London neuroscience centre to map ‘connectome’ of foetal brain

A state-of-the-art imaging facility at St Thomas’ Hospital in London has been awarded a 15m euro grant to map the development of nerve connections in the brain before and just after birth.

The Centre for the Developing Brain — which is partly funded by King’s College London (KCL) — has built a unique neonatal Magnetic Resonance Imaging Clinical Research Facility based in the intensive care unit of the Evelina Children’s Hospital at St Thomas’. It is one of two centres in the world — the other being at Imperial College — to have such a clinical research facility and associated scanner within a neonatal intensive care unit.

Over the next few years a team headed up by David Edwards, a consultant neonatologist and KCL Professor of Paediatrics and Neonatal Medicine, will build up a diagram of connections in the brain of babies as they develop in the womb and then after they are born. The aim is to understand how the human brain assembles itself from a functional and structural perspective. The resulting map is called a connectome and is the brain equivalent of the human genome. It will be made available to the research community to help improve understanding of neurological disorders.

Engineering control theory helps create dynamic brain models

Models of the human brain, patterned on engineering control theory, may some day help researchers control such neurological diseases as epilepsy, Parkinson’s and migraines, according to a Penn State researcher who is using mathematical models of neuron networks from which more complex brain models emerge.

"The dual concepts of observability and controlability have been considered one of the most important developments in mathematics of the 20th century," said Steven J. Schiff, the Brush Chair Professor of Engineering and director of the Penn State Center for Neural Engineering. "Observability and controlability theorems essentially state that if you can observe and reconstruct a system’s variables, you may be able to optimally control it. Incredibly, these theoretical concepts have been largely absent in the observation and control of complex biological systems."

Those engineering concepts were originally designed for simple linear phenomena, but were later revised to apply to non-linear systems. Such things as robotic navigation, automated aircraft landings, climate models and the human brain all require non-linear models and methods.

"If you want to observe anything that is at all complicated — having more than one part — in nature, you typically only observe one of the parts or a small subset of the many parts," said Schiff, who is also professor of neurosurgery, engineering science and mechanics, and physics, and a faculty member of the Huck Institutes of the Life Sciences. "The best way of doing that is make a model. Not a replica, but a mathematical representation that uses strategies to reconstruct from measurements of one part to the many that we cannot observe."

This type of model-based observability makes it possible today to create weather predictions of unprecedented accuracy and to automatically land an airliner without pilot intervention.

"Brains are much harder than the weather," said Schiff. "In comparison, the weather is a breeze."

There are seven equations that govern weather, but the number of equations for the brain is uncountable, according to Schiff. One of the problems with modeling the brain is that neural networks in the brain are not connected from neighbor to neighbor. Too many pathways exist.

"We make and we have been making models of the brain’s networks for 60 years," Schiff said at the recent annual meeting of the American Association for the Advancement of Science in Boston. “We do that for small pieces of the brain. How retina takes in an image and how the brain decodes that image, or how we generate simple movements are examples of how we try now to embody the equations of motion of those limited pieces. But we never used the control engineer’s trick of fusing those models with our measurements from the brain. This is the key — a good model will synchronize with the system it is coupled to.”

(Image: Photograph by Anne Keiser, National Geographic; model by Yeorgos Lampathakis)

Momentum builds in quest to find cure for childhood brain disease

Rasmussen Encephalitis strikes healthy kids; only known treatment removing half the brain.

How do you find a cure for a devastating pediatric brain disease so rare that it can take decades to build a meaningful research base?

In 2010, the parents of a patient created the Rasmussen Encephalitis (RE) Children’s Project to help solve this problem. In a short amount of time, the foundation has raised funds to establish a consortium of top researchers, build a collection of samples of the disease from around the world and support projects to study the disease tissue and search for genetic links. The goal is to find a cure.

Researchers at the David Geffen School of Medicine at UCLA have played a vital role in the ongoing research, and the foundation recently provided a second round of funding to continue their work. The gift of $125,000 builds on the organization’s donation of $111,000 made in 2011. 

"We are still in the early stages of research, but our momentum is building," said Seth H. Wohlberg, founder of the RE Children’s Project, and father of Grace, 15, who was stricken by the disease when she was 10 years old. "One of our key accomplishments has been to create an international system so that we can coordinate and transfer RE brain tissue and DNA material from the patients and parents. Collecting these samples is vital to advancing the research."

With the additional funding, UCLA researchers will apply cutting-edge DNA sequencing technology to determine whether a virus, or some other infectious agent, causes RE. They also plan to develop an animal model of the disease using cells obtained from the RE samples. 

The researchers include Dr. Gary Mathern, professor of pediatric neurosurgery and director of the UCLA Pediatric Epilepsy Program at Mattel Children’s Hospital; Carol Kruse, professor of neurosurgery; and Geoffrey Owens, visiting assistant researcher in neurosurgery.

"I am grateful to collaborate with a devoted father who has taken on the enormous task of advancing research for RE," said Mathern. "Thanks to his leadership, we now have the network to collect the tissue and DNA needed to study the brain, immunologic cells and genetics to unlock what causes this disease and develop new treatments or a cure. The RE Children’s Project has truly helped accelerate our research, bringing new information and resources that could have taken 10 more years to develop to the forefront today."

Rasmussen Encephalitis is a neurological disease that causes intractable seizures, cognitive deficits and paralysis of half of the body.  It is very rare and only a few hundred cases have been reported worldwide. RE typically affects previously normal children between the ages of two and ten years old. The disease process can run its course over a one to two year period during which time one half of the body is rendered useless and epileptic seizures continue unabated. 

An unusual feature of the disease is that it is usually confined to one hemisphere of the brain and is resistant to standard anti-seizure medicines. Currently the only known “cure” is radical- the surgical removal or disconnection of the affected side of the brain known as a hemispherectomy.

In the summer of 2008, the Wohlberg’s 10-year-old daughter Grace started to experience epileptic seizures. After months of testing, her parents learned that she had the extremely rare neurological disorder. Grace underwent an initial hemispherectomy surgery in February 2009. However, her seizures recurred so her parents then brought Grace to UCLA to complete the hemispherectomy which was performed by Mathern in March 2010. 

Today, Grace attends high school with the assistance of a full-time aide. While the surgery has stopped the seizures, Grace faces lifelong disabilities including partial blindness, cognitive issues and learning how to walk again. She is also active in helping her father promote the RE Children’s Project.

"It’s really supportive to let people know our story," said Grace. "Every year, my dad does a fundraiser and a lot of people come out to support it. It’s fun to be there and see all the people who care and want to help."

(Image: Wikimedia Commons)

Mystery disease unraveled by Stanford neurologist

At first, Marc Laderriere thought that his decreasing energy was just age catching up to him — he was about to be 50. But something about that explanation didn’t sit right.

"At one point, one of my doctors said, ‘This is definitely a little strange. I don’t know what you have, but it could be nerves,’" Laderriere recalled.

He was experiencing a set of symptoms that were unusual but did not strike him as significant: Hot weather sapped his strength and made him dizzy, but he was sweating less. In cool weather, he never got goose bumps.

As a young man growing up in France, Laderriere had always been active. “I did a lot of skiing, a lot of swimming,” he said. When he came to work in the United States, as a director of wine sales for the Vina Robles Winery & Vineyards in Paso Robles, he said he became a workaholic. “I completely accepted that way of life,” he said.

The more he traveled for his job, the less time and attention he paid to his health until he recognized, with some discomfort, that he was not in such great shape any more. He knew he should add exercise to his daily routine, but the fatigue he felt was overwhelming.

Laderriere, who lives in Paso Robles, started first with visits to local doctors. He had a variety of standard tests, with the thought that he might have developed diabetes. That was not the case. When one physician suggested it could be nerves, he went to see a local neurologist who sent him back to his original physician, still without a diagnosis. His symptoms continued and, finally, a local doctor suggested Stanford Hospital & Clinics.

During his first visit, he met with a group of physicians who asked him a lot questions,. “They were picking my brain,” he said, “asking me, ‘What’s wrong with this?’ I did not think to mention to them that I wasn’t sweating, but my wife was with me and she did. One of the doctors said, ‘Hmm, I think you may want to meet Dr. Jaradeh.’”

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Device Helps Children with Disabilities Access Tablets

Imagine not being able to touch a touch-screen device. Tablets and smartphones—with all their educational, entertaining and social benefits—would be useless.

Researchers at Georgia Tech are trying to open the world of tablets to children whose limited mobility makes it difficult for them to perform the common pinch and swipe gestures required to control the devices.

Ayanna Howard, professor of electrical and computer engineering, and graduate student Hae Won Park have created Access4Kids, a wireless input device that uses a sensor system to translate physical movements into fine-motor gestures to control a tablet.

The device, coupled with supporting open-source apps and software developed at Georgia Tech, allows children with fine motor impairments to access off-the-shelf apps such as Facebook and YouTube, as well as custom-made apps for therapy and science education.

“Every child wants access to tablet technology. So to say, ‘No you can’t use it because you have a physical limitation’ is totally unfair,” Howard said. “We’re giving them the ability to use what’s in their mind so they have an outlet to impact the world.”

The current prototype of the Access4Kids device includes three force-sensitive resistors that measure pressure and convert it into a signal that instructs the tablet. A child can wear the device around the forearm or place it on the arm of a wheelchair and hit the sensors or swipe across the sensors with his or her fist. The combination of sensor hits or swipes gets converted to different “touch-based” commands on the tablet.

Children with neurological disorders such as cerebral palsy, traumatic brain injury, spina bifida and muscular dystrophy typically suffer from fine motor impairments, which is the difficulty of controlling small coordinated movements of the hands, wrists and fingers. They tend to lack the ability to touch a specific small region with appropriate intensity and timing needed for press and swipe gestures.

Drug fights hard-to-treat depression by targeting brain receptors in a new way

A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose. 

The novel therapeutic targets brain receptors responsible for learning and memory — a very different approach from existing antidepressants. The new drug and others like it also could be helpful in treating other neurological conditions, including schizophrenia, bipolar disorder, anxiety and Alzheimer’s disease.

The results of the phase IIa clinical trial were presented (Dec. 6) at the 51st Annual Meeting of the American College of Neuropsychopharmacology in Hollywood, Fla.

Also this week a paper reporting some of the background scientific research that provided the foundation for the clinical development of GLYX-13 was published by the journal Neuropsychopharmacology.

The compound, called GLYX-13, is the result of more than two decades of work by Joseph Moskal, research professor of biomedical engineering at Northwestern’s McCormick School of Engineering and Applied Science and director of the University’s Falk Center for Molecular Therapeutics.

New Treatment for ‘Sleeping Beauty’ Syndrome?

Most of us have experienced it: that dull, dragging semi-conscious state of deadened awareness and desperate urge to nap that comes from sleep deprivation. For people with primary hypersomnia, however, this is the way they go through life, constantly feeling only half-awake but never able to get enough good sleep to arise truly refreshed. Also known as “Sleeping Beauty Syndrome,” the condition leaves those with the worst cases languishing in bed in what seems like the opposite of a fairy tale, without a prince’s kiss to cure them.

But a new study, published in Science Translational Medicine, suggests both a possible cause and a potential treatment for the condition, which may ultimately lead to treatments for other sleep disorders. The origin of primary hypersomnia, which has some genetic components is still unknown, as is the number of people who are affected by it.

One particularly striking form of the disease, Kleine-Levin syndrome, produces such tiredness and sleep-drunkenness that people are unable to attend school or work. In males, it can include hypersexual behavior, compulsive masturbation, a desire for promiscuous sex or making inappropriate sexual advances, all while in a sleepy, semi-conscious state.

In the latest study, researchers led by David Rye of Emory University in Atlanta studied 10 men and 22 women seeking treatment for primary hypersomnia. In the patients’ spinal fluid, the scientists discovered a previously uncharacterized chemical that stimulates the GABA-A receptor. This receptor is best known as the site where sleep-inducing drugs like Valium and Xanax have their effects, since activating GABA-A receptors can result in drowsiness.

The finding suggested a possible treatment. A drug, known as flumanezil can treat Valium and Xanax overdoses or to reverse the effects of related compounds used in anesthesia. Could it block or reverse the effects of the unknown agent that was activating GABA-A receptors in primary hypersomnia?

The authors conducted a brief placebo controlled trial with seven patients—including one with Kleine-Levin symptoms — to find out. Indeed, injections of flumanezil improved the participants’ ability to pay attention and remain alert. One participant has now taken the drug daily for four years. “Although her nightly sleep duration remained at 9 to 10 hours, she nearly always awakened refreshed without an alarm and daytime sleepiness was markedly reduced,” the researchers write.