Drug enhancement of athletic performance - with no drugs!

Given the gnashing of teeth in the sports world over role models outed for their drug use, this bit from an Italian group is fascinating. It turns out that after only a few administrations of a pain killer (morphine), a placebo or sham injection on the day of the athletic event has the same effect as taking the real drug! Does this count as illegal drug use before an athletic performance? Here is the abstract from Benedetti et al.:

The neurobiological investigation of the placebo effect has shown that placebos can activate the endogenous opioid systems in some conditions. So far, the impact of this finding has been within the context of the clinical setting. Here we present an experiment that simulates a sport competition, a situation in which opioids are considered to be illegal drugs. After repeated administrations of morphine in the precompetition training phase, its replacement with a placebo on the day of competition induced an opioid-mediated increase of pain endurance and physical performance, although no illegal drug was administered. The placebo analgesic responses were obtained after two morphine administrations that were separated as long as 1 week from each other. These long time intervals indicate that the pharmacological conditioning procedure has long-lasting effects and that opioid-mediated placebo responses may have practical implications and applications. For example, in the context of the present sport simulation, athletes can be preconditioned with morphine and then a placebo can be given just before competition, thus avoiding administration of the illegal drug on the competition day. However, these morphine-like effects of placebos raise the important question whether opioid-mediated placebo responses are ethically acceptable in sport competitions or whether they have to be considered a doping procedure in all respects.

The instinct to swarm

Groups of social animals whose individual members follow simple sets of rules do surprising things. This NY Times article by Carl Zimmer in the Nov. 13 science section quotes Ian Couzin, a mathematical biologist at Princeton: “No matter how much you look at an individual army ant...you will never get a sense that when you put 1.5 million of them together, they form these bridges and columns. You just cannot know that.” The article notes the simple models that predict swarming behavior by setting the population density that which individuals switch from going their own way to following others. It also describes experiments using human subjects to test Couzin's models.

Many take our brains to be a more massive and complex version of the "hive minds" displayed by groups of bees, ants, birds and fish. Brain modelers assign relatively simple properties to their model neurons and then watch amazing patterns emerge when their whole society of neurons is fired up to interact.

Exercise on the Brain

Aamodt and Wang contribute an Op-Ed piece with the title of this post in the Nov. 8 New York Times. Their main message is that all of the 'brain exercise' programs that are marketed to counter the cognitive decline associated with aging are more expensive, complicated, and vastly less effective than vigorous daily exercise (not to suggest that these are competing alternatives, it is certainly best to do both). They note that while activities like solving puzzles or remembering lists can induce lasting changes in these specialized areas, physical exercise improves “executive function,” the set of abilities that allows you to select behavior that’s appropriate to the situation, inhibit inappropriate behavior and focus on the job at hand in spite of distractions. Executive function includes basic functions like processing speed, response speed and working memory, the type used to remember a house number while walking from the car to a party. They also note studies showing the numerous theraputic effects of exercise, such as delaying both the onset of dementia and the shrinking of the frontal cortex that occurs with age.

A hormone boost to generosity...

Yet another bit of work on the magic hormone, oxytocin, that makes us more affiliative, gentle, and trusting...the abstract from Zak et al. :

Human beings routinely help strangers at costs to themselves. Sometimes the help offered is generous—offering more than the other expects. The proximate mechanisms supporting generosity are not well-understood, but several lines of research suggest a role for empathy. In this study, participants were infused with 40 IU oxytocin (OT) or placebo and engaged in a blinded, one-shot decision on how to split a sum of money with a stranger that could be rejected. Those on OT were 80% more generous than those given a placebo. OT had no effect on a unilateral monetary transfer task dissociating generosity from altruism. OT and altruism together predicted almost half the interpersonal variation in generosity. Notably, OT had twofold larger impact on generosity compared to altruism. This indicates that generosity is associated with both altruism as well as an emotional identification with another person.

Conductors’ Ears and Eyes Stay Equally Alert

Here is an interesting tidbit that makes perfect sense to me as a pianist, from Eric Nagourney reporting in the NY Times on the Society for Neuroscience Meetings:

To concentrate on a difficult task that involves listening, people tend to unconsciously divert their attention from what they are seeing. But music conductors, a new study reports, are not as apt to be distracted in this way....The researchers, who presented their findings at a recent conference of the Society for Neuroscience, used magnetic resonance imaging to compare how 20 conductors and 20 nonmusicians handled complex auditory tasks...The researchers were from Wake Forest University Baptist Medical Center and the University of North Carolina at Greensboro. They were especially interested in learning whether their subjects would continue shifting resources as the demands of listening became more complex, said the lead author, Dr. W. David Hairston of Wake Forest...The volunteers were placed in an M.R.I. scanner and asked to listen to different notes over headphones while keeping their eyes open. As the notes were played closer and closer together, they were asked to say which they heard first...In both groups, activity in the parts of the brain involved with seeing decreased, but as the task became more difficult, only the nonmusicians turned off more of their visual processing...Part of the explanation may lie in the need for conductors to make extensive use of both their eyes and ears, to read the score and “to keep track of who’s playing what,” Dr. Hairston said.

This is Your Brain on Politics

Marco Iacoboni, whose work I have mentioned before, has together with several collaborators performed brain imaging experiments on 20 swing voters who indicate willingness to vote for a candidate from either party in the Nov. 2008 presidential elections. They summarize their findings in an Op-Ed piece in the Nov. 11 New York Times. There is a slide show you might like to watch. While insiders in the imaging business go apoplectic over simplistic interpretations of averaged data taken from a small number of subjects using ambiguous protocols with dubious controls, some correlations do emerge that "make sense." (See these comments on the article as 'junk science'.) For example: anterior cingulate (conflict resolution) associates with Hillary Clinton; or amygdala (anxiety) and insula (disgust) correlates with viewing the words "Democrat" or "Republican" but not "independent". One bit I found interesting: "Barack Obama and John McCain have work to do. The scans taken while subjects viewed the first set of photos and the videos of Mr. McCain and Mr. Obama indicated a notable lack of any powerful reactions, positive or negative."

Slide 2
Photos of Hillary Clinton elicited increased activity in the anterior cingulate cortex, a part of the brain that processes conflicting impulses, in swing voters who reported having an unfavorable opinion of her.

Society for Neuroscience meeting: news from the front lines

You might like to check out the Society for Neuroscience website, which offers very accessible information for general public, press, and educators. The site contains links to these topics from the recent annual meeting:

* Antidepressant Drugs, Exercise, Young Age, Even Food Intake, Frequency, and Type, Affect Generation of New Brain Cells

* Research Sheds Light on Brain Differences in Adolescents, Understanding their Impulsive, Risk-Taking Behavior

* Training, Sensory Substitution, Thought-Reading Computers, Sleep, and Molecular Imaging Advance Stroke Research

* Thoughts, Not Arms and Hands, Can Operate Machines: New Devices May Soon Improve Lives or Physically Handicapped

* New Research Explores Dietary Effects on Amyloid in Search for Ways To Prevent, Treat Alzheimer's Disease

* New Studies Find Potential Biomarker for PTSD, Make Gains in Understanding Disorder and Why it is Difficult To Treat

The brain in glorious color - "Brainbows"

Benedict Carey describes the work of Harvard researchers:

The scientists bred mice so their brain cells had genetic inserts containing genes for three colors of fluorescent protein, red, green and blue. They prompted each insert to randomly express one color, using a genetic trigger. Because there were multiple copies of the three-gene insert in each cell, the cell itself expressed a random mixture of the three colors, some 90 shades in all. What emerged was a kind of beaded rainbow belt of neurons, with the fluorescent glow radiating out through each cell’s neural branches. The researchers called the technique “Brainbow.”

Scientists can use this technique in animals, whose brain systems work in ways similar to those of humans, to see exactly where each cell begins and ends, both within the brain and out through the spine and the limbs — and what happens in between.

“I take a view that this is like the Hubble telescope,” said Dr. Jeff Lichtman, a professor of molecular and cellular biology at Harvard who is the paper’s senior author. “We’ve never been able to look at the brain this way before. Why not just start looking and see what we observe?”

Rationalizing our choices - an early evolutionary origin

When we humans make a choice, we protect our self esteem by rationalizing that it was the correct one, even in the face of evidence to the contrary. It turns out Capuchin monkeys do the same thing. In a kind of "why didn't someone think of trying this before?" experiment, a group of Yale psychologists offered the monkeys several different colors of M&M candies. Once a monkey was observed to show an equal preference for three colors of M&M’s — say, red, blue and green — he was given a choice between two of them. If he chose red over blue, his preference changed and he downgraded blue. When he was subsequently given a choice between blue and green, it was no longer an even contest — he was now much more likely to reject the blue. Thus the monkeys are dealing with cognitive dissonance ('should I choose the blue or the green?') by downgrading or eliminating one of the options. They performed a similar experiment with little children, obtaining similar results. The fact that children and primates show the same behavior as adults suggests that this rationalization behavior is largely unconscious, and may have appeared in evolution earlier than previously thought.

MindBlog's winter home...

Internet is now up and running at the Fort Lauderdale condo, in spite of Comcast.

Susceptibility and Resistance to Social Defeat: Molecular Correlates

The research highlights section of the Nov. 1 issue of Nature points to an interesting article from Nester's group on a strain of mice susceptible to social stress. A description excerpted from a review by Hymen:

...mice are exposed to 10 bouts of social defeat in which c57bl/6 test mice are forced to intrude into space occupied by mice of a larger and more aggressive strain, leading to subordination of the test mice. Following this repeated stress, a subset of mice develop significant avoidance of social contact with mice of the same strain and exhibit other signs that are reminiscent of symptoms of human depression, including weight loss and loss of hedonic (pleasure) responses to sucrose. A strength of the social defeat stress model is that, at least in this mouse strain, the stressor convincingly separates the mice into two groups, a group that the authors designate “Susceptible,” which develop social avoidance, and a group described as “Unsusceptible,” which continue to interact with other mice at the same rate as never stressed controls. The model has other strengths. Repeated social defeat would appear to be a good model for some adverse human experience. Moreover, the traits that emerge in susceptible mice reverse only with chronic antidepressant treatment, which mirrors the requirements for treatment of depression and anxiety disorders with these drugs in humans.

Figure 1. Neural Circuits Regulating Responses to Social Defeat

The mesolimbic dopamine pathway comprises a projection from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens (NAc) and to other forebrain structure, such as the amygdala and prefrontal cortex (PFC). These dopamine projections, which act as the neural substrates of the rewarding properties of food, mating behaviors, and addictive drugs, are now shown by Krishnan et al. (2007) to mediate the response of mice to social defeat. In mice susceptible to social defeat, expression of brain-derived neurotrophic factor (BDNF) increases in the VTA. The NAc is the recipient of increased BDNF release and shows enhanced downstream signaling via the BDNF receptor.

Single cells in monkey brain trained to associate numbers with their symbols

An interesting study from Diester and Nieder showing single nerve cell activity that might be the primitive cognitive precursor that ultimately has given rise to symbolic thinking in linguistic humans. Their abstract:

The utilization of symbols such as words and numbers as mental tools endows humans with unrivalled cognitive flexibility. In the number domain, a fundamental first step for the acquisition of numerical symbols is the semantic association of signs with cardinalities. We explored the primitives of such a semantic mapping process by recording single-cell activity in the monkey prefrontal and parietal cortices, brain structures critically involved in numerical cognition. Monkeys were trained to associate visual shapes with varying numbers of items in a matching task. After this long-term learning process, we found that the responses of many prefrontal neurons to the visual shapes reflected the associated numerical value in a behaviorally relevant way. In contrast, such association neurons were rarely found in the parietal lobe. These findings suggest a cardinal role of the prefrontal cortex in establishing semantic associations between signs and abstract categories, a cognitive precursor that may ultimately give rise to symbolic thinking in linguistic humans.

Coevolution of Parochial Altruism and War

Choi and Bowles offer an interesting game theoretic analysis that suggests why the combination of loyalty towards one's own group and hostility towards outsiders seems to be such a fixed constant of human societies. Here is their abstract:

Altruism—benefiting fellow group members at a cost to oneself—and parochialism—hostility toward individuals not of one's own ethnic, racial, or other group—are common human behaviors. The intersection of the two—which we term "parochial altruism"—is puzzling from an evolutionary perspective because altruistic or parochial behavior reduces one's payoffs by comparison to what one would gain by eschewing these behaviors. But parochial altruism could have evolved if parochialism promoted intergroup hostilities and the combination of altruism and parochialism contributed to success in these conflicts. Our game-theoretic analysis and agent-based simulations show that under conditions likely to have been experienced by late Pleistocene and early Holocene humans, neither parochialism nor altruism would have been viable singly, but by promoting group conflict, they could have evolved jointly.

A review by Arrow explains the simulation:

In Choi and Bowles' simulation, 20 small groups of agents interact over thousands of generations. Agents have two genes, each with two alleles. They are either tolerant (T) or parochial (P) and either altruistic (A) or not (N). Offspring inherit their parents'traits, with occasional random mutations. Altruists help fellow group members at a personal cost; non-altruists do not. Tolerant agents have lucrative exchanges with outsiders; parochial agents do not. A high proportion of parochials in groups restricts trading opportunities for all....The societies that evolve are stable in two conditions: when either selfish traders (TN) or generous warriors (PA) are the dominant type. A few PN bullies and even fewer TA philanthropists can coexist within trader or warrior regimes. The trading regime is peaceful. Standoffs and wars are more common in the warrior regime, but even infrequent war--10 to 20% of encounters--can maintain high levels of parochial altruism. Similar findings for the impact of intermittent war on the evolution of heroism (6) suggest that war need not be "constant" to act as a powerful selective force...The convergence of altruism and parochialism in Choi and Bowles' simulation is consistent with links between the two found in behavioral studies. Selfish choices in social dilemma experiments, for example, diminish markedly when the game is embedded in an intergroup context.

The Undiscovered Planet

Harvard Magazine has an outstanding article with nice graphics on the astounding diversity of microbial life.

In terms of gene content, humans and potatoes are more closely related than these two bacteria are to each other—one measure of bacterial diversity. On the left, Vibrio cholerae; on the right, Mycobacterium tuberculosis.


The anthropocentric five-kingdom system classified all unicellular organisms lacking nuclei (archaea and bacteria) as Monera. The nucleated eukaryotes comprising plants, animals, and fungi were thought to represent the bulk of biological diversity. All other nucleated eukaryotes were grouped in a grab-bag classification known as Protista.


The modern “tree of life,” based on genetic analysis, shows that the bulk of Earth’s biodiversity resides among the Archaea, Bacteria, and that portion of the Eukarya that does not include plants, animals, and fungi.

Decision, Decisions

A recent Science Magazine issue has a special section on the underlying processes of decision-making. Here is Peter Stern's introduction to the section:

Who hasn't agonized over a major decision in life, whether to accept a job offer, move house, or perhaps switch research fields? We are confronted with a multitude of decisions on a daily basis. Many decisions are trivial and can be dealt with in seconds. However, others may have wider ramifications and can be excruciatingly complicated. In the past few years, our understanding of the underlying processes of decision-making has progressed markedly. This neuroscience special issue highlights some of the most exciting developments in this area.

Koechlin and Hyafil review recent experimental studies that provide new insights into the function and connectivity of the anterior prefrontal cortex, which forms the apex of the executive system underlying decision-making. The authors propose an original model of the anterior prefrontal function and provide a theoretical framework for addressing major unresolved issues and guiding future research on decision-making and higher cognition.

Human beings are highly social animals. Many of our decisions make sense only within a social environment. Sanfey outlines the advantages that can be gained by combining tasks and formal mathematical models from game theory with modern neuroimaging methods to characterize the processes that underlie social decision-making. He also summarizes recent research that offers good examples of how this neuroeconomic approach has already begun to illuminate our knowledge of this process.

Sometimes things can also go wrong in this complicated and well-balanced interplay between several brain regions. Paulus proposes that decision-making in psychiatric populations cannot be viewed simply as an alteration of the preference structure or the way individuals experience the outcome of the decision. Instead, it must be understood from the homeostatic balance perspective of the individual. Increased risk-taking behavior in drug addicts, for example, although maladaptive in the generic sense, may actually be adaptive for the substance user in a complex, highly unpredictable environment while attempting to respond to internal urges and cravings.

Decision theory has boomed in the past decade. Körding gives an overview of how decision theory, including normative/Bayesian approaches, can lead us to better understand the functions of the nervous system.

Mozart vs. James Bond

This is a hoot, if you are in for a moment of comic relief.

A Ramachandran lecture...

In this excellent and engaging talk, Vilayanur Ramachandran discusses how brain damage can reveal the connection between internal structures of the brain and corresponding functions of the mind. Focus is on phantom limb pain, synesthesia (when people hear color or smell sounds), and the Capgras delusion (when brain-damaged people believe their closest friends and family have been replaced with imposters.)

Thinking like a genius

Here is a stimulating stumble.

MindBlog on the road

Congress Avenue, Austin Texas
I drove from Madison, WI to Austin, Texas this past weekend, to visit my son and his wife. They now live in the family house I where I grew up. Tomorrow I hit the road again to drive to Ft. Lauderdale, MindBlog's winter home. The timing turns out to have been perfect, it is 24 degrees fahrenheit with light snow flurries in Madison right now .

Blog postings might be a bit flakey this week.

Drug craving? - Just zap your insula!

An important factor that contributes to drug-seeking in addicted individuals is the negative feelings that result from abstinence. Such mood states are monitored by the interoceptive sensory system, and particularly by a brain area called the insular cortex, known to process emotional information. Thus this abstract from Contreras et al. is of interest:

Addiction profoundly alters motivational circuits so that drugs become powerful reinforcers of behavior. The interoceptive system continuously updates homeostatic and emotional information that are important elements in motivational decisions. We tested the idea that interoceptive information is essential in drug craving and in the behavioral signs of malaise. We inactivated the primary interoceptive cortex in amphetamine-experienced rats, which prevented the urge to seek amphetamine in a place preference task. Interoceptive insula inactivation also blunted the signs of malaise induced by acute lithium administration. Drug-seeking and malaise both induced Fos expression, a marker of neuronal activation, in the insula. We conclude that the insular cortex is a key structure in the perception of bodily needs that provides direction to motivated behaviors.

The therapeutic intervention was an injection of 2% lidocaine (a sodium channel blocker to inhibit nerve activity) into the left and right insula to cause a transient shutdown of insular nerve activity (injecting adjacent cortex was not effective). Although this is a sledgehammer approach with possible dire side effects, it suggests that therapeutic interventions in the insula may help to alleviate drug cravings, .