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
Predictors Of Response To Antidepressants: Utility Of Behavioural, Neuroimaging And Genetics Data
Funder
National Health and Medical Research Council
Funding Amount
$310,071.00
Summary
Major depressive disorder (MDD) is projected to cause the second greatest global burden of disease by 2020, highlighting the urgent need for valid predictors of effective treatment response. Currently, there are no accurate predictors of response to antidepressants in MDD, and successful treatment relies greatly on 'trial and error'. This process is demanding on health resources, and may be a factor in the high suicide rates in depressed patients. Previous research on treatment response has been ....Major depressive disorder (MDD) is projected to cause the second greatest global burden of disease by 2020, highlighting the urgent need for valid predictors of effective treatment response. Currently, there are no accurate predictors of response to antidepressants in MDD, and successful treatment relies greatly on 'trial and error'. This process is demanding on health resources, and may be a factor in the high suicide rates in depressed patients. Previous research on treatment response has been limited by recruitment of small, heterogeneous patient samples, lack of placebo control, and a failure to examine task related activity in brain imaging studies. Perhaps one of the more troubling aspects of research that aims to predict treatment response to antidepressant medications is the use of commonly used outcome measures such as the Hamilton Rating Depression Scale (HAM-D), which were developed long before current classification systems of depression came into use. The US Federal Drug Administration has recently identified what they call a translational gap such that behavioural and biological measures are the most robust for detection of disorders such as depression, yet these measures remain to be translated into clinical tools that can be used to evaluate treatment. The aim of the current study therefore is to determine whether genetic variability is related to treatment outcome as defined by a more objective outcome measure (facial expression perception) using a randomised controlled design. The study will also determine whether brain measures (fMRI, EEG) enhance the prediction of SSRI response to both clinical and behavioural measures, over and above the genetic contribution.Read moreRead less
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less
Danger Ideation Reduction Therapy For Obsessive-Compulsive Checkers: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$156,447.00
Summary
Obsessive-compulsive disorder (OCD) is a psychiatric disorder that affects up to 3% of the general population. People with the disorder experience unpleasant intrusive thoughts that they find distressing and have a strong urge to perform particular behaviours. Fears about fire and burglary are common and excessive checking of electrical appliances and locks can take many hours a day. Checkers represent one of the largest OCD sub-groups. Because of the time-consuming nature of the condition, soci ....Obsessive-compulsive disorder (OCD) is a psychiatric disorder that affects up to 3% of the general population. People with the disorder experience unpleasant intrusive thoughts that they find distressing and have a strong urge to perform particular behaviours. Fears about fire and burglary are common and excessive checking of electrical appliances and locks can take many hours a day. Checkers represent one of the largest OCD sub-groups. Because of the time-consuming nature of the condition, social and occupational functioning is often severely restricted. Many sufferers will also experience extreme social isolation and depression. The World Health Organisation ranks this disorder as 20th among all causes of burden of disease. The development of effective interventions could substantially reduce the economic and social burden of this disabling anxiety disorder. The aim of this project is: (1) to compare the therapeutic efficacy of a new treatment approach (Danger Ideation Reduction Therapy) with that of Exposure and Response Prevention (ERP); It is hypothesised that: (1) subjects who receive 12 sessions of DIRT will show greater post-treatment and follow-up reductions in symptomatology than subjects who receive ERP.Read moreRead less
NPY Suppresses Seizures And Modulates Thalamocortical Activity In Animal Models Of Generalized Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled ....Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled with current medications. Recently there has been considerable interest in the role that chemical in the brain, such as neuropeptide Y (NPY), may play in epilepsy. The research proposed will examine the role of NPY in several animal models of absence epilepsy. We have recently shown that NPY suppresses absence seizures in a rat genetic model of generalised epilepsy, and that this appears to be mediated by Y2 receptors. This work will build on these novel findings, and determine the localisation of the effect within the brain, and the underlying mechanism. We will check NPY effects across several models in different species, a genetic rat model with spontaneous seizures, and in mice treated with a chemical to induce seizures. This will determine its broad applicability. We will also determine the effects of removal of NPY or NPY receptors on the effects of NPY on seizure expression. Finally, brain recording techniques will be applied to determine the mechanism and site within the brain underlying the protective actions of NPY. The project has the potential to provide novel insights into the role of NPY in the expression and modulation of absence seizures. NPY related mechanisms might represent targets for the development of a new class of therapeutic agents for the treatment of absence epilepsy. Targets that are identified as being important in the expression of absence seizures may also prove to be relevant in other types of generalised epilepsy syndromes.Read moreRead less