The life of an early career researcher

An early career researcher is an interesting creature – focussed, driven and often self-critical. Outgoing Chair of the Early Career Committee (ECC) at NeuRA, Kirsten Coupland, explains what it is like being a young scientist and the role the committee plays in supporting careers.

Early career researchers are those working in science who have completed their PhD less than six years previously or who are under the age of 40; whether studying or employed, involved in academia, or industry. There are around 120 early career researchers currently at NeuRA but this number fluctuates as people take exciting steps in their careers. These researchers are just discovering what a career in research entails. They are finding that a scientific career is not as structured as one in the corporate world; skills are learnt on the job and successful outcomes to experiments often initially elude them. Young researchers learn at the deep end. The work of the ECC, of which I am the outgoing Chair, is important for young researchers at NeuRA. We provide events and seminars that develop the skills and professional attributes young researchers need to cultivate a successful career in science.

What it takes to be a scientist

The world of research is extremely competitive and many of the things that set one scientist apart from the crowd are less tangible than research results. Being a good scientist requires the ability to communicate, have a strong network, a comprehensive knowledge base and confidence.

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Kirsten Coupland in the laboratory

What we do 

NeuRA’s ECC aims to give young researchers the ability to cultivate these assets and enjoy themselves at the same time. Events the ECC orchestrates encourage young researchers to interact with new people from different research groups. In doing so, they not only become confident at communicating their research to scientists from other fields, but they also start developing a network they will use throughout their career. Initiatives include regular seminars featuring speakers from around the country who discuss topics such as ethics, social media, and where to source funding.

Panel discussions of post-docs or non-academic science careers have helped get early career researchers thinking about what they will do with their scientific knowledge. Informal coffee meet-ups allow students to discuss their research with a mixed audience and interact with people they may not know at NeuRA. Early career researchers are the future generation of scientific research. It is important they have the skills and attributes necessary to carry out creative and exciting science that will revolutionise the way we understand the human body.    

Cannabidiol – a glimmer of hope for Alzheimer’s disease?

Alzheimer’s disease is the most common form of dementia, which affects around 330,000 Australians. In 2009 – 2010, the healthcare cost of dementia was over 4.9 billion dollars in Australia. Both of these figures are on the rise, given that our life expectancy is increasing.

People living with Alzheimer’s disease experience a range of symptoms that include social withdrawal and problems with remembering places, objects and people, and these symptoms become progressively worse with time. In the brain, aside from the increasingly well-recognised amyloid plaques and tangles, imaging and post-mortem analyses have also found extensive neuronal degeneration, inflammation, toxicity and oxidative stress, and these processes are likely to contribute to the development of Alzheimer’s disease.

Current treatments are unable to stop the disease progression, and the quest to find a viable treatment for Alzheimer’s disease continues. Many treatments have been designed to target single brain systems that are affected in Alzheimer’s disease. However, this approach is not sufficient for two reasons: 1) more than just one system is affected in the disease, and 2) it may be too late to administer these treatments once the disease has been diagnosed. Research now suggests it may be more beneficial for patients if treatments targeted a range of systems that are altered in Alzheimer’s disease and could be administered early, perhaps even before disease symptoms are prominent, as a method of prevention.

So where does one find a treatment that can exert neuroprotective, anti-oxidant and anti-inflammatory effects all at once? Well, the answer might lie in a compound known as cannabidiol. Cannabidiol has been shown to have all the above properties, which could be relevant for Alzheimer’s disease. However, there have been only a few studies that have followed up on this link, perhaps because many people might be eager to dismiss cannabidiol as a treatment due to concerns that it may exhibit the psychoactive properties of other compounds obtained from the cannabis plant. But in fact, cannabidiol is behaviourally inactive in humans when taken over long periods of time, including in people with schizophrenia and Huntington’s disease. Cannabidiol also prevents the memory-impairing effects of THC, the main psychoactive compound of cannabis. And, in promising news for Alzheimer’s research, cannabidiol has also been shown to reduce amyloid production and increase neurogenesis in brain cells. With this in mind, it is only logical that cannabidiol should be tested for its potential to benefit those with Alzheimer’s disease, as it might counter some of the main biological changes that are occurring.

David Cheng has just completed his PhD at NeuRA under the supervision of Dr Tim Karl.

David Cheng has just completed his PhD at NeuRA under the supervision of Dr Tim Karl.

My study, published in the journal Psychopharmacology, was the first to investigate the effect of cannabidiol treatment in a transgenic mouse model of Alzheimer’s disease. This mouse model carries two genetic mutations that are associated with familial Alzheimer’s disease, and the mice show behaviours that are relevant to Alzheimer’s symptoms, such as social recognition and spatial memory deficits. Since normal mice have a tendency to explore either new things or other mice, we compared how well transgenic mice fared in a test called the social preference test, which measures the amount of time that the test mouse spends exploring either a familiar or a new (never before seen) mouse. I discovered that the Alzheimer’s model mice spent the same amount of time exploring both the new and familiar mice, showing that they were unable to tell the difference between the two. Excitingly, daily cannabidiol treatment given over 3 weeks restored the social recognition memory of the transgenic mice.

In a separate study, soon to be published in the Journal of Alzheimer’s disease, cannabidiol was given to the transgenic mice every day, beginning at a very early age, to test whether it can be administered early as a prevention against the social recognition memory deficits. Promisingly, the development of recognition deficits in the disease model mice was prevented by the cannabidiol treatment. Using various biochemical techniques, I also found evidence to suggest that this effect might be mediated by the anti-inflammatory properties of cannabidiol.

These findings are extremely interesting as they show cannabidiol might have behavioural and biological effects that could benefit people with Alzheimer’s disease. Of course, we know that mice are not exactly like humans, but mouse models give researchers a great amount of insight into the effects of Alzheimer’s disease genetic mutations on both behaviour and biology. For example, links can be drawn between the social recognition deficits displayed by the Alzheimer’s disease model mice and the inability to recognise familiar faces in people with Alzheimer’s disease. Imagine what it would mean for people with Alzheimer’s disease and their friends and relatives if they could still recognise their loved ones! With more research, it will be possible to gain a better understanding of the exact mechanisms behind the beneficial effect that cannabidiol has already shown in this mouse model, paving the way for possible clinical trials in the future.

Building blocks for a fresh understanding of schizophrenia

Dr Dipesh Joshi received this year’s Leslie Kiloh paper award for his work into the understanding of schizophrenia. Since then, he has published new work linking problematic neurons to a genetic abnormality associated with schizophrenia.

He explains how his work has created a greater understanding of this disease…

Genes are a precious gift that every generation passes on to the following one since the existence of mankind. Abnormal functioning of some of these genes may lead to abnormal functioning of the brain cells leading to development of brain disorders. NRG1 and ErbB4 are two such genes that have been identified as ‘schizophrenia risk genes’.

Altered functioning or signaling of these genes contributes to the development of schizophrenia. Research shows that there are physical differences in the brains of people with schizophrenia compared with those of healthy people. To identify how genetic abnormalities lead to such physical differences remains a significant challenge. If this was known, we would be closer to understanding exactly what happens in the brain to cause the symptoms of schizophrenia, such as social withdrawal, difficulty with memory and planning, and even hallucinations, all of which can be very distressing to an individual with the illness.

What drug treatments are available now?

These days, the available antipsychotic treatments are relevant only for positive symptoms such as hearing voices, suspiciousness, feeling as though you are under constant surveillance, delusions, or making up words without a meaning, but not for negative symptoms which might include social withdrawal, cognitive deficits, difficulty in expressing emotion and an inability to feel pleasure. This highlights the urgency of having new antipsychotic drugs that have beneficial effects in treating negative symptoms and cognitive deficits in people with schizophrenia.

What are the risk genes doing in schizophrenia?

Dr Dipesh Joshi is a postdoctoral research officer at NeuRA

Dr Dipesh Joshi is a postdoctoral research officer at NeuRA

Our recent research work has been able to link schizophrenia risk genes (NRG1 and ErbB4) with a type of brain cell which maintains the inhibitory-excitatory balance in a normal brain. In schizophrenia, this particular brain cell-type, called inhibitory interneuron has been found to be reduced compared to healthy individuals. Research conducted in our laboratory is completely unique as it shows how an increase in the risk gene (ErbB4) is linked with a reduction in inhibitory brain cells. Increased levels of ErbB4 gene contributes to the inhibitory-excitatory imbalance resulting in development of schizophrenia.

These findings are crucial for brain researchers to understand how schizophrenia ‘risk genes’ adversely affect brain cells resulting in brain abnormalities found in people with schizophrenia. Our findings are a step forward in identifying new therapeutic targets for a new generation of antipsychotics that will have beneficial effects that extend beyond positive symptoms in people with schizophrenia and for us that is a very exciting prospect.

 

Are you a healthy control?

How about becoming a healthy volunteer for research and helping us Discover ~ Conquer ~ Cure? 

Do you have spare time and want to make a difference to people’s lives? Perhaps you’re willing to give up your time and participate in studies right here in Randwick?

I’m Connie Severino and my job at NeuRA is to maintain our healthy volunteer database that provides researchers with an easy way to recruit people for their studies.

We are always looking to recruit healthy volunteers because we want to make a difference to the lives of many who have suffered or are currently suffering neurological illnesses.

Healthy volunteers play an important part in supporting our research programs.

Each group within NeuRA covers a different area of research ranging from Alzheimer’s disease, chronic pain, falls and balance, Frontotemporal dementia, Parkinson’s disease, sleep apnoea, stroke, and many more. We recruit healthy volunteers for all of these areas.

We use data we collect from our healthy volunteers and compare it with the data we have from those affected with a particular neurological condition.

A healthy volunteer, often referred to as a ‘control’ or who sits within a ‘control group’, is simply a standard of comparison for checking or verifying the results of an experiment. Controls are the standard against which experimental observations are evaluated.

Becoming a volunteer does not cost you anything, however we do ask for your time and patience. Initially we ask you to complete a questionnaire and, from there, if you meet the control criteria, we register you on our Healthy Volunteer Registry that allows you to be selected up to three times a year.

What do I need to know? 

Often researchers will ask for clear specifications in controls such as age, gender, right or left handedness or walking ability. Once you are selected for a study, the researchers are notified and will contact you and ask you to participate.

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Jacqui Zheng with a volunteer for a falls and balance study at NeuRA

Each group’s tasks and activities vary but, rest assured, you will be well informed as to the specific tasks required of you before the trial begins. We endeavor to accommodate all your needs from travel arrangements, pick up and parking depending on your location and, at all times, keep you comfortable and informed.

We look for participants housed all over the country, particularly in NSW and the ACT. That said, due to most testing taking place here in Randwick, we typically invite volunteers from the Sydney metro and surrounding areas to join us, for ease of travel.

How do I get involved? 

Once you become a registered volunteer, you are not obliged to accept every invitation you are offered and you are of course free to withdraw from being on the registry at any given time.

Our registry has been active for approximately four years and has been beneficial for 30 studies to date. Some of our volunteers have returned to us multiple times as they enjoy the process and the ability to contribute to medical science in this way.

If you are interested in contributing your time, please see our website for further details or contact me directly on (02) 9399 1155. I am happy to answer any questions you might have.

It’s my belief that ‘A problem shared is a problem halved’… we thank all those who have helped in the past and who continue to volunteer.

The pain – brain relationship

Exactly how does educating patients about pain lead to better outcomes? PhD student at NeuRA, Hopin Lee, is seeking to answer that question.. 

Most of us know, through personal experience or having heard about someone else’s experience, that back pain can be troublesome. For many it’s just a niggle that can be kept under control with simple analgesics and a bit of reassurance that there is nothing sinister happening in their back. However, for some, back pain can cause major disruptions to life. While there may be some periods when symptoms ease, they often recur and eventually a longer period of persistent pain and disability ensues.

There is no doubt that in clinical practice a large number of patients present with back pain, yet it is often the most difficult condition to treat. Clinicians are often faced with a choice of assorted treatment options, ranging from localised injections to generalised physical exercise and psychological interventions. Despite the plethora of available treatments, research suggests that their effectiveness is often modest with short lived benefits.

The black box 

Most research investigating back pain treatments has focused on answering whether the treatment is successful or not. This is the so-called ‘black box’ approach where little or no attention is paid to how the treatment exerts its effect on the outcomes that we strive to improve. A limitation of this approach is that we are left without any knowledge about whether the underlying theories behind these treatments are valid. Without understanding the mechanisms that underpin treatments, we naturally return to the black box approach and move on to test a new set of treatments, without thinking about how we can improve existing ones. However, if we are able to verify or refute the underlying mechanisms of our treatments, we may be able to refine and modify existing treatments to develop better treatments informed by evidence.

Although theories and speculations about treatment mechanisms are bountiful, there has been little attempt to test theories with appropriately designed studies. A way of testing these mechanisms is to design studies so that mediation analysis can be applied. Born out of psychology, mediation analysis is considered to be an efficient method of investigating relationships between variables. This method of analysis will be the central focus of my PhD thesis – to explain how a treatment for lower back pain may have its effects on the outcomes of interest.

A Journey of understanding.. 

PhD student Hopin Lee

PhD student Hopin Lee

Our group (Moseley group) at NeuRA is conducting a NHMRC funded randomised controlled trial (PREVENT) to evaluate the effectiveness of an educational intervention for patients with acute low back pain. My PhD will investigate the theories that underpin this intervention to see if they are valid and supported by the data.

PREVENT tests, in a randomised controlled trial, whether patient education that focuses on reconceptualising how a patient thinks about pain during the acute stages can prevent their low back pain from becoming persistent. The patient education provides patients with the understanding that pain is a protective output of the brain, rather than a direct measure of tissue damage. Conveying these messages in relation to their existing beliefs and attitudes towards pain may modulate their painful experience, which may lead to better outcomes. These are some of the theories I will test in my PhD.

So how might educating patients about pain lead to better outcomes? For example one of my hypotheses is that if patients are taught to think about their pain as a protective response of the brain rather than a signal of harm to their back, this might reduce catastrophising thoughts (having a negative outlook, thinking the worst will happen). This is a plausible theory, considering that catastrophising thoughts are related to pain intensity and disability. Patients who catastrophise about the prognosis of their back pain tend to have higher levels of pain and disability which coincide with slower recovery rates. The challenge is to decipher whether PREVENT can change these mediating variables (e.g. catastrophising, beliefs and attitudes about pain) and whether this then leads to better outcomes for patients.

My vision for the future is that we seek to open the mysterious black box and peek into some of the complex mechanisms that are at work. This may allow us to move forward to logically refine our treatments based on scientific theory and reason. I think most of us would agree that a clear box provides better insight as opposed to an opaque black box… don’t you?

We are currently recruiting participants to this study. If you are you currently suffering an acute (less than 4 weeks) episode of low back pain, live in Sydney and would like to join the study please email us at prevent@neura.edu.au

 

 

The Social Brain

Dr Muireann Irish uncovers the part of the brain that underpins social cognitive deficits in semantic dementia, further unraveling mysteries behind the disease.

It may sound like the subject matter of a science fiction movie, but mind-reading is a process in which we regularly engage. On a daily basis, whenever we interact in social scenarios, we go beyond our own perspective to infer the thoughts, beliefs, and feelings of other people. This innate skill to appreciate perspectives distinct from our own allows us to function effectively within the social world. For example, we can instinctively understand how a colleague may feel when their latest publication is rejected, or we can intuitively place ourselves in a friend’s shoes when they experience a joyous event like the birth of a first child.

Theory of Mind

My latest study sheds light on the brain regions that need to be functional in order to support this ability to empathise with others. The study, published in the journal Brain, reveals that structures in the right hemisphere of the brain are essential to enable us to read the minds of others and to consider their beliefs and feelings. ‘theory of mind’ is the term used to refer to our uniquely human ability to make these inferences and is crucial for our successful functioning in the social world.

By understanding that other people think and feel in ways that are distinct from our own perspective, we can appreciate differences between individuals. This capacity to infer the mental state of others confers immense flexibility in our approach to various social scenarios. Without this ability, we would appear rigid, egocentric, and unfeeling towards others.

While appreciating the mental state of others may come relatively easy to us, the capacity for theory of mind relies upon a complex network of structures in the brain. Research on healthy individuals has revealed that when we successfully consider another person’s psychological perspective, regions in the frontal, temporal and parietal lobes of the brain activate. Such widespread brain activation reveals how complex this function truly is.

It follows that damage to any one of these brain regions will block the capacity to take another person’s perspective. Theory of mind abilities are disrupted across a number of clinical conditions such as traumatic brain injury, autism, and dementia.

Semantic dementia

In frontotemporal dementia, it is commonly reported that patients are unable to understand how their actions affect other people, or to consider that the reactions of others may differ from their own. However, up until recently, we knew relatively little regarding the capacity for theory of mind in the syndrome of semantic dementia. My recently published research reveals, for the first time, that individuals with semantic dementia experience severe difficulties in considering the mental states of others, and that such deficits are attributable to atrophy of structures in the right hemisphere of the brain.

Semantic dementia is a subtype of frontotemporal dementia, characterised by the progressive loss of general knowledge about the world. It is conceptualised as a language disorder whereby patients experience a profound loss of the meaning of words and concepts. The patient is unable to recall the names of objects, places, people, and experiences difficulties in correctly labeling popular musical tunes, or basic emotional expressions. While the predominant complaint of the patient is that of language disruption, carers of patients with semantic dementia report alterations in social functioning and interpersonal behaviour.

The Protocol

Images taken from Lough et al. (2006) Neuropsychologia,

Images taken from Lough et al. (2006) Neuropsychologia,

I used a new task to explore if patients with semantic dementia could infer the thoughts, beliefs, and feelings of the main characters in humorous cartoon scenarios. Patients were asked to describe why a selection of cartoon scenes were funny and their descriptions were analysed for language that reflected consideration of different mental states, for example “he thinks”, or “she feels”. In the cartoon scene to the left, a correct answer would be something like, “The gentleman thinks he is being held up. The lady is not aware that she is frightening the man.”

A patient with semantic dementia tended to respond as follows, “The woman is hitting the man in the back. He is putting his hands in the air”. These responses indicated that the ability to spontaneously consider the mental state of others was disrupted in semantic dementia. Importantly, I demonstrated that the failure to successfully appreciate the viewpoints of others was not a result of the language difficulties that are typically found in semantic dementia.

Using neuroimaging analysis of structural MRIs, I found that shrinkage of the right temporal lobe of the brain underpinned the theory of mind deficits in semantic dementia. This finding is surprising, as these patients are typified by damage to the left side of the brain. As the disease progresses however, pathology spreads from the left to the right hand side of the brain. The semantic dementia patient displays impairments across multiple domains, beginning with language disruption and gradually progressing to include social dysfunction.

Why is this important?

The findings of this study are unique as they reveal, for the first time, that degeneration of right temporal regions in the brain is associated with social dysfunction in semantic dementia. The right temporal lobes have been consistently implicated in studies of social functioning in healthy individuals.

Our study illuminates the complexity of social cognition and how we achieve sophisticated acts of social inference in our everyday lives. By incorporating brain mapping techniques with new experimental tasks, we can continue to unravel the mystery of mind-reading and build a coherent picture of how humans navigate within the social world.

Technology and Science, a recipe for independent living..

Dr Kim Delbaere, originally trained as a physiotherapist, has merged her passion for the physical body with technology and envisions a future where older adults can stay independent for longer using app based technology.

From the age of 65 years and older, falls happen frequently and affect quality of life. About one in three older people fall at least once a year, and about half of the falls lead to injuries that can cause mobility restriction during daily activities. Older people are often aware of the consequences of falling, with over half reporting a fear of falling.

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Thomas Davis, Dr Kim Delbaere and Ashley Woodbury design apps at NeuRA

Clinical trials have taught us that falls can be prevented at all ages. The single most effective way to prevent falls is to do specific exercises. However, in order for exercises to reduce a person’s fall risk, the person must do challenging balance training for at least two hours per week for a minimum of 6 months.

Long-term participation with these types of exercise programs can be poor due to the often boring nature of repetitive exercises. Also, many older people are not aware that exercise is a proven effective strategy for preventing falls.

Embracing technology to enable independent living for longer

We are focussed on finding solutions to support active and healthy ageing. We want to help older people do the necessary exercises so they can live independently for longer. Our pioneering work has led to the development of various new technology-based solutions that we hope to release on the market soon.

We are using new technologies to design exercise programs, individualised for each person, as no one person is the same. Our programs seek to offer a greater choice of exercises for people to keep things interesting. We have already released a range of mobile apps that assist in the assessment of fall risk, therefore working towards reducing falls. The use of technology in this area has opened up a world of possibilities like the convenience of doing the right training in the comfort of your own home wherever you are. As long as you have occasional access to the Internet, you can use our programs.

Standing Tall, we’re working on it!

We are particularly excited about one of our apps that is currently being tested, called Standing Tall. This unique program offers individually-tailored, progressive, high-intensity balance exercises, and includes an in-built coach and activity planner to encourage you to do your exercises more frequently. The activity planner lets you set your own goals and has optional reminders if you need to exercise more. The program also lets you to monitor your own progress.

So far, results show that the program is safe and easy for older people to use. Our participants have told us that they really enjoy doing the exercises Standing Tall offers and that it helps them to exercise more regularly. The next step for us is to conduct a randomised controlled trial (the gold standard for a clinical trial) to see if people keep using our program over a longer period and to test its effectiveness in falls prevention.

If successful, Standing Tall will increase the likelihood of older people taking part in, and benefiting from this type of fall prevention strategy.

Our aim is to promote healthy ageing by reducing falls, at a low cost for the health care sector. Following on from our trial, we aim to make the Standing Tall mobile app available to the general public. Watch this space…