Conducted in partnership with the University of California San Francisco (UCFC), researchers found that changes in micromovements of the brain — termed ‘headpulses’ — could detect the lasting impacts of a concussion.

Using a custom-designed headset* to evaluate headpulse biometrics among 101 amateur male and female Australian Rules Football players in South Australia, researchers identified brain abnormalities in 81% of players inflicted by concussion, signalling sustained injury beyond expected recovery times.

These headpulse alterations lasted 14 days beyond concussion symptoms and were exacerbated by return-to-play or unsupervised physical activity.

UniSA Professor of Exercise Science Kevin Norton says that headpulse measures could complement current return-to-play protocols.

“Traumatic brain injury inflicts more than 60 million people every year, with a third of these being sports-related,” Prof Norton says.

“While we know that Australia’s sports sector takes concussions seriously — via considered return-to-play protocols — we also know that objective measures of concussion recovery are not fully established.

“In this research, we used headpulses — a normal measure of brain ‘wobble’ aligned with each heartbeat — to assess any changes in frequency resulting from a concussion.

“We discovered that almost all players who received a concussion had a ‘disconnect’ between their symptoms and the headpulse, such that even when the players said they felt good, the headpulse still showed evidence of brain injury.”

While most players felt that they’d recovered 10-14 days after their injury, the research showed that some players took up to four weeks to recover and return to normal headpulse patterns.

Australian Football concussion recovery protocols require 24 to 48 hours of strict physical and cognitive rest, followed by graded individual then team training, provided there is no symptom exacerbation; the earliest allowed return-to-play after protocol completion and medical clearance is 12 days after a concussion.

The Australian Senate Committee’s report Concussions and repeated head trauma in contact sports released this month, recommends that national sporting associations should explore further rule modifications for sports to prevent and reduce the impact of concussions and repeated head traumas.

This research contributes to the growing body of knowledge that informs concussion protocols.

Notes

• *The headset is patented by UCSF and licensed by medical technology company MindRhythm.
• Data for sport-related concussions and repeated head trauma is under-reported in Australia, however the most recent AIHW data shows that 2305 sports-related concussions occurred between 2019-20. Men incurred 70% of concussions and more than a third of those hospitalised were young sportspeople aged 15-24 years.
• About 730 of concussions occurred while playing some form of football; and approximately 440 occurred while cycling

The University of Queensland-led study shows current conservation efforts typically target biodiversity protection whilst minimising conflict with economic interests, while failing to consider the huge benefits provided by ecosystems.

Alvise Dabalà, now at the University of the Azores and whose Masters project at UQ formed the basis of this study, said human activities, such as deforestation and coastal development have led to extensive mangrove loss across the globe.

“They protect infrastructure and communities from storms, sequester carbon, and provide fisheries with nursing grounds, so their rapid destruction is devastating to witness,” Mr Dabalà said.

“As it stands, current conservation efforts just aren’t doing enough to take advantage of these services.”

The team is using the United Nations’ Global Biodiversity Framework, which recommends an increase in protected areas to 30 per cent of the world as the basis of their proposal.

Researchers are recommending an optimised conservation planning perspective that operates within this framework and puts more emphasis on these ecosystem services.

“It’s somewhat of a juggling act, where we have to consider the trade-offs between biodiversity protection, economic conflicts, and ecosystem services,” Mr Dabalà said.

“But if done properly, this target has the potential to safeguard AU$25.6 billion of coastal property value, globally.

“It would also protect 6.1 million coastal-dwelling people against the impacts of flooding, and safeguard over one billion tonnes of sequestered carbon.

“In Australia alone, we’ve identified priority areas in Northern Queensland, Darwin and East Arnhem in the Northern Territory, and between Pilbara and Kimberley in Western Australia.

“Expanding Australian mangrove protection would be particularly beneficial for carbon sequestration and biodiversity conservation as they stand out as some of the most diverse, carbon-rich mangrove forests.”

UQ’s Professor Anthony Richardson said to achieve these outcomes boils down to a shift in perspective.

“In some areas of the world, we recognise that human pressure could be so high that the value of ecosystem services would not compensate for the loss and could result in complications in implementing protection,” Professor Richardson said.

“However, for multiple ecosystems, including mangroves, we’ve quantified the benefits associated with considering the services these ecosystems provide — the figures are undeniable.

“We know that long-term gains from biodiversity protection are often greater than short-term gains from anthropogenic activities, so this shift in thinking must happen soon.”

Professor Richardson said developing biodiversity and ecosystem services data should be a priority to incorporate into applied conservation plans.

“Implementation of these plans should then follow different conservation practices that target local communities’ needs specifically,” he said.

“Moving forward, decision-makers and other stakeholders need to focus on protected area implementation, management, and monitoring to provide solid conservation outcomes.”

The study may explain why some people have an increased chance of developing conditions like inflammatory bowel disease or suffer more severe reactions to infections with bacteria like Salmonella.

At a glance

• MLKL is a gene essential to triggering necroptotic cell death — a natural process that protects our body from infection. In some people this process can go awry and trigger severe tissue damage.

• Study finds a genetic variation, known to enhance the ability of MLKL to kill cells, is carried by up to 3% of the global population.

• The findings could lead to better personalised treatments for inflammation and other diseases in the future.

Immune power of ‘explosive’ cell death

Every minute, millions of cells in our bodies die on purpose. Cell death is an essential process that protects our bodies from disease by removing unwanted, damaged or dangerous cells, and preventing the spread of viruses, bacteria, and even cancer.

WEHI’s Dr Sarah Garnish is first author on the paper and said that while there are various types of cell death, necroptosis is distinguished by its ferocity — the cells essentially explode, which sounds an alarm for other cells in the body to respond.

“This is a good thing in the case of a viral infection, where necroptosis not only kills the infected cells but instructs the immune system to respond, clean things up, and start a more specific, long lived immune response,” Dr Garnish said.

“But when necroptosis is uncontrolled or excessive, the inflammatory response can actually trigger disease.”

Genetic brakes

The gatekeeper of necroptosis is the gene MLKL. When the body needs to trigger a cell death response with plenty of firepower, the cellular brakes that normally keep MLKL in-check are released. However, some of us make a form of MLKL with flimsy brakes.

Dr Garnish and her co-authors have been able to quantify this at a population level for the first time.

“For most of us, MLKL will stop when the body tells it to stop, but 2-3% of people have a form of MLKL that is less responsive to stop signals,” Dr Garnish said.

“While 2-3% doesn’t seem like much, when you consider the global population, this adds up to many millions of people carrying a copy of this gene variant.”

Project leader Dr Joanne Hildebrand said the research proposes that a common genetic change like this can combine with a person’s lifestyle, infection history and broader genetic makeup to increase the risk of inflammatory diseases and severe reactions to infections.

This is known as polygenic risk — the combined influence of multiple genes on developing a certain trait or condition.

“Taking Type 2 diabetes as an example, it’s rare that just one gene change determines whether someone will develop the condition,” Dr Hildebrand said.

“Instead many different genes play a role, as do environmental factors, like diet and smoking.”

Dr Hildebrand said it’s not as simple as directly connecting this difference in the MLKL gene with the chance of someone developing a specific condition.

“We haven’t tagged this MLKL gene variant to any one particular disease yet, but we see real potential for it to combine with other gene variants, and other environmental cues, to influence the intensity of our inflammatory response.”

Towards personalised medicine

Our understanding of MLKL has come a long way since it surfaced by chance in a WEHI lab more than 20 years ago. Today’s research opens the door for future tests and screening to determine disease risks.

Genome sequencing is becoming cheaper and more readily accessible. As more genomic data becomes available to researchers, it increases the likelihood that they can link common genetic variants, like the one described for MLKL, with disease.

In the future researchers hope to pinpoint the genetic changes that might mean someone is more likely to have a severe case of COVID-19, or less likely to bounce back after chemotherapy.

“Every piece of information like this helps us make personalised medicine more of a reality,” said Dr Garnish.

The WEHI team is also investigating whether uncontrolled necroptosis could be beneficial in some circumstances. For example, could people with the MLKL gene variant have a stronger cellular defensive response to certain viruses?

“Gene changes like this don’t usually accumulate in the population over time unless there is a reason for it — they generally get passed on because they do something good,” said Dr Garnish.

“We’re looking at the downsides of having this gene change, but we’re looking for the upsides as well.”

The research was supported by the National Health and Medical Research Council, the Victorian State Government, the Australian Government Research Training Program Stipend Scholarship and the Wendy Dowsett Scholarship.

WEHI authors: Sarah Garnish, Katherine Martin, Maria Kauppi, Victoria Jackson, Shene Chiou, Yanxiang Meng, Daniel Frank, Emma Tovey, Komal Patel, Annette Jacobsen, Georgia Atkin-Smith, Ladina Di Rago, Marcel Doerflinger, Christopher Horne, Cathrine Hall, Samuel Young, Ian Wicks, Ashley Ng, Charlotte Slade, Andre Samson, John Silke, James Murphy and Joanne Hildebrand.