Patient has 75 per cent of his skull replaced by 3D-printed implant

A man has had 75 per cent of his skull replaced with a custom-made 3D-printed implant.

The un-named patient in the United States had his head imaged by a 3D scanner before the plastic prosthetic was crafted to suit his features.

Oxford Performance Materials in Connecticut then gained approval from US regulators before the printed bone replacement was inserted in his skull during a surgical procedure earlier this week.

The ground-breaking operation has only now been revealed.

The company says it can now provide the 3D printouts to replace bone damaged by disease or trauma after the US Food and Drug Administration granted approval on February 18.

The implant is more than a simple moulded plastic plate: Tiny surface details are etched into the polyetherketoneketone to encourage the growth of cells and bone.

The company says about 500 people in the US could make use of the technology each month, with recipients ranging from injured construction workers through to wounded soldiers.

It says it can produce an implant within two weeks of obtaining 3D scans of the affected area.

Right-Handed Males, Left-Handed Females?

This is true for sugar gliders (Petaurus breviceps) and grey short-tailed opossums (Monodelphis domestica), say biologists from Saint Petersburg State University, Russia.

Their study, published in the open access journal BMC Evolutionary Biology, shows that handedness in marsupials is dependent on gender.

This preference of one hand over another has developed despite the absence of a corpus callosum, the part of the brain, which in placental mammals allows one half of the brain to communicate with the other.

Many animals show a distinct preference for using one hand (paw, hoof) over another. This is often related to posture – an animal is more likely to show manual laterality if it is upright, related to the difficulty of the task, more complex tasks show a handed preference, or even with age. As an example of all three: crawling human babies show less hand preference than toddlers.

Some species also show a distinct sex effect in handedness but among non-marsupial mammals this tendency is for left-handed males and right-handed females.

In contrast, the team from Russia shows that male quadruped marsupials, such as who walk on all fours, tend to be right-handed while the females are left-handed, especially as tasks became more difficult.

“Marsupials do not have a corpus callosum – which connects the two halves of the mammalian brain together. Reversed sex related handedness is an indication of how the marsupial brain has developed different ways of the two halves of the brain communicating in the absence of the corpus callosum,” explains senior author Dr Yegor Malashichev.

The Brain Activity Map

Researchers explain the goals and structure of a new brain-mapping project

A proposed effort to map brain activity on a large scale, expected to be announced by the White House later this month, could help neuroscientists understand the origins of cognition, perception, and other phenomena. These brain activities haven’t been well understood to date, in part because they arise from the interaction of large sets of neurons whose coördinated efforts scientists cannot currently track.

“There are all kinds of remarkable tools to study the microscopic world of individual cells,” says John Donoghue, a neuroscientist at Brown and a participant in the project. “And on the macroscopic end, we have tools like MRI and EEG that tell us about the function of the brain and its structure, but at a low resolution. There is a gap in the middle. We need to record many, many neurons exactly as they operate with temporal precision and in large areas,” he says.

An article published Thursday in Science online expands the project’s already ambitious goals beyond just recording the activity of all individual neurons in a brain circuit simultaneously. Researchers should also find ways to manipulate the neurons within those circuits and understand circuit function through new methods of data analysis and modeling, the authors write.

Understanding how neurons communicate with one another across large regions of the brain will be critical to understanding how the brain works, according to participants in the project. Other efforts to map out the physical connections in the brain are already under way (see “TR10: Connectomics” and “Mapping the Brain on a Massive Scale”), but these projects look at static brains or can only get a rough view of how regions of the brain communicate. The new project will probably start applying its novel and yet unknown technologies on simpler brains, such as those of flies, and will probably take decades to achieve its goals.

Numerous leaders from the fields of neuroscience, nanotechnology, and synthetic biology are expected to collaborate on the effort. “We need something large scale to try to build tools for the future,” says Rafael Yuste, a neurobiologist at Columbia University and a member of the project. “We view ourselves as tool builders. I think we could provide to the scientific community the methods that could be used for the next stage in neuroscience.”

In addition to deepening fundamental understanding of the brain, the project may also lead to new treatments for psychiatric and neurological disorders. “If we truly understand how things like thoughts, cognition, and other features of the brain emerge, then we should have a better understanding of mood disorders, Parkinson’s, epilepsy and other conditions that are thought to arise from brain-wide circuitry problems,” says Donoghue.

Details about which technology ideas will be given the green light and how much money will support their development are expected to be revealed in the White House announcement that is still to come. The project is likely to be supported by the National Institutes of Health, the National Science Foundation, the Defense Advanced Research Projects Agency, the Office of Science and Technology Policy, and private foundations, participants say. It’s not yet clear how much money will be needed or which technologies will be given priority.

Whichever particular technologies emerge, nanotechnology is likely to be involved, in part because of the need for smaller and faster sensors to record neuronal activity across the brain. Existing sensors can record the electrical activity of neurons, but these chips can typically monitor fewer than 100 neurons at a time and can’t record activity from neighboring neurons, which would be necessary to understand how neurons interact with one another. Paul Weiss, director of the California NanoSystems Institute at the University of California, Los Angeles, a participant in the project, says that nanofabrication techniques could address this problem, with smaller chips bearing smaller electrical and even chemical probes. “We’ve had over a decade a fairly substantial investment in science and technology to develop the capability … to control how what we make interacts with the chemical, physical, and biological worlds,” he says.

Novel optical techniques could also aid the mapping project. Currently, many research groups use calcium-sensitive fluorescent dyes to study neuron firing, but Yuste wants to develop an optical technique that uses voltage-sensitive fluorescent dyes for a faster readout. “Neurons communicate using voltage,” he says. “We would like to develop voltage imaging so we will be able to measure neuronal activity directly.”

While many things about the project are uncertain, one thing is clear—there is going to be a lot of data to store, share, and analyze. “We have just begun to scratch the surface of how you deal with data in high-dimensional spaces,” says Terry Sejnowski, a computational neuroscientist at the Salk Institute. “If you are talking about one million neurons, no one can even imagine what that looks like–it is way beyond what we can perceive in three dimensions.”

The Science article also sketches out a rough time line. Within five years, it should be possible to monitor tens of thousands of neurons; in 15 years, one million neurons should be possible. A fly’s brain has about 100,000 neurons, a mouse’s about 75 million, and a human’s about 85 billion. “With one million neurons, scientists will be able to evaluate the function of the entire brain of the zebrafish or several areas from the cerebral cortex of the mouse,” the authors write.

Chewing gum helps you concentrate for longer

Chewing gum can help you stay focused for longer on tasks that require continuous monitoring.

This is the finding of new research by Kate Morgan and colleagues from Cardiff University published in the British Journal of Psychology.

Previous research has shown that chewing gum can improve concentration in visual memory tasks. This study focussed on the potential benefits of chewing gum during an audio memory task.

Kate Morgan, author of the study explained: “It’s been well established by previous research that chewing gum can benefit some areas of cognition. In our study we focussed on an audio task that involved short-term memory recall to see if chewing gum would improve concentration; especially in the latter stages of the task.”

The study involved 38 participants being split in to two groups. Both groups completed a 30 minute audio task that involved listening to a list of numbers from 1-9 being read out in a random manner. Participants were scored on how accurately and quickly they were able to detect a sequence of odd-even-odd numbers, such as 7-2-1. Participants also completed questionnaires on their mood both before and after the task.

The results showed that participants who chewed gum had quicker reaction times and more accurate results than the participants who didn’t chew gum. This was especially the case towards the latter parts of the task.

Kate explained: “Interestingly participants who didn’t chew gum performed slightly better at the beginning of the task but were overtaken by the end. This suggests that chewing gum helps us focus on tasks that require continuous monitoring over a longer amount of time.”

The study was discussed in Radio Four Today programme.

(Image: iStock)

Scientists Identify Buphenyl as a Possible Drug for Alzheimer’s disease

Buphenyl, an FDA-approved medication for hyperammonemia, may protect memory and prevent the progression of Alzheimer’s disease. Hyperammonemia is a life-threatening condition that can affect patients at any age. It is caused by abnormal, high levels of ammonia in the blood.

Studies in mice with Alzheimer’s disease (AD) have shown that sodium phenylbutyrate, known as Buphenyl, successfully increases factors for neuronal growth and protects learning and memory, according to neurological researchers at the Rush University Medical Center.

Results from the National Institutes of Health funded study, recently were published in the Journal of Biological Chemistry.

“Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Alzheimer’s disease,” said Kalipada Pahan, PhD, the Floyd A. Davis professor of neurology at Rush and lead investigator of this study.

A family of proteins known as neurotrophic factors help in survival and function of neurons. Past research indicates that these proteins are drastically decreased in the brain of patients with Alzheimer’s disease (AD).

“Neurotrophic factor proteins could be increased in the brain by direct injection or gene delivery,” said Pahan. “However, using an oral medication to increase the level of these protein may be the best clinical option and a cost effective way to increase the level of these proteins directly in the brain.”

“Our study found that after oral feeding, Buphenyl enters into the brain, increases these beneficial proteins in the brain, protects neurons, and improves memory and learning in mice with AD-like pathology,” said Pahan.

In the brain of a patient with AD, two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. While neurons die, other brain cells like astroglia do not die.

The study findings indicate that Buphenyl increases neurotrophic factors from astroglia. Buphenyl stimulates memory-related protein CREB (cyclic AMP response element-binding protein) using another protein known as Protein Kinase C (PKC) and increases neurotrophic factors in the brain.

"Now we need to translate this finding to the clinic and test Buphenyl in Alzheimer’s disease patients,” said Pahan. “If these results are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease.”

Low incidence of venous insufficiency in MS

Results of a study using several imaging methods showed that CCSVI (chronic cerebrospinal venous insufficiency) occurs at a low rate in both people with multiple sclerosis (MS) and non-MS volunteers, contrary to some previous studies. The research by an interdisciplinary team at The University of Texas Health Science Center at Houston (UTHealth) was published in a recent early online edition of the Annals of Neurology.

“Our results in this phase of the study suggest that findings in the major veins that drain the brain consistent with CCSVI are uncommon in individuals with MS and quite similar to those found in our non-MS volunteers,” said Jerry Wolinsky, M.D., principal investigator and the Bartels Family and Opal C. Rankin Professor of Neurology at The UTHealth Medical School. “This makes it very unlikely that CCSVI could be the cause of MS, or contribute in an important manner to how the disease can worsen over time.” Wolinsky is also a member of the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston and director of the UTHealth MS Research Group.

CCSVI has been described by Italian neurosurgeon Paolo Zamboni, M.D., as a new disorder in which veins draining the central nervous system are abnormal. Zamboni’s published research linked CCSVI to MS. Not all researchers have been able to duplicate his results.

UTHealth was one of three institutions in the United States to receive an initial grant to study CCSVI in multiple sclerosis (MS). The grant was part of a $2.3 million joint commitment from the National MS Society and the MS Society of Canada.

The UTHealth team tested several imaging methods including ultrasound, magnetic resonance imaging with an intravenous contrast agent, and direct radiologic investigation of the major veins by direct injection of veins with radio-opaque contrast. The goal was to validate a consistent, reliable diagnostic approach for CCSVI, determine whether CCSVI was specific to MS and if CCSVI contributed to disease activity.

The team was blinded to the participant’s diagnosis throughout the study. Doppler ultrasound was used to investigate venous drainage in 276 people with and without MS. Using the criteria described by Zamboni for the diagnosis of CCVSI, UTHealth researchers found less prevalence of CCVSI than in some previous studies and no statistical difference between those with MS and those without MS.  Detailed experience with the other imaging approaches are being readied for publication.

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system, interrupting the flow of information within the brain and from the brain to the body. It affects more than 400,000 people in the United States and 2.1 million in the world.

Deep Brain Stimulation shows promise for patients with chronic, treatment resistant Anorexia Nervosa

In a world first, a team of researchers at the Krembil Neuroscience Centre and the University Health Network have shown that Deep Brain Stimulation (DBS) in patients with chronic, severe and treatment-resistant Anorexia Nervosa (anorexia) helps some patients achieve and maintain improvements in body weight, mood, and anxiety.

The results of this trial, entitled Deep Brain Stimulation of the Subcallosal Cingulate Area for Treatment-Refractory Anorexia Nervosa: A Phase I Pilot Trial, are published in the medical journal The Lancet. The study is a collaboration between lead author Dr. Nir Lipsman a neurosurgery resident at the University of Toronto and PhD student at the Krembil Neuroscience Centre; Dr. Andres Lozano, a neurosurgeon, at the Krembil Neuroscience Centre of Toronto Western Hospital and a professor and chairman of neurosurgery at the University of Toronto, whose research lab was instrumental in conducting the DBS research; and Dr. Blake Woodside, medical director of Canada’s largest eating disorders program at Toronto General Hospital and a professor of psychiatry at the University of Toronto.

The phase one safety trial investigated the procedure in six patients who would likely continue with a chronic illness and/or die a premature death because of the severity of their condition. The study’s participants had an average age of 38, and a mean duration of illness of 18 years. In addition to the anorexia, all patients, except one, also suffered from psychiatric conditions such as major depressive disorder and obsessive-compulsive disorder. At the time of the study, all patients currently, or had previously, suffered multiple medical complications related to their anorexia – altogether, the six patients had a history of close to 50 hospitalizations during their illnesses.

Study participants were treated with Deep Brain Stimulation (DBS), a neurosurgical procedure that moderates the activity of dysfunctional brain circuits. Neuroimaging has shown that there are both structural and functional differences between anorexia patients and healthy controls in brain circuits which regulate mood, anxiety, reward and body-perception.

Patients were awake when they underwent the procedure which implanted electrodes into a specific part of the brain involved with emotion, and found to be highly important in disorders such as depression. During the procedure, each electrode contact was stimulated to look for patient response of changes in mood, anxiety or adverse effects. Once implanted, the electrodes were connected to an implanted pulse generator below the right clavicle, much like a heart pacemaker.

Testing of patients was repeated at one, three, and six-month intervals after activation of the pulse generator device. After a nine-month period following surgery, the team observed that three of the six patients had achieved weight gain which was defined as a body-mass index (BMI) significantly greater than ever experienced by the patients. For these patients, this was the longest period of sustained weight gain since the onset of their illness. Furthermore, four of the six patients also experienced simultaneous changes in mood, anxiety, control over emotional responses, urges to binge and purge and other symptoms related to anorexia, such as obsessions and compulsions. As a result of these changes, two of these patients completed an inpatient eating disorders program for the first time in the course of their illness.

“We are truly ushering in a new of era of understanding of the brain and the role it can play in certain neurological disorders,” says Dr. Lozano. “By pinpointing and correcting the precise circuits in the brain associated with the symptoms of some of these conditions, we are finding additional options to treat these illnesses.”

While the treatment is still considered experimental, it is believed to work by stimulating a specific area of the brain to reverse abnormalities linked to mood, anxiety, emotional control, obsessions and compulsions all of which are common in anorexia. In some cases after surgery, patients are then able to complete previously unsuccessful treatments for the disease. The research may not only provide an additional therapy option for these patients in the future, but also furthers practitioners’ understanding of anorexia and the factors that cause it to be persistent.

“There is an urgent need for additional therapies to help those suffering from severe anorexia,” says Dr. Woodside. “Eating disorders have the highest death rate of any mental illness and more and more women are dying from anorexia. Any treatment that could potentially change the natural course of this illness is not just offering hope but saving the lives for those that suffer from the extreme form of this condition.”

A leading international expert in the field of DBS research, Dr. Lozano has been exploring the potential of DBS to treat a variety of conditions. Most recently, his team began the first ever DBS trial of patients with early Alzheimer’s disease, and showed that stimulation may help improve memory. This trial has now entered its second phase and expanded to medical centres in the United States.