Excessive Brain Activity Linked to Shorter Life Span

Video: New research links excess neural activity — the flickering light seen in this image — to reduced longevity. Credit: Yankner lab, Harvard Medical School.

The brain’s neural activity — long implicated in disorders ranging from dementia to epilepsy — also plays a role in how long we live.

The study, led by scientists in the Blavatnik Institute at Harvard Medical School and based on findings from human brains, mice, and worms, suggests that excessive activity in the brain is linked to shorter life spans, while suppressing overactivity can extend life.

Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, according to the researchers.

“An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span,” said study senior author Dr. Bruce Yankner, a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging.

Neural excitation appears to act along a chain of molecular events famously known to influence longevity — the insulin and insulin-like growth factor (IGF) signaling pathway, the researchers explain.

The key in this signaling cascade appears to be a protein called REST, previously shown by researchers in the Yankner Lab to protect aging brains from dementia and other stresses.

Study results could lead to the design of new therapies for conditions that involve neural overactivity, such as Alzheimer’s disease and bipolar disorder, the researchers said.

The findings also raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity, they said.

Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner added.

The researchers began their investigation by analyzing gene expression patterns — the extent to which various genes are turned on and off — in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.

The information was collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia, the researchers noted.

The researchers immediately noticed a striking difference between the older and younger study participants, Yankner said. The longest-lived people — those over 85 — had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.

Next came the question that all scientists confront: Correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span or were excitation levels directly affecting longevity? If so, how?

To answer these questions, the researchers conducted a barrage of experiments, including genetic, cell, and molecular biology tests in the model organism Caenorhabditis elegans, analyses of genetically altered mice, and additional brain tissue analyses of people who lived for more than a century.

These experiments revealed that altering neural excitation does indeed affect life span and illuminated what might be happening on a molecular level, the researchers said, noting all signs pointed to the protein REST.

REST, which is known to regulate genes, also suppresses neural excitation, the researchers found.

Blocking REST or its equivalent in the animals led to higher neural activity and earlier deaths, while boosting REST did the opposite.

The researchers also discovered that people who lived to 100 and beyond had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.

“It was extremely exciting to see how all these different lines of evidence converged,” said study co-author Dr. Monica Colaiácovo, a professor of genetics at Harvard Medical School, whose lab collaborated on the C. elegans work.

The researchers found that from worms to mammals, REST suppresses the expression of genes that are centrally involved in neural excitation, such as ion channels, neurotransmitter receptors, and structural components of synapses.

Lower excitation activates a family of proteins known as forkhead transcription factors. These proteins have been shown to mediate a “longevity pathway” via insulin/IGF signaling in many animals. It’s the same pathway that scientists believe can be activated by caloric restriction, according to the researchers.

In addition to its emerging role in staving off neurodegeneration, discovery of REST’s role in longevity provides additional motivation to develop drugs that target the protein, the researchers said.

Although it will take time and many tests to determine whether such treatments reduce neural excitation, promote healthy aging, or extend life span, the concept has captivated some researchers.

“The possibility that being able to activate REST would reduce excitatory neural activity and slow aging in humans is extremely exciting,” said Colaiácovo.

The study was published in Nature.

Source: Harvard Medical School

 

Mindfulness May Help Reduce Opioid Cravings in Chronic Pain Patients

People struggling with opioid addiction and chronic pain may experience fewer cravings and less pain if they use mindfulness techniques along with medication for opioid dependence, according to a new study published in the journal Drug and Alcohol Dependence.

Mindfulness is the meditative practice of focusing on the present moment and accepting one’s thoughts, feelings and bodily sensations, without judgment.

The study, led by researchers from Rutgers University in New Jersey, looked at the effects of mindfulness techniques and methadone therapy on 30 patients with opioid addiction and chronic pain.

The research team found that participants who received methadone and a mindfulness training-based intervention were 1.3 times better at controlling their cravings and had significantly greater improvements in pain, stress, and positive emotions, compared to participants who only received standard methadone treatment and counseling.

The findings held true even though the mindfulness participants were more aware of their cravings.

“Methadone maintenance therapy (MMT) has been an effective form of medication treatment for opioid use disorder,” said Associate Professor Nina Cooperman, a clinical psychologist in the Division of Addiction Psychiatry at Rutgers Robert Wood Johnson Medical School.

“However, nearly half of individuals on MMT continue to use opioids during treatment or relapse within six months.”

Cooperman said that people with opioid addictions often experience chronic pain, anxiety and depression while on methadone maintenance, which is why mindfulness-based, non-drug interventions are promising treatments.

The researchers said mindfulness-based interventions could help people dependent on opioids increase their self-awareness and self-control over cravings and be less reactive to emotional and physical pain.

Individuals with an opioid addiction could also be taught to change their negative thought patterns and savor pleasant events, which may help them to regulate their emotions and experience more enjoyment.

In 2017, more than 70,000 people died from a drug overdose, making it a leading cause of injury-related death in the United States. Of those deaths, almost 68% (47,600 overdose deaths) involved a prescription or illicit opioid, according to the Centers for Disease Control and Prevention (CDC). Overdose deaths involving prescription opioids were five times higher in 2017 than in 1999.

Source: Rutgers University

 

Chair Yoga May Improve Quality of Life in Dementia Patients

Chair yoga may help improve quality of life in older adults with moderate-to-severe dementia, according to a new study by Florida Atlantic University (FAU).

Chair yoga provides a safe environment for stretching, strengthening and flexibility while decreasing the risk of falls by using a chair. It also provides important breathing and relaxation techniques through stationary poses and guided relaxation of various muscle groups.

“We think that the physical poses we used in the chair yoga and chair-based exercise groups were an important factor in improving quality of life for the participants in our study,” said Juyoung Park, Ph.D., lead author and an associate professor in the Phyllis and Harvey Sandler School of Social Work within FAU’s College for Design and Social Inquiry.

“It is fascinating that, although some participants showed mild levels of agitation or wandering in the intervention room prior to the yoga session, they became calm and attentive when the yoga interventionist started demonstrating yoga poses.”

“Although they did not understand the interventionist’s verbal instructions due to their cognitive impairment associated with advanced dementia, they followed the instructor’s poses.”

For the study, published in the American Journal of Alzheimer’s Disease & Other Dementias, researchers from FAU compared chair yoga with two other types of non-pharmacological interventions: chair-based exercise and music intervention.

The study involved older adults (mean average age was 84 years old) with moderate-to-severe dementia, including Alzheimer’s disease (the largest diagnostic group), Lewy Body dementia and Parkinson disease dementia. The patients were unable to participate in regular exercise or standing yoga due to cognitive impairment, problems with balance, or fear of falling.

Participants in each of the three groups attended 45-minute sessions twice a week for 12 weeks. Researchers collected data at baseline, after six weeks and after completing the 12-week intervention.

Results showed that participants with moderate-to-severe dementia could safely adhere to non-pharmacological interventions, and more than 97% of the participants fully engaged in each session.

The findings show that those in the chair yoga group improved significantly in quality-of-life scores compared to the music intervention group. Both the chair yoga and chair-exercise groups showed improvement over time, while the music intervention group declined.

In addition, both the chair yoga and chair-based exercise groups showed lower depression across all three time points when compared to the music intervention group.

The team did not find any differences in the three intervention groups on physical function, with the exception of handgrip strength, which was higher in the chair yoga group compared to the music intervention group. None of the three groups declined significantly in any of the investigated physical functional measures.

Researchers also did not find any significant between-group differences in anxiety at any time point. There were no significant between-group differences in change in depression and anxiety. The researchers also did not find significant differences among the three intervention groups for sleep quality at any of the three time points.

“We did see an increase in agitation in the chair yoga group even though this group reported a higher quality of life score, including physical condition, mood, functional abilities, interpersonal relationships, ability to participate in meaningful activities, and final situations,” said Park.

“It’s important to note that quality of life is a more comprehensive approach to biopsychosocial and behavioral function than a mere measure of agitation. Meditation and the mind-body connection component of the chair yoga program may have increased quality of life for participants in this study. This finding is consistent with our earlier studies that showed a targeted approach was successful in increasing quality of life in patients with dementia.”

Source: Florida Atlantic University

Mindfulness Meditation May Benefit Older Adults with Mild Cognitive Impairment

Mindfulness meditation may benefit older adults with mild cognitive impairment (MCI), according to a small pilot study published in the Journal of Alzheimer’s Disease.

There’s currently no known way to prevent older adults with MCI from developing Alzheimer’s disease, but mindfulness meditation may be a safe and feasible non-pharmacological treatment that can help.

Mindfulness means maintaining a moment-by-moment, non-judgmental awareness of thoughts, feelings, bodily sensations, and surrounding environment.

“Our study showed promising evidence that adults with MCI can learn to practice mindfulness meditation, and by doing so may boost their cognitive reserve,” said Rebecca Erwin Wells, MD, MPH, associate professor of neurology at Wake Forest School of Medicine, a practicing neurologist at Wake Forest Baptist Medical Center and associate director of clinical research for its Center for Integrative Medicine.

Cognitive reserve is a person’s capacity to maintain normal cognitive function in the presence of deteriorating brain function.

“While the concept of mindfulness meditation is simple, the practice itself requires complex cognitive processes, discipline and commitment,” Wells explained. “This study suggests that the cognitive impairment in MCI is not prohibitive of what is required to learn this new skill.”

Previous research has shown that high levels of chronic stress negatively impact the hippocampus, a part of the brain involved in memory and learning, and are associated with increased incidence of MCI and Alzheimer’s. Other studies have indicated that non-drug interventions such as aerobic exercise can have positive effects on cognition, stress levels and the brain.

To determine whether a mindfulness-based stress-reduction (MBSR) program could benefit adults with MCI, the study team recruited 14 men and women between the ages of 55 and 90 with clinically diagnosed MCI and randomized them to either an eight-week course involving mindfulness meditation and yoga or a “waiting list” control group.

The researchers previously reported that the nine participants who completed the MBSR program showed trends toward improvements on measures of cognition and well-being and indications of positive impacts on the hippocampus as well as other areas of the brain associated with cognitive decline.

The new study adds context to those findings with an analysis of the MBSR participants’ responses in interviews conducted at the end of the eight-week course.

“While the MBSR course was not developed or structured to directly address MCI, the qualitative interviews revealed new and important findings specific to MCI,” Wells said. “The participants’ comments and ratings showed that most of them were able to learn the key tenets of mindfulness, demonstrating that the memory impairment of MCI does not preclude learning such skills.”

Participants who practiced at least 20 minutes a day were most likely to have understood the underlying concepts of mindfulness, Wells noted.

“Until treatment options that can prevent the progression to Alzheimer’s are found, mindfulness meditation may help patients living with MCI,” said Well.

The limitations of the study include the small sample size and that the results may not generalize to all patients with MCI, as two-thirds of the participants in this study had a college education or more. Additional research is needed to further test the preliminary hypotheses contained in this study.

Source: Wake Forest Baptist Medical Center

Mindfulness App Helps to Stop Smoking by Changing Brain Activity

Emerging research suggests a smartphone app that helps people stop smoking reduces activity in a brain region typically stimulated when a person experiences a craving to smoke. The app uses a mindfulness-based approach and was effective at reducing study participants’ self-reported daily cigarette consumption.

Researchers found that those who reduced their cigarette consumption the most also showed decreased brain reactivity to smoking-related images.

In the study, Dr. Jud Brewer, an associate professor of behavioral and social sciences and psychiatry at Brown University, and his team conducted a randomized controlled trial that compared smoking-cessation apps.

For four weeks, one group of 33 participants used a mindfulness-based app, while another group of 34 participants used a free smoking-cessation app from the National Cancer Institute (NCI).

“This is the first study to show that mindfulness training could specifically affect a mechanism in the brain and to show that changes in this brain mechanism were connected to improved clinical outcomes,” said Brewer.

“We’re moving in the direction of being able to screen someone before treatment and offer them the behavior-change interventions that will be most likely to help them. This will save everybody time and money.”

The findings appear in the journal Neuropsychopharmacology.

The mindfulness app includes daily videos and activities to help users identify their smoking triggers, become more aware of cravings and learn mindfulness methods to ride out the cravings. In contrast, the NCI app helps users track smoking triggers, provides inspirational messages and delivers distractions to help users deal with cravings.

The research team found that participants who used the mindfulness app for a month reduced their self-reported daily cigarette consumption by a wide range, with an average drop of 11 cigarettes per day.

The NCI app users also reduced cigarette consumption by a wide range, with an average decrease of nine per day. Some participants in both groups reported smoking no cigarettes by the end of the month.

Participants in both groups completed an average of 16 out of 22 stand-alone modules of the app. Participants in the mindfulness group who completed more modules were likely to have a greater reduction in their cigarette consumption; this correlation was not found for the NCI group.

Participants in the mindfulness group were also significantly more likely to say that they would recommend the app to a friend than participants in the NCI group.

As a part of the study, the researchers conducted functional magnetic resonance imaging (fMRI) brain scans of the participants as they looked at smoking-associated images or other images not associated with smoking. These scans were conducted before and after participants used one of the two apps. This procedure helped researchers determine how the mindfulness app worked in the brain.

Specifically, the researchers looked at the changes in brain activity in the posterior cingulate cortex, a ping-pong-ball-sized brain region known to be activated when someone gets caught up in craving cigarettes, cocaine or even chocolate, Brewer said.

The posterior cingulate cortex has also been shown to be deactivated by meditation, so Brewer hypothesized that this region would play a critical role in how mindfulness-based interventions — app-based or otherwise — affect the brain and change behaviors.

When the researchers directly compared the changes in brain reactivity in the target region between the two groups before and after they used the apps, they found no statistical differences.

However, when they looked at the individual level and compared the reduction in cigarettes smoked to the changes in brain reactivity, they found that the participants in the mindfulness group who had the greatest reduction in number of cigarettes per day also showed a significant reduction in brain reactivity to smoking images.

They saw no correlation between number of cigarettes smoked and brain reactivity for the participants who used the NCI app. They also noted that the correlation between number of cigarettes smoked and brain reactivity was particularly significant for women in the mindfulness group.

Therefore, investigators concluded that for some participants — those for whom the app was most effective — the training helped decrease brain reactivity to smoking urges.

Surprisingly, 13 percent of participants were non-reactive to smoking images before they used either app, a phenomenon not encountered in previous scientific literature, Brewer said.

Other participants became more reactive to smoking images after they used either app; this has been seen before in people who craved cigarettes more while trying to quit, he added.

Source: Brown University

Study: 1 in 4 Who Meditate Have Had Bad Psychological Experience

More than a quarter of people who regularly meditate have had a “particularly unpleasant” psychological experience, including feelings of fear and distorted emotions, according to a new study.

Researchers at the University of College London also found those who had attended a meditation retreat, those who only practiced deconstructive types of meditation, such as Vipassana (insight) and Koan practice (used in Zen Buddhism), and those with higher levels of repetitive negative thinking, were more likely to report a “particularly unpleasant” meditation-related experience.

However, the study, which was based on an international online survey of 1,232 people who had at least two months meditation experience, found women and those with a religious belief were less likely to have had a “particularly unpleasant” experience.

“These findings point to the importance of widening the public and scientific understanding of meditation beyond that of a health-promoting technique,” said Dr. Marco Schlosser, a researcher in the UCL Division of Psychiatry and lead author of the study. “Very little is known about why, when, and how such meditation-related difficulties can occur. More research is now needed to understand the nature of these experiences.”

“When are unpleasant experiences important elements of meditative development, and when are they merely negative effects to be avoided?” he continued.

The study, conducted with researchers at Witten/Herdecke University in Germany and the University of Ljubljana in Slovenia, was triggered by a limited but growing number of research reports and case studies that indicate psychologically unpleasant experiences can occur during meditative practice. Some traditional Buddhist texts also reference vivid accounts of similar experiences, the researchers said.

However, very little is known about the prevalence of these experiences, they noted.

In the online survey, participants answered the following question: “Have you ever had any particularly unpleasant experiences (e.g. anxiety, fear, distorted emotions or thoughts, altered sense of self or the world), which you think may have been caused by your meditation practice?”

Participants also reported how long they had been practicing meditation and the frequency of practice, whether they had attended a meditation retreat at any point in their life, and what form of meditation they practiced. They also completed measures of repetitive negative thinking and self-compassion.

The findings showed that:

  • Of the 1,232 participants, 25.6 percent indicated that they had previously encountered particularly unpleasant meditation-related experiences.
  • More male participants, 28.5 percent, experienced a particularly unpleasant experience, compared to 23 percent of female participants.
  • 30.6 percent of those who did not have a religious belief had a particularly unpleasant experience, compared to 22 percent of those who had a religious belief.
  • More people, 29.2 percent, who practiced only deconstructive types of meditation reported a particularly unpleasant experience, compared to 20.3 percent who only engaged in other meditation types.
  • And 29 percent of those who had been on a meditation retreat (at any point in life) had a particularly unpleasant experience, compared with 19.6 percent, who had never been on a retreat.

“Most research on meditation has focused on its benefits, however, the range of meditative experiences studied by scientists needs to be expanded,” Schlosser said. “It is important at this point not to draw premature conclusions about the potential negative effects of meditation.”

“Longitudinal studies will help to learn when, for whom, and under what circumstances these unpleasant experiences arise, and whether they can have long-term effects,” he continued. “This future research could inform clinical guidelines, mindfulness manuals, and meditation teacher training.”

The study was published in PLOS ONE.

Source: University College London