LIMITATIONSof the BRAIN

Issue 12 Autumn 2015

magazine

theNeuRAIdentifying RISK GENES

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6Supporting NEURA’S RESEARCH

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Neuroscience Research Australia • neura.edu.au

Increased appetite

IN FTD

Dr Julie Brown’s research is in injury prevention on our roads. She currently leads a program investigating the quality of motorcycle protective clothing.

5 minutes

with

DR JULIE BROWN

This year’s grant application round is over – drawing sighs of relief from our researchers who are paid through competitive grants from the National Health and Medical Research Council (NHMRC) and other agencies. Writing a grant application is analogous to submitting a tender: researchers are competing to have the best ideas and most relevant projects supported. With only one in six project grants being funded, it’s a competition that sees only the most compelling applications supported. The process of tendering for a continuing research career is a tough road.

Government funding agencies don’t simply want to provide a pool of money to satisfying researchers’ curiosity; rather they ask broad strategic questions about the research. Will the proposal be of significance and address an unmet health need, is it innovative in its approach, is the research plan logical and feasible, and does the research team have the skills to successfully undertake the project? In this way, the community invests in the very best ideas, and the ones which are most likely to lead to future advances in medicine, health care and wider societal benefits.

Our grant applications must deliver compelling ideas leading to worthwhile, meaningful outcomes and, in this, we continue to be highly competitive. Two recent examples of grants that have commenced this year include a NHMRC Early Career Fellowship awarded to Dr Lara Harvey for her project to examine the causes, consequences and costs of injury-related hospitalisations for people with dementia. By combining NeuRA’s strengths in dementia research and in falls prevention this project will train research leaders of the future while addressing the problems of today. In the same way, a NHMRC Project Grant awarded to Dr Kim Delbaere and colleagues will evaluate a new home-based exercise program called Standing Tall, which uses mobile technology to prevent falls in older people.

Government funding is not comprehensive and doesn’t fund the conception or piloting of research ideas, yet such preliminary data is key to convincing review panels of the merit and feasibility of a research project. It is here that philanthropy provides its unique leveraging potential. One example is Kim Delbaere’s NHMRC grant success for the Standing Tall project. While proposing an innovative approach to an unresolved health problem, Kim’s project needed financial backing in its trial stages to provide sufficient evidence for NHMRC funding.

Gandel Philanthropy made a ‘challenge’ award to meet half the funding required to develop this project, and over 100 NeuRA donors across Australia met the challenge, donating the remaining half. Our thanks go to all these supporters who have seeded a great idea, and one that is now funded by the NHMRC over the next four years to demonstrate that the Standing Tall program can prevent falls in older Australians.

Philanthropy is key to the future of improved health and medical outcomes here at NeuRA as it can hasten the process of turning ideas into cures by helping researchers clear funding hurdles. For your generous support, we sincerely thank you.

NeuRA (Neuroscience Research Australia) is a not-for profit research institute based in Sydney, Australia. Our vision is to prevent and cure disease and disability of the brain and nervous system through leadership and innovation in neuroscience research. Find out more at neura.edu.au or call 02 9399 1000.

About NeuRA

Professor Peter R Schofield PhD DSc Executive Director and CEO

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welcome

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Editor & Photography: Anne Graham Journalist: Siobhan Moylan Design: Kristian Molloy

Credits

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IDENTIFYING RISK GENES

Mental illnesses vary significantly in heritability suggesting both genetics and environmental factors play

a role. Due to the complex ways that our genes and life experiences, such as trauma, interact to cause an illness, identifying risk genes is difficult. In a systematic review,

Dr Justine Gatt and colleagues showed certain genetic risk variants to have a significant role in five different

psychiatric disorders. Identifying these ‘risky’ genes leads to a better understanding of resilient - or protective -

genes in people who have been exposed to trauma yet are flourishing. The goal of future work is to identify

‘resilient’ genes in adolescents and adults.

news

IN BRIEF

CHRONIC LOWER BACK PAIN TREATMENT Our researchers are at the forefront of developing new

and effective approaches to normalise some of the brain changes that underlie chronic pain. Using a new treatment method called ‘Sensorimotor retraining’, Dr James McAuley

and colleagues aim to help people recover from chronic low back pain by improving sensory, motor and spatial

awareness of the lumbar spine in a graded manner. The treatment method will be comprehensively tested in an NHMRC-funded randomised controlled trial, called

‘Restore’ that begins this year.

YOUR RESEARCH INTO INJURY PREVENTION IS BROAD - WHAT AREAS DO YOU COVER?

My research aims to facilitate the implementation, availability and use of safety technologies to reduce risk of injury.

The World Health Organization estimates that five million people are killed each year around the world through injury and many more require medical treatment. Almost one million of those people are under 18. Road traffic injuries are predicted to become the third leading contributor to the global burden of disease after heart disease and major depression by 2020.

One of my research programs targets motorcycle safety. Areas we are working on include better understanding of the risk factors for crashing, how new technologies might help to make motorcyclists safer on our roads, the impact of fatigue on riders and the performance of motorcycle protective clothing.

Cover Prof George Paxinos

01 Prof Peter Schofield

02 Dr James McAuley

03 Dr Justine Gatt

04 Dr Julie Brown

05 Testing effect of heat on a motorcyclist

Many riders, particularly large men and small women, have problems finding protective clothing that fits them well.

We know that there is a lot of room for improvement in the area of impact protection. We also know that some types of motorcycle clothing, if worn on long rides in hot Australian summer conditions, can lead to potentially dangerous increases in body temperature. We will be continuing our work investigating body temperature and heat discomfort.

Looking at other ways to provide better crash protection for riders, i.e. through more crash-friendly motorbike design, is also now on our radar.

HOW WILL YOUR RESEARCH MAKE THE ROADS SAFER FOR MOTORBIKE RIDERS?

We hope that our work will lead to more knowledge and better crash protection for Australian riders. Our aim is to assist manufacturers in providing the best possible equipment on the Australian market.

Making this equipment accessible to all riders, of all sizes, is a key objective of our research. If the use of good quality protective clothing increases, the number of motorcyclists being admitted to hospital will reduce, making riding safer.

WHAT HAVE YOU FOUND SO FAR - IS ALL CLOTHING CREATED EQUAL?

We’ve found that there is a big variation in the quality of protective clothing being worn by Australian riders. Some riders are offered excellent protection but sadly others aren’t. From speaking with riders, we know there is a distinct lack of information available for them when making decisions about clothing purchases.

Message from ourEXECUTIVE DIRECTOR

NEW SCHIZOPHRENIA CLINICAL TRIAL

Researchers are inviting people aged 18-55 years old, with a diagnosis of schizophrenia or schizoaffective disorder, to participate in a new clinical trial.

Our recent research has shown that ~40% of people living with schizophrenia may have brain inflammation. The study will determine whether canakinumab, a human immune cell-line antibody that reduces inflammation, can reduce symptoms and restore thinking abilities in schizophrenia.

To participate, please contact Isabella Jacomb, (02) 9399 1858, email: i.jacomb@neura.edu.au.

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“Historically, the erroneous attribution of love to the heart can be traced to the ancient Egyptians of the third millennium BC. They considered the heart to be the seat of thought, memory, will and emotion. Hearts, stomachs and intestines were considered important for afterlife, but not the brain. Before burial, the ancient Egyptians heedlessly discarded the brain, so for millennia pharaohs arrived brainless for their afterlife. The problem with the brain is that, unlike the heart, it doesn’t flutter when lovers kiss.”

The scientist credited with the discovery of the relationship between the mind and the brain was Alcmaeon (circa 520-450 BC; possibly a student of Pythagoras) who lived in the Greek-speaking colony of Kroton (Crotone of today’s southern Italy). It ’s thought Alcmaeon was led to his astonishing conclusion by observing that all senses are connected to the brain through channel-like structures. Today, we call them nerves.

Alcmaeon’s concept is thought to have passed on to the island of Kos, where Hippocrates (460-370 BC), the most significant physician of antiquity, worked. Hippocrates expressed an amazingly modern view:

Men ought to know that from the brain, and from the brain only, arise our pleasures, joys, laughter and jests, as well as our sorrows, pain, griefs and tears. Through it, in particular, we think, see, hear and distinguish the ugly from the beautiful, the bad from the good, the pleasant from the unpleasant.

Hippocrates’ view could be taught in any neuroscience department today.

A GLOBAL EFFORT TO MAP THE BRAIN IS UNDERWAY

President Obama’s “BRAIN” Initiative is underway – it is a bold, new research effort to revolutionise our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury.

Since President Obama announced the BRAIN Initiative two years ago, dozens of leading technology firms, academic institutions, scientists and other key contributors to the field of neuroscience have responded to his call and made significant commitments to advancing the global effort, including Prof Paxinos who is a grant recipient with collaborators at Cold Spring Harbor Laboratory in New York. “Our contribution will be a map of the cells and their connectivity in the mouse.”

“I am very excited to be a part of this initiative and if my work helps other scientists looking to cure disease, I am very happy for that. But in the end, we must remember it’s our brains that, on one hand, find cures for disease but, on the other, can construct weapons of mass destruction. Understanding its limitations is equally as important as praising its strengths.”

Professor George Paxinos, AO is an anatomist at Neuroscience Research Australia. He is an NHMRC Senior Principal Research Fellow, and Scientia Professor of Medical Sciences at UNSW.

The 4th edition of The Rat Nervous System edited and curated by Prof George Paxinos has just been published and appeals to researchers working on other species, including humans. The fourth edition provides the latest information in the field of research on the brain, spinal cord, and peripheral nervous system. The structure, connections and function are explained in exquisite detail.

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Frontotemporal dementia (FTD) is the second most common form of young onset dementia. Behavioural variant (bvFTD) is the most common form of FTD. Increasingly it is recognised that FTD has a strong overlap with motor neuron disease (MND) at both a pathological and clinical level.

Patients with bvFTD develop changes in personality and behaviour, but there are also significant changes in eating habits that may affect prognosis including binge eating and increased carbohydrate consumption. This behaviour is a major criterion for the diagnosis of bvFTD and is present in over 60% of FTD patients.

Dr Rebekah Ahmed and colleagues aim to better define the pattern of eating changes in FTD and are examining the effects they have on metabolism. In MND there is increasing evidence that metabolic changes may affect disease progression for the better, with factors such as hyperlipidemia and insulin resistance proving to be protective.

In a recent study, the research showed that patients with bvFTD have changes across all domains of eating including appetite, food preference, eating habits and swallowing, compared to patients with Alzheimer’s disease. The bvFTD group also had increased carbohydrate and sugar intake. These eating changes resulted in weight gain and an increase in body mass index (BMI).

A separate study showed that these eating changes are associated with an increased incidence of diabetes mellitus and increased Triglyceride and fasting insulin levels and lower HDL cholesterol levels, suggesting a state of insulin resistance.

Given that similar changes have been found to be protective in MND, the question now is whether these changes may be protective in bvFTD. One hypothesis is that they are protective in terms of muscle health, but detrimental in terms of cognition and brain health.

Rebekah now plans to investigate what brain structures control eating and the effect of eating and metabolic changes on disease progression. Finding answers may lead to interventions to modify metabolism affecting the prognosis for patients.

01 The wire diagram shows how the brain and spinal cord control the heart and other organs (source: Prof John Furness, Melb University)

02 Dr Rebekah Ahmed

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INCREASED appetite in FTD

Professor George Paxinos believes that there is one thing about the brain that is largely ignored - its cognitive, emotional and motivational limitations. He has been mapping the brain and creating detailed atlases for over four decades, and has come to the conclusion that overestimating this much-hailed organ will lead to humanity’s eventual demise unless we can understand our very human limitations.

DO WE NEED A REALITY CHECK WHEN DISCUSSING THE BRAIN?

Prof Paxinos and his colleague Prof Charles Watson have made it their life’s work to understand the brain and its mechanisms. They do this by creating maps that are published in several languages and are used globally as references. Prof Paxinos is passionate about the brain, but is calling for a reality check.

“The over-confidence we are now seeing in the abilities of the brain will be our undoing because we think that technology will solve the problems that humanity is creating. We must remember we are only animals and our emotions and intellect are hugely fallible.”

Although Prof Paxinos says we have come a long way in understanding the brain and its functions, including how we love, he warns that we have only just begun on a journey that needs to be kept in perspective. “We seem to be getting much better at what we do. We can now do the work we used to do in two years in just one month.”

ARE WE IN CONTROL - DOES SIZE REALLY MATTER?

With the knowledge Prof Paxinos has gained over the years, he posits that there is one thing he can say for sure, “the brain is only working on the basis of our genetic endowment and the environmental influences on it, neither of which we have control over.”

He believes that once we properly recognise our constraints, we might better understand our actions and be better able to solve major world problems. “If our brains were smaller we would not have language, which made science possible and the subsequent development of technology, some of which threaten humanity.”

“If on the other hand the brain were larger, then it might have been able to solve our problems. The brain is just not the right size for survival. Perhaps a reality check is needed and we should take our brains off the pedestal of infallibility.”

DO WE REALLY ONLY USE 10% OF OUR BRAINS?

A myth has been circulating for some time that we only use 10% of our brains. Prof Paxinos laughs at this notion and says, “Nobody has a proper answer to the question but my suspicion is that the brain has a lot of redundant cells just in case another group of cells dies - so that a person won’t be handicapped or develop Parkinson’s disease with a small knock on the head. The fact is we have many reserve neurons that can take over if some neurons are damaged.”

“To suggest that we have large reserves of untapped brain power is to say that spare tyres make cars attain greater speeds.”

“The human brain is one of a number of good brains that nature has produced as a mechanism to survival but it is not as powerful as people think. Not since Narcissus fell in love with his own reflection has there been such an adoration of a bodily organ.”

Superimposed on the maps Prof Paxinos creates are data relating to cells, neurotransmitters, receptors, connectivity and function - in essence, what parts are involved in memory, motor control, motion, vision and, of course, emotion. “For all these you need maps and, in fact, we know much more about love because of the maps that we build,” says Prof Paxinos, musing on one of his favourite topics – human emotion.

SO DOES LOVE LIVE IN THE BRAIN AND CAN IT BE LOCALISED?

The answer is yes. Prof Paxinos explains that science has come a long way since the Greek Philosopher Aristotle believed the brain to be a cooling mechanism (air conditioner) for the blood.

“Not since Narcissus fell in love with his own reflection has there been such adoration of a bodily organ.”

feature story

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BrainL I M I T A T I O N S

o f t h e

news

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JOIN THE NEURA RUNNERS TODAY!

11/12 April Australian Running Festival Canberra 17 May Half Marathon Sydney* 24 May Run for Reason Perth* 14 June City2South Brisbane 4 & 5 July Gold Coast Marathon 26 July Run Melbourne* 9 August City2Surf Sydney* 6 September Canberra Fun Run 20 September Blackmore’s Running Festival Sydney

*NeuRA is an official charityEmail or call Stephanie Grove E. s.grove@neura.edu.au P. 02 9399 1270 and support NeuRA.

“We wanted to help other families avoid what we had been through…”On 21 June 2014 we lost our father, Francis Inge, to multiple system atrophy (MSA), a disease we had never heard of before Dad’s diagnosis in 2007. Dad lived with MSA with incredible grace that was inspiring to us all. But seeing MSA take its toll on him over time was a tragedy for the whole family. When he passed away our mother, Rowena, was emphatic that she wanted to help other families avoid what we had been through.

Through the MSA Australia & New Zealand Facebook group, I knew that NeuRA researchers were working on MSA, so we asked for donations to NeuRA in lieu of flowers. It meant so much to us to see donations come in from friends and family all around the world. We raised $5,000 and to us, every cent was a testament to the love and respect that everyone felt for Dad and his legacy.

The ability to donate online was really helpful because so many of our friends and family are overseas. But NeuRA also organised memorial envelopes for the funeral with less than a day’s notice. They kept us informed of the donations that were coming in and sent thank you letters to every donor. When all the donations had come in, they hand-delivered a letter to Mum with a list of donors and the total amount raised. All these gestures helped us feel like we were really doing something positive to fight this disease.

Ditch OrdinaryWatching someone you love suffer is heartbreaking. Our desire is to help in any way we can. But, all too often, we end up feeling helpless, angry and alone - but there is something you can do.

Take on the Great Wall of China: Discovery Trek! Raise awareness and funds for research into the prevention, treatment and cure of brain and mind disorders and injuries.

• Trek the Great Wall as it winds between rural Chinese villages and otherworldly mountains

• Experience the contrasts of ancient and modern Beijing, from Tiananmen Square to the Forbidden City

• Discover the history of a thousand years’ past as you weave through ancient hutongs in a traditional rickshaw

• Fund innovative research into the prevention, treatment and cure of diseases and injuries of the brain or nervous system

For more information visit inspiredadventures.com.au/neura/china2016/ or call 1300 905 188.

Accounting Firm PKF Lawler Tamworth and Walcha ran the City2Surf 2014 in support of motor neurone disease (MND) research at NeuRA. Evan Brownsmith was their team leader. “We cannot directly improve the lives of MND sufferers, nor can we make it easier on their families. We cannot hope to cure this terrible disease ourselves, but we know that our contribution to NeuRA will help the very people who just might. Perhaps more importantly, through demonstrating a willingness to ‘give it a go’, we are setting a great example to the community of Tamworth. We want to show that it’s important to get out there and have a crack, not because we should, but because we still can.”

Evan Brownsmith PKF Lawler Runner

I was diagnosed with Parkinson’s in 2008 at the age of 35. For the first few years my symptoms were mild and didn’t really affect my day-to-day life. Unfortunately, over time, my tremor slowly worsened and my ability to control fine motor skills was becoming more difficult.

I was advised that I should improve my overall fitness and core strength. I started going to a gym, working with a personal trainer and I also decided that I needed a goal to aim for. My close friend Nicky, who is naturally a competent runner, wanted to run in the 2014 City to Surf so we agreed that we would run together. I knew this would motivate me to get fit and so the training began.

We wanted to raise money for a charity that was relevant to both Parkinson’s and Alzheimer’s (Nicki’s father suffers from Alzheimer’s). We knew that NeuRA was doing great work in brain and nervous system disease research and so we felt it was a perfect fit.

Most of my family, friends and work connections are aware of my condition but I do not make a habit of talking about it. I was therefore overwhelmed by the generosity of the many people who made donations. I clearly remember sending the email out to my address book one evening with the hope of raising a total of about $1,000 but, within 2 days, we had already exceeded this amount! The pressure was now on to complete the race.

I managed to finish in a better time than I had expected with my good friend Nicky encouraging me and pushing me along. By completing the race I had achieved my goal but the experience exceeded my expectations; the total amount of donations we raised was in excess of $5,500. Most importantly, I was extremely humbled by the generosity of so many people and it felt good knowing that my personal challenge had ultimately benefited many through NeuRA’s research.

Steve Hartley

01 Back row: Evan Brownsmith, Nicole Parkinson, Kelee Hawker & Blair Richards. Front row: Megan Mann, Caitlin Mann

02 Steve and Nicky at the finish

03 Rowena & Francis Inge

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NOT BECAUSE WE SHOULD, BUT BECAUSE WE STILL CAN.

My personal challenge ultimately benefited many…

Remembering A LOVED ONE

reasons to run

supportingNeuRA research

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DISCOVERY TREK 27 April to 7 May 2016

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Lici Inge

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• Mail this coupon in the reply paid envelope

• Call us on 1300 888 019 to make a donation over the phone

• Make a secure online donation at neura.edu.au/donate

• Fax this form (02) 9399 1082

Thank you for generously supporting our research into diseases of the brain and nervous system.

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Visa Mastercard American Express Diners

$50 $100 $250 or

Step 2: My gift:

Step 3: How to make a donation

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Step 1: How I choose to give my gift:

A message from the NeuRA Foundation: The NeuRA Foundation may co-operate with other like-minded reputable Australian charities to promote our work to our respective donors. If you’d prefer that NeuRA does not share your information with other charities, please phone us on1300 888 019, email us at foundation@neura.edu.au or write to us using the enclosed envelope.

DONATION & RESEARCH VOLUNTEER FORM

Neuroscience Research Australia Foundation, PO Box 1165, Randwick NSW 2031 ABN 57 008 429 96

The intricate ways the body, whether human or animal, is put together and functions; the solutions nature comes up with to ensure developmental changes occur in order; and the beauty within the patterns and networks that are repeated on different scales.

Histological images are works of art that are beautiful to the layperson and meaningful to the medical professional and have a way of showing us that we are made of patterns, designs and colours.

This image is a digital artwork created from a histology image. In the original image, communication pathways in the rat brain were stained with silver particles.

Histological images like this one are the gold standard for visualising the brain, but can only be prepared from post-mortem tissue.

Dramatic technological advances in brain MRI have made it possible to create images of the living brain in almost equally exquisite detail to histology.

By comparing MRI to histology, our researchers are improving our ability to identify structures in the living brain, which will eventually revolutionise how we diagnose brain disease.

Click on the icons on our website to view.Neuroscience Research Australia, Margarete Ainsworth Building, Barker Street, Randwick NSW 2031

Phone: 02 9399 1000 Email: info@neura.edu.au Website: neura.edu.auTo make a donation in support of our research, call 1300 888 019 or go to neura.edu.au/donate

INTRICATE BEAUTY of histology

Histology – microscopic

anatomy showing cells and their

organisation – is fascinating.

in focus