The Neurobiology Of Auditory Hallucinations: Characterisation Of Dysfunction Within A Neural Circuitry Model.
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the ....This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the source may be the same brain circuits that are involved in generating inner speech or monitoring it, but our past research has ruled out these possibilities. Instead, our recent work suggests that auditory hallucinations may be associated with poorly functioning connections within central auditory processing circuits, specifically between left and right auditory association cortical regions. We conceptualise hallucinations as an abnormal and involuntary form of memory retrieval consequent to this dysfunction. Our study will pioneer methods of measuring connectivity in the brain circuits identified in our model, using a combination of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) techniques in tandem with tests of central auditory processing. We believe that sufferers may benefit from understanding the physical processes which cause hallucinations. We also believe that a better understanding of hallucinations may lead to a better understanding of schizophrenia and the psychoses, which may in turn help in the development of better ways of treating these illnesses.Read moreRead less
An Examination Of Motor Functioning In Autism And Asperger's Disorder: An Analysis Of Gait & Cortical Brain Activity.
Funder
National Health and Medical Research Council
Funding Amount
$120,220.00
Summary
Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poo ....Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poor coordination in posture and gesture. It has been suggested that there is disruption within the basal-ganglia-thalamocortical circuitry (the region connecting the frontal and sub-cortical structures), which may cause the motor dysfunction seen in autism and Asperger's disorder. Few studies have attempted to isolate particular stages of motor functioning which may account for the coordination and motor delay observed clinically in autism and Asperger's disorder. A recent study of ours found evidence to suggest that motor planning deficiencies may account for the 'clumsy' movement patterns frequently reported in the autism - Asperger's disorder literature. Therefore, the aim of this research is to provide a comprehensive neurobehavioural and neurophysiological analysis of motor functioning in young people with autism and Asperger's disorder to further examine the exact stages of motor processing which are deficient in these disorder groups. Recent retrospective studies have shown that even as infants children with autism exhibit clear features of motor disturbance, which, if detected and clearly defined, could advance early diagnosis. In addition to advancing the clinical definition of autism and Asperger's disorder, a careful examination of motor disturbance may also illuminate the neurobiological underpinnings of these disorders.Read moreRead less
Acute Alerting Effects Of Daytime Exposure To Specific Wavelengths Of Light
Funder
National Health and Medical Research Council
Funding Amount
$446,367.00
Summary
Excessive sleepiness is the greatest identifiable and preventable cause of accidents in all modes of transportation. Shift workers working outside the 8am-5pm day, make up about 20% of the urban working population. These individuals often report excessive daytime sleepiness caused by irregular sleep-wake patterns and long-term sleep loss. Excessive sleepiness is also common in individuals with sleep disorders. While there are many stimulant and wake-promoting drugs available to counteract daytim ....Excessive sleepiness is the greatest identifiable and preventable cause of accidents in all modes of transportation. Shift workers working outside the 8am-5pm day, make up about 20% of the urban working population. These individuals often report excessive daytime sleepiness caused by irregular sleep-wake patterns and long-term sleep loss. Excessive sleepiness is also common in individuals with sleep disorders. While there are many stimulant and wake-promoting drugs available to counteract daytime fatigue such drugs have problems of side effects, interactions and in some cases dependence. Light has many beneficial effects for a wide range of medicinal, physiological, psychological, and social purposes. One well known effect is as a stimulant so that exposure to bright light, both during the night and in the middle of the day, improves alertness and attention, and decreases reaction times thus improving performance. These effects can also be measured as changes in brain activity. However we do not understand the mechanisms in the eyes which control these effects. While certain cells in the eyes called rods and cones are necessary for seeing objects clearly and for detecting colour, there appears to be another system in the eyes which may involve different specialized cells or photoreceptors that are important for the alerting effects of light. White light is made up of different wavelengths or colours of light. This study will examine which wavelength (blue, violet, red or green) of light best improves alertness and learning during the daytime. Various performance tests will be used in addition to measures of brain wave activity. By identifying the most effective wavelength of light for improving alertness in healthy young adults and better understanding the mechanisms in the eyes involved, we will be able to develop light treatment strategies in patient groups with sleep disorders and in individuals like shift workers who experience sleep loss.Read moreRead less
Epileptic convulsions are common, disrupt social life and may occasionally cause death. They can occur spontaneously in individuals whose brains appear to be physically normal. Apart from the fact that epilepsy may run in families, the processes leading to spontaneous convulsions are not known. We measure the brain's electrical rhythms (EEG) to find out which rhythms are disturbed in people with epilepsy and whether these rhythms disrupt the brain to cause attacks. In preliminary studies in pati ....Epileptic convulsions are common, disrupt social life and may occasionally cause death. They can occur spontaneously in individuals whose brains appear to be physically normal. Apart from the fact that epilepsy may run in families, the processes leading to spontaneous convulsions are not known. We measure the brain's electrical rhythms (EEG) to find out which rhythms are disturbed in people with epilepsy and whether these rhythms disrupt the brain to cause attacks. In preliminary studies in patients with generalised epilepsy, we have identified abnormally strong rhythms that are almost certainly related to epilepsy causation and our studies are in part aimed at making our findings into a diagnostic test. Our findings may even enable individuals with epilepsy to test themselves for their immediate risk of seizure. Both of these outcomes should enable improved treatment for epilepsy. In addition to benefits in epilepsy, there are potential benefits in the diagnosis of cerebral degenerative disorders if changes in the rhythms also occur in these conditions.Read moreRead less
Epilepsy is an important human disease because it causes physical trauma and sudden death in addition to immense social and economic hardship. The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby mutations produce seizures is unknown. Several mutations in the alpha4 neuronal nicotinic receptor (a4 nAChR) gene have been identified in Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). This is a rare form of inherited epilepsy character ....Epilepsy is an important human disease because it causes physical trauma and sudden death in addition to immense social and economic hardship. The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby mutations produce seizures is unknown. Several mutations in the alpha4 neuronal nicotinic receptor (a4 nAChR) gene have been identified in Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). This is a rare form of inherited epilepsy characterized by the presence of seizures during light sleep. In vitro studies using the human mutated DNA (i.e. DNA containing the genetic defect) have suggested that this mutation results in reduced activity of the receptor. Therefore a mouse in which this gene is destroyed would be relevant in understanding the human disease. We have generated an a4 nAChR knockout (KO) mouse and plan to use the mouse to test the idea that loss of function of the a4 nAChR in vivo is associated with enhanced seizure activity. The KO mice do not have unprovoked seizures but appear to have an increased number of major motor seizures in response to pentylenetetrazole, an agent which is known to cause seizures by blocking the effects of the brain inhibitory molecule GABA. Interestingly, a4 nAChRs are known to control the release of GABA. We therefore propose that our knockout mice have seizures because they tend to under produce GABA. We will also make and analyse a mouse line with the same genetic mutation as patients with ADNFLE. The experiments are aimed at understanding the way that seizures are generated and spread in the brain in these rare forms of epilepsy. The hope is that understanding these mechanisms will help us better understand and therefore treat common forms of epilepsy.Read moreRead less
Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or ....Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or not. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain that can be measured from the scalp using small stick on electrodes. It is difficult to measure EEG, particularly for longer periods, because the electrodes may fall off, the baby may move excessively or electrical interference may ruin the recording. We are proposing to measure EEG for 48 hours in babies who have suffered a lack of oxygen during delivery. We will develop, optimise and implement a new method of automatically detecting seizures, building upon 6 years of fundamental signal processing research work that we have done in the newborn. We will test this system against the 'gold standard' to determine how accurate it will be in detecting seizures. We will also try to find out whether damage in particular areas of the brain or in particular cell types within the brain is most likely to be associated with seizures. The anticipated outcome is that we will be able to accurately identify seizures. This is a major step on the path to being able to prevent injury to the brain and to monitor the effectiveness of new experimental treatments.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.