Observing rat brains as they look to the future

An emerging view is that the hippocampus is essential to imagining the future as well as remembering the past (which makes a lot sense, since we usually base our imagined future on our past experience). Johnson and Redich have now observed ensembles of cells in the CA3 region of the rat hippocampus whose firing transiently encodes paths forward of an animal at decision points in a maze, as if they are reflecting on possible futures and deciding what to do next. The figure, from Heyman's review of the work in Science, illustrates that as a rat looks in one direction, neurons representing that position (inset) fire over a half-second period. Here is the abstract of the work:

Neural ensembles were recorded from the CA3 region of rats running on T-based decision tasks. Examination of neural representations of space at fast time scales revealed a transient but repeatable phenomenon as rats made a decision: the location reconstructed from the neural ensemble swept forward, first down one path and then the other. Estimated representations were coherent and preferentially swept ahead of the animal rather than behind the animal, implying it represented future possibilities rather than recently traveled paths. Similar phenomena occurred at other important decisions (such as in recovery from an error). Local field potentials from these sites contained pronounced theta and gamma frequencies, but no sharp wave frequencies. Forward-shifted spatial representations were influenced by task demands and experience. These data suggest that the hippocampus does not represent space as a passive computation, but rather that hippocampal spatial processing is an active process likely regulated by cognitive mechanisms.

Japanese Gardens

This picture from a stroll yesterday in the Morikami Japanese Gardens in Boca Raton, Florida. An iguana is on the lawn to the right of the tree trunk, a heron to its right on the bank, the flat object on the grass to the right of the heron is a water turtle, and the orange spots in the water are Koi. (click on the picture to enlarge).

Our optimism bias - brain correlates

Sharot et al. examine the tendency of most of us to imagine more optimistic outcomes than can be justified by sober appraisal. A moderate amount of optimistic illusion has been related to mental and physical health, and the general idea is that it is adaptive and useful because it motivates us towards future goals. Their abstract, and a figure showing the relevant brain regions:

Humans expect positive events in the future even when there is no evidence to support such expectations. For example, people expect to live longer and be healthier than average, they underestimate their likelihood of getting a divorce, and overestimate their prospects for success on the job market. We examined how the brain generates this pervasive optimism bias. Here we report that this tendency was related specifically to enhanced activation in the amygdala and in the rostral anterior cingulate cortex when imagining positive future events relative to negative ones, suggesting a key role for areas involved in monitoring emotional salience in mediating the optimism bias. These are the same regions that show irregularities in depression, which has been related to pessimism. Across individuals, activity in the rostral anterior cingulate cortex was correlated with trait optimism. The current study highlights how the brain may generate the tendency to engage in the projection of positive future events, suggesting that the effective integration and regulation of emotional and autobiographical information supports the projection of positive future events in healthy individuals, and is related to optimism.

The authors collected functional magnetic resonance imaging (fMRI) data while participants thought of autobiographical events related to a description of a life episode (for example, 'winning an award' or 'the end of a romantic relationship'). The word 'past' or 'future' indicated if they should think of an event that occurred in the past or one that might occur in the future. Trials were classified into positive, negative and neutral according to participants' ratings. They found that future positive events were rated as more positive than past positive events, and were imagined to be closer in temporal proximity then future negative events and all past events. (Click on image to enlarge it)

Impairment of action chains in autism.

When we observe the start of an action sequence that can end in two possible ways (in the figure shown a piece of food is placed in the mouth or in a container on the shoulder) appropriate sympathetic muscle EMG signals are detected at the start of the sequence. Thus, if the sequence will end in food to the mouth, activity is observed in the mouth-opening mylohyoid (MH) muscle at the onset. Rizzolatti and collaborators find that typically developing children show an activation of their MH muscle already when they observe the experimenter's initial motor act, food reaching. This activation reflects their understanding of the final goal of the observed action. In children with autism this action-understanding motor activation is lacking. Further, when typically developing children actually perform the observed action, MH muscle activation is observed at the very beginning of the sequence, while in children with autism, the activation is not observed until immediately before the muscle is actually used.

Figure - Schematic representation of the tasks. (Upper) The individual reaches for a piece of food located on a touch-sensitive plate, grasps it, brings it to the mouth, and finally eats it. (Lower) The individual reaches for a piece of a paper located on the same plate, grasps it, and puts into a container placed on the shoulder.

They suggest that high-functioning autistic children may understand the intentions of others cognitively but lack the mechanism for understanding them experientially because they lack the chains of action-constrained neurons that code specific motor acts (e.g., grasping) according to the final goal of the action in which the motor act is embedded.

Distinguishing true versus illusory memories with brain imaging.

Kim and Cabeza show that true versus illusory memories held with high certainty depend on different neural mechanisms. Here is their abstract and one figure from the paper:

Although memory confidence and accuracy tend to be positively correlated, people sometimes remember with high confidence events that never happened. How can confidence correlate with accuracy but apply also to illusory memories? One possible explanation is that high confidence in veridical versus illusory memories depends on different neural mechanisms. The present study investigated this possibility using functional magnetic resonance imaging and a modified version of the Deese-Roediger-McDermott false-memory paradigm. Participants read short lists of categorized words, and brain activity was measured while they performed a recognition test with confidence rating. The study yielded three main findings. First, compared with low-confidence responses, high-confidence responses were associated with medial temporal lobe (MTL) activity in the case of true recognition but with frontoparietal activity in the case of false recognition. Second, these regions showed significant confidence-by-veridicality interactions. Finally, only MTL regions showed greater activity for high-confidence true recognition than for high-confidence false recognition, and only frontoparietal regions showed greater activity for high-confidence false recognition than for high-confidence true recognition. These findings indicate that confidence in true recognition is mediated primarily by a recollection-related MTL mechanism, whereas confidence in false recognition reflects mainly a familiarity-related frontoparietal mechanism. This account is consistent with the fuzzy trace theory of false recognition. Correlation analyses revealed that MTL and frontoparietal regions play complementary roles during episodic retrieval. In sum, the present study shows that when one focuses exclusively on high-confidence responses, the neural correlates of true and false memory are clearly different.

Figure: Activity within medial temporal lobes (A) was greater for high-confidence true recognition (HC-TR) than for high-confidence false recognition (HC-FR). Activity within a frontoparietal network (B) was greater for high-confidence false recognition than for high-confidence true recognition.

The moment of recognition...

Ploran et al. use fMRI to observe brain activity leading up to recognition of a perceptual object's identity. Here is their abstract, followed by a composite graphic extracted from figures in the paper.

Decision making can be conceptualized as the culmination of an integrative process in which evidence supporting different response options accumulates gradually over time. We used functional magnetic resonance imaging to investigate brain activity leading up to and during decisions about perceptual object identity. Pictures were revealed gradually and subjects signaled the time of recognition (TR) with a button press. We examined the time course of TR-dependent activity to determine how brain regions tracked the timing of recognition. In several occipital regions, activity increased primarily as stimulus information increased, suggesting a role in lower-level sensory processing. In inferior temporal, frontal, and parietal regions, a gradual buildup in activity peaking in correspondence with TR suggested that these regions participated in the accumulation of evidence supporting object identity. In medial frontal cortex, anterior insula/frontal operculum, and thalamus, activity remained near baseline until TR, suggesting a relation to the moment of recognition or the decision itself. The findings dissociate neural processes that function in concert during perceptual recognition decisions.

Composite extracted from figures in paper (click on graphic to enlarge and see labels): From interpolation analyzes, the top row shows brain regions of interest for initial sensory processing, the second row regions active in accumulation, and the bottom row regions active when recognition of the stimulus is signalled.

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.