Meditation as object of medical research

Mindfulness meditation produces personal experiences that are not readily interpretable by scientists who want to study its psychiatric benefits in the brain. At a conference near Boston April 5, 2014, Brown University researchers will describe how they’ve been able to integrate mindfulness experience with hard neuroscience data to advance more rigorous study.

Mindfulness is always personal and often spiritual, but the meditation experience does not have to be subjective. Advances in methodology are allowing researchers to integrate mindfulness experiences with brain imaging and neural signal data to form testable hypotheses about the science — and the reported mental health benefits — of the practice.

A team of Brown University researchers, led by junior Juan Santoyo, will present their research approach at 2:45 p.m on Saturday, April 5, 2014, at the 12th Annual International Scientific Conference of the Center for Mindfulness at the University of Massachusetts Medical School. Their methodology employs a structured coding of the reports meditators provide about their mental experiences. That can be rigorously correlated with quantitative neurophysiological measurements.

“In the neuroscience of mindfulness and meditation, one of the problems that we’ve had is not understanding the practices from the inside out,” said co-presenter Catherine Kerr, assistant professor (research) of family medicine and director of translational neuroscience in Brown’s Contemplative Studies Initiative. “What we’ve really needed are better mechanisms for generating testable hypotheses – clinically relevant and experience-relevant hypotheses.”

Now researchers are gaining the tools to trace experiences described by meditators to specific activity in the brain.

“We’re going to [discuss] how this is applicable as a general tool for the development of targeted mental health treatments,” Santoyo said. “We can explore how certain experiences line up with certain patterns of brain activity. We know certain patterns of brain activity are associated with certain psychiatric disorders.”

Structuring the spiritual

At the conference, the team will frame these broad implications with what might seem like a small distinction: whether meditators focus on their sensations of breathing in their nose or in their belly. The two meditation techniques hail from different East Asian traditions. Carefully coded experience data gathered by Santoyo, Kerr, and Harold Roth, professor of religious studies at Brown, show that the two techniques produced significantly different mental states in student meditators.

“We found that when students focused on the breath in the belly their descriptions of experience focused on attention to specific somatic areas and body sensations,” the researchers wrote in their conference abstract. “When students described practice experiences related to a focus on the nose during meditation, they tended to describe a quality of mind, specifically how their attention ‘felt’ when they sensed it.”

The ability to distill a rigorous distinction between the experiences came not only from randomly assigning meditating students to two groups – one focused on the nose and one focused on the belly – but also by employing two independent coders to perform standardized analyses of the journal entries the students made immediately after meditating.

This kind of structured coding of self-reported personal experience is called “grounded theory methodology.” Santoyo’s application of it to meditation allows for the formation of hypotheses.

For example, Kerr said, “Based on the predominantly somatic descriptions of mindfulness experience offered by the belly-focused group, we would expect there to be more ongoing, resting-state functional connectivity in this group across different parts of a large brain region called the insula that encodes visceral, somatic sensations and also provides a readout of the emotional aspects of so-called ‘gut feelings’.”

Unifying experience and the brain

The next step is to correlate the coded experiences data with data from the brain itself. A team of researchers led by Kathleen Garrison at Yale University, including Santoyo and Kerr, did just that in a paper in Frontiers in Human Neuroscience in August 2013. The team worked with deeply experienced meditators to correlate the mental states they described during mindfulness with simultaneous activity in the posterior cingulate cortex (PCC). They measured that with real-time functional magnetic resonance imaging.

They found that when meditators of several different traditions reported feelings of “effortless doing” and “undistracted awareness” during their meditation, their PCC showed little activity, but when they reported that they felt distracted and had to work at mindfulness, their PCC was significantly more active. Given the chance to observe real-time feedback on their PCC activity, some meditators were even able to control the levels of activity there.

“You can observe both of these phenomena together and discover how they are co-determining one another,” Santoyo said. “Within 10 one-minute sessions they were able to develop certain strategies to evoke a certain experience and use it to drive the signal.”

Toward therapies

A theme of the conference, and a key motivator in Santoyo and Kerr’s research, is connecting such research to tangible medical benefits. Meditators have long espoused such benefits, but support from neuroscience and psychiatry has been considerably more recent.

In a February 2013 paper in Frontiers in Human Neuroscience, Kerr and colleagues proposed that much like the meditators could control activity in the PCC, mindfulness practitioners may gain enhanced control over sensory cortical alpha rhythms. Those brain waves help regulate how the brain processes and filters sensations, including pain, and memories such as depressive cognitions.

Santoyo, whose family emigrated from Colombia when he was a child, became inspired to investigate the potential of mindfulness to aid mental health beginning in high school. Growing up in Cambridge and Somerville, Mass., he observed the psychiatric difficulties of the area’s homeless population. He also encountered them while working in food service at Cambridge hospital.

“In low-income communities you always see a lot of untreated mental health disorders,” said Santoyo, who meditates regularly and helps to lead a mindfulness group at Brown. He is pursuing a degree in neuroscience and contemplative science. “The perspective of contemplative theory is that we learn about the mind by observing experience, not just to tickle our fancy but to learn how to heal the mind.”

It’s a long path, perhaps, but Santoyo and his collaborators are walking it with progress.

Even if there was no God, even if human beings had no soul, it would still be true that evolution had created a remarkable animal — the human animal — during its millions of years of labor. So very like our closest biological relatives, the chimpanzees, yet so different. For our study of the chimpanzees had helped to pinpoint not only the similarities between them and us, but also those ways in which we are most different. Admittedly, we are not the only beings with personalities, reasoning powers, altruism, and emotions like joy and sorrow; nor are we the only beings capable of mental as well as physical suffering. But our intellect has grown mighty in complexity since the first true men branched off from the ape-man stock some two million years ago. And we, and only we, have developed a sophisticated spoken language. For the first time in evolution, a species evolved that was able to teach its young about objects and events not present, to pass on wisdom gleaned from the successes — and the mistakes — of the past, to make plans for the distant future, to discuss ideas so that they could grow, sometimes out of all recognition, through the combined wisdom of the group.

Happy 80th Birthday, Jane Goodall: The Beloved Primatologist on Science, Religion, and Our Human Responsibilities

Positive, negative thinkers’ brains revealed

The ability to stay positive when times get tough – and, conversely, of being negative – may be hardwired in the brain, finds new research led by a Michigan State University psychologist.

The study, which appears in the Journal of Abnormal Psychology, is the first to provide biological evidence validating the idea that there are, in fact, positive and negative people in the world.

“It’s the first time we’ve been able to find a brain marker that really distinguishes negative thinkers from positive thinkers,” said Jason Moser, lead investigator and assistant professor of psychology.

For the study, 71 female participants were shown graphic images and asked to put a positive spin on them while their brain activity was recorded. Participants were shown a masked man holding a knife to a woman’s throat, for example, and told one potential outcome was the woman breaking free and escaping.

The participants were surveyed beforehand to establish who tended to think positively and who thought negatively or worried. Sure enough, the brain reading of the positive thinkers was much less active than that of the worriers during the experiment.

“The worriers actually showed a paradoxical backfiring effect in their brains when asked to decrease their negative emotions,” Moser said. “This suggests they have a really hard time putting a positive spin on difficult situations and actually make their negative emotions worse even when they are asked to think positively.”

The study focused on women because they are twice as likely as men to suffer from anxiety related problems and previously reported sex differences in brain structure and function could have obscured the results.

Moser said the findings have implications in the way negative thinkers approach difficult situations.

“You can’t just tell your friend to think positively or to not worry – that’s probably not going to help them,” he said. “So you need to take another tack and perhaps ask them to think about the problem in a different way, to use different strategies.”

Negative thinkers could also practice thinking positively, although Moser suspects it would take a lot of time and effort to even start to make a difference.

A Brain Region for Resisting Alcohol’s Allure

As recovering spring breakers are regretting binge drinking escapades, it may be hard for them to appreciate that there is a positive side to the nausea, sleepiness, and stumbling. University of Utah neuroscientists report that when a region of the brain called the lateral habenula is chronically inactivated in rats, they repeatedly drink to excess and are less able to learn from the experience. The study, published online in PLOS ONE on April 2, has implications for understanding behaviors that drive alcohol addiction.

While complex societal pressures contribute to alcoholism, physiological factors are also to blame. Alcohol is a drug of abuse, earning its status because it tickles the reward system in the brain, triggering the release of feel-good neurotransmitters. The dreaded outcomes of overindulging serve the beneficial purpose of countering the pull of temptation, but little is understood about how those mechanisms are controlled.

U of U professor of neurobiology and anatomy Sharif Taha, Ph.D., and colleagues, tipped the balance that reigns in addictive behaviors by inactivating in rats a brain region called the lateral habenula. When the rats were given intermittent access to a solution of 20% alcohol over several weeks, they escalated their alcohol drinking more rapidly, and drank more heavily than control rats.

“In people, escalation of intake is what eventually separates a social drinker from someone who becomes an alcoholic,” said Taha. “These rats drink amounts that are quite substantial. Legally they would be drunk if they were driving.”

The lateral habenula is activated by bad experiences, suggesting that without this region the rats may drink more because they fail to learn from the negative outcomes of overindulging. The investigators tested the idea by giving the rats a desirable, sweet juice then injecting them with a dose of alcohol large enough to cause negative effects.

“It’s the same kind of learning that mediates your response in food poisoning. You taste something and then you get sick, and then of course you avoid that food in future meals,” explained Taha.

Yet rats with an inactivated lateral habenula sought out the juice more than control animals, even though it meant a repeat of the bad experience.

“The way I look at it is the rewarding effects of drinking alcohol compete with the aversive effects,” explained Andrew Haack, who is co-first author on the study with Chandni Sheth, both neuroscience graduate students. “When you take the aversive effects away, which is what we did when we inactivated the lateral habenula, the rewarding effects gain more purchase, and so it drives up drinking behavior.”

The group’s findings may help explain results from previous clinical investigations demonstrating that men who were less sensitive to the negative effects of alcohol drank more heavily, and were more likely to become problem drinkers later in life.

The researches think the lateral habenula likely works in one of two ways. The region may regulate how badly an individual feels after over-drinking. Alternatively, it may control how well an individual learns from their bad experience. Future work will resolve between the two.

“If we can understand the brain circuits that control sensitivity to alcohol’s aversive effects, then we can start to get a handle on who may become a problem drinker,” said Taha.

Noisy brain signals: How the schizophrenic brain misinterprets the world

People with schizophrenia often misinterpret what they see and experience in the world. New research provides insight into the brain mechanisms that might be responsible for this misinterpretation. The study from the Montreal Neurological Institute and Hospital – The Neuro - at McGill University and McGill University Health Centre, reveals that certain errors in visual perception in people with schizophrenia are consistent with interference or ‘noise’ in a brain signal known as a corollary discharge. Corollary discharges are found throughout the animal kingdom, from bugs to fish to humans, and they are thought to be crucial for monitoring one’s own actions. The study, published in the April 2 issue of the Journal of Neuroscience, identifies a corollary discharge dysfunction in schizophrenia, which could aid with diagnosis and treatment of this difficult disorder. It was carried out in collaboration with researchers Veronica Whitford, Gillian O’Driscoll, and Debra Titone in the Department of Psychology, McGill University.

“A corollary discharge is a copy of a nervous system message that is sent to other parts of the brain, in order to make us aware that we are doing something,” said Dr. Christopher Pack, neuroscientist at The Neuro and lead investigator on the study. “For example, if we want to move our arm, the motor area of the brain sends a signal to the muscles to produce a movement. A copy of this command, which is the corollary discharge, is sent to other regions of the brain, to inform them of the impending movement. If you were moving your arm, and you didn’t have the corollary discharge signal, you might assume that someone else was moving your arm. Similarly, if you generated a thought, and you had an impaired corollary discharge, then you might assume that someone else placed the thought in your mind. Corollary discharges ensure that different areas of the brain are communicating with each other, so that we are aware that we are moving our own arm, talking, or thinking our own thoughts.”

Schizophrenia is a disorder that interferes with the ability to think clearly and to manage emotions. People with schizophrenia often attribute their own thoughts and actions to external sources, as in the case of auditory hallucinations. Other common symptoms include delusions and disorganized thinking and speech. 

Recent research has suggested that an impaired corollary discharge can account for some of these symptoms. However, the nature of the impairment was unknown. In their study, Dr. Pack and his colleagues (including Dr. Alby Richard, neurology resident at The Neuro) used a test called a perisaccadic localization task, to investigate corollary discharge activity. In this test, subjects are asked to make quick eye movements to follow a dot on a computer screen. At the same time they are also asked to localize visual stimuli that appear briefly on the screen from time to time. In order to perform this task accurately, subjects need to know where on the screen they are looking – in other words they use corollary discharges signals that arise from the brain structures that control the eye muscles.

The results showed that people with schizophrenia were less accurate in figuring out where they were looking. Consequently they made more mistakes in estimating the position of the stimuli that were flashed on the screen. “What is interesting and potentially clinically important is that the pattern of mistakes made by the patients correlated with the extent of their symptoms,” said Dr. Pack. “This is particularly interesting because the circuits that control eye movements include the best-understood structures in the brain. So we are optimistic that we can work backward from the behavioral data to the biological basis of the corollary discharge effects. We have already started to do this with computational modeling. Mathematically we can convert the corollary discharge of a healthy control into the corollary discharge of a patient with schizophrenia by adding noise and randomness. It is not that people with schizophrenia have no corollary discharge, or a corollary discharge with delayed or weaker amplitude. Rather the patients appear primarily to have a noisy corollary discharge signal. This visual test is very easy thing to do and quite sensitive to individual differences.“

The study shows that patients with schizophrenia make larger errors in localizing visual stimuli compared to controls. These results could be explained by a corollary discharge signal, which also predicts patient symptom severity, suggesting a possible basis for some of the most common symptoms of schizophrenia. This work was supported by The Natural Sciences and Engineering Research Council of Canada, The Brain & Behavior Research Foundation (NARSAD) and the EJLB Foundation.

New Method Could Improve Ultrasound Imaging

One day while casually reading a review article, Caltech chemical engineer Mikhail Shapiro came across a mention of gas vesicles—tiny gas-filled structures used by some photosynthetic microorganisms to control buoyancy. It was a light-bulb moment. Shapiro is always on the lookout for new ways to enhance imaging techniques such as ultrasound or MRI, and the natural nanostructures seemed to be just the ticket to improve ultrasound imaging agents.

Now Shapiro and his colleagues from UC Berkeley and the University of Toronto have shown that these gas vesicles, isolated from bacteria and from archaea (a separate lineage of single-celled organisms), can indeed be used for ultrasound imaging. The vesicles could one day help track and reveal the growth, migration, and activity of a variety of cell types—from neurons to tumor cells—using noninvasive ultrasound, one of the most widely used imaging modalities in biomedicine.

A paper describing the work appears as an advance online publication in the journal Nature Nanotechnology. 

"People have struggled to make synthetic nanoscale imaging agents for ultrasound for many years," says Shapiro. "To me, it’s quite amazing that we can borrow something that nature has evolved for a completely different purpose and use it for in vivo ultrasound imaging. It shows just how much nature has to offer us as engineers."

Read more

teded:

When you eat something loaded with sugar, your taste buds, your gut and your brain all take notice. This activation of your reward system is not unlike how bodies process addictive substances such as alcohol or nicotine — an overload of sugar spikes dopamine levels and leaves you craving more.

From the TED-Ed Lesson How sugar affects the brain - Nicole Avena

Animation by STK Films