Super song learners

Most songbirds learn their songs from an adult model, mostly from the father. However, there are relatively large differences in the accuracy how these songs are copied. Researchers from the Max Planck Institute for Ornithology in Seewiesen now found in juvenile zebra finches a possible mechanism that is responsible for the differences in the intensity of song learning. They provided the nerve growth factor “BDNF” to the song control system in the brain. With this treatment the learning ability in juvenile males could be enhanced in such a way that they were able to copy the songs of the father as good as it had been observed in the best learners in a zebra finch nest.

The improvement of cognitive abilities plays an important role in the therapy of neurological and psychiatric diseases. In this context research focusses more and more on the protein BDNF (Brain Derived Neurotrophic Factor). BDNF is mainly responsible for the preservation, growth and differentiation of nerve cells. Moreover, from experiments in mice it is known that BDNF enhances the ability to solve complex cognitive tasks.

In a learning experiment with zebra finches, researchers from the Max Planck Institute for Ornithology in Seewiesen in collaboration with scientists from the Free University of Amsterdam could now show for the first time in songbirds that BDNF acts as cognitive enhancer. They investigated zebra finch brother pairs that grew up with their genetic parents. In this setup juvenile birds will readily learn the songs from their fathers. However there are differences in the intensity of song learning among siblings of the same age. The worst learners have only a similarity of 20% with their fathers’ songs, whereas the best learners copy almost the entire songs of their fathers.

By now knowing the normal distribution of the learned songs within a zebra finch nest, as a next step the researchers were able to investigate the impact of BDNF on song learning. In one of the two brothers they enhanced the expression of BDNF in the song control system in the brain while the other brother did not get such a treatment. By analysing the songs the researchers found that those sons that received more BDNF had a higher similarity with the song of their fathers compared to normally reared juveniles. Remarkably, the learning efficiency in the BDNF-treated birds was as high as it has been previously observed in the best learners within the nest. This was due to an earlier onset of syllable copying in BDNF-treated birds and these birds also copied more and sang fewer improvised syllables. Therefore it is likely that the presence of BDNF in the song control system could correct possible inaccuracies in the song learning process, state the scientists around Manfred Gahr, who is the senior author of the study.

Seeing the Song

How and when the auditory system registers complex auditory-visual synchrony

New biological links between sleep deprivation and the immune system discovered

Population-level studies have indicated that insufficient sleep increases the risk of cardiovascular diseases and type 2 diabetes. These diseases are known to be linked to inflammatory responses in the body.

University of Helsinki researchers have now shown what kinds of biological mechanisms related to sleep loss affect the immune system and trigger an inflammatory response. They identified the genes which are most susceptible to sleep deprivation and examined whether these genes are involved in the regulation of the immune system. The study was published in the journal PLOS ONE on October 23, 2013.

Conducted at the sleep laboratory of the Finnish Institute of Occupational Health, the study restricted the amount of sleep of a group of healthy young men to four hours per night for five days, imitating the schedule of a normal working week. Blood samples were taken before and after the sleep deprivation test. White blood cells were isolated from the samples, and the expression of all genes at the time of the sampling was examined using microarrays. The results were compared with samples from healthy men of comparable age who had been sleeping eight hours per night for the week.

"We compared the gene expression before and after the sleep deprivation period, and focused on the genes whose behaviour was most strongly altered," explains researcher Vilma Aho. "The expression of many genes and gene pathways related to the functions of the immune system was increased during the sleep deprivation. There was an increase in activity of B cells which are responsible for producing antigens that contribute to the body’s defensive reactions, but also to allergic reactions and asthma. This may explain the previous observations of increased asthmatic symptoms in a state of sleep deprivation."

The amount of certain interleukins, or signalling molecules which promote inflammation, increased, as did the amount of associated receptors such as Toll-like receptors (TLR). On the gene level, this was apparent in the higher-than-normal expression of the TLR4 gene after sleep loss. CRP level was also elevated, indicating inflammation.

The researchers also wanted to examine the impact that long-term sleep deprivation could have on the immune system. For this follow-up study, they used material from the national FINRISKI health survey. Participants in this population study underwent blood tests but also answered questions about their health, for example whether they were getting enough sleep.

The researchers compared participants who believed they were sleeping sufficiently with those who felt that they were not sleeping enough. Some of the gene-level changes observed in the experimental working week sleep restriction study were repeated in the population sample. These results may help explain the connection between shorter sleep and the development of inflammatory diseases, such as cardiovascular disease and diabetes, which has been established in epidemiological studies.

"These results corroborate the idea that sleep does not only impact brain function, but also interacts with our immune system and metabolism. Sleep loss causes changes to the system that regulates our immune defence. Some of these changes appear to be long-term, and may contribute to the development of diseases that have been linked to sleep deprivation in epidemiological research,” Aho states.

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.

Theatre offers promise for youth with autism

A novel autism intervention program using theatre to teach reciprocal communication skills is improving social deficits in adolescents with the disorder that now affects an estimated one in 88 children, Vanderbilt University researchers released today in the journal Autism Research.

The newly released study assessed the effectiveness of a two-week theatre camp on children with autism spectrum disorder and found significant improvements were made in social perception, social cognition and home living skills by the end of the camp. There were also positive changes in the participants’ physiological stress and reductions in self-reported parental stress.

Called SENSE Theatre, the Social Emotional Neuroscience & Endocrinology (SENSE) program evaluates the social functioning of children with autism and related neurodevelopmental disorders.

Camp participants ages 8 to 17 years join with typically developing peers who are specially trained to serve as models for social interaction and communication, skills that are difficult for children with autism. The camp uses techniques such as role-play and improvisation and culminates in public performances of a play.

“The findings show that treatment can be delivered in an unconventional setting, and children with autism can learn from unconventional ‘interventionists’ – their typically developing peer,” said lead author Blythe Corbett, Ph.D., associate professor of Psychiatry.

Social perception and interaction skills were measured before and after the camp using neuropsychological measures, play with peers and parental reporting. Significant differences were found in face processing, social awareness and social cognition, and duration of interaction with familiar peers increased significantly over the course of the camp.

Additionally, the stress hormone cortisol was measured through saliva samples taken both at home and throughout the camp to compare the stress level of participants at home, at the beginning of the camp and at the end of the camp. Cortisol levels rose on the first day of camp when compared to home values but declined by the end of treatment and during post-treatment play with peers.

“Our findings show that the SENSE Theatre program contributes to improvement in core social deficits when engaging with peers both on and off the stage,” Corbett said. “This research also shows it’s never too late to make a significant difference in the lives of children and youth with autism spectrum disorder, as [this program] targets children who are much older than kids who are participating in early intervention, yet we are still seeing significant gains in the core deficits of autism, and in a rather brief intervention.”

This research was supported by the Martin McCoy-Jesperson Discovery Grant in Positive Psychology and a grant from the National Institute of Mental Health (Grant No. R01 MH085717).

Corbett will continue using theatre techniques to study areas of social functioning among children with autism through a newly awarded grant from the National Institute of Mental Health (Grant No. R34 MH097793). This forthcoming study will explore treatment length and peer familiarity as factors in optimizing and generalizing gains and will enroll more than 30 youth with autism ages 8 to 16 in a 10-week program model beginning January 2014.

Study points to possible treatment for brain disorders

Clemson University scientists are working to determine how neurons are generated, which is vital to providing treatment for neurological disorders like Tuberous Sclerosis Complex (TSC).

TSC is a rare genetic disease that causes the growth of tumors in the brain and other vital organs and may indicate such disorders as autism, epilepsy and cognitive impairment that may arise from the abnormal generation of neurons.

“Current medicine is directed at inhibiting the mammalian target of rapamycin (mTOR), a common feature within these tumors that have abnormally high activity,” said David M. Feliciano, assistant professor of biological sciences. “However, current treatments have severe side effects, likely due to mTOR’s many functions and playing an important role in cell survival, growth and migration.”

Feliciano and colleagues published their findings in journal Cell Reports.

“Neural stem cells generate the primary communicating cells of the brain called neurons through the process of neurogenesis, yet how this is orchestrated is unknown,” said Feliciano.

The stem cells lie at the core of brain development and repair, and alterations in the cells’ self-renewal and differentiation can have major consequences for brain function at any stage of life, according to researchers.

To better understand the process of neurogenesis, the researchers used a genetic approach known as neonatal electroporation to deliver pieces of DNA into neural stem cells in young mice, which allowed them to express and control specific components of the mTOR pathway.

The researchers found that when they increase activity of the mTOR pathway, neural stem cells make neurons at the expense of making more stem cells. They also found that this phenomenon is linked to a specific mTOR target known as 4E-BP2, which regulates the production of proteins. 

Ultimately, this study points to a possible new treatment, 4E-BP2, for neurodevelopmental disorders like TSC and may have fewer side effects.

Future experiments are aimed at identifying which proteins are synthesized due to this pathway in neurological disorders.