Posts tagged amygdala
Articles and news from the latest research reports.
Neuroscientists Determine How Treatment for Anxiety Disorders Silences Fear Neurons
Excessive fear can develop after a traumatic experience, leading to anxiety disorders such as post-traumatic stress disorder and phobias. During exposure therapy, an effective and common treatment for anxiety disorders, the patient confronts a fear or memory of a traumatic event in a safe environment, which leads to a gradual loss of fear. A new study in mice, published online today in Neuron, reports that exposure therapy remodels an inhibitory junction in the amygdala, a brain region important for fear in mice and humans. The findings improve our understanding of how exposure therapy suppresses fear responses and may aid in developing more effective treatments. The study, led by researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts, was partially funded by a New Innovator Award from the Office of the Director at the National Institutes of Health.
A fear-inducing situation activates a small group of neurons in the amygdala. Exposure therapy silences these fear neurons, causing them to be less active. As a result of this reduced activity, fear responses are alleviated. The research team sought to understand how exactly exposure therapy silences fear neurons.
The researchers found that exposure therapy not only silences fear neurons but also induces remodeling of a specific type of inhibitory junction, called the perisomatic synapse. Perisomatic inhibitory synapses are connections between neurons that enable one group of neurons to silence another group of neurons. Exposure therapy increases the number of perisomatic inhibitory synapses around fear neurons in the amygdala. This increase provides an explanation for how exposure therapy silences fear neurons.
“The increase in number of perisomatic inhibitory synapses is a form of remodeling in the brain. Interestingly, this form of remodeling does not seem to erase the memory of the fear-inducing event, but suppresses it,” said senior author, Leon Reijmers, Ph.D., assistant professor of neuroscience at Tufts University School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
Reijmers and his team discovered the increase in perisomatic inhibitory synapses by imaging neurons activated by fear in genetically manipulated mice. Connections in the human brain responsible for suppressing fear and storing fear memories are similar to those found in the mouse brain, making the mouse an appropriate model organism for studying fear circuits.
Mice were placed in a box and experienced a fear-inducing situation to create a fear response to the box. One group of mice, the control group, did not receive exposure therapy. Another group of mice, the comparison group, received exposure therapy to alleviate the fear response. For exposure therapy, the comparison group was repeatedly placed in the box without experiencing the fear-inducing situation, which led to a decreased fear response in these mice. This is also referred to as fear extinction.
The researchers found that mice subjected to exposure therapy had more perisomatic inhibitory synapses in the amygdala than mice who did not receive exposure therapy. Interestingly, this increase was found around fear neurons that became silent after exposure therapy.
“We showed that the remodeling of perisomatic inhibitory synapses is closely linked to the activity state of fear neurons. Our findings shed new light on the precise location where mechanisms of fear regulation might act. We hope that this will lead to new drug targets for improving exposure therapy,” said first author, Stéphanie Trouche, Ph.D., a former postdoctoral fellow in Reijmers’ lab at Tufts and now a medical research council investigator scientist at the University of Oxford in the United Kingdom.
“Exposure therapy in humans does not work for every patient, and in patients that do respond to the treatment, it rarely leads to a complete and permanent suppression of fear. For this reason, there is a need for treatments that can make exposure therapy more effective,” Reijmers added.
(Source: now.tufts.edu)
Nurturing may protect kids from brain changes linked to poverty
Growing up in poverty can have long-lasting, negative consequences for a child. But for poor children raised by parents who lack nurturing skills, the effects may be particularly worrisome, according to a new study at Washington University School of Medicine in St. Louis.
Among children living in poverty, the researchers identified changes in the brain that can lead to lifelong problems like depression, learning difficulties and limitations in the ability to cope with stress. The study showed that the extent of those changes was influenced strongly by whether parents were nurturing.
The good news, according to the researchers, is that a nurturing home life may offset some of the negative changes in brain anatomy among poor children. And the findings suggest that teaching nurturing skills to parents — particularly those living in poverty — may provide a lifetime benefit for their children.
The study is published online Oct. 28 and will appear in the November issue of JAMA Pediatrics.
Using magnetic resonance imaging (MRI), the researchers found that poor children with parents who were not very nurturing were likely to have less gray and white matter in the brain. Gray matter is closely linked to intelligence, while white matter often is linked to the brain’s ability to transmit signals between various cells and structures.
The MRI scans also revealed that two key brain structures were smaller in children who were living in poverty: the amygdala, a key structure in emotional health, and the hippocampus, an area of the brain that is critical to learning and memory.
“We’ve known for many years from behavioral studies that exposure to poverty is one of the most powerful predictors of poor developmental outcomes for children,” said principal investigator Joan L. Luby, MD, a Washington University child psychiatrist at St. Louis Children’s Hospital. “A growing number of neuroscience and brain-imaging studies recently have shown that poverty also has a negative effect on brain development.
“What’s new is that our research shows the effects of poverty on the developing brain, particularly in the hippocampus, are strongly influenced by parenting and life stresses that the children experience.”
Luby, a professor of psychiatry and director of the university’s Early Emotional Development Program, is in the midst of a long-term study of childhood depression. As part of the Preschool Depression Study, she has been following 305 healthy and depressed kids since they were in preschool. As the children have grown, they also have received MRI scans that track brain development.
“We actually stumbled upon this finding,” she said. “Initially, we thought we would have to control for the effects of poverty, but as we attempted to control for it, we realized that poverty was really driving some of the outcomes of interest, and that caused us to change our focus to poverty, which was not the initial aim of this study.”
In the new study, Luby’s team looked at scans from 145 children enrolled in the depression study. Some were depressed, others healthy, and others had been diagnosed with different psychiatric disorders such as ADHD (attention-deficit hyperactivity disorder). As she studied these children, Luby said it became clear that poverty and stressful life events, which often go hand in hand, were affecting brain development.
The researchers measured poverty using what’s called an income-to-needs ratio, which takes a family’s size and annual income into account. The current federal poverty level is $23,550 for a family of four.
Although the investigators found that poverty had a powerful impact on gray matter, white matter, hippocampal and amygdala volumes, they found that the main driver of changes among poor children in the volume of the hippocampus was not lack of money but the extent to which poor parents nurture their children. The hippocampus is a key brain region of interest in studying the risk for impairments.
Luby’s team rated nurturing using observations made by the researchers — who were unaware of characteristics such as income level or whether a child had a psychiatric diagnosis — when the children came to the clinic for an appointment. And on one of the clinic visits, the researchers rated parental nurturing using a test of the child’s impatience and of a parent’s patience with that child.
While waiting to see a health professional, a child was given a gift-wrapped package, and that child’s parent or caregiver was given paperwork to fill out. The child, meanwhile, was told that s/he could not open the package until the caregiver completed the paperwork, a task that researchers estimated would take about 10 minutes.
Luby’s team found that parents living in poverty appeared more stressed and less able to nurture their children during that exercise. In cases where poor parents were rated as good nurturers, the children were less likely to exhibit the same anatomical changes in the brain as poor children with less nurturing parents.
“Parents can be less emotionally responsive for a whole host of reasons,” Luby said. “They may work two jobs or regularly find themselves trying to scrounge together money for food. Perhaps they live in an unsafe environment. They may be facing many stresses, and some don’t have the capacity to invest in supportive parenting as much as parents who don’t have to live in the midst of those adverse circumstances.”
The researchers also found that poorer children were more likely to experience stressful life events, which can influence brain development. Anything from moving to a new house to changing schools to having parents who fight regularly to the death of a loved one is considered a stressful life event.
Luby believes this study could provide policymakers with at least a partial answer to the question of what it is about poverty that can be so detrimental to a child’s long-term developmental outcome. Because it appears that a nurturing parent or caregiver may prevent some of the changes in brain anatomy that this study identified, Luby said it is vital that society invest in public health prevention programs that target parental nurturing skills. She suggested that a key next step would be to determine if there are sensitive developmental periods when interventions with parents might have the most powerful impact.
“Children who experience positive caregiver support don’t necessarily experience the developmental, cognitive and emotional problems that can affect children who don’t receive as much nurturing, and that is tremendously important,” Luby said. “This study gives us a feasible, tangible target with the suggestion that early interventions that focus on parenting may provide a tremendous payoff.”
New role for ‘hunger hormone’
About a dozen years ago, scientists discovered that a hormone called ghrelin enhances appetite. Dubbed the “hunger hormone,” ghrelin was quickly targeted by drug companies seeking treatments for obesity — none of which have yet panned out.
MIT neuroscientists have now discovered that ghrelin’s role goes far beyond controlling hunger. The researchers found that ghrelin released during chronic stress makes the brain more vulnerable to traumatic events, suggesting that it may predispose people to posttraumatic stress disorder (PTSD).
Drugs that reduce ghrelin levels, originally developed to try to combat obesity, could help protect people who are at high risk for PTSD, such as soldiers serving in war, says Ki Goosens, an assistant professor of brain and cognitive sciences at MIT, and senior author of a paper describing the findings in the Oct. 15 online edition of Molecular Psychiatry.
“Perhaps we could give people who are going to be deployed into an active combat zone a ghrelin vaccine before they go, so they will have a lower incidence of PTSD. That’s exciting because right now there’s nothing given to people to prevent PTSD,” says Goosens, who is also a member of MIT’s McGovern Institute for Brain Research.
Lead author of the paper is Retsina Meyer, a recent MIT PhD recipient. Other authors are McGovern postdoc Anthony Burgos-Robles, graduate student Elizabeth Liu, and McGovern research scientist Susana Correia.
Stress and fear
Stress is a useful response to dangerous situations because it provokes action to escape or fight back. However, when stress is chronic, it can produce anxiety, depression and other mental illnesses.
At MIT, Goosens discovered that one brain structure that is especially critical for generating fear, the amygdala, has a special response to chronic stress. The amygdala produces large amounts of growth hormone during stress, a change that seems not to occur in other brain regions.
In the new paper, Goosens and her colleagues found that the release of the growth hormone in the amygdala is controlled by ghrelin, which is produced primarily in the stomach and travels throughout the body, including the brain.
Ghrelin levels are elevated by chronic stress. In humans, this might be produced by factors such as unemployment, bullying, or loss of a family member. Ghrelin stimulates the secretion of growth hormone from the brain; the effects of growth hormone from the pituitary gland in organs such as the liver and bones have been extensively studied. However, the role of growth hormone in the brain, particularly the amygdala, is not well known.
The researchers found that when rats were given either a drug to stimulate the ghrelin receptor or gene therapy to overexpress growth hormone over a prolonged period, they became much more susceptible to fear than normal rats. Fear was measured by training all of the rats to fear an innocuous, novel tone. While all rats learned to fear the tone, the rats with prolonged increased activity of the ghrelin receptor or overexpression of growth hormone were the most fearful, assessed by how long they froze after hearing the tone. Blocking the cell receptors that interact with ghrelin or growth hormone reduced fear to normal levels in chronically stressed rats.
When rats were exposed to chronic stress over a prolonged period, their circulating ghrelin and amygdalar growth hormone levels also went up, and fearful memories were encoded more strongly. This is similar to what the researchers believe happens in people who suffer from PTSD.
“When you have people with a history of stress who encounter a traumatic event, they are more likely to develop PTSD because that history of stress has altered something about their biology. They have an excessively strong memory of the traumatic event, and that is one of the things that drives their PTSD symptoms,” Goosens says.
New drugs, new targets
Over the last century, scientists have described the hypothalamic-pituitary-adrenal (HPA) axis, which produces adrenaline, cortisol (corticosterone in rats), and other hormones that stimulate “fight or flight” behavior. Since then, stress research has focused almost exclusively on the HPA axis.
After discovering ghrelin’s role in stress, the MIT researchers suspected that ghrelin was also linked to the HPA axis. However, they were surprised to find that when the rats’ adrenal glands — the source of corticosterone, adrenaline, and noradrenaline — were removed, the animals still became overly fearful when chronically stressed. The authors also showed that repeated ghrelin-receptor stimulation did not trigger release of HPA hormones, and that blockade of the ghrelin receptor did not blunt release of HPA stress hormones. Therefore, the ghrelin-initiated stress pathway appears to act independently of the HPA axis. “That’s important because it gives us a whole new target for stress therapies,” Goosens says.
Pharmaceutical companies have developed at least a dozen possible drug compounds that interfere with ghrelin. Many of these drugs have been found safe for humans, but have not been shown to help people lose weight. The researchers believe these drugs could offer a way to vaccinate people entering stressful situations, or even to treat people who already suffer from PTSD, because ghrelin levels remain high long after the chronic stress ends.
PTSD affects about 7.7 million American adults, including soldiers and victims of crimes, accidents, or natural disasters. About 40 to 50 percent of patients recover within five years, Meyer says, but the rest never get better.
The researchers hypothesize that the persistent elevation of ghrelin following trauma exposure could be one of the factors that maintain PTSD. “So, could you immediately reverse PTSD? Maybe not, but maybe the ghrelin could get damped down and these people could go through cognitive behavioral therapy, and over time, maybe we can reverse it,” Meyer says.
Working with researchers at Massachusetts General Hospital, Goosens’ lab is now planning to study ghrelin levels in human patients suffering from anxiety and fear disorders. They are also planning a clinical trial of a drug that blocks ghrelin to see if it can prevent relapse of depression.
(Source: web.mit.edu)
Sticks and stones: Brain releases natural painkillers during social rejection
Finding that the opioid system can act to ease social pain, not just physical pain, may aid understanding of depression and social anxiety
A brain image showing in orange/red one area of the brain where the natural painkiller (opioid) system was highly active in research volunteers who are experiencing social rejection. This region, called the amygdala, was one of several where the U-M team recorded the first images of this system responding to social pain, not just physical pain. Studying this response, and the variation between people, could aid understanding of depression and anxiety. Credited to UofM Health.
“Sticks and stones may break my bones, but words will never hurt me,” goes the playground rhyme that’s supposed to help children endure taunts from classmates. But a new study suggests that there’s more going on inside our brains when someone snubs us – and that the brain may have its own way of easing social pain.
The findings, recently published in Molecular Psychiatry by a University of Michigan Medical School team, show that the brain’s natural painkiller system responds to social rejection – not just physical injury.
What’s more, people who score high on a personality trait called resilience – the ability to adjust to environmental change – had the highest amount of natural painkiller activation.
(Source: uofmhealth.org)
Did you have a good time? We know where you’ll store the memory of it!
Where do you go for a tasty bite and where the food is not so good? Where are you likely to meet an attractive partner and where you risk damage to your health? For every person – but also for animals – the information about pleasant and unpleasant experiences is of key importance. Researchers from the Nencki Institute in Warsaw discovered how and where nice memories are stored.
As shown by researchers from the Nencki Institute of Experimental Biology in Warsaw, Poland, nice memories are stored in an area of the brain known as the central nucleus of the amygdala. The results obtained by the group of Prof. Leszek Kaczmarek and Dr. Ewelina Knapska, which were published in the well-known Journal of Neuroscience show that just one protein plays the key role in the process of memorizing pleasant experiences. In the future these results may help design more effective treatment of addictions, depression and schizophrenia.
“We want our research to help us understand the relation between the mind and the brain by studying memory, which is of fundamental importance for the mind. Without memory there is no mind”, Prof. Kaczmarek explains context of the research.
Neurobiologists differentiate between many types of memory, the most basic types of which are characterized by clear duality. For example we have short and long term memories, declarative (referring to events/data) and procedural (memory of actions). Researchers from the Nencki Institute focused on another dichotomy of great importance to every animal. They focused on appetitive memory related to memories of pleasant experiences and aversive memory related to unpleasant experiences.
Experimental research on human memory often comes across a very basic problem: there are no volunteers for the experiments. No one of sound mind will agree to participate in experiments involving his or her own memory. Fortunately having a mind is not limited to humans. Many mental activities typical for humans take place also in the minds of animals. Therefore scientists from the Nencki Institute conducted their experiments on mice.
These novel experiments on memory have been conducted on mice placed in the so-called IntelliCages. In each corner of such cage two water bottles have been placed. In order to get water a mouse has to get to the corner and nose poke on a small gate of a given bottle. Depending on the type of experiment, the mouse will either get water or harmless but unpleasant puff of air on the nose. All mice in the cage have individual ID chips and therefore researchers are able to tell exactly what decisions are made by each mouse.
IntelliCages make it possible to conduct different experiments. If for example in one corner sweet water (that is an appetitive stimulus) bottles are placed, the effectiveness of spatial memory in mice can be investigated. More subtle experiments are also possible by placing only one sweet water bottle in a selected corner. Then the mouse needs to remember not only the corner where the sweet water bottle is, but also which of two bottles contains sweet water.
Twenty five years ago Nencki researchers have observed changes in the activity of a gene known as c-fos in the nervous cell nuclei during learning. One of the proteins, the production of which is regulated by a protein encoded by the c-fos gene, is the MMP-9 enzyme active outside of the cell. Researchers decided to investigate the role of MMP-9 in memorizing pleasant and unpleasant experiences. In order to do this a series of experiments was conducted on control mice and on mice either lacking this protein entirely or with its selective blocking only within the central amygdala.
The amygdala is a small structure within the cerebral hemisphere and it is located at the base of the brain, close to the hippocampus. It consists of two groups of nuclei responsible for innate and acquired emotional reactions, such as laughter or fear.
Researchers were surprised by the experiments. When placed in the IntelliCages, the control mice after three days of learning almost always chose the corner with sweet water. Mice lacking MMP-9 behaved distinctly different: they showed no preference for any of the corners. At the same time all mice equally well remembered the corner where they received the unpleasant puff on their noses. Furthermore, selective blocking of MMP-9 just in the central amygdala produced the same effect – the memory for the sweet water location could not be formed.
“The results are clear. Pleasant experiences are memorised due to changes in plasticity within the neurons of the central nucleus of the amygdala. At the same time we have shown that just one protein, the MMP-9, is responsible for learning about pleasant experiences themselves and memorizing them. At the same time this protein has no impact on the memory of unpleasant experiences. These are important discoveries and to tell the truth making them was… very pleasant”, says Prof. Kaczmarek.
These research results, which stem from experiments conducted at the Nencki Institute for the past 25 years, hold great scientific significance for they explain the processes of learning and appetitive memory by referring to two seemingly very distant domains of neurobiology: system – investigating entire neuronal structures (such as the central nucleus of the amygdala) – and molecular, investigating physical and chemical processes responsible for various functions of nervous cells (in which the MMP-9 protein takes part).
A neurological basis for the lack of empathy in psychopaths
When individuals with psychopathy imagine others in pain, brain areas necessary for feeling empathy and concern for others fail to become active and be connected to other important regions involved in affective processing and decision-making, reports a study published in the open-access journal Frontiers in Human Neuroscience.
Psychopathy is a personality disorder characterized by a lack of empathy and remorse, shallow affect, glibness, manipulation and callousness. Previous research indicates that the rate of psychopathy in prisons is around 23%, greater than the average population which is around 1%.
To better understand the neurological basis of empathy dysfunction in psychopaths, neuroscientists used functional magnetic resonance imaging (fMRI) on the brains of 121 inmates of a medium-security prison in the USA.
Participants were shown visual scenarios illustrating physical pain, such as a finger caught between a door, or a toe caught under a heavy object. They were by turns invited to imagine that this accident happened to themselves, or somebody else. They were also shown control images that did not depict any painful situation, for example a hand on a doorknob.
Participants were assessed with the widely used PCL-R, a diagnostic tool to identify their degree of psychopathic tendencies. Based on this assessment, the participants were then divided in three groups of approximately 40 individuals each: highly, moderately, and weakly psychopathic.
When highly psychopathic participants imagined pain to themselves, they showed a typical neural response within the brain regions involved in empathy for pain, including the anterior insula, the anterior midcingulate cortex, somatosensory cortex, and the right amygdala. The increase in brain activity in these regions was unusually pronounced, suggesting that psychopathic people are sensitive to the thought of pain.
But when participants imagined pain to others, these regions failed to become active in high psychopaths. Moreover, psychopaths showed an increased response in the ventral striatum, an area known to be involved in pleasure, when imagining others in pain.
This atypical activation combined with a negative functional connectivity between the insula and the ventromedial prefrontal cortex may suggest that individuals with high scores on psychopathy actually enjoyed imagining pain inflicted on others and did not care for them. The ventromedial prefrontal cortex is a region that plays a critical role in empathetic decision-making, such as caring for the wellbeing of others.
Taken together, this atypical pattern of activation and effective connectivity associated with perspective taking manipulations may inform intervention programs in a domain where therapeutic pessimism is more the rule than the exception. Altered connectivity may constitute novel targets for intervention. Imagining oneself in pain or in distress may trigger a stronger affective reaction than imagining what another person would feel, and this could be used with some psychopaths in cognitive-behavior therapies as a kick-starting technique, write the authors.
First evidence that fear memories can be reduced during sleep
A fear memory was reduced in people by exposing them to the memory over and over again while they slept. It’s the first time that emotional memory has been manipulated in humans during sleep, report Northwestern Medicine® scientists.
The finding potentially offers a new way to enhance the typical daytime treatment of phobias through exposure therapy by adding a nighttime component. Exposure therapy is a common treatment for phobia and involves a gradual exposure to the feared object or situation until the fear is extinguished.
"It’s a novel finding," said Katherina Hauner, a postdoctoral fellow in neurology at Northwestern University Feinberg School of Medicine. "We showed a small but significant decrease in fear. If it can be extended to pre-existing fear, the bigger picture is that, perhaps, the treatment of phobias can be enhanced during sleep."
Hauner did the research in the lab of Jay Gottfried, associate professor of neurology at Feinberg and senior author of the paper.
The study will be published Sept. 22 in the journal Nature Neuroscience.
Previous projects have shown that spatial learning and motor sequence learning can be enhanced during sleep. It wasn’t previously known that emotions could be manipulated during sleep, Northwestern investigators said.
In the study, 15 healthy human subjects received mild electric shocks while seeing two different faces. They also smelled a specific odorant while viewing each face and being shocked, so the face and the odorant both were associated with fear. Subjects received different odorants to smell with each face such as woody, clove, new sneaker, lemon or mint.
Then, when a subject was asleep, one of the two odorants was re-presented, but in the absence of the associated faces and shocks. This occurred during slow wave sleep when memory consolidation is thought to occur. Sleep is very important for strengthening new memories, noted Hauner, also a research scientist at the Rehabilitation Institute of Chicago.
"While this particular odorant was being presented during sleep, it was reactivating the memory of that face over and over again which is similar to the process of fear extinction during exposure therapy," Hauner said.
When the subjects woke up, they were exposed to both faces. When they saw the face linked to the smell they had been exposed to during sleep, their fear reactions were lower than their fear reactions to the other face.
Fear was measured in two ways: through small amounts of sweat in the skin, similar to a lie detector test, and through neuroimaging with fMRI (functional magnetic resonance imaging). The fMRI results showed changes in regions associated with memory, such as the hippocampus, and changes in patterns of brain activity in regions associated with emotion, such as the amygdala. These brain changes reflected a decrease in reactivity that was specific to the targeted face image associated with the odorant presented during sleep.
Brain circuit can tune anxiety
New findings may help neuroscientists pinpoint better targets for antianxiety treatments.
Anxiety disorders, which include posttraumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.
To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.
“The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says.
In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels.
Lead authors of the paper, which appears in the Aug. 21 issue of Neuron, are technical assistant Ada Felix-Ortiz and postdoc Anna Beyeler. Other authors are former research assistant Changwoo Seo, summer student Christopher Leppla and research scientist Craig Wildes.
Measuring anxiety
Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.
To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus.
The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.
When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges.
Complex interactions
In a study published in 2011, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs.
“Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have totally opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.”
The Neuron study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets, says Joshua Gordon, an associate professor of psychiatry at Columbia University.
“The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection — synaptic proteins or ion channels, for example — that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon, who was not part of the research team.
In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.
Making the Brain Take Notice of Faces in Autism
A new study in Biological Psychiatry explores the influence of oxytocin
Difficulty in registering and responding to the facial expressions of other people is a hallmark of autism spectrum disorder (ASD). Relatedly, functional imaging studies have shown that individuals with ASD display altered brain activations when processing facial images.
The hormone oxytocin plays a vital role in the social interactions of both animals and humans. In fact, multiple studies conducted with healthy volunteers have provided evidence for beneficial effects of oxytocin in terms of increased trust, improved emotion recognition, and preference for social stimuli.
This combination of scientific work led German researchers to hypothesize about the influence of oxytocin in ASD. Dr. Gregor Domes, from the University of Freiburg and first author of the new study, explained: “In the present study, we were interested in the question of whether a single dose of oxytocin would change brain responses to social compared to non-social stimuli in individuals with autism spectrum disorder.”
They found that oxytocin did show an effect on social processing in the individuals with ASD, “suggesting that oxytocin may help to treat a basic brain function that goes awry in autism spectrum disorders,” commented Dr. John Krystal, Editor of Biological Psychiatry.
To conduct this study, they recruited fourteen individuals with ASD and fourteen control volunteers, all of whom completed a face- and house-matching task while undergoing imaging scans. Each participant completed this task and scanning procedure twice, once after receiving a nasal spray containing oxytocin and once after receiving a nasal spray containing placebo. The order of the sprays was randomized, and the tests were administered one week apart.
Using two sets of stimuli in the matching task, one of faces and one of houses, allowed the researchers to not only compare the effects of the oxytocin and placebo administrations, but also allowed them to discriminate findings between specific effects to only social stimuli and non-specific effects to more general brain processing.
What they found was intriguing. The data indicate that oxytocin specifically increases responses of the amygdala to social stimuli in individuals with ASD. The amygdala, the authors explain, “has been associated with processing of emotional stimuli, threat-related stimuli, face processing, and vigilance for salient stimuli”.
This finding suggests oxytocin might promote the salience of social stimuli in ASD. Increased salience of social stimuli might support behavioral training of social skills in ASD.
These data support the idea that oxytocin may be a promising approach in the treatment of ASD and could stimulate further research, even clinical trials, on the exploration of oxytocin as an add-on treatment for individuals with autism spectrum disorder.
(Source: alphagalileo.org)
Brain differences seen in depressed preschoolers
A key brain structure that regulates emotions works differently in preschoolers with depression compared with their healthy peers, according to new research at Washington University School of Medicine in St. Louis.
The differences, measured using functional magnetic resonance imaging (fMRI), provide the earliest evidence yet of changes in brain function in young children with depression. The researchers say the findings could lead to ways to identify and treat depressed children earlier in the course of the illness, potentially preventing problems later in life.
“The findings really hammer home that these kids are suffering from a very real disorder that requires treatment,” said lead author Michael S. Gaffrey, PhD. “We believe this study demonstrates that there are differences in the brains of these very young children and that they may mark the beginnings of a lifelong problem.”
The study is published in the July issue of the Journal of the American Academy of Child & Adolescent Psychiatry.
Depressed preschoolers had elevated activity in the brain’s amygdala, an almond-shaped set of neurons important in processing emotions. Earlier imaging studies identified similar changes in the amygdala region in adults, adolescents and older children with depression, but none had looked at preschoolers with depression.
For the new study, scientists from Washington University’s Early Emotional Development Program studied 54 children ages 4 to 6. Before the study began, 23 of those kids had been diagnosed with depression. The other 31 had not. None of the children in the study had taken antidepressant medication.
Although studies using fMRI to measure brain activity by monitoring blood flow have been used for years, this is the first time that such scans have been attempted in children this young with depression. Movements as small as a few millimeters can ruin fMRI data, so Gaffrey and his colleagues had the children participate in mock scans first. After practicing, the children in this study moved less than a millimeter on average during their actual scans.
While they were in the fMRI scanner during the study, the children looked at pictures of people whose facial expressions conveyed particular emotions. There were faces with happy, sad, fearful and neutral expressions.
“The amygdala region showed elevated activity when the depressed children viewed pictures of people’s faces,” said Gaffrey, an assistant professor of psychiatry. “We saw the same elevated activity, regardless of the type of faces the children were shown. So it wasn’t that they reacted only to sad faces or to happy faces, but every face they saw aroused activity in the amygdala.”
Looking at pictures of faces often is used in studies of adults and older children with depression to measure activity in the amygdala. But the observations in the depressed preschoolers were somewhat different than those previously seen in adults, where typically the amygdala responds more to negative expressions of emotion, such as sad or fearful faces, than to faces expressing happiness or no emotion.
In the preschoolers with depression, all facial expressions were associated with greater amygdala activity when compared with their healthy peers.
Gaffrey said it’s possible depression affects the amygdala mainly by exaggerating what, in other children, is a normal amygdala response to both positive and negative facial expressions of emotion. But more research will be needed to prove that. He does believe, however, that the amygdala’s reaction to people’s faces can be seen in a larger context.
“Not only did we find elevated amygdala activity during face viewing in children with depression, but that greater activity in the amygdala also was associated with parents reporting more sadness and emotion regulation difficulties in their children,” Gaffrey said. “Taken together, that suggests we may be seeing an exaggeration of a normal developmental response in the brain and that, hopefully, with proper prevention or treatment, we may be able to get these kids back on track.”
(Source: news.wustl.edu)