Train your brain: left vs. right brain activation

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The difference between the left and right sides of the human brain has long fascinated scientists and non-scientists alike. The idea that the left hemisphere supports language and rational thought, while the right hemisphere supports creative processes has firmly taken root in popular culture, and has led some to call for an increase in “right-brain thinking”. Such imprecise use of the scientific literature may seem cringeworthy to scientists, myself certainly included. How exactly, I would ask indignantly after hearing such calls, are we supposed to consciously control activity in one brain half over the other?

Turns out that that part of the problem might actually be fairly simple. New research from the lab of Fabien Robineau in Switzerland suggests that an fMRI scanner and a thermometer may be all that is required.

The experiments make use of Neurofeedback, in which subjects are trained to control activity in specific parts of their brain. Typically, they are instructed to engage in a mental activity that is known to activate the area of interest, while undergoing fMRI scanning. A thermometer on a monitor feeds the degree of activation of the brain region back to the subject, and the goal is to maximize the thermometer reading. One of the truly amazing features of the brain is that it can learn to control almost anything if provided with appropriate feedback, as evidenced by the dazzling variety of skills humans can learn. And indeed, subjects can learn to increase of decrease activity in many parts of their own brains with such procedures.

This approach could be very useful, because many psychiatric and neurological conditions are associated with over-activation of brain areas. In one of the more impressive applications of neurofeedback to date, scientists demonstrated that chronic pain patients could learn to down-regulate activity in a part of the brain that mediates pain, which resulted in substantial reductions in pain perception.

In the Robineau paper, these procedures were applied to selectively activate one side of the brain over the other. Subjects were placed in an fMRI scanner and watched a thermometer that showed the degree of activation of one side of their visual cortex compared to the other side. The instructions were to engage in mental visual imagery in order to maximize the thermometer reading. Amazingly, over three such sessions, most subjects learned to control the degree of activation of the left versus right visual cortex, and they could even reproduce this activation in the absence of feedback.

The authors looked at visual perception because of its relevance to hemispatial neglect, which is a neurological condition that may be caused by imbalanced in activation of the left and right visual cortex. However, in principle similar procedures could be applied to functions that are more likely to ignite the popular imagination, such as creativity, language and rationality. The only caveat there is that research has shown that such broad functions are partly supported by both hemispheres.

Still, it’s a clear proof of principle, and what is to say science will not prove the sceptics wrong once again?

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A disheartening view of honesty

Dishonesty

We all know what honesty is, but what drives us to behave honestly? Opposing views suggest that honest behavior happens either automatically (the “Grace” hypothesis), or requires willpower to resist temptation (the “Will” hypothesis).

New research from Nobuhito Abe at Kyoto University suggests an intriguing answer to this question. Their subjects were tested for basic reward anticipation and dishonest behavior while undergoing fMRI brain scanning. In order to test for dishonest behavior, subjects predicted whether a coin would come up heads or tails, and they won money if their prediction was correct. Crucially, in one condition the subjects were allowed to disclose their prediction after the outcome of the coin flip was known, providing an opportunity for financial gain by dishonesty. Although dishonest behavior could not be proven at the level of individual trials, the aggregate performance of some 30% of the subjects was so improbable (“correctly” predicting the outcome 83% of coin flips) that the experimenters felt confident to classify them as dishonest.

On a side note, if this task sounds familiar, it has recently been used to show that people who were brought up in communist East Berlin cheated twice as much as people who were brought up in capitalist West Berlin.

The Abe paper reports two main findings. First, low activation in the nucleus accumbens in the basic reward anticipation task predicted honest behavior. Secondly, dishonest subjects were exceptionally slow to respond on the few occasions when they reported a wrong prediction (i.e. were being honest), and showed some evidence for activation of cognitive control regions in the brain (the dorsolateral prefrontal cortex) under these conditions.

Thus, these results confirm that honest behavior may be effortless for some, while it requires active resistance of temptation for others. More interestingly, the results suggest that honest behavior may not be a consequence of superior moral fiber. We tend to see honesty as an essential characteristic that separates good from bad, but these results paint a less exalting picture; honest individuals may simply not feel the same temptation as dishonest individuals do. One hopes that that there is more to honest behavior than simple lack of incentive, but these findings do give pause for thought.

And what happened to those dishonest subjects in the experiment, you ask? They were rewarded with up to $75 more than their honest counterparts.

So it goes.

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Cocaine use impairs insight in rats (?)

thinking-rat

One of the most fascinating aspects of drug addiction is the sheer self-destructiveness of frequent drug use. Addicts are often in denial about the detrimental consequences of their behavior, or they may simply fail to act on that knowledge. Thus, deficit in insight is a hallmark of drug addiction.

New research from the lab of Geoffrey Schoenbaum claims to shed light on the biological mechanism of reduced insight in rats. In their research, the authors show that cocaine consumption reduced a measure of insight by impairing the functioning of neurons in the orbitofrontal cortex. Artificial stimulation of those neurons then restored the measure of insight back to normal.

But what, you ask, could possibly count as insight in the humble rat? Perhaps cocaine use prompted the animals to engage in a searing self-examination? Not quite.

According to the authors, Pavlovian over-expectation fits the bill. In this task, animals are trained to expect a food reward when either a sound is played or a visual stimulus is presented, much like Pavlov’s dogs. Then, when the sound and visual stimuli are presented together, the animals expect more than one food reward, even though they never experienced both stimuli together before.

Hardly Pinky and the Brain type stuff, but the authors argue that “insight requires the ability to mentally simulate the causes and likely outcomes of one’s behavior. The ability to mentally simulate or imagine likely outcomes can be revealed in situations in which the outcomes have not been directly experienced previously.”

To some degree this makes sense, and the behavioral and neural investigations detailed in the paper are certainly impressive. At the very least, the paper shows that cocaine use impairs the functioning of a region that is known to be very important for reward guided behavior in humans, and might thus be a useful target for therapeutic intervention.

Whether expecting two food rewards when two stimuli are presented together qualifies as insight is another question though.

You be the judge of this one.

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Predicting alcohol abuse: neuroimaging vs. questionnaires

Alcohol

The lifetime prevalence of alcohol dependence is a staggering 10% of the population in Western countries. Although it is clear that genetics and the environment contribute about equally to the risk for alcohol dependence, not much is known on the intermediaries through which nature and nurture come together to affect alcohol use outcome.

A hugely impressive longitudinal study led by Hugh Garavan now identifies some of the brain characteristics, life experiences and personality factors that predict the development of alcohol abuse, and quantifies their relative influence. The authors studied 14 year old adolescents through questionnaires that determined life history and personality, and through structural and functional brain imaging. Two years later, they verified alcohol abuse outcome at the age of 16.

The question that the authors then asked is to what degree the data that they obtained at age 14 could predict subsequent alcohol abuse two years later. What makes this study so interesting is that it pits the predictive power of age-old questionnaires against the might of modern brain imaging.

For the brain imaging data, the authors looked at the grey matter content and activation (in a set of cognitive tasks) of thousands of standardized miniscule subsections of the brain (each 3 mm3 in size). This obviously included regions that support functions that are important for addiction (such as impulsivity or self-control). However, perhaps more interestingly, this also included regions of the brain of which the precise function is not completely clear. In scientific jargon, this is referred to as a bottom-up approach, and it can lead to novel and unexpected findings.

So, when pitted against questionnaires, surely the enormously detailed brain imaging data would do a better job of predicting future alcohol use, right?

Surprisingly, no. By itself, the brain imaging data was less effective in predicting alcohol abuse than either life history, or personality (although all three had reasonable predictive power).

Apparently, the window of observation that current brain neuroimaging affords is not quite as revealing as we imagined. For one thing, the brain data clearly did not explain the differences in personality (even at the time of testing itself); otherwise it would have been at least equally good in predicting alcohol abuse.

Of course it remains possible that much more detailed information on the precise state of the neurons in the brain could outperform questionnaire data in terms of prediction, but for the moment we do not have access to that information.

Nowadays, funding bodies require almost all research proposals on the topic of mental health to include some degree of neuroscience, much to the chagrin of psychologists.

Perhaps this study should give some pause for reconsideration.

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Far-sighted living

Future

How to improve self-control without willpower

The ability to control one’s impulses and plan for the future is a strong predictor of success in life, whether financial, academic, or social. But it’s not always easy to take the long view. This is spectacularly apparent in conditions like drug addiction, but self-control can be difficult to achieve for most (if not all) people. Just think of the times you decided to, say, go to the gym more often, and how difficult it can be to stick to those intentions.

One way to achieve self-control is to exercise willpower. Resisting temptation by inhibiting impulsive tendencies is certainly possible, but very difficult. In addition, there is evidence that willpower is a limited resource that depletes over time. Thus, in order to improve our quality of life, other sources of self-control would be very helpful.

Recent work by Eran Magen and colleagues suggests that it is possible to increase self-control in the absence of additional willpower. Scientists who study self-control generally allow subjects to choose between a small immediate reward and a larger delayed reward, and choice of the larger delayed reward is taken as evidence for self-control.

For instance, a subject might be asked to choose between $ 5 now, or $ 10 a week later. However, by subtly reframing the same choice as between $ 5 now and $ 0 later, or $ 0 now and $ 10 later, the value of the delayed reward for the subjects increased by 15%. Thus, by making the zero explicit, choice behavior can be influenced quite substantially. So far so good, but how can the authors tell if this increase in self-control appeared in the absence of more willpower? To answer this question they turned to fMRI imaging.

Previous work has shown that the striatum is activated by expected rewards, while the dorsolateral prefrontal cortex is activated by the exertion of willpower. The authors found that the framing manipulation that increased self-control reduced the “value” activation of the striatum, while leaving the “willpower” activation in the dorsolateral prefrontal cortex unchanged. Of course a lack of increase in activity in a region that is normally activated under conditions of willpower is not conclusive proof that willpower was not increased, but it is certainly suggestive.

How beneficial could reframing of choices be in real life? In terms of public policy, Cass Sunstein and Richard Thaler have explored this idea in their book “Nudge: Improving Decisions about Health, Wealth, and Happiness”. One wonders if we could perhaps learn to reframe our own choices to improve self-control.

Let’s give that a try: slouching on the couch watching television now and no weight loss in the future, or going to the gym and losing a few pounds by next week. Ok, ok, I’m going already.

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The Biology of Beauty

Beauty

The perception of beauty is shown to be regulated by opioid receptors

 

“In every man’s heart there is a secret nerve that answers to the vibrations of beauty” wrote the American journalist Christopher Morley. Indeed, labor market studies have confirmed the existence of a beauty premium (and a converse plainness penalty) in career tracks. However, how exactly the nervous system translates perceived beauty into disposition is not well known.

 Scientists that study rewards distinguish between liking something and wanting it. In order to study aesthetic perception of beauty, researchers generally ask participants to rate different faces on an attractiveness scale (liking) and press a “keep” button in order to keep viewing a particular face (wanting). As expected, male subjects will press to keep viewing attractive female faces. Clever behavioral economics studies further suggest that males were willing to pay small amounts of money to watch attractive female faces, while females were not willing to pay for attractive male faces, but were uniquely willing to pay money to forego watching unattractive male faces. Ouch.

Researchers have used these techniques to study male brain responses to female faces, and (surprise, surprise) the nucleus accumbens (the reward processing center of the brain) has been shown to be activated by beauty. Of course correlated activation does not reveal much about causal mechanisms, but more recent work by Olga Chelnokova from the University of Oslo shows that the opioid neurotransmitter system has a direct role in both the aesthetic perception of beauty and consequent social motivation. It has long been known that μ opioid receptors have a pivotal role in reward processing, as activation of these receptors by natural endorphins or heroin produces a strong pleasurable sensation.

The authors gave male subjects a drug that either activated the μ opioid receptors (morphine), or prevented their natural activation (naltrexone). Morphine injections increased ratings of attractiveness and “keep” button presses, but only for the most attractive faces. Naltrexone also only affected ratings and “keep” presses for the most attractive faces, but had the opposite effect.

Thus, these results firmly establish that the brain’s reward circuits are active in the perception of beauty, but only for attractive faces. Given that we know the physical features that result in perception of beauty and the fact that beauty activates reward circuits, it would be fascinating to know how the brain translates certain visual facial features into activation of reward circuits.

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Booting up the brain

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Intriguing new research shows that brain activity cycles through multiple stable states before consciousness is recovered

Transitions in and out of conscious awareness have long held the interest of scientists and philosophers. Although notoriously difficult to study due to its subjective nature, recent work has made some progress in clarifying the neural correlates of consciousness. The brain is often depicted as a static mass of tissue, but dynamic electrical interactions between neurons and brain regions appear to be critical mediators of shifts in consciousness.

During wakefulness, as the brain is engaged in varying types of information processing, most cortical neurons do not fire in the same rhythm, and those that do fire together at high frequencies. Scientists assume that the moment to moment content of consciousness is based on a fleeting entrainment of neural activity in disparate regions. For example, during the appreciation of a beautiful painting, the visual cortex (for the perception of the painting), the associative cortex (for the processing of meaning), and reward regions (for the accompanying sense of enjoyment) could all briefly lock in a high frequency rhythm to produce a moment of conscious awareness of the painting.

Conversely, slow wave sleep, with greatly diminished awareness, is characterized by highly rhythmic activity at low frequencies. Further, research has shown that the ultimate loss of consciousness (death) is accompanied by a wave of strongly synchronized electrical activity that lasts about 10 seconds, which was rather sinisterly dubbed “The Wave of Death”. Although this activity is more suggestive of deep sleep than wakefulness, one does wonder if it may have anything to do with near death experiences.

More optimistically, researchers are beginning to explore the dynamics that underlie the recovery of consciousness after sleep, anesthesia or coma. One might have expected that the electrical activity of the brain simply transitions from slow oscillations to high frequency desynchronized activity, but recent work by the lab of Alex Proekt at Rockefeller University shows that this process is considerably more complex. The authors probed the electrical activity in multiple brain regions in rats as they recovered from anesthesia, and found a number of stable states of brain activity that preceded the recovery of consciousness. Further, as animals woke up, the activity in their brains progressed through a relatively ordered sequence of such states.

Although these results are fascinating, it will be even more interesting to know what the function of these intermediate states are.

The findings bring to mind the image of a rebooting computer, moving through various start up screens before being fully operational. It might be a while yet though before we know exactly what is happening inside the computer.

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Pain, no gain: age related decline caused by pain perception

Pain

The perception of pain is undoubtedly beneficial for longevity, as patients with congenital analgesia (insensitivity to pain) face a reduced life expectancy. Nevertheless, too much of a good thing can be harmful, and this seems to hold for pain as well. It was already known that patients with chronic pain live less long, but one might have thought that the pathogenic causes of chronic pain were the real culprits responsible for that correlation. However, recent work from the Dillin lab at UC Berkeley published in Cell suggests that pain perception itself drives reductions in lifespan.

During normal ageing, metabolic function slowly declines, as cells in the body become less sensitive to insulin, leading to high blood glucose levels, which increases age related pathologies and mortality.

The authors of the Cell paper looked at the lifespan of mice that were engineered to lack the TRPV1 pain receptor that is normally activated by a host of noxious stimuli in the body, but can also be activated by consumption of capsaicin, which gives chili peppers its spicy taste.

Surprisingly, the mice that lacked TRPV1 pain receptors did not show normal metabolic decline with ageing, had lower incidence of tumors, better cognitive functioning, and a 10 to 15% longer lifespan. In depth-investigation of the mechanisms by which TRPV1 activation drove age-related decline revealed that activation of TRPV1 receptors on pain sensory neurons in the spinal cord inhibited insulin secretion in the β cells of the pancreas, leading to insulin resistance and its adverse consequences.

Thus, these results suggest that pain perception itself is a major driver of age related decline. This will be welcome news for pharmaceutical companies that are developing TRPV1 antagonists to treat pain, as these drugs may additionally reduce the incidence of diabetes, cognitive decline and potentially even tumors. Not a bad list of indications in terms of potential sales.

However, we may already have a natural remedy for TRPV1 overactivation. As discussed above, TRPV1 receptors can be activated by capsaicin, so one could be forgiven for assuming that spicy food would be detrimental to metabolic functioning during ageing. In fact, prolonged application of capsaicin leads to desensitization of TRPV1 receptors, which may explain why diets that are rich in capsaicin have been shown to have a protective effect on metabolic ageing.

In other words, keep those chili peppers coming.

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Male Mice Step up to the Plate

The humble male mouse is a favored research subject in labs across the world. Experimenters often change the natural behavior of the mice by adjusting the functioning of neurons in the brain, and the results are not always pretty. Take for instance this paper, in which scientists reported that impairing pheromone receptors in adult male mice caused active sexual behavior towards juvenile prepubescent females. Yikes.
 
In case you’re wondering, the point of this paper was that juvenile female mice excrete a pheromone in their tears that normally inhibits sexual approach by adult male mice. This seems to make perfect evolutionary sense, and although human social behavior is thought to be less dependent on pheromones, one might expect that a similar mechanism normally inhibits sexual interest in prepubescent humans. If true, it begs the question whether such a mechanism could be damaged.

 

Mice

 

In any case, luckily the things that scientists make male mice do in the lab are not always for the worse. A recent paper in Nature from the Dulac lab at Harvard in particular managed to score high on the animal cuteness scale. In their work, the authors looked at parenting behaviors, starting with the observation that sexually experienced males and females and virgin females all show parental care for pups from other parents, while virgin males exhibit aggression.
 
If this may sound familiar, analogous experiments in humans have shown that the pupils of male and female parents and non-parent females widen when viewing pictures of babies, while the pupils of male non-parents narrow considerably. Of course narrowing pupils do not equate to aggression, but who knows what thoughts occurred behind those narrowing pupils. 
 
In the paper from the Dulac lab, the authors showed that normal parenting behavior is regulated by the activity of a group of neurons in the hypothalamus that express the galanin neurotransmitter. Normal male virgin mice that were put in a cage with young pups quickly attacked the pups, and the experimenters often had to step in to protect the pups. However, when the galanin expressing neurons were artificially activated, male virgin mice ceased attacking the pups, and spend much of their time licking and sniffing the little pups in an expert display of parental care.  
 
Surely a Youtube video of the virgin males fussing over the little pups would be worth a few likes.
 
As the authors note, this was particularly interesting because it suggests that typical female responses can in fact be elicited from the male brain. Conversely, the authors have previously shown that female mice that lack normal pheromone receptors “show notable male-like mounting and courting displays”, suggesting that typical male responses can also be elicited from the female brain.
 
Perhaps then gender differences are less hard-wired in the brain than previously assumed.

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Sex and Violence at the Turn of a Dial

Increasingly, modern neuroscientists try to investigate the function of small populations of cells within larger brain regions. In essence, they strive to find ways to activate and silence these defined groups of cells to see how the behavior of the animal is affected.

Take for instance a recent report from the lab of David Anderson at Caltech in the journal Nature. This paper focuses on the hypothalamus, which is a region of the brain that senses the internal state of the organism through circulating hormones, and initiates appropriate behavioral responses. The authors had previously found that activation of a part of the hypothalamus in male mice could prompt attack of nearby males and females within seconds. Interestingly, the mice would also attack nearby inanimate objects, indicating that the approach of the experimenters was still a little heavy-handed. Further experiments suggested that a subtype of neurons that express the estrogen receptor could be responsible for the aggression effect, and the scientists therefore developed ingenuous ways to activate and silence these neurons through genetic manipulations.

And indeed, selective activation of the neurons that expressed the estrogen receptor elicited aggressive responses in male mice, which must have surely elicited approving nods from the observing experimenters. However, when the investigators dialed down the intensity of stimulation, something much less expected happened. Weaker stimulation of these same neurons produced mounting of nearby female mice. In fact, male mice would even mount nearby male mice, although, as the report notes, “when directed towards males, it was typically abortive and did not proceed to pelvic thrusting or ejaculation”. Such a scene must surely have elicited a few befuddled looks.

In principle one might have expected attack and mating to be regulated by different circuits, perhaps in a mutually inhibitory fashion. Indeed, earlier work by this group had suggested that mating might inhibit aggression circuits, but these results show an at least partially shared neural basis for attack and mating responses. Although the authors carefully refrain from speculation, one can’t help but wonder if the long-known link between male sexuality and aggression may have a physical basis in these neurons. If true, it would be quite ironic that these cells can be defined by expression of the estrogen receptor.

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