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, .

Music and Dancing

Daniel Levitin has offered this brief essay in the New York Times Op-Ed section.

Less SAD with more sun and serotonin

Welberg offers a summary and review of work by Willeit et al. on the role of serotonin, and a serotonin transporter, in seasonal affective disorder. Here is an portion of the review:

Short, dark winter days put most of us in a gloomy mood, but in people with seasonal affective disorder (SAD), they can cause severe clinical depression. Fortunately, this depression can be treated with bright-light therapy (BLT), and it disappears altogether in summer. Willeit et al. now show that these changes in mood are associated with alterations in the efficiency of the serotonin (5-hydroxytryptamine) transporter (5-HTT) in the patients' blood platelets.

One theory of depression posits that impaired functioning of monoamine neurotransmitters, such as serotonin, causes the disorder, but it is unknown how this impairment might arise. Serotonin levels in the synapse are controlled by the 5-HTT, and Willeit and colleagues therefore investigated whether alterations in 5-HTT functioning might underlie depression in SAD.

The authors compared people with SAD with healthy volunteers, and assessed 5-HTT functioning in winter, after 4 weeks of BLT and in summer. They did this by measuring 5-HTT-mediated inward and outward transport in blood platelets (which are easily obtainable). In winter, both inward transport rate and outward transport were enhanced in the platelets of SAD patients compared with healthy controls. Importantly, these differences in platelet 5-HTT functioning disappeared after 4 weeks of BLT and were absent in summer. The number of 5-HTTs and their affinity for serotonin did not change with BLT or with the seasons, indicating that the increased 5-HTT inward transport that was found in SAD patients was due to increased efficiency of the transporter.

The authors also assessed the patients' depression levels at the three time points, using a structured interview. They found that post-treatment, both inward transport rate and outward transport correlated with depression scores in SAD patients. Moreover, patients whose depression did not decrease after treatment did not show a change in 5-HTT-mediated outward transport after treatment.

Are we having fun?

This is an engaging bit of fluff, be happy! (if the Strauss waltz repeated in a loop doesn't drive you crazy.)

Short-term meditation training improves attention and self-regulation

An interesting study from Tang et al. showing that even short term meditation training can influence attention and self-regulation. The integrative meditation method used:

...stresses no effort to control thoughts, but instead a state of restful alertness that allows a high degree of awareness of body, breathing, and external instructions from a compact disc. It stresses a balanced state of relaxation while focusing attention. Thought control is achieved gradually through posture and relaxation, body–mind harmony, and balance with the help of the coach rather than by making the trainee attempt an internal struggle to control thoughts in accordance with instruction.

Their abstract:

Recent studies suggest that months to years of intensive and systematic meditation training can improve attention. However, the lengthy training required has made it difficult to use random assignment of participants to conditions to confirm these findings. This article shows that a group randomly assigned to 5 days of meditation practice with the integrative body–mind training method shows significantly better attention and control of stress than a similarly chosen control group given relaxation training. The training method comes from traditional Chinese medicine and incorporates aspects of other meditation and mindfulness training. Compared with the control group, the experimental group of 40 undergraduate Chinese students given 5 days of 20-min integrative training showed greater improvement in conflict scores on the Attention Network Test, lower anxiety, depression, anger, and fatigue, and higher vigor on the Profile of Mood States scale, a significant decrease in stress-related cortisol, and an increase in immunoreactivity. These results provide a convenient method for studying the influence of meditation training by using experimental and control methods similar to those used to test drugs or other interventions.

Another window into the minds of chimps and humans

Rilling et al. compare resting-state brain activity in humans and chimpanzees:

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individual's perspective. Here we use [18F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing.

Our Brains on Music, and Musicophilia

Steven Pinker has called music useless, with no adaptive value. Oliver Sacks and Daniel Levitin beg to differ. I'm currently reading and enjoying Oliver Sacks' new book: Musicophilia: Tales of Music and the Brain. I'm linking you to a review of this book by Laura Garwin in the current issue of Nature that notes that our brains seem to be finely tuned to music, and asks of what use are our musical powers and passions? She also reviews Levitin's "This is Your Brain on Music: Understanding a Human Obsession." I also thoroughly enjoyed reading this book this past spring, it has a very accessible introduction of the fundamentals of music structure and brain mechanisms associated with music processing.

The hash realities

Murray et al. offer an interesting history and analysis of Cannabis use, with several interesting graphics (PDF here):

Cannabis has been known for at least 4,000 years to have profound effects on the mind — effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use.

A Consciousness Debate

Christof Koch and Susan Greenfield offer a written version of their Oxford University Debate in the summer of 2006 in the Oct. 2007 issue of Scientific American. While they make a point of contrasting their models of the neuronal correlates of consciousness, I think a blending of the two may most closely approach the real situation.

What happens in your brain when you see a dog, hear a voice, suddenly feel sad or have any other subjective experience?

KOCH'S MODEL
A coalition of pyramidal neurons linking the back and front of the cortex fires in a unique way. Different coalitions activate to represent different stimuli from the senses (left). In a mouse cortex (right) these pyramidal cells (green) lie in brain layer 5, surrounded by nonneuronal cells (blue).


GREENFIELD'S MODEL
Neurons across the brain fire in synchrony (green) and prevail until a second stimulus prompts a different assembly to arise (orange). Various assemblies coalesce and disband moment to moment, while incorporating feedback from the body. In a rat brain (bottom), an assembly in the cortex forms (a, b), peaks (c), then decays (d) within 0.35 second after the thalamus is electrically stimulated.

Christof Koch is professor of cognitive and behavioral biology at the California Institute of Technology, where he teaches and has conducted research on the neuronal basis of visual attention and consciousness for more than two decades.

Susan Greenfield is professor of pharmacology at the University of Oxford, director of the Royal Institution of Great Britain and member of the British Parliament's House of Lords. Her research focuses on novel brain mechanisms, including those underlying neurodegenerative diseases.

A new consiousness and philosophy of mind bibliography

David Chalmers and David Bourget are offering a more extensive online service, outlined in this message from ASSC (Assoc. for Sci.Stud. Cons.):

We are pleased to announce the launch of MindPapers, a new website
with a bibliography covering around 18000 published papers and online
papers in the philosophy of mind and the science of consciousness.
This site grew out of a combination of David Chalmers' bibliography in
philosophy of mind and his page of online papers on consciousness, but
it is much larger and has many new capacities, programmed by David
Bourget. The site address is:

http://consc.net/mindpapers/

There is also a separate front end for "Online Papers on
Consciousness". Where MindPapers now combines both offline published
papers and online papers from free and commercial sites, Online Papers
on Consciousness is devoted to free online papers (currently around
4700). It is based on the same database as MindPapers, but is
organized in a way to emphasize issues concerning consciousness and
cognitive science rather than the philosophy of mind. The address is

http://consc.net/online/

The MindPapers database contains 2773 papers on the philosophy of
consciousness (under 59 topics and subtopics) and 3917 papers on the
science of consciousness (under 71 topics and subtopics), as well as
thousands of papers on such related topics as perception,
intentionality, the philosophy of AI, and the philosophy of cognitive
science.

Capacities include (i) links and citation information throughout, (ii)
flexible navigation, display, and search options, (iii) the ability to
submit and edit entries, (iv) the capacity for automated off-campus
proxy access to commercial sites, and (v) a wealth of statistical
information.

We encourage everyone to try these sites to submit any relevant
material that we are missing (for a start, try searching on your own
name). There are tools on the site for submitting entries, as well as
for correcting entries and notifying us of any bugs and suggestions.

--David Chalmers and David Bourget
chalmers@anu.edu.au; david.bourget@anu.edu.au

Sleep deprivation diminishes recall of neutral and positive, but not of negative, events.

We remember emotional events, particularly negative ones, better than neutral events. Sterpenich et al. show that while consolidation of neutral and posititive memories is diminished by sleep deprivation, recall of negative events is less compromised. They show that after sleep deprivation, recollection of negative, potentially dangerous, memories recruits an alternate amygdalo-cortical network, which would keep track of emotional information despite sleep deprivation. Here is their description of the work:

Declarative memories, which can be consciously and verbally retrieved, are initially critically dependent on the hippocampus. However, reliable retrieval of long-term memory depends on a process of consolidation, which partly occurs during sleep, when memories are thought to be progressively transferred to long-term cortical stores. Because people tend to remember emotional memories better than neutral ones, we wondered whether the emotional significance of a memory would enhance its consolidation in a sleep-dependent manner. During a first session, participants viewed pictures with neutral and emotional content without realizing that their memory of the pictures and their content would be tested later (called incidental encoding). Three days later, during a functional MRI scanning session, subjects indicated whether they recognized previously viewed and new pictures. Half of the subjects were totally sleep deprived during the first post-encoding night, but all subjects slept as usual during the second and third post-encoding nights. We show here that the recollection of emotional stimuli elicited larger responses in the hippocampus and various cortical areas in the well-rested group than in the sleep-deprived group, suggesting that emotional significance boosts memory consolidation of the information during sleep. Interestingly, in sleep-deprived subjects, recollection of negative items recruited another network including the amygdala, as if an alternate consolidation process allowed them to keep track of negative, potentially dangerous, information despite the cognitive aftermath of sleep deprivation.