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ForeFront

RESEARCH CENTRE

Our laboratory research

At disease onset, focal pathology restricted to distinct brain areas is a feature of FTD and MND. However, the disease progresses and spreads by unknown mechanisms and the pattern of spread over time is poorly documented.

ForeFront will examine how progression occurs in the different clinical syndromes and proteinopathies using three main branches of laboratory-based research.

1. Human brain pathology – Prof Glenda Halliday and Prof Jillian Kril

Prof Halliday coordinated the first clinicopathological and survival studies published on frontotemporal disease and her laboratory developed the tool now used internationally to stage the disease. Prof Kril developed postmortem volumetric techniques, and is recognised for her quantitative studies on these and other neurodegenerative conditions. Their data are been used in all the pathological criteria for these diseases.

Key area of research for the first year:

Retrospective clinical analyses (Halliday and Hodges) – Postmortem cases will be stratified according to clinical syndromes and a range of defined candidate cognitive, linguistic, behavioural and radiological features assessed using multivariate statistics.

Retrospective pathological analyses (Kril) – We will apply a full range to immunohistological stains to the large clinically well-documented cohort of postmortem patients with particular clinical syndromes and multivariate statistics applied to identify features predictive of the underlying pathology.

2. Cellular and molecular studies – Assoc Prof Lars Ittner

Assoc Prof Ittner recently identified the mechanism of interaction between tau and Abeta, and has recently published cell TDP models using his new neuronal culture system.

Key area of research for the first year:
Molecular mechanisms of toxicity – A wide range of molecular mechanisms and pathways will be studied in primary cell culture to determine the contribution to cell death induced by different species (e.g. those identified above as contributing to progression) and mutant forms of tau, TDP43 and FUS. The protein-specific toxicity profiles will be compared to establish a complex network of shared and distinct modes of pathogenic pathways.

identification of vulnerability genes by forward genetics
3. Animal modelling – Prof Jürgen Götz

Prof Götz, who developed the first transgenic mouse model of frontotemporal disease, has continued to develop animal models and other tools to look at a variety of disease mechanisms.

Key area of research for the first year:

Identifying genes that confer protection – To identify protective genes, Affymetrix gene chips and differential gene expression will be used for transcriptional profiling of laser-captured dopamine neurons from K3 mice and non-transgenic controls, and validated with quantitative RT-PCR. We expect to identify several hundred candidate genes differentially expressed in dopamine neurons, a small subset of which will confer protection to tau-mediated neurodegeneration. To determine whether the ‘persisting’ genes confer ‘survival’, we will use in situ hybridisation and immunohistochemistry to analyse brain sections of a wide age range of K3 and non-transgenic control mice to determine which genes discriminate vulnerable from protected neurons.

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What is the analgesic effect of EEG neurofeedback for people with chronic pain? A systematic review

Researchers: A/Prof Sylvia Gustin, Dr Negin Hesam-Shariati, Dr Wei-Ju Chang, A/Prof James McAuley, Dr Andrew Booth, A/Prof Toby Newton-John, Prof Chin-Teng Lin, A/Prof Zina Trost Chronic pain is a global health problem, affecting around one in five individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic (EEG) neurofeedback attempts to modulate the power of maladaptive EEG frequency powers to decrease chronic pain. Although several studies provide promising evidence, the effect of EEG neurofeedback on chronic pain is uncertain. This systematic review aims to synthesise the evidence from randomised controlled trials (RCTs) to evaluate the analgesic effect of EEG neurofeedback. The search strategy will be performed on five electronic databases (Cochrane Central, MEDLINE, Embase, PsycInfo, and CINAHL) for published studies and on clinical trial registries for completed unpublished studies. We will include studies that used EEG neurofeedback as an intervention for people with chronic pain. Risk of bias tools will be used to assess methodological quality of the included studies. RCTs will be included if they have compared EEG neurofeedback with any other intervention or placebo control. The data from RCTs will be aggregated to perform a meta-analysis for quantitative synthesis. In addition, non-randomised studies will be included for a narrative synthesis. The data from non-randomised studies will be extracted and summarised in a descriptive table. The primary outcome measure is pain intensity assessed by self-report scales. Secondary outcome measures include depressive symptoms, anxiety symptoms, and sleep quality measured by self-reported questionnaires. Further, we will investigate the non-randomised studies for additional outcomes addressing safety, feasibility, and resting-state EEG analysis.
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