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 researchers found that running prevents the activation of new neurons in response to stress. In sedentary mice, stress activated new neurons in the hippocampus (red and green cell above), but after 6 weeks of running, the stress-induced activation of both new and mature neurons disappeared. The red cells are new neurons and the green cells are activated mature neurons. (Photo courtesy of the Gould laboratory)

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.

The paper, "Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus," was published May 1 in the Journal of Neuroscience. This research was supported by National Institute of Mental Health grant MH091567.

Via: http://www.princeton.edu

Feeling edgy? Get some sleep

A lack of sleep, which is common in anxiety disorders, may play a key role in firing up brain regions that contribute to excessive worrying.

Sleep deprivation amplifies anticipatory anxiety by activating the brain’s amygdala and insular cortex regions associated with emotional processing.

The resulting pattern mimics the abnormal neural activity seen in anxiety disorders.

Furthermore, research suggests that innate worriers people who are naturally more anxious and therefore more likely to develop a full-blown anxiety disorder are acutely vulnerable to the effect of insufficient sleep.

“These findings help us realize that those people who are anxious by nature are the same people who will suffer the greatest harm from sleep deprivation,” says Matthew Walker, professor of psychology and neuroscience at the University of California, Berkeley.

The results suggest that people suffering from such maladies as generalized anxiety disorder, panic attacks, and post-traumatic stress disorder, may benefit substantially from sleep therapy.

“If sleep disruption is a key factor in anxiety disorders, as this study suggests, then it’s a potentially treatable target,” Walker says. “By restoring good quality sleep in people suffering from anxiety, we may be able to help ameliorate their excessive worry and disabling fearful expectations.”

While previous research has indicated that sleep disruption and psychiatric disorders often occur together, this latest study, published in the Journal of Neuroscience, is the first to causally demonstrate that sleep loss triggers excessive anticipatory brain activity associated with anxiety.

“It’s been hard to tease out whether sleep loss is simply a byproduct of anxiety, or whether sleep disruption causes anxiety,” says Andrea Goldstein, a doctoral student in psychology and lead author of the study. “This study helps us understand that causal relationship more clearly.”

In their experiments, researchers scanned the brains of 18 healthy young adults as they viewed dozens of images, first after a good night’s rest, and again after a sleepless night. The images were neutral, disturbing, or alternated between both.

Participants in the experiments reported a wide range of baseline anxiety levels, but none fit the criteria for a clinical anxiety disorder. After getting a full night’s rest at the lab, which researchers monitored by measuring neural electrical activity, their brains were scanned via functional MRI as they waited to be shown, and then viewed 90 images during a 45-minute session.

To trigger anticipatory anxiety, researchers primed the participants using one of three visual cues prior to each series of images. A large red minus sign signaled to participants that they were about to see a highly unpleasant image, such as a death scene. A yellow circle portended a neutral image, such as a basket on a table.

Perhaps most stressful was a white question mark, which indicated that either a grisly image or a bland, innocuous one was coming, and kept participants in a heightened state of suspense.

When sleep-deprived and waiting in suspenseful anticipation for a neutral or disturbing image to appear, activity in the emotional brain centers of all the participants soared, especially in the amygdala and the insular cortex. Notably, the amplifying impact of sleep deprivation was most dramatic for those people who were innately anxious to begin with.

“This discovery illustrates how important sleep is to our mental health,” says Walker. “It also emphasizes the intimate relationship between sleep and psychiatric disorders, both from a cause and a treatment perspective.”

The National Institute of Mental Health funded the research.

Source: http://www.futurity.org

Scientists decode how meditation relieves anxiety

Scientists have found that meditation can reduce anxiety by as much as 39 per cent and have also identified the brain functions involved.

Buddhist monks and Zen masters have known for years that meditation can lower anxiety, but the mechanism has not been clear, until now.

“Although we’ve known that meditation can reduce anxiety, we hadn’t identified the specific brain mechanisms involved in relieving anxiety in healthy individuals,” said Fadel Zeidan, postdoctoral research fellow in neurobiology and anatomy at Wake Forest Baptist and lead author of the study.

“In this study, we were able to see which areas of the brain were activated and which were deactivated during meditation-related anxiety relief,” Mr. Zeidan said.

For the study, 15 healthy volunteers with normal levels of everyday anxiety were recruited for the study. These individuals had no previous meditation experience or anxiety disorders.

All subjects participated in four 20-minute classes to learn a technique known as mindfulness meditation. In this form of meditation, people are taught to focus on breath and body sensations and to non-judgmentally evaluate distracting thoughts and emotions.

Both before and after meditation training, the study participants’ brain activity was examined using a special type of imaging — arterial spin labelling magnetic resonance imaging — that is very effective at imaging brain processes, such as meditation.

In addition, anxiety reports were measured before and after brain scanning.

The majority of study participants reported decreases in anxiety. Researchers found that meditation reduced anxiety ratings by as much as 39 per cent.

“This showed that just a few minutes of mindfulness meditation can help reduce normal everyday anxiety,” Mr. Zeidan said.

The study revealed that meditation-related anxiety relief is associated with activation of the anterior cingulate cortex and ventromedial prefrontal cortex, areas of the brain involved with executive-level function.

During meditation, there was more activity in the ventromedial prefrontal cortex, the area of the brain that controls worrying. In addition, when activity increased in the anterior cingulate cortex — the area that governs thinking and emotion — anxiety decreased.

“Mindfulness is premised on sustaining attention in the present moment and controlling the way we react to daily thoughts and feelings,” Mr. Zeidan said.

“Interestingly, the present findings reveal that the brain regions associated with meditation-related anxiety relief are remarkably consistent with the principles of being mindful,” Zeidan said.

The study was published in the journal Social Cognitive and Affective Neuroscience.

Source: www.thehindu.com