Brain markers that predict vulnerability to psychosis.

Honey et al. offer an interesting study in the Journal for Neuroscience. As indicated in these slightly edited clips from text and abstract:

They used a drug model of psychosis to relate presymptomatic physiology to symptom outcome. Ketamine induces transient psychotic symptoms in healthy volunteers and exacerbates existing symptoms in patients. They assessed brain responses, separately under placebo and ketamine treatments, in healthy volunteers across four cognitive challenges, each theoretically related to a symptom of psychosis. Two of the tasks (verbal working memory and attention) are associated with negative symptoms, which may result from social and cognitive disengagement attributable to reduced processing capacity of prefrontal cortex, leading to difficulties in concentration and maintaining task set. They predicted that prefrontal activity during the attention and working memory tasks would be associated with vulnerability to negative symptoms under ketamine.

A failure to monitor "inner speech" may provide a mechanism leading to auditory hallucinations, whereby self-generated speech is misattributed externally. Comparing verbal self-monitoring (imagining speech spoken by another person) with inner speech (minimal self-monitoring) increases prefrontal and temporal cortex activation in patients with auditory hallucinations. Ketamine produces auditory illusory experiences similar to the heightened auditory and visual awareness described by patients during the prodromal phase, and it has been suggested that these contribute to the development of hallucinations. The authors predicted that prefrontal and temporal cortex activation during a self-monitoring task would be associated with vulnerability to the auditory illusory experiences under ketamine.

Finally, a sentence completion task was used to engage brain regions associated with semantic processing. Thought disorder involves difficulty in constraining semantic threads of language, making speech disjointed and chaotic, as also observed under ketamine. In patients, the requirement to generate an appropriate semantic response to complete a sentence is associated with increased activation of left frontal and temporal cortex. They predicted that frontotemporal responses to a sentence completion task would predict vulnerability to thought disorder induced by ketamine.

They in fact found that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.

Young and old brains differ in encoding positive information

A number of studies have revealed a "positivity shift" with aging; whereas young adults are more likely to remember negative information than positive or neutral information, older adults may be at least as likely (or even more likely) to remember positive information compared with negative information. It has been proposed that this "positivity shift" may occur because older adults put more emphasis on emotion regulation goals than do young adults, with older adults having a greater motivation to derive emotional meaning from life and to maintain positive affect. In the service of these goals, older adults may focus their attention on things that will elicit pleasant feelings and may process positive information in a more self-referential fashion. Thus this work (slightly edited) from Kensinger and Schacter probing the issue is of interest:

Young and older adults are more likely to remember emotional information than neutral information. The authors performed a magnetic resonance imaging study examining the neural processes supporting young (ages 18–35) and older (ages 62–79) adults' successful encoding of positive, negative, and neutral objects (e.g., a sundae, a grenade, a canoe). The results revealed general preservation of the emotional memory network across the age groups. Both groups recruited the amygdala and the orbito-frontal cortex during the successful encoding of positive and negative information. Both ages also showed valence-specific recruitment: right fusiform activity was greatest during the successful encoding of negative information, whereas left prefrontal and temporal activity was greatest during the successful encoding of positive information. These valence-specific processes are consistent with behavioral evidence that negative information is processed with perceptual detail, whereas positive information is processed at a conceptual or schematic level. The only age differences in emotional memory emerged during the successful encoding of positive items: Older adults showed more activity in the medial prefrontal cortex and along the cingulate gyrus than young adults. Because these regions often are associated with self-referential processing, these results suggest that older adults' mnemonic boost for positive information may stem from an increased tendency to process this information in relation to themselves.

Figure - Regions that showed a stronger correspondence to subsequent general recognition (i.e., subsequently recognized > subsequently forgotten) for the positive items than for the neutral or negative items. Red regions showed this correspondence for both young and older adults. Green regions showed this correspondence for the older adults but not for the young adults. No regions showed this correspondence for the young adults but not the older adults, consistent with the behavioral finding that only older adults showed mnemonic enhancement for the positive items.

Retaliation for unfairness - depends on serotonin

Nature highlights an article by Crockett et al. showing that serotonin modulates our reaction to unfairness. The experimenters:

...temporarily lowered serotonin (5-HT) levels in 20 volunteers and had them play the part of responder in the 'ultimatum game'. The responder can either accept the division of a sum of money offered by the game's proposer, in which case they both get their share, or reject it and deprive both players of the amounts proposed.

Although mood, fairness judgments, basic reward processing, or response inhibition, remained unchanged when players' serotonin levels were lowered, they were more likely to reject unfair and very unfair offers, defined as 30% and 20% of the stake, respectively.

Incense is psychoactive.

Mechoulam and colleagues find that incensole acetate (IA), an ingredient of Boswellia resin (frankincense), stimulates a little understood brain ion channel (TRPV3) to cause anti-anxiety and antidepressive behaviors in mice. This suggest that TRPV3 channels in the brain may play a role in emotional regulation. IA has no effect on 27 other receptors, ion channels, and transport proteins in the brain. The suggests the potential for an entirely new class of depression and anxiety drugs.

Obama and Neuroeconomics

In the New York Review of Books John Cassidy offers an interesting review of Nudge: Improving Decisions About Health, Wealth, and Happiness by Richard H. Thaler and Cass R. Sunstein.

If Obama isn't an old-school Keynesian, what is he? One answer is that he is a behavioralist—the term economists use to describe those who subscribe to the tenets of behavioral economics, an increasingly popular discipline that seeks to marry the insights of psychology to the rigor of economics...One of the reasons this approach has proved so popular is that it appears to provide a center ground between the Friedmanites and the Keynesians, whose intellectual jousting dominated economics for most of the twentieth century...Thaler and Sunstein lay out a number of principles that can be used to encourage better choice-making, and they apply them to various topical issues, including retirement saving, health care, and the environment. In a number of cases, the measures that Thaler and Sunstein recommend are mirrored by proposals in Obama's voluminous policy papers, which can be downloaded from his Web site.

Body odors - brain processing different from similar common odors

Here is an edited paste-up of text and abstract from Lundström et al.

Humans are highly accurate at identifying individuals based solely on their body odors, being able to use signals conveyed in body odor to make accurate kin–nonkin judgments, and to detect minute differences in genetic composition of unknown individuals. While visual and auditory stimuli of high social and ecological importance are processed in the brain by specialized neuronal networks, such specialized processing has not yet been demonstrated for olfactory stimuli. The authors used positron emission tomography to ask whether the central processing of body odors differs from perceptually similar non-body odors as women smelled odors collected from friends and non-friends who had slept for seven nights with tight cotton t-shirts with cotton nursing pads sewn into the underarm area. Body odors activated a network consisting of the posterior cingulate cortex, occipital gyrus, angular gyrus, and the anterior cingulate cortex, none of which is believed to be related to olfactory processing. However, together they form an interesting pattern. Posterior cingulate cortex is known to be active in response to emotional stimuli, whereas the anterior cingulate cortex is believed to regulate attentional efforts. This suggests processing of body odors is similar to what previously has been demonstrated for highly emotional stimuli, such as visual images of snakes, where the posterior cingulate cortex works in concert with the anterior cingulate cortex. A separation in the processing of odors based on their source was observed. Smelling a friend's body odor activated regions previously seen for familiar stimuli, whereas smelling a stranger activated amygdala and insular regions akin to what has previously been demonstrated for fearful stimuli.

The data provide evidence that social olfactory stimuli of high ecological relevance are processed by specialized neuronal networks, just as has been demonstrated for auditory and visual stimuli.

Are you a morning person? - mood and body clocks

From from PJH at editor's choice, Science Magazine.

Some neurotransmitters, such as dopamine, have been implicated in adjusting a person's mood. The circadian clock mechanisms, meanwhile, keep the organism's physiology tuned for appropriate responses to day or night. Hampp et al. have demonstrated how the molecular signaling pathways for circadian rhythms might intersect with the brain's establishment of general mood. They found that the promoter of the gene encoding monoamine oxidase A (Maoa), which stabilizes some aspects of mood and breaks down dopamine and serotonin, contains binding sites for several clock proteins and showed that circadian oscillation was driven by the Maoa promoter in neuroblastoma cells. Mice lacking Per2, a gene that stabilizes circadian rhythms, showed damped expression from the Maoa promoter. Observations of the Per2 mutant mice in response to an unavoidable problematic situation--taken as a proxy for despair in humans--showed correlations with disorders of mood.

Brain imaging of belief, disbelief, and uncertainty

A fascinating fMRI study by Sam Harris and colleagues has used functional magnetic resonance imaging (fMRI) to study the brains of 14 adults while they judged written statements to be true (belief), false (disbelief), or undecidable (uncertainty). (Yes, this is the same Sam Harris who wrote "The End of Faith" and "Letter to a Christian Nation."). To characterize belief, disbelief, and uncertainty in a content-independent manner, they included statements from a wide range of categories: autobiographical, mathematical, geographical, religious, ethical, semantic, and factual. They show that belief, disbelief, and uncertainty are mediated primarily by regions in the medial PFC, the anterior insula, the superior parietal lobule, and the caudate. The acceptance and rejection of propositional truth-claims appear to be governed, in part, by the same regions that judge the pleasantness of tastes and odors.

...the final acceptance of a statement as true or its rejection as false appears to rely on more primitive, hedonic processing in the medial prefrontal cortex and the anterior insula. Truth may be beauty, and beauty truth, in more than a metaphorical sense, and false propositions may actually disgust us.
...When compared with both belief and uncertainty, disbelief was associated in our study with bilateral activation of the anterior insula..., a primary region for the sensation of taste. The anterior insula has been regularly linked to pain perception and even to the perception of pain in others. This region, together with left frontal operculum (also active in the contrast disbelief - belief), appears to mediate negatively valenced feelings such as disgust. Studies of olfaction have shown that the left frontal operculum is engaged when subjects are required to make active judgments about the unpleasantness of odors. Thus, regions that have been regularly implicated in the hedonic appraisal of stimuli, often negative, appeared in our study to respond preferentially when subjects rejected written statements as false. Our results appear to make sense of the emotional tone of disbelief, placing it on a continuum with other modes of stimulus appraisal and rejection.
...Several psychological studies appear to support Spinoza’s conjecture that the mere comprehension of a statement entails the tacit acceptance of its being true, whereas disbelief requires a subsequent process of rejection...Understanding a proposition may be analogous to perceiving an object in physical space: We seem to accept appearances as reality until they prove otherwise...subjects assessed true statements as believable faster than they judged them as unbelievable or undecidable. Further, because the brain appears to process false or uncertain statements in regions linked to pain and disgust, especially in judging tastes and odors, this study gives new meaning to a claim passing the “taste test” or the “smell test.”

Brain monoamine oxidase activity predicts male aggression

Here is an edited version of the abstract from Alia-Klein et al.:

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. In humans, studies provide evidence linking the MAOA genotypes and violent behavior but only through interaction with severe environmental stressors during childhood. The authors asked whether in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. They measured brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A. Trait aggression was measured with the multidimensional personality questionnaire (MPQ). They show for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits)...the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both high and low MAO A genotype groups) contributing to more than one-third of the variability. Trait aggression is a measure used to predict antisocial behavior, and thus these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression.

Want to chill out? Exaggerate you abilities.

An interesting article by Gramzow et al. in the Feburary issue of Emotion finds that exaggeration (such as students inflating their grade-point average) doesn't induce the anxiety that usually goes with lying or keeping secrets. Some clips from Benedict Carey's discussion of the article:

...embroiderers often work to live up to the enhanced self-images they project. The findings imply that some kinds of deception are aimed more at the deceiver than at the audience, and they may help in distinguishing braggarts and posers from those who are expressing personal aspirations, however clumsily...The researchers pulled the students’ records, with permission, and found that almost half had exaggerated their average by as much as six-tenths of a point. Yet the electrode readings showed that oddly enough, the exaggerators became significantly more relaxed while discussing their grades...It was a robust effect, the sort of readings you see when people are engaged in a positive social encounter, or when they’re meditating...The ones who exaggerated the most appeared the most calm and confident.

Here is the Gramzow et al. abstract:

Students who exaggerate their current grade point averages (GPAs) report positive emotional and motivational orientations toward academics. It is conceivable, however, that these self-reports mask underlying anxieties. The current study examined cardiovascular reactivity during an academic interview in order to determine whether exaggerators respond with a pattern suggestive of anxiety or, alternatively, equanimity. Sixty-two undergraduates were interviewed about their academic performance. Participants evidenced increased sympathetic activation (indexed with preejection period) during the interview, suggesting active task engagement. Academic exaggeration predicted parasympathetic coactivation (increased respiratory sinus arrhythmia). Observer ratings indicated that academic exaggeration was coordinated with a composed demeanor during the interview. Together, these patterns suggest that academic exaggeration is associated with emotional equanimity, rather than anxiety. The capacity for adaptive emotion regulation--to keep a cool head when focusing on academic performance--offers one explanation for why exaggerators also tend to improve academically. These findings have implications for the broader literature on self-evaluation, emotion, and cardiovascular reactivity.

An integrated view of our subjective energies.

I recently attended the Wisconsin Symposium on Emotion (Now in its 14th year). Its topic was "Emotion, Consciousness and Psychopathology." I want to mention the talk given by A.D.(Bud) Craig, which was a real tour de force, the kind of science I feel I can integrate with my own personal experience. Its title was "How do you feel? The neurobiological basis for human awareness of feelings from the body." I have referenced Craig's work in previous posts, also check here. Here are PDFs of his two recent review articles in Trends in Cognitive Science (2005) and Nature Reviews Neuroscience (2002) which I recommend.

His view is that in our nervous systems, there is a fundamental bilateral partitioning or separation, from basic spinal cord and brain stem homeostatic systems to our highest prefrontal lobe functions, in which the right side spends energy and the left side brings it in. This reflects the relative activities of the sympathetic versus parasympathetic nervous systems. (enter 'parasympathetic' in the google search box in the left column to see some previous mindblog posts on autonomic regulation of chilling out versus getting excited).

The right and left insula appear to be central in processing feelings, all the way from basic (interoceptive) body sensing (posterior insula) up through subjective feelings, disgust, trust, anger, social hurt, empathic happiness, lust, pain, etc. All of these are homeostatic emotional currency that help regular body balance all the way from from blood pressure, glucose, heart rate, salt regulation, up through social self image. Here is a graphic from his 2005 article that shows the central role of the left and right anterior insula (which act as the sensory cortex of limbic system) in receiving information about body state and feeling from sympathetic and parasympathetic input and then interacting with anterior cingulate (the motor cortex of the limbic system) and frontal cortex. (click to enlarge):


Positive emotions (pleasant music, maternal emotions) correlate with enhanced left parasympathic, left anterior insula, left anterior cingulate and left frontal activation, while negative emotions (anger, fear, etc.) enhance activation of the corresponding structures on the right side.

Some very simple manipulations can stroke the relative activation of these two systems. Slowing one's breathing, as usually happens during meditation dials up the left anterior insula system, while breathing more rapidly increases anxiety and right anterior insula activity. In fact, giving instruction to a subject to breathe more slowly or more rapidly can change their emotional reaction to stimuli. In one experiment mentioned by Craig, a picture of a baby seal elicited warm nuturing emotions when breathing was slowed, but when breathing was increased, subjects were more likely to suspect the seal might attack or bite them! Experiments are now being attempted to measure whether oxytocin (the affiliative, trusting hormone) correlate with left insular activation while right insula activation correlates with cortisone (the stress hormone) release.

This sort of global description fascinates me, because it instructs us in how integrated a package we are, and how attention to some of the basement details of our daily life (such as breathing) can fundamentally alter our mood and temperament.

Fairness activates brain reward circuitry.

Some interesting observations from Tabibnia et al. They:

...examined self-reported happiness and neural responses to fair and unfair offers while controlling for monetary payoff. Compared with unfair offers of equal monetary value, fair offers led to higher happiness ratings and activation in several reward regions of the brain. Furthermore, the tendency to accept unfair proposals was associated with increased activity in right ventrolateral prefrontal cortex, a region involved in emotion regulation, and with decreased activity in the anterior insula, which has been implicated in negative affect. This work provides evidence that fairness is hedonically valued and that tolerating unfair treatment for material gain involves a pattern of activation resembling suppression of negative affect.

Figure legend - Ventromedial prefrontal cortex (VMPFC), ventral striatum, and amygdala activation associated with fairness preference. The illustration (a) shows the location of clusters with significantly greater activation in response to fair compared with unfair offers.



Figure legend - Brain activation associated with the tendency to accept unfair offers. The illustrations show the location of areas in (a) left anterior insula and (c) right ventrolateral prefrontal cortex (right VLPFC) whose activation predicted this tendency.

The secret life of emotions.

Another demonstration that we can be nudged by unconscious emotional stimuli - that both global and specific emotional responses can be induced without awareness. From the discussion of an article with the title of this post from Ruys and Stapel, whose results show:

...that specific emotions can be elicited without conscious awareness of their cause...disgusting pictures (presented for 120 msec, not perceived) increased cognitive accessibility of disgust words and feelings of disgust. Similarly, fearful pictures increased cognitive accessibility of fear words and feelings of fear. When exposure to the priming stimuli was super-quick (40 msec), global mood, rather than a specific emotion, was evoked. These findings... empirically demonstrate (a) that specific emotions can be evoked without conscious awareness of their cause, (b) that unconscious exposure to emotion-eliciting pictures can evoke the specific corresponding emotion and does not evoke other emotions of similar valence, and (c) that unconscious emotion induction develops from elicitation of global affect to elicitation of specific emotions.

Light deprivation damages neurons and causes depression

Experiments from Gonzalez and Aston-Jones on how light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats:

Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep–waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood.

Emonomics

Berreby offers an entertaining review of Ariely's new book "Predictably Irrational," which deals with behavioral economics - the experimental study of what people actually do when they buy, sell, change jobs, marry and make other real-life decisions. The book is a concise summary of why today’s social science increasingly treats the markets-know-best model as a fairy tale.

To see how arousal alters sexual attitudes, for example, Ariely and his colleagues asked young men to answer a questionnaire — then asked them to answer it again, only this time while indulging in Internet pornography on a laptop wrapped in Saran Wrap. (In that state, their answers to questions about sexual tastes,, violence and condom use were far less respectable.) To study the power of suggestion, Ariely’s team zapped volunteers with a little painful electricity, then offered fake pain pills costing either 10 cents or $2.50 (all reduced the pain, but the more expensive ones had a far greater effect). To see how social situations affect honesty, they created tests that made it easy to cheat, then looked at what happened if they reminded people right before the test of a moral rule. (It turned out that being reminded of any moral code — the Ten Commandments, the non-existent “M.I.T. honor system” — caused cheating to plummet.)

The brain and emotion-laden images: two pathways

A collaborative study has considered several models that might explain why our behavior can be rapidly influenced by an emotional stimulus (a snake like shape that we jump away from) before the stimulus has been fully processed (and we realize that it is a coil of rope). Information influences action before perception is complete. The data can only be accounted for by a two-pathway architecture by which emotional visual information proceeds more directly via one pathway to the amygdala (and thus influences action) and at the same time more slowly by the second conventional visual pathway that establishes the perception of the actual nature of the stimulus. I'm showing here the abstract and then the basic figure describing the models.

Visual attention can be driven by the affective significance of visual stimuli before full-fledged processing of the stimuli. Two kinds of models have been proposed to explain this phenomenon: models involving sequential processing along the ventral visual stream, with secondary feedback from emotion-related structures ("two-stage models"); and models including additional short-cut pathways directly reaching the emotion-related structures ("two-pathway models"). We tested which type of model would best predict real magnetoencephalographic responses in subjects presented with arousing visual stimuli, using realistic models of large-scale cerebral architecture and neural biophysics. The results strongly support a "two-pathway" hypothesis. Both standard models including the retinotectal pathway and nonstandard models including cortical–cortical long-range fasciculi appear plausible.

Tested models. (Click on image to enlarge) a, Basic components of the generic model, including all the possible types of connections used in this report, within and between two connected regions. Top, Cortical regions are modeled as three layered columns with three types of neuronal populations (pyramidal, excitatory spiny, and inhibitory interneurons), connected through intrinsic and extrinsic (feedforward and backward) connections. Bottom, The dynamics is mathematically expressed at the level of neural populations and is defined by nonlinear differential equations in which the change of state of each unit dxi/dt depends on its current state xi(t); thalamic inputs ui(t); average firing rate of afferents S(xj(t – {delta}ij)); transmission delays {delta}ij; forward, backward, and intrinsic effective connectivity matrices CF, CB, Ci, and other parameters. The MEG signal M is assumed to be related to the local average current density x generated by pyramidal populations through a linear forward model M = GX. b, Lateral, mesial, and ventral views of the mapping of the regions of interest common to all models on a reference cortical tessellation [for color code, see c (top row)]. c, Schematic representation of the architecture of the tested models. All the models share the same basic layout (see text). Null model, Simple feedforward model. Model 1, Adjunction of connectivity modulation. Model 2 (2-stage model), Adjunction of local feedbacks. Model 3 (2-stage model), Adjunction of long-range feedbacks from structures of the AAS (anterior affective system). Model 4 (2-pathway model), Adjunction of a direct subcortical retinotectal short-cut pathway to the AAS. Model 5 (2-pathway model), Alternative short-cut pathways to the AAS via the inferior longitudinal and frontal–occipital fasciculi. Model 6 (2-pathway model), Combination of models 4 and 5. Orange circles, "Synapses" at which modulation by emotional competence of the stimuli is implemented.

Why smoking pot chills you out...

The title of the article by Phan et al. in J. Neuroscience is "Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans" and their abstract says it clearly:

The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of {Delta}9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB1 receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid system for disorders of anxiety and social fear.


Figure - THC effects on amygdala activation. A, B, Statistical t maps overlaid on a canonical brain rendering (MNI coronal y-plane = 0) showing right lateral amygdala activation to threat (>nonthreat) faces is present during the PBO session but absent during the THC session. C, Statistical t map overlaid on a canonical brain rendering (MNI coronal y-plane = 0) showing greater threat-related amygdala reactivity in the PBO relative to the THC session (PBO > THC). For additional information, see Results. Statistical t score scale is shown at the bottom of the brain rendering. R, Right.

Adolescent outbursts related to prefrontal and amygdala sizes

Whittle et al. have done fMRI experiments on adolescents that focused on three key brain regions which are known to represent critical nodes in neural networks supporting affective regulation: the amygdala, anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Increased amygdala volume and a relative decrease of left versus right paralimbic ACC volumes were associated with increased duration of aggressive behaviors during parent-child interactions, with the latter association being apparent in males but not females. Decreased relative volume of left vs. right OFC was associated with greater reciprocity of dysphoric behaviors, the association also being specific to males. An absence of mean gender differences in affective behaviors suggests that the neural circuits underlying affective behaviors may differ for male and female adolescents during this age period. Here are some (slightly edited) comments by the authors:

The maturation of the prefrontal cortex and its inhibitory connections with the subcortex are key outcomes of the adolescent neurodevelopment that underlies the development of emotional and behavioral regulatory abilities. The associations of increased amygdala volume and decreased left frontal asymmetries with more negative affective behaviors may represent a delay in brain maturation. Longitudinal research would be needed to examine whether these findings have implications for the development of affective and behavioral dysregulation later in life.

The male specificity of this finding adds to a growing body of evidence that the neural mechanisms underlying affective processing differ between males and females. Males have been found to exhibit structural and functional brain asymmetries to a greater extent than females in a number of prefrontal areas, including the cingulate region. It has been suggested that these asymmetries may render males more vulnerable to certain disorders involving dysfunction of the frontal lobes such as ADHD, autism, and dyslexia. Although males in the present study did not display more aggressive behavior than females, the more pronounced relationship between ACCP asymmetry and aggressive affective behaviors in males suggests that aggressive affect in male adolescents may function as a mechanism by which their brain asymmetry is implicated in their risk for psychopathology.

Here is a useful figure that shows you the locations and variations in the anatomy of the cingulate structures being discussed:

Figure-Example of changes in the location and extent of the limbic (ACCL; highlighted in green) and paralimbic (ACCP; highlighted in blue) anterior cingulate cortices as a function of variations in the cingulate sulcus (CS; green arrow, Upper row) and paracingulate sulcus (PCS; blue arrow, Upper row). A PCS is absent in the left-hand case and present in the right-hand case. The Upper row presents parasagittal slices through an individual's T1-weighted image. The coronal section illustrates the distinction between absent (left-hand side) and present (right-hand side) cases. Notice that the ACCP is buried in the depths of the CS when the PCS is absent and extends over the paracingulate gyrus when the PCS is present. The same principle applies throughout consecutive coronal sections.

Brain imaging of our parental instinct

A group of collaborators reports in PLOS ONE a specific and rapid neural signature for our parental instinct:

Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of one's own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG) in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC), an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA)....These findings provide evidence in humans of a potential brain basis for the “innate releasing mechanisms” described by Lorenz for affection and nurturing of young infants.


The group analysis reveals a significant peak in the medial orbitofrontal cortex in the 10–30 Hz band in the 0–250 ms (first two columns), 100–350 ms (third column) and 200–450 ms (fourth column) windows when participants viewed infant (upper row) and not when they viewed adult faces (lower row). The fifth column shows the integrated map over the three time windows...In order to see the extent of the spread of activity over the fusiform cortices elicited by faces, the group activity is superimposed on a ventral view of the human brain (with the cerebellum removed).

Reasoning about our irrational ways

Elizabert Kolbert writes an interesting review in The New Yorker of several books on our irrational economic and political behaviors, the field of behavioral economics. It seems very likely that as politicians and governments become more knowledgeable about the patterns and emotional mechanisms governing our blunders, they will begin to nudge people towards more rational choices. The 'opt out' plans for increasing the numbers of people with health insurance plans or retirement savings are one example of this. Obama's campaign is making very good use of some basic neuro-economics and some of his people are aware of Westin's work (see my July 11 post), as well as Lakoff's (see Jan 31 post). Hillary doesn't seem to have a clue......