Prof Caroline (Lindy) Rae

TEAM LEADER PROFILE

Conjoint Senior Principal Scientist, NeuRA Professor of Brain Sciences, UNSW
Director (Medicine) EPICentre, UNSW
Director (Research) NeuRA Imaging
Honorary Associate, Macquarie Centre for Cognitive Science, Macquarie University, Sydney
School of Medical Sciences, UNSW

+612 9399 1211


Prof Caroline Rae is a biochemist with a background in magnetic resonance and interdisciplinary brain research. She graduated with a PhD in biochemistry and NMR from The University of Sydney in 1993 and spent four years in Oxford, UK, as a Nuffield Medical Fellow where she pioneered the use of magnetic resonance spectroscopy as a tool in cognitive brain research. In 2005 she was appointed to UNSW as a NewSouth Global Professor, one of only a handful of NHMRC R Douglas Wright Fellows subsequently appointed to chairs. She is currently director of the UNSW Node of the National Imaging Facility and holds a cross-disciplinary (STEAM) appointment in medical data visualisation as a Director of the UNSW Expanded Perception and Interaction Centre (EPICentre).

Projects Prof Caroline (Lindy) Rae is currently involved with

CURRENT PROJECTS

Determining new targets and approaches for treating sleep apnoea

We are running a range of projects to determine how existing treatments for sleep apnoea work so that we can optimise therapy and improve treatment success.

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Determining new targets and approaches for treating sleep apnoea

Regulation of brain energy metabolism by NAD and sirtuins

This project is investigating control of metabolism by sirtuins and by NAD+ availability using an innovative, pharmacogenetic approach to metabolism research and “world-first” cell-specific introduction of enzymes into tissue in vivo. It will deliver an integrated picture of how SIRTs 1-3 and NAD+ interact with metabolism, crucial for development of next generation treatments based on this system. Finally, in preclinical translation, we will test the therapeutic effects of manipulating this system to combat decreased NAD+ availability and SIRT activity within the aging brain.

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Regulation of brain energy metabolism by NAD and sirtuins

New methods for analysis and visualisation of metabolic data

We are developing new approaches that allow representation of metabolomic data as a network, while still retaining some elements of data reduction in order to remove the immense complexity associated with analysis.

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New methods for analysis and visualisation of metabolic data

Brain network discovery in medical research

Scientists discovered some time ago that they could use magnetic resonance imaging (MRI) to map brain activity when a person was repetitively performing a task, like looking at flashing lights or doing serial maths calculations. More recently, they found that these MRI signals could also provide useful information when the scanned subject was not doing anything. They called these signals “resting state” signals. Our new analysis approach for resting state data uniquely provides repeatable, reliable results from single scanning sessions. We are developing methods for network comparison and are applying our new approaches across a targeted range of patient data.

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Brain network discovery in medical research

Binge drinking and the adolescent brain

This study is examining effects of binge alcohol consumption in 16-17 year olds using questionnaires, magnetic resonance imaging and cognitive testing. It aims to determine whether binge consumption of alcohol is impacting adolescent brain and cognitive development.

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Binge drinking and the adolescent brain

Novel brain biomarkers of neurobehavioural dysfunction in obstructive sleep apnoea

This study aims to investigate the relationship between brain biomarkers measured at baseline, with neurobehavioural dysfunction during a subsequent extended wakefulness “load” that will uncover the individual variation in neurobehavioral dysfunction in patients with obstructive sleep apnoea.

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Novel brain biomarkers of neurobehavioural dysfunction in obstructive sleep apnoea

THE EPICENTRE WEBSITE (URL COMING!)

GOOGLE SCHOLAR

RESEARCHER ID

RESEARCH TEAM

Mark Schira

DR MARK SCHIRA Honorary Senior Research Officer : +612 9399 1131

Sylvia Gustin

DR SYLVIA GUSTIN Senior Research Officer

Zoey Isherwood

ZOEY ISHERWOOD PhD student

Ben Rowlands

BEN ROWLANDS PhD student

PUBLICATIONS

Hand function is impaired in healthy older adults at risk of Parkinson's disease.

Todd G, Haberfield M, Faulkner PL, Rae C, Hayes M, Wilcox RA, Taylor JL, Gandevia SC, Godau J, Berg D, Piguet O, Double KL

Abnormal substantia nigra morphology in healthy individuals, viewed with transcranial ultrasound, is a significant risk factor for Parkinson's disease. However, little is known about the functional consequences of this abnormality (termed 'hyperechogenicity') on movement. The aim of the current study was to investigate hand function in healthy older adults with (SN+) and without (SN-) substantia nigra hyperechogenicity during object manipulation. We hypothesised that SN+ subjects would exhibit increased grip force and a slower rate of force application compared to SN- subjects. Twenty-six healthy older adults (8 SN+ aged 58 ± 8 years, 18 SN- aged 57 ± 6 years) were asked to grip and lift a light-weight object with the dominant hand. Horizontal grip force, vertical lift force, acceleration, and first dorsal interosseus EMG were recorded during three trials. During the first trial, SN+ subjects exhibited a longer period between grip onset and lift onset (i.e. preload duration; 0.27 ± 0.25 s) than SN- subjects (0.13 ± 0.08 s; P = 0.046). They also exerted a greater downward force prior to lift off (-0.54 ± 0.42 N vs. -0.21 ± 0.12 N; P = 0.005) and used a greater grip force to lift the object (19.5 ± 7.0 N vs. 14.0 ± 4.3 N; P = 0.022) than SN- subjects. No between group differences were observed in subsequent trials. SN+ subjects exhibit impaired planning for manipulation of new objects. SN+ individuals over-estimate the grip force required, despite a longer contact period prior to lifting the object. The pattern of impairment observed in SN+ subjects shares similarities with de novo Parkinson's disease patients.

Brain activity: connectivity, sparsity, and mutual information.

Cassidy B, Rae C, Solo V

We develop a new approach to functional brain connectivity analysis, which deals with four fundamental aspects of connectivity not previously jointly treated. These are: temporal correlation, spurious spatial correlation, sparsity, and network construction using trajectory (as opposed to marginal) Mutual Information. We call the new method Sparse Conditional Trajectory Mutual Information (SCoTMI). We demonstrate SCoTMI on simulated and real fMRI data, showing that SCoTMI gives more accurate and more repeatable detection of network links than competing network estimation methods.

Metabolomic Approaches to Defining the Role(s) of GABAρ Receptors in the Brain.

Rae C, Nasrallah FA, Balcar VJ, Rowlands BD, Johnston GA, Hanrahan JR

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) acts through various types of receptors in the central nervous system. GABAρ receptors, defined by their characteristic pharmacology and presence of ρ subunits in the channel structure, are poorly understood and their role in the cortex is ill-defined. Here, we used a targeted pharmacological, NMR-based functional metabolomic approach in Guinea pig brain cortical tissue slices to identify a distinct role for these receptors. We compared metabolic fingerprints generated by a range of ligands active at GABAρ and included these in a principal components analysis with a library of other metabolic fingerprints obtained using ligands active at GABAA and GABAB, with inhibitors of GABA uptake and with compounds acting to inhibit enzymes active in the GABAergic system. This enabled us to generate a metabolic "footprint" of the GABAergic system which revealed classes of metabolic activity associated with GABAρ which are distinct from other GABA receptors. Antagonised GABAρ produce large metabolic effects at extrasynaptic sites suggesting they may be involved in tonic inhibition.

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