An injury to one part of the brain changes the connections between nerve cells across the whole brain, new research has revealed.
Traumatic brain injury (TBI) affects one in three people and can lead to physical, cognitive and emotional disabilities.
One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.
In a new study from University of California, Irvine, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent.
The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialised microscopes.
With the enhanced brain clearing processes, the UCI team mapped neural connections throughout the entire brain.
The researchers focused on connections to inhibitory neurons, which are extremely vulnerable to dying after a brain injury.
“Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders,” said Dr Robert Hunt, associate professor of anatomy and neurobiology and director of the Epilepsy Research Center at UCI School of Medicine whose lab conducted the study.
The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus.
In both cases, the imaging showed that inhibitory neurons gain many more connections from neighbouring nerve cells after TBI, but they become disconnected from the rest of the brain.
“We’ve known for a long time that the communication between different brain cells can change very dramatically after an injury,” said Dr Hunt.
“But, we haven’t been able to see what happens in the whole brain until now.”
To get a closer look at the damaged brain connections, Dr Hunt and his team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.
The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.
“It looks like the entire brain is being carefully rewired to accommodate for the damage, regardless of whether there was direct injury to the region or not,” explained Alexa Tierno, a graduate student and co-first author of the study.
“But different parts of the brain probably aren’t working together quite as well as they did before the injury.”
The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, Hunt and his team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the team’s earlier research demonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.
The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, Hunt said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.
“Some people have proposed interneuron transplantation might rejuvenate the brain by releasing unknown substances to boost innate regenerative capacity, but we’re finding the new neurons are really being hard wired into the brain,” said Dr Hunt.
Dr Hunt hopes to eventually develop cell therapy for people with TBI and epilepsy. The UCI team is now repeating the experiments using inhibitory neurons produced from human stem cells.
“This work takes us one step closer to a future cell-based therapy for people,” he said.
”Understanding the kinds of plasticity that exists after an injury will help us rebuild the injured brain with a very high degree of precision. However, it is very important that we proceed step wise toward this goal, and that takes time.”
New therapy reduces veteran headaches after brain injury
Cognitive Behavioural Therapy for Headache also shown to have positive impact on PTSD symptoms
The first therapy to be developed specifically for post-traumatic headaches significantly reduced related disability in veterans following a traumatic brain injury (TBI), a study has revealed.
Cognitive Behavioural Therapy for Headache (CBTH) was also shown to reduce co-occurring symptoms of post-traumatic stress disorder (PTSD) comparably to a gold-standard PTSD treatment.
Furthermore, the therapy was shown to be appealing to patients with low drop-out rates, and is easy for therapists to learn and deliver, increasing its potential to be widely used and to improve the lives of servicemen and women and veterans globally.
CBTH, which uses cognitive behavioural therapy concepts to reduce headache disability and improve mood, includes key components such as relaxation, setting goals for activities patients want to resume, and planning for those situations.
“We are excited by this development in the treatment of post-traumatic headache, which along with TBI is poorly understood and for which treatment options are so limited,” said Dr Don McGeary, associate professor at The University of Texas Health Science Center at San Antonio (UT Health San Antonio).
“To find the first major treatment success for post-traumatic headache, which is arguably the most debilitating symptom of TBI, and that the treatment also significantly reduces co-morbid PTSD symptoms, is a major breakthrough.”
Both TBI and PTSD are prevalent in post-9/11 military conflicts, and the two conditions commonly occur together.
Post-traumatic headaches, or headaches that develop or worsen following a head or neck injury, become chronic and debilitating in a large percentage of those who experience a TBI such as a concussion, inhibiting their ability to engage in the activities of daily life.
When PTSD is co-occurring, it can worsen the headaches and make them more difficult to treat.
Effective treatments exist for PTSD but not for post-traumatic headache, which along with TBI, scientists are still working to understand.
Migraine medications commonly used to alleviate the headache pain do not relieve related disability. They also often have unwanted side effects, and their overuse can worsen headaches.
In the study, Dr McGeary and his team developed CBTH by modifying a psychotherapy for migraine headaches. They evaluated its efficacy with co-occurring post-traumatic headache and PTSD symptoms.
The study was conducted at the Polytrauma Rehabilitation Center of the South Texas Veterans Health Care System.
Participants had clinically significant PTSD symptoms and headaches persisting more than three months following a TBI. They were randomly assigned to receive either CBTH, a leading PTSD treatment called Cognitive Processing Therapy (CPT), or the usual care provided at the VA Polytrauma Center.
At the end of treatment, researchers found that, compared to usual care, those receiving CBTH reported significant reductions in disability and in negative impact on function and quality of daily life.
They also showed improvement in PTSD symptoms comparable to the group that received CPT. All of these treatment gains were maintained six months after treatment completion.
CPT, on the other hand, led to significant and lasting improvements in PTSD symptoms, but on its own did not improve headache disability.
“This was a surprise,” said Dr McGeary.
“If theories about PTSD driving post-traumatic headache are correct, you’d expect CPT to help both PTSD and headache. Our findings call that into question.”
Interestingly, CBTH did not reduce headache intensity or frequency compared to usual care.
Dr McGeary said its dramatic reductions on negative life impact are likely due to its building patients’ confidence that they could control or manage their headaches, a concept known as “self-efficacy.”
That sense of control was key to helping patients “get their lives back,” he said.
“If you can improve a person’s belief that they can control their headache, they function better,” Dr McGeary said.
“That’s because, when dealing with a long-term, disabling pain condition, people make decisions about whether they’re going to actively engage in any kind of activity, especially if the activity exacerbates the pain condition.
“They make those decisions based on their perceptions of their ability to handle their pain.”
In comparison to CPT, CBTH requires fewer and shorter therapy sessions—typically eight sessions of 30-45 minutes each. CPT typically involves 12 sessions lasting 60-90 minutes each.
CBTH requires only two hours to train clinicians to deliver the therapy, compared to CPT, a complex treatment that requires significant training and acquired skill.
The research team now hope to broaden their study to be as representative as possible.
Dr McGeary said: “We need more women, more racial and ethnic diversity, veterans as well as active military of different branches, with varying comorbidities, in different geographic regions attached to different hospitals and medical systems because we’re comparing to usual care.”
Pioneering project could revolutionise capacity assessment
Sector-leading research is set to generate a framework of wellbeing indicators for patients
Specialist neurological care provider PJ Care has partnered with the University of Leicester for a sector-leading research project that could revolutionise the assessment and care of residents who lack capacity.
The two have come together in a knowledge transfer partnership (KTP) to support the creation of a centralised system at PJ Care to create algorithms that will generate a framework of wellbeing indicators for those who are non-verbal as a result of their neurological condition.
So far, a review has been completed of existing research into this area, which will be published jointly by PJ Care and the University of Leicester later this year.
Leading the project is Dr Allan Perry, consultant clinical neuropsychologist and director of clinical services at fast-growing PJ Care.
“The current models for assessing the health and wellbeing of those without capacity and who cannot readily communicate their feelings and experiences are limited and don’t take advantage of the recent advances in technology and data analysis that can give us much more detailed information,” he explains.
“There is a wealth of monitoring technology that we use which allows us to collect real-time data on a number of wellbeing indicators such as a person’s oxygen levels, heart rate, fluid intake and the number of steps they take to reach a certain distance.
“We believe this data can be analysed by an algorithm to provide insights into personal wellbeing, sense of agency, independence and self-determination, that are more accurate than those offered by traditional methods. We can then apply this information to tailor our care to that individual.
“While there is plenty of information on bringing more technology into the care sector and using the data being created by it, this isn’t being married with the questions posed by a person’s capacity as yet. We don’t believe any other care provider is delivering anything like what we are proposing to.”
PJ Care is a specialist neurological care provider with three specialist care centres – the first of which has just celebrated its 21st anniversary – for more than 200 adults with progressive conditions such as young onset dementia and Huntington’s disease, and care and rehabilitation for people with acquired brain injuries.
Dr Zehra Turel holds a PhD in cognitive neuroscience from the University of Leicester and serves as KTP research associate for the project, working with Professor John Maltby and Professor Elizabeta Mukaetova-Ladinska of Leicester’s Department of Neuroscience, Psychology and Behaviour.
She says there is an urgent need for an accurate assessment tool for those who have difficulty communicating.
“We have so far uncovered that the available wellbeing measurements neglect or fail in understanding of the clinical populations such as cognitively impaired individuals, with or without capacity,” says Dr Turel.
“This project will provide micro and macro insights about residents’ health and wellbeing, and support decision-making at both resident and business level.
“With the increasing use of new data-driven technologies and streamlined data collection at PJ Care, this project will improve personalised care and provide more accurate and faster predictive and preventive measures, and more informed decision-making along with lowering costs and simplifying internal operations.”
“This KTP has the potential to develop resources that could not just be transformative for PJ Care and how our staff support people without capacity, but, eventually, for the whole care sector,” says Dr Perry.
“We will be looking to market this if it proves to be as effective as we believe it will be.”
World Rugby increases post-concussion break to 12 days
In response to increasing scientific research and evidence, the minimum stand-down period has been raised from seven days
World Rugby is introducing new protocols for players diagnosed with concussion, having increased the break for a player post-concussion from seven to a minimum of 12 days.
The body said its change to Graduated Return to Play (GRTP) protocols for the elite game comes in response to the latest review of scientific evidence and rugby-specific research.
The new stand-down approach, to be implemented globally from July 1, will see players – including those with a history of concussion, or who are removed from a match with obvious concussion symptoms – sit out from play for a minimum of 12 days, likely missing their next competitive match.
No player will return earlier than the seventh day after injury, and any player’s return will need to be approved by an independent concussion consultant.
“This individualised rehabilitation approach supports our mission that the welfare of players comes first. It mirrors our promise to continually monitor, review and evolve our protocols based on scientific advice and evidence,” says World Rugby Chief Medical Officer, Dr Eanna Falvey.
“Rugby is a leading sport in head injury management, but we never stand still. It’s not just a new protocol – it’s going to be a new mindset for coaches and players.
“Our approach means it is now overwhelmingly likely a player diagnosed with a concussion won’t play in their team’s next match.
“World Rugby firmly believes that scientific evidence supports our protocols, but we are continually monitoring and testing them to ensure that they are fit for the modern game.
“We recognise that there are differences in concussion symptoms and concussion history and this process enables us to further protect elite players by individualising their rehabilitation.
“It also keeps in place all the benefits of the previous protocols which have been so successful in beginning to tackle under reporting of symptoms which evidence shows that, while improving, remains an issue.”
World Rugby CEO Alan Gilpin added: “World Rugby will never stand still on player welfare and once again we are putting those words into action in line with our six point plan.
“We will continue to work with players across the world, at all levels of the game, to educate the importance of brain health and of reporting symptoms where they occur, while doing everything we can to reduce the risks.
“Rugby is a game that bring immense benefits to those who play, benefits which far outweigh the risks. However, we know that any collision sport such as ours will result in injury and it is incumbent upon us to provide our players with the best advice we can and that is exactly what we’re doing with these Individualised Rehabilitation protocols.”
The move has been welcomed, against a background of mounting evidence as to the long-term impact of concussion, with the Concussion Legacy Foundation urging CTE to also be prioritised in World Rugby’s approach.
“I’m really pleased to see that World Rugby have sharpened their return to play process to delay the minimum stand-down times for those with a concussion history or with the most alarming symptoms. This is a step forward and we need to demand continuing to put player safety first.” said Dr Adam White, executive director of the Concussion Legacy Foundation UK.
International Rugby Players’ head of player welfare, Conrad Smith, said players reporting their injury is vital to the protection they can receive.
“The key to this working – and the important part in changing the culture around concussion – is that players report their head injuries and any symptoms,” he said.
“Seeing first-hand the amount of work and research that is going into this extremely complex issue, I have confidence in the approach taken and that the authorities are looking after the player’s best interests.”
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