How to learn successfully even under stress

Predicting the weather under stress

The team from Bochum has examined 80 subjects, 50 per cent of whom were given a drug blocking mineralocorticoid receptors in the brain. The remaining participants took a placebo drug. Twenty participants from each group were subjected to a stress-inducing experience. Subsequently, all participants underwent a learning test, the so-called weather prediction task. The subjects were shown playing cards with different symbols and had to learn which combinations of cards meant rain and which meant sunshine. The researchers used MRI to record the respective brain activity.

Learning unconsciously or consciously

There are two different approaches to master the weather prediction test: some subjects tried consciously to formulate a rule that would enable them to predict sunshine and rain. Others learned unconsciously to give the right answer, following their gut feeling, as it were. The team of Lars Schwabe demonstrated in August 2012 that, under stress, the brain prefers unconscious to conscious learning. “This switch to another memory system happens automatically,” says Lars Schwabe. “It makes sense for the organism to react in this manner. Thus, learning efficiency can be maintained even under stress.” However, this works only with fully functional mineralocorticoid receptors. Once the researchers blocked these receptors by applying the drug Spironolactone, the participants switched over to the unconscious strategy less frequently, thus demonstrating a poorer learning efficiency.

Effects also visible in brain activity

These effects also became evident in MRI data. Usually, stress causes the brain activity to shift from the hippocampus – a structure for conscious learning – to the dorsal striatum, which manages unconscious learning. However, this stress-induced switch took place only in the placebo group, not in subjects who had been given the mineralocorticoid receptor blocker. Consequently, the mineralocorticoid receptors play a crucial role in enabling the brain to adapt to stressful situations.

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The Brain on Stress: Vulnerability and Plasticity of the Prefrontal Cortex over the Life Course

The prefrontal cortex (PFC) is involved in working memory and self-regulatory and goal-directed behaviors and displays remarkable structural and functional plasticity over the life course. Neural circuitry, molecular profiles, and neurochemistry can be changed by experiences, which influence behavior as well as neuroendocrine and autonomic function. Such effects have a particular impact during infancy and in adolescence. Behavioral stress affects both the structure and function of PFC, though such effects are not necessarily permanent, as young animals show remarkable neuronal resilience if the stress is discontinued. During aging, neurons within the PFC become less resilient to stress. There are also sex differences in the PFC response to stressors. While such stress and sex hormone-related alterations occur in regions mediating the highest levels of cognitive function and self-regulatory control, the fact that they are not necessarily permanent has implications for future behavior-based therapies that harness neural plasticity for recovery.

Exposure to Stress Even Before Conception Causes Genetic Changes to Offspring

A female’s exposure to distress even before she conceives causes changes in the expression of a gene linked to the stress mechanism in the body — in the ovum and later in the brains of the offspring from when they are born, according to a new study on rats conducted by the University of Haifa.

“The systemic similarity in many instances between us and mice raises questions about the transgenerational influences in humans as well, for example, the effects of the Second Lebanon War or the security situation in the South on the children of those who went through those difficult experiences,” the researchers said. “If until now we saw evidence only of behavioral effects, now we’ve found proof of effects at the genetic level.”

In previous studies in Prof. Micah Leshem’s lab, it was found that exposing rats to stress before they had even conceived (and even at their “teen” stage) influences the behavior of their offspring. This study, conducted in the lab of Dr. Inna Gaisler-Salomon by PhD student Hiba Zaidan, in cooperation with Prof. Leshem, the researchers sought to examine whether there was an influence on genetic expression.

In the study, which was recently published in the journal Biological Psychiatry, the researchers focused on the gene known as CRF-1, a gene linked to the body’s stress-control system that expresses itself in many places in the brain under stress.

The researchers took female rats that were 45 days old, which is parallel to human adolescence. Some of the rats were exposed to “minor” stress, which included changes in temperature and daily routine for seven days, and compared them to a control group that was not exposed to stress at all. The rats were mated and conceived two weeks later.

In the first part of the study, the researchers examined the ova of the rats that were exposed to stress even before they conceived, and they found that at that stage there was enhanced expression of the CRF-1 gene. For the second part, the researchers examined the brains of newborn rats immediately after birth, before the mother could have any influence on them, and found that even at the neonatal stage, there was enhanced expression of the CRF-1 gene in the brains of the rats born to mothers who had been exposed to stress.

During the third stage, the researchers exposed the offspring – both those whose mothers had been exposed to stress and those whose mothers were not – to stress when they reached adulthood. It emerged that the expression of CRF-1 among the offspring was dependent on three factors: The sex of the offspring, the stress undergone by the mother and the stress to which the offspring were exposed. The female rats whose mothers had been exposed to stress and who themselves underwent a “stressful” behavioral test showed higher levels of CRF-1 than other groups.

“This is the first time that we showed that the genetic response to stress in rats is linked to the experiences their mothers underwent long before they even got pregnant with them,” the researchers said. “We are learning more and more about intergenerational genetic transfer and in light of the findings, and in light of the fact that in today’s reality many women are exposed to stress even before they get pregnant, it’s important to research the degree to which such phenomenon take place in humans.”

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Exercise reorganizes the brain to be more resilient to stress

Physical activity reorganizes the brain so that its response to stress is reduced and anxiety is less likely to interfere with normal brain function, according to a research team based at Princeton University.

The researchers report in the Journal of Neuroscience that when mice allowed to exercise regularly experienced a stressor — exposure to cold water — their brains exhibited a spike in the activity of neurons that shut off excitement in the ventral hippocampus, a brain region shown to regulate anxiety.

These findings potentially resolve a discrepancy in research related to the effect of exercise on the brain — namely that exercise reduces anxiety while also promoting the growth of new neurons in the ventral hippocampus. Because these young neurons are typically more excitable than their more mature counterparts, exercise should result in more anxiety, not less. The Princeton-led researchers, however, found that exercise also strengthens the mechanisms that prevent these brain cells from firing.

The impact of physical activity on the ventral hippocampus specifically has not been deeply explored, said senior author Elizabeth Gould, Princeton’s Dorman T. Warren Professor of Psychology. By doing so, members of Gould’s laboratory pinpointed brain cells and regions important to anxiety regulation that may help scientists better understand and treat human anxiety disorders, she said.

From an evolutionary standpoint, the research also shows that the brain can be extremely adaptive and tailor its own processes to an organism’s lifestyle or surroundings, Gould said. A higher likelihood of anxious behavior may have an adaptive advantage for less physically fit creatures. Anxiety often manifests itself in avoidant behavior and avoiding potentially dangerous situations would increase the likelihood of survival, particularly for those less capable of responding with a “fight or flight” reaction, she said.

"Understanding how the brain regulates anxious behavior gives us potential clues about helping people with anxiety disorders. It also tells us something about how the brain modifies itself to respond optimally to its own environment," said Gould, who also is a professor in the Princeton Neuroscience Institute.

The research was part of the graduate dissertation for first author Timothy Schoenfeld, now a postdoctoral fellow at the National Institute of Mental Health, as well as part of the senior thesis project of co-author Brian Hsueh, now an MD/Ph.D. student at Stanford University. The project also included co-authors Pedro Rada and Pedro Pieruzzini, both from the University of Los Andes in Venezuela.

For the experiments, one group of mice was given unlimited access to a running wheel and a second group had no running wheel. Natural runners, mice will dash up to 4 kilometers (about 2.5 miles) a night when given access to a running wheel, Gould said. After six weeks, the mice were exposed to cold water for a brief period of time.

The brains of active and sedentary mice behaved differently almost as soon as the stressor occurred, an analysis showed. In the neurons of sedentary mice only, the cold water spurred an increase in “immediate early genes,” or short-lived genes that are rapidly turned on when a neuron fires. The lack of these genes in the neurons of active mice suggested that their brain cells did not immediately leap into an excited state in response to the stressor.

Instead, the brain in a runner mouse showed every sign of controlling its reaction to an extent not observed in the brain of a sedentary mouse. There was a boost of activity in inhibitory neurons that are known to keep excitable neurons in check. At the same time, neurons in these mice released more of the neurotransmitter gamma-aminobutyric acid, or GABA, which tamps down neural excitement. The protein that packages GABA into little travel pods known as vesicles for release into the synapse also was present in higher amounts in runners.

The anxiety-reducing effect of exercise was canceled out when the researchers blocked the GABA receptor that calms neuron activity in the ventral hippocampus. The researchers used the chemical bicuculine, which is used in medical research to block GABA receptors and simulate the cellular activity underlying epilepsy. In this case, when applied to the ventral hippocampus, the chemical blocked the mollifying effects of GABA in active mice.

Stress Test and Brain Scans Pinpoint Two Distinct Forms of Gulf War Illness

Researchers at Georgetown University Medical Center say their new work suggests that Gulf War illness may have two distinct forms depending on which brain regions have atrophied. Their study of Gulf War veterans, published online today in PLOS ONE, may help explain why clinicians have consistently encountered veterans with different symptoms and complaints.

Using brain imaging that was acquired before and after exercise tests, the researchers studied the effects of physical stress on the veterans and controls. Following exercise, subgroups were evident. In 18 veterans, they found that pain levels increased after completion of the exercise stress tests exercised; fMRI scans in these participants showed loss of brain matter in adjacent regions associated with pain regulation.  

During cognitive tasks, this group showed an increased use of the basal ganglia — a potential compensatory strategy the brain uses that is also seen in neurodegenerative disorders such as Alzheimer’s disease. Following exercise, this group lost the ability to employ their basal ganglia, suggesting an adverse response to a physiological stressor.

In addition, “a separate group of 10 veterans had a very different clinical alteration,” says lead author Rakib Rayhan, a researcher in the lab of the study’s senior investigator, James Baraniuk, MD, a professor of medicine at GUMC.

In these 10 veterans, the researchers found substantial increases in heart rate. They also discovered that this subgroup had atrophy in the brain stem, which regulates heart rate. .

In addition, brain scans during a cognitive task performed prior to exercise showed increased compensatory use of the cerebellum, again a trait seen in neurodegenerative disorders. Like the other group, this cohort lost the ability to use this compensatory area after exercise.

Alterations in cognition, brain structure and exercise-induced symptoms found in the veterans were absent in the 10-participant matched control group, the researchers say.

“The use of other brain areas to compensate for a damaged area is seen in other disorders, such as Alzheimer’s disease, which is why we believe our data show that these veterans are suffering from central nervous system dysfunction,” Rayhan explains. He adds, however, that because such changes are similar to other neurodegenerative states, it doesn’t mean that veterans will progress to Alzheimer’s or other diseases.

These findings — a surprise to researchers — follow a study in Gulf War veterans published in March in PLOS ONE that reported abnormalities in the bundle of nerve fibers connecting the brain areas involved in the processing and perception of pain and fatigue.

Gulf War Illness is the mysterious malady believed to have affected more than 200,000 military personnel who served in the 1990-1991 Operation Desert Shield and Desert Storm.

Although veterans were exposed to nerve agents, pesticides and herbicides (among other toxic chemicals), no one has definitively linked any single exposure or underlying mechanism to Gulf War illness.

The symptoms of Gulf War illness — which have not been widely accepted by the public or medical professionals — range from mild to debilitating and can include widespread pain, fatigue and headache, as well as cognitive and gastrointestinal dysfunctions.

“Our findings help explain and validate what these veterans have long said about their illness,” Rayhan says.

Researchers find out why some stress is good for you

Overworked and stressed out? Look on the bright side. Some stress is good for you.

“You always think about stress as a really bad thing, but it’s not,” said Daniela Kaufer, associate professor of integrative biology at the University of California, Berkeley. “Some amounts of stress are good to push you just to the level of optimal alertness, behavioral and cognitive performance.”

New research by Kaufer and UC Berkeley post-doctoral fellow Elizabeth Kirby has uncovered exactly how acute stress – short-lived, not chronic – primes the brain for improved performance.

In studies on rats, they found that significant, but brief stressful events caused stem cells in their brains to proliferate into new nerve cells that, when mature two weeks later, improved the rats’ mental performance.

“I think intermittent stressful events are probably what keeps the brain more alert, and you perform better when you are alert,” she said.

Kaufer, Kirby and their colleagues in UC Berkeley’s Helen Wills Neuroscience Institute describe their results in a paper published April 16 in the new open access online journal eLife.

The UC Berkeley researchers’ findings, “in general, reinforce the notion that stress hormones help an animal adapt – after all, remembering the place where something stressful happened is beneficial to deal with future situations in the same place,” said Bruce McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University, who was not involved in the study.

Kaufer is especially interested in how both acute and chronic stress affect memory, and since the brain’s hippocampus is critical to memory, she and her colleagues focused on the effects of stress on neural stem cells in the hippocampus of the adult rat brain. Neural stem cells are a sort of generic or progenitor brain cell that, depending on chemical triggers, can mature into neurons, astrocytes or other cells in the brain. The dentate gyrus of the hippocampus is one of only two areas in the brain that generate new brain cells in adults, and is highly sensitive to glucocorticoid stress hormones, Kaufer said.

Much research has demonstrated that chronic stress elevates levels of glucocorticoid stress hormones, which suppresses the production of new neurons in the hippocampus, impairing memory. This is in addition to the effect that chronically elevated levels of stress hormones have on the entire body, such as increasing the risk of chronic obesity, heart disease and depression.

Less is known about the effects of acute stress, Kaufer said, and studies have been conflicting.

To clear up the confusion, Kirby subjected rats to what, to them, is acute but short-lived stress – immobilization in their cages for a few hours. This led to stress hormone (corticosterone) levels as high as those from chronic stress, though for only a few hours. The stress doubled the proliferation of new brain cells in the hippocampus, specifically in the dorsal dentate gyrus.

Kirby discovered that the stressed rats performed better on a memory test two weeks after the stressful event, but not two days after the event. Using special cell labeling techniques, the researchers established that the new nerve cells triggered by the acute stress were the same ones involved in learning new tasks two weeks later.

“In terms of survival, the nerve cell proliferation doesn’t help you immediately after the stress, because it takes time for the cells to become mature, functioning neurons,” Kaufer said. “But in the natural environment, where acute stress happens on a regular basis, it will keep the animal more alert, more attuned to the environment and to what actually is a threat or not a threat.”

They also found that nerve cell proliferation after acute stress was triggered by the release of a protein, fibroblast growth factor 2 (FGF2), by astrocytes — brain cells formerly thought of as support cells, but that now appear to play a more critical role in regulating neurons.

“The FGF2 involvement is interesting, because FGF2 deficiency is associated with depressive-like behaviors in animals and is linked to depression in humans,” McEwen said.

Kaufer noted that exposure to acute, intense stress can sometimes be harmful, leading, for example, to post-traumatic stress disorder. Further research could help to identify the factors that determine whether a response to stress is good or bad.

“I think the ultimate message is an optimistic one,” she concluded. “Stress can be something that makes you better, but it is a question of how much, how long and how you interpret or perceive it.”

Reframing Stress: Stage Fright Can Be Your Friend

Fear of public speaking tops death and spiders as the nation’s number one phobia. But new research shows that learning to rethink the way we view our shaky hands, pounding heart, and sweaty palms can help people perform better both mentally and physically.

Before a stressful speaking task, simply encouraging people to reframe the meaning of these signs of stress as natural and helpful was a surprisingly effective way of handling stage fright, found the study to be published online April 8 in Clinical Psychological Science.

"The problem is that we think all stress is bad," explains Jeremy Jamieson, the lead author on the study and an assistant professor of psychology at the University of Rochester. "We see headlines about ‘Killer Stress’ and talk about being ‘stressed out.’" Before speaking in public, people often interpret stress sensations, like butterflies in the stomach, as a warning that something bad is about to happen, he says.

"But those feelings just mean that our body is preparing to address a demanding situation," explains Jamieson. "The body is marshaling resources, pumping more blood to our major muscle groups and delivering more oxygen to our brains." Our body’s reaction to social stress is the same flight or fight response we produce when confronting physical danger. These physiological responses help us perform, whether we’re facing a bear in the forest or a critical audience.

For many people, especially those suffering from social anxiety disorder, the natural uneasiness experienced before giving a speech can quickly tip over into panic. “If we think we can’t cope with stress, we will experience threat. When threatened, the body enacts changes to concentrate blood in the core and restricts flow to the arms, legs, and brain,” he explains. So, “cold feet” is a real physiological response to threat, not just a colorful expression.

"Lots of current advice for anxious people focuses on learning to ‘relax,’—you know, deep, even breathing and similar tips," says Jamieson. Such calming techniques, write the authors, may be helpful in situations that do not require peak performance. But when gearing up for a high-stakes exam, a job interview, or, yes, a speaking engagement, reframing how we think about stress may be a better strategy.

Then how can people reap the benefits of being stressed without being overwhelmed by dread? To answer that question, Jamieson and co-authors Matthew Nock, of Harvard University and Wendy Berry Mendes of the University of California in San Francisco, turned to the Trier Social Stress Test. Developed in 1993 by Clemens Kirschbaum and colleagues, this experiment relies on fear of public speaking and has become one of the most reliable laboratory methods for eliciting threat responses.

In the study, 69 adults were asked to give a five-minute talk about their strengths and weaknesses with only three minutes to prepare. Roughly half of the participants had a history of social anxiety and all participants were randomly assigned to two groups. The first group was presented information about the advantages of the body’s stress response and encouraged to “reinterpret your bodily signals during the upcoming public speaking task as beneficial.” That group also was asked to read summaries of three psychology studies that showed the benefits of stress. The second group received no information about reframing stress.

Participants delivered their speech to two judges. On purpose, the judges provided negative nonverbal feedback throughout the entire five-minute presentations, shaking their heads in disapproval, tapping on their clipboards, and staring stone-faced ahead. If study subjects ran out of things to say, the judges insisted that they continue speaking for the full five minutes. Following the speech, participants were asked to count backwards for five minutes in steps of seven beginning with the number 996. The evaluators again provided negative feedback throughout and insisted that participants start over if they made any mistakes.

Confronted with scowling judges, participants who received no stress preparation experienced a threat response, as captured by cardiovascular measures. But the group that was prepped about the benefits of stress weathered the trial better. That group reported feeling that they had more resources to cope with the public speaking task and, perhaps more tellingly, their physiological responses confirmed those perceptions. The prepped group pumped more blood through the body per minute compared to the group that did not receive instruction.

Surprisingly, this study also found that individuals who suffer from social anxiety disorder actually experienced no greater increase in physiological arousal while under scrutiny than their non-anxious counterparts, despite reporting more intense feelings of apprehension. This disconnect, argue the authors, supports the theory that our experience of acute or short-term stress is shaped by how we interpret physical cues. “We construct our own emotions,” says Jamieson.