Patient in ‘vegetative state’ not just aware, but paying attention

Research raises possibility of devices in the future to help some patients in a vegetative state interact with the outside world.

A patient in a seemingly vegetative state, unable to move or speak, showed signs of attentive awareness that had not been detected before, a new study reveals. This patient was able to focus on words signalled by the experimenters as auditory targets as successfully as healthy individuals. If this ability can be developed consistently in certain patients who are vegetative, it could open the door to specialised devices in the future and enable them to interact with the outside world.

The research, by scientists at the Medical Research Council Cognition and Brain Sciences Unit (MRC CBSU) and the University of Cambridge, is published today, 31 October, in the journal Neuroimage: Clinical.

For the study, the researchers used electroencephalography (EEG), which non-invasively measures the electrical activity over the scalp, to test 21 patients diagnosed as vegetative or minimally conscious, and eight healthy volunteers. Participants heard a series of different words  - one word a second over 90 seconds at a time - while asked to alternatingly attend to either the word ‘yes’ or the word ‘no’, each of which appeared 15% of the time. (Some examples of the words used include moss, moth, worm and toad.) This was repeated several times over a period of 30 minutes to detect whether the patients were able to attend to the correct target word.

They found that one of the vegetative patients was able to filter out unimportant information and home in on relevant words they were being asked to pay attention to. Using brain imaging (fMRI), the scientists also discovered that this patient could follow simple commands to imagine playing tennis. They also found that three other minimally conscious patients reacted to novel but irrelevant words, but were unable to selectively pay attention to the target word.

These findings suggest that some patients in a vegetative or minimally conscious state might in fact be able to direct attention to the sounds in the world around them.

Dr Srivas Chennu at the University of Cambridge, said: ”Not only did we find the patient had the ability to pay attention, we also found independent evidence of their ability to follow commands – information which could enable the development of future technology to help patients in a vegetative state communicate with the outside world.

“In order to try and assess the true level of brain function and awareness that survives in the vegetative and minimally conscious states, we are progressively building up a fuller picture of the sensory, perceptual and cognitive abilities in patients. This study has added a key piece to that puzzle, and provided a tremendous amount of insight into the ability of these patients to pay attention.”

Dr Tristan Bekinschtein at the MRC Cognition and Brain Sciences Unit said: “Our attention can be drawn to something by its strangeness or novelty, or we can consciously decide to pay attention to it. A lot of cognitive neuroscience research tells us that we have distinct patterns in the brain for both forms of attention, which we can measure even when the individual is unable to speak. These findings mean that, in certain cases of individuals who are vegetative, we might be able to enhance this ability and improve their level of communication with the outside world.”

This study builds on a joint programme of research at the University of Cambridge and MRC CBSU where a team of researchers have been developing a series of diagnostic and prognostic tools based on brain imaging techniques since 1998. Famously, in 2006 the group was able to use fMRI imaging techniques to establish that a patient in a vegetative state could respond to yes or no questions by indicating different, distinct patterns of brain activity.

Unravelling the true identity of the brain of Carl Friedrich Gauss

Preserved specimens of the brains of mathematician Carl Friedrich Gauss and Göttingen physician Conrad Heinrich Fuchs, taken over 150 years ago, were switched – and this probably happened soon after the death of both men in 1855. This is the surprising conclusion reached by Renate Schweizer, a neuroscientist at Biomedizinische NMR Forschungs GmbH at the Max Planck Institute for Biophysical Chemistry. She has now correctly identified the two brains, both of which are archived in a collection at the University Medical Center Göttingen. Working with experts from other disciplines, she extensively documented brain slices with a magnetic resonance imaging scanner.

Walnut-like structures appear on the computer screen. They reveal what’s inside the MRI scanner at Biomedizinische NMR Forschungs GmbH: a 150-year-old slice from the brain of mathematician Carl Friedrich Gauss. Renate Schweizer monitors the measurements as the internal tissue comes into view layer by layer. Then she carefully places another brain on the examination table, more commonly used to slowly move test subjects into the “tube”. This is the brain of Conrad Heinrich Fuchs – who, like Gauss, died in 1855 and was a medical scholar and founder of the University of Göttingen’s anatomical pathology collection. There is a specific reason for this latest examination of the historical brains from the collection at the Institute of Ethics and History of Medicine at University Medical Center Göttingen: “What scientists had long been examining in the belief that it was Gauss’s brain was not his brain at all, but actually belonged to Fuchs. The two scientists’ brains had been switched many years ago, and so they need to be documented again,” says Schweizer, a biologist and psychologist, describing the surprising findings of her investigations.

The scientist made this unexpected discovery while working in her research field – the region of the brain around the so-called central fissure. The gyri running along the central fissure are where the brain processes stimuli, like touch, heat or pain, and where it controls movements. Renate Schweizer suspected that Gauss’s brain featured a rare anatomical variation: a visible division of the central fissure. This is found in less than one percent of the population. Normally, it is of no significance to the people affected, though in a few cases it can cause minimal changes in motor and sensory function.

Schweizer spotted one of those central fissure divisions in the MRI scans believed to be of Gauss’s brain, taken in 1998 by Jens Frahm and his team at Biomedizinische NMR Forschungs GmbH and searched through the primary literature to confirm her findings. Rudolf Wagner, an anatomist in Göttingen and friend of Gauss, had prepared the brain slices of both Gauss and Fuchs before studying them and documenting the images in publications dating back to 1860 and 1862. But contrary to what she expected to see, Schweizer did not find the divided central fissure in the images of Gauss’s brain. Instead, her MRI images were a perfect match for Wagner’s picture of Fuchs’s brain.

When Schweizer visited the collection at the Institute of Ethics and History of Medicine, her initial suspicion was confirmed: the original brain taken from Gauss was indeed in a glass jar labelled ‘C. H. Fuchs’, while Fuchs’s brain was in a jar marked ‘C. F. G__ss’. “My theory, according to the information currently available, is that the brains were probably put into the wrong jars relatively soon after Wagner’s examinations, at the time when the surface of the cerebral cortex was being measured again,” says the neuroscientist. After that, there were no further comparative studies of the brains of Gauss and Fuchs, which is why no one noticed the subsequent mix-up. It is also significant for the Göttingen-based Gauss Society to know that the brains of Gauss and Fuchs are now assigned to their proper owners once more. “The Gauss Society’s Director, Axel Wittmann, was an active supporter of the project from the start and his extensive knowledge was extremely helpful in uncovering the mistake made so many years ago,” reports Schweizer.

Her discovery shows how important historic collections are for modern-day research. Schweizer confirms: “It’s a stroke of luck that the brains in the collection, which are in perfect condition, are still accessible to researchers more than 150 years down the line.” That is what enabled the mix-up to be identified without a shadow of a doubt and the historical brains to be examined in the MRI scanner. Schweizer collaborated closely with former team colleague Gunther Helms, who works with brain slice MRIs in the MR Research Service Unit at the Department of Cognitive Neurology at University Medical Center Göttingen. As Jens Frahm, Director of Biomedizinische NMR Forschungs GmbH, emphasises: “We are not looking for the genie in the gyri of the brain. What we are most interested in is documenting specimens for the long term future to provide a foundation for continuing basic research.” All MRI images and photographs of the historic brains are therefore being digitally archived, thus protecting them as long-term scientific assets. They are a significant impetus for new research projects: Schweizer herself is currently using the MRI images to study the divided central fissure in Fuchs’s brain both above and below the surface of the cerebral cortex.

The MRI images also enable the scientists to demonstrate that earlier publications on what was believed to be Gauss’s brain did not contain incorrect information. In those works, the mathematician’s brain was described as normal. Walter Schulz-Schaeffer, who is head of the Prion and Dementia Research Unit of the Institute of Neuropathology at University Medical Center Göttingen, made a first examination of the recent MRI images and was able to confirm that the brain of the brilliant mathematician and astronomer Gauss, like that of the physician Fuchs, is largely anatomically unremarkable. The two organs are also similar in size and weight. “The age-related changes in Gauss’s brain are normal for a man of 78. Changes in the basal ganglia are indicative of high blood pressure,” comments the neuropathologist.

Not every MRI scan of a historical slice allows for such a clear assertion. That is why neuropathologists and MRI scientists are currently working together to study how tissue and organs change as a result of decades or centuries of storage in alcohol, and how adapted MRI methods can improve the interpretation of the images obtained.

The historical brains have, meanwhile, again found their well-earned rest in the university collection – with no chance of a mix-up ever again.

New imaging research shows increased iron in the brain in earliest stages of MS

While it’s been known for over a century that iron deposits in the brain play a role in the pathology of Multiple Sclerosis (MS), new imaging research from Western University (London, Canada) helps to answer the question of whether these accumulations are a cause or consequence of the disease. The study led by Ravi Menon, PhD, of the Robarts Research Institute found iron deposits in deep gray matter, suggesting the accumulation occurs very early in the disease course. The researchers also found evidence casting further doubt on the controversial liberation therapy for MS. The research is in early publication online in Multiple Sclerosis and Related Disorders.

Menon and PhD candidate Matthew Quinn used 3-Tesla Magnetic Resonance Imaging (MRI) to scan 22 patients with clinically isolated syndrome (CIS). These are patients who’ve had a single clinical attack, at least half of whom will go on to be diagnosed with MS. The others may have a different disease. Sixteen age and sex matched controls were also studied.

"We wanted to know if the iron deposits happen early in the process, or whether it’s something that accumulates with time as the disease progresses," says Menon, who holds a Canada Research Chair in Functional Magnetic Imaging. "We also studied the veins that drain from the brain and looked for a correlation between the diameter of of these veins and iron accumulation. One of the reasons to do this, of course was the hypothesis proposed by Paolo Zamboni that if you had narrow jugular veins, this would give rise to additional iron and in turn cause MS."

The scientists found iron deposits in the CIS group were well above the amounts found in the control group. The MRIs also revealed for the first time, subtle damage to the brain’s white matter even at this early stage. The researchers also found no correlation between the iron deposits and diameter of the veins.

"So while the iron in the brain correlates with the disability of the subjects, the iron in the brain does not correlate with the actual diameter of the jugular veins. So the Zamboni hypothesis is incorrect as far as the iron being related to some kind of obstruction." Menon found narrowed veins in the control group as well as the CIS group, and both groups had narrower veins on one side compared to the other.

Menon hopes this imaging research will lead to the earlier diagnosis of MS. He plans to follow the patients every four months for the next two years, to see retrospectively, what characterizes those patients that go on to be diagnosed with MS compared to those who do not.

"We’re looking at a couple of different approaches to diagnostics using this imaging research. In suspected MS cases –the very first time they appear in clinic, if they have an abnormally high amount of iron in the frontal cortex of the brain –that’s probably a pretty good sign they have MS or some other white matter disease." This research was funded primarily by the Canadian Institutes of Health Research.

MS is the most common neurological disease affecting young adults, with symptoms that include loss of balance, impaired speech, double vision, extreme fatigue and paralysis.

Neuroscientists discover new ‘mini-neural computer’ in the brain

Dendrites, the branch-like projections of neurons, were once thought to be passive wiring in the brain. But now researchers at the University of North Carolina at Chapel Hill have shown that these dendrites do more than relay information from one neuron to the next. They actively process information, multiplying the brain’s computing power.

“Suddenly, it’s as if the processing power of the brain is much greater than we had originally thought,” said Spencer Smith, PhD, an assistant professor in the UNC School of Medicine.

His team’s findings, published October 27 in the journal Nature, could change the way scientists think about long-standing scientific models of how neural circuitry functions in the brain, while also helping researchers better understand neurological disorders.

Axons are where neurons conventionally generate electrical spikes, but many of the same molecules that support axonal spikes are also present in the dendrites. Previous research using dissected brain tissue had demonstrated that dendrites can use those molecules to generate electrical spikes themselves, but it was unclear whether normal brain activity uses those dendritic spikes. For example, could dendritic spikes be involved in how we see?

The answer, Smith’s team found, is yes. Dendrites effectively act as mini-neural computers, actively processing neuronal input signals themselves.

Directly demonstrating this required a series of intricate experiments that took years and spanned two continents, beginning in senior author Michael Hausser’s lab at University College London, and being completed after Smith and Ikuko Smith, PhD, DVM, set up their own lab at the University of North Carolina. They used patch-clamp electrophysiology to attach a microscopic glass pipette electrode, filled with a physiological solution, to a neuronal dendrite in the brain of a mouse. The idea was to directly “listen” in on the electrical signaling process.

“Attaching the pipette to a dendrite is tremendously technically challenging,” Smith said. “You can’t approach the dendrite from any direction. And you can’t see the dendrite. So you have to do this blind. It’s like fishing but all you can see is the electrical trace of a fish.” And you can’t use bait. “You just go for it and see if you can hit a dendrite,” he said. “Most of the time you can’t.”

But Smith built his own two-photon microscope system to make things easier.

Once the pipette was attached to a dendrite, Smith’s team took electrical recordings from individual dendrites within the brains of anesthetized and awake mice. As the mice viewed visual stimuli on a computer screen, the researchers saw an unusual pattern of electrical signals – bursts of spikes – in the dendrite.

Smith’s team then found that the dendritic spikes occurred selectively, depending on the visual stimulus, indicating that the dendrites processed information about what the animal was seeing.

To provide visual evidence of their finding, Smith’s team filled neurons with calcium dye, which provided an optical readout of spiking. This revealed that dendrites fired spikes while other parts of the neuron did not, meaning that the spikes were the result of local processing within the dendrites.

Study co-author Tiago Branco, PhD, created a biophysical, mathematical model of neurons and found that known mechanisms could support the dendritic spiking recorded electrically, further validating the interpretation of the data.

“All the data pointed to the same conclusion,” Smith said. “The dendrites are not passive integrators of sensory-driven input; they seem to be a computational unit as well.”

His team plans to explore what this newly discovered dendritic role may play in brain circuitry and particularly in conditions like Timothy syndrome, in which the integration of dendritic signals may go awry.

National Robotics Initiative grant will provide surgical robots with a new level of machine intelligence

Providing surgical robots with a new kind of machine intelligence that significantly extends their capabilities and makes them much easier and more intuitive for surgeons to operate is the goal of a major new grant announced as part of the National Robotics Initiative.

The five-year, $3.6 million project, titled Complementary Situational Awareness for Human-Robot Partnerships, is a close collaboration among research teams directed by Nabil Simaan, associate professor of mechanical engineering at Vanderbilt University; Howie Choset, professor of robotics at Carnegie Mellon University; and Russell Taylor, the John C. Malone Professor of Computer Science at Johns Hopkins University.

“Our goal is to establish a new concept called complementary situational awareness,” said Simaan. “Complementary situational awareness refers to the robot’s ability to gather sensory information as it works and to use this information to guide its actions.”

“I am delighted to be working with Nabil Simaan on a medical robotics project,” Choset said. “I believe him to be a thought leader in the field.” Taylor added, “This project advances our shared vision of human surgeons, computers and robots working together to make surgery safer, less invasive and more effective.”

One of the project’s objectives is to restore the type of awareness surgeons have during open surgery – where they can directly see and touch internal organs and tissue – which they have lost with the advent of minimally invasive surgery because they must work through small incisions in a patient’s skin. Minimally invasive surgery has become increasingly common because patients experience less pain, blood loss and trauma, recover more quickly and get fewer infections, and is less expensive than open surgery.

Surgeons have attempted to compensate for the loss of direct sensory feedback through pre-operative imaging, where they use techniques like MRI, X-ray imaging and ultrasound to map the internal structure of the body before they operate. They have employed miniaturized lights and cameras to provide them with visual images of the tissue immediately in front of surgical probes. They have also developed methods that track the position of the probe as they operate and plot its position on pre-operative maps.

Simaan, Choset and Taylor intend to take these efforts to the next level. They intend to create a system that acquires data from a number of different types of sensors as an operation is underway and integrates them with pre-operative information to produce dynamic, real time maps that precisely track the position of the robot probe and show how the tissue in its vicinity responds to its movements.

For example, adding pressure sensors to robot probes will provide real time information on how much force the probe is exerting against the tissue surrounding it. Not only does this make it easier to work without injuring the tissue but it can also be used to “palpate” tissue to search for hidden tumor edges, arteries and aneurisms. Such sensor data can also feed into computer simulations that predict how various body parts shift in response to the probe’s movements.

To acquire sensory data during surgery, the VU team lead by Simaan will develop methods that allow surgical snake-like robots explore the shapes and variations in stiffness of internal organs and tissues. The team will generate models that estimate locations of hidden anatomical features such as arteries and tumors and provide them to the JHU and CMU teams to create adaptive telemanipulation techniques that assist surgeons in carrying out various surgical procedures.

To create these dynamic, three-dimensional maps, the CMU team led by Choset will employ a technique called Simultaneous Localization and Mapping that allows mobile robots to navigate in unexplored areas. This class of algorithms was developed for navigating through rigid environments, such as buildings, landforms and streets, so the researchers must extend the technique so it will work in the flexible environment of the body. These maps will form the foundation of the Complementary Situation Awareness (CSA) framework.

Once they can create these maps, the collaborators intend to use them to begin semi-automating various surgical sub-tasks, such as tying off a suture, resecting a tumor or ablating tissue. For example, the resection sub-task would allow a surgeon to instruct his robot to resect tissue from point “a” to “b” to “c” to “d” to a depth of five millimeters and the robot would then cut out the tissue specified.

The researchers also intend to create what they call “virtual fixtures.” These are pre-programmed restrictions on the robot’s actions. For example, a robot might be instructed not to cut in an area where a major blood vessel has been identified. Not only would this prevent the robot from cutting a blood vessel when operating autonomously, but it would also prevent a surgeon from doing so accidently when operating the robot manually.

“We will design the robot to be aware of what it is touching and then use this information to assist the surgeon in carrying out surgical tasks safely,” Simaan said.

The Johns Hopkins team led by Taylor will develop the system infrastructure for the CSA framework, with special emphasis on the interfaces used by the surgeon. The software will be based on Johns Hopkins’ open-source “Surgical Assistant Workstation” toolkit, permitting researchers both within and outside the team to access the results of the research and adapt them for other projects.

The teams will be using several different experimental robots during this research, but all the systems will share a common surgeon interface based on mechanical components from early model da Vinci surgical robots donated by Intuitive Surgical (Sunnyvale, California) and interfaced to control electronics designed by Johns Hopkins.

Although these prototypes are not intended for use on human patients, the research results could eventually lead to advances in surgical care.

Although the development effort is focused on surgical robots, the CSA modeling and control framework could have a major impact in other applications as well.

According to Simaan, CSA could be used by a bomb squad robot to disarm a bomb or by a human user operating a robotic excavator to dig out the foundation of a new building without damaging the underground pipes or by rescue robots searching deep tunnels for injured miners.

“In the past we have used robots to augment specific manipulative skills,” said Simaan. “This project will be a major change because the robots will become partners not only in manipulation but in sensory information gathering and interpretation, creation of a sense of robot awareness and in using this robot awareness to complement the user’s own awareness of the task and the environment”

A Trace of Memory: Researchers Watch Neurons in the Brain During Learning and Memory Recall

A team of neurobiologists led by Simon Rumpel at the Research Institute of Molecular Pathology (IMP) in Vienna succeeded in tracking single neurons in the brain of mice over extended periods of time. Advanced imaging techniques allowed them to establish the processes during memory formation and recall. The results of their observations are published this week in PNAS Early Edition.

Most of our behavior – and thus our personality – is shaped by previous experience. To store the memory of these experiences and to be able to retrieve the information at will is therefore considered one of the most basic and important functions of the brain. The current model in neuroscience poses that memory is stored as long-lasting anatomical changes in synapses, the specialized structures by which nerve cells connect and signal to each other.

At the Research Institute of Molecular Pathology (IMP) in Vienna, Simon Rumpel and Kaja Moczulska used mice to study the effects of learning and memorizing on the architecture of synapses. They employed an advanced microscopic technique called in vivo two-photon imaging that allows the analysis of structures as small as a thousandth of a millimetre in the living brain.

Using this technology, the neurobiologists tracked individual neurons over the course of several weeks and analysed them repeatedly. They focussed their attention on dendritic spines that decorate the neuronal processes and correspond to excitatory synapses. The analyses were combined with behavioral experiments in which the animals underwent classic auditory conditioning. The results showed that the learning experience triggered the formation of new synaptic connections in the auditory cortex. Several of these new structures persisted over time, suggesting a long-lasting trace of memory and confirming an important prediction of the current model.

Apart from the changes during memory formation, the IMP-scientists were interested in the act of remembering. Earlier studies had shown that memory recall is associated with molecular processes similar to the initial formation of memory. These similarities have been suggested to reflect remodelling of memory traces during recall.

To test this hypothesis, previously trained mice were exposed to the auditory cue a week after conditioning while tracking dendritic spines in the auditory cortex. The results showed that although some molecular processes indeed resembled those during memory formation, the anatomical structure of the synapses did not change. These findings suggest that memory retrieval does not lead to a modification of the memory trace per se. Instead, the molecular processes triggered by memory formation and recall could reflect the stabilization of previously altered or recently retrieved synaptic connections.

The primary goal of elucidating the processes during memory formation and recall is to increase our basic knowledge. Insights gained from these studies might however help us to understand diseases of the nervous system that affect memory. They may also, in the future, provide the basis for treatments that offer relief to traumatized patients.

Traumatic Brain Injury Research Advances with $18.8M NIH Award

The National Institutes of Health is awarding $18.8 million over five years to support worldwide research on concussion and traumatic brain injury.

The NIH award, part of one of the largest international research collaborations ever coordinated by funding agencies, will be administered through UC San Francisco.

The award supports a team of U.S. researchers at more than 20 institutions throughout the country who are participating in the International Traumatic Brain Injury (InTBIR) Initiative, a collaborative effort of the European Commission, the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH) and the U.S. Department of Defense (DOD).

Although the potential long-term harms due to concussions and blows to the head have gained more attention recently – due in part to media coverage of the experiences of athletes and of soldiers returning from the Middle East – traumatic brain injuries, or TBI, that results from automobile crashes or other common accidents impacts many more people.

Many of those who are affected by TBI are never diagnosed, according to UCSF neurosurgeon Geoffrey Manley, MD, PhD, a principal investigator for the grant who will serve as the U.S. research team’s primary liaison to the NIH, and the chief of neurosurgery at the UCSF-affiliated San Francisco General Hospital, a Level-1 trauma center. SFGH was the first medical center in the nation to achieve certification from the Joint Commission for the treatment of TBI.

The U.S. Centers for Disease Control and Prevention estimates that 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion.

“Each year in the United States, at least 1.7 million people seek medical attention for TBI,” Manley said. “It is a contributing factor in a third of all injury-related deaths.”

In the work funded by the NIH grant – which also is supported by contributions from the private sector and from the nonprofit One Mind for Research – the researchers aim to refine and improve diagnosis and treatment of TBI, which often has insidious health effects, but which frequently is undiagnosed, misdiagnosed, inadequately understood and undertreated, according to Manley.

New Approach to Lead to Patient-Specific Treatments

“After three decades of failed clinical trials, a new approach is needed,” Manley said. “We expect that our approach will permit researchers to better characterize and stratify patients, will allow meaningful comparisons of treatments and outcomes, and will improve the next generation of clinical trials. The work will advance our understanding of TBI and lead to more effective, patient-specific treatments.”

Since 2009, Manley and Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging at UCSF, have helped lay the groundwork for the continuing TBI research by leading the NIH-funded TRACK-TBI project, through which they and their research collaborators have demonstrated the value of gathering common data across research sites, including a standardized approach to imaging, clinical data, bio-specimens, and tracking outcomes.

Already, TRACK-TBI researchers have made progress toward more useful classification and prognosis of TBI.

Earlier this year, they reported that cases of concussion, or TBI that are classified as “mild” by standard criteria but that show abnormalities on early magnetic resonance imaging (MRI) scans, are much more likely to have worse outcomes three months after the scan in comparison to cases in which scans reveal no abnormalities. Furthermore, the researchers found that elevated blood levels of a protein released during brain injury was associated with the likelihood of an abnormal CT scan.

The new NIH award funds a continuation and expansion of TRACK-TBI. Among the goals is the creation of a widely accessible, comprehensive “TBI information commons” to integrate clinical, imaging, proteomic, genomic and outcome biomarkers from subjects across the age and injury spectra. Another goal is to establish the value of biomarkers that will improve classification of TBI and better optimize selection and assignment of patients for clinical trials.

The researchers also aim to evaluate measures to assess patient outcomes across all phases of recovery and at all levels of TBI severity, to determine which tests, treatments, and services are effective and appropriate – depending on the nature of TBI in particular patients.

In addition to Manley and Mukherjee, principal investigators for the newly funded project include Claudia Robertson, MD, Baylor College of Medicine; Joseph Giacino, PhD, Harvard University; Ramon Diaz-Arrastia, MD, PhD, Uniformed Services University of the Health Sciences; David Okonkwo, MD, PhD, University of Pittsburgh; and Nancy Temkin, PhD, University of Washington. Each of these leading experts has worked in the TBI field for two decades or more.

“The principal investigators bring expertise in neurosurgery, neurology, neuroradiology, critical care medicine, rehabilitation medicine, neuropsychology and biostatistics, all of which are essential and do not reside in any single individual,” Manley said.

International Funding and Collaboration

TRACK-TBI clinical enrollment sites throughout the United States will enroll 3,000 patients across the spectrum of mild to severe brain injuries. Clinical, imaging, proteomic, genomic and clinical outcome databases will be linked into a shared platform that will promote a model for collaboration among scientists within InTBIR and elsewhere.

In addition to the U.S. award, the European Commission, the executive body of the European Union, has awarded €35.2 million to fund the Collaborative European NeuroTrauma Effectiveness-TBI (CENTER-TBI) consortium, also part of the InTBIR. This project will collect data in over 5,000 patients across Europe, where 38 scientific institutes and more than 60 hospitals will participate.

In Canada, CIHR and its national partners also have made a multimillion dollar investment in TBI research, the details of which will be formally announced in the near future.

The InTBIR Scientific Advisory Committee met in Vancouver, British Columbia, on Oct. 17-18, and awardees from all three jurisdictions (EU, USA, Canada) now are aligning efforts to share resources and collaborate on strategies for achieving the InTBIR goals.