Beliefs can regulate effects of nicotine on the human brain

Two identical cigarettes led to a new discovery. Study participants inhaled nicotine, yet they showed significantly different brain activity. Why the difference? Some subjects were told their cigarettes were nicotine free. Credit: © Nomad_Soul / Fotolia
Two identical cigarettes led to a discovery by scientists at the Virginia Tech Carilion Research Institute. Study participants inhaled nicotine, yet they showed significantly different brain activity. Why the difference? Some subjects were told their cigarettes were nicotine free.

"Our research group has begun to show that beliefs are as powerful a physical influence on the brain as neuroactive drugs," said Read Montague, director of the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute and lead author of a study published this week in the Proceedings of the National Academy of Sciences.

Nicotine has formidable effects throughout the brain, especially in the reward-based learning pathways. Nicotine teaches the brain that smoking leads to reward. Once the brain learns that correlation, the addictive chemical cycle is difficult to break. In this study, scientists tracked the brain responses using functional magnetic resonance imaging.

"We suspected that we would be able to see neural signals based on the subjects' belief rather than their actual nicotine intake," said Montague, who is also a professor of physics in Virginia Tech's College of Science.

After smoking cigarettes, volunteers played a reward-based learning game while their brains were scanned. The subjects viewed a historical stock price graph, made an investment, and repeated the cycle multiple times.

Researchers used computational models of learning signals thought to be generated by the brain during these kinds of tasks. In each subject, the individually tracked signals were specifically influenced by beliefs about nicotine.

Montague and his team found that the people who believed they had smoked nicotine cigarettes made different choices and had different neural signals than the other participants, despite the fact that both groups had consumed the same substance.

The scientists also found people who believed they had smoked nicotine had significantly higher activity in their reward-learning pathways. Those who did not believe they had smoked nicotine did not exhibit those same signals.

"It was the belief alone that modulated activity in the learning pathway," Montague said. "This goes beyond the placebo effect."

Multiple studies support the placebo effect, showing sham treatments can improve a patient's condition simply because the person believed it would be helpful. In the current study, however, researchers found belief alone could actually erase or enhance the effects of nicotine in participants who were under the influence of the active drug.

The study was featured in an editorial commentary by Nora Volkow, director of the National Institute on Drug Abuse, in the Proceedings of the National Academy of Sciences.

"The current findings extend the relevance of dopamine-guided learning processes to the experience of how drug intoxication influences the way the human brain works and orchestrates our behaviors," Volkow wrote in the commentary.

Volkow suggested previously shrouded mechanisms behind beliefs and learned responses could be manipulated as a target for new addiction treatments.

"Nothing is more convincing than how a drug can make you feel differently," Montague said. "A drug can induce a belief state, which itself causes the change."

Scientists might be able to harness this belief system, capable of inducing physiological changes, to reverse-engineer addiction.

"Just as drugs micromanage the belief state," Montague said, "maybe we can micromanage beliefs to better effect behavior change in addiction."

Source: Virginia Tech

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Genetically speaking, mammals are more like their fathers

Newborn baby and his father's hand. Specifically, the research shows that although we inherit equal amounts of genetic mutations from our parents -- the mutations that make us who we are and not some other person -- we actually "use" more of the DNA that we inherit from our dads. Credit: © millaf / Fotolia

You might resemble or act more like your mother, but a novel research study from UNC School of Medicine researchers reveals that mammals are genetically more like their dads. Specifically, the research shows that although we inherit equal amounts of genetic mutations from our parents -- the mutations that make us who we are and not some other person -- we actually "use" more of the DNA that we inherit from our dads.

The research, published in the journal Nature Genetics, has wide implications for the study of human disease, especially when using mammalian research models. For instance, in many mouse models created for the study of gene expression related to disease, researchers typically don't take into account whether specific genetic expression originates from mothers or fathers. But the UNC research shows that inheriting a mutation has different consequences in mammals, depending on whether the genetic variant is inherited from the mother or father.

"This is an exceptional new research finding that opens the door to an entirely new area of exploration in human genetics," said Fernando Pardo-Manuel de Villena, PhD, professor of genetics and senior author of the paper. "We've known that there are 95 genes that are subject to this parent-of-origin effect. They're called imprinted genes, and they can play roles in diseases, depending on whether the genetic mutation came from the father or the mother. Now we've found that in addition to them, there are thousands of other genes that have a novel parent-of-origin effect."

These genetic mutations that are handed down from parents show up in many common but complex diseases that involve many genes, such as type-2 diabetes, heart disease, schizophrenia, obesity, and cancers. Studying them in genetically diverse mouse models that take parent-of-origin into account will give scientists more precise insights into the underlying causes of disease and the creation of therapeutics or other interventions.

The key to this research is the Collaborative Cross -- the most genetically diverse mouse population in the world, which is generated, housed, and distributed from UNC. Traditional lab mice are much more limited in their genetic diversity, and so they have limited use in studies that try to home in on important aspects of diseases in humans. The Collaborative Cross bred together various wild type mice to create wide diversity in the mouse genome. Pardo-Manuel de Villena said that this diversity is comparable to the variation found in the human genome. This helps scientists study diseases that involve various levels of genetic expression across many different genes.

Gene expression connects DNA to proteins, which then carry out various functions inside cells. This process is crucial for proper human health. Mutations that alter gene expression are called regulatory mutations.

"This type of genetic variation is probably the most important contributor -- not to simple Mendelian diseases where there's just one gene mutation [such as cystic fibrosis] -- but to much more common and complex diseases, such as diabetes, heart disease, neurological conditions, and a host of others," Pardo-Manuel de Villena said. "These diseases are driven by gene expression, not of one gene but of hundreds or thousands of genes.

"The Collaborative Cross and the expertise we have at UNC allow us to look at different gene expression for every gene in the genome of every kind of tissue," said Pardo-Manuel de Villena, who directs the Collaborative Cross.

For the Nature Genetics study, Pardo-Manuel de Villena's team, including first author James Crowley, PhD, assistant professor of genetics, selected three genetically diverse inbred strains of mice that were descended from a subspecies that evolved on different continents. These mice were bred to create nine different types of hybrid offspring in which each strain was used as both father and mother. When the mice reached adulthood, the researchers measured gene expression in four different kinds of tissue, including RNA sequencing in the brain. They then quantified how much gene expression was derived from the mother and the father for every single gene in the genome.

"We found that the vast majority of genes -- about 80 percent -- possessed variants that altered gene expression," Crowley said. "And this was when we discovered a new, genome-wide expression imbalance in favor of the dad in several hundred genes. This imbalance resulted in offspring whose brain gene expression was significantly more like their father's."

For every gene a scientist is interested in, Pardo-Manuel de Villena's team can create mice that have low, intermediate, or high expression of genes. And they can explore if that expression is associated with a specific disease.

"This expression level is dependent on the mother or the father," Pardo-Manuel de Villena said. "We now know that mammals express more genetic variance from the father. So imagine that a certain kind of mutation is bad. If inherited from the mother, the gene wouldn't be expressed as much as it would be if it were inherited from the father. So, the same bad mutation would have different consequences in disease if it were inherited from the mother or from the father."

These types of genetic mutations across hundreds of genes are hard to study and a major bottleneck to realizing the promises of the post-genome era. But Pardo-Manuel de Villena said, "Thanks to the Collaborative Cross, the mouse can be used to model how these genes work and how they impact health and disease in any kind of tissue in the body."

Source: University of North Carolina Health Care

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Old-looking galaxy in a young universe: Astronomers find dust in the early universe

This spectacular view from the NASA/ESA Hubble Space Telescope shows the rich galaxy cluster Abell 1689. The huge concentration of mass bends light coming from more distant objects and can increase their total apparent brightness and make them visible. One such object, A1689-zD1, is located in the box -- although it is still so faint that it is barely seen in this picture. New observations with ALMA and ESO's VLT have revealed that this object is a dusty galaxy seen when the Universe was just 700 million years old.  Credit: NASA; ESA; L. Bradley (Johns Hopkins University); R. Bouwens (University of California, Santa Cruz); H. Ford (Johns Hopkins University); and G. Illingworth (University of California, Santa Cruz)

Dust plays an extremely important role in the universe -- both in the formation of planets and new stars. But dust was not there from the beginning and the earliest galaxies had no dust, only gas. Now an international team of astronomers, led by researchers from the Niels Bohr Institute, has discovered a dust-filled galaxy from the very early universe. The discovery demonstrates that galaxies were very quickly enriched with dust particles containing elements such as carbon and oxygen, which could form planets. The results are published in the scientific journal, Nature.

Cosmic dust are smoke-like particles made up of either carbon (fine soot) or silicates (fine sand). The dust is comprised primarily of elements such as carbon, silicon, magnesium, iron and oxygen. The elements are synthesised by the nuclear combustion process in stars and driven out into space when the star dies and explodes. In space, they gather in clouds of dust and gas, which form new stars, and for each generation of new stars, more elements are formed. This is a slow process and in the very earliest galaxies in the history of the universe, dust had not yet formed.

But now a team of researchers have discovered a very distant galaxy that contains a large amount of dust, changing astronomers' previous calculations of how quickly the dust was formed.

"It is the first time dust has been discovered in one of the most distant galaxies ever observed -- only 700 million years after the Big Bang. It is a galaxy of modest size and yet it is already full of dust. This is very surprising and it tells us that ordinary galaxies were enriched with heavier elements far faster than expected," explains Darach Watson, an astrophysicist with the Dark Cosmology Centre at the Niels Bohr Institute at the University of Copenhagen.

Darach Watson led the project, with Lise Christensen from the Dark Cosmology Centre and researchers from Sweden, Scotland, France and Italy.

Lucky location

Because the galaxy is very distant and therefore incredibly faint, it would not usually be detectable from Earth. But a fortunate circumstance means the light from it has been amplified. This is because a large cluster of galaxies called Abell 1689, lies between the galaxy and Earth. The light is refracted by the gravity of the galaxy cluster, thus amplifying the distant galaxy. The phenomenon is called gravitational lensing and it works like a magnifying glass.

"We looked for the most distant galaxies in the universe. Based on the colours of the light observed with the Hubble Space Telescope we can see which galaxies could be very distant. Using observations from the very sensitive instrument, the X-shooter spectrograph on the Large Telescope, VLT in Chile, we measured the galaxy's spectrum and from that calculated its redshift, i.e. the change in the light's wavelength as the object recedes from us. From the redshift we can calculate the galaxy's distance from us and it turned out to be, as we suspected, one of the most distant galaxies we know of to date," explains Lise Christensen, an astrophysicist at the Dark Cosmology Centre at the Niels Bohr Institute.

Early planet formation

Darach Watson explains that they then studied the galaxy with the ALMA telescopes, which can observe far-infrared wavelengths and then it became really interesting, because now they could see that the galaxy was full of dust. He explains that young stars in early galaxies emit hot ultraviolet light. The hot ultraviolet radiation heats the surrounding ice-cold dust, which then emits light in the far-infrared.

"It is this far-infrared light, which tells us that there is dust in the galaxy. It is very surprising and it is the first time that dust has been found in such an early galaxy. The process of star formation must therefore have started very early in the history of the universe and be associated with the formation of dust. The detection of large amounts of solid material shows that the galaxy was enriched very early with solids which are a prerequisite for the formation of complex molecules and planets," explains Darach Watson.

Now the researchers hope that future observations of a large number of distant galaxies using the ALMA telescopes could help unravel how frequently such evolved galaxies occur in this very early epoch of the history of the universe.

Source: University of Copenhagen - Niels Bohr Institute

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Newborn neurons in adult brain may help us adapt to environment

Neurons . "New neurons may serve as a means to fine-tune the hippocampus to the predicted environment," Opendak says. "In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain.
Credit: © ktsdesign / Fotolia
The discovery that the human brain continues to produce new neurons in adulthood challenged a major dogma in the field of neuroscience, but the role of these neurons in behavior and cognition is still not clear. In a review article published by Cell Press February 21st in Trends in Cognitive Sciences, Maya Opendak and Elizabeth Gould of Princeton University synthesize the vast literature on this topic, reviewing environmental factors that influence the birth of new neurons in the adult hippocampus, a region of the brain that plays an important role in memory and learning.

The authors discuss how the birth of such neurons may help animals and humans adapt to their current environment and circumstances in a complex and changing world. They advocate for testing these ideas using naturalistic designs, such as allowing laboratory rodents to live in more natural social burrow settings and observing how circumstances such as social status influence the rate at which new neurons are born.

"New neurons may serve as a means to fine-tune the hippocampus to the predicted environment," Opendak says. "In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain. However, more naturalistic experimental conditions may be a necessary step toward understanding the adaptive significance of neurons born in the adult brain."

In recent years, it has become increasingly clear that environmental influences have a profound effect on the adult brain in a wide range of mammalian species. Stressful experiences, such as restraint, social defeat, exposure to predator odors, inescapable foot shock, and sleep deprivation, have been shown to decrease the number of new neurons in the hippocampus. By contrast, more rewarding experiences, such as physical exercise and mating, tend to increase the production of new neurons in the hippocampus.

The birth of new neurons in adulthood may have important behavioral and cognitive consequences. Stress-induced suppression of adult neurogenesis has been associated with impaired performance on hippocampus-dependent cognitive tasks, such as spatial navigation learning and object memory. Stressful experiences have also been shown to increase anxiety-like behaviors that are associated with the hippocampus. In contrast, rewarding experiences are associated with reduced anxiety-like behavior and improved performance on cognitive tasks involving the hippocampus.

Although scientists generally agree that our day-to-day actions change our brains even in adulthood, there is some disagreement on the adaptive significance of new neurons. For instance, the literature presents mixed findings on whether new neurons generated under a specific experimental condition are geared toward the recognition of that particular experience or if they provide a more naive pool of new neurons that enable environmental adaptation in the future.

Gould and her collaborators recently proposed that stress-induced decreases in new neuron formation might improve the chances of survival by increasing anxiety and inhibiting exploration, thereby prioritizing safety and avoidant behavior at the expense of performing optimally on cognitive tasks. On the other hand, reward-induced increases in new neuron number may reduce anxiety and facilitate exploration and learning, leading to greater reproductive success.

"Because the past is often the best predictor of the future, a stress-modeled brain may facilitate adaptive responses to life in a stressful environment, whereas a reward-modeled brain may do the same but for life in a low-stress, high-reward environment," says Gould, a professor of psychology and neuroscience at Princeton University.

However, when aversive experiences far outnumber rewarding ones in both quantity and intensity, the system may reach a breaking point and produce a maladaptive outcome. For example, repeated stress produces continued reduction in the birth of new neurons, and ultimately the emergence of heightened anxiety and depressive-like symptoms.

"Such a scenario could represent processes that are engaged under pathological conditions and may be somewhat akin to what humans experience when exposed to repeated traumatic stress," Opendak says.

Because many studies that investigate adult neurogenesis use controlled laboratory conditions, the relevance of the findings to real-world circumstances remains unclear. The use of a visible burrow system--a structure consisting of tubes, chambers, and an open field--has allowed researchers to recreate the conditions that allow for the production of dominance hierarchies that rats naturally form in the wild, replicating the stressors, rewards, and cognitive processes that accompany this social lifestyle.

"This more realistic setting has revealed individual differences in adult neurogenesis, with more new neurons produced in dominant versus subordinate male rats," Gould says. "Taking findings from laboratory animals to the next level by exploring complex social interactions in settings that maximize individual variability, a hallmark of the human experience, is likely to be especially illuminating."

Source: Cell Press

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