Autism and its milder forms affect approximately 6 per 1,000 children. The biological basis of the disorder is unknown, so considerable research is being invested in identifying cognitive processes that are atypical in children with autism because this may help identify key areas of the brain affected by the disorder. This research has established that children with autism often outperform their typically developing peers on tasks that require detailed analysis of visual information. In contrast ....Autism and its milder forms affect approximately 6 per 1,000 children. The biological basis of the disorder is unknown, so considerable research is being invested in identifying cognitive processes that are atypical in children with autism because this may help identify key areas of the brain affected by the disorder. This research has established that children with autism often outperform their typically developing peers on tasks that require detailed analysis of visual information. In contrast, visual tasks that require integrating information often reveal impaired performance in children with autism. Human vision is achieved through two pathways in the brain - a dorsal pathway most responsive to changing (e.g. moving or flickering) stimuli and a ventral pathway most responsive to enduring stimulus features (e.g. colour, pattern). Increasingly complex visual processing is achieved at higher levels in each pathway through integrating information from lower levels. One objective of our work is to identify which levels of processing in each of the dorsal and ventral pathways show atypical functioning (either enhanced or impaired) in autism. We will do this using tasks designed to establish thresholds for different perceptual judgements, such as identifying patterns in a field of dots. Children with autism will be compared to typically developing children and also to children with Specific Language Impairment (SLI). This will enable us to establish whether the same profile of strengths and weaknesses in perception and cognition are observed in autism and SLI, or whether they can be distinguished on this basis. The significance of the work is that it will advance considerably the understanding of atypical visual processing in autism and SLI. Also, by identifying perceptual and cognitive differences in children with autism, we may be able to develop tests to identify infants affected by the disorder and commence remediation at an early age.Read moreRead less
The Roles Of Lipoprotein Multigene Families In Pathogenesis Of Mycoplasma Pneumoniae
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Mycoplasma pneumoniae is one of the most common causes of community acquired pneumonia. Although it can usually be successfully treated with antibiotics, it can result in more severe diseases and can be difficult to diagnose accurately. It has been identified as a target for vaccine development, but this has been hampered by the limited understanding we have of how it causes disease. The attempts at vaccination that have been made have resulted in vaccines which induced more severe, rather than ....Mycoplasma pneumoniae is one of the most common causes of community acquired pneumonia. Although it can usually be successfully treated with antibiotics, it can result in more severe diseases and can be difficult to diagnose accurately. It has been identified as a target for vaccine development, but this has been hampered by the limited understanding we have of how it causes disease. The attempts at vaccination that have been made have resulted in vaccines which induced more severe, rather than less severe, disease. Investigations of several other related bacteria have shown that they are able to vary their surface proteins and thus may evade the immune system, permitting them to cause more prolonged disease. Better understanding how this occurs, and what this enables the bacteria to do, may assist in developing improved vaccine strategies. This project aims to investigate the six gene families in Mycoplasma pneumoniae which are known to encode surface proteins and establish how and why the bacteria switch from one gene to another during infection. In addition the capacity of bacteria expressing different versions of the six surface proteins to adhere to different tissues will be investigated. Once this is known, these mechanisms may be able to be specifically disrupted to prevent a strain of Mycoplasma pneumoniae from being able to establish prolonged infections. Such a strain might be a useful basis for an effective vaccine.Read moreRead less
Molecular Pharmacology Of Beta Adrenoreceptors In Multiple Disease States
Funder
National Health and Medical Research Council
Funding Amount
$578,812.00
Summary
Obesity is a major and increasing health concern for almost half the adult population, and is associated with serious medical conditions including diabetes and heart disease. Changes in behaviour such as increasing physical activity and eating less high-calorie food help many people reduce their body weight, however many others have a genetic predisposition to become overweight and behavioural measures are ineffective. Although anti-obesity drugs should be a valuable adjunct to lifestyle changes ....Obesity is a major and increasing health concern for almost half the adult population, and is associated with serious medical conditions including diabetes and heart disease. Changes in behaviour such as increasing physical activity and eating less high-calorie food help many people reduce their body weight, however many others have a genetic predisposition to become overweight and behavioural measures are ineffective. Although anti-obesity drugs should be a valuable adjunct to lifestyle changes, the currently available appetite suppressants are not ideal. Our work involves studying particular cell-surface proteins (receptors) which normally respond to hormones such as adrenaline. The beta(3)-adrenergic receptor is known to mediate the breakdown of fats and increased heat production in adipose tissue and possibly muscle. Administration of beta(3)-selective drugs to obese mice promotes weight loss and a reduction of diabetic symptoms, and a number of drugs targetting the human beta(3)-adrenergic receptor are being developed by pharmaceutical companies. We are trying to understand more about the properties of this receptor, as this information will assist in designing drugs which are more selective and more potent. Sometimes drugs act at more than one receptor, and there is evidence that this may be the case for two drugs called CGP 12177 and BRL 37344 which stimulate the beta(3)-adrenergic receptor. The second major aim of our project is to find out whether these drugs act at a novel receptor which is related to the beta(3)-adrenergic receptor and also mediates energy expenditure and heat production in adipose tissue and skeletal muscle. The discovery of a new receptor would provide additional scope for the development of effective anti-obesity treatments.Read moreRead less
Orientation-specific Contextual Modulation In Human Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$290,413.00
Summary
Context has a strong infuence on our visual perception. We will study patterns of activity in the normal human brain to identify the cortical signature of contextual modulation in vision. The correspondences between patterns of brain activity and visual perception in the normal human brain will provide data against which brain activity in disorders such as schizophrenia and bipolar disorder can be assessed.
Functional Interactions Between Primate Cortical Areas In Tasks Involving Attention And Short-term Memory
Funder
National Health and Medical Research Council
Funding Amount
$267,280.00
Summary
To navigate and operate in the cluttered and dynamic sensory world around us, our brains need to be able to attend to specific objects or features in the environment, identify them and also know where they exist at any one instant of time, prior to performing the appropriate action. The attention, memory, decision and motor components involved in this process possibly involve a variety of cortical areas and neuronal operations. The special primate preparation we have developed permits us to eluc ....To navigate and operate in the cluttered and dynamic sensory world around us, our brains need to be able to attend to specific objects or features in the environment, identify them and also know where they exist at any one instant of time, prior to performing the appropriate action. The attention, memory, decision and motor components involved in this process possibly involve a variety of cortical areas and neuronal operations. The special primate preparation we have developed permits us to elucidate at a neuronal level many of these brain mechanisms. By recording neuronal activities in two different cortical areas simultaneously as the monkey performs a memory task that he has been trained on, we will test the following ideas: (1) A cortical region in the dorsal, parietal stream directs spatial attention by gating other visual areas to process only a selected region of the visual world (2) A region in the ventral, temporal stream directs attention to specific features in the visual world by gating earlier cortical areas (3) The parietal cortical areas that mediate intention for action hold the relevant information in working memory till it is forwarded to the more anterior premotor areas. These experiments have the potential to reveal the basic neuronal scheme that underpins functions such as attention, visual recognition and memory, which are impaired in many neurological disorders.Read moreRead less
Functional Connectivity Between Visual Cortical Areas In The Non-human Primate
Funder
National Health and Medical Research Council
Funding Amount
$387,585.00
Summary
Visual information going from the eyes to the brain is processed in different parts of the brain to extract useful information. However, to be able to select what is important from among the vast number of objects in the scene, top-down signals from higher areas need to act on incoming signals in earlier areas. This project aims to identify what sort of neural pathways are involved in this and how it is done at the cellular level.
Brain And Skin Blood Flow: New Animal Model For Understanding Psychiatric Disorders And Evaluating Psychotropic Agents
Funder
National Health and Medical Research Council
Funding Amount
$874,840.00
Summary
We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-bloo ....We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to predict whether proposed new antipsychotic agents will be therapeutically effective.Read moreRead less