The relaxation response correlates with changes in gene expression

Herbert Benson's book "The Relaxation Response" which appeared about 25 years ago, has had great influence in shaping public awareness of the debilitating effects of stress and anxiety and measure that can be taken to counter it. His institute at the Mass General Hospital has generated an interesting study of changes in gene expression profiles observed in short and long term relaxation response (RR) practitioners. A bit of context is provided in the introduction:

Mind-body approaches that elicit the RR include: various forms of meditation, repetitive prayer, yoga, tai chi, breathing exercises, progressive muscle relaxation, biofeedback, guided imagery and Qi Gong. One way that the RR can be elicited is when individuals repeat a word, sound, phrase, prayer or focus on their breathing with a disregard of intrusive everyday thoughts. The non-pharmacological benefit of the RR on stress reduction and other physiological as well as pathological parameters has attracted significant interest in recent years to decipher the physiological effects of the RR. In addition to decreased oxygen consumption, other consistent physiologic changes observed in long-term practitioners of RR techniques include decreased carbon dioxide elimination, reduced blood pressure, heart and respiration rate, prominent low frequency heart rate oscillations and alterations in cortical and subcortical brain regions.

The authors observed changes in gene expression profiles regulating molecular and biochemical pathways involved in cellular metabolism, oxidative phosphorylation, generation of reactive oxygen species and response to oxidative stress. They suggest that these changes to some degree serve to ameliorate the negative impact of stress (which is known to increase oxidative stress and promote a pro-inflammatory milieu).

Persistence of anxious temperament - brain correlates

The temperament we display in early childhood (introvesion versus extroversion, high versus low reactivity, anxiety in unfamiliar versus familiar situations, etc) is largely genetically determined and persists through life. The work of Kagan and others has shown that children classed as highly reactive as babies are more likely to be subdued in unfamiliar situations and report a dour mood and anxiety over the future. Anxious temperament is an early predictor of the later risk to develop anxiety, depression and drug abuse related to self-medicating. It becomes increasingly clear that people with anxious temperaments are come wired that way, telling them to calm down just doesn't work. Kalin and his colleagues here at Wisconsin have produced an interesting study on the relevant brain correlates of this behavior by looking at brain activity, anxious behavior and stress hormones in adolescent rhesus monkeys, which have been used in numerous studies as models to understand anxious temperament in human children. They found that individuals with the most anxious temperaments showed higher activity in the amygdala, which regulates emotion and triggers reactions to anxiety, such as the fight or flight response. These anxious monkeys had more metabolic activity in the amygdala in both secure and threatening situations. These differences remained over several years of testing. From their abstract:

Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In addition, the findings provide an explanation for why individuals with anxious temperament have difficulty relaxing in environments that others perceive as non-stressful.

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.

Social heirarchy, stress, and diet

I become increasingly convinced over time that much of what runs our behavior is is the same stuff that runs a macaque monkey, with the human self conscious rationalizing overlay mainly being a window dressing. This is why I find numerous bits of work that have emerged from Yerkes Primate Research group (the subject of this and other previous posts) so fascinating.

A recent report from Wilson et al. is an extension of work by Seligman and many others that has shown that one's role in a hierarchy, or relative position in a gradient of personal helplessness to power, is a fundamental determinant of individual well being in both animal and human societies. Subordinate individuals show more chronic stress, anxiety-like behaviors, and susceptibility to disease. Wilson et al. show that socially subordinate macaque females consume more high caloric food and weigh more, and feed both during daylight and night (unlike dominants) .

Tierney notes the similarity of this result and the famous Whitehall study of British civil servants, which found that lower-ranking workers were more obese than higher-status workers. Even though the subordinate workers were neither poor nor lacked health care, their lower status correlated with more health problems. He also mentions the experiments of Zellner, who:

...tested both men and women by putting bowls of potato chips, M&Ms, peanuts and red grapes on a table as the participants in the study worked on solving anagrams. Some of the people were given unsolvable anagrams, and they understandably reported being more stressed than the ones given easy anagrams...The stress seemed to affect snacking in different ways for each sex. The women given solvable puzzles ate more grapes than M&Ms, while the women under stress preferred M&Ms. The men ate more of the high-fat snacks when they were not under stress, apparently because the ones who got the easy anagrams had more time to relax and have a treat.

Healing and sedative effects of music.

An article by David Dobbs describes the work of musician/surgeon Claudius Conrad, who suggests that music may exert healing and sedative effects partly through a paradoxical stimulation of a growth hormone generally associated with stress rather than healing. His study, published in Critical Care Medicine:

...was fairly simple. The researchers fitted 10 postsurgical intensive-care patients with headphones, and in the hour just after the patients’ sedation was lifted, 5 were treated to gentle Mozart piano music while 5 heard nothing...The patients listening to music showed several responses that Dr. Conrad expected, based on other studies: reduced blood pressure and heart rate, less need for pain medication and a 20 percent drop in two important stress hormones, epinephrine and interleukin-6, or IL-6. Amid these expected responses was the study’s new finding: a 50 percent jump in pituitary growth hormone...The question is whether the jump in growth hormone actually drives the sedative effect or is part of something else going on.

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 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.

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.

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.

An antidepressant enhances brain plasticity

The title of the article by Vetencourt et al. is "The Antidepressant Fluoxetine Restores Plasticity in the Adult Visual Cortex. " [Fluoxetine hydrochloride, i.e. Prozac, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.] Here is their abstract:

We investigated whether fluoxetine, a widely prescribed medication for treatment of depression, restores neuronal plasticity in the adult visual system of the rat. We found that chronic administration of fluoxetine reinstates ocular dominance plasticity in adulthood and promotes the recovery of visual functions in adult amblyopic animals, as tested electrophysiologically and behaviorally. These effects were accompanied by reduced intracortical inhibition and increased expression of brain-derived neurotrophic factor in the visual cortex. Cortical administration of diazepam prevented the effects induced by fluoxetine, indicating that the reduction of intracortical inhibition promotes visual cortical plasticity in the adult. Our results suggest a potential clinical application for fluoxetine in amblyopia as well as new mechanisms for the therapeutic effects of antidepressants and for the pathophysiology of mood disorders.

A mouse model for PTSD suggests a therapy

Pibiri et al. have performed experiments on mice that model the emotional hyper-reactivity (including enhanced contextual fear and impaired contextual fear extinction) that is observed in human post traumatic stress disorder (PTSD) patients. They suggest that activation of neuronal steroid synthesis might be useful in PTSD therapy. The edited abstract:

Mice subjected to social isolation (3–4 weeks) exhibit enhanced contextual fear responses and impaired fear extinction. These responses are time-related to a decrease of ... allopregnanolone (Allo) levels in selected neurons of the medial prefrontal cortex, hippocampus, and basolateral amygdala...In socially isolated mice, S-norfluoxetine, in doses that increase brain Allo levels but fail to inhibit serotonin reuptake, greatly attenuates enhanced contextual fear response. The drug SKF decreases corticolimbic Allo levels and enhances the contextual fear response in group housed mice... A recent clinical study reported that cerebrospinal fluid Allo levels also are down-regulated in human PTSD patients and correlate negatively with PTSD symptoms and negative mood. Thus, protracted social isolation of mice combined with tests of fear conditioning may be a suitable model to study emotional behavioral components associated with neurochemical alterations relating to PTSD. Importantly, selective brain steroidogenic stimulants such as S-norfluoxetine, which rapidly increase corticolimbic Allo levels, normalize the exaggerated contextual fear responses resulting from social isolation, suggesting that selective activation of neurosteroidogenesis may be useful in PTSD therapy.

Even brief stress can zap your brain...

Well...to be sure, we're talking about rat brains, but the message is probably there for us as well. An interesting (and sobering) piece of work from Sapolsky's laboratory shows that a single dose of corticosterone, i.e. an increase in its levels of the sort that would be induced by temporary stress, is sufficient to induce the hyper-growth of nerve cell dendrites in the basolateral amygdala and heighten anxiety behaviors. Here is the complete abstract, followed by a figure from the paper:

Stress is known to induce dendritic hypertrophy in the basolateral amygdala (BLA) and to enhance anxiety. Stress also leads to secretion of glucocorticoids (GC), and the BLA has a high concentration of glucocorticoid receptors. This raises the possibility that stress-induced elevation in GC secretion might directly affect amygdaloid neurons. To address the possible effects of GC on neurons of amygdala and on anxiety, we used rats treated either acutely with a single dose or chronically with 10 daily doses of high physiological levels of corticosterone (the rat-specific glucocorticoid). Behavior and morphological changes in neurons of BLA were measured 12 days after the initiation of treatment in both groups. A single acute dose of corticosterone was sufficient to induce dendritic hypertrophy in the BLA and heightened anxiety, as measured on an elevated plus maze. Moreover, this form of dendritic hypertrophy after acute treatment was of a magnitude similar to that caused by chronic treatment. Thus, plasticity of BLA neurons is sufficiently sensitive so as to be saturated by a single day of stress. The effects of corticosterone were specific to anxiety, as neither acute nor chronic treatment caused any change in conditioned fear or in general locomotor activity in these animals.

Figure - Representative camera lucida drawing of neurons from animals treated either acutely (A) or chronically (B) with CORT (Right) compared with their respective vehicle-treated controls (i.e. injection without the hormone) (Left).

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.

Antidepressant effects of eating less.

I notice that when I get paranoid about my weight creeping up and suddenly eat less for several days, my general mood improves considerably.... I wonder if the chemistry described in these (admittedly more extreme) experiments on rodents done by Lutter et al. is what is going on. The experiments deal with the orexin neuropeptides, which can stimulate food seeking activity in mice and decrease anxiety-like behaviors in helplessness and social defeat model of stress. (Decreased levels of orexin-A have been reported in the CSF of suicidal patients with major depressive disorder, supporting chronic social defeat stress as a model of major depression.) The title of the article is "Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction" Here is the abstract:

During periods of reduced food availability, animals must respond with behavioral adaptations that promote survival. Despite the fact that many psychiatric syndromes include disordered eating patterns as a component of the illness, little is known about the neurobiology underlying behavioral changes induced by short-term calorie restriction. Presently, we demonstrate that 10 d of calorie restriction, corresponding to a 20–25% weight loss, causes a marked antidepressant-like response in two rodent models of depression and that this response is dependent on the hypothalamic neuropeptide orexin (hypocretin). Wild-type mice, but not mice lacking orexin, show longer latency to immobility and less total immobility in the forced swim test after calorie restriction. In the social defeat model of chronic stress, calorie restriction reverses the behavioral deficits seen in wild-type mice but not in orexin knock-out mice. Additionally, chronic social defeat stress induces a prolonged reduction in the expression of prepro-orexin mRNA via epigenetic modification of the orexin gene promoter, whereas calorie restriction enhances the activation of orexin cells after social defeat. Together, these data indicate that orexin plays an essential role in mediating reduced depression-like symptoms induced by calorie restriction.

Anxiety: fear in seach of a cause

The title of this post is a pithy definition that Patricia Pearson gives in her recent book, "A BRIEF HISTORY OF ANXIETY... Yours and Mine", reviewed by William Grimes in the NY Times. From that review some clips:

Everywhere and nowhere, anxiety... In many cases it is the fear of fear itself, a free-floating, nebulous entity that, like a mutant virus, feeds on any available host. Reason is powerless against it. Ms. Pearson argues, in fact, that rationalism, intended to banish superstition and fear, has instead removed one of the most effective weapons against anxiety, namely religious faith and ritual.

...the worship of reason and science, by encouraging the notion that human beings can control their environment, has created a terrible fault line in the modern psyche, although not all societies suffer equally. Mexicans have lots to worry about but don’t. The World Mental Health Survey, conducted in 2002, found that only 6.6 percent of Mexicans had ever experienced a major episode of anxiety or depression. Meanwhile, to their north, 28.8 percent of the American population has been afflicted with anxiety, the highest level in the world. Mexicans who move to the United States adapt, becoming more anxious.

Depressing news: antidepressants don't work?

In the April issue of Nature Reviews Neuroscience, Claudia Wiedemann reviews reactions to a meta analysis by Kirsch et al. of data on antidepressant drugs submitted to the Food and Drug Administration that resulted in the licensing of four of the most commonly prescribed antidepressants: the selective serotonin reuptake inhibitors (SSRIs) Prozac, Seroxat, Effexor and Serzone. For anything but the most severe depression, there was no difference between the drugs and placebos. Kirsch suggests that there is little reason to prescribe anti-depressant medication to any but the most severely depressed patients. The conclusion of the study:

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

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.

Upset? Reduce your blood pressure by switching to 3rd person view.

How we view our own stories, immersed within them or viewing them as outside observer, can have a big effect on our ability to change (see 5/30/07 post). Negative feelings and stress are known to enhance vulnerability to cardiac disease, and a problem with ruminating over these negative feelings or events is that the effort can backfire, and instead maintain or enhance negativity. Ayduk and
Kross ask whether the outcome of self analysis depends on the type of self-perspective that is adopted, self-immersed (1st person) or self-distanced (3rd person).

Their experiments recruited 90 undergraduates who:

...were cued to recall an experience when they were angry and indicated that they had recalled an appropriate experience by pressing the space bar (i.e., recall phase); the computer recorded their recall times. Then they were told, "Go back to the time and place of the conflict and see the scene in your mind's eye." They were then randomly assigned to one of two perspective conditions (the manipulation phase). In the self-immersed condition, participants were told: "Relive the situation as if it were happening to you all over again … Reexperience the interaction as it progresses in your mind's eye."

In the self-distanced condition, participants were told: "Take a few steps back … . Move away from the situation to a point where you can now watch the conflict from a distance … . Watch the conflict unfold as if it were happening all over again to the distant you. Replay the interaction as it progresses in your mind's eye."

At the end students filled out a questionnaires (the recovery phase) rating the extent to which and the intensity with which they re-experienced their original feelings during the experiment. Blood pressure (mean arterial pressure, or MAP) was monitored throughout the three phases of the experiments.

The authors expected and found no difference between the two groups in MAP reactivity during recall. In contrast, participants in the self-distanced group showed lower MAP reactivity than those in the self-immersed group during both the manipulation and the recovery phases of the experiment. (That is, they were more chilled out, had lower blood pressure.)

Innate fear of snakes in young humans

Monkeys very rapidly learn to fear snakes simply from seeing another monkey react fearfully to the presence of a snake. There has been a question of whether our human aversion to snake forms requires such learning, or might develop autonomously. Experiments by LoBue and DeLoache support the idea that our visual systems employ an innate developmental sequence to develop a heightened awareness of snake like forms very early in development, independent of actual direct or indirect experience of snakes. 3-5 year olds preferentially attended to snake pictures, even compared with pictures of caterpillars (as well as pictures of flowers or frogs), and this preference was the same in the presence or absence of previous exposure to snakes or snake images.
A preschool child identifying the single flower target among eight snake distractors by touching the flower image on a touch-screen monitor.

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.