How associative fear memory is formed in the brain
March 13, 2020
Science Daily/University of California - Riverside
How does the brain form "fear memory" that links a traumatic event to a particular situation? A pair of researchers at the University of California, Riverside, may have found an answer.
Using a mouse model, the researchers demonstrated the formation of fear memory involves the strengthening of neural pathways between two brain areas: the hippocampus, which responds to a particular context and encodes it, and the amygdala, which triggers defensive behavior, including fear responses.
Study results appear today in Nature Communications.
"It has been hypothesized that fear memory is formed by strengthening the connections between the hippocampus and amygdala," said Jun-Hyeong Cho, an assistant professor in the Department of Molecular, Cell and Systems Biology and the study's lead author. "Experimental evidence, however, has been weak. Our study now demonstrates for the first time that the formation of fear memory associated with a context indeed involves the strengthening of the connections between the hippocampus and amygdala."
According to Cho, weakening these connections could erase the fear memory.
"Our study, therefore, also provides insights into developing therapeutic strategies to suppress maladaptive fear memories in post-traumatic stress disorder patients," he said.
Post-traumatic stress disorder, or PTSD, affects 7% of the U.S. population. A psychiatric disorder that can occur in people who have experienced or witnessed a traumatic event, such as war, assault, or disaster, PTSD can cause problems in daily life for months, and even years, in affected persons.
Cho explained the capability of our brains to form a fear memory associated with a situation that predicts danger is highly adaptive since it enables us to learn from our past traumatic experiences and avoid those dangerous situations in the future. This process is dysregulated, however, in PTSD, where overgeneralized and exaggerated fear responses cause symptoms including nightmares or unwanted memories of the trauma, avoidance of situations that trigger memories of the trauma, heightened reactions, anxiety, and depressed mood.
"The neural mechanism of learned fear has an enormous survival value for animals, who must predict danger from seemingly neutral contexts," Cho said. "Suppose we had a car accident in a particular place and got severely injured. We would then feel afraid of that -- or similar -- place even long after we recover from the physical injury. This is because our brains form a memory that associates the car accident with the situation where we experienced the trauma. This associative memory makes us feel afraid of that, or similar, situation and we avoid such threatening situations."
According to Cho, during the car accident, the brain processes a set of multisensory circumstances around the traumatic event, such as visual information about the place, auditory information such as a crash sound, and smells of burning materials from damaged cars. The brain then integrates these sensory signals as a highly abstract form -- the context -- and forms a memory that associates the traumatic event with the context.
The researchers also plan to develop strategies to suppress pathological fear memories in PTSD.
https://www.sciencedaily.com/releases/2020/03/200313112137.htm
The late effects of stress: New insights into how the brain responds to trauma
December 28, 2016
Science Daily/National Centre for Biological Sciences
A new study has shown how a single instance of severe stress can lead to delayed trauma. A stressful incident can lead to increased electrical activity in a brain region known as the amygdala. This activity is delayed and is dependent on a molecule known as the N-Methyl-D-Aspartate Receptor (NMDA-R), a protein on nerve cells known to be crucial for memory functions.
Mrs. M would never forget that day. She was walking along a busy road next to the vegetable market when two goons zipped past on a bike. One man's hand shot out and grabbed the chain around her neck. The next instant, she had stumbled to her knees, and was dragged along in the wake of the bike. Thankfully, the chain snapped, and she got away with a mildly bruised neck. Though dazed by the incident, Mrs. M was fine until a week after the incident.
Then, the nightmares began.
She would struggle and yell and fight in her sleep every night with phantom chain snatchers. Every bout left her charged with anger and often left her depressed. The episodes continued for several months until they finally stopped. How could a single stressful event have such extended consequences?
A new study by Indian scientists has gained insights into how a single instance of severe stress can lead to delayed and long-term psychological trauma. The work pinpoints key molecular and physiological processes that could be driving changes in brain architecture.
The team, led by Sumantra Chattarji from the National Centre for Biological Sciences (NCBS) and the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, have shown that a single stressful incident can lead to increased electrical activity in a brain region known as the amygdala. This activity sets in late, occurring ten days after a single stressful episode, and is dependent on a molecule known as the N-Methyl-D-Aspartate Receptor (NMDA-R), an ion channel protein on nerve cells known to be crucial for memory functions.
The amygdala is a small, almond-shaped groups of nerve cells that is located deep within the temporal lobe of the brain. This region of the brain is known to play key roles in emotional reactions, memory and making decisions. Changes in the amygdala are linked to the development of Post-Traumatic Stress Disorder (PTSD), a mental condition that develops in a delayed fashion after a harrowing experience.
Previously, Chattarji's group had shown that a single instance of acute stress had no immediate effects on the amygdala of rats. But ten days later, these animals began to show increased anxiety, and delayed changes in the architecture of their brains, especially the amygdala. "We showed that our study system is applicable to PTSD. This delayed effect after a single episode of stress was reminiscent of what happens in PTSD patients," says Chattarji. "We know that the amygdala is hyperactive in PTSD patients. But no one knows as of now, what is going on in there," he adds.
Investigations revealed major changes in the microscopic structure of the nerve cells in the amygdala. Stress seems to have caused the formation of new nerve connections called synapses in this region of the brain. However, until now, the physiological effects of these new connections were unknown.
In their recent study, Chattarji's team has established that the new nerve connections in the amygdala lead to heightened electrical activity in this region of the brain.
"Most studies on stress are done on a chronic stress paradigm with repeated stress, or with a single stress episode where changes are looked at immediately afterwards -- like a day after the stress," says Farhana Yasmin, one of the Chattarji's students. "So, our work is unique in that we show a reaction to a single instance of stress, but at a delayed time point," she adds.
Furthermore, a well-known protein involved in memory and learning, called NMDA-R has been recognised as one of the agents that bring about these changes. Blocking the NMDA-R during the stressful period not only stopped the formation of new synapses, it also blocked the increase in electrical activity at these synapses. "So we have for the first time, a molecular mechanism that shows what is required for the culmination of events ten days after a single stress," says Chattarji. "In this study, we have blocked the NMDA Receptor during stress. But we would like to know if blocking the molecule after stress can also block the delayed effects of the stress. And if so, how long after the stress can we block the receptor to define a window for therapy," he adds.
Chattarji's group first began their investigations into how stress affects the amygdala and other regions of the brain around ten years ago. The work has required the team to employ an array of highly specialised and diverse procedures that range from observing behaviour to recording electrical signals from single brain cells and using an assortment of microscopy techniques. "To do this, we have needed to use a variety of techniques, for which we required collaborations with people who have expertise in such techniques," says Chattarji. "And the glue for such collaborations especially in terms of training is vital. We are very grateful to the Wadhwani Foundation that supports our collaborative efforts and to the DBT and DAE for funding this work," he adds.
https://www.sciencedaily.com/releases/2016/12/161228102418.htm
Real-Life Exposure to Violence Disrupts a Child's Sleep Habits
June 13, 2012
Science Daily/American Academy of Sleep Medicine
When violence shatters a child's world, the torment can continue into their sleep, according to researchers in Cleveland. The impact is measurable and affected by the severity of the violence, and the effects can last over time.
The study, being presented June 12 at SLEEP 2012, shows how the severity of a violent event affects a child's quality and quantity of sleep. The more severe the violence, the more sleep is impacted. Trouble with nightmares and insomnia have long been associated with exposure to violence, but the Cleveland study found that characteristics of the violent act touch different aspects of the child's sleep.
http://www.sciencedaily.com/releases/2012/06/120613091043.htm
Poor sleep quality linked to lower physical activity in people with PTSD
July 16, 2014
Science Daily/American Academy of Sleep Medicine
A new study shows that worse sleep quality predicts lower physical activity in people with post-traumatic stress disorder. Results show that PTSD was independently associated with worse sleep quality at baseline, and participants with current PTSD at baseline had lower physical activity one year later.
"We found that sleep quality was more strongly associated with physical activity one year later than was having a diagnosis of PTSD," said lead author Lisa Talbot, postdoctoral fellow at the San Francisco VA Medical Center and the University of California, San Francisco. "The longitudinal aspect of this study suggests that sleep may influence physical activity."
Further analysis found that sleep quality completely mediated the relationship between baseline PTSD status and physical activity at the one-year follow-up, providing preliminary evidence that the association of reduced sleep quality with reduced physical activity could comprise a behavioral link to negative health outcomes such as obesity.
"This study adds to the literature that shows that better sleep leads to healthier levels of exercise, and previous research has shown that better sleep leads to healthier food choices," said American Academy of Sleep Medicine President Dr. Timothy Morgenthaler. "It is clear that healthy sleep is an essential ingredient in the recipe for a healthy life."
"The findings also tentatively raise the possibility that sleep problems could affect individuals' willingness or ability to implement physical activity behavioral interventions," she said. "Sleep improvements might encourage exercise participation."
According to the National Center for PTSD of the U.S. Department of Veterans Affairs, PTSD symptoms such as nightmares or flashbacks usually start soon after a traumatic event, but they may not appear until months or years later. Symptoms that last longer than four weeks, cause great distress or interfere with daily life may be a sign of PTSD.
http://www.sciencedaily.com/releases/2014/07/140716123841.htm
Combat Veterans Suffering from PTSD, 'Fear Circuitry' in the Brain Never Rests
May 18, 2013 —
Science Daily/NYU Langone Medical Center
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or under-react in response to stressful tasks, such as recalling a traumatic event or reacting to a photo of a threatening face. Now, researchers at NYU School of Medicine have explored for the first time what happens in the brains of combat veterans with PTSD in the absence of external triggers.
Their results, published in Neuroscience Letters, and presented today at the annual meeting of the American Psychiatry Association in San Francisco, show that the effects of trauma persist in certain brain regions even when combat veterans are not engaged in cognitive or emotional tasks, and face no immediate external threats. The findings shed light on which areas of the brain provoke traumatic symptoms and represent a critical step toward better diagnostics and treatments for PTSD.
A chronic condition that develops after trauma, PTSD can plague victims with disturbing memories, flashbacks, nightmares and emotional instability. Among the 1.7 million men and women who have served in the wars in Iraq and Afghanistan, an estimated 20% have PTSD. Research shows that suicide risk is higher in veterans with PTSD. Tragically, more soldiers committed suicide in 2012 than the number of soldiers who were killed in combat in Afghanistan that year.
"It is critical to have an objective test to confirm PTSD diagnosis as self reports can be unreliable," says co-author Charles Marmar, MD, the Lucius N. Littauer Professor of Psychiatry and chair of NYU Langone's Department of Psychiatry. Dr. Marmar, a nationally recognized expert on trauma and stress among veterans, heads The Steven and Alexandra Cohen Veterans Center for the Study of Post-Traumatic Stress and Traumatic Brain Injury at NYU Langone Medical Center.
The study, led by Xiaodan Yan, a research fellow at NYU School of Medicine, examined "spontaneous" or "resting" brain activity in 104 veterans of combat from the Iraq and Afghanistan wars using functional MRI, which measures blood-oxygen levels in the brain. The researchers found that spontaneous brain activity in the amygdala, a key structure in the brain's "fear circuitry" that processes fearful and anxious emotions, was significantly higher in the 52 combat veterans with PTSD than in the 52 combat veterans without PTSD. The PTSD group also showed elevated brain activity in the anterior insula, a brain region that regulates sensitivity to pain and negative emotions.
Moreover, the PTSD group had lower activity in the precuneus, a structure tucked between the brain's two hemispheres that helps integrate information from the past and future, especially when the mind is wandering or disengaged from active thought. Decreased activity in the precuneus correlates with more severe "re-experiencing" symptoms -- that is, when victims re-experience trauma over and over again through flashbacks, nightmares and frightening thoughts.
http://www.sciencedaily.com/releases/2013/05/130518153257.htm