Neuroscience

An experimental treatment for Parkinson’s disease reduced by nearly two hours on average the period each day when medication failed to control patients’ slowness and shaking, according to results from a double-blind, phase III clinical trial published in December 2013, in Lancet Neurology. 

The study compared AbbVie’s levodopa-carbidopa intestinal gel against the same medication in pill form in patients with advanced disease. 

The University of Alabama at Birmingham was among the sites for the study, with David G. Standaert, M.D., Ph.D., chair of the UAB Department of Neurology, an author. Led by the Mount Sinai School of Medicine, preliminary results from the study were first presented at the annual meeting of the American Academy of Neurology in April 2012. 

Parkinson’s disease results from the loss of brain cells that make dopamine, which helps to control movement. As dopamine levels fall, patients experience tremors, muscle stiffness and loss of balance. A commonly prescribed treatment, the levodopa-carbidopa combination works as the body converts levodopa into dopamine and carbidopa escorts levodopa to the right part of the brain. The problem is that patients face hours of uncontrolled slowness, freezing and tremors each day — called “off-time” — as the treatment gets into place or wears off.

One reason for the break in treatment coverage is that it comes in a pill, and pills sit in the stomach for up to six hours waiting for it to empty into the small intestine. It is only there that levodopa encounters the proteins capable of transporting it into the bloodstream en route to the brain. Thus, researchers envisioned a system that steadily delivers levodopa gel directly into the small intestine through a surgically placed tube, and with the help of a pump worn on the belt.

“The results are very exciting, considering that other recently approved drugs on the market reduce off-time by, at most, just over an hour,” said Standaert. “In the study, the gel treatment helped patients who had run out of alternatives with current medications. We believe it may be an important new option for patients with severe Parkinson’s, with benefits comparable to more invasive techniques like deep brain stimulation.”

Patients using the gel system saw an average reduction in daily off-time of 1.91 hours, and an increase in “on-time” without troublesome dyskinesia of 1.86 hours compared with the pill form. Nearly all subjects experienced at least one side effect, although most were short-lived and moderate.

QBI scientists at The University of Queensland have found that honeybees use the pattern of polarised light in the sky invisible to humans to direct one another to a honey source.

The study, conducted in Professor Mandyam Srinivasan’s laboratory at the Queensland Brain Institute, a member of the Australian Research Council Centre of Excellence in Vision Science (ACEVS), demonstrated that bees navigate to and from honey sources by reading the pattern of polarised light in the sky.

“The bees tell each other where the nectar is by converting their polarised ‘light map’ into dance movements,” Professor Srinivasan said.

“The more we find out how honeybees make their way around the landscape, the more awed we feel at the elegant way they solve very complicated problems of navigation that would floor most people – and then communicate them to other bees,” he said.

The discovery shines new light on the astonishing navigational and communication skills of an insect with a brain the size of a pinhead.

The researchers allowed bees to fly down a tunnel to a sugar source, shining only polarised light from above, either aligned with the tunnel or at right angles to the tunnel.

They then filmed what the bees ‘told’ their peers, by waggling their bodies when they got back to the hive.

“It is well known that bees steer by the sun, adjusting their compass as it moves across the sky, and then convert that information into instructions for other bees by waggling their body to signal the direction of the honey,” Professor Srinivasan said.

“Other laboratories have shown from studying their eyes that bees can see a pattern of polarised light in the sky even when the sun isn’t shining: the big question was could they translate the navigational information it provides into their waggle dance.”

The researchers conclude that even when the sun is not shining, bees can tell one another where to find food by reading and dancing to their polarised sky map.

In addition to revealing how bees perform their remarkable tasks, Professor Srinivasan says it also adds to our understanding of some of the most basic machinery of the brain itself.

Professor Srinivasan’s team conjectures that flight under polarised illumination activates discrete populations of cells in the insect’s brain.

When the polarised light was aligned with the tunnel, one pair of ‘place cells’ – neurons important for spatial navigation – became activated, whereas when the light was oriented across the tunnel a different pair of place cells was activated.

The researchers suggest that depending on which set of cells is activated, the bee can work out if the food source lies in a direction toward or opposite the direction of the sun, or in a direction ninety degrees to the left or right of it.

Children are likely to have stronger muscles if their mothers had a higher level of vitamin D in their body during pregnancy, according to new research from the Medical Research Council Lifecourse Epidemiology Unit (MRC LEU) at the University of Southampton.

Low vitamin D status has been linked to reduced muscle strength in adults and children, but little is known about how variation in a mother’s status during pregnancy affects her child.

Low vitamin D concentrations are common among young women in the UK, and although women are recommended to take an additional 10μg/day of vitamin D in pregnancy, supplementation is often not taken up.

In the research, published in the January edition of the Journal of Clinical Endocrinology and Metabolism, vitamin D levels were measured in 678 mothers in the later stages of pregnancy.

When the children were four years old, grip strength and muscle mass were measured. Results showed that the higher the levels of vitamin D in the mother, the higher the grip strength of the child, with an additional, but less pronounced association between mother’s vitamin D and child’s muscle mass.

Lead researcher Dr Nicholas Harvey, Senior Lecturer at the MRC LEU at the University of Southampton, comments: “These associations between maternal vitamin D and offspring muscle strength may well have consequences for later health; muscle strength peaks in young adulthood before declining in older age and low grip strength in adulthood has been associated with poor health outcomes including diabetes, falls and fractures. It is likely that the greater muscle strength observed at four years of age in children born to mothers with higher vitamin D levels will track into adulthood, and so potentially help to reduce the burden of illness associated with loss of muscle mass in old age.”

The 678 women who took part in the study are part of the Southampton Women’s Survey, one of the largest and best characterised such studies globally.

Professor Cyrus Cooper, Professor of Rheumatology and Director of the MRC LEU at the University of Southampton, who oversaw this work, added: “This study forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit and University of Southampton in which we are seeking to understand how factors such as diet and lifestyle in the mother during pregnancy influence a child’s body composition and bone development. This work should help us to design interventions aimed at optimising body composition in childhood and later adulthood and thus improve the health of future generations.”

Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were reported online in the journal Diabetes.

If a gene called MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, says Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC and lead author of the paper.

Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.

In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Insulin allows glucose to enter cells where it can be used as energy, keeping glucose levels in the blood within a narrow range. People with type 2 diabetes don’t produce enough insulin or are resistant to its effects. They must closely monitor their blood glucose throughout the day and, when medication fails, inject insulin.

In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes in Europeans and Han Chinese.

People with this mutation had high blood glucose and problems of insulin secretion – the “hallmarks of type 2 diabetes,” Prabhakar said. But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with type 2 diabetes.

To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.

“We didn’t see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly,” Prabhakar said. Examination of the beta cells revealed that they were packed with insulin. “The cells were producing plenty of insulin, they just weren’t secreting it,” he said.

The finding shows that type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone, Prabhakar said. “Without the gene, insulin can’t leave the beta cells, and blood glucose levels are chronically high.”

Prabhakar now hopes to investigate the effect of a drug that allows for the secretion of insulin in MADD-deficient beta cells.

“If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes,” he said.

In the journal Neurology, researchers report a novel technique that enables a patient with “word blindness” to read again.

Word blindness is a rare neurological condition. (The medical term is “alexia without agraphia.”) Although a patient can write and understand the spoken word, the patient is unable to read.

The article is written by Jason Cuomo, Murray Flaster, MD, PhD and Jose Biller, MD, of Loyola University Medical Center.

Here’s how the technique works: When shown a word, the patient looks at the first letter. Although she clearly sees it, she cannot recognize it. So beginning with the letter A, she traces each letter of the alphabet over the unknown letter until she gets a match. For example, when shown the word Mother, she will trace the letters of the alphabet, one at a time, until she comes to M and finds a match. Three letters later, she guesses correctly that the word is Mother.

"To see this curious adaption in practice is to witness the very unique and focal nature" of the deficit, the authors write.

The authors describe how word blindness came on suddenly to a 40-year-old kindergarten teacher and reading specialist. She couldn’t make sense of her lesson plan, and her attendance sheet was as incomprehensible as hieroglyphs. She also couldn’t tell time.

The condition was due to a stroke that probably was caused by an unusual type of blood vessel inflammation within the brain called primary central nervous system angiitis.

Once a passionate reader, she was determined to learn how to read again. But none of the techniques that she had taught her students – phonics, sight words, flash cards, writing exercises, etc. – worked. So she taught herself a remarkable new technique that employed tactile skills that she still possessed.

The woman can have an emotional reaction to a word, even if she can’t read it. Shown the word “dessert,” she says “Oooh, I like that.” But when shown “asparagus,” she says, “Something’s upsetting me about this word.”

Shown two personal letters that came in the mail, she correctly determined which was sent by a friend of her mother’s and which was sent by one of her own friends. “When asked who these friends were, she could not say, but their names nevertheless provoked an emotional response that served as a powerful contextual clue,” the authors write.

What she most misses is reading books to children. She teared up as she told the authors: “One day my mom was with the kids in the family, and they were all curled up next to each other, and they were reading. And I started to cry, because that was something I couldn’t do.”

It is a common belief that consciously thinking about what we are doing interferes with our performance. The origins of this idea go far back. Consider, for instance, the centipede’s dilemma:

A centipede was happy – quite!
Until a toad in fun
Said, “Pray, which leg moves after which?”
This raised her doubts to such a pitch,
She fell exhausted in the ditch
Not knowing how to run. 

The centipede performs a very complex task with ease, unless she thinks about the task. The story was thought to illustrate something fundamental about human nature. English psychologist George Humphrey wrote “[the poem] contains a profound truth which is illustrated daily in the lives of all of us.” Humphrey and others thought that not having to think about everything that we do provides a great advantage. According to the famed philosopher Alfred North Whitehead, “Civilization advances by extending the number of important operations which we can perform without thinking about them.” Whitehead believed that thinking must be reserved only for decisive moments.

Though common, this idea is misleading. It is never optimal to run on autopilot. Even the motor tasks that we have learned to do fluently without much cognitive control are better performed while engaged. The key is to realize that we can apply cognitive control at a higher level. Moreover, gaining fluency at a motor task often comes at a cost. The cost is rigidity and deliberately breaking the flow in response to changing contexts often pays off. Musicians, athletes, public speakers, architects, designers, and others whose jobs require complex sequential actions can increase their performance if they understand that they are not trapped in the centipede’s dilemma.  

In a fascinating paper, Brain researchers Eitan Globerson and Israel Nelken started with the observation that piano playing involves a very complex sequential motor task. The task is often executed in speeds that do not allow cognitive control of individual muscle movements. Through practice, pianists learn to execute fast and complex motor tasks with little cognitive control. Once this is achieved, it is possible to play in a disengaged way with little cognitive involvement. However, Globerson and Nelken suggest another way. Instead of focusing on individual finger movements or not focusing on anything, pianists may focus on higher-level mental events, such as the character of a longer musical phrase. This allows constant engagement with the music making and deliberate control without disrupting the mechanics of playing. Globerson and Nelken argue that this may dramatically improve performance.

If we follow their argument, it is easy to come up with our own examples about how to use higher-level cognitive control. While playing, a pianist may actively focus on the relationships between different musical ideas. A public speaker may develop a “mental script” that includes bigger-picture ideas, the connections between those ideas, where the climax of the speech should be, and what general effects should the speech make on the audience. During the speech, the public speaker may be constantly engaged with this mental script instead of trying to select words individually or mechanically replicating a previous performance. While shooting, a basketball player may focus on the arc that the ball should follow instead of focusing on arm movements or focusing on nothing. You can create your own examples of higher-level cognitive control for dancing, driving a car, designing a house, or doing the work of a carpenter.

Experts have long been aware of the power of focusing on higher-level mental processes. In 1924, Russian pianist and piano teacher Josef Lhevinne wrote the book Basic Principles in Pianoforte Playing, which later became a classic. In his discussion of memory, he wrote, “the thing to remember is the thought, not the symbols. When you remember a poem you do not remember the alphabetical symbols, but the poet’s beautiful vision, his thought pictures. … Get the thought, the composer’s idea; that is the thing that sticks.”

Higher-level cognitive control is capable of changing the motor action in a beneficial way. When a pianist decides to play a passage in an expressive fashion, for instance, this high-level command changes the character of playing through initiating a sequence of associated motor movements. There is experimental evidence that suggests that performance in highly automatized tasks can be improved by increasing the level of engagement. Musicians in symphony orchestras are typically asked to play the same pieces many times over the course of their careers. The playing of these pieces becomes mostly automatic; and the job satisfaction of orchestra players is typically dismal. Psychologists Ellen Langer, Timothy Russell, and Noah Eisenkraft recently asked a symphony orchestra to record, under different experimental conditions, the finale from Brahms’s Symphony No. 1. A local community chorus listened to and rated the recordings. The musicians were either asked to replicate a previous fine performance or to offer “subtle new nuances” to their performance. Musicians enjoyed the latter performance more; and the majority of the listeners preferred the recording of the latter performance.

There is always an unconscious component of the link between our intentions and the motor actions those intentions create. Even if I deliberately stretch my arm to grab a coffee mug, I do not have conscious control over the way the individual muscles in my arm operate to give rise to the specific stretching movement. Deliberate cognitive control is always less complex than the actual motor action. However, we often learn to apply cognitive control in an even more summary-like way. That is, we can learn to apply cognitive control in a single step over longer and more complex sequences of motor actions. Through practice, sequences of motor actions merge into a single unit that can be initiated by a single deliberate command. This is often called chunking. When children first learn how to brush their teeth or lace their shoes, they deliberately control individual movements that make up the task. After some practice, the individual movements are chunked and the whole sequence can be initiated by a single mental command. Many other daily activities such as riding a bike or writing one’s signature involve chunking. It is possible to merge chunked sequences into even longer sequences and reduce cognitive involvement even more.

Once initiated, a chunked motor sequence is executed automatically. As a consequence, we lose control over individual movements. This type of rigidity is often undesirable because we live in a constantly changing environment. In her book The Power of Mindful Learning Harvard psychologist Ellen Langer talks about how automaticity may get in the way of adapting to new circumstances. Overlearned driving skills may put one in danger while driving in a different country or in different weather conditions. Holding a baseball bat in the same overlearned way after getting older or stronger will hinder performance.

We can disrupt automaticity and appropriately respond to the situation at hand by orienting ourselves in the present and being sensitive to different contexts. We can think at a level higher than the mechanics of the motor action. We can be engaged with the task by making use of these two approaches simultaneously. In any case, thinking should never be reserved.

In the largest ever assessment of substance use among people with severe psychiatric illness, researchers at Washington University School of Medicine in St. Louis and the University of Southern California have found that rates of smoking, drinking and drug use are significantly higher among those who have psychotic disorders than among those in the general population.

The study is published online in the journal JAMA Psychiatry.

The finding is of particular concern because individuals with severe mental illness are more likely to die younger than people without severe psychiatric disorders.

“These patients tend to pass away much younger, with estimates ranging from 12 to 25 years earlier than individuals in the general population,” said first author Sarah M. Hartz, MD, PhD, assistant professor of psychiatry at Washington University. “They don’t die from drug overdoses or commit suicide — the kinds of things you might suspect in severe psychiatric illness. They die from heart disease and cancer, problems caused by chronic alcohol and tobacco use.”

The study analyzed smoking, drinking and drug use in nearly 20,000 people. That included 9,142 psychiatric patients diagnosed with schizophrenia, bipolar disorder or schizoaffective disorder — an illness characterized by psychotic symptoms such as hallucinations and delusions, and mood disorders such as depression.

The investigators also assessed nicotine use, heavy drinking, heavy marijuana use and recreational drug use in more than 10,000 healthy people without mental illness.

The researchers found that 30 percent of those with severe psychiatric illness engaged in binge drinking, defined as drinking four servings of alcohol at one time. In comparison, the rate of binge drinking in the general population is 8 percent.

Among those with mental illness, more than 75 percent were regular smokers. This compares with 33 percent of those in the control group who smoked regularly. There were similar findings with heavy marijuana use: 50 percent of people with psychotic disorders used marijuana regularly, versus 18 percent in the general population. Half of those with mental illness also used other illicit drugs, while the rate of recreational drug use in the general population is 12 percent.

“I take care of a lot of patients with severe mental illness, many of whom are sick enough that they are on disability,” said Hartz. “And it’s always surprising when I encounter a patient who doesn’t smoke or hasn’t used drugs or had alcohol problems.”

Hartz said another striking finding from the study is that once a person develops a psychotic illness, protective factors such as race and gender don’t have their typical influence.

Previous research indicates that Hispanics and Asians tend to have lower rates of substance abuse than European Americans. The same is true for women, who tend to smoke, drink and use illicit drugs less often than men.

“We see protective effects in these subpopulations,” Hartz explained. “But once a person has a severe mental illness, that seems to trump everything.”

That’s particularly true, she said, with smoking. During the last few decades, smoking rates have declined in the general population. People over age 50 are much more likely than younger people to have been regular smokers at some point in their lives. For example, about 40 percent of those over 50 used to smoke regularly. Among those under 30, fewer than 20 percent have been regular smokers. But among the mentally ill, the smoking rate is more than 75 percent, regardless of the patient’s age.

“With public health efforts, we’ve effectively cut smoking rates in half in healthy people, but in the severely mentally ill, we haven’t made a dent at all,” she said.

Until recently, smoking was permitted in most psychiatric hospitals and mental wards. Hartz believes that many psychiatrists decided that their sickest patients had enough problems without having to worry about quitting smoking, too. There also were concerns about potential dangers from using nicotine-replacement therapy, while continuing to smoke since smoking is so prevalent among the mentally ill. Recent studies, however, have found those concerns were overblown.

The question, she said, is whether being more aggressive in trying to curb nicotine, alcohol and substance use in patients with severe psychiatric illness can lengthen their lives. Hartz believes health professionals who treat the mentally ill need to do a better job of trying to get them to stop smoking, drinking and using drugs.

“Some studies have shown that although we psychiatrists know that smoking, drinking and substance use are major problems among the mentally ill, we often don’t ask our patients about those things,” she said. “We can do better, but we also need to develop new strategies because many interventions to reduce smoking, drinking and drug use that have worked in other patient populations don’t seem to be very effective in these psychiatric patients.”

University of Queensland (UQ) researchers have made a significant discovery that could one day halt a number of neurodegenerative diseases.

Scientists at the Queensland Brain Institute (QBI) have identified a gene that protects against spontaneous, adult-onset progressive nerve degeneration.

Dr Massimo Hilliard said that the discovery of gene mec-17 causing axon (nerve fibre) degeneration could open the door to better understand the mechanisms of neuronal injury and neurodegenerative diseases characterised by axonal pathology, such as motor neuron disease, Parkinson’s, Alzheimer’s and Huntington’s diseases.

“This is an important step to fully understand how axonal degeneration occurs, and thus facilitates development of therapies to prevent or halt this damaging biological event,” Dr Hilliard said.

Dr Hilliard runs a laboratory at QBI specialising in neuronal development, and focuses on how nerves both degenerate and regenerate.

The team found that mec-17 protects the neuron by stabilising its cytoskeletal structure, allowing proper transport of essential molecules and organelles, including mitochondria, throughout the axon.

This discovery has also the potential to accelerate the identification of human neurodegenerative conditions caused by mutations in genes similar to mec-17.

“It’s our hope that this could one day lead to more effective treatments for patients suffering from conditions causing neuronal degeneration,” Dr Hilliard said.

This discovery highlights the axon as a major focal point for the health of the neuron.

Findings of the research have been published in journal Cell Reports, and lead author Dr Brent Neumann anticipates that the research into the gene will soon lead to further discoveries.

“This study demonstrates that mec-17 normally functions to protect the nervous system from damage,” Dr Neumann said.

“This knowledge can now be used to understand precisely how the gene achieves this and to discover other molecules that are used by the nervous system for similar protective functions,” he said.

“We can now start to look into means of bypassing the function of mec-17, such as activating other genes or alternative mechanisms that can protect the nervous system from damage.”

Previous research has shown that mec-17 is conserved across species, including humans, suggesting a possible shared function of protection.

“We identified mec-17 from a genetic screening method aimed at identifying molecules that cause axonal degeneration when they become inactive through genetic mutations,” Dr Neumann said.

Stroke rehabilitation researchers report improvement in spatial neglect with prism adaptation therapy. This new study supports behavioral classification of patients with spatial neglect as a valuable tool for assigning targeted, effective early rehabilitation. Results of the study, “Presence of motor-intentional aiming deficit predicts functional improvement of spatial neglect with prism adaptation” were published ahead of print in Neurorehabilitation and Neural Repair on December 27, 2013.

The article is authored by Kelly M. Goedert, PhD, of Seton Hall University, Peii Chen, PhD, of Kessler Foundation, Raymond C. Boston, PhD, of the University of Pennsylvania, Anne L. Foundas, MD, of the University of Missouri, and A.M. Barrett, MD, director of Stroke Rehabilitation Research at Kessler Foundation, and chief of Neurorehabilitation Program Innovation at Kessler Institute for Rehabilitation. Drs. Barrett and Chen have faculty appointments at Rutgers New Jersey Medical School.

Spatial neglect, an under-recognized but disabling disorder, often complicates recovery from right brain stroke,” noted Dr. Barrett. “Our study suggests we need to know what kind of neglect patients have in order to assign treatment.” The research team tested the hypothesis that classifying patients by their spatial neglect profile, i.e., by Where (perceptional-intentional) versus Aiming (motor-intentional) symptoms, would predict response to prism adaptation therapy. Moreover, they hypothesized that patients with Aiming bias would have better response to prism adaptation recovery than those with isolated Where bias.

The study involved 24 patients with right brain stroke who completed 2 weeks of prism adaptation treatment. Participants also completed the Behavioral Inattention Test and Catherine Bergego Scale (CBS) tests of neglect recovery weekly for 6 weeks. Results showed that those with only Aiming deficits improved on the CBS, whereas those with only Where deficits did not improve. Participants with both types of deficits demonstrated intermediate improvement. “These findings suggest that patients with spatial neglect and Aiming deficits may benefit the most from early intervention with prism adaptataion therapy,” said Dr. Barrett. “More broadly, classifying spatial deficits using modality-specific measures should be an important consideration of any stroke trial intending to obtain the most valid, applicable, and valuable results for recovery after right brain stroke.”

Reaching for Froot Loops and grabbing Lego pieces to build a tower are different challenges for toddlers. Depending on what they’re trying to do, tots tend to develop handedness for different tasks at different ages, according to new research.

Most people are right-handed. Babies start using their right hand to reach for cereal nuggets by age 1. However, children take until age 4 to show such a preference when building Lego models. The findings, published in this month’s issue of Developmental Psychobiology, imply tendencies to use one hand more than the other emerge depending on the tasks kids confront, rather than their age.

Preference for the right or left hand is, in part, genetic. Prior studies have shown that some of these one-sided tendencies emerge early. Fetuses suck their right thumb more often than their left; newborns on their back turn to the right more frequently. Most children grow up to be right-handed—in part because of these innate, early leanings, scientists believe.

But the timing of when one hand emerges as the dominant one for most tasks remained unclear.

"As a parent and a scientist, I was surprised to find researchers thought 3-year-olds don’t display a hand preference," said neurobiologist Claudia Gonzalez of the University of Lethbridge in Alberta, Canada.

To study how handedness emerged between ages 1 to 5, Gonzalez and her colleagues assigned about 50 tiny participants to a familiar task: grabbing a colorful object or a tasty tidbit. Children ages 1 to 2 picked up Froot Loops or Cheerios to munch at snack time. Four- and 5-year-olds grasped Lego blocks to build a small model. Three-year-old subjects tackled both tasks.

Even the youngest children had strong right-handed leanings when reaching for food, the team found. Three-year-olds were right-handed eaters, but they were just as likely to use their left hand when playing with blocks. The 4- and 5-year-olds used their left hand to hold the base of their model steady, but they manipulated blocks into the correct positions with their other hand—a clear preference for right-handedness.

"There is a developmental milestone between the ages of 3 and 4 when something clicks," Gonzalez said. "Maybe they become more skilled, or they understand the task better."

Until that developmental “click,” this study shows hand preference isn’t constant across tasks – regardless of a child’s age.

The study “uses a very clever design to get at the question of how handedness varies across tasks,” said Klaus Libertus, an infant development researcher at the University of Pittsburgh. “We did not know handedness is connected to tasks in this way. I would have expected the 3-year-olds to show the same pattern on both tasks, especially since the demands were so similar.”

Developing a hand preference might also correlate with other functions that rely strongly on just one side of the brain, such as language and certain decision-making skills, Gonzalez noted. Preliminary data from children in her lab suggests that when handedness is evident earlier, these other functions also mature more quickly.

Finding the right task to study handedness at different ages will give researchers a firmer grasp on how young brains develop right - or left -handed tendencies, she said.

"You could say hand preference develops before 1, or you could say it doesn’t emerge until age 4—just depending on what task you are looking at," said Gonzalez.

“Good to see you. I’m sorry. It sounds like you’ve had a tough, tough, week.”  Spoken by a doctor to a cancer patient, that statement is an example of compassionate behavior observed by a University of Rochester Medical Center team in a new study published by the journal Health Expectations.

Rochester researchers believe they are the first to systematically pinpoint and catalogue compassionate words and actions in doctor-patient conversations. By breaking down the dialogue and studying the context, scientists hope to create a behavioral taxonomy that will guide medical training and education.

“In health care, we believe in being compassionate but the reality is that many of us have a preference for technical and biomedical issues over establishing emotional ties,” said senior investigator Ronald Epstein, M.D., professor of Family Medicine, Psychiatry, Oncology, and Nursing and director of the UR Center for Communication and Disparities Research.

Epstein is a national and international keynote speaker and investigator on mindfulness and communication in medical education.

His team recruited 23 oncologists from a variety of private and hospital-based oncology clinics in the Rochester, N.Y., area. The doctors and their stage III or stage IV cancer patients volunteered to be recorded during routine visits. Researchers then analyzed the 49 audio-recorded encounters that took place between November 2011 and June 2012, and looked for key observable markers of compassion.  

In contrast to empathy – another quality that Epstein and his colleagues have studied in the medical community — compassion involves a deeper and more active imagination of the patient’s condition. An important part of this study, therefore, was to identify examples of the three main elements of compassion: recognition of suffering, emotional resonance, and movement towards addressing suffering.

Emotional resonance, or a sense of sharing and connection, was illustrated by this dialogue: Patient: “I should just get a room here.” Oncologist: “Oh, I hope you don’t really feel like you’re spending that much time here.”

Another conversation included this response from a physician to a patient, who complained about a drug patch for pain: “Who wants a patch that makes you drowsy, constipated and fuzzy? I’ll pass, thank you very much.”

Some doctors provided good examples of how they use humor to raise a patient’s spirits without deviating from the seriousness of the situation. In one case, for example, a patient was concerned that he would not be able to drink two liters of barium sulfite in preparation for a CT scan.

Doctor: “If you just get down one little cup it will tell us what’s going on in the stomach. What I tell people when we’re not being recorded is to take a cup and then pour the rest down the toilet and tell them you drank it all (laughter)… Just a creative interpretation of what you are supposed to take.”

Patient: “I love it, I love it. Well, I thank you for that. I’m prepared to do what I’ve got to do to get this right.”

Researchers evaluated tone of voice, animation that conveyed tenderness and understanding, and other ways in which doctors gave reassurances or psychology comfort.

Here’s an instance in which an oncologist encouraged a reluctant patient to follow through with a planned trip to Arizona: “You know, if you decide to do it, break down and allow somebody to meet you at the gates and use a cart or wheelchair to get you to your next gate and things like that. And having just sent my father-in-law off to Hawaii and told him he had to do that, he said no, no, I can get there. Just, it’s okay. Nobody is gonna look at you and say, ‘What’s an able-bodied man doing in a cart?’ Just, it’s okay. It’s part of setting limits.”

Researchers also observed non-verbal communication, such as pauses or sighs at appropriate times, as well as speech features and voice quality (tone, pitch, loudness) and other metaphorical language that conveyed certain attitudes and meaning.

Compassion unfolds over time, researchers concluded. During the process, physicians must challenge themselves to stay with a difficult discussion, which opens the door for the patient to admit uncertainty and grieve the loss of normalcy in life.

“It became apparent that compassion is not a quality of a single utterance but rather is made up of presence and engagement that suffuses an entire conversation,” the study said. First author, Rachel Cameron, B.A., is a student at the University of Rochester School of Medicine and Dentistry; the audio-recordings were reviewed by a diverse group of medical professionals with backgrounds in literature and linguistics, as well as palliative care specialists.

People who tell themselves to get excited rather than trying to relax can improve their performance during anxiety-inducing activities such as public speaking and math tests, according to a study published by the American Psychological Association.

“Anxiety is incredibly pervasive. People have a very strong intuition that trying to calm down is the best way to cope with their anxiety, but that can be very difficult and ineffective,” said study author Alison Wood Brooks, PhD, of Harvard Business School. “When people feel anxious and try to calm down, they are thinking about all the things that could go badly. When they are excited, they are thinking about how things could go well.”

Several experiments conducted at Harvard University with college students and members of the local community showed that simple statements about excitement could improve performance during activities that triggered anxiety. The study was published online in APA’s Journal of Experimental Psychology: General^®.

In one experiment, 140 participants (63 men and 77 women) were told to prepare a persuasive public speech on why they would be good work partners. To increase anxiety, a researcher videotaped the speeches and said they would be judged by a committee. Before delivering the speech, participants were instructed to say “I am excited” or “I am calm.” The subjects who said they were excited gave longer speeches and were more persuasive, competent and relaxed than those who said they were calm, according to ratings by independent evaluators.

“The way we talk about our feelings has a strong influence on how we actually feel,” said Brooks, an assistant professor of business administration at Harvard Business School.

In another experiment, 188 participants (80 men and 108 women), were given difficult math problems after they read “try to get excited” or “try to remain calm.” A control group didn’t read any statement. Participants in the excited group scored 8 percent higher on average than the calm group and the control group, and they reported feeling more confident about their math skills after the test.

In a trial involving karaoke, 113 participants (54 men and 59 women) were randomly assigned to say that they were anxious, excited, calm, angry or sad before singing a popular rock song on a video game console. A control group didn’t make any statement. All of the participants monitored their heart rates using a pulse meter strapped onto a finger to measure their anxiety.

Participants who said they were excited scored an average of 80 percent on the song based on their pitch, rhythm and volume as measured by the video game’s rating system. Those who said they were calm, angry or sad scored an average of 69 percent, compared to 53 percent for those who said they were anxious. Participants who said they were excited also reported feeling more excited and confident in their singing ability.

Since both anxiety and excitement are emotional states characterized by high arousal, it may be easier to view anxiety as excitement rather than trying to calm down to combat performance anxiety, Brooks said.

“When you feel anxious, you’re ruminating too much and focusing on potential threats,” she said. “In those circumstances, people should try to focus on the potential opportunities. It really does pay to be positive, and people should say they are excited. Even if they don’t believe it at first, saying ‘I’m excited’ out loud increases authentic feelings of excitement.”

Ischemic strokes, caused by blood clots that can develop in the brain and cut off blood flow, make up more than 80 percent of strokes suffered in the U.S. annually. To date, the most effective treatment is the clot-dissolving thrombolysis drug tissue plasminogen activator, tPA. But tPA is a far-from-perfect solution, says Andrew Barreto, a neurologist at the University of Texas Health Science Center in Houston. “IV-tPA will help about 30 of 100 patients who receive it within the first 4.5 hours after stroke symptom onset,” Barreto says. “But, many patients are still disabled, so we need better treatments.”

Barreto and some of his colleagues think that ultrasound could be one of those treatments. Ultrasound has been a valuable tool for diagnosing and tracking strokes in the brain for years. Now, a wide variety of new technologies are making it possible for neurosurgeons to use ultrasound waves, which travel at frequencies too high for the human ear to pick up, to not only identify the signs of stroke such as blood clots in the brain but also to help treat them.

Barreto was a principal researcher in the recent study of the Clotbust device, a headband-like piece of equipment placed on a patient’s head that aims to use ultrasound directed to increase tPA’s effectiveness in breaking up clots in the brain. A preliminary test of the device, which fires 2-MHz pulses of ultrasound from a series of 18 transducers at 5-second intervals, found that it was safe to use in stroke patients. Now, the device is in the midst of effectiveness testing on a group of 830 stroke patients worldwide.

One of the sites involved in testing the device is Swedish Neuroscience Center in Seattle, where chief of neuroscience David Newell notes that preliminary results from the trial were promising. In safety trials, the Clotbust device combined with the thrombolysis drug tPA cleared 40 percent of clots in ischemic strokes in the first two hours after being used. That’s twice as effective as the 20 percent clearance rate usually achieved by tPA alone.

Clotbust isn’t the only tool of its kind being tested at Swedish. Newell and his colleagues are involved in testing three different types of ultrasound technologies for a variety of neurological ailments. Those include one technique devised by. Newell in collaboration with EKOS corporation, a Seattle-area company specializing in ultrasound-emitting catheters, which are designed to travel up a blood vessel and transmit ultrasound from an emitter at its tip, to help loosen blood clots. Newell and his colleagues have been testing a modified version of the EkoSonic catheter, which can more easily be placed directly in the brain and used to detect a different type of stroke known as intracerebral hemorrhage (ICH).

Caused by bleeding from ruptured blood vessels deep in the brain, ICH strokes are much harder to treat because of their location. They are also particularly deadly, with a mortality rate north of 50 percent. Even those who survive are likely to be left disabled or with long roads to recovery. The tPA may be effective in treating these strokes as well, breaking up the clots in the brain that form around the bleed and allowing fluid to be drained off before it can do lasting harm.

While the effectiveness of tPA in treating ICH is still being studied, Newell and his team used the repurposed EkoSonic catheter to improve delivery of clot-busting drugs to bleed sites deep in the brain, and their early results are promising. In an introductory round of tests on nine patients at Swedish, Newell and his colleagues found that clots accompanying hemorrhagic strokes were cleared three times faster by a combination of ultrasound and tPA than they were by drugs alone. By combining the two techniques, Newell said, he and his team could clear clots from most patients in the first day of treatment. He’s now working with the company that developed the technology on creating a new type of catheter, designed specifically for use within the brain, that combines drug delivery, ultrasound emission, and drainage in one tool.

Neither Clotbust nor the EkoSonic catheter uses ultrasound to physically destroy clots. Instead, the blasts of high-frequency sound produce “a micromechnical action that makes the lytic effect of tPA a lot more effective,” by improving the efficiency with which it is delivered. “Injecting tPA is like putting an ice cube in a drink and waiting for it to melt,” says Newell. “With ultrasound, it’s more akin to creating a snow flurry. The drug binds to more binding sites, and it does so a lot faster.”

That’s not the case in the third ultrasound device being tested at Swedish. The ExAblate Neuro device developed by Israeli company InsighTec uses thousands of beams of ultrasound focused on one spot to create intense heat at a targeted point in the brain. The ExAblate Neuro mimics the effects of a tool used in neurosurgery for years, the gamma knife, which uses highly focused radiation energy to cut out material like tumors or to create lesions that can lessen the effects of diseases like Parkinson’s or epilepsy. In the case of stroke, the Neuro could potentially superheat solidified clots, turning them to more easily cleared liquid.

Since it uses focused ultrasound rather than the dangerous radiation associated with the gamma knife, says Newell, ExAblate has the potential to perform similar surgeries that are more easily repeatable. Current gamma knife surgeries have to get it right the first time, as exposing patients to powerful radiation over and over again can be dangerous. Since ultrasound energy doesn’t carry the same exposure dangers, doctors could potentially do the same sort of treatments in smaller steps without raising concerns over patient health.

All three of these new methods are still in their experimental phases, but each one has the potential to transform—and improve—the way strokes and other ailments in the brain are treated. And that may be only the beginning of the potential for the techniques. “Ultrasound technology represents almost a whole new field in neurosurgery,” said Newell.

Researchers at Penn Medicine report in the December 25 issue of JAMA that a modified form of prolonged exposure therapy – in which patients revisit and recount aloud their trauma-related thoughts, feelings and situations – shows greater success than supportive counseling for treating adolescent PTSD patients who have been sexually abused.

Despite a high prevalence of posttraumatic stress disorder (PTSD) in adolescents, evidence-based treatments like prolonged exposure therapy for PTSD in this population have never been established. 

“We hypothesized that prolonged exposure therapy could fill this gap and were eager to test its ability to provide benefit for adolescent patients,” says Edna Foa, PhD, professor of Clinical Psychology in the department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania, who developed prolonged exposure therapy.  

The concern has been that prolonged exposure therapy, while the most established evidence-based treatment for adults with PTSD, could exacerbate PTSD symptoms in adolescent patients who have not mastered the coping skills necessary for this type of exposure to be safely provided.

Adolescence is often a time when children begin to test limits and are in and out of situations, both good and bad – situations that often determine the path their lives take into adulthood.

The six-year (2006-2012) study examined the benefit of a prolonged exposure program called prolonged exposure-A (PE-A), that was modified to meet the developmental stage of adolescents, and compared it with supportive counseling in 61 adolescent girls, ages 13-18, with sexual abuse-related PTSD. In the single-blind randomized clinical trial, 31 received prolonged exposure-A, and 30 got supportive counseling. 

Each received 14 60- to- 90 minute sessions of either therapy in a community mental health setting.  The counselors were familiar with supportive counseling but naïve to PE-A before the study; their PE-A training consisted of a 4-day workshop followed by supervision every second week. 

Outcomes were assessed before treatment, mid-treatment and after treatment and at three, six and 12-month follow up.  During treatment, patients receiving PE-A demonstrated greater decline in PTSD and depression symptom severity, and improvement in overall functioning.  These differences were maintained throughout the 12-month follow up period.

“Another key finding of this research was that prolonged therapy can be administered in a community setting by professionals with no prior training in evidence-based treatments and can have a positive impact on this population,” Foa says.