Posts tagged neuroscience

ScienceDaily (July 17, 2012) — A buildup of sodium in the brain detected by magnetic resonance imaging (MRI) may be a biomarker for the degeneration of nerve cells that occurs in patients with multiple sclerosis (MS), according to a new study published online in the journal Radiology.

The study found that patients with early-stage MS showed sodium accumulation in specific brain regions, while patients with more advanced disease showed sodium accumulation throughout the whole brain. Sodium buildup in motor areas of the brain correlated directly to the degree of disability seen in the advanced-stage patients.

"A major challenge with multiple sclerosis is providing patients with a prognosis of disease progression," said Patrick Cozzone, Ph.D., director emeritus of the Center for Magnetic Resonance in Biology and Medicine, a joint unit of National Center for Scientific Research (CNRS) and Aix-Marseille University in Marseille, France. "It’s very hard to predict the course of the disease."

In MS, the body’s immune system attacks the protective sheath (called myelin) that covers nerve cells, or neurons, in the brain and spinal cord. The scarring affects the neurons’ ability to conduct signals, causing neurological and physical disability. The type and severity of MS symptoms, as well as the progression of the disease, vary from one patient to another.

Dr. Cozzone, along with Wafaa Zaaraoui, Ph.D., research officer at CNRS, Jean-Philippe Ranjeva, Ph.D., professor in neuroscience at Aix-Marseille University and a European team of interdisciplinary researchers used 3 Tesla (3T) sodium MRI to study relapsing-remitting multiple sclerosis (RRMS), the most common form of the disease in which clearly defined attacks of worsening neurologic function are followed by periods of recovery. Sodium MRI produces images and information on the sodium content of cells in the body.

"We collaborated for two years with chemists and physicists to develop techniques to perform 3T sodium MRI on patients," Dr. Zaaraoui said. "To better understand this disease, we need to probe new molecules. The time has come for probing brain sodium concentrations."

Using specially developed hardware and software, the researchers conducted sodium MRI on 26 MS patients, including 14 with early-stage RRMS (less than five years in duration) and 12 with advanced disease (longer than five years), and 15 age- and sex-matched control participants.

In the early-stage RRMS patients, sodium MRI revealed abnormally high concentrations of sodium in specific brain regions, including the brainstem, cerebellum and temporal pole. In the advanced-stage RRMS patients, abnormally high sodium accumulation was widespread throughout the whole brain, including normal appearing brain tissue.

"In RRMS patients, the amount of sodium accumulation in gray matter associated with the motor system was directly correlated to the degree of patient disability," Dr. Zaaraoui said.

Current treatments for MS are only able to slow the progress of the disease. The use of sodium accumulation as a biomarker of neuron degeneration may assist pharmaceutical companies in developing and assessing potential treatments.

"Brain sodium MR imaging can help us to better understand the disease and to monitor the occurrence of neuronal injury in MS patients and possibly in patients with other brain disorders," Dr. Ranjeva said.

Source: Science Daily

ScienceDaily (July 17, 2012) — Using adult stem cells, Johns Hopkins researchers and a consortium of colleagues nationwide say they have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage.

Their experiments on cells in the laboratory, reported in the July 4 issue of the journal Science Translational Medicine, could speed the search for new drugs to treat the incurable neurodegenerative disease, but also, they say, may lead them back to better ways of using medications that previously failed in clinical trials.

"Our study suggests that some failed drugs should actually work if they were used earlier, and especially if we could diagnose PD before tremors and other symptoms first appear," says one of the study’s leaders, Ted M. Dawson, M.D., Ph.D., a professor of neurology at the Johns Hopkins University School of Medicine.

Dawson and his colleagues, working as part of a National Institute of Neurological Disorders and Stroke consortium, created three lines of induced pluripotent stem (iPS) cells derived from the skin cells of adults with PD. Two of the cell lines had the mutated LRKK2 gene, a hallmark of the most common genetic cause of PD. Induced pluripotent stem cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body.

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ScienceDaily (July 17, 2012) — A stroke can weaken one side of the body, raising the dangerous possibility of unstable walking and debilitating falls. Physical therapy can help patients learn to shift their body weight slightly to the weaker, stroke-affected side to help regain balance, but for some patients, the weakness returns after their therapy ends.

University of Illinois at Chicago physical therapy professor Alexander Aruin has developed an inexpensive, simple way to deal with the problem, training the brain to rebalance body weight using a simple shoe insole he calls a “compelled body weight shift.” It slightly lifts and tilts the body toward the stroke-affected side, restoring balance without the patient having to think about it.

Aruin along with colleagues at UIC and Marianjoy Rehabilitation Hospital in Wheaton, Ill., studied two patient groups: one group at UIC who just had strokes, and one at Marianjoy who had strokes over a year ago.

"We tried a purely biomechanical approach," Aruin said. "We mechanically lifted the healthy side so the patient cannot resist. The mechanics force body weight to where it is distributed almost 50/50. When patients ambulate in such a condition, they learn how to bear weight equally through both extremities. It’s quite simple."

The two test groups followed slightly different protocols and were tested for various lengths of time. Their results were measured against those of control groups, who did not get the small therapeutic shoe insole, which measures less than half an inch thick. patients in all groups also received standard post-stroke physical therapy.

After the testing period ended, patients stopped using the insole. About three months afterward they were tested again to see if they retained the ability to keep their balance. Aruin and his colleagues found that physical therapy helped both the insole-user and control groups, but the insole group got an added boost.

"They showed more symmetrical body weight distribution and bore more weight on their affected side, and their gait velocity improved," he said. "The outcome looks promising. The technique is very simple and inexpensive and has potential, which is exciting."

Aruin hopes other physical therapists use the simple devices on stroke patients to see if they too benefit from it. His associates are also considering ways to use the insole to improve posture in post-stroke patients.

Source: Science Daily

ScienceDaily (July 17, 2012) — Scientists at the California Institute of Technology (Caltech) pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder.

Scientists at Caltech pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder. (Credit: Elaine Hsiao)

What has remained unanswered, however, is whether the immune changes play a causative role in the development of the disease or are merely a side effect. Now a new Caltech study suggests that specific changes in an overactive immune system can indeed contribute to autism-like behaviors in mice, and that in some cases, this activation can be related to what a developing fetus experiences in the womb.

The results appear in a paper this week in the Proceedings of the National Academy of Sciences (PNAS).

"We have long suspected that the immune system plays a role in the development of autism spectrum disorder," says Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at Caltech, who led the work. "In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring."

The first step in the work was establishing a mouse model that tied the autism-related behaviors together with immune changes. Several large epidemiological studies — including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005 — have found a correlation between viral infection during the first trimester of a mother’s pregnancy and a higher risk for autism spectrum disorder in her child. To model this in mice, the researchers injected pregnant mothers with a viral mimic that triggered the same type of immune response a viral infection would.

"In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson’s lab and lead author of the PNAS paper.

The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder — repetitive or stereotyped behaviors, decreased social interactions, and impaired communication. In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.

Next, the researchers characterized the immune system of the offspring of mothers that had been infected and found that the offspring display a number of immune changes. Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a key role in suppressing the immune response. Taken together, the observed immune alterations add up to an immune system in overdrive — one that promotes inflammation.

"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. "This tells us that a prenatal challenge can result in long-term consequences for health and development."

With the mouse model established, the group was then able to test whether the offspring’s immune problems contribute to their autism-related behaviors. In the most revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like behavioral impairments.

The researchers emphasize that because the work was conducted in mice, the results cannot be readily extrapolated to humans, and they certainly do not suggest that bone-marrow transplants should be considered as a treatment for autism. They also have yet to establish whether it was the infusion of stem cells or the bone-marrow transplant procedure itself — complete with irradiation — that corrected the behaviors.

However, Patterson says, the results do suggest that immune irregularities in children could be an important target for innovative immune manipulations in addressing the behaviors associated with autism spectrum disorder. By correcting these immune problems, he says, it might be possible to ameliorate some of the classic developmental delays seen in autism.

In future studies, the researchers plan to examine the effects of highly targeted anti-inflammatory treatments on mice that display autism-related behaviors and immune changes. They are also interested in considering the gastrointestinal (GI) bacteria, or microbiota, of such mice. Coauthor Sarkis Mazmanian, a professor of biology at Caltech, has shown that gut bacteria are intimately tied to the function of the immune system. He and Patterson are investigating whether changes to the microbiota of these mice might also influence their autism-related behaviors.

Source: Science Daily

July 17, 2012

(Medical Xpress) — You’re headed out the door and you realize you don’t have your car keys. After a few minutes of rifling through pockets, checking the seat cushions and scanning the coffee table, you find the familiar key ring and off you go. Easy enough, right? What you might not know is that the task that took you a couple seconds to complete is a task that computers — despite decades of advancement and intricate calculations — still can’t perform as efficiently as humans: the visual search.

Pictured is part of the research team in front of the magnetic resonance imaging device at the UCSB Brain Imaging Center. From left to right: researcher Tim Preston; associate professor of psychological and brain sciences Barry Giesbrecht; and professor of psychological and brain sciences Miguel P. Eckstein. Not pictured: Koel Das, now a faculty member at the Indian Institute of Science in Bangalore, Karnatka, India; and lead author Fei Guo, now in the software industry. Credit: UCSB

"Our daily lives are comprised of little searches that are constantly changing, depending on what we need to do," said Miguel Eckstein, UC Santa Barbara professor of psychological and brain sciences and co-author of the recently released paper "Feature-Independent Neural Coding of Target Detection during Search of Natural Scenes," published in the Journal of Neuroscience. "So the idea is, where does that take place in the brain?"

A large part of the human brain is dedicated to vision, with different parts involved in processing the many visual properties of the world. Some parts are stimulated by color, others by motion, yet others by shape.

However, those parts of the brain tell only a part of the story. What Eckstein and co-authors wanted to determine was how we decide whether the target object we are looking for is actually in the scene, how difficult the search is, and how we know we’ve found what we wanted.

They found their answers in the dorsal frontoparietal network, a region of the brain that roughly corresponds to the top of one’s head, and is also associated with properties such as attention and eye movements. In the parts of the human brain used earlier in the processing stream, regions stimulated by specific features like color, motion, and direction are a major part of the search. However, in the dorsal frontoparietal network, activity is not confined to any specific features of the object.

"It’s flexible," said Eckstein. Using 18 observers, an MRI machine, and hundreds of photos of scenes flashed before the observers with instructions to look for certain items, the scientists monitored their subjects’ brain activity. By watching the intraparietal sulcus (IPS), located within the dorsal frontoparietal network, the researchers were able to note not only whether their subjects found the objects, but also how confident they were in their finds.

The IPS region would be stimulated even if the object was not there, said Eckstein, but the pattern of activity would not be the same as it would had the object actually existed in the scene. The pattern of activity was consistent, even though the 368 different objects the subjects searched for were defined by very different visual features. This, Eckstein said, indicates that IPS did not rely on the presence of any fixed feature to determine the presence or absence of various objects. Other visual regions did not show this consistent pattern of activity across objects.

"As you go further up in processing, the neurons are less interested in a specific feature, but they’re more interested in whatever is behaviorally relevant to you at the moment," said Eckstein. Thus, a search for an apple, for instance, would make red, green, and rounded shapes relevant. If the search was for your car keys, the interparietal sulcus would now be interested in gold, silver, and key-type shapes and not interested in green, red, and rounded shapes.

"For visual search to be efficient, we want those visual features related to what we are looking for to elicit strong responses in our brain and not others that are not related to our search, and are distracting," Eckstein added. "Our results suggest that this is what is achieved in the intraparietal sulcus, and allows for efficient visual search."

For Eckstein and colleagues, these findings are just the tip of the iceberg. Future research will dig more deeply into the seemingly simple yet essential ability of humans to do a visual search and how they can use the layout of a scene to guide their search.

"What we’re trying to really understand is what other mechanisms or strategies the brain has to make searches efficient and easy," said Eckstein. "What part of the brain is doing that?"

Provided by University of California - Santa Barbara

Source: medicalxpress.com

July 16, 2012 By Maureen Salamon

(HealthDay) — Evidence is building that poor sleep patterns may do more than make you cranky: The amount and quality of shuteye you get could be linked to mental deterioration and Alzheimer’s disease, four new studies suggest.

Inadequate shuteye associated with mental decline in four new studies.

Too little or too much sleep was equated with two years’ brain aging in one study. A separate study concluded that people with sleep apnea — disrupted breathing during sleep — were more than twice as likely to develop mild thinking problems or dementia compared to problem-free sleepers. Yet another suggests excessive daytime sleepiness may predict diminished memory and thinking skills, known as cognitive decline, in older people.

"Whether sleep changes, such as sleep apnea or disturbances, are signs of a decline to come or the cause of decline is something we don’t know, but these four studies … shed further light that this is an area we need to look into more," said Heather Snyder, senior associate director of medical and scientific relations for the Alzheimer’s Association in Chicago, who was not involved in the studies.

The studies are scheduled for presentation Monday at the Alzheimer’s Association annual meeting in Vancouver.

The largest of the studies, which examined data on more than 15,000 women in the U.S. Nurses’ Health Study, suggested that those who slept five hours a day or less, or nine hours a day or more, had lower average mental functioning than participants who slept seven hours per day. Too much or too little sleep was cognitively equivalent to aging by two years, according to the research, which followed the women over 14 years beginning in middle age.

The study also observed that women whose sleep duration changed by two hours or more a day from mid- to later life had worse brain function than participants with no change in sleep duration — a finding that held true regardless of how long they usually slept at the beginning of the study.

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