Neuroscience

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.

A new study has provided insight into the behavioral damage caused by repeated blows to the head. The research provides a foundation for scientists to better understand and potentially develop new ways to detect and prevent the repetitive sports injuries that can lead to the condition known as chronic traumatic encephalopathy (CTE).

The research – which appears online this week in the Journal of Neurotrauma – shows that mice with mild, repetitive traumatic brain injury (TBI) develop many of the same behavioral problems, such as difficultly sleeping, memory problems, depression, judgment and risk-taking issues, that have been associated with the condition in humans.

One of the barriers to potential treatments for TBI and CTE is that no model of the disease exists. Animal equivalents of human diseases are a critical early-stage tool in the scientific process of understanding a condition, developing new ways to diagnose it, and evaluating experimental therapies. 

“This new model captures both the clinical aspects of repetitive mild TBI and CTE,” said Anthony L. Petraglia, M.D., a neurosurgeon with the University of Rochester School of Medicine and Dentistry and lead author of the study. “While public awareness of the long-term health risk of blows to the head is growing rapidly, our ability to scientifically study the fundamental neurological impact of mild brain injuries has lagged.”

There has been a great deal of discussion in recent years regarding concussions as a result of blows to the head in sports. An estimated 3.8 million sports-related concussions occur every year. Mild traumatic brain injury is also becoming more common in military personnel deployed in combat zones. Over time, the frequency and degree of these injuries can lead short and long-term neurological impairment and, in extreme examples, to CTE, a form of degenerative brain disease. 

The experiments described in the study were designed in a manner that simulates the type of mild TBI that may occur in sports or other blows to the head. The researchers evaluated the mice’s performance in a series of tasks designed to measure behavior. These included tests to measure spatial and learning memory, anxiety and risk-taking behavior, the presence of depression-like behavior, sleep disturbances, and the electrical activity of their brain. The mice with repetitive mild TBI did poorly in every test and this poor performance persisted over time.

“These results resemble the spectrum of neuro-behavioral problems that have been reported and observed in individuals who have sustained multiple mild TBI and those who were subsequently diagnosed with CTE, including behaviors such as poor judgment, risk taking, and depression,” said Petraglia.  

Petraglia and his colleagues also used the model to examine the damage that was occurring in the brains of the mice over time. The results, which will be published in a forthcoming paper, provide insight on the interaction between the brains repair mechanisms – in the forms of astrocytes and microglia – and the protein tau, which can have a toxic effect when triggered by mild traumatic brain injury. 

“Undoubtedly further work is needed,” said Petraglia. “However, this study serves as a good starting point and it is hoped that with continued investigation this novel model will allow for a controlled, mechanistic analysis of repetitive mild TBI and CTE in the future, because it is the first to encapsulate the spectrum of this human phenomenon.”

You know what you’re going to say before you say it, right? Not necessarily, research suggests. A study from researchers at Lund University in Sweden shows that auditory feedback plays an important role in helping us determine what we’re saying as we speak. The study is published in Psychological Science, a journal of the Association for Psychological Science.

“Our results indicate that speakers listen to their own voices to help specify the meaning of what they are saying,” says researcher Andreas Lind of Lund University, lead author of the study.

Theories about how we produce speech often assume that we start with a clear, preverbal idea of what to say that goes through different levels of encoding to finally become an utterance.

But the findings from this study support an alternative model in which speech is more than just a dutiful translation of this preverbal message:

“These findings suggest that the meaning of an utterance is not entirely internal to the speaker, but that it is also determined by the feedback we receive from our utterances, and from the inferences we draw from the wider conversational context,” Lind explains.

For the study, Lind and colleagues recruited Swedish participants to complete a classic Stroop test, which provided a controlled linguistic setting. During the Stroop test, participants were presented with various color words (e.g., “red” or “green”) one at a time on a screen and were tasked with naming the color of the font that each word was printed in, rather than the color that the word itself signified.

The participants wore headphones that provided real-time auditory feedback as they took the test — unbeknownst to them, the researchers had rigged the feedback using a voice-triggered playback system. This system allowed the researchers to substitute specific phonologically similar but semantically distinct words (“grey”, “green”) in real time, a technique they call “Real-time Speech Exchange” or RSE.

Data from the 78 participants indicated that when the timing of the insertions was right, only about one third of the exchanges were detected.

On many of the non-detected trials, when asked to report what they had said, participants reported the word they had heard through feedback, rather than the word they had actually said. Because accuracy on the task was actually very high, the manipulated feedback effectively led participants to believe that they had made an error and said the wrong word.

Overall, Lind and colleagues found that participants accepted the manipulated feedback as having been self-produced on about 85% of the non-detected trials.

Together, these findings suggest that our understanding of our own utterances, and our sense of agency for those utterances, depend to some degree on inferences we make after we’ve made them.

Most surprising, perhaps, is the fact that while participants received several indications about what they actually said — from their tongue and jaw, from sound conducted through the bone, and from their memory of the correct alternative on the screen — they still treated the manipulated words as though they were self-produced.

This suggests, says Lind, that the effect may be even more pronounced in everyday conversation, which is less constrained and more ambiguous than the context offered by the Stroop test.

“In future studies, we want to apply RSE to situations that are more social and spontaneous — investigating, for example, how exchanged words might influence the way an interview or conversation develops,” says Lind.

“While this is technically challenging to execute, it could potentially tell us a great deal about how meaning and communicative intentions are formed in natural discourse,” he concludes.

When police in Spain tried to locate two murder victims last year, they sought assistance on places to search from a tool that measured the brain activity of the convicted and confessed killers.

The technology, known as Brain Fingerprinting, developed by the American-based company Government Works Inc., basically seeks to use brain wave data in response to certain stimuli or details to determine whether a person is telling the truth. U.S. courts have sparingly allowed the higher-tech version of the traditional polygraph test or lie detector, and it has aided in both exoneration and conviction in American cases.

As the use of Brain Fingerprinting has expanded beyond the United States, a University of Kansas researcher argues the technology is based on an incorrect assumption about how human memory works.

"At the very least, we need to ask them to do several more methodological checks and make sure that whenever these technologies are used in legal contexts, we make clear the limitations of that technology," said Sarah Robins, an assistant professor of philosophy who studies the philosophy of neuroscience and related issues in neuroethics. “Maybe there’s a stronger claim here that this should never make it into court, but my stance is to say: ‘Let’s think about the technology and the assumptions behind it.’”

Robins details the theoretical issues surrounding Brain Fingerprinting in her essay “Memory Traces, Memory Errors, and the Possibility of Neural Lie Detection,” which will appear in “Brain Theory,” edited by Charles Wolfe. Also in Wolfe’s book, John Symons, a KU professor of philosophy, has co-authored the chapter “Computing with Bodies: Morphology, Function, and Computational Theory.”

Wolfe, a research fellow of the Department of Philosophy and Moral Sciences at the University of Ghent in Belgium, is scheduled to speak at 7 p.m. Friday, May 2, at the Kansas Room of the Kansas Union.

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Scientists’ inability to replicate research findings using mice and rats has contributed to mounting concern over the reliability of such studies.

Now, an international team of pain researchers led by scientists at McGill University in Montreal may have uncovered one important factor behind this vexing problem: the gender of the experimenters has a big impact on the stress levels of rodents, which are widely used in preclinical studies.

In research published online April 28 in Nature Methods, the scientists report that the presence of male experimenters produced a stress response in mice and rats equivalent to that caused by restraining the rodents for 15 minutes in a tube or forcing them to swim for three minutes. This stress-induced reaction made mice and rats of both sexes less sensitive to pain.

Female experimenters produced no such effects.

“Scientists whisper to each other at conferences that their rodent research subjects appear to be aware of their presence, and that this might affect the results of experiments, but this has never been directly demonstrated until now,” says Jeffrey Mogil, a psychology professor at McGill and senior author of the paper.

The research team, which included pain experts from Haverford College and the Karolinska Institutet in Sweden and a chemosensory expert from Université de Montreal, found that the effect of male experimenters on the rodents’ stress levels was due to smell. This was shown by placing cotton T shirts, worn the previous night by male or female experimenters, alongside the mice; the effects were identical to those caused by the presence of the experimenters, themselves.

Further experiments proved that the effects were caused by chemosignals, or pheromones, that men secrete from the armpit at higher concentrations than women. These chemosignals signal to rodents the presence of nearby male animals. (All mammals share the same chemosignals).

These effects are not limited to pain. The researchers found that other behavioural assays sensitive to stress were affected by male but not female experimenters or T-shirts.

“Our findings suggest that one major reason for lack of replication of animal studies is the gender of the experimenter – a factor that’s not currently stated in the methods sections of published papers,” says Robert Sorge, a psychology professor at the University of Alabama, Birmingham. Sorge led the study as a postdoctoral fellow at McGill.

The good news, Mogil says, is that “the problem is easily solved by simple changes to experimental procedures. For example, since the effect of males’ presence diminishes over time, the male experimenter can stay in the room with the animals before starting testing.  At the very least, published papers should state the gender of the experimenter who performed the behavioral testing.”

Experimental studies have shown that deep brain stimulation (DBS) within the subcallosal cingulate (SCC) white matter of the brain is an effective treatment for many patients with treatment-resistant depression. Response rates are between 41 percent and 64 percent across published studies to date. One of the proposed mechanisms of action is through modulation of a network of brain regions connected to the SCC. Identifying the critical connections within this network for successful antidepressant response is an important next step.  

A new study using MRI analysis of the white matter connections examined the architecture of this network in patients who demonstrated significant response to SCC DBS. Researchers found that all responders showed a common pattern defined by three distinct white matter bundles passing through the SCC. Non-responders did not show this pattern.

The study is published online in the journal Biological Psychiatry, with the title “Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.”

"This study shows that successful DBS therapy is not due solely to local changes at the site of stimulation but also in those regions in direct communication with the SCC," says Helen Mayberg, MD, senior author of the article, professor of psychiatry, neurology and radiology and the Dorothy C. Fuqua Chair in Psychiatric Imaging and Therapeutics at Emory University School of Medicine.

"Precisely delineating these white matter connections appears to be very important to a successful outcome with this procedure. From a practical point of view, these results may help us to choose the optimal contact for stimulation and eventually to better plan the surgical placement of the DBS electrodes."

Led by researchers at Emory University, Case Western Reserve University and Dartmouth University, the study included 16 patients with treatment-resistant depression who previously received SCC DBS at Emory. Computerized tomography was used post-operatively to localize the DBS contacts on each electrode. The activation volumes around the active contacts were modeled for each patient. Sophisticated neuroimaging combined with computerized analysis was used to derive and visualize the specific white matter fibers affected by ongoing DBS.

Therapeutic outcome was evaluated at six months and at two years. Six of the patients had responded positively to DBS at six months, and by two years these six plus six more patients responded positively. All shared common involvement of three distinct white matter bundles: the cingulum, the forceps minor and the uncinate fasciculus.

The conversion of six of the patients who were not responding at six months to being responders at two years was explained by the inclusion of all three bundles due to changes in stimulation settings. Non-responders at both six months and two years showed incomplete involvement of these three tracts. 

"In the past, placement of the electrode relied solely on anatomical landmarks with contact selection and stimulation parameter changes based on a trial-and-error method," says Patricio Riva-Posse, MD, Emory assistant professor of psychiatry and behavioral sciences and first author of the paper. "These results suggest that clinical outcome can be significantly influenced by optimally modulating the response network defined by tractography. This obviously will need to be tested prospectively in additional subjects here and by other teams exploring the use of this experimental treatment."

This new information will allow us to develop a refined algorithm for guiding surgical implantation of electrodes and optimizing the response through fine tuning of stimulation parameters,” notes Mayberg. “That said, improving anatomical precision alone doesn’t account for all non-responders, so that is an important next focus of our research.”

The researchers now plan to study DBS therapy in a prospective protocol of similar treatment-resistant depressed patients, using presurgical mapping of an individual patient’s network structure, precisely targeting the three SCC fiber bundles, and systematically testing the stimulation contacts.

A brain area activated by group decisions can distinguish people more likely to conform to the will of a group, say researchers from UCL.

The team, led by Dr Tali Sharot, UCL Affective Brain Lab, monitored the brain activity of individuals in groups of five people choosing food or drink they’d like to consume before and after being told the most popular choice in their group.

The results showed that people were likely to conform to the most popular choice in their group if their original preference was different.

Caroline Charpentier (UCL Institute of Cognitive Neuroscience) said: “Most people don’t think their everyday decisions, such as having eggs on toast for breakfast or a pint of lager at the pub, are influenced by other people’s preferences.”

She added: “But our results suggest that when other people make different choices than you, for example your friends order beer while you order wine, your brain records this information and this signal is mirrored in your brain later on, for example when you order another drink, making you more likely to choose beer, even if you initially preferred wine”.

The team, led by Dr Tali Sharot, used functional magnetic resonance imaging (fMRI) to monitor the brain responses of 20 volunteers during a decision-making task, while 78 more volunteers completed the task simultaneously on computers located outside the MRI room. They came to the lab in small groups of five.

In one session, volunteers were shown 60 pairs of food and drink items and asked to select which item of each pair they would prefer to consume at the end of the experiment. Straight after making this choice, the participants were told which item most people in their group selected. This part of the experiment provided the volunteers with social feedback.

Volunteers then took part in a following session a few minutes later, when they opted again for which item they would prefer to consume from the same series of pairs, but this time made the choice for themselves and did not receive any social feedback.  

After the experiment, the participants completed a personality questionnaire that assessed trait conformity, which measures their general tendency to follow other people’s ideas and behaviours. Comparison of results from the choice experiment and conformity questionnaire indeed showed that people who scored high on trait conformity were about twice as likely to change their food choices to agree with the group decision as people who scored low for conformity.

What differed between the brains of people who were more likely to conform and people who held on to their own opinion?

The imaging study showed that the orbito-frontal cortex (OFC) – a region at the front of the brain that has been associated with emotional and social behaviour – was active during the two choice sessions and distinguished between these two groups of people.

Miss Charpentier said: “The orbito-frontal cortex was the only region specifically activated, and the first area to react to group disagreement. This region was activated both at the time of the initial social conflict (when your friends all choose beer while you prefer wine) and also later when you make an individual choice (when you order another drink for yourself).”

The OFC has previously been associated with emotions and social behaviour. Some clinical studies have suggested that people with brain damage in the OFC may behave inappropriately in groups.

Miss Charpentier concluded: “When OFC activity during the initial social conflict is mirrored in your brain at a later time when you make an individual choice, you are more likely to change your choice and follow the group. This is what happens in ‘high conformers’. In other words, it is the temporal dynamics of the OFC that distinguishes “conformers” from people who hold on to their own initial opinion”.

Each year, approximately 2 million traumatic brain injuries (TBIs) occur in the USA, according to the Centers for Disease Control and Prevention. That number includes troops wounded in Iraq and Afghanistan, for whom TBI is considered an invisible wound of war, one that has few successful treatments. “We have nothing beyond ibuprofen for most TBIs,” said Dr. Angus Scrimgeour, who has been investigating the effects of low zinc diets on cell stress following a blast injury. “The adult brain does not self-repair from this kind of trauma.”

Scrimgeour works for the US Army Research Institute of Environmental Medicine and recently looked at the effects of 5-weeks of low and adequate zinc diets on a specific protein in muscle cells called MMP. The study recreated blast injuries in 32 rats similar to what soldiers experience from IEDs, including loss of consciousness. An equal number of rats served as a control group. Results suggest that zinc supplementation reduces blast-induced cell stress. He presented the results of his research at the American Society for Nutrition’s Scientific Sessions & Annual Meeting at EB on Sunday, April 27.

“We know that soldiers’ brain tissue cannot repair on low zinc diets,” said Scrimgeour. “And they are losing zinc through diarrhea and sweating.” The question moving forward is whether prevention through diet supplementation or post-blast treatment works best to repair behavioral deficits associated with mild TBI.

Scrimgeour added that further research is planned to investigate nutrient combinations for treating mild TBI, including omega-3, vitamin D, glutamine and/or zinc. Although the Army is conducting this research, the results can be applied outside of the military, according to Scrimgeour. “As the blast impact experienced by Soldiers are similar to those experienced during head injuries received in a car accident or during an NFL concussion, these findings could translate from the Soldier to the civilian population.” Scrimgeour cautioned, however, that what works in animals doesn’t always work in soldiers, which is why more research is needed.