The placebo effect is hard wired into the brain

It has been assumed that 'higher' brain structures linked to expectation are involved with sham treatments that can relieve pain, and natural opioid pathways are known to be important players. Now Eippert and colleagues have imaged the brains of volunteers given a sham ointment to relieve a mild burning pain. Half of them had been treated with naloxone, a chemical that blocks opioid signalling. They observed that placebo-related brain activity occurs in both the prefrontal cortex and more hard-wired areas, such as the amygdala, hypothalamus and parts of the brainstem. Here is more detail from their abstract:

Naloxone reduced both behavioral and neural placebo effects as well as placebo-induced responses in pain-modulatory cortical structures, such as the rostral anterior cingulate cortex (rACC). In a brainstem-specific analysis, we observeda similar naloxone modulation of placebo-induced responses in key structures of the descending pain control system, including the hypothalamus, the periaqueductal gray (PAG), and the rostral ventromedial medulla (RVM). Most importantly, naloxone abolished placebo-induced coupling between rACC and PAG, which predicted both neural and behavioral placebo effects as well as activation of the RVM. These findings show that opioidergic signaling in pain-modulating areas and the projections to downstream effectors of the descending pain control system are crucially important for placebo analgesia.

Brain changes correlating with bipolar disorder.

Three-dimensional model of the brain showing regions of increased volume in the insula, cerebellar vermis, and substantia nigra in individuals with genetic predisposition for bipolar disorder. The image has been reformatted in a style inspired by Vincent van Gogh, the most famous painter with bipolar disorder. For more information, see article by Kempton et al.

How did economists get it so wrong?

Krugman's article in the New York Times Sunday Magazine is really worth reading.

Monkey music

It is generally assumed that music, especially its emotional or affective components, has played an important role in human evolution. The music like component of language, prosody, is central in the "motherese" sounds made to calm human infants. Non-human primates, however, are almost completely indifferent to the sounds of human music. Now Chuck Snowdon here at Wisconsin has collaborated with musician David Teie in an interesting bit of work that demonstrates that cotton-top tamarin monkeys respond to 'tamarin music' synthesized from their affective vocalization sounds. Some interesting samples of the music are here, and here is the abstract of their work, which suggests that affective components in human music may have evolutionary origins in the structure of calls of non-human animals:

Theories of music evolution agree that human music has an affective influence on listeners. Tests of non-humans provided little evidence of preferences for human music. However, prosodic features of speech (‘motherese’) influence affective behaviour of non-verbal infants as well as domestic animals, suggesting that features of music can influence the behaviour of non-human species. We incorporated acoustical characteristics of tamarin affiliation vocalizations and tamarin threat vocalizations into corresponding pieces of music. We compared music composed for tamarins with that composed for humans. Tamarins were generally indifferent to playbacks of human music, but responded with increased arousal to tamarin threat vocalization based music, and with decreased activity and increased calm behaviour to tamarin affective vocalization based music. Affective components in human music may have evolutionary origins in the structure of calls of non-human animals. In addition, animal signals may have evolved to manage the behaviour of listeners by influencing their affective state.

Reducing anxiety caused by early life social isolation.

For rats (and humans) early social isolation causes anxiety-like behavior in adulthood. Work by Lukkes et al. now shows that an antagonist of a brain membrane corticotropin-releasing factor (CRF) receptor (delivered by a brain cannula) partially reverses this effect. Will we be seeing clinical trials of this approach in humans before long? The abstract:

Social isolation of rats during the early part of development increases social anxiety-like behavior in adulthood. Furthermore, early-life social isolation increases the levels of corticotropin-releasing factor (CRF) receptors in the serotonergic dorsal raphe nucleus (dRN) of adult rats. Interactions between serotonin and CRF systems are thought to mediate anxiety behavior. Therefore, we investigated the effects of CRF receptor antagonism within the dRN on social anxiety-like behavior after early-life social isolation. Male rats were reared in isolation or in groups from weaning until midadolescence, and rehoused in groups and allowed to develop into adulthood. Adult rats underwent surgery to implant a drug cannula into the dRN. After recovery from surgery and acclimation to the testing arena, rats were infused with vehicle or the CRF receptor antagonist D-Phe-CRF_(12-41) (50 or 500 ng) into the dRN before a social interaction test. Isolation-reared rats pretreated with vehicle exhibited increased social anxiety-like behavior compared with rats reared in groups. Pretreatment of the dRN with D-Phe-CRF_(12-41) significantly reduced social anxiety-like behaviors exhibited by isolation-reared rats. Overall, this study shows that early-life social stress results in heightened social anxiety-like behavior, which is reversed by CRF antagonism within the dRN. These data suggest that CRF receptor antagonists could provide a potential treatment of stress-related social anxiety.

Our brains have separate hard wired categories for living and non-living objects

Evolution apparently has selected for hard-wiring that separates neural categories for animals — towards which humans have important emotional responses — from those for non-living things. Here is the abstract from Mahon et al.

Distinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses inthe medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimulicompared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.

Viva Happy Hour!

I have a daily happy hour - a ritual I have imbued with an almost religious aura, in which the single daily drink is sufficient to put me in "the zone." In spite of a literature that mostly says that a little booze is good for you, I still worry that I might be pickling more little gray cells than is desirable. Thus a recent little gem from the American Journal of Geriatric Psychiatry is reassuring. A meta-analysis combining many studies concludes that compared with abstainers, male drinkers reduced their risk for dementia by 45 percent, and women by 27 percent. This is consonant with evidence from other studies that moderate alcohol consumption can increase HDL, or “good cholesterol,” improve blood flow to the brain and decrease blood coagulation. You can check the article for the various caveats to the study.

Happiness and unhappiness in East and West

From Uchida et al.:

Cultural folk models of happiness and unhappiness are likely to have important bearings on social cognition and social behavior. At present, however, little is known about the nature of these models. Here, the authors systematically analyzed American and Japanese participants’ spontaneously produced descriptions of the two emotions and observed, as predicted, that whereas Americans associated positive hedonic experience of happiness with personal achievement, Japanese associated it with social harmony. Furthermore, Japanese were more likely than Americans to mention both social disruption and transcendental reappraisal as features of happiness. As also predicted, unlike happiness, descriptions of unhappiness included various culture-specific coping actions: Whereas Americans focused on externalizing behavior (e.g., anger and aggression), Japanese highlighted transcendental reappraisal and self-improvement.

Brief early exposure to high fat diet changes long term dietary habits

Yet another study of how early environment can cause virtually irreversible changes in later life habits. From Teegarden et al.

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho–dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, ΔFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.

Weight as an embodyment of importance.

Jostman et al. do some interesting experiments that indicate that our abstract concept of importance is grounded in bodily experiences of weight. This is not a surprise, for weight is a metaphor for importance in many languages. People "weigh" the value of different options before making a decision, they "add weight" to place emphasis on important ideas, and their opinion "carries weight" if they fill an influential position. The experiments suggest that the link between weight and importance exists not only on a linguistic level, but also is an embodied cognition grounded in our bodily experiences of weight.

Participants provided judgments of importance while they held either a heavy or a light clipboard. Holding a heavy clipboard increased judgments of monetary value (Study 1) and made participants consider fair decision-making procedures to be more important (Study 2). It also caused more elaborate thinking, as indicated by higher consistency between related judgments (Study 3) and by greater polarization of agreement ratings for strong versus weak arguments (Study 4). In line with an embodied perspective on cognition, these findings suggest that, much as weight makes people invest more physical effort in dealing with concrete objects, it also makes people invest more cognitive effort in dealing with abstract issues.

Gene variants that correlate with both psychosis and creativity?

Even though a number of studies have discounted an association between creativity and madness, the persistence of the idea may have some basis in fact. Kéri has studied the relationship between a functional promoter polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992; C vs. T) and creativity in 200 healthy participants with high intellectual and academic performance who filled out a creative achievement questionnaire. (Neuregulin 1 - which affects neuronal development, synaptic plasticity, glutamatergic neurotransmission, and glial functioning - is one of the most actively investigated candidate genes for psychosis.) His results suggest that polymorphism of the promoter region TT, T/C, C/C is associated with creativity in people with high intellectual and academic performance. Intriguingly, the highest creative achievements and creative-thinking scores are found in people who carried the T/T genotype, which has been shown to be related to psychosis risk and altered prefrontal activation.

Fleeing from Facebook

Virginia Heffernan writes an interesting piece on the small but noticeable group who are fleeing from Facebook — some of them ostentatiously. Many apparently feel a sense of creeping disillusionment, and that Facebook is stalking them.

Is Facebook doomed to someday become an online ghost town, run by zombie users who never update their pages and packs of marketers picking at the corpses of social circles they once hoped to exploit? Sad, if so. Though maybe fated, like the demise of a college clique.

Woodland Peace

Predicting child temperament - genes, brain and behavior

Work from Schmidt et al. on correlations between frontal EEG asymmetry, variations in a dopamine receptor gene, and later temperament:

Gene-environment interactions involving exogenous environmental factors are known to shape behavior and personality development. Although gene-environment interactions involving endogenous environmental factors are hypothesized to play an equally important role, this conceptual approach has not been empirically applied in the study of early-developing temperament in humans. Here we report evidence for a gene-endoenvironment (i.e., resting frontal brain electroencephalogram, EEG, asymmetry) interaction in predicting child temperament. The dopamine D4 receptor (DRD4) gene (long allele vs. short allele) moderated the relation between resting frontal EEG asymmetry (left vs. right) at 9 months and temperament at 48 months. Children who exhibited left frontal EEG asymmetry at 9 months and who possessed the DRD4 long allele were significantly more soothable at 48 months than other children. Among children with right frontal EEG asymmetry at 9 months, those with the DRD4 long allele had significantly more difficulties focusing and sustaining attention at 48 months than those with the DRD4 short allele. Resting frontal EEG asymmetry did not influence temperament in the absence of the DRD4 long allele. We discuss how the interaction of genetic and endoenvironmental factors may confer risk and protection for different behavioral styles in children.

Multitasking - bad for the brain?

From the random samples section of the Aug. 28 issue of Science, reporting unsettling news from one of the first-ever studies of chronic multitaskers:

A team headed by psychologist Eyal Ophir compared 19 "heavy media multitaskers" (HMMs), identified by questionnaires on media use, with 22 "light media multitaskers" (LMMs). They tested how well the subjects could filter relevant information from the environment, filter relevant information in their memories, and quickly switch cognitive tasks. One filtering test, for example, required viewers to note changes in red rectangles while ignoring blue rectangles in the same pictures.

HMMs did worse than LMMs across the board. Surprisingly, says co-author Clifford Nass, "they're bad at every cognitive control task necessary for multitasking." Nass, a sociologist, says the study has "disturbing" implications in an age when more and more people are simultaneously working on computers, listening to music, surfing the Web, and texting or talking on a phone. Also troubling, he notes, is that "people who chronically multitask believe they're good at it." The findings are reported this week in the Proceedings of the National Academy of Sciences.

The team hopes to investigate whether multitasking really scrambles brains or whether people with poor filtering and attentional abilities are more attracted to it to begin with. Psychologist Anthony Wagner suspects that media multitasking offers instant rewards that reinforce "exploratory" behavior at the expense of the ability to concentrate on a particular task.

Five second touch sufficient to convey emotion.

Bakalar reports on work of Herenstein and others who show the sophistication and rapidity of our human ability to communicate emotions such as anger, fear, happiness, sadness, disgust, love, gratitude or sympathy with a brief touch.

Our sense of smell is binaral.

When different images are presented to each of our two eyes, or different sounds to each of our two ears, our perception usually switches back and forth between the two alternatives. Now Zhou and Chen have found that the same applies to two odors separately presented to each nostril. This binaral rivalry involves both cortical and peripheral (olfactory receptor) adaptations. (If one of two odors is first presented to a nostril, and then after a brief interval it is again presented to the nostril while a second odor of equal initial power is presented to the other nostril, the second odor is predominantly sensed.)

Get aroused and be stronger.

From Schmidt et al.:

Effort magnitude is commonly thought to reflect motivation, but little is known about the influence of emotional factors. Here, we manipulated the emotional state of subjects, via the presentation of pictures, before they exerted physical effort (squeezing a hand grip) to win money. After highly arousing pictures, subjects produced more force and reported lower effort sensation, regardless of monetary incentives. Functional neuroimaging revealed that emotional arousal, as indexed by postscan ratings, specifically correlated with bilateral activity in the ventrolateral prefrontal cortex. We suggest that this region, by driving the motor cortex, constitutes a brain pathway that allows emotional arousal to facilitate physical effort.

Figure - The emotional incentive force task. Successive screens displayed in every trial are shown from left to right, with durations in milliseconds. Emotional pictures that could be neutral or arousing (with positive or negative valence) were shown before physical effort. Effort was triggered by simultaneously showing the amount of money at stake, materialized as coin images (1 cent, 10 cents, or 1 {euro}), and a thermometer in which fluid level represented the force exerted on the hand grip. Subjects knew that the top of the thermometer corresponded to the monetary incentive, such that the more they squeezed the hand grip, the more money they would win. The last screen informed subjects about the cumulative total of monetary earnings.

Oxytocin Increases Envy and Schadenfreude (Gloating)

Work from Shamay-Tsoory et al. suggests that oxytocin plays a role in a wider range of social emotion-related behaviors than just positive pro-social behaviors.

Fifty-six participants participated in a double-blind, placebo-controlled, within-subject study. Following the administration of oxytocin or a placebo, participants played a game of chance with another (fake) participant who either won more money (envy manipulation), lost more money (schadenfreude manipulation), or won/lost equal amounts of money. In comparison with the placebo, oxytocin increased the envy ratings during unequal monetary gain conditions involving relative loss (when the participant gained less money than another player). Oxytocin also increased the ratings of gloating during relative gain conditions (when the participant gained more money than the other player). By contrast, oxytocin had no effect on the emotional ratings following equal monetary gains nor did it affect general mood ratings.

More on "Running helps your knees?" and exercise

I received an email from Dan Peterson, reacting to my comment in my Aug. 27 post that I "feel strange if I have missed a day of going to the university gym to swim, run, or do weights." He had just done a story on a study by Robin Kanarek of Tufts University on the endorphin-fueled addictive qualities of running/exercise in rats. Here is Peterson's blog.