2010 December 16 Thursday
Lack Of Amygdala Function Makes Woman Fearless

Fearlessness comes from an underactive amygdala.

A new study, published online on December 16 in Current Biology, a Cell Press publication, offers new insight into the emotional life of a unique individual who completely lacks the function of an almond-shaped structure in the brain known as the amygdala. Studies over the last 50 years have shown that the amygdala plays a central role in generating fear reactions in animals from rats to monkeys. Based on the detailed case study of the woman identified only as SM, it now appears that the same is true of humans.

She knows no fear.

To explore this role of the amygdala, Feinstein and his Univeristy of Iowa team observed and recorded SM's responses in a variety of situations that would make most people feel fear. They exposed her to snakes and spiders, took her to one of the world's scariest haunted houses, and had her watch a series of horror films. They also had her fill out questionnaires probing different aspects of fear, from the fear of death to the fear of public speaking. On top of that, SM faithfully recorded her emotions at various times throughout the day while carrying around an electronic diary over a 3-month period. Across all questionnaires, measures, and scenarios, SM failed to experience fear.

That apparent lack of fear mirrored her personal experience, Feinstein said. "In everyday life, SM has encountered numerous traumatic events which have threatened her very existence, and by her report, have caused no fear. Yet, she is able to feel other emotions such as happiness and sadness. Taken together, these findings suggest that the human amygdala is a pivotal area of the brain for triggering a state of fear."

Drugs to suppress the amygdala might help those with post-traumatic stress syndrome. Or perhaps right after a traumatic experience soldiers could be given drugs to disable the amygdala to prevent conditioning to feel severe fear? Her emotional core is immune to the horrors of life.

"This past year, I've been treating veterans returning home from Iraq and Afghanistan who suffer from PTSD. Their lives are marred by fear, and they are oftentimes unable to even leave their home due to the ever-present feeling of danger," Feinstein said. "In striking contrast, the patient in this study is immune to these states of fear and shows no symptoms of post-traumatic stress. The horrors of life are unable to penetrate her emotional core. In essence, traumatic events leave no emotional imprint on her brain."

My theory: the cowardly lion had an over-active amygdala.

By Randall Parker    2010 December 16 11:49 PM   Entry Permalink | Comments (3)
2010 August 11 Wednesday
Angry People Respond More To Rewards Than Threats?

Make someone angry so they'll respond more to the prospect of rewards?

Anger is a negative emotion. But, like being happy or excited, feeling angry makes people want to seek rewards, according to a new study of emotion and visual attention. The researchers found that people who are angry pay more attention to rewards than to threats—the opposite of people feeling other negative emotions like fear. 

Previous research has shown that emotion affects what someone pays attention to. If a fearful or anxious person is given a choice of a rewarding picture, like a sexy couple, or a threatening picture, like a person waving a knife threateningly, they’ll spend more time looking at the threat than at the rewarding picture. People feeling excitement, however, are the other way—they’ll go for the reward. 

But nobody knows whether those reactions occur because the emotions are positive or negative, or because of something else, says Brett Q. Ford of Boston College, who wrote the study with Maya Tamir, also of Boston College, and four other authors. For example, she says, “emotions can vary in what they make you want to do. Fear is associated with a motivation to avoid, whereas excitement is associated with a motivation to approach. It can make you want to seek out certain things, like rewards.” The research is published in Psychological Science, a journal of the Association for Psychological Science. 

Can you manipulate a person's behavior by careful sequencing of the emotional states you evoke in them? Seems that way. Though you obviously need the means by which to evoke the sequence of emotional states.

The anger that you evoke doesn't have to be aimed at you. If you know, for example, the political affiliations of someone you can point out something bound to make them angry about their evil political opponents. Then offer them some reward for doing something you want them to do.

By Randall Parker    2010 August 11 10:47 PM   Entry Permalink | Comments (3)
2008 October 29 Wednesday
Immune System Changes Emotional Reactions

Hello again puppets. Add immune system mast cells to our list of puppeteers. Anyone still think we have free will?

In the first study ever to genetically link the immune system to normal behavior, scientists at Rockefeller and Columbia universities show that mast cells, known as the pharmacologic bombshells of the immune system, directly influence how mice respond to stressful situations. The work, to appear this week in The Proceedings of The National Academy of Sciences and to be highlighted in Science, chips away at the increasingly stale idea that the two most complex systems in the body have entirely separate modes of operation.

Eight years ago, scientists from Columbia University discovered that mast cells travel to the brain from other organs early on in development. “We now knew that mast cells resided in the brain but we didn’t know their function,” says Rockefeller University’s Donald Pfaff, head of the Laboratory of Neurobiology and Behavior. “But we know that they synthesize a large number of important chemical mediators that could potentially have severe neurophysiological effects.”

Since the immune system ages and becomes less vigorous that suggests that aging of the immune system alters our emotional reactions.

If aging people could get their immune systems rejuvenated they might become more adventurous.

In their work, Pfaff and postdoc Ana Ribeiro, and the Columbia team, led by senior author Rae Silver and graduate student Kate Nautiyal, bred mice that lacked mast cells and compared their behavior in stressful situations to the behavior of mice that had a full or a moderate arsenal of mast cells. The researchers observed how willing the mice were to navigate open and lit environments and high spaces, which mice find anxiety-producing. In the wild, if a mouse is down in its own burrow, it’s not visible to predation. But if it’s bold, that is, if it has low anxiety, it will go out where it can potentially be seen by predators and hunted.

The results were striking. When the researchers placed the mice in an elevated maze with four long arms -- two simulated a canyon and the other two a cliff -- mice that lacked mast cells preferred to stay in the canyons, entering and investigating the doors to the cliffs significantly fewer times than mice with mast cells. When placed in a square box, mast cell-deficient mice preferred to scuttle against the walls, and were more hesitant to venture out to the center of the box than mice with mast cells. They also defecated more, a physiological sign of anxiety. However, the genetically different mice did not show differences in overall arousal or locomotion, suggesting that their behavioral changes were specific to their anxious state.

So an unhealthy immune system can increase anxiety. Do anxious people get colds and flus more often?

By Randall Parker    2008 October 29 08:00 AM   Entry Permalink | Comments (12)
Brain Scans Of People Full Of Hate Show Unique Hate Signature

Coming from Professor Semir Zeki and John Romaya of the Wellcome Laboratory of Neurobiology at the University College London, a new research paper in Plos One on how hatred activates and deactivates areas of the brain shows hate creates a unique pattern of brain activates which includes some overlap with brain areas activated by love.

In this work, we address an important but unexplored topic, namely the neural correlates of hate. In a block-design fMRI study, we scanned 17 normal human subjects while they viewed the face of a person they hated and also faces of acquaintances for whom they had neutral feelings. A hate score was obtained for the object of hate for each subject and this was used as a covariate in a between-subject random effects analysis. Viewing a hated face resulted in increased activity in the medial frontal gyrus, right putamen, bilaterally in premotor cortex, in the frontal pole and bilaterally in the medial insula. We also found three areas where activation correlated linearly with the declared level of hatred, the right insula, right premotor cortex and the right fronto-medial gyrus. One area of deactivation was found in the right superior frontal gyrus. The study thus shows that there is a unique pattern of activity in the brain in the context of hate. Though distinct from the pattern of activity that correlates with romantic love, this pattern nevertheless shares two areas with the latter, namely the putamen and the insula.

Hatred does not activate the amygdala which is activated by fear.

It is important to note that the pattern revealed is distinct from that of other, closely related, emotions such as fear, anger, aggression and danger, even though it shares common areas with these other sentiments. Thus, the amygdala which is strongly activated by fear (Noesselt et al. 2005 [9], Morris et al. 2002 [10], Hadjikhani et al. 2008 [11]) and by aggression (Beaver et al., 2008 [12]) was not activated in our study. Nor were the anterior cingulate, hippocampus, medial temporal regions, and orbitofrontal cortex, apparently conspicuous in anger and threat (Denson et al. 2008 [13]; Bufkin and Luttrell 2007 [14]; McClure et al. 2004 [15]), evident in our study. It would thus seem that, though these sentiments may constitute part of the behaviour that results from hatred, the neural pathways for hate are distinct.

Parts of the brain involved in motor function get activated - perhaps so one can move in and attack the object of one's hate?

The 'hate circuit' includes structures in the cortex and in the sub-cortex and has components that are important in generating aggressive behaviour, and translating this into action through motor planning, as if the brain becomes mobilised to take some action. It also involves a part of the frontal cortex that has been considered critical in predicting the actions of others, probably an important feature when one is confronted by a hated person.

The subcortical activity involves two distinct structures, the putamen and insula. The former, which has been implicated in the perception of contempt and disgust, may also be part of the motor system that is mobilised to take action, since it is known to contain nerve cells that are active in phases preparatory to making a move.

Professor Zeki added: "Significantly, the putamen and insula are also both activated by romantic love. This is not surprising. The putamen could also be involved in the preparation of aggressive acts in a romantic context, as in situations when a rival presents a danger. Previous studies have suggested that the insula may be involved in responses to distressing stimuli, and the viewing of both a loved and a hated face may constitute such a distressing signal.

While love shuts down areas of the brain associated with judgment and reasoning by contrast those consumed with hate have very active reasoning facilities. It takes logic to figure out how to attack your enemy. So that makes sense. Only those in love think they can afford to let their guard down, become zombies, and feel bliss around the object of their affection.

"A marked difference in the cortical pattern produced by these two sentiments of love and hate is that, whereas with love large parts of the cerebral cortex associated with judgment and reasoning become de-activated, with hate only a small zone, located in the frontal cortex, becomes de-activated. This may seem surprising since hate can also be an all-consuming passion, just like love. But whereas in romantic love, the lover is often less critical and judgmental regarding the loved person, it is more likely that in the context of hate the hater may want to exercise judgment in calculating moves to harm, injure or otherwise extract revenge.

In countries where suspected criminals have no right to privacy or right to keep silent brain scans could be used to determine whether a suspected killer hated his victim and by how much.

"Interestingly, the activity in some of these structures in response to viewing a hated face is proportional in strength to the declared intensity of hate, thus allowing the subjective state of hate to be objectively quantified. This finding may have legal implications in criminal cases, for example."

One could imagine a police state in which opponents of the regime get tested with brain scans and pictures of dictators to identify enemies of the state. With more time it will become possible for governments to turn hatred into love. Then all enemies of the state will get turned into supporters of it. Of course, individuals will try to do this on a smaller scale as well.

Contrast these results with the research into love. See my previous posts Love Deactivates Brain Areas For Fear, Planning, Critical Social Assessment, Love Like Addiction In Brain Scans, What Brain Scans Of People Falling In Love Tell Us, Romantic Love Seen As Motivation Or Drive Rather Than Emotional State, and Love Is Blind: Couples In Love Can't Identify Who Else Is In Love.

By Randall Parker    2008 October 29 12:09 AM   Entry Permalink | Comments (9)
2007 October 24 Wednesday
Video Games Reduce Perception Of Social Threats

By learning with video games people can be trained to feel less stress and produce less cortisol stress hormone.

A video game designed by McGill University researchers to help train people to change their perception of social threats and boost their self-confidence has now been shown to reduce the production of the stress-related hormone cortisol. The new findings appear in the October issue of the American Psychological Association's Journal of Personality and Social Psychology.

"We already knew that it was possible to design games to allow people to practise new forms of social perception, but we were surprised by the impact this had when we took the games out of the lab and into the context of people's stressful lives," said McGill psychology professor Mark Baldwin.

Prof. Baldwin and his team - McGill PhD graduates Stephane Dandeneau and Jodene Baccus and graduate student Maya Sakellaropoulo - have been developing a suite of video games that train players in social situations to focus more on positive feedback rather than being distracted and deterred by perceived social slights or criticisms. The games are based on the emerging science of social intelligence, which has found that a significant part of daily stress comes from our social perceptions of the world.

These video games could be useful.

By Randall Parker    2007 October 24 10:37 PM   Entry Permalink | Comments (0)
Neural Network For Optimism Found In Brain

If you are feeling optimistic it is all down to your rostral anterior cingulate cortex (rACC) and amygdala.

A neural network that may generate the human tendency to be optimistic has been identified by researchers at New York University. As humans, we expect to live longer and be more successful than average, and we underestimate our likelihood of getting a divorce or having cancer. The results, reported in the most recent issue of Nature, link the optimism bias to the same brain regions that show irregularities in depression.

Every report like this one reminds me that we are eventually going to gain the ability to very precisely manipulate our emotions. If we precisely manipulate our own emotions rather than governments or other organizations doing it to us (which is a real possibility) will we become more free?

Anyone want a switch to flip in your brain that activates the optimism circuitry?

The study was conducted by a team of researchers from the laboratory of NYU Professor Elizabeth Phelps. The lead author is Tali Sharot, now a post-doctoral fellow at University College London.

The NYU researchers used functional magnetic resonance imaging (fMRI) to examine brain function while participants thought of possible future life events (such as “winning an award” or “the end of a romantic relationship”).

“When participants imagined positive future events relative to negative ones, enhanced activation was detected in the rostral anterior cingulate and amygdala, which are the same brain areas that seem to malfunction in depression,” said Sharot. “Activation of the rostral anterior cingulate was correlated with trait optimism, with more optimistic participants showing greater activity in this region when imagining future positive events.”

What I wonder: can avoidance of depression somehow be uncoupled from optimism? I'm thinking optimism causes people to mispredict the future and make less than optimal choices.

Remember that scene at the end of Life Of Brian when they are all up on the crosses singing? The updated scientific version of the song would go "use your amygdala and the rostral anterior cingulated cortex to always look on the bright side of life".

By Randall Parker    2007 October 24 10:00 PM   Entry Permalink | Comments (4)
2007 September 12 Wednesday
Lonely People Have Different Gene Expression Patterns

Being lonely probably changes the level of expression of over 200 of your genes.

Cole and colleagues at UCLA and the University of Chicago used DNA microarrays to survey the activity of all known human genes in white blood cells from 14 individuals in the Chicago Health, Aging, and Social Relations Study. Six participants scored in the top 15 percent of the UCLA Loneliness Scale, a widely used measure of loneliness that was developed in the 1970s; the others scored in the bottom 15 percent. The researchers found 209 gene transcripts (the first step in the making of a protein) were differentially expressed between the two groups, with 78 being overexpressed and 131 underexpressed. “Leukocyte (white blood cell) gene expression appears to be remodelled in chronically lonely individuals,” said. Cole.

Genes overexpressed in lonely individuals included many involved in immune system activation and inflammation. But interestingly, several other key gene sets were underexpressed, including those involved in antiviral responses and antibody production. “These findings provide molecular targets for our efforts to block the adverse health effects of social isolation,” said Cole.

“We found that what counts at the level of gene expression is not how many people you know, it’s how many you feel really close to over time.” In the future, he said, the transcriptional fingerprint they’ve identified might become useful as a ‘biomarker’ to monitor interventions designed to reduce the impact of loneliness on health.

An obvious follow-up would be to find a way to make a group of lonely people a lot less lonely and then see if their gene expression levels change.

Being lonely is bad for your health and shortens your life expectancy.

It is already known that a person's social environment can affect their health, with those who are socially isolated suffering from higher all-cause mortality, and higher rates of cancer, infection and heart disease. Researchers are trying to determine whether these adverse health consequences result from of reduced social resources (e.g., physical or economic assistance) or from the biological impact of social isolation on the function of the human body. "What this study shows us," said lead author Dr. Steven Cole, of the University of California Los Angeles (UCLA) School of Medicine, "is that the biological impact of social isolation reaches down into some of our most basic internal processes - the activity of our genes."

Does some subgroup of isolated people have an immunity toward the effects of isolation? Do their genes express at levels similar to those of non-lonely people?

Also, why less immune activity in lonely people? Maybe that's an adaptation. If you aren't exposed to other people you are at lower risk of getting a disease from them. So maybe less immune response was needed in the past among lonely people. Though today with more urban environments even lonely people can frequently come into contact with others and therefore be at risk of getting infections.

By Randall Parker    2007 September 12 10:57 PM   Entry Permalink | Comments (0)
2007 June 02 Saturday
Anxiety By Type In Different Brain Areas

Anxiety comes in several types and 2 of those types differ in the parts of the brain involved.

CHAMPAIGN, Ill. — All anxiety is not created equal, and a research team at the University of Illinois now has the data to prove it. The team has found the most compelling evidence yet of differing patterns of brain activity associated with each of two types of anxiety: anxious apprehension (verbal rumination, worry) and anxious arousal (intense fear, panic, or both).

Worriers have more activity in their left inferior frontal lobe. Whereas people feeling panic or fear are feeling the effects of activity in the right inferior temporal lobe.

The researchers used functional Magnetic Resonance Imaging (fMRI) to map the brain areas with heightened neural activity during a variety of psychological probes.

As the researchers had predicted, the anxious apprehension group exhibited enhanced left-brain activity and the anxious arousal group had heightened activity in the right brain. The anxious apprehension group showed increased activity in a region of the left inferior frontal lobe that is associated with speech production. The anxious arousal group had more activity in a region of the right-hemisphere inferior temporal lobe that is believed to be involved in tracking and responding to information signaling danger.

Better understanding eventually brings with it better ability to manipulate and control. Picture a future where nanotubes can get extended up arteries into the brain. The nanotubes could be used to locally deliver drugs or electrical pulses to excite or suppress activity in particular parts of the brain.

Of course the ability to stimulate particular kinds of emotions and mental states would enable some pretty severe abuse and manipulation of human behavior. But individuals could use such technology to control crippling emotional conditions. Plus, imagine turning up the motivation to work hard when you want to get more done.

By Randall Parker    2007 June 02 03:37 PM   Entry Permalink | Comments (1)
2006 October 01 Sunday
Brain Circuit Found That Resolves Emotional Conflicts

Neuroscientists using functional Magnetic Resonance Imaging (fMRI) brain scans have discovered a connection between two parts of the brain that allows one part of the brain to dampen down emotional conflicts so that the brain's ability to think does not become impaired.

New York, NY (Sept. 20, 2006) – Columbia University Medical Center researchers have identified an emotional control circuit in the human brain which keeps emotionally intense stimuli from interfering with mental functioning. These results significantly enhance understanding of the neurobiology underlying psychiatric disorders involving emotional control, such as post traumatic stress disorder (PTSD) or depression.

The ability to prevent PTSD and depression would eliminate the brain damage that those mental diseases cause and therefore cause a substantial portion of the population to function at a higher level than would otherwise be the case.

Negative emotions are processed by the amygdala and the scientists decided to figure out which part of the brain exerted a dampening effect upon feelings of fear. They previously had found that people who are more anxious tend to react more to fearful stimuli if they are not consciously aware that they see something fearful.

The current findings extend on a previous Neuron paper (Dec 16, 2004) in which Drs. Etkin, Kandel and Hirsch found that anxious individuals show more activity in the amygdala, a central brain region involved in the processing of negative emotions, when unconsciously perceiving fearful stimuli (please click here to read the Columbia press release). When these stimuli were perceived consciously, however, the amygdalas of subject with both high and low levels of anxiety responded similarly.

Dr. Hirsch explained that this previous finding suggested that subjects were somehow able to control their conscious emotional responses, but that their unconscious responses may be more automatic.  “Following the discovery of the amygdala’s role in fear response, we decided to explore the finer points of the neurocircuitry of fear – how it is regulated and controlled in the brain,” said Dr. Hirsch.

The scientists were able to identify the brain circuitry that resolves emotional conflicts.

To study emotional regulation, Dr. Etkin collaborated with Tobias Egner, Ph.D., a post-doctoral fellow in Dr. Hirsch’s lab, who has used fMRI to study non-emotional forms of attentional control. In the 2006 Neuron paper, subjects were asked to identify the facial expressions in photos shown to them as either happy or fearful. Across each face were the words FEAR or HAPPY, and were either congruent or conflicting from the facial expressions. When the word and face clashed, subjects experienced an emotional conflict, which slowed their performance and made them less accurate in identifying facial expressions.

Using a clever behavioral trick, however, the researchers were able to discriminate between brain circuitry that detected this emotional conflict from circuitry that resolved this conflict. They found that the amygdala generates the signal telling the brain that an emotional conflict is present; this conflict then interferes with the brains ability to perform the task. The rostral anterior cingulate cortex, a region of the frontal lobe, was activated to resolve the conflict. Critically, the rostral cingulate dampened activity in the amygdala, so that the emotional response did not overwhelm subjects’ performance, thus achieving emotional control.

Do people with anxiety problems have smaller or less active rostral anterior cingulate cortexes? Or is the connection from that region to the amygdala smaller?

Seems to me this study suggests where we could intervene in the brain to reduce distractions caused by emotional conflicts. Imagine a brain stimulator device that sends a signal to the amygdala saying "chill out dude".

The greater our understanding of human emotions becomes the better we'll be able to manipulate our own emotions. Will most people decide to function under the influence of biotechnologically manipulated emotions?

If people decide to manipulate their emotions which types of manipulations will they choose? On the one hand, I can see competitive pressures for people to manipulate their emotions so that they work harder and get more done. On the other hand, I can imagine a future in which very large numbers of people manipulate their emotions so that they do not feel the need to compete and so that they feel happy and satisfied with less material goods and lower social statuses.

By Randall Parker    2006 October 01 07:14 PM   Entry Permalink | Comments (2)
2006 February 15 Wednesday
Emotional Distractions Hobble Memory Formation

Emotionally powerful distractions hobble memory formation.

For the first time, researchers have seen in action how the "hot" emotional centers of the brain can interfere with "cool" cognitive processes such as those involved in memory tasks. Their functional magnetic resonance imaging (fMRI) images of human volunteers exposed to emotional distraction revealed a "see-saw" effect, in which activation of emotional centers damped activity in the "executive" centers responsible for such processing.

The findings of the Duke University Medical Center researchers provide insight into the basic brain mechanisms responsible for the distraction caused by emotional stimuli that are irrelevant to a task. Moreover, they said, the findings offer a new approach to understanding how people with depression and post-traumatic stress disorder cope with traumatic events and memories. It is known that people with such problems are far more affected by emotional distraction.

The researchers compared the effects of three different kinds of distracters on the ability to memorize faces.

In their experiments, the researchers asked volunteer subjects to memorize sets of images of three human faces. Next, they exposed the subjects to one of three types of distracters -- emotional images such as injured people or aggressive behavior; neutral images such as people shopping or working; and scrambled images that meant nothing. The subjects were then showed a face image and asked to determine whether it was one of the original "to-be-memorized" faces or a new face.

Throughout the tests, the subjects' brains were scanned using fMRI. This widely used technique involves using harmless magnetic fields and radio waves to scan the brain to detect levels of blood flow, which indicates increased or decreased brain activity.

Stimuli that evoke an emotional reaction not only activate the ventral system of the brain but also reduce activity in the dorsal regions involved in rational thinking.

In earlier studies, the researchers had found that emotional images activated a "ventral affective system" in the brain that encompasses regions involved in emotional processing. In contrast, they found, cognitive tasks involving memory processes activated a "dorsal executive system." To their surprise, the researchers also found that the emotional distracters not only activated the ventral system, but also deactivated the dorsal regions.

In the new study, the researchers observed the same patterns of activation and deactivation of the regions. The emotional images produced greater activation of the ventral system and deactivation of the dorsal system than did the neutral or scrambled images, they found.

But most importantly, they found graded behavioral effects of the images. The emotional distracters produced the most detrimental effect on memory performance, the neutral distracters impaired performance to a lesser extent; and the scrambled images impaired performance very little. "Along with the fMRI results, these findings provide the first direct evidence concerning the neural mechanisms mediating cognitive interference by emotional distraction," said Dolcos.

Emotional distracter: That sounds like a technical term for "girlfriend".

People who could inhibit their emotional response were less distracted.

The researchers also found individual differences among the subjects in their response to the images. Those people who showed greater activity in a brain region associated with the inhibition of response to emotional stimuli rated the emotional distracters as less distracting. Said Dolcos, "One interpretation of this finding is that, because this region is associated with inhibitory process, people who engage that region more could cope better with distracting emotions."

I bet that genetic variations are partially responsible for people differing in their abilities to inhibit their emotional responses. For some inhibition of their emotions comes easy and surely the ability exists on a sliding scale. Also, there's probably not a single ability to inhibit all emotions. Some probably can more easily inhibit sadness and others anger and so on. If you have a particular form of emotion you have a hard time inhibiting then when you need to think clearly you are best off avoiding situations that will present stimuli that'll trigger that emotion.

This report of how emotional stimuli shut down areas of the brain involved in rational thought reminds me of another recent post of mine: "Political Partisans Addicted To Irrational Defense Of Their Tribes". This latest report throws more light on that previous report. People who are emotionally worked up about politics have a hobbled ability to think rationally.

By Randall Parker    2006 February 15 10:47 PM   Entry Permalink | Comments (5)
2005 May 09 Monday
Gene Version Prevents Cingulate From Suppressing Amygdala Fear Response

Having one or two copies of the short version of the serotonin transporter gene prevents enough connections from being formed in the brain between the cingulate and amygdala. As a result fearful and stressful situations cause the amygdala to be too active and the neural circuitry in the cingulate lacks the connectivitiy needed to dampen down the amygdala fear response, leading to anxiety and depression.

The gene codes for the serotonin transporter, the protein in brain cells that recycles the chemical messenger after it's been secreted into the synapse, the gulf between cells. Since the most widely prescribed class of antidepressants act by blocking this protein, researchers have focused on possible functional consequences of a slight variation in its DNA sequence across individuals. Everyone inherits two copies of the gene, one from each parent, which comes in two common versions: short and long. The short version makes less protein, resulting in less recycling, increased levels of serotonin in the synapse, and more serotonin-triggered cellular activity. Previous NIMH-supported studies had shown that inheriting the short variant more than doubles risk of depression following life stresses,** boosts amygdala activity while viewing scary faces,*** and has been linked to anxious temperament. Yet, how it works at the level of brain circuitry remained a mystery.

The NIMH research team first scanned 114 healthy subjects using magnetic resonance imaging (MRI). Those with at least one copy of the short variant had less gray matter, neurons and their connections, in the amygdala-cingulate circuit than those with two copies of the long variant.

Next, using functional magnetic resonance imaging (fMRI), the researchers monitored the brain activity of 94 healthy participants while they were looking at scary faces, which activates fear circuitry. Those with the short variant showed less functional connectivity, in the same circuit.

Nearly 30 percent of subjects' scores on a standard scale of "harm avoidance," an inherited temperament trait associated with depression and anxiety, was explained by how well the mood-regulating circuit was connected.

"Until now, it's been hard to relate amygdala activity to temperament and genetic risk for depression," said Dr. Andreas Meyer-Lindenberg, a lead author. "This study suggests that the cingulate's ability to put the brakes on a runaway amygdala fear response depends upon the degree of connectivity in this circuit, which is influenced by the serotonin transporter gene."

Since serotonin activity plays a key role in wiring the brain's emotion processing circuitry during early development, the researchers propose that the short variant leads to stunted coupling in the circuit, a poorly regulated amygdala response and impaired emotional reactivity – resulting in increased vulnerability to persistent bad moods and eventually depression as life's stresses take their toll.

One can imagine a couple of ways that future biotechnological advances will provide ways to treat this problem. First off, cell therapies, gene therapies, or nerve growth factor therapies could be used to encourage the growth of neurons between the cingulate and the amygdala. Another more "cyborg-ish" possibility would be to implant electrodes in the brain to deliver artificial signals into the amygdala to suppress the fear response.

Note how these scientists combined genetic test results with brain scan results. Once DNA sequencing and testing costs drop by orders of magnitude brain scan tests will be comparable to all the genetic variations in the genome to find other genetic variations that influence emotions and other aspects of cognition.

By Randall Parker    2005 May 09 05:24 PM   Entry Permalink | Comments (3)
2005 February 10 Thursday
Severe Emotional Stress Can Release Chemicals That Mimic Heart Attack

Catecholamines released in response to sudden emotional stress can cause life-threatening heart failure called stress cardiomyopathy that can be misdiagnosed as a conventional heart attack.

Now, researchers at Johns Hopkins have discovered that sudden emotional stress can also result in severe but reversible heart muscle weakness that mimics a classic heart attack. Patients with this condition, called stress cardiomyopathy but known colloquially as "broken heart" syndrome, are often misdiagnosed with a massive heart attack when, indeed, they have suffered from a days-long surge in adrenalin (epinephrine) and other stress hormones that temporarily "stun" the heart.

"Our study should help physicians distinguish between stress cardiomyopathy and heart attacks," says study lead author and cardiologist Ilan Wittstein, M.D., an assistant professor at The Johns Hopkins University School of Medicine and its Heart Institute. "And it should also reassure patients that they have not had permanent heart damage."

In the Hopkins study, to be published in The New England Journal of Medicine online Feb. 10, the research team found that some people may respond to sudden, overwhelming emotional stress by releasing large amounts of catecholamines (notably adrenalin and noradrenalin, also called epinephrine and norepinephrine) into the blood stream, along with their breakdown products and small proteins produced by an excited nervous system. These chemicals can be temporarily toxic to the heart, effectively stunning the muscle and producing symptoms similar to a typical heart attack, including chest pain, fluid in the lungs, shortness of breath and heart failure.

Upon closer examination, though, the researchers determined that cases of stress cardiomyopathy were clinically very different from a typical heart attack.

"After observing several cases of 'broken heart' syndrome at Hopkins hospitals - most of them in middle-aged or elderly women - we realized that these patients had clinical features quite different from typical cases of heart attack, and that something very different was happening," says Wittstein. "These cases were, initially, difficult to explain because most of the patients were previously healthy and had few risk factors for heart disease."

For example, examination by angiogram showed no blockages in the arteries supplying the heart. Blood tests also failed to reveal some typical signs of a heart attack, such as highly elevated levels of cardiac enzymes that are released into the blood stream from damaged heart muscle. Magnetic resonance imaging (MRI) scans confirmed that none of the stressed patients had suffered irreversible muscle damage. Of greatest surprise, the team says, was that recovery rates were much faster than typically seen after a heart attack. Stressed patients showed dramatic improvement in their hearts' ability to pump within a few days and had complete recovery within two weeks. In contrast, partial recovery after a heart attack can take weeks or months and, frequently, the heart muscle damage is permanent.

The researchers collected detailed histories and conducted several tests, including blood work, echocardiograms, electrocardiograms, coronary angiograms, MRI scans and heart biopsies, on a total of 19 patients who came to Hopkins between November 1999 and September 2003. All had signs of an apparent heart attack immediately after some kind of sudden emotional stress, including news of a death, shock from a surprise party, fear of public speaking, armed robbery, a court appearance and a car accident. Eighteen of the stressed patients were female, between the age of 27 and 87, with a median age of 63. The results were then compared to seven other patients, all of whom had suffered classic, severe cases of heart attack, called a Killip class III myocardial infarction.

When results from both groups were compared, the researchers found that initial levels of catecholamines in the stress cardiomyopathy patients were two to three times the levels among patients with classic heart attack, and seven to 34 times normal levels.

Catecholamine metabolites, such as metanephrine and normetanephrine, were also massively elevated, as were other stress-related proteins, such as neuropeptide Y, brain natriuretic peptide and serotonin. These results provided added confirmation that the syndrome was stress induced. Heart biopsies also showed an injury pattern consistent with a high catecholamine state and not heart attack.

Note that 18 out of the 19 patients diagnosed with stress cardiomyopathy were women. Do men suppress their emotional responses and thereby lower their risk of stress cardiomyopathy?

I predict that some day people will have embedded drug dispensers in their bodies that have integrated sensors that will be able to detect the chemicals released by a severe emotional stress episode. The sensor devices embedded in a body will have integrated drug dispensers that together will act like an extension of the endocrine system. The artificial endocrine organs will be able to react to the severe stress reaction by releasing compounds that will damp down the stress response to put the stress response back within a safe range by neutralizing the catecholamines and other compounds released in response to severe emotional stress.

Severe emotional stress is bad for your health. To the extent that it is practically possible structure your life to avoid circumstances and events that will elicit intense emotional feelings of stress.

By Randall Parker    2005 February 10 01:15 AM   Entry Permalink | Comments (21)
2004 December 21 Tuesday
Brain Scan Shows Fast Reaction To Fearful Face Pictures

If images of fearful faces are flashed in front of a person too quickly for the person to recognize a face a part of the brain still reacts to the fearful expression.

Using a high-resolution version of functional magnetic resonance imaging (fMRI) the researchers observed a structure in the brain important for emotional processing - the amygdala - lights up with activity when people unconsciously detected the fearful faces.

Although the study was conducted in people who had no anxiety disorders, the researchers says that the findings should also apply to people with anxiety disorders.

“Psychologists have suggested that people with anxiety disorders are very sensitive to subliminal threats and are picking up stimuli the rest of us do not perceive,” says Dr. Joy Hirsch, professor of neuroradiology and psychology and director of the fMRI Research Center at Columbia University Medical Center, where the study was conducted. “Our findings now demonstrate a biological basis for that unconscious emotional vigilance.”

A part of the brain involved in the feeling of anxious reactions responded to fearful pictures even if the pictures were flashed up too quickly for the conscious mind to become aware of the pictures.

In the study, the researchers presented images of fearful facial expressions, which are powerful signals of danger in all cultures, to 17 different subjects. None of the 17 volunteers had any anxiety disorders, but their underlying anxiety varied from the 6th to the 85th percentile of undergraduate norms, as measured by a well-validated questionnaire.

“These are the type of normal differences that would be apparent if these people got stuck in an elevator,” Dr. Hirsch says. “Some of them would go to sleep; some would climb the walls.”

While the subjects were looking at a computer, the researchers displayed an image of a fearful face onto the monitor for 33 milliseconds, immediately followed by a similar neutral face. The fearful face appeared and disappeared so quickly that the subjects had no conscious awareness of it.

But the fMRI scans clearly revealed that the brain had registered the face and reacted, even though the subjects denied seeing it. These scans show that the unconsciously perceived face activates the input end of the amygdala, along with regions in the cortex that are involved with attention and vision.

Brain activity varies with level of anxiety

The researchers also noticed that the amount of brain activity varied from person to person, depending on their scores on the anxiety quiz.

The amygdalas of anxious people was far more active than the amygdalas of less anxious people. And anxious subjects showed more activity in the attention and vision regions of the cortex, which manifested itself in faster and more accurate answers when the subjects were asked questions about the neutral face.

“What we think we’ve identified is a circuit in the brain that’s responsible for enhancing the processing of unconsciously detected threats in anxious people,” says Amit Etkin, the study’s first author. “An anxious person devotes more attention and visual processing to analyze the threat. A less anxious person uses the circuit to a lesser degree because they don’t perceive the face as much as a threat.”

Unconscious vs. conscious processing of fearful faces

In contrast to unconscious processing of fearful faces, the researchers found that when subjects looked at the fearful faces for 200 milliseconds, long enough for conscious recognition, a completely different brain circuit was used to process the information. And the activity in that circuit did not vary according to the subject’s level of anxiety.

“Our study shows that there’s a very important role for unconscious emotions in anxiety,” Etkin says.

This reminds me of claims decades ago that some movie theaters were supposedly splicing pictures of food in with movies using durations too short to be consciously registered but still long enough to make someone want to go buy some popcorn and candy. Well, can the flashing up of food pictures for periods too short to be registered by the conscious mind still manage to provoke a hunger pang just like these scary faces provoke the beginning of an anxiety reaction?

This technique could be used in movies to create anxious reactions to scary scenes. Though how well it worked would depend on each movie watcher's proneness to anxiety.

Also, could this technique be used in interrogations to increase the anxiety of a subject of interrogation? Would that help the interrogators succeed in getting useful information? Imagine the subject being left in a room to watch a seemingly soothing TV show that has 33 millisecond flashes of anxious faces spliced into the video stream.

Then there are the anxious and fearful people of the world: They shouldn't look at each other's faces. They probably feed off of each other's fear. They should have pictures of happy and relaxed people on walls near their work desks and at home.

By Randall Parker    2004 December 21 02:14 AM   Entry Permalink | Comments (4)
2004 January 29 Thursday
Women Hold Babies On The Left To Connect To Emotional Half Of the Brain

Victoria Bourne and Brenda Todd of the University of Sussex in England have found that women hold babies on the side of their bodies that connect to that side of the brain which is dominant in the processing of emotions.

The right side of the brain controls the left side of the body and usually helps to process emotions, explains Bourne. So holding the baby on the left-hand side may help to direct the sight of emotionally charged information, such as tears or laughter, to the specialized right hemisphere for processing, she says.

Keep in mind that the left brain gets input from the right side of the body and the right brain gets input from the left side. It is interesting to note that the heart is traditionally associated with the seat of emotions and it happens to be on the left side of the body and that side is the side that connects to the center of emotional processing in the brain in most people.

If you want to find out which side of your brain does most of your emotional processing then take this quick test. The test is too short to be definitive. If anyone knows of a longer test with more pictures please post a link to it in the comments.

The abstract for the research paper more clearly explains what they did. The researchers used both people who have left-brain dominance for emotional processing and people who did not.

Previous research has indicated that 70-85% of women and girls show a bias to hold infants, or dolls, to the left side of their body. This bias is not matched in males (e.g. deChateau, Holmberg & Winberg, 1978; Todd, 1995). This study tests an explanation of cradling preferences in terms of hemispheric specialization for the perception of facial emotional expression. Thirty-two right-handed participants were given a behavioural test of lateralization and a cradling task. Females, but not males, who cradled a doll on the left side were found to have significantly higher laterality quotients than right cradlers. Results indicate that women cradle on the side of the body that is contralateral to the hemisphere dominant for face and emotion processing and suggest a possible explanation of gender differences in the incidence of cradling.

One thing that would be interesting to discover is whether less emotionally intense women are less likely to prefer one side over the other for holding a baby.

By Randall Parker    2004 January 29 05:12 PM   Entry Permalink | Comments (8)
2002 October 30 Wednesday
Depression Tied To Hippocampal Stem Cells

Since this story is written for the layman they use the term "cell birth". But what is really happening is that adult stem cells in the hippocampus divide. One cell remains an adult stem cell and stays in the hippocampus. The other travels up into the brain and converts itself into a nerve cell. Well, this process is probably happening in order to form new memories, possibly new reflexes, and to replace damaged cells that die. Suppression of this process may either cause depression or possibly it doesn't cause the initial depression but does prolong it. Anti-depressants are known to stimulate hippocampal adult stem cells to divide and so the thinking is that this stimulation may be one of the ways that anti-depressant drugs relieve depression. There are now many scientists pursuing this line of thought and looking for drugs that will more quickly stimulate hippocampal adult stem cells to divide.

Stress, which plays a key role in triggering depression, suppresses neurogenesis in the hippocampus.

Antidepressants, on the other hand, encourage the birth of new brain cells.

Animals must take antidepressants for two or three weeks before they bump up the birth rate of brain cells, and the cells take another two weeks to start functioning. That's consistent with the lag time antidepressants show before they lift moods in people.

If an antidepressant is given during a period of chronic stress, it prevents the decline in neurogenesis that normally occurs.

You can also fiind the previous article here.

In a related report stress hampers learning ability in female rats but Prozac prevents stress's effects:

Shors and her research team, Benedetta Leuner, Jacqueline Falduto and Sabrina Mendolia, studied adult female rats treated with the antidepressant Prozac and a control group that received no treatment. They found that after a stressful event, learning was impaired in the control group but not in the group treated with Prozac. The researchers also found that only chronic treatment with Prozac was effective, which is consistent with reported efficacy of Prozac in patients with depression and other mental disorders.

"Importantly," Shors pointed out, "unstressed females treated with Prozac did not differ from unstressed, untreated females, indicating that Prozac itself did not affect learning."

Shors noted that males and females differ in their responses to stressful experiences. The researchers have found that exposure to a stressful experience that impairs new learning in females actually enhances new learning in males.

These results also suggest a reason why depression is more common in old folks: their adult stem cells are also aged and very likely not as able to divide and differentiate into nerve cells. In order to rejuvenate people and make their bodies young again it will be essential to rejuvenate the adult stem cells in various adult stem cell reservoirs throughout the body. If hippocampal adult stem cells could be rejuvenated it might be possible to reduce the incidence of depression, improve memory, and even to raise intelligence. Since the demand for more effective anti-depressant treatments is so large this theory about hippocampal adult stem cells having a role in prolonging depression may cause depression researchers to develop methods to rejuvenate hippocampal adult stem cells. Hence attempts to develop more advanced anti-depressant treatments may contribute to the development of anti-aging therapies.

By Randall Parker    2002 October 30 04:45 PM   Entry Permalink | Comments (0)
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