Brain imaging shows enhanced executive brain function in people with musical training

A controlled study using functional MRI brain imaging reveals a possible biological link between early musical training and improved executive functioning in both children and adults, report researchers at Boston Children’s Hospital. The study, appearing online June 17 in the journal PLOS ONE, uses functional MRI of brain areas associated with executive function, adjusting for socioeconomic factors.

Executive functions are the high-level cognitive processes that enable people to quickly process and retain information, regulate their behaviors, make good choices, solve problems, plan and adjust to changing mental demands.

"Since executive functioning is a strong predictor of academic achievement, even more than IQ, we think our findings have strong educational implications," says study senior investigator Nadine Gaab, PhD, of the Laboratories of Cognitive Neuroscience at Boston Children’s. "While many schools are cutting music programs and spending more and more time on test preparation, our findings suggest that musical training may actually help to set up children for a better academic future."

While it’s already clear that musical training relates to cognitive abilities, few previous studies have looked at its effects on executive functions specifically. Among these studies, results have been mixed and limited by a lack of objective brain measurements, examination of only a few aspects of executive function, lack of well-defined musical training and control groups, and inadequate adjustment for factors like socioeconomic status.

Gaab and colleagues compared 15 musically trained children, 9 to 12, with a control group of 12 untrained children of the same age. Musically trained children had to have played an instrument for at least two years in regular private music lessons. (On average, the children had played for 5.2 years and practiced 3.7 hours per week, starting at the age of 5.9.) The researchers similarly compared 15 adults who were active professional musicians with 15 non-musicians. Both control groups had no musical training beyond general school requirements.

Since family demographic factors can influence whether a child gets private music lessons, the researchers matched the musician/non-musician groups for parental education, job status (parental or their own) and family income. The groups, also matched for IQ, underwent a battery of cognitive tests, and the children also had functional MRI imaging (fMRI) of their brains during testing.

On cognitive testing, adult musicians and musically trained children showed enhanced performance on several aspects of executive functioning. On fMRI, the children with musical training showed enhanced activation of specific areas of the prefrontal cortex during a test that made them switch between mental tasks. These areas, the supplementary motor area, the pre-supplementary area and the right ventrolateral prefrontal cortex, are known to be linked to executive function.

"Our results may also have implications for children and adults who are struggling with executive functioning, such as children with ADHD or [the] elderly," says Gaab. "Future studies have to determine whether music may be utilized as a therapeutic intervention tools for these children and adults."

The researchers note that children who study music may already have executive functioning abilities that somehow attract them to music and predispose them to stick with their lessons. To establish that musical training influences executive function, and not the other way around, they hope to perform additional studies that follow children over time, assigning them to musical training at random.

Understanding the unique nature of children’s bodies and brains

With the increase in childhood obesity and the associated increase in type 2 diabetes among children and adolescents, there is growing interest in how children’s bodies process the foods they eat and how obesity and diabetes begin to develop at early ages. Two studies presented at the American Diabetes Association’s 74th Scientific Sessions® help to shed light on this topic.

One study, by researchers at the Yale School of Medicine, compared how the brains of adolescents and adults differed in their response to ingestion of a glucose drink. It found that in adolescents, glucose increased the blood flow in the regions of the brain implicated in reward-motivation and decision-making, whereas in adults, it decreased the blood flow in these regions.

"While we cannot speculate directly about how glucose ingestion may influence behavior, certainly we have shown that there are differences in how adults and adolescents respond to glucose," said lead researcher Ania Jastreboff, MD, PhD, an Assistant Professor of Medicine and Pediatrics at the Yale School of Medicine. "This is important because adolescents are the highest consumers of dietary added sugars. This is just the first step in understanding what is happening in the adolescent brain in response to consumption of sugary drinks. Ultimately, it will be important to investigate whether such exposure to sugar during adolescence impacts food and drink consumption, and whether it relates to the development of obesity."

Another study, by researchers in Germany at the University Children’s Hospital in Leipzig, compared fat cell composition and biology in lean and obese children and adolescents. They found that when children become obese, beginning as early as age six, there was an increase in the number of adipose cells, and that they are larger in size than the cells found in the bodies of lean children. The researchers also found evidence of dysfunction of the fat cells of obese children, including signs of inflammation, which can lead to insulin resistance, diabetes and other problems, such as high blood pressure.

"Our research shows that obese children start to have not only more but also larger adipocytes, or fat cells, at a very young age and that this is associated with increased inflammation and is linked to impaired metabolic function," said lead researcher Antje Körner, MD, Professor of Pediatrics and Pediatric Researcher at the Pediatric Research Center, University Children’s Hospital, Leipzig. "What we were interested in was seeing whether something was already going on with the adipose tissue itself if the children become obese at an early age, and it appears that there is. It’s important because this can contribute to the development of comorbidities of obesity in children, such as diabetes."

(Image caption: Brain scans show high activity in the medial prefrontal cortex (top) and striatum (bottom) while playing a competitive game. UC Berkeley and UIUC researchers have now found genetic variations in dopamine-regulating genes in the prefrontal cortex and striatum associated with differences in belief learning and reinforcement learning, respectively. Credit: Ming Hsu)

Your genes affect your betting behavior

Investors and gamblers take note: your betting decisions and strategy are determined, in part, by your genes.

Researchers from the University of California, Berkeley, National University of Singapore and University of Illinois at Urbana-Champaign (UIUC) have shown that betting decisions in a simple competitive game are influenced by the specific variants of dopamine-regulating genes in a person’s brain.

Dopamine is a neurotransmitter – a chemical released by brain cells to signal other brain cells – that is a key part of the brain’s reward and pleasure-seeking system. Dopamine deficiency leads to Parkinson’s disease, while disruption of the dopamine network is linked to numerous psychiatric and neurodegenerative disorders, including schizophrenia, depression and dementia.

While previous studies have shown the important role of the neurotransmitter dopamine in social interactions, this is the first study tying these interactions to specific genes that govern dopamine functioning.

“This study shows that genes influence complex social behavior, in this case strategic behavior,” said study leader Ming Hsu, an assistant professor of marketing in UC Berkeley’s Haas School of Business and a member of the Helen Wills Neuroscience Institute. “We now have some clues about the neural mechanisms through which our genes affect behavior.”

The implications for business are potentially vast but unclear, Hsu said, though one possibility is training workforces to be more strategic. But the findings could significantly affect our understanding of diseases involving dopamine, such as schizophrenia, as well as disorders of social interaction, such as autism.

“When people talk about dopamine dysfunction, schizophrenia is one of the first diseases that come to mind,” Hsu said, noting that the disease involves a very complex pattern of social and decision making deficits. “To the degree that we can better understand ubiquitous social interactions in strategic settings, it may help us understand how to characterize and eventually treat the social deficits that are symptoms of diseases like schizophrenia.”

Hsu, UIUC graduate student Eric Set and their colleagues, including Richard P. Ebstein and Soo Hong Chew from the National University of Singapore, will publish their findings the week of June 16 in the online early edition of the Proceedings of the National Academy of Sciences.

Two brain areas involved in competition

Hsu established two years ago that when people engage in competitive social interactions, such as betting games, they primarily call upon two areas of the brain: the medial prefrontal cortex, which is the executive part of the brain, and the striatum, which deals with motivation and is crucial for learning to acquire rewards. Functional magnetic resonance imaging (fMRI) scans showed that people playing these games displayed intense activity in these areas.

“If you think of the brain as a computing machine, these are areas that take inputs, crank them through an algorithm, and translate them into behavioral outputs,” Hsu said. “What is really interesting about these areas is that both are innervated by neurons that use dopamine.”

Hsu and Set of UIUC’s Department of Economics wanted to determine which genes involved in regulating dopamine concentrations in these brain areas were associated with strategic thinking, so they enlisted as subjects a group of 217 undergraduates at the National University of Singapore, all of whom had had their genomes scanned for some 700,000 genetic variants. The researchers focused on only 143 variants within 12 genes involved in regulating dopamine. Some of the 12 are primarily involved in regulating dopamine in the prefrontal cortex, while others primarily regulate dopamine in the striatum.

The competition was a game called patent race, commonly used by social scientists to study social interactions. It involves one person betting, via computer, with an anonymous opponent.

“We know from brain imaging studies that when people compete against one another, they actually engage in two distinct types of learning processes,” Set said, referring to Hsu’s 2012 study. “One type involves learning purely from the consequences of your own actions, called reinforcement learning. The other is a bit more sophisticated, called belief learning, where people try to make a mental model of the other players, in order to anticipate and respond to their actions.”

Trial-and-error learning vs belief learning

Using a mathematical model of brain function during competitive social interactions, Hsu and Set correlated performance in reinforcement learning and belief learning with different variants or mutations of the 12 dopamine-related genes, and discovered a distinct difference.

They found that differences in belief learning – the degree to which players were able to anticipate and respond to the actions of others, or to imagine what their competitor is thinking and respond strategically – was associated with variation in three genes which primarily affect dopamine functioning in the medial prefrontal cortex.

In contrast, differences in trial-and-error reinforcement learning – how quickly they forget past experiences and how quickly they change strategy – was associated with variation in two genes that primarily affect striatal dopamine.

Hsu said that the findings correlate well with previous brain studies showing that the prefrontal cortex is involved in belief learning, while the striatum is involved in reinforcement learning.

“We were surprised by the degree of overlap, but it hints at the power of studying the neural and genetic levels under a single mathematical framework, which is only beginning in this area,” he said.

Hsu is currently collaborating with other scientists to correlate career achievements in older adults with genes and performance on competitive games, to see which brain regions and types of learning are most important for different kinds of success in life.

Caffeine affects boys and girls differently after puberty

Caffeine intake by children and adolescents has been rising for decades, due in large part to the popularity of caffeinated sodas and energy drinks, which now are marketed to children as young as four. Despite this, there is little research on the effects of caffeine on young people.

One researcher who is conducting such investigations is Jennifer Temple, PhD, associate professor in the Department of Exercise and Nutrition Sciences, University at Buffalo School of Public Health and Health Professions.

Her new study finds that after puberty, boys and girls experience different heart rate and blood pressure changes after consuming caffeine. Girls also experience some differences in caffeine effect during their menstrual cycles.

The study, “Cardiovascular Responses to Caffeine by Gender and Pubertal Stage,” will be published online June 16 in the July 2014 edition of the journal Pediatrics.

Past studies, including those by this research team, have shown that caffeine increases blood pressure and decreases heart rate in children, teens and adults, including pre-adolescent boys and girls. The purpose here was to learn whether gender differences in cardiovascular responses to caffeine emerge after puberty and if those responses differ across phases of the menstrual cycle.

Temple says, “We found an interaction between gender and caffeine dose, with boys having a greater response to caffeine than girls, as well as interactions between pubertal phase, gender and caffeine dose, with gender differences present in post-pubertal, but not in pre-pubertal, participants.

“Finally,” she says, “we found differences in responses to caffeine across the menstrual cycle in post-pubertal girls, with decreases in heart rate that were greater in the mid-luteal phase and blood pressure increases that were greater in the mid-follicular phase of the menstrual cycle.

“In this study, we were looking exclusively into the physical results of caffeine ingestion,” she says.

Phases of the menstrual cycle, marked by changing levels of hormones, are the follicular phase, which begins on the first day of menstruation and ends with ovulation, and the luteal phase, which follows ovulation and is marked by significantly higher levels of progesterone than the previous phase.

Future research in this area will determine the extent to which gender differences are mediated by physiological factors such as steroid hormone level or by differences in patterns of caffeine use, caffeine use by peers or more autonomy and control over beverage purchases, Temple says.

This double-blind, placebo-controlled, dose-response study was funded by a grant from the National Institute on Drug Abuse of the National Institutes of Health. 

It examined heart rate and blood pressure before and after administration of placebo and two doses of caffeine (1 and 2 mg/kg) in pre-pubertal (8- to 9-year-old; n = 52) and post-pubertal (15- to 17-year-old; n = 49) boys (n = 54) and girls (n = 47).

Rescue of Alzheimer’s Memory Deficit Achieved by Reducing ‘Excessive Inhibition’

A new drug target to fight Alzheimer’s disease has been discovered by a research team led by Gong Chen, a Professor of Biology and the Verne M. Willaman Chair in Life Sciences at Penn State University. The discovery also has potential for development as a novel diagnostic tool for Alzheimer’s disease, which is the most common form of dementia and one for which no cure has yet been found. A scientific paper describing the discovery will be published in Nature Communications on 13 June 2014. 

Chen’s research was motivated by the recent failure in clinical trials of once-promising Alzheimer’s drugs being developed by large pharmaceutical companies. “Billions of dollars were invested in years of research leading up to the clinical trials of those Alzheimer’s drugs, but they failed the test after they unexpectedly worsened the patients’ symptoms,” Chen said. The research behind those drugs had targeted the long-recognized feature of Alzheimer’s brains: the sticky buildup of the amyloid protein known as plaques, which can cause neurons in the brain to die. “The research of our lab and others now has focused on finding new drug targets and on developing new approaches for diagnosing and treating Alzheimer’s disease,” Chen explained.

"We recently discovered an abnormally high concentration of one inhibitory neurotransmitter in the brains of deceased Alzheimer’s patients," Chen said. He and his research team found the neurotransmitter, called GABA (gamma-aminobutyric acid), in deformed cells called "reactive astrocytes" in a structure in the core of the brain called the dentate gyrus. This structure is the gateway to hippocampus, an area of the brain that is critical for learning and memory.  

Chen’s team found that the GABA neurotransmitter was drastically increased in the deformed versions of the normally large, star-shaped “astrocyte” cells which, in a healthy individual, surround and support individual neurons in the brain. “Our research shows that the excessively high concentration of the GABA neurotransmitter in these reactive astrocytes is a novel biomarker that we hope can be targeted in further research as a tool for the diagnosis and treatment of Alzheimer’s disease,” Chen said. 

Chen’s team developed new analysis methods to evaluate neurotransmitter concentrations in the brains of normal and genetically modified mouse models for Alzheimer’s disease (AD mice). “Our studies of AD mice showed that the high concentration of the GABA neurotransmitter in the reactive astrocytes of the dentate gyrus correlates with the animals’ poor performance on tests of learning and memory,” Chen said. His lab also found that the high concentration of the GABA neurotransmitter in the reactive astrocytes is released through an astrocyte-specific GABA transporter, a novel drug target found in this study, to enhance GABA inhibition in the dentate gyrus. With too much inhibitory GABA neurotransmitter, the neurons in the dentate gyrus are not fired up like they normally would be when a healthy person is learning something new or remembering something already learned.

Importantly, Chen said, “After we inhibited the astrocytic GABA transporter to reduce GABA inhibition in the brains of the AD mice, we found that they showed better memory capability than the control AD mice. We are very excited and encouraged by this result because it might explain why previous clinical trials failed by targeting amyloid plaques alone. One possible explanation is that while amyloid plaques may be reduced by targeting amyloid proteins, the other downstream alterations triggered by amyloid deposits, such as the excessive GABA inhibition discovered in our study, cannot be corrected by targeting amyloid proteins alone. Our studies suggest that reducing the excessive GABA inhibition to the neurons in the brain’s dentate gyrus may lead to a novel therapy for Alzheimer’s disease. An ultimate successful therapy may be a cocktail of compounds acting on several drug targets simultaneously.”