March 8, 2012 By Katie Neith

(Medical Xpress) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies—which are called frequency-modulated (FM) sweeps—is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

Knowing the direction of an FM sweep—if it is rising or falling, for example—and decoding its meaning, is important in every language. The significance of the direction of an FM sweep is most evident in tone languages such as Mandarin Chinese, in which rising or dipping frequencies within a single syllable can change the meaning of a word.

In their paper, the researchers pinpointed the brain region in rats where the task of sorting FM sweeps begins.

"This type of processing is very important for understanding language and speech in humans," says Guangying Wu, principal investigator of the study and a Broad Senior Research Fellow in Brain Circuitry at Caltech. "There are some people who have deficits in processing this kind of changing frequency; they experience difficulty in reading and learning language, and in perceiving the emotional states of speakers. Our research might help us understand these types of disorders, and may give some clues for future therapeutic designs or designs for prostheses like hearing implants."

This diagram shows areas in the midbrain region where direction- selective neurons were found.Credit: Guangying Wu/Caltech

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March 7, 2012

Neurons (nerve cells) are labeled with green fluorescent protein, and other neurons in the brain are labeled in the background with either red or blue tracers. The small bulbs (i.e., dendritic spines) on the spidery dendrites show places where nerve cells connect and communicate, called synapses, and when these spines shrank over time, this predicted vocal degradation in the songbirds. Credit: Katie Tschida, Duke Department of Neurobiology

Portions of a songbird’s brain that control how it sings have been shown to decay within 24 hours of the animal losing its hearing.

The findings, by researchers at Duke University Medical Center, show that deafness penetrates much more rapidly and deeply into the brain than previously thought. As the size and strength of nerve cell connections visibly changed under a microscope, researchers could even predict which songbirds would have worse songs in coming days.

"When hearing was lost, we saw rapid changes in motor areas in that control song, the bird’s equivalent of speech," said senior author Richard Mooney, Ph.D., professor of neurobiology at Duke. "This study provided a laser-like focus on what happens in the living songbird brain, narrowed down to the particular cell type involved."

The study was published in Neuron journal online on March 7, 2012.

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ScienceDaily (Mar. 6, 2012) — A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer’s disease.

Published in the March 6 issue of the Journal of Alzheimer’s Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.

Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer’s patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta. But the researchers didn’t know how it worked.

"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer’s disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

For the study, scientists drew blood samples from Alzheimer’s patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.

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ScienceDaily (Mar. 6, 2012) — Antibodies that block the process of synapse disintegration in Alzheimer’s disease have been identified, raising hopes for a treatment to combat early cognitive decline in the disease.

Amyloid beta (cyan blue) binds to nerve cells of the hippocampus (red) and attacks synapses resulting in the loss of memories in Alzheimer’s disease. New research has led to important insights into the mechanisms that induce synapse loss. The discovery brings hope for the development of new therapies that protect synapses and therefore prevent memory loss in Alzheimer’s disease. (Credit: Silvia Purro/Patricia Salinas/UCL)

Alzheimer’s disease is characterized by abnormal deposits in the brain of the protein Amyloid-ß, which induces the loss of connections between neurons, called synapses.

Now, scientists at UCL have discovered that specific antibodies that block the function of a related protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-ß on synapses. The findings are published March 6 in the Journal of Neuroscience.

Professor Patricia Salinas (UCL Department of Cell & Developmental Biology) who led the study, said: “These novel findings raise the possibility that targeting this secreted Dkk1 protein could offer an effective treatment to protect synapses against the toxic effect of Amyloid-ß.

"Importantly, these results raise the hope for a treatment and perhaps the prevention of cognitive decline early in Alzheimer’s disease."

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March 6, 2012

Patients with epilepsy who underwent brain surgery soon after failing to respond to drug treatment, but who also continued to receive drug therapy, had a lower risk of seizures during the 2nd year of follow-up compared to patients who received drug treatment alone, according to a study in the March 7 issue of JAMA.

"Epilepsy is a worldwide serious health concern, accounting for 1 percent of the global burden of disease, equivalent to lung cancer in men and breast cancer in women. The 20 percent to 40 percent of patients who have medically intractable epilepsy account for 80 percent of the cost of epilepsy. Temporal lobe epilepsy (TLE) is the most common cause of drug-resistant seizures, but it can be treated surgically," according to background information in the article. The American Academy of Neurology practice parameter recommends surgery as the treatment of choice for medically intractable TLE, but use of this treatment is delayed and underutilized. Patients who are referred for surgery have had epilepsy for an average of 22 years, more than 10 years after failure of 2 antiepileptic drugs (AEDs). Because earlier surgery could prevent significant illness and premature death, it has been recommended that a randomized controlled trial be conducted to evaluate its efficacy.

Jerome Engel Jr., M.D., Ph.D., of the University of California, Los Angeles, and colleagues conducted a study to compare outcomes of surgery for epilepsy with those of continued drug treatment. The clinical trial, performed at 16 U.S. epilepsy surgery centers, included 38 participants (18 men and 20 women; age 12 years or older) who had mesial temporal lobe (a section of the brain) epilepsy (MTLE) and disabling seizures for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Eligibility for anteromesial temporal resection (AMTR; surgery/removal of tissue of a section of the brain) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome measure for the study was freedom from disabling seizures during year 2 of follow-up. Other outcomes included measures on health-related quality of life (QOL) and cognitive function. 

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March 6, 2012

Schematic diagrams of a normal brain (left) and an autistic brain (right) highlight the white matter alterations in autism. Credit: Carnegie Mellon University

New research from Carnegie Mellon University’s Marcel Just provides an explanation for some of autism’s mysteries — from social and communication disorders to restricted interests — and gives scientists clear targets for developing intervention and treatment therapies.

Autism has long been a scientific enigma, mainly due to its diverse and seemingly unrelated symptoms until now.

Published in the journal Neuroscience and Biobehavioral Reviews, Just and his team used brain imaging and computer modeling to show how the brain’s white matter tracts — the cabling that connects separated brain areas — are altered in autism and how these alterations can affect brain function and behavior. The deficiencies affect the tracts’ bandwidth — the speed and rate at which information can travel along the pathways.

"White matter is the unsung hero of the human brain," said Just, the D.O. Hebb Professor of Psychology within CMU’s Dietrich College of Humanities and Social Sciences and director of the university’s Center for Cognitive Brain Imaging. "In autistic individuals, we can measure the quality of the white matter, and our computer model can predict how coordinated their brain activity will be. This gives us a precise account of the underlying alterations affecting autistic thought."

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March 6, 2012

Thromboembolic stroke, caused by a blood clot in the brain, results in damage to the parts of the brain starved of oxygen. Breaking up the clot with tissue plasminogen activator (tPA) reduces the amount of damage, however, there is a very short time window when the value of the treatment outweighs the side effects. New research published in BioMed Central’s open access journal Experimental & Translational Stroke Medicine shows that, during the first 24 hours after a stroke, mild hypothermia (34C) can reduce the side effects of tPA and potentially increase the window of opportunity for tPA treatment.

When a blood clot blocks off blood flow in the brain (ischemic stroke) the part starved of oxygen quickly begins to die. In order to prevent significant damage tPA must be given to the patient as early as possible after the onset of symptoms - doctors recommend that it must be administered within the first four and a half hours. Delayed treatment also increases the patient’s risk of intracerebral hemorrhage and brain swelling (edema).

Mild hyperthermia is known to be neuroprotective and to reduce damage caused by the return of blood flow to an area of the brain starved of oxygen by a clot. Researchers from the University of Erlangen, led by Dr Rainer Kollmar, tested whether mild hyperthermia could also prevent damage to the brain due to tPA treatment in rats. After 24 hours they found that, while hypothermia reduced the amount of swelling and damaged tissue in the brain after a stroke, tPA (administered 90 minutes after the onset of stroke) increased it. However, they also discovered that hypothermia therapy was able to offset the damage due to tPA.

This seemed to be true for all the measurements they looked at. Dr Kollmar explained, “Patients often loose brain function such as control over parts of their body, speech or memory after stroke. We looked at ‘neuroscore’, to examine how much control of the body had been affected, and at markers for inflammation (TIMP-1 and sICAM) or evidence of damage to the blood brain barrier. In all cases hypothermia was able to offset the side effects of tPA.”

While these results are still experimental, new techniques which prevent shivering mean that this technique is easier to administer in conscious patients. Preliminary clinical trials are also beginning to show that it is possible to treat patients, who have had a stroke, with tPA plus hypothermia. Our results suggest that hypothermia can offset the side effects of tPA and further studies will show if it is also able to increase the window of opportunity of tPA treatment in patients.

Provided by BioMed Central

Source: medicalxpress.com

March 6, 2012

Getting rid of a protein increases the birth of new nerve cells and shortens the time it takes for antidepressants to take effect, according to an animal study in the March 7 issue of The Journal of Neuroscience. The protein, neurofibromin 1, normally helps prevent uncontrolled cell growth. The findings suggest therapeutic strategies aimed at stimulating new nerve cell birth may help treat depression better than current antidepressants that commonly take several weeks to reach full efficacy.

Throughout life, a section of the hippocampus — the brain’s learning and memory center — produces new nerve cells. This process, called neurogenesis, is made possible by specialized cells called neural progenitor cells (NPCs). While previous studies show adult neurogenesis declines with age and stress, therapies known to alleviate symptoms of depression, such as exercise and antidepressants, increase neurogenesis.

In the new study, a team of scientists directed by Luis Parada, PhD, of the University of Texas Southwestern, examined neurogenesis after deleting the neurofibromin 1 (Nf1) gene from NPCs in adult mice. Removal of Nf1 increased the number and maturation of newborn nerve cells in the adult hippocampus. Nf1 mutant mice showed reductions in depressive- and anxiety-like behaviors following 7 days of antidepressant treatment, whereas mice without the mutation took longer to show improvements.

"Our findings establish an important role for Nf1 in controlling neurogenesis in the hippocampus and demonstrate that activation of adult NPCs is enough to regulate depression- and anxiety-like behaviors," said study co-author Renee McKay, PhD, of the University of Texas Southwestern. "Our work is among the first to demonstrate the feasibility of altering mood via direct manipulation of adult neurogenesis," McKay added.

To determine if deleting Nf1 in adult NPCs leads to long-term behavioral changes in mice, the scientists ran 8-month-old mice through a battery of tests designed to measure anxiety- and depressive-like behaviors. Compared with other mice, the mutant mice showed less signs of anxiety and demonstrated resistance to the effects of chronic mild, unpredictable stress. The finding shows even without antidepressants, the deletion of Nf1 from NPCs in adult mice decreases symptoms of depression and anxiety.

"This study demonstrates that inducing neurogenesis is sufficient to produce antidepressant behavioral actions, and provides novel targets for therapeutic interventions," said Ronald Duman, PhD, a neurogenesis expert from Yale University.

Provided by Society for Neuroscience

Source: medicalxpress.com

ScienceDaily (Mar. 5, 2012) — A new marker of Alzheimer’s disease can predict how rapidly a patient’s memory and other mental abilities will decline after the disorder is diagnosed, researchers at Washington University School of Medicine in St. Louis have found.

In 60 patients with early Alzheimer’s disease, higher levels of the marker, visinin-like protein 1 (VILIP-1), in the spinal fluid were linked to a more rapid mental decline in the years that followed.

Scientists need to confirm the results in larger studies, but the new data suggest that VILIP-1 potentially may be a better predictor of Alzheimer’s progression than other markers.

“VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer’s disease,” says lead author Rawan Tarawneh, MD, now an assistant professor of neurology at the University of Jordan. “That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials.”

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