My mistake or yours? How the brain decides

Humans and other animals learn by making mistakes. They can also learn from observing the mistakes of others. The brain processes self-generated errors in a region called the medial frontal cortex (MFC) but little is known about how it processes the observed errors of others. A Japanese research team led by Masaki Isoda and Atsushi Iriki of the RIKEN Brain Science Institute has now demonstrated that the MFC is also involved in processing observed errors.

The team studied the brains of monkeys while the animals performed the same task. Two monkeys sat opposite each other and took turns to choose between a yellow and green button, one of which resulted in a liquid reward for both. Each monkey’s turn consisted of two choices.

After blocks of between 5 and 17 choices, the button that resulted in reward was switched unpredictably, usually causing an error on the next choice. The choices made by each monkey immediately after such errors, or errors that were random, showed that they used both their own errors and their partner’s to guide their subsequent choices. While the monkeys performed this task, the researchers recorded activity of single neurons in their brains.

In this way they were able to determine which behavioural aspect was most closely associated with each neuron’s activity, explains Isoda. “We found that many neurons in the medial frontal cortex were not activated when the monkey made an error itself, but they became active when their partner made an error.” This brain activity shows that it is the MFC which processes observations of another’s error, and the corresponding behavior shows that observing and processing such errors guides subsequent actions.

“Such error identification and subsequent error correction are of crucial importance for developing and maintaining successful social communities,” says Isoda. “Humans are tuned into other people’s mistakes not only for competitive success, but also for cooperative group living. If non-invasive techniques become available in humans, then we should be able to identify medial frontal neurons that behave similarly.”

Having identified the MFC as being involved, Isoda now wants to delve deeper into the process. “The next steps will be to clarify whether the inactivation of medial frontal cortex neurons reduces the ability to identify others’ errors, and to determine whether other brain regions are also involved in the processing of others’ errors.”

Banded mongooses structure monosyllabic sounds in a similar way to humans

Animals are more eloquent than previously assumed. Even the monosyllabic call of the banded mongoose is structured and thus comparable with the vowel and consonant system of human speech. Behavioral biologists from the University of Zurich have thus become the first to demonstrate that animals communicate with even smaller sound units than syllables.

When humans speak, they structure individual syllables with the aid of vowels and consonants. Due to their anatomy, animals can only produce a limited number of distinguishable sounds and calls. Complex animal sound expressions such as whale and bird songs are formed because smaller sound units – so-called “syllables” or “phonocodes” – are repeatedly combined into new arrangements. However, it was previously assumed that monosyllabic sound expressions such as contact or alarm calls do not have any combinational structures. Behavioral biologist Marta Manser and her doctoral student David Jansen from the University of Zurich have now proved that the monosyllabic calls of banded mongooses are structured and contain different information. They thus demonstrate for the first time that animals also have a sound expression structure that bears a certain similarity to the vowel and consonant system of human speech.

David A.W.A.M. Jansen, Michael A. Cant, and Marta B. Manser. Segmental concatenation of individual signatures and context cues in banded mongoose (Mungos mungo) close calls. BMC Biology

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Confocal micrograph of a primary human fibroblast cell grown in culture stained blue for actin, a highly abundant protein that makes up the cytoskeleton of cells. Energy-producing mitochondria are shown in green. Image courtesy of Matthew Daniels, University of Oxford and Wellcome Images.

Regulating Single Protein Prompts Fibroblasts to Become Neurons

Repression of a single protein in ordinary fibroblasts is sufficient to directly convert the cells – abundantly found in connective tissues – into functional neurons. The findings, which could have far-reaching implications for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s, will be published online in advance of the January 17 issue of the journal Cell.

In recent years, scientists have dramatically advanced the ability to induce pluripotent stem cells to become almost any type of cell, a major step in many diverse therapeutic efforts.  The new study focuses upon the surprising and singular role of PTB, an RNA-binding protein long known for its role in the regulation of alternative RNA splicing.

In in vitro experiments, scientists at University of California, San Diego School of Medicine and Wuhan University in China describe the protein’s notable regulatory role in a feedback loop that also involves microRNA – a class of small molecules that modulate the expression of up to 60 percent of genes in humans. Approximately 800 miRNAs have been identified and characterized to various degrees.

One of these miRNAs, known as miR-124, specifically modulates levels of PTB during brain development. The researchers found that when diverse cell types were depleted of PTB, they became neuronal-like cells or even functional neurons – an unexpected effect. The protein, they determined, functions in a complicated loop that involves a group of transcription factors dubbed REST that silences the expression of neuronal genes in non-neuronal cells.

According to principal investigator Xiang-Dong Fu, PhD, professor of cellular and molecular medicine at UC San Diego, it’s not known which neuronal signal or signals turn on the loop, which in principle can happen at any point in the circle. But the ability to artificially manipulate PTB levels in cells, inducing them to become neurons, offers tantalizing possibilities for scientists seeking new treatments for an array of neurodegenerative diseases.

It is estimated that over a lifetime, one in four Americans will suffer from a neurodegenerative disease, from Alzheimer’s and Parkinson’s to multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease).

“All of these diseases are currently incurable. Existing therapies focus on simply trying to preserve neurons or slow the rate of degeneration,” said Fu. “People are working with the idea of replacing lost neurons using embryonic stem cells, but there are a lot of challenges, including issues like the use of foreign DNA and the fact that it’s a very complex process with low efficiency.”

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The pilot and autopilot within our mind-brain connection

Have you ever driven to work so deep in thought that you arrive safely yet can’t recall the drive itself? And if so, what part of “you” was detecting cars and pedestrians, making appropriate stops and turns? Although when you get to work you can’t remember the driving experience, you are likely to have exquisite memory about having planned your day.

How does one understand this common experience? This is the question posed by Professor of Biology, John Lisman and his former undergraduate student, Eliezer J. Sternberg, now in medical school, in a recent paper in the Journal of Cognitive Neuroscience. Lisman explains that once a task such as driving has become a habit, you can perform another task at the same time, such as planning your day. But looking closer at these two behaviors, driving and planning, one can see interesting differences. The Habit system that is driving you to work is non-flexible: if the new parking regulations at work require you to go left instead or right, the likelihood that you’ll go right is very high. On the other hand, if you heard yesterday that your boss has scheduled a group meeting for noon, the likehood that you’ll plan your day accordingly is high. In other words, your non-habit system is flexible.

What interests Lisman and Sternberg is the relationship of the habit/non-habit systems to concepts of conscious vs unconscious. These concepts were popularized by Freud, who posited a duality of the human mind. Behavior can be influenced by both the conscious system and unconscious system. Freud compared the mind to an iceberg——with the small conscious system above water and the larger unconscious system below. Modern cognitive neuroscience now accepts this duality.

The mind can be described as having an unconscious and conscious part. And the brain can be described as having both habit and non-habit systems. Lisman and Sternberg argue that these two views can be merged: there is a habit system of which we are unconscious and a non-habit system of which we are conscious.

This simple equation turns out to have enormous implications for research on the mind-brain connection. Experiments on consciousness are done in humans because you can ask them to report their awareness, something you can’t do with animals. On the other hand, there are many invasive procedures for studying what’s happening in the brain of animals. So how can you study consciousness in rats?

Lisman and Sternberg provide a simple answer — ask whether rats have habit and non-habits. Scientific literature demonstrates that rats indeed have both habits and non-habits. For instance, when a rat comes to a choice point on a maze (and the reward site is to left), rats display very different behavior depending on how much experience they’ve had with that maze. With relatively little experience, rats pause at the choice point and look both ways before making a decision; in contrast, a highly experienced rats zooms left without stopping. Experiments have shown that different parts of the brain are involved in these two phases. Lisman and Sternberg make two conclusions: first, that rats, like us, have conscious and unconscious parts of the brain and second, that from experiments on rats we can learn to identify the parts of the brain that mediate conscious vs unconscious processes.

In their paper, Lisman and Sternberg also discuss potential objections to their hypothesis, and suggest further tests.

(Photo: GETTY)

Are Crows Mind Readers … Or Just Stressed Out?

Are crows mind readers? Recent studies have suggested that the birds hide food because they think others will steal it — a complex intuition that has been seen in only a select few creatures. Some critics have suggested that the birds might simply be stressed out, but new research reveals that crows may be gifted after all.

Cracks first began forming in the crow mind-reading hypothesis last year. One member of a research team from the University of Groningen in the Netherlands spent 7 months in bird cognition expert Nicola Clayton’s University of Cambridge lab in the United Kingdom studying Western scrub jays, a member of the crow family that is often used for these studies. The Groningen team then developed a computer model in which "virtual jays" cached food under various conditions. In PLOS ONE, they argued that the model showed the jays’ might be moving their food—or recaching it—not because they were reading the minds of their competitors, but simply because of the stress of having another bird present (especially a more dominant one) and of losing food to thieves. The result contradicted previous work by Clayton’s group suggesting that crows might have a humanlike awareness of other creatures’ mental states—a cognitive ability known as theory of mind that has been claimed in dogs, chimps, and even rats.

In the new study, Clayton and her Cambridge graduate student James Thom decided to test the stress hypothesis. First, they replicated earlier work on scrub jays by letting the birds hide peanuts in trays of ground corn cobs—either unobserved or with another bird watching—and later giving them a chance to rebury them. As in previous studies, the jays recached a much higher proportion of the peanuts if another bird could see them: nearly twice as much as in private, the team reports online today in PLOS ONE.

Dopamine regulates the motivation to act

The widespread belief that dopamine regulates pleasure could go down in history with the latest research results on the role of this neurotransmitter. Researchers have proved that it regulates motivation, causing individuals to initiate and persevere to obtain something either positive or negative.

The neuroscience journal Neuron publishes an article by researchers at the Universitat Jaume I of Castellón that reviews the prevailing theory on dopamine and poses a major paradigm shift with applications in diseases related to lack of motivation and mental fatigue and depression, Parkinson’s, multiple sclerosis, fibromyalgia, etc. and diseases where there is excessive motivation and persistence as in the case of addictions.

"It was believed that dopamine regulated pleasure and reward and that we release it when we obtain something that satisfies us, but in fact the latest scientific evidence shows that this neurotransmitter acts before that, it actually encourages us to act. In other words, dopamine is released in order to achieve something good or to avoid something evil", explains Mercè Correa.

Studies had shown that dopamine is released by pleasurable sensations but also by stress, pain or loss. These research results however had been skewed to only highlight the positive influence, according to Correa. The new article is a review of the paradigm based on the data from several investigations, including those conducted over the past two decades by the Castellón group in collaboration with the John Salamone of the University of Connecticut (USA), on the role of dopamine in the motivated behaviour in animals.

The level of dopamine depends on individuals, so some people are more persistent than others to achieve a goal. “Dopamine leads to maintain the level of activity to achieve what is intended. This in principle is positive, however, it will always depend on the stimuli that are sought: whether the goal is to be a good student or to abuse of drugs” says Correa. High levels of dopamine could also explain the behaviour of the so-called sensation seekers as they are more motivated to act.

Application for depression and addiction

To know the neurobiological parameters that make people be motivated by something is important to many areas such as work, education or health. Dopamine is now seen as a core neurotransmitter to address symptoms such as the lack of energy that occurs in diseases such as depression. “Depressed people do not feel like doing anything and that’s because of low dopamine levels,” explains Correa. Lack of energy and motivation is also related to other syndromes with mental fatigue such as Parkinson’s, multiple sclerosis or fibromyalgia, among others.

In the opposite case, dopamine may be involved in addictive behaviour problems, leading to an attitude of compulsive perseverance. In this sense, Correa indicates that dopamine antagonists which have been applied so far in addiction problems probably have not worked because of inadequate treatments based on a misunderstanding of the function of dopamine.