(Image caption: Positron-Emission-Tomography (PET) of a depressive patient without medication (left) with elevated monoamine-oxidase-A-levels (green, yellow, red) and after a six-week-treatment with the monoamine-oxidase-A-inhibitor moclobemid (right). Credit: © Sacher et al., 2011, J Psy Neurosci.)

Monoamine oxidase A: biomarker for postpartum depression

Many women suffer from baby blues after giving birth. Some even develop full-blown postpartum depression in the weeks that follow. Monoamine oxidase A, an enzyme responsible for the breakdown of neurotransmitters like dopamine and serotonin, plays an important role in this condition. In comparison to healthy women, women who experience postpartum depression present strongly elevated levels of the enzyme in their brains. This was discovered by a Canadian-German research team including Julia Sacher from the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig. Their findings could help in the prevention of postpartum depression and in the development of new drugs for its treatment.

For most women, the birth of their baby is one of the most strenuous but also happiest days in their lives. However, joy and happiness are often followed by fatigue and exhaustion. The vast majority of women experience a temporary drop in mood for a few days after birth. These symptoms of “baby blues” are not an illness; however, in some cases they can represent early signs of an imminent episode of depression: in 13 percent of mothers, the emotional turmoil experienced after childbirth leads to the development of a full-blown postpartum depression. Postpartum depression is harmful not only to the mother, but also to the baby. It is difficult to treat this condition effectively, as its precise neurobiological causes have remained unidentified to date.

The new study shows that postpartum depression is accompanied by strongly elevated monoamine oxidase A in the brain, particularly in the prefrontal cortex and in the anterior cingulate cortex. In women with postpartum depression, the values recorded were 21 percent higher than those of women who were not plagued by negative feelings after giving birth. Women who did not develop full-blown depression but found themselves crying more often than usual due to depressed mood also presented moderately elevated values.

“Therefore, we should promote strategies that help to reduce monoamine oxidase A levels in the brain, and avoid everything that makes these values rise,” explains Sacher. Such factors include heavy smoking, alcohol consumption and chronic stress, for example when the mother feels neglected and abandoned by her partner and family. “My ultimate goal is to provide women and their families with very concrete lifestyle recommendations that will enable them to prevent postpartum depression,” explains the psychiatrist.

A new generation of long-established drugs could also play an important role in the treatment of postpartum depression in future. Up to now, depressed mothers are mainly given drugs that increase the concentration of serotonin in the brain. However, because monoamine oxidase A breaks down not only serotonin but also other monoamines like dopamine and noradrenaline, a treatment that directly targets monoamine oxidase A could have a higher success rate, particularly in very serious cases: this alternative is provided by selective and reversible monoamine-oxidase- A inhibitors. “The first monoamine oxidase inhibitors often had severe side effects, for example hypertensive crises, which necessitated adherence to a strict diet,” explains Sacher. “However, the new selective and reversible drugs are better tolerated,” she adds. In the next stage of this research involving clinical trials, the scientists intend to test the effectiveness of these reversible monoamine oxidase A inhibitors in the treatment of postpartum depression.

Because the measurement of this enzyme in the brain requires complex technology, it is not suitable for routine testing. Thus, the researchers are also looking for a peripheral marker of this enzyme that can be detected in saliva or blood.

Four years ago, Julia Sacher and her colleagues at the Centre for Addiction and Mental Health CAMH in Toronto already succeeded in showing that, in the first week postpartum, the concentration of the enzyme monoamine oxidase A in the brain is on average 40 percent higher than in women who had not recently given birth. “The monoamine oxidase A values behave in the opposite way to oestrogen levels. When oestrogen levels drop acutely after childbirth, the concentration of monoamine oxidase A rises. This drastic change also influences serotonin levels, known as the happiness hormone,” explains Dr. Sacher. In most women, the values quickly return to normal. In others, they remain raised – and thereby promote the development of depression.

Brain’s dynamic duel underlies win-win choices

People choosing between two or more equally positive outcomes experience paradoxical feelings of pleasure and anxiety, feelings associated with activity in different regions of the brain, according to research led by Amitai Shenhav, an associate research scholar at the Princeton Neuroscience Institute at Princeton University.

In one experiment, 42 people rated the desirability of more than 300 products using an auction-like procedure. Then they looked at images of paired products with different or similar values and were asked to choose between them. Their brain activity was scanned using functional magnetic resonance imaging (fMRI). After the scan, participants reported their feelings before and during each choice. They received one of their choices at the end of the study.

Choices between two highly valued items (high-high), such as a digital camera and a camcorder, were associated with the most positive feelings and the greatest anxiety, compared with choices between items of low value (low-low), like a desk lamp and a water bottle, or between items of different values (low-high). Functional MRI scans showed activity in two regions of the brain, the striatum and the prefrontal cortex, both known to be involved in decision-making. Interestingly, lower parts of both regions were more active when subjects felt excited about being offered the choice, while activity in upper parts was strongly tied to feelings of anxiety.

This evidence that parallel brain circuits are associated with opposing emotional reactions helps to answer a puzzling question, according to Shenhav: “Why isn’t our positivity quelled by our anxiety, or our anxiety quelled by the fact that we’re getting this really good thing at the end? This suggests that it’s because these circuits evolved for two different reasons,” he said. “One of them is about evaluating the thing we’re going to get, and the other is about guiding our actions and working out how difficult the choice will be.”

The study, “Neural correlates of dueling affective reactions to win-win choices,” was published July 14 in the Proceedings of the National Academy of Sciences. Shenhav conducted the research as a graduate student at Harvard University, along with Professor of Psychology and Neuroscience Randy Buckner, the study’s senior author.

A second fMRI experiment showed that the same patterns of emotional reactions and brain activity persisted even when the participants were told before each choice how similarly they had valued the items. Their anxiety didn’t abate, despite knowing how little they stood to lose by making a “wrong” choice. In a third experiment, Shenhav and Buckner tested whether giving people more than two choices increased their levels of anxiety. Indeed, they found that providing six options led to higher levels of anxiety than two options, particularly when all six of the options were highly valued items. But positive feelings about being presented with the choice were similar for two or six options.

This suggests that the anxiety stems from the conflict of making the decision, rather than the opportunity cost of the choice — an economic concept that refers to the lost value of the second-best option. The opportunity cost should be the same, regardless of the number of choices. In addition, subjects in this final study were given an unlimited amount of time to make a decision, compared with 1.5 seconds in the first two studies. The results showed that time pressure was not the main source of anxiety during the choices.

At the end of each study, participants had a surprise opportunity to reverse their earlier choices. Higher activity in a part of the brain called the anterior cingulate cortex around the time of an initial choice predicted whether that decision would later be reversed. Previous work has shown that this brain region is involved in assessing how conflicted an individual feels over a particular choice; this result suggests that some choices may have continued to elicit conflict after the participant made a decision, Shenhav said. The researchers also found that people who reported more anxiety in their daily lives were more likely to change their minds. 

This work could explain why ostensibly positive options can evoke a mixture of positive and negative responses, which are not explained by purely economic analyses of choice. “Rationally, there’s no reason why when you put one good thing with another good thing, you should feel worse about the situation,” said Brian Knutson, an associate professor of psychology and neuroscience at Stanford University, who is familiar with the work but was not involved in it. “The neuroimaging tells us that these different mechanisms are fighting with each other,” he said. “Understanding that dynamic can help us understand why decisions that we think should make us feel better can actually make us feel worse.”

According to Shenhav, this research could shed light on the neural processes that can make more momentous choices so paralyzing for some people — for instance, deciding where to go to college or which job offer to take. But he admits that even more trivial decisions can be tough for him. “I probably experience more win-win choice anxiety than the average person,” he said. “I’m even terrible at choosing where to eat dinner.”

Try, try again? Study says no

When it comes to learning languages, adults and children have different strengths. Adults excel at absorbing the vocabulary needed to navigate a grocery store or order food in a restaurant, but children have an uncanny ability to pick up on subtle nuances of language that often elude adults. Within months of living in a foreign country, a young child may speak a second language like a native speaker.

Brain structure plays an important role in this “sensitive period” for learning language, which is believed to end around adolescence. The young brain is equipped with neural circuits that can analyze sounds and build a coherent set of rules for constructing words and sentences out of those sounds. Once these language structures are established, it’s difficult to build another one for a new language.

In a new study, a team of neuroscientists and psychologists led by Amy Finn, a postdoc at MIT’s McGovern Institute for Brain Research, has found evidence for another factor that contributes to adults’ language difficulties: When learning certain elements of language, adults’ more highly developed cognitive skills actually get in the way. The researchers discovered that the harder adults tried to learn an artificial language, the worse they were at deciphering the language’s morphology — the structure and deployment of linguistic units such as root words, suffixes, and prefixes.

“We found that effort helps you in most situations, for things like figuring out what the units of language that you need to know are, and basic ordering of elements. But when trying to learn morphology, at least in this artificial language we created, it’s actually worse when you try,” Finn says.

Finn and colleagues from the University of California at Santa Barbara, Stanford University, and the University of British Columbia describe their findings in the July 21 issue of PLoS One. Carla Hudson Kam, an associate professor of linguistics at British Columbia, is the paper’s senior author.

Too much brainpower

Linguists have known for decades that children are skilled at absorbing certain tricky elements of language, such as irregular past participles (examples of which, in English, include “gone” and “been”) or complicated verb tenses like the subjunctive.

“Children will ultimately perform better than adults in terms of their command of the grammar and the structural components of language — some of the more idiosyncratic, difficult-to-articulate aspects of language that even most native speakers don’t have conscious awareness of,” Finn says.

In 1990, linguist Elissa Newport hypothesized that adults have trouble learning those nuances because they try to analyze too much information at once. Adults have a much more highly developed prefrontal cortex than children, and they tend to throw all of that brainpower at learning a second language. This high-powered processing may actually interfere with certain elements of learning language.

“It’s an idea that’s been around for a long time, but there hasn’t been any data that experimentally show that it’s true,” Finn says.

Finn and her colleagues designed an experiment to test whether exerting more effort would help or hinder success. First, they created nine nonsense words, each with two syllables. Each word fell into one of three categories (A, B, and C), defined by the order of consonant and vowel sounds.

Study subjects listened to the artificial language for about 10 minutes. One group of subjects was told not to overanalyze what they heard, but not to tune it out either. To help them not overthink the language, they were given the option of completing a puzzle or coloring while they listened. The other group was told to try to identify the words they were hearing.

Each group heard the same recording, which was a series of three-word sequences — first a word from category A, then one from category B, then category C — with no pauses between words. Previous studies have shown that adults, babies, and even monkeys can parse this kind of information into word units, a task known as word segmentation.

Subjects from both groups were successful at word segmentation, although the group that tried harder performed a little better. Both groups also performed well in a task called word ordering, which required subjects to choose between a correct word sequence (ABC) and an incorrect sequence (such as ACB) of words they had previously heard.

The final test measured skill in identifying the language’s morphology. The researchers played a three-word sequence that included a word the subjects had not heard before, but which fit into one of the three categories. When asked to judge whether this new word was in the correct location, the subjects who had been asked to pay closer attention to the original word stream performed much worse than those who had listened more passively.

“This research is exciting because it provides evidence indicating that effortful learning leads to different results depending upon the kind of information learners are trying to master,” says Michael Ramscar, a professor of linguistics at the University of Tübingen who was not part of the research team. “The results indicate that learning to identify relatively simple parts of language, such as words, is facilitated by effortful learning, whereas learning more complex aspects of language, such as grammatical features, is impeded by effortful learning.”

Turning off effort

The findings support a theory of language acquisition that suggests that some parts of language are learned through procedural memory, while others are learned through declarative memory. Under this theory, declarative memory, which stores knowledge and facts, would be more useful for learning vocabulary and certain rules of grammar. Procedural memory, which guides tasks we perform without conscious awareness of how we learned them, would be more useful for learning subtle rules related to language morphology.

“It’s likely to be the procedural memory system that’s really important for learning these difficult morphological aspects of language. In fact, when you use the declarative memory system, it doesn’t help you, it harms you,” Finn says.

Still unresolved is the question of whether adults can overcome this language-learning obstacle. Finn says she does not have a good answer yet but she is now testing the effects of “turning off” the adult prefrontal cortex using a technique called transcranial magnetic stimulation. Other interventions she plans to study include distracting the prefrontal cortex by forcing it to perform other tasks while language is heard, and treating subjects with drugs that impair activity in that brain region.

Do not disturb! How the brain filters out distractions

You know the feeling? You are trying to dial a phone number from memory… you have to concentrate…. then someone starts shouting out other numbers nearby. In a situation like that, your brain must ignore the distraction as best it can so as not to lose vital information from its working memory. A new paper published in Neuron by a team of neurobiologists led by Professor Andreas Nieder at the University of Tübingen gives insight into just how the brain manages this problem.

The researchers put rhesus monkey in a similar situation. The monkeys had to remember the number of dots in an image and reproduce the knowledge a moment later. While they were taking in the information, a distraction was introduced, showing a different number of dots. And even though the monkeys were mostly able to ignore the distraction, their concentration was disturbed and their memory performance suffered.

Measurements of the electrical activity of nerve cells in two key areas of the brain showed a surprising result: nerve cells in the prefrontal cortex signaled the distraction while it was being presented, but immediately restored the remembered information (the number of dots) once the distraction was switched off. In contrast, nerve cells in the parietal cortex were unimpressed by the distraction and reliably transmitted the information about the correct number of dots.

These findings provide important clues about the strategies and division of labor among different parts of the brain when it comes to using the working memory. “Different parts of the brain appear to use different strategies to filter out distractions,” says Dr. Simon Jacob, who carried out research in Tübingen before switching to the Psychiatric Clinic at the Charité hospitals in Berlin. “Nerve cells in the parietal cortex simply suppress the distraction, while nerve cells in the prefrontal cortex allow themselves to be momentarily distracted – only to return immediately to the truly important memory content.”

The researchers were surprised by the two brain areas’ difference in sensitivity to distraction. “We had assumed that the prefrontal cortex is able to filter out all kinds of distractions, while the parietal cortex was considered more vulnerable to disturbances,” says Professor Nieder. “We will have to rethink that. The memory-storage tasks and the strategies of each brain area are distributed differently from what we expected.”

Upfront and personal: Scientists model human reasoning in the brain’s prefrontal cortex

Located at the forward end of the brain’s frontal lobe, the mammalian prefrontal cortex (PFC) is the seat of many of our most unique cognitive abilities – collectively referred to as executive function – including planning, decision-making, and coordinating thoughts and actions with internal goals. That said, perhaps its most important attribute – one that is apparently unique to H. sapiens – is reasoning which, based on Bayesian, or probabilistic, inference, mitigates uncertainty by informing adaptive behavior. While the structural details of this remarkable process have historically remained elusive, scientists at Institut National de la Santé et de la Recherche Médicale, Paris, and Ecole Normale Supérieure, Paris and Université Pierre et Marie Curie, Paris have recently employed computational modeling and neuroimaging to show that the human prefrontal cortex involves two interactive reasoning pathways that embody hypothesis testing for evaluating, accepting and rejecting behavioral strategies. More specifically, their model describes behavior guided by reason in the form of an online algorithm combining Bayesian inference applied to multiple stored strategies with hypothesis testing that can update these strategies. In addition – as proposed in a previous work – the scientists conclude that since the frontopolar cortex (FPC), located in the anterior-most portion of the frontal lobes, is human-specific and is a key component in executive function decision-making, the ability to make inferences on concurrent strategies and decide to switch directly to one of these alternative strategies is unique to humans as well.

Prof. Etienne Koechlin discussed the paper that he, Dr. Maël Donoso and Dr. Anne G. E. Collins published in Science.

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How the brain processes visual information

MSU’s Behrad Noudoost was a co-author with Marc Zirnsak and other neuroscientists from the Tirin Moore Lab at Stanford University in publishing a recent paper on the research in Nature, an international weekly journal for natural sciences.

Noudoost and the team studied saccadic eye movements—those movements where the eye jumps from one point of focus to another—in an effort to determine exactly how this happens without us being overcome by our brains processing too much visual information.

To introduce the study, Noudoost first gets his audience to think about eye movements at the most basic level. “Look in the mirror and stare at one eye,” Noudoost said. “Then look at the other eye. We are essentially blind during eye movement as we cannot see our eyes move, even though we know they did.”

According to Noudoost, scientists have been trying to learn exactly how the brain processes these visual stimuli during saccadic eye movement and this research offers new evidence that the prefrontal cortex of the brain is responsible for visual stability.

"Visual stability is what keeps our vision stable in spite of changing input. It is similar to the stabilizer button on a video camera," Noudoost said.

"We wanted to know what causes the brain to filter out un-necessary information when we shift our vision from one focal target to another," Noudoost said. "Without that filter the visual information would overwhelm us."

According to the scientists, the study offers evidence neurons in the prefrontal cortex of the brain start processing information in anticipation of where we are going to look before we ever do it, suggesting that selective processing might be the mechanism for visual stability.

Noudoost said this new information can help scientists better understand the underlying causes of problems such as dyslexia and attention deficit disorders.

According to Frances Lefcort, the head of the Department of Cell Biology and Neuroscience, the team’s basic research may have implications for understanding a myriad of mental health issues.

"Schizophrenia and attention deficit disorders have been linked to visual stability, so the work Behrad is doing offers valuable knowledge to other scientists working in cognitive neuroscience," Lefcort said.

"Understanding how a healthy brain works is important in terms of knowing its impact on cognitive functions such as memory, learning and in this case attention," Noudoost said. "By exploring normal brain function, we can better understand what happens in someone with a mental illness."

According to Lefcort, Noudoost and neuroscience professor Charles Gray are strengthening MSU’s contribution to the field of cognitive neuroscience.

"Behrad is an exquisitely trained neuroscientist. He offers students a viewpoint as both scientist and a physician," Lefcort said. "We are thrilled to have him and he has already brought new energy and is bolstering our impact on the growing field of brain research."

Noudoost joined MSU’s Department of Cell Biology and Neuroscience last summer from Stanford University and has already been awarded a $225,000 Whitehall Foundation grant for neuroscience. Whitehall Foundation grants are awarded to established scientists working in neurobiology.

"I am colorblind and I wanted to see the world as others could see it," Noudoost said explaining why he was first drawn into this type of research. "Although I still don’t see the world in the same colors as everyone else, I am more amazed everyday by the brain."