Dr Frances Corrigan

Current position:

• Senior Lecturer, Division of Health Sciences, University of South Australia

Achievements:

• South Australia Tall Poppy
• Fresh Science Finalist

Research area:

I am interested in investigated what happens in the brain following a traumatic brain injury, so that new treatments can be developed to treat not only the acute sequela, but also prevent the emergence of cognitive deficits in later life. In particular emerging evidence suggests that a history of traumatic brain injury increases the risk of later dementia, although the mechanisms driving this are not yet known. My research explores potential mechanisms including the inflammatory response. In addition I am also interested in determining how age at which at traumatic brain injury occurs can affect later outcome- research suggests that young children and adolescents actually have worse long-term outcomes following traumatic brain injury as the injury prevents normal maturation. Current projects include

• Testing a novel therapeutic to prevent axonal injury and thus improve outcome following TBI
• Investigating which whether a particular stage of adolescence is associated with worse outcome following concussive impacts and whether there is a particular imaging signature that can predict worse outcome
• Determining whether TBI alters risk for later alcohol use disorder and whether problematic alcohol use worsens long-term outcomes following TBI

NRF Funded Projects:

Neurodegeneration Research: The role of alcohol in promoting the development of neurodegeneration following a repeated concussion (2018)

A history of repeated concussions has been linked to three times higher risk of developing a neurodegenerative disease, to which there are currently no effective treatments. How repeated concussion promotes neurodegeneration, and what role alcohol abuse plays in that process, is poorly understood, making it difficult to intervene in the disease process. Work is ongoing to characterize the effects of chronic alcohol exposure on pathological changes following repeated concussion and determine whether this leads to long-term changes in behaviour, particularly cognition, depressive-like behaviour, and anxiety. This is particularly important given the accepted usage of alcohol within the community and the lack of understanding of what constitutes a safe level of alcohol consumption following a mild traumatic brain injury.

Concussion Research: Developing imaging biomarkers that predict pre-frontal cortex deficits following concussive insults in adolescence (2017)

Traumatic brain injury (TBI) is common during childhood and adolescence, with most injuries classified as mild (concussions), but these can still have long-lasting consequences. Indeed, the paediatric population take longer to recover from concussive insults than adults and report higher rates of impulsivity, attention deficits and cognitive impairment post-injury. This longer recovery may relate to ongoing brain development in this population. In particular the pre-frontal cortex which continues to mature into early adulthood is important for the development of executive functions which control judgement, planning, impulsivity, and working memory. As such the age of onset of a concussion may interrupt the normal maturation processes within this region leading to ongoing impairment of executive functions. This project aims to investigate whether the age at which a concussive impact occurs can have differential effects on the development of the pre-frontal cortex. This will be through examination of effects on executive function in adulthood- by examining impulsivity, working memory and judgement and linking this to changes in the key neurotransmitter systems within this region of the brain. Importantly this will be linked to magnetic resonance imaging (MRI) measures that will identify whether there are any signature alterations that can be linked to persistent behavioural changes.

Concussion Research: The role of the SP-NK1 system in promoting the vulnerability to concussion in adolescence (2016)

My research examines how concussion – particularly repeated concussion – may increase the risk of developing cognitive deficits later in life. Existing research suggests that adolescents are at the highest risk of suffering a concussion, the majority of which occur while participating in sporting activities such as AFL. This matters because adolescents may take longer to recover from the effects of a concussion, experiencing cognitive symptoms for twice as long as adults. My team is interested in the role of the inflammatory mediator substance P (SP), which is released when TRPV1 receptors are activated by the mechanical input caused during a concussion when the brain moves within the skull. Importantly, previous research has suggested that levels of this TRPV1 receptor are higher in adolescents and thus they may have a greater inflammatory response to a concussive insult than an adult. We will be investigating whether blockade of this inflammatory response – by preventing the actions of SP – will prevent the development of cognitive deficits following concussion in adolescence.

Neurodegeneration Research: The role of toll like receptor 4 activation following repeated concussion in promoting neurodegeneration (2015)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease which appears to be exclusively related to repeated concussion. (Concussion is an especially common injury in contact sports such as football.) CTE generally develops in midlife, long after the initial injury, and is characterised by memory disturbances, attention deficits and behavioural problems. The disease appears to be caused by a build-up in the brain of an abnormal protein, hyperphosphorylated tau. The exact mechanism by which concussion promotes the build-up of this protein is poorly understood. This research looks into the mechanisms by which systemic inflammation accelerates the disease process, promoting tau and leading to neuronal cell death. A better understanding of the progression of CTE will allow therapeutics to be developed which may halt the process.

Publications supported by the NRF:

For a full list of her publications please visit her Google Scholar page.

Lola Kaukas, Joshua L Holmes, Freshta Rahimi , Lyndsey Collins-Praino , Frances Corrigan. Injury during adolescence leads to sex-specific executive function deficits in adulthood in a pre-clinical model of mild traumatic brain injury (2020)

Collins-Praino LE, Corrigan F. Cerebrovascular contribution to dementia development after traumatic brain injury: promises and problems. Annals of Translational Medicine (2018) In Press

Collins-Praino LE, Arulsamy A, Katharesan V, Corrigan F. The effect of an acute systemic inflammatory insult on the chronic effects of a single mild traumatic brain injury. Behav Brain Res. (2018) 336:22-31.

Collins-Praino LE, Corrigan F. Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury? Brain, Behavior and Immunity (2016) 60, 369-382

Corrigan F, Arulsamy A, Collins-Praino LE, Holmes JL, Vink R, Toll like receptor 4 activation can be either detrimental or beneficial following mild repetitive traumatic brain injury depending on timing of activation. Brain, Behavior, Immunity (2017) 64 ,123-139

McAteer KM, Turner RJ, Corrigan F, Animal models of chronic traumatic encephalopathy Concussion (2017) 2(2)

Corrigan F, Mander KA, Leonard AV, Vink R. Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation. Journal of Neuroinflammation (2016) 13 (1), 264

McAteer KM, Corrigan F, Thornton E, Turner RJ, Vink R. Short and Long-term behavioral and pathological changes in a novel rodent model of repetitive mild traumatic brain injury. Plos One (2016) 11 (8) e0160220