I will use non-invasive brain stimulation to study the operation of the corticospinal pathway in humans while they perform tasks requiring precise control of fingers and thumb. This pathway from brain to spinal cord is important for independent finger movements, and these experiments will provide insight into the cortical mechanisms by which independent finger movements are produced. I will also investigate relationships between patterns of corticospinal activation (which I have shown differ bet ....I will use non-invasive brain stimulation to study the operation of the corticospinal pathway in humans while they perform tasks requiring precise control of fingers and thumb. This pathway from brain to spinal cord is important for independent finger movements, and these experiments will provide insight into the cortical mechanisms by which independent finger movements are produced. I will also investigate relationships between patterns of corticospinal activation (which I have shown differ between subjects and hands) and digital dexterity. While it seems reasonable to assume that digital dexterity is dependent on the operation of the corticospinal system, the relationship is obscure, even at a gross level. Digital dexterity can vary considerably between subjects, and even between hands in the same subject. Are people more skilled with their hands because they are better able to engage the corticospinal system in control of the digits? The present study will address this fundamental question. The brain stimulation techniques that I will use are the only techniques presently available which can answer these questions in humans. This information will assist us to understand how normal subjects perform skilled tasks with their hands, as well as helping us to understand how damage to the nervous system (e.g., stroke, multiple sclerosis, Parkinson's disease) produces deficits in movement control. The information gained may suggest training regimes for skill acquisition in normal subjects, and to promote recovery of function in patients with neurological damage or disease.Read moreRead less
NEURONAL RESPONSES ELICITED BY VIEWING HUMAN BODY MOTION AND GESTURE.
Funder
National Health and Medical Research Council
Funding Amount
$135,822.00
Summary
This project aims to study human brain regions active in viewing movements of the body, face and hands, as well as gestures (i.e. movements with meaning). We will map the location of these human motion sensitive brain regions relative to brain areas dealing with other visual functions. We will use a new method of brain scanning (functional MRI) and recordings of the electrical activity of the brain to achieve these goals. Subjects for this project will be epilepsy patients undergoing investigati ....This project aims to study human brain regions active in viewing movements of the body, face and hands, as well as gestures (i.e. movements with meaning). We will map the location of these human motion sensitive brain regions relative to brain areas dealing with other visual functions. We will use a new method of brain scanning (functional MRI) and recordings of the electrical activity of the brain to achieve these goals. Subjects for this project will be epilepsy patients undergoing investigation for seizure surgery at the A and RMC and Royal Children's Hospitals in Melbourne. Functional MRI - a new non-invasive method for studying brain function - will locate the brain structures involved in the detection and analysis of human motion. Recording electrodes are surgically placed inside the brains of these patients in order to find the source of their seizures, and these electrodes will be utilised for this study. A number of facial, hand and body movement and gestural stimuli will be used. First, brain locations responding to face, hand and body movements will be identified. It is predicted that regions sensitive to hand motion could be located near areas known to participate in adjusting the subject's own visually-guided reaching behaviour. Similarly, regions sensitive to facial motion could be located near areas thought to deal with lip-reading. Second, differences in brain activity to gestures and movements of the face and hand will be studied, so as identify brain regions that process increasingly complex information. Third, differences in brain responses to incompatible (e.g. head facing left and moving right) versus compatible human motion will be studied. A brain 'map' with locations of these human motion sensitive regions relative to visually sensitive regions will be generated. These data will not only aid planning for future seizure surgery, but have implications for our understanding of the visual aspects of motor apraxia.Read moreRead less
Mechanisms Of Cortical Plasticity And Facilitation Of Functional Recovery Following Stroke
Funder
National Health and Medical Research Council
Funding Amount
$427,500.00
Summary
Specific regions of the human brain have been shown to reorganise following damage to the brain or peripheral nerves. This reorganisation is seen in both young and older subjects and is thought to be useful in helping to restore function. For example, following a stroke a patient may, initially, be unable to move one arm. However, in the following weeks and months some function may return. A number of mechanisms may be responsible for this improvement. However, it is likely that at least some of ....Specific regions of the human brain have been shown to reorganise following damage to the brain or peripheral nerves. This reorganisation is seen in both young and older subjects and is thought to be useful in helping to restore function. For example, following a stroke a patient may, initially, be unable to move one arm. However, in the following weeks and months some function may return. A number of mechanisms may be responsible for this improvement. However, it is likely that at least some of the improvement is due to reorganisation within the sensorimotor cortex. Following the stroke the control of the arm may be taken over by adjacent undamaged regions of the brain. This reorganisation allows impressive functional recoveries to occur. We have preliminary evidence to support the idea that patterns of activity generated in peripheral nerves (afferent input) following stroke may be crucial for the development of the organisational changes seen within the brain. We have shown that by applying specific patterns of sensory input we are able to produce organisational changes within the motor cortex of control subjects. Also, we have been able to induce similar changes in stroke patients. These changes have been accompanied by improvements in motor control. These novel and exciting findings support our hypothesis that by applying certain patterns of afferent input to patients following stroke we will be able to facilitate functional recovery by maximising reoganisation within the cortex. In the present project we will establish the organisation patterns in the brain of stroke patients and contrast the findings with control subjects. Secondly we will investigate the potential for facilitating recovery of stroke patients by the application of specific patterns of afferent input. These novel experiments may lead to important therapeutic developments that will benefit the large population of patients suffering strokes.Read moreRead less
Vestibular Reflexes Evoked By Brief Lateral Head Acclerations: A New Measure Of Utricular Function
Funder
National Health and Medical Research Council
Funding Amount
$225,357.00
Summary
The vestibular (balance) organs are difficult to investigate as they lie deep within bone. Disease of these organs may cause severe vertigo, imbalance and difficulty with vision. This project attempts to build on earlier developments in my laboratory and thereby improve understanding and diagnosis of these disorders. This grant relates to a new form of stimulation which may allow simple assessment of an important part of the vestibular apapratus, the utricle.
Assessment Of Vestibular Function And Balance In Humans
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
This proposal focuses upon the function of the vestibular apparatus and the related problem of impaired balance. The vestibular apparatus contains receptors which help us to maintain balance. Their clinical assessment is difficult because they are small and lie deep within the skull. With previous NH and MRC support, I have been able to develop a series of new tests to assess the function of the vestibular apparatus and these are having significant clincal impact. Amongst the findings has been a ....This proposal focuses upon the function of the vestibular apparatus and the related problem of impaired balance. The vestibular apparatus contains receptors which help us to maintain balance. Their clinical assessment is difficult because they are small and lie deep within the skull. With previous NH and MRC support, I have been able to develop a series of new tests to assess the function of the vestibular apparatus and these are having significant clincal impact. Amongst the findings has been a clear demonstration that vestibular function declines with age, starting relatively early. This proposal builds upon the findings of the previous application. Two main types of investigations are planned. In one a new technique of activating the vestibular apparatus (localised skull vibration) will be used to study the brain areas that receive its signals (evoked potentials). This will be the first time that it has been possible to study the connections between the balance organs and the cortex of the brain in intact humans. I will apply the technique to patients with disturbed vestibular function to improve our knowledge of how the brain adapts to disease of these organs. In the second part of this study, a series of recordings will be done measuring sway under a variety of conditions both in normal volunteers and in patients with some common disease states affecting balance. This should reveal new information about both the factors that affect normal balance function and why balance is disturbed in these diseases.Read moreRead less
The Role Of Neuropeptides In The Acute And Long-term Effects Of MDMA, Methamphetamine And GHB
Funder
National Health and Medical Research Council
Funding Amount
$472,321.00
Summary
The widespread use of 'party drugs' (ecstasy, methamphetmaine and GHB) is a major health issue in Australia. We propose a novel hypothesis that key acute and long-term effects of these drugs may involve an action on the neuropeptide oxytocin. A number of experiments are planned to test this hypothesis. The findings from this project will be used to better understand and to explore novel treatments for people who suffer problems as a result of using these drugs.
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
Neural Coding Of A Cue To Auditory Space, In Noisy Environments
Funder
National Health and Medical Research Council
Funding Amount
$180,160.00
Summary
GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the ba ....GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the background, and is even more severely disrupted when the environment is noisy. SCIENTIFIC BACKGROUND : Our localization ability depends on the way neurons in the brain code the position of a source of sound we wish to detect. From studies in animals we know a lot about the way in which neurons do this coding in silence. However, we know almost nothing about how this coding is affected by a noisy background. Further, we know absolutely nothing about how this coding, whether in silence or when there is noise, is affected when there is also a hearing loss. SIGNIFICANCE : If we are to understand the effects of hearing losses on coding of the location of a sound signal we need to know first how noise affects the coding in cases of normal hearing. This project aims to gain that information. I will then extend this to studying the detailed basis of these effects, ie., exactly what mechanisms are affected in the neurons. Then I will determine how noise from different positions affects the coding of signal sounds at differnt positions. These data will provide us the essential base from which we can, later, go on to study how noise affects coding by neurons of the location of a signal. I plan to increase the value of the current study by developing, from the data gained in the studies in animals, computer-based models that will allow us to predict how coding of sound signal location is affected by hearing loss, and how this is exacerbated by noisy environments.Read moreRead less