New research with scanning techniques has confirmed older ideas about the complementary functions of the two hemispheres of the human brain. One major contrast between the two hemispheres concerns their cognitive and emotional styles. The left hemisphere plans and confidently smooths over discrepancies that do not fit the plan while the right hemisphere looks at all possibilities and cautiously highlights the discrepancies. This research project studies the switch between the two hemispheres tha ....New research with scanning techniques has confirmed older ideas about the complementary functions of the two hemispheres of the human brain. One major contrast between the two hemispheres concerns their cognitive and emotional styles. The left hemisphere plans and confidently smooths over discrepancies that do not fit the plan while the right hemisphere looks at all possibilities and cautiously highlights the discrepancies. This research project studies the switch between the two hemispheres that alternately activates these contrasting, but equally valid, viewpoints. The switch is studied directly by optical recording from animal brains. The switch can also be studied in humans using a recent discovery from our laboratory:- that the perceptual rivalries are mediated by a hemispheric switch mechanism. Perceptual rivalry is a phenomenon where continuous, but ambiguous, stimulation leads to a back-and-forth alternation of complementary percepts, a phenomenon that fascinated Salvador Dali and is featured in many of his paintings. The nature of the perceptual switch during rivalry has been debated for centuries. New experiments link perceptual rivalry to the switch of attention between the hemispheres. Using perceptual rivalry as an indirect way to monitor hemispheric switching in humans, we discovered a remarkable feature. The back-and-forth switching process of perceptual rivalry is significantly slower in subjects with bipolar disorder (manic depression), even when they are between episodes and their mood is normal. The timing of the switching process is very stable in an individual, and appears to be similar in identical twins. The speed of the switch mechanism may therefore be inherited. Altered neural rhythms may underly the predisposition, known to run in familes, from which bipolar disorder can be triggered. The aim of the project is to test these propositions about the basis of this common disorder, affecting 1-2% of the population..Read moreRead less
Development Of A Diagnostic Test For Bipolar Disorder (BD)
Funder
National Health and Medical Research Council
Funding Amount
$140,330.00
Summary
A unique test that monitors the rate of switching between the hemispheres of the brain in response to visual stimuli has been devised. A patent application covers an apparatus and test to measure the switching rate between the hemispheres and the way in which such measurements can be used as a means to diagnose bipolar disorder (BD). BD, also called manic depression, is a form of depression that currently affects over six million people worldwide with about three million in the USA alone. The co ....A unique test that monitors the rate of switching between the hemispheres of the brain in response to visual stimuli has been devised. A patent application covers an apparatus and test to measure the switching rate between the hemispheres and the way in which such measurements can be used as a means to diagnose bipolar disorder (BD). BD, also called manic depression, is a form of depression that currently affects over six million people worldwide with about three million in the USA alone. The condition has phases of mania and depression and periods of remittance. Full cycles of BD can occur as many as three times a year and for many patients, this is a lifelong condition. BD is effectively treated, once it is diagnosed. It is estimated that 20% of sufferers go undiagnosed and many more are misdiagnosed. The cost of mis- or non-diagnosis is measured by suicides, the financial burden on society with health care, loss of productivity etc, effects on family and associates, crime, etc. Diagnosis to date is achieved mainly by subjective means such as questionnaires. These instruments do not conclusively separate BD from other forms of depression and schizophrenia, for which treatment is quite different. Nor do they allow for factors such as substance abuse and other medical conditions that the patient may be suffering. BD is hereditary with the slow hemispheric switch rate being an indicator of the genetic trait. This phenomenon allows for an objective test for BD, even if an individual has not had an episode of BD. The slow switch allows relatively easy separation of a BD patient from those exhibiting symptoms that may have other causes.Read moreRead less
Influences Of Oestrogen On Neurodegeneration And Behaviours
Funder
National Health and Medical Research Council
Funding Amount
$620,352.00
Summary
More women develop Alzheimer's disease whereas more men develop Parkinson's disease. This study will try to understand whether sex hormones play a part in the devlopment of these diseases. This study will also try to answer how the female sex hormone, oestrogen, influences behaviour and or development of mental health problems such as depression and obsessive-compulsive disorder.
Regulation And Substrate Identification Of Parkinsons Disease Causative Leucine-rich Repeat Kinase 2 (LRRK2)
Funder
National Health and Medical Research Council
Funding Amount
$699,456.00
Summary
Parkinson's disease afflicts 100,000 Australians. Mutations in the recently identified enzyme Leucine-rich Repeat Kinase-2 are a common cause of Parkinson's disease. This project will use biochemical methods to understand how this brain enzyme causes disease by investigating its enzymology, modes of regulation, and target substrates that it modifies by addition of phosphate groups. Characterization of this enzyme will facilitate design of inhibitors to slow the course of Parkinson's disease.
Nerve cells have unique properties like their ability to put out axons that reach long distances from the cell body (differentiation), their ability to make contacts with other cells and initiate communication by the release of neurotransmitters from synaptic vesicles inside nerve endings (exocytosis) and the recycling of those synaptic vesicles (endocytosis). These events are mainly controlled by a large number of synapse-specific proteins, and partly regulated by a signalling molecule, cGMP, w ....Nerve cells have unique properties like their ability to put out axons that reach long distances from the cell body (differentiation), their ability to make contacts with other cells and initiate communication by the release of neurotransmitters from synaptic vesicles inside nerve endings (exocytosis) and the recycling of those synaptic vesicles (endocytosis). These events are mainly controlled by a large number of synapse-specific proteins, and partly regulated by a signalling molecule, cGMP, which mainly stimulates the enzyme PKG. In previous studies supported by the NHMRC we identified many proteins that are phosphorylated and activated by PKG. One of them, septin 3, is the focus of this proposal. We initially cloned septin 3 as a new member of a family of 10 genes that are essential for cell division. Some septins assemble as filaments that allow the two new daughter cells to finally separate. When the filament formation is perturbed certain septins end up in microscopic clumps that are found in the post-mortem brains of people affected by Alzheimer's disease, suggesting they might contribute to the disease. However, septin 3 is unlike most septins because it is a brain-specific septin, which we found in neurons and found to be highly concentrated in nerve terminals, locations not normally associated with cell division. The only other known brain-specific septin, CDCrel-1, regulates the protein machinery of exocytosis. We will examine the hypothesis that G-septin is also a regulator of synaptic vesicle endocytosis. We will determine whether septin represents a convergence point for cGMP signalling to control endocytosis. A better understanding of septin 3 and endocytosis is crucial to understanding brain disorders and ultimately developing better therapies.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less