Posts tagged amygdala
Articles and news from the latest research reports.
Early life stress can leave lasting impacts on the brain
For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it — chronic, toxic stress like poverty, neglect and physical abuse — can have lasting negative impacts.
A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion. These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.
The study, published in the journal Biological Psychiatry, could be important for public policy leaders, economists and epidemiologists, among others, says study lead author and recent UW Ph.D. graduate Jamie Hanson.
"We haven’t really understood why things that happen when you’re 2, 3, 4 years old stay with you and have a lasting impact," says Seth Pollak, co-leader of the study and UW-Madison professor of psychology.
Yet, early life stress has been tied before to depression, anxiety, heart disease, cancer, and a lack of educational and employment success, says Pollak, who is also director of the UW Waisman Center’s Child Emotion Research Laboratory.
"Given how costly these early stressful experiences are for society … unless we understand what part of the brain is affected, we won’t be able to tailor something to do about it," he says.
For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.
Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children’s brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.
Hanson and the team outlined by hand each child’s hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children (the word amygdala is Greek for almond, reflecting its size and shape in adults), and Hanson and Pollak say the automated software measurements from other studies may be prone to error.
Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes. Putting the same images through automated software showed no effects.
Behavioral problems and increased cumulative life stress were also linked to smaller hippocampus and amygdala volumes.
Why early life stress may lead to smaller brain structures is unknown, says Hanson, now a postdoctoral researcher at Duke University’s Laboratory for NeuroGenetics, but a smaller hippocampus is a demonstrated risk factor for negative outcomes. The amygdala is much less understood and future work will focus on the significance of these volume changes.
"For me, it’s an important reminder that as a society we need to attend to the types of experiences children are having," Pollak says. "We are shaping the people these individuals will become."
But the findings, Hanson and Pollak say, are just markers for neurobiological change; a display of the robustness of the human brain, the flexibility of human biology. They aren’t a crystal ball to be used to see the future.
"Just because it’s in the brain doesn’t mean it’s destiny," says Hanson.
People with tinnitus process emotions differently from their peers
Patients with persistent ringing in the ears – a condition known as tinnitus – process emotions differently in the brain from those with normal hearing, researchers report in the journal Brain Research.
Tinnitus afflicts 50 million people in the United States, according to the American Tinnitus Association, and causes those with the condition to hear noises that aren’t really there. These phantom sounds are not speech, but rather whooshing noises, train whistles, cricket noises or whines. Their severity often varies day to day.
University of Illinois speech and hearing science professor Fatima Husain, who led the study, said previous studies showed that tinnitus is associated with increased stress, anxiety, irritability and depression, all of which are affiliated with the brain’s emotional processing systems.
“Obviously, when you hear annoying noises constantly that you can’t control, it may affect your emotional processing systems,” Husain said. “But when I looked at experimental work done on tinnitus and emotional processing, especially brain imaging work, there hadn’t been much research published.”
She decided to use functional magnetic resonance imaging (fMRI) brain scans to better understand how tinnitus affects the brain’s ability to process emotions. These scans show the areas of the brain that are active in response to stimulation, based upon blood flow to those areas.
Three groups of participants were used in the study: people with mild-to-moderate hearing loss and mild tinnitus; people with mild-to-moderate hearing loss without tinnitus; and a control group of age-matched people without hearing loss or tinnitus. Each person was put in an fMRI machine and listened to a standardized set of 30 pleasant, 30 unpleasant and 30 emotionally neutral sounds (for example, a baby laughing, a woman screaming and a water bottle opening). The participants pressed a button to categorize each sound as pleasant, unpleasant or neutral.
The tinnitus and normal-hearing groups responded more quickly to emotion-inducing sounds than to neutral sounds, while patients with hearing loss had a similar response time to each category of sound. Over all, the tinnitus group’s reaction times were slower than the reaction times of those with normal hearing.
Activity in the amygdala, a brain region associated with emotional processing, was lower in the tinnitus and hearing-loss patients than in people with normal hearing. Tinnitus patients also showed more activity than normal-hearing people in two other brain regions associated with emotion, the parahippocampus and the insula. The findings surprised Husain.
“We thought that because people with tinnitus constantly hear a bothersome, unpleasant stimulus, they would have an even higher amount of activity in the amygdala when hearing these sounds, but it was lesser,” she said. “Because they’ve had to adjust to the sound, some plasticity in the brain has occurred. They have had to reduce this amygdala activity and reroute it to other parts of the brain because the amygdala cannot be active all the time due to this annoying sound.”
Because of the sheer number of people who suffer from tinnitus in the United States, a group that includes many combat veterans, Husain hopes her group’s future research will be able to increase tinnitus patients’ quality of life.
“It’s a communication issue and a quality-of-life issue,” she said. “We want to know how we can get better in the clinical realm. Audiologists and clinicians are aware that tinnitus affects emotional aspects, too, and we want to make them aware that these effects are occurring so they can better help their patients.”
Neural sweet talk: Taste metaphors emotionally engage the brain
So accustomed are we to metaphors related to taste that when we hear a kind smile described as “sweet,” or a resentful comment as “bitter,” we most likely don’t even think of those words as metaphors. But while it may seem to our ears that “sweet” by any other name means the same thing, new research shows that taste-related words actually engage the emotional centers of the brain more than literal words with the same meaning.
Researchers from Princeton University and the Free University of Berlin report in the Journal of Cognitive Neuroscience the first study to experimentally show that the brain processes these everyday metaphors differently than literal language. In the study, participants read 37 sentences that included common metaphors based on taste while the researchers recorded their brain activity. Each taste-related word was then swapped with a literal counterpart so that, for instance, “She looked at him sweetly” became “She looked at him kindly.”
The researchers found that the sentences containing words that invoked taste activated areas known to be associated with emotional processing, such as the amygdala, as well as the areas known as the gustatory cortices that allow for the physical act of tasting. Interestingly, the metaphorical and literal words only resulted in brain activity related to emotion when part of a sentence, but stimulated the gustatory cortices both in sentences and as stand-alone words.
Metaphorical sentences may spark increased brain activity in emotion-related regions because they allude to physical experiences, said co-author Adele Goldberg, a Princeton professor of linguistics in the Council of the Humanities. Human language frequently uses physical sensations or objects to refer to abstract domains such as time, understanding or emotion, Goldberg said. For instance, people liken love to a number of afflictions including being “sick” or shot through the heart with an arrow. Similarly, “sweet” has a much clearer physical component than “kind.” The new research suggests that these associations go beyond just being descriptive to engage our brains on an emotional level and potentially amplify the impact of the sentence, Goldberg said.
"You begin to realize when you look at metaphors how common they are in helping us understand abstract domains," Goldberg said. "It could be that we are more engaged with abstract concepts when we use metaphorical language that ties into physical experiences."
If metaphors in general elicit an emotional response from the brain that is similar to that caused by taste-related metaphors, then that could mean that figurative language presents a “rhetorical advantage” when communicating with others, explained co-author Francesca Citron, a postdoctoral researcher of psycholinguistics at the Free University’s Languages of Emotion research center.
"Figurative language may be more effective in communication and may facilitate processes such as affiliation, persuasion and support," Citron said. "Further, as a reader or listener, one should be wary of being overly influenced by metaphorical language."
Colloquially, metaphors seem to be employed precisely to evoke an emotional reaction, yet the actual emotional effect of figurative phrases on the person hearing them has not before been deeply explored, said Benjamin Bergen, an associate professor of cognitive science at the University of California-San Diego who studies language comprehension, and metaphorical language and thought.
"There’s a lot of research on the conceptual effects of metaphors, such as how they allow people to think about new or abstract concepts in terms of concrete things they’re familiar with. But there’s very little work on the emotional impact of metaphor," said Bergen, who had no role in the research but is familiar with it.
"Emotional impact seems to be one of the main reasons people use metaphors to begin with. For instance, a senator might describe a bill as ‘job-killing’ to evoke an emotional reaction," he said. "These results suggest that using certain metaphorical expressions induces more of an emotional reaction than saying the same thing literally. Those expressions that have this property are likely to have the effects on reasoning, inference, judgment and decision-making that emotion is known to have."
The brain areas that taste-related words did not stimulate are also an important outcome of the study, Citron said. Existing research on metaphors and neural processing has shown that figurative language generally requires more brainpower than literal language, Citron and Goldberg wrote. But these bursts of neural activity have been related to higher-order processing from thinking through an unfamiliar metaphor.
The brain activity Citron and Goldberg observed did not correlate with this process. In order to create the metaphorical- and literal-sentence stimuli, they had a group of people separate from the study participants rate sentences for familiarity, apparent arousal, imageability — which is how easily a phrase can be imagined in the reader’s mind — and how positive or negative each sentence was interpreted as being. The metaphorical and literal sentences were equal on all of these factors. In addition, each metaphorical phrase and its literal counterpart were rated as being highly similar in meaning.
These steps helped to ensure that the metaphorical and literal sentences were equally as easy to comprehend. Thus, the brain activity the researchers recorded was not likely to be in response to any additional difficulty study participants had in understanding the metaphors.
"It is important to rule out possible effects of familiarity, since less familiar items may require more processing resources to be understood and elicit enhanced brain responses in several brain regions," Citron said.
Citron and Goldberg plan to follow up on their results by examining if figurative language is remembered more accurately than literal language, if metaphors are more physically stimulating, and if metaphors related to other senses also provoke an emotional response from the brain.
Anxious Children have Bigger “Fear Centers” in the Brain
The amygdala is a key “fear center” in the brain. Alterations in the development of the amygdala during childhood may have an important influence on the development of anxiety problems, reports a new study in the current issue of Biological Psychiatry.
Researchers at the Stanford University School of Medicine recruited 76 children, 7 to 9 years of age, a period when anxiety-related traits and symptoms can first be reliably identified. The children’s parents completed assessments designed to measure the anxiety levels of the children, and the children then underwent non-invasive magnetic resonance imaging (MRI) scans of brain structure and function.
The researchers found that children with high levels of anxiety had enlarged amygdala volume and increased connectivity with other brain regions responsible for attention, emotion perception, and regulation, compared to children with low levels of anxiety. They also developed an equation that reliably predicted the children’s anxiety level from the MRI measurements of amygdala volume and amygdala functional connectivity.
The most affected region was the basolateral portion of the amygdala, a subregion of the amygdala implicated in fear learning and the processing of emotion-related information.
“It is a bit surprising that alterations to the structure and connectivity of the amygdala were so significant in children with higher levels of anxiety, given both the young age of the children and the fact that their anxiety levels were too low to be observed clinically,” commented Dr. Shaozheng Qin, first author on this study.
Dr. John Krystal, Editor of Biological Psychiatry, commented, “It is critical that we move from these interesting cross-sectional observations to longitudinal studies, so that we can separate the extent to which larger and better connected amygdalae are risk factors or consequences of increased childhood anxiety.”
“However, our study represents an important step in characterizing altered brain systems and developing predictive biomarkers in the identification for young children at risk for anxiety disorders,” Qin added. “Understanding the influence of childhood anxiety on specific amygdala circuits, as identified in our study, will provide important new insights into the neurodevelopmental origins of anxiety in humans.”
(Source: elsevier.com)
Dad’s Brain Becomes More ‘Maternal’ When He’s Primary Caregiver
Fathers who spend more time taking care of their newborn child undergo changes in brain activity that make them more apt to fret about their baby’s safety, a new study shows.
(Image: Shutterstock)
In particular, fathers who are the primary caregiver experience an increase in activity in their amygdala and other emotional-processing systems, causing them to experience parental emotions similar to those typically experienced by mothers, the researchers noted.
The findings suggest there is a neural network in the brain dedicated to parenting, and that the network responds to changes in parental roles, said study senior author Ruth Feldman, a researcher in the department of psychology and the Gonda Brain Sciences Center at Bar-Ilan University in Israel.
"Pregnancy, childbirth and lactation are very powerful primers in women to worry about their child’s survival," said Feldman, who also serves as an adjunct professor at the Yale Child Study Center at Yale University. "Fathers have the capacity to do it as well as mothers, but they need daily caregiving activities to ignite that mothering network."
Releasing the brakes for learning
Learning can only occur if certain neuronal “brakes” are released. As the group led by Andreas Lüthi at the Friedrich Miescher Institute for Biomedical Research has now discovered, learning processes in the brain are dynamically regulated by various types of interneurons. The new connections essential for learning can only be established if inhibitory inputs from interneurons are reduced at the right moment. These findings have now been published in Nature.
Image caption: Example of a dendrite of a principal neuron (white) and synaptic contacts (yellow arrowheads) from SOM1 interneurons.
For some years, most neurobiologists studying learning processes have assumed that the new connections required for learning can only be established and ultimately reinforced if certain neuronal “brakes” are released – a process known as disinhibition. It has also been supposed for some time that various types of interneurons could be involved in disinhibition. Interneurons are nerve cells that surround and – via their connections – inhibit the activity of principal neurons. It has not been clear, however, whether these cell types actually play a role in disinhibition and how they control learning.
Andreas Lüthi and his group at the Friedrich Miescher Institute for Biomedical Research have now demonstrated for the first time how a learning process is dynamically regulated by specific types of interneurons.
In Lüthi’s experiments, mice were trained to associate a sound with an unpleasant stimulus, so that the animals subsequently knew what would happen when they heard the auditory cue. The researchers showed that, during the learning process, the sound stimulus released a brake in some of the principal neurons. More precisely, it induced the activation of parvalbumin-positive (PV+) interneurons, leading indirectly – via somatostatin-positive (SOM+) interneurons – to disinhibition of the principal neurons. The latter thus became receptive to further sensory inputs. If this was immediately followed by the unpleasant stimulus, then another brake was released. Once again, PV+ interneurons were involved, but this time the principal neurons were directly disinhibited. Steffen Wolff, a postdoc in Lüthi’s group and first author of the publication, explains: “The principal neurons temporarily reached a level of activation enabling neuronal connections to be reinforced in such a way that the animal could learn the association between the sound and the unpleasant stimulus.”
Lüthi comments: “This is the first time we’ve been able to identify so clearly the function of defined interneurons in a learning process, and to show how successive disinhibition can enable this process. We assume that interneurons disinhibit the principal neurons in a highly dynamic manner. They integrate, as it were, the state of numerous different neural networks, activated for example by sensory input, earlier experiences or emotional states, and thus permit or prevent learning. I think these findings are also of interest in the context of conditions where learning processes are impaired or dysfunctional, as in the case of anxiety disorders.”
(Source: fmi.ch)
A New Target for Alcoholism Treatment: Kappa Opioid Receptors
The list of brain receptor targets for opiates reads like a fraternity: Mu Delta Kappa. The mu opioid receptor is the primary target for morphine and endogenous opioids like endorphin, whereas the delta opioid receptor shows the highest affinity for endogenous enkephalins. The kappa opioid receptor (KOR) is very interesting, but the least understood of the opiate receptor family.
Until now, the mu opioid receptor received the most attention in alcoholism research. Naltrexone, a drug approved by the U.S. Food and Drug Administration for the treatment of alcoholism, acts by blocking opiate action at brain receptors and is most potent at the mu opioid receptor. In addition, research has suggested that a variant of the gene that codes for the mu opioid receptor (OPRM1) may be associated with the risk for alcoholism and the response to naltrexone treatment.
However, naltrexone also acts at the kappa opioid receptor and it has not been clear whether this effect of naltrexone is relevant to alcoholism treatment.
A growing body of research in animals implicates the KOR in alcoholism. Stimulation of the KOR, which occurs with alcohol intake, is thought to produce unpleasant and aversive effects. This receptor is hypothesized to play a role in alcohol dependence, at least in part, by promoting negative reinforcement processes. In other words, the theory postulates that during development of alcohol dependence, the KOR system becomes overstimulated, producing dysphoria and anhedonia, which then leads to further alcohol seeking and escalation of alcohol intake that serves to self-medicate those negative symptoms.
A new study in Biological Psychiatry, led by Dr. Brendan Walker at Washington State University, used a rat model of alcohol dependence to directly investigate the KOR system following chronic alcohol exposure and withdrawal.
They found that the KOR system is dysregulated in the amygdala of alcohol-dependent rats, a vital brain region with many functions, including regulation of emotional behavior and decision-making. Chronic alcohol consumption is known to cause neuroadaptations in the amygdala. In this study specifically, they found increased dynorphin A and increased KOR signaling in the amygdala of alcohol-dependent rats.
When the rats were in acute alcohol withdrawal, the researchers administered different drugs, each of which target the KOR system in precise ways, directly into the amygdala. Using this site-specific antagonism, they observed that alcohol dependence-related KOR dysregulation directly contributes to the excessive alcohol consumption that occurs during withdrawal.
“These data provide important new support for the hypothesis that kappa opioid receptor blockers might play a role in the treatment of alcoholism,” said Dr. John Krystal, Editor of Biological Psychiatry. “This study suggests that one role might be to prevent a relapse to alcohol use among patients recently withdrawn from alcohol.”
“This dataset demonstrates the extensive nature of the neuroadaptations the brain undergoes when chronically exposed to alcohol. The implications of these results are far reaching and should help guide pharmacotherapeutic development efforts for the treatment of alcohol use disorders,” said Walker. “Pharmacological compounds that alleviate the negative emotional / mood states that accompany alcohol withdrawal, by attenuating the excessive signaling in the dynorphin / kappa-opioid receptor system, should result in enhanced treatment compliance and facilitate the transition away from alcohol dependence.”
Additional extensive research will be necessary to identify and test the effectiveness of specific drugs that act on the KOR system, but these findings provide researchers with a potentially successful path forward to developing new drugs for the treatment of alcoholism.
(Image caption: Dendrite of an amygdala principal neuron with dendritic spines (white). Inhibitory synaptic contacts are shown in red. Credit: © MPI f. Brain Research/ J. Letzkus)
A brain capable of learning is important for survival: only those who learn can endure in the natural world. When it learns, the brain stores new information by changing the strength of the junctions that connect its nerve cells. This process is referred to as synaptic plasticity. Scientists at the Max-Planck Institute for Brain Research in Frankfurt, working with researchers from Basel, have demonstrated for the first time that inhibitory neurons need to be at least partly blocked during learning. This disinhibition is a bit like taking the foot off the brake in a car: if the inhibitory neurons are less active, learning is accelerated.
Learning is often a matter of timing: different stimuli become strongly associated if they occur in close succession. The Max Planck scientists made use of this phenomenon in conditioning experiments in which mice learned to react to a tone. For this learning effect to occur, the synapses of the so-called principal neurons in the amygdala need to become more sensitive. The researchers concentrated on two types of inhibitory neurons which produce the proteins parvalbumin and somatostatin and inhibit the principal neurons of the amygdala.
The results obtained by the Max Planck researchers show that both cell types are inhibited during different phases of the learning process. This disinhibition enhances the activation of the principal neurons. Moreover, the scientists were able to control the learning behaviour of the mice through the use of optogenetics. In these experiments, they equipped both types of inhibitory neurons in the amygdala with light-sensitive ion channels, allowing them to use light to switch the neurons on or off as required. “When we prevent disinhibition, the mice learn less well. In contrast, enhancing the disinhibition leads to intensified learning”, says Johannes Letzkus from the Max Planck Institute for Brain Research. Next, the scientists aim to identify the nerve pathways which are involved in disinhibition.
Temper trap: the genetics of aggression and self-control
Everyone knows someone with a quick temper – it might even be you. And while scientists have known for decades that aggression is hereditary, there is another biological layer to those angry flare-ups: self-control.
In a paper published earlier this year in the Journal of Cognitive Neuroscience, my colleagues and I found that people who are genetically predisposed toward aggression try hard to control their anger, but have inefficient functioning in brain regions that control emotions.
In other words, self-control is, in part, biological.
Psilocybin inhibits the processing of negative emotions in the brain
When emotions are processed in a negatively biased manner in the brain, an individual is at risk to develop depression. Psilocybin, the bioactive component of the Mexican magic mushroom, seems to intervene positively in the emotion-processing mechanism. Even a small amount of the natural substance attenuates the processing of negative emotions and brightens mood as shown by UZH researchers using imaging methods.
Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role – above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.
Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could “point the way to novel approaches to treatment” comments the lead author Rainer Krähenmann on the results which have now been published in the renowned medical journal “Biological Psychiatry”.
Psilocybin inhibits the processing of negative emotions in the amygdala
The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann’s research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.
Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). “Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions”, continues Krähenmann. The study clearly shows that the modulation of amygdala activity is directly linked to the experience of heightened mood.
Next study with depressive patients
According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressed patients - and may consequently lead to improved mood in these patients.
Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.
(Source: mediadesk.uzh.ch)