PCC in memory and learning. In addition, this work may be of great importance in the treatment and rehabilitation of patients with memory disorders.Read moreRead less
Relationship Between Anterior Cingulate Morphology, Neuronal Integrity And Function In Schizophrenia And OCD
Funder
National Health and Medical Research Council
Funding Amount
$312,813.00
Summary
Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface betw ....Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface between the emotional, feeling part of the brain and the controlling, thinking part. Many, if not all, of the functions performed by the anterior cingulate are disturbed in both schizophrenia and OCD, meaning that studying this region may provide important clues to the nature of the two illnesses. One important characteristic of the anterior cingulate which has not been considered in previous research is its division into three distinct subregions, each with their own specific function. In particular, there is a cognitive region, which deals with response selection and information processing, and an emotional region, which assesses motivational content and controls emotional learning. Because of the nature of the two disorders we intend to study, we believe that schizophrenia will be associated with more abnormalities of the cognitive region, while OCD will be associated with changes in the emotional region. Another important feature of our research design is that we intend to collect data from the same subjects using four separate brain imaging techniques, which provide information about different levels of brain structure and function. This will allow us to interpret our findings from measures of brain chemistry in the context of our findings of brain function. Hopefully this will help us to clarify the pathophysiology of schizophrenia and OCD, and provide potential ways to assess the effect of different treatment strategies in these illnesses.Read moreRead less
Analysis Of FGF Receptor Signalling Involved In Lens Cell Proliferation And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$343,028.00
Summary
Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family pla ....Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family play pivotal roles in lens developmental biology by influencing lens cell proliferation and differentiation. An important finding from our laboratory is that FGF induces lens epithelial cell proliferation and differentiation at different concentrations. The FGFs elicit intracellular responses upon binding to and activating cell surface FGF receptors (FGFRs). The FGFRs are membrane bound tyrosine kinases which upon activation, activate specific signalling pathways leading to a specific cellular response. To understand how FGFs mediate and regulate different responses in lens cells, namely cell proliferation and fibre differentiation, we plan to examine the role of FGFRs in normal lens development using genetically altered FGFRs that will be expressed specifically in lenses of transgenic mice. While it is known that four different FGF receptor genes are expressed by the normal developing lens, it is unknown what role each of these play in the process of lens cell proliferation and differentiation. In addition, as we can reproduce a specific FGF-induced lens cellular response in vitro, we will use our lens explant culture system to dissect the signalling pathway(s) downstream from specific receptor activation and correlate this with a specific cellular response. By identifying the molecules and mechanisms that control the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.Read moreRead less
A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Combining input from vision and hearing greatly enhances perception when information from one of these senses is degraded or incomplete, such as when tracking objects in foggy, dark or noisy places. This enhancement is of considerable importance because degraded input is the daily situation faced by many people with hearing or vision impairment. We will study the neural processes underlying our ability to combine vision and hearing to create a more reliable and accurate perception of the world.
The Role Of Integrins In The Regulation Of Scleral Remodelling During Pathological Myopia Development
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change and this is a complex process, driven by the scleral cells and involving the synthesis of structural components and activity of enzymes which breakdown scleral structure. The aim of this project is to investigate the role of specific scleral proteins (integrins) in high myopia. Integrins reside on the surface of the scleral cells and communicate information about the changes going on in the surrounding sclera. We predict these proteins are important in keeping the cell informed of the local biochemical and biomechanical changes in the sclera and in driving the cell to rapidly adapt to these changes. The project will provide a greater understanding of the process of scleral thinning in high myopia and allow us to test the potential of integrins as therapeutic targets in the sclera, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.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. 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