Visualisation Of Functionally Activated Circuitry In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain cont ....We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain control of bodily function. Up until now, there has been no direct way of being able to directly visualise which of those billions of connections are involved in the formation of a circuit for any particular brain function. We plan to use a genetic approach to help to visualise functionally activated brain circuits. We know that some genes are turned on in the nerve cells which are activated during a brain function. We will use this knowledge to generate a new line of genetically engineered mice. In these mice, the genes which are turned on during brain activation will in turn be used to turn on special markers which will light up the activated circuits. This will be of great signficance in our understanding of brain function. It should also help us to understand what happens to these circuits in different diseases of the brain, such as following stroke, in senility, and Alzheimer's disease.Read moreRead less
Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.Read moreRead less
Brain Adaptation Associated With Spontaneous And Training-induced Recovery Of Touch Sensation Post-stroke.
Funder
National Health and Medical Research Council
Funding Amount
$339,950.00
Summary
Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation ....Brain networks may reorganize to optimise stroke recovery. However, little is known about brain mechanisms underlying natural and training-induced recovery after stroke, particularly following loss of body sensations. Knowledge of the experiences that may facilitate brain reorganisation is a prerequisite for the development and evaluation of optimal stroke rehabilitation strategies. We aim to provide novel information on the potential benefits of specific training in facilitating reorganisation of the brain after stroke. Specifically we will: (i) locate areas of brain activity associated with natural and training-induced recovery of touch sensation following stroke and (ii) investigate the relationship between brain activation, sensory recovery and intervening experience. Site and extent of brain activation associated with recovery of touch sensation will be investigated over time using serial functional magnetic resonance imaging (fMRI), a controlled sensory task and clinical measures of recovery. Thirty stroke patients with impaired touch sensation of the upper limb will be studied at 2-6 weeks and 6 months post-stroke to investigate changes in brain activation associated with natural recovery (Study 1). Ten healthy controls will also be studied over 6 months. Those patients who still have sensory loss at 6 months will then receive specific sensory training or placebo intervention to study the effect of training-induced recovery on brain activity (Study 2). The whole brain will be studied and activation sites will be interpreted relative to individual and standard brain maps. We expect that the findings will advance our knowledge of the relationship between clinical recovery, training and neural plastic changes in the brain. This information will provide direction for the development of scientifically based treatments designed to maximise recovery and help identify patients who are likely to show natural recovery and-or benefit from training.Read moreRead less
The Relationship Between Cognition And Interictal Discharges: Language Organization And Spike Localisation In BECTS
Funder
National Health and Medical Research Council
Funding Amount
$216,500.00
Summary
Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy ari ....Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy arises near the face area of the motor cortex, but this remains unproven. Functional magnetic resonance imaging (fMRI) is a safe and non-invasive way of imaging cerebral function, to reveal the brain at work . The technology is contributing to major advances in understanding of basic human functions such as language. Recent developments at the Brain Research Institute in Melbourne mean it is now possible to record EEG during fMRI. This has permitted visualisation of spike activity in the brain. The BRI is the only centre in Australia, and one of only a handful in the world that is able to perform such studies. One purpose of this study is reveal the location of spikes in BECTS. Recent studies have revealed subtle language and learning difficulties in BECTS children. Our preliminary EEG-fMRI studies have suggested spikes arise from brain regions adjacent to important language areas. It is possible that the frequent spikes of BECTS are interfering with adjacent cognitive processes. In addition to spike mapping, we will perform functional imaging of language to look for interactions between spike and language areas, and compare with patterns of language activation seen in normal children. The demonstration of spike related affects on cognition may lead to a reassessment of current epilepsy management strategies, which focus predominately on seizure control. This study, with researchers in Cairns and Melbourne, shares the benefits of world class research with regional Australia.Read moreRead less
Functional Neuroimaging Of Prepulse Inhibition In Schizophrenia And Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$446,750.00
Summary
Inhibition deficits have been consistently demonstrated in a broad spectrum of neuropsychiatric conditions that have been implicated with altered neurotransmitter function of the brain. These conditions include mental disorders like schizophrenia, obsessive-compulsive disorder, and pathological gambling and neurological disorders like Huntington's disease, Gilles-de-la-Tourette syndrome and other conditions which are characterised by impaired impulse control. Studies on animal models suggest tha ....Inhibition deficits have been consistently demonstrated in a broad spectrum of neuropsychiatric conditions that have been implicated with altered neurotransmitter function of the brain. These conditions include mental disorders like schizophrenia, obsessive-compulsive disorder, and pathological gambling and neurological disorders like Huntington's disease, Gilles-de-la-Tourette syndrome and other conditions which are characterised by impaired impulse control. Studies on animal models suggest that an impaired dopamine neurotransmission - either genetically pre-determined and-or stress-induced by environmental factors - may significantly contribute to a common pathological mechanism across these conditions that, in turn, results in impaired 'sensory motor gating', a physiological measure of inhibitory brain processes. Traditionally, sensory motor gating is indirectly measured using the acoustic startle eye-blink response. However, this peripheral measure cannot directly assess the brain processes underlying sensory motor gating. This study will apply new functional brain imaging methodology and EEG-based source localisation techniques to assess the neural substrates of inhibitory processes involved in sensory motor gating in two neuropsychiatric conditions that involve dysfunctional dopaminergic mechanisms: schizophrenia and Parkinson's disease.Read moreRead less
The Neural Reaction To Injury: Clues To The Cause And Prevention Of Acquired Brain Damage And Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$390,326.00
Summary
The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the compl ....The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the complex cellular and gene expression changes that determine the ultimate fate of the cell. Both acquired brain injury and degenerative conditions such as Alzheimer?s disease represent an enormous health, social and economic burden. Furthermore, with predictions that Alzheimer?s disease will increase by 3-4 times by the middle of the next century due to the Oaging? of the population, it is becoming even more crucial to establish effective therapeutic interventions. The animal models investigated in this project can be used to unravel the crucial neuronal alterations associated with head trauma and the early stages of Alzheimer?s disease and, more importantly, may be the key to discovering novel strategies to prevent neuronal degeneration in these conditions.Read moreRead less
What Drives Abnormal Cerebral Activity In Secondary Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$565,809.00
Summary
Secondary Generalised epilepsy (2GE) is a severe, disabling epilepsy syndrome characterised by childhood onset frequent, treatment resistant seizures and developmental delay. Although one of the four major categories of epilepsy, it is poorly understood. This project uses combined EEG (brainwave testing) and MRI to reveal which brain areas are involved in the epileptic activity of 2GE. Advanced analysis techniques will explore which brain regions initiate 2GE epileptic activity.