Musical training increases blood flow in the brain

Research by the University of Liverpool has found that brief musical training can increase the blood flow in the left hemisphere of our brain. This suggests that the areas responsible for music and language share common brain pathways.

Researchers from the University’s Institute of Psychology, Health and Society carried out two separate studies which looked at brain activity patterns in musicians and non-musicians.

The first study looking for patterns of brain activity of 14 musicians and 9 non-musicians whilst they participated in music and word generation tasks. The results showed that patterns in the musician’s brains were similar in both tasks but this was not the case for the non-musicians.

In the second study, brain activity patterns were measured in a different group of non-musical participants who took part in a word generation task and a music perception task.

The measurements were also taken again following half an hour’s musical training. The measurements of brain activity taken before the musical training* showed no significant pattern of correlation. However, following the training significant similarities were found.

Amy Spray, who conducted the research as part of a School of Psychology Summer Internship Scheme, said: “The areas of our brain that process music and language are thought to be shared and previous research has suggested that musical training can lead to the increased use of the left hemisphere of the brain.

This study looked into the modulatory effects that musical training could have on the use of the different sides of the brain when performing music and language tasks.”

Amy added: “It was fascinating to see that the similarities in blood flow signatures could be brought about after just half an hour of simple musical training.”

Liverpool Psychologist, Dr Georg Mayer, explained: “This suggests that the correlated brain patterns were the result of using areas thought to be involved in language processing. Therefore we can assume that musical training results in a rapid change in the cognitive mechansims utilised for music perception and these shared mechanisms are usually employed for language.”

Brain Noise Found to Nurture Synapses

A study has shown that a long-overlooked form of neuron-to-neuron communication called miniature neurotransmission plays an essential role in the development of synapses, the regions where nerve impulses are transmitted and received. The findings, made in fruit flies, raise the possibility that abnormalities in miniature neurotransmission may contribute to neurodevelopmental diseases. The findings, by researchers at Columbia University Medical Center (CUMC), were published today in the online edition of the journal Neuron.

The primary way in which neurons communicate with each another is through “evoked neurotransmission.” This process begins when an electrical signal, or action potential, is transmitted along a long, cable-like extension of the neuron called an axon. Upon reaching the axon’s terminus, the signal triggers the release of chemicals called neurotransmitters across the synapse. Finally, the neurotransmitters bind to and activate receptors of the neuron on the other side of the synapse. Neurotransmitters are packaged together into vesicles, which are released by the hundreds, if not thousands, with each action potential. Evoked neurotransmission was first characterized in the 1950s by Sir Bernard Katz and two other researchers, who were awarded the 1970 Nobel Prize in Physiology or Medicine for their efforts.

“Dr. Katz also found that even without action potentials, lone vesicles are released now and then at the synapse,” said study leader Brian D. McCabe, PhD, assistant professor of pathology and cell biology and of neuroscience in the Motor Neuron Center. “These miniature events — or minis — have been found at every type of synapse that has been studied. However, since minis don’t induce neurons to fire, people assumed they were inconsequential, just background noise.”

Recent cell-culture studies, however, have suggested that minis do have some function and even their own regulatory mechanisms. “This led us to wonder why there would be such complicated mechanisms for regulating something that was just noise,” said Dr. McCabe.

To learn more about minis, the CUMC team devised new genetic tools to selectively up- or down-regulate evoked and miniature neurotransmission in fruit flies (a commonly used model organism for neuronal function and development). This was the first study to identify a unique role for minis in an animal model.

The researchers found that when both types of neurotransmission were blocked, synapse development was abnormal. However, inhibiting or stimulating evoked neurotransmission alone had no effect on synaptic development. “But when we blocked minis, synapses failed to develop,” said Dr. McCabe, “and when we stimulated the release of more minis, synapses got bigger.”

The study also showed that minis regulate synapse development by activating a signaling pathway in neurons involving Trio and Rac1 proteins in presynaptic neurons. These proteins are also found in humans.

It remains to be seen exactly how minis are exerting their effects. “Parallel communication occurs in computer networks,” Dr. McCabe said. “Computers communicate primarily by sending bursts of data bundled into packets. But individual computers also send out pings, or tiny electronic queries, to determine if there is a connection to other computers. Similarly, neurons may be using minis to ping connected neurons, saying in effect, ‘We are connected and I am ready to communicate.’”

The researchers are currently looking into whether minis have a functional role in the mature nervous system. If so, it’s possible that defects in minis could contribute to neurodegenerative disease.

Sleep Researchers at SRI International Identify Promising New Treatment for Narcolepsy

Neuroscientists at SRI International have found that a form of baclofen, a drug used to treat muscle spasticity, works better at treating narcolepsy than the best drug currently available when tested in mice.

According to the National Institute of Neurological Disorders and Stroke (NINDS), narcolepsy, a chronic neurologic disorder characterized by excessive daytime sleepiness, is not a rare condition, but is under-recognized and under-diagnosed. It is estimated to impact 1 in 2,000 people worldwide.

In back-to-back papers published in the May 7 issue of The Journal of Neuroscience, Thomas Kilduff, Ph.D., who directs the Center for Neuroscience within SRI Biosciences, Sarah Wurts Black, Ph.D., a research scientist in the Center for Neuroscience, and colleagues present a mouse model of narcolepsy that mimics the human disorder better than other models currently in use. Kilduff, Black and the SRI team then used the new narcolepsy model alongside a standard model to investigate a novel therapeutic pathway and to identify a promising way of treating narcolepsy.

"Our work is an example of how basic research can lead to a potential new therapy for a disease," said Kilduff. His team found that a form of baclofen, R-baclofen, works in both mouse models much better than the leading FDA-approved therapeutic for narcolepsy. (Baclofen, which has been available for more than 50 years, is a chemical compound that exists as a mixture of two isomers, designated R and S.)  "The next step would be to perform a study in narcoleptic patients to determine its potential for treatment of human narcolepsy."

In humans, narcolepsy onset is typically during adolescence or later, but diagnosis may take more than a decade, making it difficult to study the progression of the disease. The lack of definitive mechanisms to explain what goes awry in the brain’s ability to regulate sleep-wake cycles has consequently yielded drugs that only address the symptoms, rather than the underlying causes, of narcolepsy.

In the first of the two papers, “Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function,” Kilduff and Black teamed with colleagues at five institutions in Japan to generate a model of narcolepsy that better mimics the human disorder. The existing model, called “Ataxin mice,” has been available for over 10 years. Although Ataxin mice have enabled researchers to study narcolepsy, an important limitation is that these mice are born with the deficiency of the neurotransmitter hypocretin that has been implicated in causing narcolepsy, whereas the onset of human narcolepsy typically occurs after puberty.

"The mouse model developed by Dr. Kilduff and his colleagues offers a new approach to study narcolepsy and to explore potential therapies for this devastating sleep disorder. This new model allows more precise control of the timing and extent of hypocretin/orexin neuron loss, and thus may better mimic human narcolepsy," said Janet He, Ph.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

In collaboration with Professor Akihiro Yamanaka of Nagoya University in Japan, formerly an SRI International Fellow in Dr. Kilduff’s laboratory, the research team genetically engineered a mouse in which the hypocretin neurons could be selectively eliminated at any age simply by removal of an antibiotic in the mouse food. In the new “DTA” model, degeneration of hypocretin neurons can be initiated after puberty, causing the mice to exhibit the two major symptoms of narcolepsy: excessive daytime sleepiness and cataplexy, the brief loss of muscle tone experienced by most narcoleptics.

In the second paper, “GABA_B Agonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy,” Black, Kilduff and colleagues used the new DTA model and the Ataxin model to compare R-baclofen against gamma-hydroxybutyrate (GHB).  Sodium oxybate, the sodium salt of GHB, was approved by the FDA in 2002 as the only therapeutic for narcolepsy that simultaneously alleviates cataplexy, excessive daytime sleepiness and nocturnal sleep disruption. However, it remains unclear how this drug exerts its beneficial effects.

It was suspected that GHB works by affecting brain cells that respond to a neurotransmitter known as gamma-aminobutyric acid (GABA), which primarily functions to inhibit excitability and regulate muscle tone. To study the mechanism of action of GHB, SRI Biosciences’ researchers tested R-baclofen, which blocks the GABA receptors suspected to be the target of GHB.

The research team found that R-baclofen promoted sleep time and longer bouts of wakefulness during the appropriate times for mice and also suppressed cataplexy. GHB modestly reduced cataplexy and increased sleep intensity, but did not improve other symptoms of narcolepsy to the extent that R-baclofen did. “The improvement in wakefulness that we observed after R-baclofen was a particularly unexpected and important finding,” said Black.

"R-Baclofen works better than GHB in these two mouse models, but it remains to be determined whether it will work better in humans," cautioned Kilduff. "Although baclofen is already known to be safe for use in humans, the dose that is effective for spasticity may be different than the dose of R-baclofen that has the potential to treat narcolepsy."

‘Exploding head syndrome’ a real, overlooked sleep disorder

It sounds like a phrase from Urban Dictionary or the title of an animated gif, but a Washington State University researcher says “exploding head syndrome” is an authentic and largely overlooked phenomenon that warrants a deeper look.

“It’s a provocative and understudied phenomenon,” said Brian Sharpless, a WSU assistant professor and director of the university psychology clinic who recently reviewed the scientific literature on the disorder for the journal Sleep Medicine Reviews. “I’ve worked with some individuals who have it seven times a night, so it can lead to bad clinical consequences as well.”

People with the syndrome typically perceive abrupt, loud noises—door slams, fireworks, gunshots—as they are going to sleep or waking up. While harmless, the episodes can be frightening.

“Some people start to become anxious when they go into their bedroom or when they try to go to sleep,” said Sharpless. “Daytime sleepiness can be another problem.”

Some patients report mild pain. Some hear an explosion in one ear, others in both ears and yet others within their heads. Some also see what looks like lightning or bright flashes.

Researchers do not know how widespread the problem is, but Sharpless is fielding enough reports of people with the disorder that he thinks it is more widespread than presumed. Just this week, a story on the disorder in Britain’s Daily Mail prompted several people with the syndrome to contact him. (See http://www.dailymail.co.uk/health/article-2620837/Is-exploding-head-syndrome-reason-sleep.html)

The term “exploding head syndrome” dates to a 1988 article in Lancet, but it was described clinically as “snapping of the brain” in 1920. Silas Weir Mitchell, an American physician, wrote in 1876 of two men who experienced explosive-sounding “sensory discharges.”

While the syndrome is recognized in the International Classification of Sleep Disorders, studies using electroencephalogram recordings have only documented the disruptions in periods of relaxed but awake drowsiness.

As with many sleep phenomena, it is largely mysterious.

“In layman’s terms, our best guess is that it occurs when the body doesn’t shut down for sleep in the correct sequence,” said Sharpless. “Instead of shutting down, certain groups of neurons actually get activated and have us perceive the bursts of noise. Behavioral and psychological factors come into play as well, and if you have normally disrupted sleep, the episodes will be more likely to occur.”

Judging from the limited scientific literature and available statistics, Sharpless said the syndrome is more common in women than men. Some medical treatments are available for it, but one possible intervention can be simply reassuring a patient that it is not a dangerous condition.

(Image caption: Uncinate fasiculus, an important tract with the greatest concentration of progesterone receptors, show greater injury in males than females after mild traumatic brain injury (mTBI). (a) Axial and (b) coronal images show regions of decreased fractional anisotropy in male patients with mTBI relative to female mTBI patients, involving the uncinate fasiculus (red) bilaterally.)

Gender May Contribute to Recovery Time After Concussion

A study of concussion patients using diffusion tensor imaging (DTI) found that males took longer to recover after concussion than females did. Results of the study, which show that DTI can be used as a bias-free way to predict concussion outcome, are published online in the journal Radiology.

Each year, more than 17 million Americans suffer a mild traumatic brain injury (mTBI), more commonly known as a concussion, of which approximately 15 percent suffer persistent symptoms beyond three months.

Assessing outcomes and recovery time after concussion can be very subjective. Typically, physicians must rely on patient cooperation to assess injury severity.

"MRI and CT brain images of concussion patients are often normal," said Saeed Fakhran, M.D., assistant professor of neuroradiology at the University of Pittsburgh School of Medicine. "Diffusion tensor imaging is the first imaging technique that shows abnormalities associated with concussion, because it is able to see white matter tracts at a microscopic level."

DTI is an advanced form of MRI that allows researchers to assess microscopic changes in the brain’s white matter. The brain’s white matter is composed of millions of nerve fibers called axons that act like communication cables connecting various regions of the brain. DTI produces a measurement, called fractional anisotropy (FA), of the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform and measures high in FA. When water movement is more random, FA values decrease. Abnormally low FA is associated with cognitive impairment in patients with brain injuries.

The research team examined the medical records and imaging results of 69 patients diagnosed with mTBI between 2006 and 2013, including 47 males and 22 females, and 21 controls consisting of 10 males and 11 females (median age of males: 17; median age of females: 16). Of the 47 males with mTBI, 32 (68 percent) were injured while playing a sport, as were 10 of the 22 females (45 percent).

All patients underwent the same evaluation, including a computerized neurocognitive test and DTI of the brain. The DTI scans of the mTBI patients revealed abnormalities within the uncinate fasciculi (UF), a white matter tract that connects the frontal and temporal lobes of the brain. Although its exact role is controversial, the UF tract is believed to allow temporal lobe-based memory associations to modify behavior though interactions with another area of the brain.

The DTI scans revealed that compared to the female mTBI patients, the male mTBI patients had significantly decreased UF FA values.

"In the future, we would like to look at the issue of gender and concussions more in depth to determine who does better and why," Dr. Fakhran said.

A statistical analysis of the data revealed that UF FA value was a stronger predictor of recovery time than initial symptom severity based on neurocognitive testing. The most substantial risk factor for a recovery time longer than three months was decreased UF FA. Male gender also directly correlated with increased recovery time.

"The potential of DTI and UF FA to predict outcome after concussion has great clinical impact," Dr. Fakhran said. "Currently, we are heavily reliant on patient reporting, and patients may have ulterior motives, such as wanting to get back to play. But you can’t trick an MR scanner."

The average time to symptom recovery for all concussion patients was 54 days. However, compared to the female patients who recovered in an average of 26.3 days, recovery was significantly longer for the male patients (an average of 66.9 days), irrespective of initial symptom severity.

"Male gender and UF FA values are independent risk factors for persistent post-concussion symptoms after three months and stronger predictors of time to recovery than initial symptom severity or neurocognitive test results," Dr. Fakhran said.

He said results of the study indicate a potential role for UF FA values in triaging concussion patients in the future.

"There’s prognostic value in DTI for both children participating in sports as well as for professional athletes," he said. "Lower FA values in the uncinate fasciculi could offer a metric for evaluating the severity of mild traumatic brain injuries and predicting clinical outcome. We’re not at the point where DTI can provide individual prognoses yet, but that’s the hope and goal."

Molecular Switches for Age-Related Memory Decline? A Genetic Variant Protects Against Brain Aging

Even among the healthiest individuals, memory and cognitive abilities decline with age. This aspect of normal aging can affect an individual’s quality of life and capability to live independently but the rate of decline is variable across individuals. There are many factors that can influence this trajectory, but perhaps none more importantly than genetics.

Scientists are seeking to identify key molecular switches that control age-related memory impairment. When new molecules are identified as critical to the process of memory consolidation, they are then tested to determine whether they contribute to the memory problems of the elderly.

One of these proteins is called KIBRA and the gene responsible for its production is WWC1. KIBRA is known to play a role in human memory and so researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Dr. Venkata Mattay, conducted a study to determine the effects of genetic variants in WWC1 on memory. Their findings are published in the current issue of Biological Psychiatry.

“Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function,” explained Mattay.

Using imaging genetics, a method that combines genetics with brain imaging technology, the team explored the effect of a variant in the WWC1 gene on age-related changes in memory function. The particular WWC1 variant under investigation has three potential forms – CC, TT, or CT.

They recruited 233 healthy volunteers, who ranged in age from 18-89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan.

They found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age.

“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”

Dr. John Krystal, Editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”