Neuroscience

Extraordinarily complex networks of circuits that transmit signals from the brain to the spinal cord control voluntary movements. Researchers have been challenged to identify the controlling circuits, but they lacked the tools needed to dissect, at the neural level, the way the brain produces voluntary movements.

Recently, Dr. John Martin, medical professor in City College’s Sophie Davis School of Biomedical Education, postdoctoral fellow Dr. Najet Serradi and other colleagues employed a sensitive genetic technique that eliminated a particular gene in the cerebral cortex and, in the process, changed the circuitry.

The team hypothesized that the corticospinal tract, which stretches from cerebral cortex to the spinal cord, is important for voluntary reaching movements, but not for more routine and stereotypic walking movements. “We reasoned that if we genetically altered the corticospinal tract we would affect voluntary reaching movements, but not walking.” Professor Martin said.

In genetically intact mice, corticospinal tract signals are transmitted from one side of the cerebral cortex to the opposite side of the spinal cord. Such mice reach with one arm, or the other – but not both arms together.

Professor Martin and colleagues used specially bred mice, i.e. knockout mice, with the gene EphA4 removed from the cerebral cortex. These mice reached with both forelimbs together, rather than with one. This happened because the genetic manipulation changed the circuit; it caused the signal to move to be transmitted from one side of the cerebral cortex to both sides of the spinal cord.

However, their stereotypic walking was unaffected. Professor Martin said this shows that while voluntary movements depend on the corticospinal tract walking depends on circuits in other parts of the brain and spinal cord, which are not affected by the gene manipulation.

The findings, he added, “etch away at the vexing problem of achieving a deeper understanding of how the brain functions in voluntary movement.” In addition greater knowledge of how voluntary circuits function could lead to new understanding of cerebral palsy, a condition in which the corticospinal tract is injured around the time of birth and people often make “mirror movements” of both arms when they intend to move only one, he said.

The research, which is funded by the National Institute of Neurological Diseases and Stroke, aims to understand the brain and spinal cord circuits for voluntary movement. Using similar genetic tools, his team hopes to further dissect the connections and functions of the corticospinal tract movement circuits in ways to restore movements after brain or spinal cord injury.

A collaborative discovery involving Kansas State University researchers may lead to the first universal treatment for dystonia, a neurological disorder that affects nearly half a million Americans.

Michal Zolkiewski, associate professor of biochemistry and molecular biophysics at Kansas State University, and Jeffrey Brodsky at the University at Pittsburgh co-led a study that focused on a mutated protein associated with early onset torsion dystonia, or EOTD, the most severe type of dystonia that typically affects adolescents before the age of 20. Dystonia causes involuntary and sustained muscle contractions that can lead to paralysis and abnormal postures.

"It’s a painful and debilitating disease for which there is no cure or treatment that would be effective for all patients," Zolkiewski said. "There are some treatments that are being tested, but nothing is really available to those patients that would cure the symptoms completely."

In addition to Zolkiewski and Brodsky, researchers involved in the study included Hui-Chuan Wu, Kansas State University doctoral student in biochemistry and molecular biophysics, Taiwan, and colleagues at the University of Texas Southwestern Medical Center and the University of Adelaide in Australia.

The Journal of Biological Chemistry recently published the team’s study, "The BiP molecular chaperone plays multiple roles during the biogenesis of TorsinA, a AAA+ ATPase associated with the neurological disease Early-Onset Torsion Dystonia." The study was funded by the Dystonia Medical Research Foundation.

Researchers built the study on a decade-old discovery that patients with early onset torsion dystonia typically have a mutated gene that encodes the protein TorsionA.

"TorsinA is a protein that all people have in their bodies," Zolkiewski said. "It appears to perform an important role in the nervous system, but currently nobody knows what that role is. There also is no understanding of the link between the mutation and dystonia."

In order to study protein expression in a living organism, researchers used yeast — one of the simplest living systems. The yeast was engineered to produce the human protein TorsionA.

Observations revealed that a second protein named BiP — pronounced “dip” — helps process the TorsinA protein and maintain its active form. Additionally, researchers found that BiP also guides TorsinA to being destroyed by cells if the protein is defective. Humans carry the BiP protein as well as the TorsinA protein.

"BiP is a molecular chaperone that assists other proteins in maintaining their function," Zolkiewski said. "In this study we found that BiP really has a dual role. On one hand it’s helping TorsinA and on the other it’s leading to its degradation."

Future studies may focus on BiP as a target for treating dystonia, as modulating BiP in human cells would affect TorsinA, Zolkiewski said.

"Because we don’t know what exactly the function of TorsinA is, we may not be able to design a treatment based on that protein," Zolkiewski said. "We know what BiP does, however. It is a pretty well-studied chaperone, which makes it much easier to work with."

Automation in the cockpit is traditionally believed to free pilots’ attention from mundane flight tasks and allow them to focus on the big picture or prepare for any unexpected events during flight. However, a new study published in Human Factors indicates that pilots may have a hard time concentrating on the automated systems that now carry out many of the tasks once completed by humans.

“The automated systems in today’s cockpits assume many of the tasks formerly performed by human pilots and do it with impressive reliability,” says Stephen Casner, coauthor of “Thoughts in Flight: Automation Use and Pilots’ Task-Related and Task-Unrelated Thought” and research psychologist at NASA’s Ames Research Center. “This leaves pilots to watch over the automation as it does its work, but people can only concentrate on something uneventful for so long. Humans aren’t robots. We can’t stare at a green light for hours at a stretch without getting tired, bored, or going crazy.”

Researchers Casner and coauthor Jonathan Schooler designed a flight simulation study in which they asked pilots to follow a published arrival procedure into New York’s busy John F. Kennedy International Airport. As the pilots navigated the flight, they were asked about what they were thinking during various levels of automation and to assign their thoughts to three categories: the specific task at hand, higher-level thoughts (for example planning ahead), or thoughts unrelated to the flight (e.g., what’s for dinner).

The pilots reported an increase in big-picture flight-related thoughts when using higher levels of automation, but when the flight was progressing according to plan and pilots were not interacting with the automation, their thoughts were more likely to wander.

“The mind is restless,” says Schooler, a professor of psychological and brain sciences at the University of California, Santa Barbara. “When we’re not given something specific to think about, we come up with something else to think about.”

“Pilots limited their off-task thoughts to times in which the automation was doing the flying and all was going according to plan,” adds Casner. “Nevertheless, there seem to be potential costs to situations in which pilots disengage from a highly-automated task. What happens when something suddenly goes amiss after long periods of uneventful flight?”

The study’s authors concluded that although automation frees pilots’ minds from tedious tasks and enables them to focus on the overall flight, it might inadvertently encourage them to devote time to unrelated thoughts. Casner notes that on the basis of these findings, researchers studying cockpit automation might consider rethinking the interaction between humans and machines.

“As technology grows in capability, we seem to be taking the approach of using humans as safety nets for computers,” he says. “We need to sort out the strengths and weaknesses of both humans and computers and think of work environments that combine and exploit the best features of both to keep humans meaningfully engaged in their work.”

George Washington University (GW) researcher David Mendelowitz, Ph.D., was recently published in the Journal of Neuroscience for his research on how heart rate increases in response to alertness in the brain. Specifically, Mendelowitz looked at the interactions between neurons that fire upon increased attention and anxiety and neurons that control heart rate to discover the “why,” “how,” and “where to next” behind this phenomenon.

“This study examines how changes in alertness and focus increase your heart rate,” said Mendelowitz, vice chair and professor of pharmacology and physiology at the GW School of Medicine and Health Sciences. “If you need to focus on a new task at hand, or suddenly need to become more alert, your heart rate increases. We sought to understand the mechanisms of how that happens.”

While the association between vigilance and increased heart rate is long accepted, the neurobiological link had not yet been identified. In this study, Mendelowitz found that locus coeruleus (LC) noradrenergic neurons — neurons critical in generating alertness — directly influence brainstem parasympathetic cardiac vagal neurons (CVNs) — neurons responsible for controlling heart rate. LC noradrenergic neurons were shown to inhibit the brainstem CVNs that generate parasympathetic activity to the heart. The receptors activated within this pathway may be targets for new drug therapies to promote slower heart rates during heightened states.

“Our results have important implications for how we may treat certain conditions in the future, such as post-traumatic stress disorder, chronic anxiety, or even stress,” said Mendelowitz. “Understanding how these events alter the cardiovascular system gives us clues on how we may target these pathways in the future.”

University of Florida researchers have advice for older adults who need to remember detailed written information: Don’t just read it, tell someone about it.

That recommendation comes from a new UF study that showed that older adults who read a text and then described what they had read to someone else remembered more details of the text than older adults who simply re-read the passage multiple times.

The findings appear in the April issue of the journal Aphasiology.

Older adults are better able than younger adults to recall the gist of information they learn, but they have more difficulty remembering details, said lead investigator Yvonne Rogalski, who conducted the research as part of her doctoral dissertation work at the UF College of Public Health and Health Professions.

“Older adults can rely on things they’ve learned in the past and they can build on that vast wealth of semantic information that they’ve collected over the years. That works as long as the information is familiar, but where it breaks down is when they have to read something that is unfamiliar and has a lot of details,” said Rogalski, now an assistant professor in the department of speech-language pathology and audiology at Ithaca College.

As a doctoral student Rogalski developed a training technique called Read Attentively, Summarise and Review, or RASR, which requires participants to read a passage aloud and then summarize from memory what they’ve read after each paragraph. The training is designed to help people “encode” information and commit it to memory.

“In the reading aloud portion, attention is heightened because you know you’re going to have to recall something,” she said. “Then retrieving that information through the summaries has the ability to act as a secondary encoding. Reading and recalling the text paragraph by paragraph instead of the whole text is designed to reduce the information processing demands.”  

For the UF study, 44 healthy adults ages 60 to 75 used one of two methods to recall details from texts on real — but unusual — animals. Participants who used a technique called Read and Reread Attentively read the entire passage aloud once, and then re-read each paragraph three times aloud in succession. Those in the RASR group read the whole text aloud once, then for each paragraph they read it aloud, summarized it from memory and then re-read it aloud again. Participants in both groups were tested immediately after studying and 24 hours later.

The researchers found that participants who summarized the information aloud remembered more details about the texts than those who just re-read the material. In addition, combining the summarization method with an immediate post-test showed the most benefit for remembering text details after a 24-hour delay.

“We think it is effective because by reading the information and then putting it into your own words you have to do quite a bit of processing of not only the information, but also the relationships among bits of information,” said Lori Altmann, an associate professor in the UF department of speech, language, and hearing sciences, and a study co-author along with John Rosenbek, also a professor in the department. “Picking out the relationships that are important to you as you see them can help to order the information in your own memory.”

Older adults can put the principles of the summarization technique to work for themselves whenever they want or need to learn detailed information, such as a magazine article or medication plan, the researchers say. They suggest that people read the information and then describe it from memory to a partner who can check for accuracy.

“The RASR method is a very functional treatment and it’s something that healthy older adults or even people with mild dementias could use on their own to try and improve their memory,” Altmann said. “It doesn’t involve anything high-tech, and that’s the beauty of it.”

People who claim to see “Jesus in toast” may no longer be mocked in the future thanks to a new study by researchers at the University of Toronto and partner institutions in China.

Researchers have found that the phenomenon of “face pareidolia”– where onlookers report seeing images of Jesus, Virgin Mary, or Elvis in objects such as toasts, shrouds, and clouds — is normal and based on physical causes.

“Most people think you have to be mentally abnormal to see these types of images, so individuals reporting this phenomenon are often ridiculed”, says lead researcher Prof. Kang Lee of the University of Toronto’s Eric Jackman Institute of Child Study. “But our findings suggest that it’s common for people to see non-existent features because human brains are uniquely wired to recognize faces, so that even when there’s only a slight suggestion of facial features the brain automatically interprets it as a face,” said Lee.

Although this phenomenon has been known for centuries, little is understood about the underlying neural mechanisms that cause it. In the first study of its kind, researchers studied brain scans and behavioural responses to individuals seeing faces and letters in different patterns. They discovered face paredilia isn’t due to a brain anomaly or imagination but is caused by the combined work of the frontal cortex which helps generate expectations and sends signals to the posterior visual cortex to enhance the interpretation stimuli from the outside world.

Researchers also found that people can be led to see different images — such as faces or words or letters — depending on what they expect to see, which in turn activates specific parts of the brain that process such images. Seeing “Jesus in toast” reflects our brain’s normal functioning and the active role that the frontal cortex plays in visual perception. Instead of the phrase “seeing is believing” the results suggest that “believing is seeing.”

Pregnant women show increased activity in the area of the brain related to emotional skills as they prepare to bond with their babies, according to a new study by scientists at Royal Holloway, University of London.

The research, which will be presented at the British Psychological Society’s annual conference today (Wednesday 7 May), found that pregnant women use the right side of their brain more than new mothers do when they look at faces with emotive expressions.

“Our findings give us a significant insight into the ‘baby brain’ phenomenon that makes a woman more sensitive during the child bearing process”, said Dr Victoria Bourne, from the Department of Psychology at Royal Holloway. “The results suggest that during pregnancy, there are changes in how the brain processes facial emotions that ensure that mothers are neurologically prepared to bond with their babies at birth.”

Researcher examined the neuropsychological activity of 39 pregnant women and new mothers as they looked at images of adult and baby faces with either positive or negative expressions. The results showed that pregnant women used the right side of their brain more than new mothers, particularly when processing positive emotions.

The study used the chimeric faces test, which uses images made of one half of a neutral face combined with one half of an emotive face to see which side of the participants’ brain is used to process positive and negative emotions.

Dr Bourne said: “We know from previous research that pregnant women and new mothers are more sensitive to emotional expressions, particularly when looking at babies’ faces. We also know that new mothers who demonstrate symptoms of post-natal depression sometimes interpret their baby’s emotional expressions as more negative than they really are.

“Discovering the neuropsychological processes that may underpin these changes is a key step towards understanding how they might influence a mother’s bonding with her baby.”

Environmental factors are more important than previously thought in understanding the causes of autism, and equally as important as genes, according to the largest study to date to look at how autism runs in families.

The study also shows that children with a brother or sister with autism are 10 times more likely to develop autism; 3 times if they have a half-brother or sister; and 2 if they have a cousin with autism, providing much needed information for parents and clinicians for assessing individual risk.

The study, which looked at over 2 million people, was led by researchers at King’s College London, Karolinska Institutet in Sweden and Mount Sinai in the US, and is published in JAMA today.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder defined by impairments in social interaction and communication and the presence of restrictive and repetitive behaviours. The exact causes are unknown but evidence has shown it is likely to include a range of genetic and environmental risk factors.

Using Swedish national health registers, the researchers analysed anonymous data from all 2 million children born in Sweden in between 1982 and 2006, 14,516 of which had a diagnosis of ASD. The researchers analysed pairs of family members: identical and non-identical twins, siblings, maternal and paternal half-siblings and cousins.

The study involved two separate measures of autism risk – heritability, which is the proportion of risk in the population that can be attributed to genetic factors; and Relative Recurrent Risk which measures individual risk for people who have a relative with autism.

Most previous studies have suggested that heritability of autism may be as high as 80-90%, but one study has hinted at a lower estimate. The new study is the largest and most comprehensive to date and estimates heritability of autism to be 50%, with the other 50% explained by non-heritable or environmental factors.

Environmental factors are split into ‘shared environments’ which are shared between family members (such as family socio-economic status), and ‘non-shared environments’ which are unique to the individual (such as birth complications or maternal infections or medication during the pre and perinatal period). In this study, factors which are unique to the individual, or ‘non-shared environments’ were the major source of environmental risk.

Professor Avi Reichenberg, author of the study from Mount Sinai Seaver Center for Autism Research, who led the study whilst at King’s College London, says: “Heritability is a population measure, so whilst it does not tell us much about risk at an individual level, it does tell us where to look for causes. We were surprised by our findings as we did not expect the importance of environmental factors in autism to be so strong. Recent research efforts have tended to focus on genes, but it’s now clear that we need much more research to focus on identifying what these environmental factors are. In the same way that there are multiple genetic factors to consider, there will likely be many different environmental factors contributing to the development of autism.”

In the other part of the study, the researchers looked at individual risk. In the general population, autism affects approximately 1 in 100 children. The researchers found that children with a brother or sister with autism were 10.3 times more likely to develop autism; 3.3-2.9 times if they had a half-brother or sister with autism; and 2.0 times if they had a cousin with autism. There were no differences in relative risk between genders. This is the first study to provide such a comprehensive and far reaching analysis of individual risk extended as far as cousins.

Dr Sven Sandin, author of the study from King’s College London and Karolinska, says: “Our study was prompted by a very basic question which parents often ask: ‘if I have a child with autism, what is the risk my next child will too?’ Our study shows that at an individual level, the risk of autism increases according to how close you are genetically to other relatives with autism. We can now provide accurate information about autism risk which can comfort and guide parents and clinicians in their decisions.”

People with multiple sclerosis who for one year followed a plant-based diet very low in saturated fat had much less MS-related fatigue at the end of that year — and significantly less fatigue than a control group of people with MS who didn’t follow the diet, according to an Oregon Health & Science University study being presented today at the American Academy of Neurology’s annual meeting in Philadelphia, Pa.

The study was the first randomized-controlled trial to examine the potential benefits of the low fat diet on the management of MS. The study found no significant differences between the two groups in brain lesions detected on MRI brain scans or on other measures of MS. But while the number of trial participants was relatively small, study leaders believe the significantly improved fatigue symptoms merited further and larger studies of the diet.

"Fatigue can be a debilitating problem for many people living with relapsing-remitting MS," said Vijayshree Yadav, M.D., an associate professor of neurology in the OHSU School of Medicine and clinical medical director of the OHSU Multiple Sclerosis Center. "So this study’s results — showing some notable improvement in fatigue for people who follow this diet — are a hopeful hint of something that could help many people with MS."

The study investigated the effects of following a diet called the McDougall Diet, devised by John McDougall, M.D. The diet is partly based on an MS-fighting diet developed in the 1940s and 1950s by the late Roy Swank, M.D., a former head of the division of neurology at OHSU. The McDougall diet, very low in saturated fat, focuses on eating starches, fruits and vegetables and does not include meat, fish or dairy products.

The study, which began in 2008, looked at the diet’s effect on the most common form of MS, called relapsing-remitting MS. About 85 percent of people with MS have relapsing-remitting MS, characterized by clearly defined attacks of worsening neurological function followed by recovery periods when symptoms improve partially or completely.

The study measured indicators of MS among a group of people who followed the McDougall Diet for 12 months and a control group that did not. The study measured a range of MS indicators and symptoms, including brain lesions on MRI brain scans of study participants, relapse rate, disabilities caused by the disease, body weight and cholesterol levels.

It found no difference between the diet group and the control group in the number of MS-caused brain lesions detected on the MRI scans. It also found no difference between the two groups in relapse rate or level of disability caused by the disease. People who followed the diet did lose significantly more weight than the control group and had significantly lower cholesterol levels. People who followed the diet also had higher scores on a questionnaire that measured their quality of life and overall mood.

The study’s sample size was relatively small. Fifty-three people completed the study, with 27 in the control group and 22 people in the diet group who complied with the diet’s restrictions.

"This study showed the low-fat diet might offer some promising help with the fatigue that often comes with MS," said Dennis Bourdette, M.D., F.A.A.N., chair of OHSU’s Department of Neurology, director of OHSU’s MS Center and a study co-author. "But further study is needed, hopefully with a larger trial where we can more closely look at how the diet might help fatigue and possibly affect other symptoms of MS."

Case Western Reserve researchers have discovered that a protein previously implicated in disease plays such a positive role in learning and memory that it may someday contribute to cures of cognitive impairments. The findings regarding the potential virtues of fatty acid binding protein 5 (FABP5) — usually associated with cancer and psoriasis — appear in the May 2 edition of The Journal of Biological Chemistry.

“Overall, our data show that FABP5 enhances cognitive function and that FABP5 deficiency impairs learning and memory functions in the brain hippocampus region,” said senior author Noa Noy, PhD, a professor of pharmacology at the School of Medicine. “We believe if we could find a way to upregulate the expression of FABP5 in the brain, we might have a therapeutic handle on cognitive dysfunction or memory impairment in some human diseases.”

FABP5 resides in many tissues and is especially highly expressed in the brain. Noy and her Case Western Reserve School of Medicine and National Institute on Alcohol Abuse and Alcoholism colleagues particularly wanted to understand how this protein functioned in neurons. They performed imaging studies comparing the activation of a key transcription factor in the brain tissue of normal mice and in FABP5-deficient mice. (Transcription factor is a protein the controls the flow of genetic information). The investigations revealed that FABP5 performs two different functions in neurons. First, it facilitates the degradation of endocannabinoids, which are neurological modulators controlling appetite, pain sensation, mood and memory. Second, FABP5 regulates gene expression, a process that essentially gives cells their marching orders on structure, appearance and function.

“FABP5 improves learning and memory both because it delivers endocannabinoids to cellular machinery that breaks them down and because it shuttles compounds to a transcription factor that increases the expression of cognition-associated genes,” Noy said.

Even though endocannabinoids affect essential physiological processes from appetite to memory, the “cannabinoid” part of the word signifies that these natural biological compounds act similarly to drugs such as marijuana and hashish. Too much endocannabinoid can lead to impaired learning and memory.

In simple terms, FABP5 transports endocannabinoids for processing. FABP5 functions like a bus and carries the brain’s endocannabinoids and their biological products to two stations within the neuron cell. FABP5 captures endocannabinoids entering the neuron and delivers them to an enzyme that degrades them (station 1). Then, that degraded product is picked up by the same protein (FABP5) and shuttled to the cell nucleus — specifically, to a transcription factor within it (station 2). Binding of the degraded product activates the transcription factor and allows it to induce expression of multiple genes. The genes that are induced in this case tell the cells to take steps that promote learning and memory.

Noy and associates also compared memory and learning in FABP5-deficient mice and in normal ones. In one test, both sets of mice repeatedly swam in mazes that had a platform in one established location where they could climb out of the water. During subsequent swims, the wild-type mice reached the platform quickly because they had learned — and remembered — its location. Their FABP5-deficient counterparts took much longer, typically finding the platform’s location by chance.

“In addition to regulating cell growth as in skin and in cancer cells, for example, FABP5 also plays a key role in neurons of the brain,” Noy said. “FABP5 controls the biological actions of small compounds that affect memory and learning and that activate a transcription factor, which regulates neuronal function.”

Autopsies have revealed that some individuals develop the cellular changes indicative of Alzheimer’s disease without ever showing clinical symptoms in their lifetime.

Vanderbilt University Medical Center memory researchers have discovered a potential genetic variant in these asymptomatic individuals that may make brains more resilient against Alzheimer’s.

“Most Alzheimer’s research is searching for genes that predict the disease, but we’re taking a different approach. We’re looking for genes that predict who among those with Alzheimer’s pathology will actually show clinical symptoms of the disease,” said principal investigator Timothy Hohman, Ph.D., a post-doctoral research fellow in the Center for Human Genetics Research and the Vanderbilt Memory and Alzheimer’s Center.

The article, “Genetic modification of the relationship between phosphorylated tau and neurodegeneration,” was published online recently in the journal Alzheimer’s and Dementia.

The researchers used a marker of Alzheimer’s disease found in cerebrospinal fluid called phosphorylated tau. In brain cells, tau is a protein that stabilizes the highways of cellular transport in neurons. In Alzheimer’s disease tau forms “tangles” that disrupt cellular messages.

Analyzing a sample of 700 subjects from the Alzheimer’s Disease Neuroimaging Initiative, Hohman and colleagues looked for genetic variants that modify the relationship between phosphorylated tau and lateral ventricle dilation — a measure of disease progression visible with magnetic resonance imaging (MRI). One genetic mutation (rs4728029) was found to relate to both ventricle dilation and cognition and is a marker of neuroinflammation.

“This gene marker appears to be related to an inflammatory response in the presence of phosphorylated tau,” Hohman said.

“It appears that certain individuals with a genetic predisposition toward a ‘bad’ neuroinflammatory response have neurodegeneration. But those with a genetic predisposition toward no inflammatory response, or a reduced one, are able to endure the pathology without marked neurodegeneration.”

Hohman hopes to expand the study to include a larger sample and investigate gene and protein expression using data from a large autopsy study of Alzheimer’s disease.

“The work highlights the possible mechanism behind asymptomatic Alzheimer’s disease, and with that mechanism we may be able to approach intervention from a new perspective. Future interventions may be able to activate these innate response systems that protect against developing Alzheimer’s symptoms,” Hohman said.

Activity in areas of the brain related to reward and self-control may offer neural markers that predict whether people are likely to resist or give in to temptations, like food, in daily life, according to research in Psychological Science, a journal of the Association for Psychological Science.

“Most people have difficulty resisting temptation at least occasionally, even if what tempts them differs,” say psychological scientists Rich Lopez and Todd Heatherton of Dartmouth College, authors on the study. “The overarching motivation of our work is to understand why some people are more likely to experience this self-regulation failure than others.”

The research findings reveal that activity in reward areas of the brain in response to pictures of appetizing food predicts whether people tend to give in to food cravings and desires in real life, whereas activity in prefrontal areas during taxing self-control tasks predicts their ability to resist tempting food.

Lopez and colleagues used functional MRI (fMRI) to explore the interplay between activity in prefrontal brain regions associated with self-control (e.g., inferior frontal gyrus) and subcortical areas involved in affect and reward (e.g., nucleus accumbens), and to see whether the interplay between these regions predicts how successful (or unsuccessful) people are in controlling their desires to eat on a daily basis.

The researchers recruited 31 female participants to take part in an initial fMRI scanning session that included two important tasks.

For the first task, the participants were presented with various images, including some of high-calorie foods, like dessert items, fast-food items, and snacks. The participants were simply asked to indicate whether each image was set indoors or outdoors — the researchers were specifically interested in measuring activity in the nucleus accumbens in response to the food-related images.

For the second task, the participants were asked to press or not press a button based on the specific cues provided with each image, a task designed to gauge self-control ability. During this task, the researchers measured activity in the inferior frontal gyrus (IFG).

The fMRI scanning session was followed by 1 week of so-called “experience sampling,” in which participants were signaled several times a day on a smartphone and asked to report their food desires and eating behaviors. Any time participants reported a food desire, they were then asked about the strength of the desire and their resistance to it. If they ultimately gave in to the craving, they were asked to say how much they had eaten.

As expected, participants who had relatively higher activity in the nucleus accumbens in response to the food images tended to experience more intense food desires. More importantly, they were also more likely to give in to their food cravings and eat the desired food.

The researchers were surprised by how robust this association was:

“Reward-related brain activity, which can be considered an implicit measure, predicted who gave in to temptations to eat, as well as who ate more, above and beyond the desire strength reported by participants in the moment,” say Lopez and Heatherton. “This could help to explain a previous finding from our lab that people who show this kind of brain activity the most are also the most likely to gain weight over six months.”

But brain activity also predicted who was more likely to be able to resist temptation: Participants who showed relatively higher IFG activity on the self-control task acted on their cravings less often.

When the researchers grouped the participants according to their IFG activity, the data revealed that participants who had high IFG activity were more successful at controlling how much they ate in particularly tempting situations than those who had low IFG activity. In fact, participants with low IFG activity were about 8.2 times more likely to give in to a food desire than those who had high IFG activity.

“Taken together, the results from the present study provide initial evidence for neural markers of everyday eating behaviors that can identify individuals who are more likely than others to give in to temptations to eat,” the researchers write.

Lopez, Heatherton, and colleagues are currently conducting studies focused on groups of people who are especially prone to self-regulation failure: chronic dieters.

They’re investigating, for example, how dieters’ brains respond to food cues after they’ve exhausted their self-control resources. The researchers hypothesize that depleting self-control may heighten reward-related brain activity, effectively “turning up the volume on temptations,” and predicting behaviors like overeating in daily life.

“Failures of self-control contribute to nearly half of all death in the United States each year,” the researchers note. “Our findings and future research may ultimately help people learn ways to resist their temptations.”

Tests of a new long-acting version of one of the oldest multiple sclerosis (MS) drugs on the market show it worked significantly better than placebo in reducing the number of patient relapses and developments of new or active lesions, researchers report. Most important, they add, the updated version was effective even though injections were given every two weeks instead of every other day, and it appears that fewer patients develop resistance to it.

The industry-funded, international clinical trial led by a Johns Hopkins scientist found that pegylated interferon beta worked far better than placebo for people with the most common form of MS. The beneficial effects seen in this study were comparable to what was found in previous studies in which the standard formulation of interferon beta (which must be taken more frequently) was compared to placebo.

In a report on the trial, published May 1 in The Lancet Neurology, the researchers say they also found that while roughly 20 percent of MS patients typically develop antibodies against the drug that ultimately neutralize its effects, fewer than 1 percent in the new study did, suggesting far more patients could benefit from the new formulation.

“While this isn’t a brand new blockbuster drug, I do think it will improve compliance and tolerability and therefore positively impact the quality of life of people with MS who take interferon beta,” says study leader Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine. “If it gets FDA approval, this new formulation would allow patients to get the same effect, but instead of the burden of injecting themselves every other day, they only have to do it twice a month. For an MS patient, that’s a huge advance.”

“The data are very, very clear,” Calabresi adds. “We can make things easier for our patients without dangerous side effects just by tweaking what we know to be a safe, 20-year-old drug.”

MS is considered an autoimmune disorder, caused when the immune system wrongly attacks a person’s own tissues; in this case, it’s the fatty protein myelin sheath that insulates nerves that send electrical signals to control movement, speech and other functions. The immune system primes so-called T cells in the body’s lymph nodes, preparing them to seek out and destroy myelin, a process that can lead to debilitating symptoms such as blurred vision, weakness and numbness.

In 1993, interferon beta became the first drug federally approved for MS because of its ability to block certain types of immune cell activation and the trafficking of immune cells into the brain. While some studies suggest its effects are modest in controlling MS, Calabresi says it works very well in some patients, overall reducing relapses by one-third and inflammation as measured using MRI by more than two-thirds.

Side effects trouble many patients — including flu-like symptoms that tend to occur in the six to eight hours after each injection — but Calabresi says the drug is safer for routine care than some newer oral medications.

Calabresi says his team was eager to test the new formulation, because many MS patients forgo its benefits because of the frequent injection schedule and side effects.

The new version modifies interferon beta by attaching polyethylene glycol (PEG) polymer chemical chains that stabilize the drug. PEG has been proven safe in other medications, shampoos, toothpaste and moisturizers.

For the study, researchers recruited more than 1,500 subjects with MS from 183 sites in 26 countries. For a year, one-third of patients got a placebo shot every two weeks, one-third got 125 micrograms of pegylated interferon beta shots every two weeks and the third group got 125 micrograms of pegylated interferon beta-1a once a month, with a placebo shot given at every other visit.

After a year, those who got pegylated interferon beta-1a every two weeks experienced a 36 percent reduction in the yearly relapse rate compared to the placebo group; the every-four-week group saw a 28 percent reduction. MRI scans revealed 67 percent fewer new or active lesions in the two-week group, while those injected every four weeks only had 28 percent fewer of those lesions.

Both the two- and four-week groups had 38 percent reduction in disability progression on a scale that measures walking speed, vision, strength and sensation, as compared to a placebo group.

The new formulation appeared just as safe as the older one, though Calabresi says that the flu-like symptoms from the long-acting drug lasted closer to 24 hours after each injection in some patients. He called this a trade-off his patients would deem worthwhile.

Data presented April 29 at the American Academy of Neurology suggests that receiving pegylated interferon beta every two weeks is the best dosing schedule.

Multiple sclerosis researchers have found that brain reserve and cognitive reserve confer a long-term protective effect against cognitive decline.

“Our research aims to answer these questions,” explained Dr. DeLuca. “Why do some people with MS experience disabling symptoms of cognitive decline, while others maintain their cognitive abilities despite neuroimaging evidence of significant disease progression? Can the theories of brain reserve and cognitive reserve explain this dichotomy? Can we identify predictors of cognitive decline?”

In this study, memory, cognitive efficiency, vocabulary (a measure of intellectual enrichment/cognitive reserve), brain volume (a measure of brain reserve), and disease progression on MRI, were evaluated in 40 patients with MS at baseline and at 4.5-year followup. After controlling for disease progression, scientists looked at the impact of brain volume and intellectual enrichment on cognitive decline.

Results supported the protective effects of brain reserve and cognitive reserve,” noted Dr. Sumowski. “Patients with greater intellectual enrichment experienced lesser degrees of cognitive decline. Those with greater brain reserve showed a protective effect for cognitive efficiency. This study not only confirms these protective effects of brain and cognitive reserve, it shows that these beneficial effects persist for years.”

Neuroscientists at Mayo Clinic in Florida have defined a subtype of Alzheimer’s disease (AD) that they say is neither well recognized nor treated appropriately.

The variant, called hippocampal sparing AD, made up 11 percent of the 1,821 AD-confirmed brains examined by Mayo Clinic researchers — suggesting this subtype is relatively widespread in the general population. The Alzheimer’s Association estimates that 5.2 million Americans are living with AD. And with nearly half of hippocampal sparing AD patients being misdiagnosed, this could mean that well over 600,000 Americans make up this AD variant, researchers say.

In an oral presentation at the annual meeting of the American Academy of Neurology in Philadelphia, scientists say hippocampal sparing AD often produces symptoms that are substantially different from the most commonly known form of AD, which affects the hippocampus, the center of memory.

The patients, mostly male, are afflicted at a much younger age, and their symptoms can be bizarre — behavioral problems such as frequent and sometimes profane angry outbursts, feelings that their limbs do not belong to them and are controlled by an “alien” unidentifiable force, or visual disturbances in the absence of eye problems, researchers say.

They also decline at a much faster rate than do patients with the most common form of AD.

“Many of these patients, however, have memories that are near normal, so clinicians often misdiagnose them with a variety of conditions that do not match the underlying neuropathology,” says the study’s lead author, Melissa Murray, Ph.D., an assistant professor of neuroscience at Mayo Clinic in Florida.

Many of these patients are diagnosed with frontotemporal dementia, a disorder characterized by changes in personality and social behavior, or corticobasal syndrome, characterized by movement disorders and cognitive dysfunction. Language dysfunction is also more common in hippocampal sparing AD, although patients do not have vocal or hearing deficits.

“What is tragic is that these patients are commonly misdiagnosed and we have new evidence that suggests drugs now on the market for AD could work best in these hippocampal sparing patients — possibly better than they work in the common form of the disease,” Dr. Murray says.

The researchers benefit greatly from one of the largest brain banks in the country — more than 6,500 brain donations — as well as a collaborative environment between neuroscience research and neurology at Mayo Clinic, she says.

Both hallmark proteins of AD — amyloid beta (Aβ), which forms Aβ plaques, and tau, which produces tangles — are found across all subtypes of AD, including hippocampal sparing AD. The researchers developed a mathematical algorithm to classify AD subtypes using tangle counts. “What is fascinating is that all the AD patient subtypes had the same amount of amyloid, but for some reason tau tangles were found in strategic cortical regions disproportionate to the hippocampus.”

In these patients, tau preferentially damages and eventually destroys neurons in parts of the brain involved in behavior, motor awareness and recognition, as well as use of speech and vision, Dr. Murray says.

She says she hopes this research, the second high-profile Mayo study to highlight hippocampal sparing AD, will “open the minds” of clinicians who are trying to diagnose dementia, helping them understand that loss of memory is not present in every AD patient.

“Our studies support the notion that dementia related to AD does not necessarily equate to a loss of memory, and points to the need for more research in amyloid and tau imaging biomarkers to help clinicians accurately diagnose AD — regardless of subtype,” Dr. Murray says.