People worldwide may feel mind-body connections in same way

Many phrases reflect how emotions affect the body: Loss makes you feel “heartbroken,” you suffer from “butterflies” in the stomach when nervous, and disgusting things make you “sick to your stomach.”

Now, a new study from Finland suggests connections between emotions and body parts may be standard across cultures.

The researchers coaxed Finnish, Swedish and Taiwanese participants into feeling various emotions and then asked them to link their feelings to body parts. They connected anger to the head, chest, arms and hands; disgust to the head, hands and lower chest; pride to the upper body; and love to the whole body except the legs. As for anxiety, participants heavily linked it to the mid-chest.

"The most surprising thing was the consistency of the ratings, both across individuals and across all the tested language groups and cultures," said study lead author Lauri Nummenmaa, an assistant professor of cognitive neuroscience at Finland’s Aalto University School of Science.

However, one U.S. expert, Paul Zak, chairman of the Center for Neuroeconomics Studies at Claremont Graduate University in California, was unimpressed by the findings. He discounted the study, saying it was weakly designed, failed to understand how emotions work and “doesn’t prove a thing.”

But for his part, Nummenmaa said the research is useful because it sheds light on how emotions and the body are interconnected.

"We wanted to understand how the body and the mind work together for generating emotions," Nummenmaa said. "By mapping the bodily changes associated with emotions, we also aimed to comprehend how different emotions such as disgust or sadness actually govern bodily functions."

For the study, published online Dec. 30 in Proceedings of the National Academy of Sciences, the researchers showed two silhouettes of bodies to about 700 people. Depending on the experiment, they tried to coax feelings out of the participants by showing them emotional words, stories, clips from movies and facial expressions. Then the participants colored the silhouettes to reflect the body areas they felt were becoming most or least active.

The idea was to not mention emotions directly to the participants but instead to make them “feel different emotions,” Nummenmaa said.

The researchers noted that some of the emotions may cause activity in specific areas of the body. For example, most basic emotions were linked to sensations in the upper chest, which may have to do with breathing and heart rate. And people linked all the emotions to the head, suggesting a possible link to brain activity.

But Zak said the study failed to consider that people often feel more than one emotion at a time. Or that a person’s own comprehension of emotion can be misleading since the “areas in the brain that process emotions tend to be largely outside of our conscious awareness,” he said.

It would make more sense, Zak said, to directly measure activity in the body, such as sweat and temperature, to make sure people’s perceptions have some basis in reality. Nummenmaa said he expects future research to go in that direction.

How might the current research be useful? Zak is skeptical that it could be, but the study lead author is hopeful.

"Many mental disorders are associated with altered functioning of the emotional system, so unraveling how emotions coordinate with the minds and bodies of healthy individuals is important for developing treatments for such disorders,” Nummenmaa said.

Next, the researchers want to see if these emotion-body connections change in people who are anxious or depressed. “Also, we are interested in how children and adolescents experience their emotions in their bodies,” Nummenmaa said.

Toward a Molecular Explanation for Schizophrenia

Surprisingly little is known about schizophrenia. It was only recognized as a medical condition in the past few decades, and its exact causes remain unclear. Since there is no objective test for schizophrenia, its diagnosis is based on an assortment of reported symptoms. The standard treatment, antipsychotic medication, works less than half the time and becomes increasingly ineffective over time.

Now, Prof. Illana Gozes — the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, the director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine, and a member of the Sagol School of Neuroscience at Tel Aviv University — has discovered that an important cell-maintenance process called autophagy is reduced in the brains of schizophrenic patients. The findings, published in Nature’s Molecular Psychiatry, advance the understanding of schizophrenia and could enable the development of new diagnostic tests and drug treatments for the disease.

"We discovered a new pathway that plays a part in schizophrenia," said Prof. Gozes. "By identifying and targeting the proteins known to be involved in the pathway, we may be able to diagnose and treat the disease in new and more effective ways."

Graduate students Avia Merenlender-Wagner, Anna Malishkevich, and Zeev Shemer of TAU, Prof. Brian Dean and colleagues of the University of Melbourne, and Prof. Galila Agam and Joseph Levine of Ben Gurion University of the Negev and Beer Sheva’s Psychiatry Research Center and Mental Health Center collaborated on the research.

Mopping up

Autophagy is like the cell’s housekeeping service, cleaning up unnecessary and dysfunctional cellular components. The process — in which a membrane engulfs and consumes the clutter — is essential to maintaining cellular health. But when autophagy is blocked, it can lead to cell death. Several studies have tentatively linked blocked autophagy to the death of brain cells seen in Alzheimer’s disease.

Brain-cell death also occurs in schizophrenics, so Prof. Gozes and her colleagues set out to see if blocked autophagy could be involved in the progression of that condition as well. They found RNA evidence of decreased levels of the protein beclin 1 in the hippocampus of schizophrenia patients, a brain region central to learning and memory. Beclin 1 is central to initiating autophagy — its deficit suggests that the process is indeed blocked in schizophrenia patients. Developing drugs to boost beclin 1 levels and restart autophagy could offer a new way to treat schizophrenia, the researchers say.

"It is all about balance," said Prof Gozes. "Paucity in beclin 1 may lead to decreased autophagy and enhanced cell death. Our research suggests that normalizing beclin 1 levels in schizophrenia patients could restore balance and prevent harmful brain-cell death."

Next, the researchers looked at protein levels in the blood of schizophrenia patients. They found no difference in beclin 1 levels, suggesting that the deficit is limited to the hippocampus. But the researchers also found increased levels of another protein, activity-dependent neuroprotective protein (ADNP), discovered by Prof. Gozes and shown to be essential for brain formation and function, in the patients’ white blood cells. Previous studies have shown that ADNP is also deregulated in the brains of schizophrenia patients.

The researchers think the body may boost ADNP levels to protect the brain when beclin 1 levels fall and autophagy is derailed. ADNP, then, could potentially serve as a biomarker, allowing schizophrenia to be diagnosed with a simple blood test.

An illuminating discovery

To further explore the involvement of ADNP in autophagy, the researchers ran a biochemical test on the brains of mice. The test showed that ADNP interacts with LC3, another key protein regulating autophagy — an interaction predicted by previous studies. In light of the newfound correlation between autophagy and schizophrenia, they believe that this interaction may constitute part of the mechanism by which ADNP protects the brain.

Prof. Gozes discovered ADNP in 1999 and carved a protein fragment, NAP, from it. NAP mimics the protein nerve cell protecting properties. In follow-up studies Prof. Gozes helped develop the drug candidate davunetide (NAP). In Phase II clinical trials, davunetide (NAP) improved the ability of schizophrenic patients to cope with daily life. A recent collaborative effort by Prof. Gozes and Dr. Sandra Cardoso and Dr. Raquel Esteves showed that NAP improved autophagy in cultures of brain-like cells. The current study further shows that NAP facilitates the interaction of ADNP and LC3, possibly accounting for NAP’s results in schizophrenia patients. The researchers hope NAP will be just the first of their many discoveries to improve understanding and treatment of schizophrenia.

(Image: Shutterstock)

Enzyme that produces melatonin originated 500 million years ago

An international team of scientists led by National Institutes of Health researchers has traced the likely origin of the enzyme needed to manufacture the hormone melatonin to roughly 500 million years ago.

Their work indicates that this crucial enzyme, which plays an essential role in regulating the body’s internal clock, likely began its role in timekeeping when vertebrates (animals with spinal columns) diverged from their nonvertebrate ancestors.

An understanding of the enzyme’s function before and after the divergence may contribute to an understanding of such melatonin-related conditions as seasonal affective disorder, jet lag, and to the understanding of disorders involving vision.

The findings provide strong support for the theory that the time-keeping enzyme originated to remove toxic compounds from the eye and then gradually morphed into the master switch for controlling the body’s 24-hour cyclic changes in function.

The researchers isolated a second, nonvertebrate form of the enzyme from sharks and other contemporary animals thought to resemble the prototypical early vertebrates that lived 500 million years ago.

The study, published online in PNAS, was conducted by senior author David C. Klein, Ph.D., Chief of the Section on Neuroendocrinology in the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and colleagues at NIH, and at institutions in France, Norway, and Japan.

Melatonin is a key hormone that regulates the body’s day and night cycle. Dr. Klein explained that it is manufactured in the brain’s pineal gland and is found in small amounts in the retina of the eye. Melatonin is produced from the hormone serotonin, the end result of a multistep sequence of chemical reactions. The next-to-last step in the assembly process consists of attaching a small molecule — the acetyl group — to the nearly finished melatonin molecule. This step is performed by an enzyme called arylalkylamine N-acetyltransferase, or AANAT.

Because of its key role in producing the body clock-regulating melatonin, AANAT is often referred to as the timezyme, Dr. Klein added.

The form of AANAT found in vertebrates occurs in the brain’s pineal gland and, in small amounts, in the retina. Another form of the enzyme, termed nonvertebrate AANAT, has been found only in other forms of life, such as bacteria, plants and insects.

“Nonvertebrate AANAT appears to detoxify a broad range of potentially toxic chemicals,” Dr. Klein said. “In contrast, vertebrate AANAT is highly specialized for adding an acetyl group to melatonin. The two are as different from each another as a Ferrari is from a Model-T Ford, considering the speed of the reaction and how fast it can be turned on and off.”

In 2004, Dr. Klein and his coworkers published a theory that melatonin was at first a kind of cellular waste, a by-product created in cells of the eye when normally toxic substances were rendered harmless. Because melatonin accumulated at night, the ancestors of today’s vertebrates became dependent on melatonin as a signal of darkness. As the need for greater quantities of melatonin grew, the pineal gland developed as a structure separate from the eyes, to keep serotonin and other toxic substances needed to make melatonin away from sensitive eye tissue.

“The pineal glands of birds and reptiles can detect light,” Dr. Klein said. “And the retinas of human beings and other species also make melatonin. So it would appear that both tissues evolved from a common, ancestral, light-detecting tissue.”

Before the current study, the researchers lacked proof of their theory, particularly in regard to the question of how the vertebrate form of the enzyme originated because it did not appear to exist in non-vertebrates and had been found only in bony fishes, reptiles, birds, and mammals — all of which lacked the non-vertebrate form.

The first evidence of how the vertebrate form of the enzyme originated came when study co-author Steven L. Coon, also of NICHD, discovered genes for the nonvertebrate and vertebrate forms of AANAT in genomic sequences from the elephant shark, considered to be a living representative of early vertebrates.

This finding indicated that the vertebrate form of AANAT may have resulted after a phenomenon known as gene duplication, Dr. Klein said. Gene duplication, he added, typically results from any of a number of genetic mishaps during cell division. Instead of one copy of a gene resulting from the process, an additional copy results, so that there are two versions of a gene where only one existed previously. The phenomenon is thought to be a major factor influencing evolutionary change.

The researchers theorized that following duplication, one form of AANAT remained unchanged and the other gradually evolved into the vertebrate form. Dr. Klein said that at some point after vertebrate AANAT developed, vertebrates appear to have stopped making the nonvertebrate form, perhaps because it was no longer needed or because its function was replaced by a similar enzyme.

Before the researchers could continue, they needed to confirm their finding, to rule out that the nonvertebrate AANAT they found didn’t result from accidental contamination with bacteria or some other organism. The NICHD researchers sought assistance from other research teams around the world. DNA from Mediterranean sharks and sea lampreys was obtained via fishermen’s catches by Jack Falcon of the Arago Laboratory, a marine biology facility that is part of the CNRS and the Pierre and Marie Curie University in France. Samples from a close relative of the elephant shark — the ratfish — were provided by Even-Jorgensen at the Arctic University of Norway. Finally, Susumo Hyodo of the University of Tokyo contributed samples from elephant sharks he collected off the coast of Australia.

Next, the Hyodo and Falcon groups isolated RNA from the retinas and pineal glands of the animals. RNA is used to direct the assembly of amino acids into proteins. From these RNA sequences, it was possible to assemble working versions of AANAT molecules — both the vertebrate and nonvertebrate forms.

The sequences of the proteins encoded by the AANAT genes were analyzed by Eugene Koonin and Yuri Wolf of the National Library of Medicine using computer techniques designed to study evolution. Peter Steinbach, of NIH’s Center for Information Technology, examined the three-dimensional structures of nonvertebrate and vertebrate AANAT in the study animals and determined that the two forms of the enzyme likely had a common ancestor.

Taken together, their results provide evidence for the hypothesis that nonvertebrate AANAT resulted from duplication of the non-vertebrate AANAT gene about 500 million years ago and that following this event one copy of the duplicated gene eventually changed into the gene for vertebrate AANAT.

In addition to providing information on the origin of melatonin and the evolution of AANAT, the findings also have implications for research on disorders affecting vision. Vertebrate AANAT and melatonin are found in small amounts in the eyes of humans and other vertebrates. Although they may play a role in detoxifying compounds, it is also reasonable to consider that this detoxifying function is shared with other enzymes.

“It’s possible that a malfunction in these other enzymes might lead to an accumulation of chemicals known as arylalkamines — in the same family as serotonin — and this might contribute to eye disease,” Dr. Klein said. “Consequently, research into how these enzymes function might lead to therapies to protect vision.”

Five mysteries of the brain

For centuries, the brain was a mystery. Only in the last few decades have scientists begun to unravel its secrets. In recent years, using the latest technology and powerful computers further key discoveries have been made.

However, much remains to be understood about how the brain works. Here are five important areas of study attempting to unlock the last secrets of the brain.

How to fix it

When we think, move, speak, dream and even love - it all happens in the grey matter. But our brains are not simply one colour. White matter matters too.

Much of the research into dementia has focused on the tell-tale plaques of beta amyloid and tau protein tangles which occur in the grey matter.

But one British scientist, Dr Atticus Hainsworth says the white matter - and its blood supply - may be equally important.

The white colour results from fatty sheaths around the axons - which are extensions of the nerve cell bodies and help the cells to communicate.

He is using banks of donated brains, in Oxford and Sheffield, to analyse white matter for potential triggers such as leaking blood vessels.

"Some of the cases had an MRI or CT scan and that information can help give more clues about whether there was disease in the white matter - and what its basis might be," says Dr Hainsworth.

If leaking blood vessels in white matter do play a key role in the development of dementia then it may offer up a another potential route for new drug therapies.

How to make us all geniuses

For years caffeine was used to enhance alertness. But popping a pill to get straight-A’s may soon become the norm.

At Cambridge University neuroscientist Barbara Sahakian is investigating cognitive enhancers - drugs which make us smarter.

She studies how they can improve the performance of surgeons or pilots and asks if they could even be used to make us more entrepreneurial.

But she warns that there is no long-term safety information on these drugs and as a society we need to talk about their use.

She says the scientific and ethical challenges created by drugs which affect the production of brain chemicals like dopamine and noradrenaline - which induce pleasurable or “fight or flight” responses - need to be debated in order to decide whether drug-tests become routine before taking an exam.

Dr Sahakian adds: “I frequently talk to students about cognitive-enhancing drugs and a lot of students take them for studying and exams.

"But other students feel angry about this, they feel those students are cheating."

How can we harness our unconscious?

People need to be on top of their game when mastering skills like playing a musical instrument or detecting a bomb.

But research suggests that our unconscious can be harnessed to help us excel.

Repeatedly playing a tricky piece of music obviously helps develop a familiarity with the bits that are most difficult.

But cellist Tania Lisboa, who’s also a researcher in the Centre for Performance Science at London’s Royal College of Music, says it also helps to send the trickier parts of a piece from her conscious to the unconscious part of her brain.

After hours of practice, a fluent musician’s brain stores how to play the piece in an area at the back of the brain called the cerebellum - literally “the little brain”.

Neuroscientist Prof Anil Seth, of Sussex University, says: “It has more brain cells than the rest of the brain put together.

"It helps to promote fluid movements.. So the conscious effort of learning how to bow a cello is moved from the cortical areas which are involved when it’s new or difficult over to the cerebellum, which is very good at producing unconscious fluent behaviour on demand."

Music and defence may not appear to have much in common, but the unconscious can also help detect potential threats, whether it’s a suspicious person in a crowd or the presence of an improvised explosive device.

The unconscious brain is really good at spotting patterns - a skill which Paul Sajda at Colombia University in New York exploits - right at the boundary of the conscious/sub-conscious.

"I can flash 10 images a second and if one of those images has something out of the ordinary..that will essentially cause me to re-orient my brain to that image - but I’m not exactly aware of what that is."

Brain activity is monitored whilst the analyst looks at images so that researchers can later see which images triggered reactions.

What dreams are for

It’s just 60 years since scientists in Chicago first noted the tell-tale “rapid eye movement” or REM sleep which we now associate with dreaming.

But our fascination with dreams dates back at least 5,000 years to ancient Mesopotamia when people believed that the soul moved out of a sleeping body to visit the places they dreamed of.

REM sleep - which occurs every 90 minutes or so - begins with signals from the base of the brain which eventually reach the cerebral cortex - the outer layer of the brain which is responsible for learning and thought.

These nerve impulses are also directed to the spinal cord, inducing temporary paralysis of the limbs.

Prof Robert Stickgold, from the Beth Israel Deaconess Medical Center for Sleep and Cognition in Boston, believes that dreams are vital for processing memory associations.

He has asked the subjects of some of his sleep studies to play Tetris - and then noted their descriptions of how they floated amongst geometric shapes in their dreams.

He’s an admirer of Japanese scanning research where the scientists could “read” the dreams of subjects as they had MRI scans.

But he says it’s hard to get people to sleep in a noisy, expensive scanner.

And the future? “I would like to see research which reveals the rules for dream construction - and how it relates to the larger concept of memory processing during sleep.”

One even more elusive goal: how to dream just happy dreams and ditch the bad ones, especially nightmares.

Can we cure unreachable pain?

Excruciating chronic pain is one of medicine’s most difficult problems to solve.

Untouched by conventional treatments like painkilling drugs, surgeons are now testing their theory that deep brain stimulation could provide relief.

It is a brain surgery technique which involves electrodes being inserted to reach targets deep inside the brain.

The target areas are stimulated via the electrodes which are connected to a battery-powered pacemaker surgically placed under the patient’s collar bone.

One of the pioneers of this technique is Prof Tipu Aziz at the John Radcliffe Hospital in Oxford.

Deep brain stimulation has been used in the past for Parkinson’s disease and depression, and is now being trialled on obsessive compulsive disorder patients as well as those in chronic pain.

One of his patients, Clive, has suffered from terrible pain for nearly a decade after an operation to remove a disc in his neck.

"Sometimes I thought that if I had an axe, I’d chop my own arm off, if I thought it would get rid of the pain."

The doctors explained to him that his brain was getting signals from his arm to his brain confused and that the electrodes could help.

In Clive’s case this was an area of the brain called the anterior cingulate.

A week after his surgery he was one of the fortunate 70% of patients for whom the deep brain stimulation provides relief.

"It’s great to be out of that pain now. Since having the implant I can sit down for longer, I am able to walk further, everything is an improvement."

Prof Aziz is treating medical conditions. But he is aware of ethical dilemmas which could arise if the technique was applied to other areas.

"Putting electrodes in targets to improve memory.

"Or you could put electrodes into people to make them indifferent to danger and create the perfect soldier."

Human brain development is a symphony in three movements

The human brain develops with an exquisitely timed choreography marked by distinct patterns of gene activity at different stages from the womb to adulthood, Yale researchers report in the Dec. 26 issue of the journal Neuron.

The Yale team conducted a large-scale analysis of gene activity in cerebral neocortex —an area of the brain governing perception, behavior, and cognition — at different stages of development. The analysis shows the general architecture of brain regions is largely formed in the first six months after conception by a burst of genetic activity, which is distinct for specific regions of the neocortex. This rush is followed by a sort of intermission beginning in the third trimester of pregnancy. During this period, most genes that are active in specific brain regions are quieted — except for genes that spur connections between all neocortex regions. Then in late childhood and early adolescence, the genetic orchestra begins again and helps subtly shape neocortex regions that progressively perform more specialized tasks, a process that continues into adulthood.

The analysis is the first to show this “hour glass” sketch of human brain development, with a lull in genetic activity sandwiched between highly complex patterns of gene expression, said Nenad Sestan, professor of neurobiology at Yale’s Kavli Institute for Neuroscience and senior author of the study. Intriguingly, say the researchers, some of the same patterns of genetic activity that define this human “hour glass” sketch were not observed in developing monkeys, indicating that they may play a role in shaping the features specific to human brain development.

The findings emphasize the importance of the proper interplay between genes and environment in the child’s earliest years after birth when the formation of synaptic connections between brain cells becomes synchronized, which shape how brain structures will be used later in life, said Sestan. For instance, disruptions of in synchronization of synaptic connections during child’s earliest years have been implicated in autism.

Sestan says the human brain is more like a neighorhood, which is better defined by the community living within its borders than its buildings.

“The neighborhoods get built quickly and then everything slows down and the neocortex focuses solely on developing connections, almost like an electrical grid,” said Sestan.  “Later when these regions are synchronized, the neighborhoods begin to take on distinct functional identities like Little Italy or Chinatown.”

Are concussions related to Alzheimer’s disease?

A new study suggests that a history of concussion involving at least a momentary loss of consciousness may be related to the buildup of Alzheimer’s-associated plaques in the brain. The research is published in the December 26, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Interestingly, in people with a history of concussion, a difference in the amount of brain plaques was found only in those with memory and thinking problems, not in those who were cognitively normal," said study author Michelle Mielke, PhD, with Mayo Clinic in Rochester, Minn.

For the study, people from Olmsted County in Minnesota were given brain scans; these included 448 people without any signs of memory problems and 141 people with memory and thinking problems called mild cognitive impairment. Participants, who were all age 70 or older, were also asked about whether they had ever experienced a brain injury that involved any loss of consciousness or memory.

Of the 448 people without any thinking or memory problems, 17 percent reported a brain injury and 18 percent of the 141 with memory and thinking difficulties reported a concussion or head trauma.

The study found no difference in any brain scan measures among the people without memory and thinking impairments, whether or not they had head trauma. However, people with memory and thinking impairments and a history of head trauma had levels of amyloid plaques an average of 18 percent higher than those with no head trauma history.

"Our results add merit to the idea that concussion and Alzheimer’s disease brain pathology may be related," said Mielke. "However, the fact that we did not find a relationship in those without memory and thinking problems suggests that any association between head trauma and amyloid is complex."