Never make a decision on an empty stomach… or a full stomach…

You are hungry already and dinner is hours away.  You’re getting irritable and making stupid decisions that you normally wouldn’t.  Or maybe you just had a big meal and you’re sated.  Your friend who is seated next to you turns and asks for a favor; you pleasantly agree and sink into your chair sleepily.  What’s going on?

An underappreciated fact about the neuromodulatory system is that release of these molecules can have diffuse and widespread effects all across the brain.  Take dopamine and leptin. Dopamine is a chemical that drives decision-making – among other things, but it really does have an important role in this – while leptin is generally thought to signal satiety.  Leptin is released from the fat cells of the body and we typically think of it acting on the hypothalamus, an area responsible for many metabolic behaviors.  When more leptin is circulating in the blood stream, you will eat less food and increase more energy which makes it a natural candidate for yet another failed diet pill.  Since leptin interacts with motivation to eat food, an alternative set of areas it could interact with are the dopamine regions .  And in those regions, in the striatum in particular, the response to food and food pictures will be reduced when there is increased leptin.

It would be nice to know mechanistically how the two systems interact.  One method of going about this is to activate dopamine release through a stress pathway: by keeping pain at a constant self-reported score, a robust and constant amount of dopamine will be released.  Yes, for some reason people actually volunteer for these experiments.  Now we can exploit the fact that there are known variants in the gene responsible for leptin, LEP.  If you look at how people with these variants respond, you get large differences in dopamine release, which seems to preferentially effect the D2/3 receptors.  Although different researchers seem to disagree on which specific regions of the striatum are modified by leptin, a good guess it that this is highly dependent on the task and leptin will change the amount of dopamine available to the areas.

What affect might this have on behavior?  One behavior that these D2/3 receptors are involved in is risky decision-making.  We all have our own preferences for risky bets.  Some people prefer small bets that they are guaranteed whereas others prefer the risky option (these are the compulsive gamblers).  But it’s a bit more complicated than that.  Sure, you’d take a risky bet when the option was between a sure 5 cents and a “risky” $1.  But maybe you wouldn’t if you were guaranteed $100 with a risky option of $2000 or nothing.  How sensitive you are to these bets turns out to rely on the concentration of D2/3 receptors in the dorsal striatum.  Putting two and two together, we can bet that the leptin that has an effect on dopamine levels also has an effect on how willing you are to take a risk as the stakes get larger.

This means that all of our body is linked, together, with the state of the world.  Periods of hunger or bounty will cause people to behave in very different ways, with behavior linked to the body’s hormone signaling.  Particularly prevalent here is that hormones that are generally thought of as responding purely to food may have a broader role in signaling to the body how to properly respond to all sorts of situations.


Burghardt, P., Love, T., Stohler, C., Hodgkinson, C., Shen, P., Enoch, M., Goldman, D., & Zubieta, J. (2012). Leptin Regulates Dopamine Responses to Sustained Stress in Humans Journal of Neuroscience, 32 (44), 15369-15376 DOI: 10.1523/JNEUROSCI.2521-12.2012

Cocker, P., Dinelle, K., Kornelson, R., Sossi, V., & Winstanley, C. (2012). Irrational Choice under Uncertainty Correlates with Lower Striatal D2/3 Receptor Binding in Rats Journal of Neuroscience, 32 (44), 15450-15457 DOI: 10.1523/JNEUROSCI.0626-12.2012

Dunn, J., Kessler, R., Feurer, I., Volkow, N., Patterson, B., Ansari, M., Li, R., Marks-Shulman, P., & Abumrad, N. (2012). Relationship of Dopamine Type 2 Receptor Binding Potential With Fasting Neuroendocrine Hormones and Insulin Sensitivity in Human Obesity Diabetes Care, 35 (5), 1105-1111 DOI: 10.2337/dc11-2250

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Testosterone and social aggression

Testosterone will probably always be linked in people’s minds with aggressive behaviors, but its role in behavior is a source of controversy.  Why it rises when it does – and whether it causes aggression or merely responds to it – is not clear, although recent studies that directly inject testosterone into an animal has begun to clarify things a little.  A little.  But we still don’t know whether increases in testosterone cause increases in aggression.

Birds are very territorial animals that have evolved signals to prevent the need from actually fighting over territory (too much).  Some of them have pretty fun ways to show off, too; the male red grouse grows a comb over its eyes almost like a rooster, with larger combs being a way to show off dominance.  Don’t want to mess with that guy, he’s got a really large red thing on his head!  In many animals, dominance and aggressive behaviors go hand-in-hand.  If your fellow red grouse is going to beat you silly over and over again, you’ll probably let him do what he wants.  But if aggression and testosterone are somehow related, and if aggression and dominance are somehow related, does testosterone control dominance?  We can start to answer this question by looking at red grouse comb size.

It turns out that testosterone kind of controls comb size.  When Vergara and Martinez-Padilla injected birds with testosterone, over time they grew larger combs, just as one would presuppose.  However, if you go ahead and stick a needle in the other birds – the ones that didn’t get the testosterone injection – they also had an increase in testosterone level.  In fact, they had the same level of testosterone in their bloodstream as those with the injection.  But these birds had smaller combs!  The lack of relationship between testosterone level and comb size (ie, dominance) shows that it doesn’t control displays of dominance.  Perhaps it’s a measure of one individual’s testosterone versus the population’s?  Or perhaps the birds who had increased testosterone started a feedback cycle in the population where everybody needed more testosterone, but only those birds with the initial increase got the rewards from it?

So testosterone levels per se don’t mediate (historical) dominance.  It’s also not at all clear whether testosterone is needed for aggression.  Take the example of another bird, the dark-eyed junco.  Dark-eyed juncos will defend their territory by squawking at unwanted intruders.  Some researchers like to go out and mess with these poor juncos by placing a little toy bird equipped with a speaker in the junco territory.  The result is a lot of swooping in, harassment and yelling at the decoys, in a futile attempt to make them go away.  And if you measure junco testosterone levels before and after introducing the fake bird, you’ll see the levels increase.  Now, if you go and put out just a speaker box – but not a fake bird – the local birds will still come out and and harass the speaker; they’ll approach close up and scream and throw a general fit.  But their testosterone levels don’t increase!  When Rosvall et al examined the baseline testosterone levels, though, it seems like these levels are (very weakly) correlated with how quickly the birds will quickly they’ll approach the speaker and how close they’ll get.  They can see this in a PCA analysis, but don’t mention the raw data so I don’t know if that’s significant; and it certainly isn’t for number of songs.  Just looking at the data makes me worry about outliers but who knows?  But at least for certain behaviors, testosterone surges aren’t associated with aggressive social behavior.

Aggressive behaviors clearly do not all require increases in testosterone, but perhaps it depends on the type of behavior.  In the Rosvall study, maybe the birds did not think they were in physical danger because they could never actually see the darn thing.  And maybe testosterone isn’t the right thing to measure at all!  Androgen and oestregon receptors regulate other genes after being activated by testosterone, and aromatase is a step required for testosterone to be useful.  If you measure the mRNA levels of these genes, they are significantly correlated with aggressive behaviors.  So the behavioral difference between individuals may not be the result of higher levels of the hormone itself, but levels of the receptor.  And since this is measured so quickly after the birds are observed to react to the false bird for six minutes (a mean of 4.5 minutes after the behavior), it seems unlikely that the transcript levels are changing because of the fake bird, but rather was there beforehand.

What role does testosterone play in aggression?  It doesn’t seem to be causing it, because aggressive behaviors happen without changes in testosterone.  It certainly doesn’t control dominance, because you can get the same increase in testosterone levels in birds with different levels of dominance displays.  But this doesn’t mean that testosterone is unrelated to aggression, because it could be receptor level that causes differences in behavior; one bird can do more with the testosterone it has than another.

Here’s my current working hypothesis: testosterone is more important as a way to prepare the body for the effects of aggression than for aggression itself.  Look at the studies above – the researchers only detected surges in testosterone level when it seemed like the bird saw another bird – when it thought it would need to be prepared to fight.  And since testosterone’s effect seems to be changes in gene transcription rather than direct depolarization of neural membranes, it is the role of the receptors to prepare the brain to respond to a different level of environmental aggression.  But hey, I’m new to the testosterone field so we’ll see what I think next week 😉


Rosvall KA, Bergeon Burns CM, Barske J, Goodson JL, Schlinger BA, Sengelaub DR, & Ketterson ED (2012). Neural sensitivity to sex steroids predicts individual differences in aggression: implications for behavioural evolution. Proceedings. Biological sciences / The Royal Society, 279 (1742), 3547-55 PMID: 22673360

Vergara P, & Martínez-Padilla J (2012). Social context decouples the relationship between a sexual ornament and testosterone levels in a male wild bird. Hormones and behavior PMID: 22841824

KA Rosvall, DG Reichard, SM Ferguson, DJ Whittaker, & ED Ketterson (2012). Robust behavioral effects of song playback in the absence of testosterone or
corticosterone release Hormones and Behavior DOI: 10.1016/j.yhbeh.2012.07.009

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“Social” reward

We’ll file this paper under “things I kind of wish I didn’t know”.  Apparently, the Syrian hamster really likes to hang out in areas smeared with female hamster vaginal secretions.  So, I guess these hamsters will be sniffing around their cage like, oh this smells like vagina!  I’ll hang out here!  Oh but that area has a much more vagina-like smell, maybe I should move over there?

In case you’re wondering, the paper also investigates whether testosterone mediates this behavior and it doesn’t.  Good to know?  I guess poor grad students are going to have to continue collecting hamster vagina juice and smearing it all over the place.

That’s science.  I’ll just leave you with a picture of a hamster, so you can ponder what he’s thinking about right now.

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Oxytocin, the complicated hormone

Over at the Notes&Theories blog, there is a good post about the complicated role of oxytocin.  Oxytocin is commonly called the ‘love hormone’, a striking simplification that should immediately set off your Overly Anthropomorphized radar.  Meadow voles are the promiscuous cousins of the monogamous prairie voles:

But oxytocin and vasopressin are released in brains of all mammals, not just those that are monogamous. The differences between species have nothing to do with how much oxytocin or vasopressin is released, but rather they depend on exactly where these hormones act. Vasopressin and oxytocin act only at specific receptors – and in the brain, these receptors are only made in certain places…Then they modified a harmless virus in such a way that it carried the code for making prairie vole vasopressin receptors, and injected it into a small part of the brains of male meadow voles. This part of the brain now began to make vasopressin receptors where none had been before – and the meadow voles began to behave like prairie voles, forming strong attachments to their current sexual partners.

Like so many things in the nervous system, oxytocin and vasopressin have a multitude of possibly contradictory roles that are determined by when they are released, where their receptors are expressed, and what else is released at the same time.  A burst of dopamine+oxytocin and a burst of oxytocin+testosterone will surely have different meanings in the brain!  And with highly plastic gene expression, what they mean will vary between individuals.

Investigating Wall Street through neuroscience

There’s a good collection of links on metafilter about decision-making in finance, and includes a bit about John Coates, who investigates the role of testosterone and cortisone in decision-making.  This article from Businessweek about how this ex-trader got interested in neuroscience:

The more Coates learned, the more he became convinced that traders were, as he put it, “a clinical population.” The stimuli of a trading floor triggered chemical changes in people’s brains, emotionally whipsawing them. During the tech bubble, he recalls, “People just really slipped their moorings: They were motor-mouthing, they weren’t sleeping, they were on this high. It was initially reasonable to assume it was cocaine, but I don’t know many traders that do that. There was something going on, it was just incredibly noticeable, and I realized that at times I had also felt that way.”

I think this is true not just about financial traders, but about anyone in a high-stress occupation during good times.  I know I get this way when everything is working perfectly in lab.

With enough victories, though, testosterone can reach levels that make the animal act foolishly. He picks fights he can’t win, tries to claim too much territory, and roams around in the open where predators might pick him off. A human being on a trading floor might take massive, risky bets on the strength of the American housing market or on U.S. corporate bonds. One of the traders Coates studied went on a hot streak, making twice his average profit-and-loss ratio for five days in a row. By the end of it his testosterone levels had risen 80 percent. If Coates had followed the trader long enough, he believes, there was a good chance “he would be irrationally exuberant and blow up.”

For losers, the effect is the opposite: The stress and worry of losing money cause the endocrine system to flood the body with cortisol, which makes people afraid to take even favorable bets. In the wake of a financial crisis, it’s not just Wall Street traders who suffer from this, but anyone making decisions about money, whether it’s an employer who balks at hiring or a bank officer leery of making a loan even when the Federal Reserve is offering her free money to do so.

Obviously, testosterone and cortisol have wider effects, and the effects they have are contingent on a lot of other environmental variables.  Studying testosterone and cortisol on the trading floor will elucidate just one (important!) aspect of their function.

How little we know about the neuroscience of fatherhood

Fathers caring for their children is the general rule across most vertebrates; almost all nonmammalian vertebrates use fathers as a prime caregiver.  And yet, the world of neuroscience knows little about paternal care. This is partly because the males of our common laboratory species, the lab mouse and rat, are more likely to eat their young than show any special care for them.  The resulting deficit in knowledge is obvious with any cursory look through a textbook on the neurobiology of parental behavior: after ten chapters detailing maternal behavior, there might be one perfunctory chapter detailing how little we know about paternal behavior.  But here’s a cool fact I learned from one of those chapters: did you know that male Djungarian hamsters assist in delivering pups by tearing away the membranes just after birth.  They play midwife!

It seems like the precise neural circuitry for maternal and paternal care are different; lesioning the amygdala decreases paternal care and increases maternal care.  Likewise, many neurohormones that cause maternal behavior have little effect on males.  But some of these pathways are likely to be the same.  I’ll quickly discuss a paper which describes the influence of the neuropeptides prolactin and oxytocin on paternal care.  Oxytocin is the ‘love hormone’ and strongly stimulates pair-bonding, influences social recognition, and has strong effects on general sociality.  Although it is typically thought of as having a pro-social influence, the reality is a bit more complicated (of course!).  Prolactin is a bit of a sex hormone, providing the body with sexual gratification after intercourse and counteracting the effects of testosterone, estrogen, and dopamine.  It clearly has a stronger social effect as well or I wouldn’t be talking about it in relation to child-rearing!

In order to assess the relationship between these two neuropeptides and fatherhood, Gordon et al. first measured  their concentration in fathers across time and found them to be fairly stable.  When they compared the of these neuropeptides to the propensity of the fathers to play with their children, they found them to be strongly related.  Each were associated with a specific paternal behavior: prolactin with facilitation of a child’s exploratory behavior and oxytocin with how much the fathers matched their facial emotions with that of their children.  Since this is only a correlational study, we cannot say for sure whether or not these neuropeptides are directly causing these behaviors.  However, these are similar to what are seen with maternal behaviors, allowing the researchers to compare their results to the richer maternal literature in the future.  It will be interesting to see if future work can relate receptor variants for these neuropeptides to differences in paternal behavior.  Perhaps we can get a genetics of daddyhood?


Gordon I, Zagoory-Sharon O, Leckman JF, & Feldman R (2010). Prolactin, Oxytocin, and the development of paternal behavior across the first six months of fatherhood. Hormones and behavior, 58 (3), 513-8 PMID: 20399783

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Testosterone: cooperation or competition?

In my last post, I gave an introduction into a couple aspects of testosterone: how it rises and falls, and how it affects decision-making.  I forgot to mention that, neurally, it appears to act substantially through three areas of the brain: the nucleus accumbens, amygdala, and orbitofrontal cortex (OFC).  The nucleus accumbens is a major dopaminergic center, the molecule generally seen as responsible for decision-making and action selection.  Amygdala, as we all know, mediates fear and emotional responses (generally…).  The more interesting area is OFC, which is typically thought to be an area that is involved in self-control.  I couldn’t find many papers that I really wanted to talk about on this aspect of testosterone, so I’ll wait for another day to delve into it.

So let’s look at how testosterone affects social behavior.  In what must have been the Most Fun Study To Participate In Ever, Oxford et al. asked subjects to play Unreal Tournament in teams.  When men are playing the game against other teams, the players that contribute the most show increases in testosterone.  However, when men are forced to play against their own teammates, they have decreased testosterone!  And the subjects who contributed the most to a win showed the largest change.

But if testosterone is increasing during competition against other groups, what affect might it have on social behavior?  Eisenegger et al. used the ultimatum game, where a pair of subjects are given a small amount of money.  One of the subjects then makes an offer of part of the money to the other subject, who can either accept the money or reject it; when the second subject rejects it, neither subject gets any money.  It is well-known that people will generally reject unfair offers.  Following the framework of past studies, female subjects were given either testosterone or placebo and asked to play the game.  They found that subjects who were given testosterone made larger offers than placebo subjects.  Although the authors try to make the claim that this is because being turned down is a ‘status concern’, it could just be because they think that they will make more money that way?  Maybe this is risk-aversion?  I should also note that different study found that subjects given testosterone and asked to be the second subject will also reject more unfair offers.  But the most interesting part about the study is that the subjects who thought that they had received testosterone made much smaller offers – presumably because they already thought they knew what testosterone should do, even though they were wrong!

In a response, van Honk et al. tried using a different game.  He used the ‘public good game’ which is where all players receive 3 moneys, and can contribute some to the public good.  When at least two players contribute to the public good, all players receive 6 moneys.  Note that in this version of the game, with the contribution rate of other players, the expected value is highest when you contribute to the public good.  And subject who have testosterone administered to them give more often to the public good!  So it’s not clear whether they are being more pro-social or just smarter…

The interesting thing about this paper, though is that they also measured the ratio of ring to index finger.  This is a measure of prenatal testosterone exposure, although it doesn’t predict adult levels of testosterone.  Those with a high 2D:4D ratio (ie, those with low maternal testosterone, figure left) are most likely to contribute to the common good, and the less prenatal testosterone, the more of an effect the testosterone given to subjects has.  van Honk et al. suggest that prenatal exposure may change something physically to make subjects more receptive to testosterone, whether it is metabolism or receptor level.  They had found a similar result in a previous study which showed that suspicious individuals didn’t become any more suspicious from testosterone, but the most trusting individuals became much more suspicious when given testosterone (figure right).

The data is a bit hard to interpret, but the general feeling now is that testosterone can act as either a pro-social hormone, or one that makes you more concerned about your social status (egocentrism?).  Although I’d love to give a good clean explanation here, I cannot come up with – and have not yet found – a good unifying framework that unites all the social effects of testosterone .


Eisenegger, C., Naef, M., Snozzi, R., Heinrichs, M., & Fehr, E. (2010). Prejudice and truth about the effect of testosterone on human bargaining behaviour Nature, 463 (7279), 356-359 DOI: 10.1038/nature08711

van Honk, J., Montoya, E., Bos, P., van Vugt, M., & Terburg, D. (2012). New evidence on testosterone and cooperation Nature, 485 (7399) DOI: 10.1038/nature11136

Oxford, J., Ponzi, D., & Geary, D. (2010). Hormonal responses differ when playing violent video games against an ingroup and outgroup Evolution and Human Behavior, 31 (3), 201-209 DOI: 10.1016/j.evolhumbehav.2009.07.002

Testosterone: an introduction

Today I want to talk about testosterone.  I had intended for this post to be a short one, but then I kept digging and digging and, well, it turns out that testosterone is a pretty interesting subject.  What I’m going to do today is give a bit of a review on it, and talk about the effect that it has on personal decision-making.  In the next post, I’ll relate testosterone to social decision-making.

Testosterone does a lot of things, and most of them seem to revolve around social status effects – although that simplification may end up making things more confusing.  What testosterone does do is, over time, enhance muscle performance and redistribute immune resources to prepare for injury (remember my post on social status and healing?).  Several things cause increased levels of testosterone, with competition and sex being foremost among them.  This isn’t just physically aggressive competition, either; chess will give you bursts of testosterone.  Historically, calorically stressed populations will see seasonal variations in testosterone levels when men need to suppress aggressive behaviors during child rearing, or get ready for fighting and healing from fighting for status and mates.  But don’t think that testosterone directly will make an individual wildly aggressive.  As Robert Sapolsky notes in The Trouble With Testosterone

Round up some male monkeys…number 3, for example, can pass his day throwing around his weight with numbers 4 and 5, ripping off their monkey chow, forcing them to relinquish the best spots to sit in, but, at the same time, remembering to deal with numbers 1 and 2 with shit-eating obsequiousness…Take that third monkey and inject him with testosterone.  Inject a ton of it in him…And no surprise, when you check the behavioral data, it turns out that he will probably be participating in more aggressive actions than before…Is he now raining aggressive terror on any and all in the group, frothing in an androgenic glaze of indiscriminate violence?  Not at all.  He’s still judiciously kowtowing to numbers 1 and 2 but has become a total bastard to numbers 4 and 5.

Males in industrialized societies, however, don’t have any caloric needs causing them to suppress testosterone.  In order to examine testosterone in a more ‘natural’ setting, Trumble et al. turned to ‘pathogenically stressed forager-horticulturalists of the Bolivia Amazon’ (ie, poor and hungry people of the Amazon) who do indeed have lower testosterone levels.  These tribal people were brought together and organized into teams for a soccer tournament.  They found that testosterone was higher after the game in all participants, whether they won or lost.  But pay attention to this: the individuals who thought they performed better had larger increases in testosterone immediately following the game.  An hour later?  The difference disappeared.

It’s this type of effect of confidence that caused (Wright et al. 2012) to examine the effect of testosterone on group collaboration.  They put pairs of female subjects in a room and gave them a visual task where they had to decide which of two sets of bars were brighter.  When the subjects disagreed, they were allowed to discuss it and then one of the pair had to make a decision based on the joint beliefs.  But some of those subjects were given testosterone injections!  And the ones who were given testosterone were more likely to trust their own injections.  Although this seems like a nice result, we don’t really know what is happening during the verbal discussion.  Does the testosteroned subject just verbally browbeat the other subject?  What’s going on there?

So testosterone may act to reinforce egocentric behavior.  How about risk-taking?  That’s a little more complicated.  In a gambling game – with the subject only competing against themselves – (Stanton et al. 2011) showed that high risk taking in a gambling task is associated with high testosterone, but the same group later showed that (Stanton et al. 2011 [2]) there is actually a U-shaped curve.  Subjects with intermediate levels of testosterone are actually risk-averse, while low and high levels are risk-neutral.  This is an important point, and something to keep in mind; often we are not sampling the whole distribution of testosterone levels, and the simple ‘high’ versus ‘low’ dichotomy may be misleading.

So we have seen that testosterone probably goes up and down based on caloric resources and in the presence of competition and mates (or mating).  We’ll conclude next time with a discussion of how testosterone affects sociality, and how things are even more complicated than high/low or U-shaped.


Trumble, B., Cummings, D., von Rueden, C., O’Connor, K., Smith, E., Gurven, M., & Kaplan, H. (2012). Physical competition increases testosterone among Amazonian forager-horticulturalists: a test of the ‘challenge hypothesis’ Proceedings of the Royal Society B: Biological Sciences, 279 (1739), 2907-2912 DOI: 10.1098/rspb.2012.0455
Wright, N., Bahrami, B., Johnson, E., Di Malta, G., Rees, G., Frith, C., & Dolan, R. (2012). Testosterone disrupts human collaboration by increasing egocentric choices Proceedings of the Royal Society B: Biological Sciences, 279 (1736), 2275-2280 DOI: 10.1098/rspb.2011.2523

Stanton, S., Liening, S., & Schultheiss, O. (2011). Testosterone is positively associated with risk taking in the Iowa Gambling Task Hormones and Behavior, 59 (2), 252-256 DOI: 10.1016/j.yhbeh.2010.12.003

Stanton, S., Mullette-Gillman, O., McLaurin, R., Kuhn, C., LaBar, K., Platt, M., & Huettel, S. (2011). Low- and High-Testosterone Individuals Exhibit Decreased Aversion to Economic Risk Psychological Science, 22 (4), 447-453 DOI: 10.1177/0956797611401752
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