Neuroscience

ScienceDaily (Mar. 26, 2012) — Repeated stress triggers the production and accumulation of insoluble tau protein aggregates inside the brain cells of mice, say researchers at the University of California, San Diego School of Medicine in a new study published in the March 26 Online Early Edition of the Proceedings of the National Academy of Sciences.

Exposing mice to 14 days of repeated stress resulted in an accumulation of insoluble phosphorylated tau protein aggregates in brain cells, visualized in this electron micrograph. (Credit: Image courtesy of Robert Rissman, UC San Diego)

The aggregates are similar to neurofibrillary tangles or NFTs, modified protein structures that are one of the physiological hallmarks of Alzheimer’s disease. Lead author Robert A. Rissman, PhD, assistant professor of neurosciences, said the findings may at least partly explain why clinical studies have found a strong link between people prone to stress and development of sporadic Alzheimer’s disease (AD), which accounts for up to 95 percent of all AD cases in humans.

"In the mouse models, we found that repeated episodes of emotional stress, which has been demonstrated to be comparable to what humans might experience in ordinary life, resulted in the phosphorylation and altered solubility of tau proteins in neurons," Rissman said. "These events are critical in the development of NFT pathology in Alzheimer’s disease."

The effect was most notable in the hippocampus, said Rissman, a region of the brain linked to the formation, organization and storage of memories. In AD patients, the hippocampus is typically the first region of the brain affected by tau pathology and the hardest-hit, with substantial cell death and shrinkage.

Not all forms of stress are equally threatening. In earlier research, Rissman and colleagues reported that acute stress — a single, passing episode — does not result in lasting, debilitating long lasting changes in accumulation of phosphorylated tau. Acute stress-induced modifications in the cell are transient, he said, and on the whole, probably beneficial.

"Acute stress may be useful for brain plasticity and helping to facilitate learning. Chronic stress and continuous activation of stress pathways may lead to pathological changes in stress circuitry. It may be too much of a good thing." As people age, perhaps their neuronal circuits do too, he said, becoming less robust and perhaps less capable of completely rebounding from the effects of stress.

"Age is the primary, known risk factor for Alzheimer’s disease. It may be that as we age, our neurons just aren’t as plastic as they once were and some succumb."

The researchers observed that stress cues impacted two key corticotropin-releasing factor receptors, suggesting a target for potential therapies. Rissman noted drugs already exist and are in human trials (for other conditions) that modulate the activity of these receptors.

"You can’t eliminate stress. We all need to be able to respond at some level to stressful stimuli. The idea is to use an antagonist molecule to reduce the effects of stress upon neurons. The stress system can still respond, but the response in the brain and hippocampus would be toned down so that it doesn’t result in harmful, permanent damage."

The authors dedicate this work to long time mentor and colleague, Dr. Wylie Vale, whose years of pioneering work deciphering and describing the stress system were fundamental to this paper. Vale passed away earlier this year at the age of 70.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Individuals with major depressive disorder (MDD) often undergo multiple courses of antidepressant treatment during their lives. This is because the disorder can recur despite treatment and because finding the right medication for a specific individual can take time.

While the relationship between prior treatment and the brain’s response to subsequent treatment is unknown, a new study by UCLA researchers suggests that how the brain responds to antidepressant medication may be influenced by its remembering of past antidepressant exposure.

Interestingly, the researchers used a harmless placebo as the key to tracking the footprints of prior antidepressant use.

Aimee Hunter, the study’s lead author and an assistant professor of psychiatry at UCLA’s Semel Institute for Neuroscience and Human Behavior, and colleagues showed that a simple placebo pill, made to look like actual medication for depression, can “trick” the brain into responding in the same manner as the actual medication.

The report was published online March 23 in the journal European Neuropsychopharmacology.

The investigators examined changes in brain function in 89 depressed persons during eight weeks of treatment, using either an antidepressant medication or a similar-looking placebo pill. They set out to compare the two treatments — medication versus placebo — but they also added a twist: They separately examined the data for subjects who had never previously taken an antidepressant and those who had.

The researchers focused on the prefrontal cortex, an area of the brain thought to be involved in planning complex cognitive behavior, personality expression, decision-making and moderating social behavior, all things depressed people wrestle with.

Brain changes were assessed using electroencephalograph (EEG) measures developed at UCLA by study co-authors Dr. Ian Cook, UCLA’s Miller Family Professor of Psychiatry, and Dr. Andrew Leuchter, a professor of psychiatry and director of the Laboratory of Brain, Behavior and Pharmacology at UCLA’s Semel Institute. The EEG measure, recorded from scalp electrodes, is linked to blood flow in the cerebral cortex, which suggests the level of brain activity.

The antidepressant medication given during the study appeared to produce slight decreases in prefrontal brain activity, regardless of whether subjects had received prior antidepressant treatment during their lifetime or not. (A decrease in brain activity is not necessarily a bad thing, the researchers note; with depression, too much activity in the brain can be as bad as too little.)

However, the researchers observed striking differences in the power of placebo, depending on subjects’ prior antidepressant use. Subjects who had never been treated with an antidepressant exhibited large increases in prefrontal brain activity during placebo treatment. But those who had used antidepressant medication in the past showed slight decreases in prefrontal activity — brain changes that were indistinguishable from those produced by the actual drug.

"The brain’s response to the placebo pill seems to depend on what happened previously — on whether or not the brain has ever ‘seen’ antidepressant medication before," said Hunter, who is a member of the placebo research team at the Laboratory of Brain, Behavior and Pharmacology. "If it has seen it before, then the brain’s signature ‘antidepressant-exposure’ response shows up."

According to Hunter, the effect looks conspicuously like a classical conditioning phenomenon, wherein prior exposure to the actual drug may have produced the specific prefrontal brain response and subsequent exposure to the cues surrounding drug administration — the relationship with the doctor or nurse, the medical treatment setting, the act of taking a prescribed pill and so forth — came to elicit a similar brain response through ‘conditioning’ or ‘associative learning.’

While medication can have a powerful effect on our physiology, said Hunter, “the behaviors and cues in the environment that are associated with taking medication can come to elicit their own effects. One’s personal treatment history is one of the many factors that influence the overall effects of treatment.”

Still, she noted, there are other possible explanations, and further research is needed to tease out changes in brain function that are related to antidepressant exposure, compared with brain changes that are related to clinical improvement during treatment.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Smoking alters the impact of a schizophrenia risk gene. Scientists from the universities of Zurich and Cologne demonstrate that healthy people who carry this risk gene and smoke process acoustic stimuli in a similarly deficient way as patients with schizophrenia. Furthermore, the impact is all the stronger the more the person smokes.

Schizophrenia has long been known to be hereditary. However, as a melting pot of disorders with different genetic causes is concealed behind manifestations of schizophrenia, research has still not been able to identify the main gene responsible to this day.

In order to study the genetic background of schizophrenia, the frequency of particular risk genes between healthy and ill people has mostly been compared until now. Pharmacopyschologist Professor Boris Quednow from University Hospital of Psychiatry, Zurich, and Professor Georg Winterer’s workgroup at the University of Cologne have now adopted a novel approach. Using electroencephalography (EEG), the scientists studied the processing of simple acoustic stimuli (a sequence of similar clicks). When processing a particular stimulus, healthy people suppress the processing of other stimuli that are irrelevant to the task at hand. Patients with schizophrenia exhibit deficits in this kind of stimulus filtering and thus their brains are probably inundated with too much information. As psychiatrically healthy people also filter stimuli with varying degrees of efficiency, individual stimulus processing can be associated with particular genes.

Smokers process stimuli less effectively

In a large-scale study involving over 1,800 healthy participants from the general population, Boris Quednow and Georg Winterer examined how far acoustic stimulus filtering is connected with a known risk gene for schizophrenia: the so-called “transcription factor 4” gene (TCF4). TCF4 is a protein that plays a key role in early brain development. As patients with schizophrenia often smoke, the scientists also studied the smoking habits of the test subjects.

The data collected shows that psychiatrically healthy carriers of the TCF4 gene also filter stimuli less effectively — like people who suffer from schizophrenia. It turned out that primarily smokers who carry the risk gene display a less effective filtering of acoustic impressions. This effect was all the more pronounced the more the people smoked. Non-smoking carriers of the risk gene, however, did not process stimuli much worse. “Smoking alters the impact of the TCF4 gene on acoustic stimulus filtering,” says Boris Quednow, explaining this kind of gene-environment interaction. “Therefore, smoking might also increase the impact of particular genes on the risk of schizophrenia.”

The results could also be significant for predicting schizophrenic disorders and for new treatment approaches, says Quednow and concludes: “Smoking should also be considered as an important cofactor for the risk of schizophrenia in future studies.” A combination of genetic (e.g. TCF4), electrophysiological (stimulus filtering) and demographic (smoking) factors could help diagnose the disorder more rapidly or also define new, genetically more uniform patient subgroups.

Source: Science Daily

ScienceDaily (Mar. 26, 2012) — Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.

According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays.

"We want to encourage parents to become good observers of their children’s development so that they can see the earliest indicators of delays in a baby’s communication, social and motor skills," says Dr. Landa, who also cautions that some children who develop ASD don’t show signs until after the second birthday or regress after appearing to develop typically.

For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old.

Dr. Landa recommends that as parents play with their infant (6 — 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders:

1. Rarely smiles when approached by caregivers 2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges 3. Delayed or infrequent babbling 4. Does not respond to his or her name with increasing consistency from 6 — 12 months 5. Does not gesture to communicate by 10 months 6. Poor eye contact 7. Seeks your attention infrequently 8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors 9. Does not reach up toward you when you reach to pick him or her up 10. Delays in motor development, including delayed rolling over, pushing up and crawling

"If parents suspect something is wrong with their child’s development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert," says Dr. Landa. "Don’t adopt a ‘wait and see’ perspective. We want to identify delays early in development so that intervention can begin when children’s brains are more malleable and still developing their circuitry."

Source: Science Daily

March 26, 2012

A meta-analysis of previously published studies found that the ratio of blood plasma amyloid-β (Aβ) peptides Aβ42:Aβ40 was significantly associated with development of Alzheimer disease and dementia, according to a report published Online First by Archives of Neurology.

"Plasma levels of amyloid-β (Aβ) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data," the authors write as background in the study.

Alain Koyama, S.M., then of Harvard School of Public Health and Brigham and Women’s Hospital, Boston, now with the University of California, San Francisco, and colleagues conducted a meta-analysis of 13 previously published studies to examine the association between plasma amyloid-β and development of dementia, Alzheimer disease (AD) and cognitive decline.

The 13 studies included in the analysis had a total of 10,303 participants, and were published between 1995 and 2011. The studies also included measurement of at least one relevant plasma amyloid-β species (Aβ40, Aβ42, or Aβ42: Aβ40 ratio) and reported an effect estimate for dementia, AD or cognitive decline.

The authors found that lower Aβ42: Aβ40 ratios were significantly associated with development of Alzheimer disease and dementia, with most studies in the analysis reporting similar findings. Plasma levels of Aβ40 and Aβ42 alone, however, were not significantly associated with either outcome.

"In conclusion, despite the limitations of existing research and heterogeneity across the studies considered, this systematic review and meta-analysis suggests that the ratio of plasma Aβ42: Aβ40 may have value in predicting the risk for later development of dementia or AD and merits further investigation."

More information: Arch Neurol. Published online March 26, 2012. doi:10.1001/archneurol.2011.1841

Provided by JAMA and Archives Journals

Source: medicalxpress.com

March 26, 2012

Dr. Judith Edersheim, co-founder and co-director of the Center for Law, Brain and Behavior at Massachusetts General Hospital, explores how neuroscience can enhance the pursuit of justice.

Dr. Judith Edersheim of the Center for Law, Brain and Behavior delivered the 13th annual Francine and Michael Saferstein Memorial Lecture in Forensic Science on Tuesday. Photo by Dominick Reuter.

“If neuroscience could shed light on mental states, it might be able to illuminate whether someone meant the crime or intended to harm someone,” Edersheim told approximately 200 students, faculty, staff and community members who filled Northeastern’s Raytheon Amphitheater on Tuesday for the 13th annual Francine and Michael Saferstein Memorial Lecture in Forensic Science.

The lecture series — which is co-sponsored by the Barnett Institute of Chemical and Biological Analysis and the School of Criminology and Criminal Justice — was established by forensic scientist Richard Saferstein in memory of his wife and child, who were killed in 1978 when a bomb discharged inside the family’s garage.

Barry Karger — the James L. Waters Chair in Analytical Chemistry in Northeastern’s College of Science and director of the Barnett Institute of Chemical and Biological Analysis — introduced Edersheim by praising her for “performing a broad range of psychiatric evaluations in criminal and civil forensic settings.”

Edersheim, who holds both an MD and JD, said “neurolaw” is similar to  “neuropolitics” and “neuromarketing,” in that the field tries to incorporate both neuroscience and psychology into a more established practice.

One’s genetic composition as well as the electrical activity and physical structure of the working brain, she explained, can all be explored to shed light on the question of criminal responsibility.

But Edersheim added a note of caution in taking this approach: If biology single-handedly determines behavior, then the very notion of free will becomes compromised. Technological, procedural, constitutional and deterministic limitations, she said, must all be considered when applying neuroscience to the law.

“The science has to be respected in the community and it has to be peer reviewed,” Edersheim said. “It has to be reliable, reproducible and there have to be known error rates. Judges are gatekeepers and they should keep evidence out that doesn’t meet those tests.”

Edersheim also addressed the constitutionality of neurolaw. If brain scans are examples of involuntary search and seizure or if they force defendants to unwillingly incriminate themselves, then the procedure, she said, could be in violation of the Fourth and Fifth amendments, respectively.

“Thoughts may be subject to constitutional protection,” Edersheim explained, adding that the law and the brain “live in different worlds.”

The law, she said, gives us a set of rules we must abide by, but we must decide as a society whether neurobiological explanations of human behavior should matter when determining criminality.

Edersheim said the Center for Law, Brain and Behavior has an “operational philosophy for the faithful translation of law into neuroscience,” meaning that courtroom use of neurological and biological data should be limited to instances when the science is inextricably and causally linked to a behavior.

Provided by Northeastern University

Source: medicalxpress.com

ScienceDaily (Mar. 26, 2012) — A new study, using brain imaging technology, reveals structural adaptations in short-track speed skaters’ brains which are likely to explain their extraordinary balance and co-ordination skills.

Short track speed skaters. (Credit: © sarah besson / Fotolia)

The work by Im Joo Rhyu from the Korea University College of Medicine, and colleagues, is published online in Springer’s journal Cerebellum.

The cerebellum in the brain plays an essential role in balance control, coordinated movement, and visually guided movement, which are key abilities required for short-track speed skaters as they glide on perfectly smooth ice, cornering and passing at high speeds. Previous studies have shown that damage to the cerebellum results in impaired balance and coordination. In addition, structural changes in the brain have been documented following training of complex motor skills, in both jugglers and basketball players for instance. Are these changes sports-specific?

To assess the effect of short-track speed skating training on the relative structure and size of the two brain hemispheres, the authors analyzed brain MRI scans of 16 male professional short-track speed skaters. They compared them to scans of 18 non-skaters, who did not engage in regular exercise.

They found that skaters had larger right hemispheres of the cerebellum and vermian lobules VI-VII (the lobes connecting the left and right parts of the cerebellum) than non-skaters. These results suggest that the specialized abilities of balance and coordination in skaters are associated with a certain amount of flexibility in the structure of the right hemisphere of the cerebellum and vermian VI-VII.

Why do the structural changes occur to the right side of the cerebellum? Gliding on smooth ice requires specialized abilities to control dynamic balance and coordination. During cornering at high speed, short-track speed skaters turn only to the left while maintaining balance on their right foot. Standing on the right foot activates the right lobes of the cerebellum.

In addition, learning a visually guided task is thought to occur in the right side of the brain. Therefore the larger volume of the right hemisphere of the cerebellum in these skaters is likely to be associated with the type of movements which the sport requires, for strong visual guidance while cornering and passing.

The authors conclude: “Short-track speed skaters’ specialized abilities of balance and coordination stimulate specific structural changes in the cerebellum, following extensive training. These changes reflect the effects of extraordinary abilities of balance and coordination on the right region of the brain.”

Source: Science Daily

March 26, 2012 by Bob Yirka

(Medical Xpress) — A research team made up of people from a wide variety of biological sciences has found that mice fed a diet high in fat tend to see an increase in the number of neurons created in the hypothalamus, a region of the brain associated with regulating energy use in the body. The team, as they describe in their paper published in Nature Neuroscience, write that the increase in neurons occurs in a part of the hypothalamus called the median eminence, which lies outside the blood-brain barrier.

Hypothalamic proliferative zone. For more details, Nature Neuroscience (2012) doi:10.1038/nn.3079

Suspecting that something unusual goes on with the hypothalamus and the median eminence in particular, when mice eat more fat, the research team put a group of mice on a diet very high in it. In the lab, mice are usually fed a diet that is approximately thirty five percent fat, which keeps them from gaining weight. In this study, the fat content was raised to sixty percent, which of course caused the mice to get fat. But, the team found, it also caused the creation of new brain cells in the median eminence to increase, from one to five percent.

Next the researchers forced the mouse brains to stop creating new brain cells while continuing to feed the mice the high fat diet. And surprisingly, the mice weight gain slowed and the mice demonstrated more energy. Adding to the good news was the fact that the median eminence lies outside of the blood-brain area (a separation of blood and brain fluid that prevents many materials in blood from reaching brain cells) meaning that the possibility of developing a therapy based on this research to help humans lose weight might be possible.

The researchers are quick to point out however, that there is no evidence yet that increased neuron production occurs in people who eat extra amounts of fat, or even in any other animal. They also say they don’t yet understand why new neuron growth occurs when mice are fed a high fat diet, but speculate that it may have something to do with detecting chemicals in the bloodstream and responding by sending signals to the rest of the hypothalamus.

More information: Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche, Nature Neuroscience (2012) doi:10.1038/nn.3079

Source: medicalxpress.com

March 26, 2012 By Angela Herring

All human languages contain two levels of structure, said Iris Berent, a psychology professor in Northeastern’s College of Science. One is syntax, or the ordering of words in a sentence. The other is phonology, or the sound structure of individual words.

Berent — whose research focuses on the phonological structure of language — examines the nature of linguistic competence, its origins and its interaction with reading. While previous studies have all centered on adult language acquisition, she is now working with infants to address two core questions.

“First,” she said, “do infants have the capacity to encode phonological rules? And, second, are some phonological rules innate?”

To address the first issue, Berent collaborated with neuroscientists Janet Werker, of the University of British Columbia, and Judit Gervain, of the Paris-based Centre National de la Recherche Scientifique.

By utilizing an optical brain imaging technique called near-infrared spectroscopy, or NIRS, the researchers found that newborns have the capacity to learn linguistic rules. This finding — published this month in the Journal of Cognitive Neuroscience — suggests that the neural foundations of language acquisition are present at birth.

Armed with this knowledge, Berent has begun conducting behavioral studies on more than two-dozen infants to explore whether linguistic rules are innate or entirely learned.

“We want to see whether infants prefer certain sound patterns to others even if neither occurs in their language,” Berent explained. “For instance, we know that human languages prefer sequences such as bnog over bdog. Would six-month-old infants show this preference even if their language (English) does not include either sequence?”

For the study, each child is placed in front of a video screen that displays an image pulsing in coordination with rotating sounds, such as “bnog” and “bdog.” Berent hypothesized that infants would look longer at the video screen when they hear sounds to which they are innately biased.

Preliminary results have upheld the hypothesis, but Berent is still accepting new subjects for the study. Her entire research program forms part of a new book called “The Phonological Mind,” which will be published by Cambridge University Press this year.

Provided by Northeastern University

Source: medicalxpress.com

March 26, 2012

(Medical Xpress) — Storytelling is a skill not everyone can master, but even the most crashing bore gets help from their audience’s brain which ‘talks over’ their monotonous quotes, according to scientists.

Researchers from the University of Glasgow’s Institute of Neuroscience and Psychology investigated the ‘voice-selective’ areas of the brain and revealed that when listening to someone monotonously repeating direct speech quotations, the brain will ‘talk over’ the speaker to make the quotes more vivid.

Previously, the researchers had shown the brain ‘talks’ when silently reading direct quotations.

Dr Bo Yao, the principal investigator of the study, said: “You may think the brain need not produce its own speech while listening to one that is already available.

“But, apparently, the brain is very picky on the speech it hears. When the brain hears monotonously-spoken direct speech quotations which it expects to be more vivid, the brain simply ‘talks over’ the speech it hears with more vivid speech utterances of its own.”

Dr Bo Yao explains why the brain ‘talks over’ boring speech: 

[Audio]

The research was conducted by Dr Yao and colleagues Professor Pascal Belin and Professor Christoph Scheepers within the Institute’s Centre for Cognitive Neuroimaging.

The team enlisted 18 participants in the study and scanned their brains using functional magnetic resonance imaging (fMRI) while they listened to audio clips of short stories containing direct or indirect speech quotations. The direct speech quotations — e.g., Mary said excitedly: “The latest Sherlock Holmes film is fantastic!” – were either spoken ‘vividly’ or ‘monotonously’ (i.e., with or without much variation in speech melody).

The results showed that listening to monotonously spoken direct speech quotations increased brain activity in the ‘voice-selective areas’ of the brain. These voice-selective areas – originally discovered by Prof Belin – are certain areas of the auditory cortex which are particularly interested in human voices when stimulated by actual speech sounds perceived by the ears.

However, the present and previous studies also reveal that these areas can be activated by different linguistic reporting styles – such as direct versus indirect speech.

Prof Scheepers said: “Direct speech quotations are generally assumed to be more vivid and perceptually engaging than indirect speech quotations as they are more frequently associated with depictions of voices, facial expressions and co-speech gestures.

“When the brain does not receive actual stimulation of auditory speech during silent reading, it tends to produce its own to enliven written direct speech quotations – a phenomenon commonly referred to as the ‘inner voice’ during silent reading. Now it appears the brain does the same even when listening to monotonously-spoken direct speech quotations.”

Dr Yao added: “This research demonstrates that human speech processing is an active process in which the brain generates models for the incoming speech utterances in order to predict actual auditory input.

“By doing so, the brain attempts to optimise the processing of the incoming speech, ensuring more speedy and accurate responses.

“These predictions are probably grounded in our past experiences in which direct speech is frequently associated with vivid depictions of the reported speaker’s voice whereas indirect speech is usually stated in a more flat and steady tone.

“The brain’s ‘talking over’ monotonously spoken direct quotes seems to reflect that it tries to bridge the incongruence between the expected speech utterances (vivid) and the actually perceived speech (monotonous) by simulating or imagining the expected vivid vocal depictions.

“We believe that such a simulation mechanism is an integral part of language comprehension — we naturally recruit our sensory and motor systems to interpret the language input. Language processing, in this sense, is embodied.”

The research paper ‘Brain “talks over” boring quotes: Top-down activation of voice-selective areas while listening to monotonous direct speech quotations’ is published in NeuroImage.

Provided by University of Glasgow

Source: medicalxpress.com 

March 24, 2012

(HealthDay) — Neurodegenerative diseases may be characterized by specific regions of the brain that are critical network epicenters, with disease-related vulnerability associated with shorter paths to the epicenter and greater total connectional flow, according to a study published in the March 22 issue of Neuron.

Neurodegenerative diseases may be characterized by specific regions of the brain that are critical network epicenters, with disease-related vulnerability associated with shorter paths to the epicenter and greater total connectional flow, according to a study published in the March 22 issue of Neuron.

To investigate how intrinsic connectivity in health predicts regional vulnerability to neurodegenerative disease, Juan Zhou, Ph.D., from the University of California in San Francisco, and colleagues used task-free functional magnetic resonance imaging to identify the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to five neurodegenerative diseases (Alzheimer’s disease, behavioral variant frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, and corticobasal syndrome).

The investigators found that, for each neurodegenerative disease, specific regions emerged as critical network epicenters, and their normal connectivity profile was most similar to the disease-linked pattern of atrophy. In healthy subjects, greater disease-related vulnerability was consistently associated with regions with shorter functional paths to the epicenters and also with higher total connectional flow.

"These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures," the authors write.

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Mar. 24, 2012) — Researchers are suggesting that there is a link between the number of friends you have and the size of the region of the brain — known as the orbital prefrontal cortex — that is found just above the eyes. A new study shows that this brain region is bigger in people who have a larger number of friendships.

Friends. Researchers are suggesting that there is a link between the number of friends you have and the size of the region of the brain — known as the orbital prefrontal cortex — that is found just above the eyes. (Credit: © Rido / Fotolia)

Their study is published on 1 February 2012 in the journal, Proceedings of the Royal Society B.

The research was carried out as part of the British Academy Centenary ‘Lucy to Language’ project, led by Professor Robin Dunbar of the University of Oxford in a collaboration with Dr Joanne Powell and Dr Marta Garcia-Finana at Liverpool University, Dr Penny Lewis at Manchester University and Professor Neil Roberts at Edinburgh University.

The study suggests that we need to employ a set of cognitive skills to maintain a number of friends (and the keyword is ‘friends’ as opposed to just the total number of people we know). These skills are described by social scientists as ‘mentalising’ or ‘mind-reading’- a capacity to understand what another person is thinking, which is crucial to our ability to handle our complex social world, including the ability to hold conversations with one another. This study, for the first time, suggests that our competency in these skills is determined by the size of key regions of our brains (in particular, the frontal lobe).

Professor Dunbar, from the Institute of Cognitive and Evolutionary Anthropology, explained: ‘“Mentalising” is where one individual is able to follow a natural hierarchy involving other individuals’ mind states. For example, in the play ‘Othello’, Shakespeare manages to keep track of five separate mental states: he intended that his audience believes that Iago wants Othello to suppose that Desdemona loves Cassio [the italics signify the different mind states]. Being able to maintain five separate individuals’ mental states is the natural upper limit for most adults.’

The researchers took anatomical MR images of the brains of 40 volunteers at the Magnetic Resonance and Image Analysis Research Centre at the University of Liverpool to measure the size of the prefrontal cortex, the part of the brain used in high-level thinking. Participants were asked to make a list of everyone they had had social, as opposed to professional, contact with over the previous seven days. They also took a test to determine their competency in mentalising.

Professor Robin Dunbar, said: ‘We found that individuals who had more friends did better on mentalising tasks and had more neural volume in the orbital frontal cortex, the part of the forebrain immediately above the eyes. Understanding this link between an individual’s brain size and the number of friends they have helps us understand the mechanisms that have led to humans developing bigger brains than other primate species. The frontal lobes of the brain, in particular, have enlarged dramatically in humans over the last half million years.’

Dr Joanne Powell, from the Department of Psychology, University of Liverpool, said: ‘Perhaps the most important finding of our study is that we have been able to show that the relationship between brain size and social network size is mediated by mentalising skills. What this tells us is that the size of your brain determines your social skills, and it is these that allow you have many friends.’

Professor Dunbar said: ‘All the volunteers in this sample were postgraduate students of broadly similar ages with potentially similar opportunities for social activities. Of course, the amount of spare time for socialising, geography, personality and gender all influence friendship size, but we also know that at least some of these factors, notably gender, also correlate with mentalising skills. Our study finds there is a link between the ability to read how other people think and social network size.’

Professor Dunbar’s research was funded by the British Academy Centenary Research Project and by the British Academy Research Professorship. His research has already examined the different brain sizes of different species, but this study looks at the differences within species. Professor Dunbar published a paper last year, which found that people living near to the Poles needed larger brains for visual processing because of the dimmer light conditions.

Source: Science Daily

ScienceDaily (Mar. 23, 2012) — Nodding off in class may not be such a bad idea after all. New research from the University of Notre Dame shows that going to sleep shortly after learning new material is most beneficial for recall.

New research shows that going to sleep shortly after learning new material is most beneficial for recall. (Credit: © Claudia Nagel / Fotolia)

Notre Dame psychologist Jessica Payne and colleagues studied 207 students who habitually slept for at least six hours per night. Participants were randomly assigned to study declarative, semantically related or unrelated word pairs at 9 a.m. or 9 p.m., and returned for testing 30 minutes, 12 hours or 24 hours later. Declarative memory refers to the ability to consciously remember facts and events, and can be broken down into episodic memory (memory for events) and semantic memory (memory for facts about the world). People routinely use both types of memory every day — recalling where we parked today or learning how a colleague prefers to be addressed.

At the 12-hour retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs; there was no sleep-wake difference for related word pairs. At the 24-hour retest, with all subjects having received both a full night of sleep and a full day of wakefulness, subjects’ memories were superior when sleep occurred shortly after learning, rather than following a full day of wakefulness.

"Our study confirms that sleeping directly after learning something new is beneficial for memory. What’s novel about this study is that we tried to shine light on sleep’s influence on both types of declarative memory by studying semantically unrelated and related word pairs," Payne says.

"Since we found that sleeping soon after learning benefited both types of memory, this means that it would be a good thing to rehearse any information you need to remember just prior to going to bed. In some sense, you may be ‘telling’ the sleeping brain what to consolidate."

Source: Science Daily

March 23, 2012 by Cathryn Delude

Our fond or fearful memories — that first kiss or a bump in the night — leave memory traces that we may conjure up in the remembrance of things past, complete with time, place and all the sensations of the experience. Neuroscientists call these traces memory engrams.

But are engrams conceptual, or are they a physical network of neurons in the brain? In a new MIT study, researchers used optogenetics to show that memories really do reside in very specific brain cells, and that simply activating a tiny fraction of brain cells can recall an entire memory — explaining, for example, how Marcel Proust could recapitulate his childhood from the aroma of a once-beloved madeleine cookie.

“We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells, in this case by light,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study reported online today in the journal Nature. “This is the rigorously designed 21st-century test of Canadian neurosurgeon Wilder Penfield’s early-1900s accidental observation suggesting that mind is based on matter.”

In that famous surgery, Penfield treated epilepsy patients by scooping out parts of the brain where seizures originated. To ensure that he destroyed only the problematic neurons, Penfield stimulated the brain with tiny jolts of electricity while patients, who were under local anesthesia, reported what they were experiencing. Remarkably, some vividly recalled entire complex events when Penfield stimulated just a few neurons in the hippocampus, a region now considered essential to the formation and recall of episodic memories.

Scientists have continued to explore that phenomenon but, until now, it has never been proven that the direct reactivation of the hippocampus was sufficient to cause memory recall.

Shedding light on the matter

Fast forward to the introduction, seven years ago, of optogenetics, which can stimulate neurons that are genetically modified to express light-activated proteins. “We thought we could use this new technology to directly test the hypothesis about memory encoding and storage in a mimicry experiment,” says co-author Xu Liu, a postdoc in Tonegawa’s lab. 

Read More →

ScienceDaily (Mar. 23, 2012) — Insulin resistance in the brain precedes and contributes to cognitive decline above and beyond other known causes of Alzheimer’s disease, according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Insulin is an important hormone in many bodily functions, including the health of brain cells. The team identified extensive abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer’s disease. These pathways could be targeted with new or existing medicines to potentially help resensitize the brain to insulin and possibly slow down or even improve cognitive decline.

This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer’s disease. The study is now online in the Journal of Clinical Investigation.

"Our research clearly shows that the brain’s ability to respond to insulin, which is important for normal brain function, is going offline at some point. Insulin in the brain not only modulates glucose uptake, but also promotes the health of brain cells — their growth, survival, remodeling, and normal functioning. We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer’s disease," said senior author, Steven E. Arnold, MD, professor of Psychiatry and Neurology. Arnold is also the director of the Penn Memory Center, a National Institute on Aging-designated Alzheimer’s Disease Core Center. "If we can prevent brain insulin resistance from occurring, or re-sensitize brain cells to insulin with any of the currently available insulin-sensitizing diabetes medicines, we may be able to slow down, prevent, or perhaps even improve cognitive decline.

The risk of developing Alzheimer’s disease is increased by 50 percent in people with diabetes. Type 2 diabetes is due to insulin resistance and accounts for 90 percent of all diabetes. The defining clinical feature of Type 2 diabetes (and Type 1 “juvenile” diabetes) is hyperglycemia — high levels of sugar in the blood — but there is no evidence that the brain in Alzheimer’s is hyperglycemic. Insulin acts differently in the brain than in the rest of the body. Researchers found that insulin resistance of the brain occurs in Alzheimer’s disease independent of whether someone has diabetes, by excluding people with a history of diabetes from this study.

The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer’s disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways. There was less insulin activation in Alzheimer’s cases than in tissue from people who had died without brain disease. Other proteins linked to insulin action in the brain were abnormal in Alzheimer’s disease samples. These abnormalities were highly correlated with episodic memory and other cognitive disabilities in the Alzheimer’s disease patients.

In tissue from people with Alzheimer’s disease and mild cognitive impairment (MCI), researchers found that changes to a protein called insulin receptor substrate-1 (IRS-1 pS636/639 and pS616) in brain cells were linked to the severity of memory impairments regardless of age, sex, diabetes history, or apolipoprotein E (APOE) gene status. Levels of IRS-1 were also significantly associated with, but not likely to affect, the presence of amyloid beta plaques and neurofibrillary tangles, the signature markers of Alzheimer’s disease. This suggests that insulin resistance contributes to cognitive decline independent of the classical pathology of Alzheimer’s disease.

Researchers noted that three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer’s disease and MCI. “Clinical trials would need to be conducted to determine the impact the drugs have on Alzheimer’s disease and MCI in non-diabetic patients,” said Dr. Arnold.

Source: Science Daily

March 23, 2012

One cup or two faces? What we believe we see in one of the most famous optical illusions changes in a split second; and so does the path that the information takes in the brain. In a new theoretical study, scientists of the Max Planck Institute for Dynamics and Self-Organization, the Bernstein Center Göttingen and the German Primate Center now show how this is possible without changing the cellular links of the network. The direction of information flow changes, depending on the time pattern of communication between brain areas. This reorganisation can be triggered even by a slight stimulus, such as a scent or sound, at the right time.

The way how the different regions of the brain are connected with each other plays a significant role for information processing. This processing can be changed by the assembling and disassembling of nerve fibres joining distant brain circuits. But such events are much too slow to explain rapid changes in perception. From experimental studies it was known that the responsible actions must be at least two orders of magnitude faster. The Göttingen scientists now show for the first time that it is possible to change the information flow in a tightly interconnected network in a simple manner.

Many areas of the brain display a rhythmic nerve cell activity. “The interacting brain areas are like metronomes that tick at the same speed and in a distinct temporal pattern,” says the physicist and principal investigator Demian Battaglia. The researchers were now able to demonstrate that this temporal pattern determines the information flow. “If one of the metronomes is affected, e.g. through an external stimulus, then it changes beat, ticking in an altered temporal pattern compared to the others. The other areas adapt to this new situation through self-organisation and start playing a different drum beat as well. It is therefore sufficient to impact one of the areas in the network to completely reorganize its functioning, as we have shown in our model,” explains Battaglia.

The applied perturbation does not have to be particularly strong. “It is more important that the ‘kick’ occurs at exactly the right time of the rhythm,” says Battaglia. This might play a significant role for perception processes: “When viewing a picture, we are trained to recognize faces as quickly as possible – even if there aren’t any,” points out the Göttingen researcher. “But if we smell a fragrance reminiscent of wine, we immediately see the cup in the picture. This allows us to quickly adjust to things that we did not expect, changing the focus of our attention.”

Next, the scientists want to test the model on networks with a more realistic anatomy. They also hope that the findings inspire future experimental studies, as Battaglia says: “It would be fantastic if, in some years, certain brain areas could be stimulated so finely and precisely that the theoretically predicted effects can be measured through imaging methods.”

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

ScienceDaily (Mar. 22, 2012) — Anxious people have a heightened sense of smell when it comes to sniffing out a threat, according to a new study by Elizabeth Krusemark and Wen Li from the University of Wisconsin-Madison in the US.

In animals, the sense of smell is an essential tool to detect, locate and identify predators in the surrounding environment. In fact, the olfactory-mediated defense system is so prominent in animals, that the mere presence of predator odors can evoke potent fear and anxiety responses.

Smells also evoke powerful emotional responses in humans. Krusemark and Li hypothesized that in humans, detection of a particular bad smell may signal danger of a noxious airborne substance, or a decaying object that carries disease.

Their work is published online in Springer’s journal Chemosensory Perception. The study is part of a special issue of this journal on neuroimaging the chemical senses.

The researchers exposed 14 young adult participants to three types of odors: neutral pure odor, neutral odor mixture, and negative odor mixture. They asked them to detect the presence or absence of an odor in an MRI scanner. During scanning, the researchers also measured the skin’s ability to conduct electricity (a measure of arousal level) and monitored the subjects’ breathing patterns. Once the odor detection task was over, and the subjects were still in the scanner, they were asked to rate their current level of anxiety. The authors then analyzed the brain images obtained.

They found that as anxiety levels rose, so did the subjects’ ability to discriminate negative odors accurately — suggesting a ‘remarkable’ olfactory acuity to threat in anxious subjects. The skin conductance results showed that anxiety also heightened emotional arousal to smell-induced threats.

The authors uncovered amplified communication between the sensory and emotional areas of the brain in response to negative odors, particularly in anxiety. This increased connectivity could be responsible for the heightened arousal to threats.

Krusemark and Li conclude: “This enhanced sensory-emotional coupling could serve as a critical mechanism to arouse adequate physiological alertness to potential insults.”

Source: Science Daily

March 22, 2012

Scripps Research Institute scientists and their colleagues have successfully harnessed neurons in mouse brains, allowing them to at least partially control a specific memory. Though just an initial step, the researchers hope such work will eventually lead to better understanding of how memories form in the brain, and possibly even to ways to weaken harmful thoughts for those with conditions such as schizophrenia and post traumatic stress disorder.

The results are reported in the March 23, 2012 issue of the journal Science.

Researchers have known for decades that stimulating various regions of the brain can trigger behaviors and even memories. But understanding the way these brain functions develop and occur normally—effectively how we become who we are—has been a much more complex goal.

"The question we’re ultimately interested in is: How does the activity of the brain represent the world?" said Scripps Research neuroscientist Mark Mayford, who led the new study. "Understanding all this will help us understand what goes wrong in situations where you have inappropriate perceptions. It can also tell us where the brain changes with learning."

On-Off Switches and a Hybrid Memory

As a first step toward that end, the team set out to manipulate specific memories by inserting two genes into mice. One gene produces receptors that researchers can chemically trigger to activate a neuron. They tied this gene to a natural gene that turns on only in active neurons, such as those involved in a particular memory as it forms, or as the memory is recalled. In other words, this technique allows the researchers to install on-off switches on only the neurons involved in the formation of specific memories.

For the study’s main experiment, the team triggered the “on” switch in neurons active as mice were learning about a new environment, Box A, with distinct colors, smells and textures.

Next the team placed the mice in a second distinct environment—Box B—after giving them the chemical that would turn on the neurons associated with the memory for Box A. The researchers found the mice behaved as if they were forming a sort of hybrid memory that was part Box A and part Box B. The chemical switch needed to be turned on while the mice were in Box B for them to demonstrate signs of recognition. Alone neither being in Box B nor the chemical switch was effective in producing memory recall.

"We know from studies in both animals and humans that memories are not formed in isolation but are built up over years incorporating previously learned information," Mayford said. "This study suggests that one way the brain performs this feat is to use the activity pattern of nerve cells from old memories and merge this with the activity produced during a new learning session."

Future Manipulation of the Past

The team is now making progress toward more precise control that will allow the scientists to turn one memory on and off at will so effectively that a mouse will in fact perceive itself to be in Box A when it’s in Box B.

Once the processes are better understood, Mayford has ideas about how researchers might eventually target the perception process through drug treatment to deal with certain mental diseases such as schizophrenia and post traumatic stress disorder. With such problems, patients’ brains are producing false perceptions or disabling fears. But drug treatments might target the neurons involved when a patient thinks about such fear, to turn off the neurons involved and interfere with the disruptive thought patterns.

Provided by The Scripps Research Institute

Source: medicalxpress.com

ScienceDaily (Mar. 21, 2012) — Scientists at the Stanford University School of Medicine have shown for the first time how brain function differs in people who have math anxiety from those who don’t.

A series of scans conducted while second- and third-grade students did addition and subtraction revealed that those who feel panicky about doing math had increased activity in brain regions associated with fear, which caused decreased activity in parts of the brain involved in problem-solving.

"The same part of the brain that responds to fearful situations, such as seeing a spider or snake, also shows a heightened response in children with high math anxiety," said Vinod Menon, PhD, the Stanford professor of psychiatry and behavioral sciences who led the research.

In their new study, published online March 20 in Psychological Science, a journal of the Association for Psychological Science, Menon’s team performed functional magnetic resonance imaging brain scans on 46 second- and third-grade students with low and high math anxiety. Outside the fMRI scanner, the children were assessed for math anxiety with a modified version of a standardized questionnaire for adults, and also received standard intelligence and cognitive tests.

Read More →

ScienceDaily (Mar. 21, 2012) — Healthy individuals who carry a gene variation linked to an increased risk of autism have structural differences in their brains that may help explain how the gene affects brain function and increases vulnerability for autism. The results of this innovative brain imaging study are described in an article in the groundbreaking neuroscience journal Brain Connectivity, a bimonthly peer-reviewed publication from Mary Ann Liebert, Inc. The article is available free online at the Brain Connectivity website.

"This is one of the first papers demonstrating a linkage between a particular gene variant and changes in brain structure and connectivity in carriers of that gene," says Christopher Pawela, PhD, Co-Editor-in-Chief and Assistant Professor, Medical College of Wisconsin. "This work could lead to the creation of an exciting new line of research investigating the impact of genetics on communication between brain regions."

Although carriers of the common gene variant CNTNAP2 — identified as an autism risk gene — may not develop autism, there is evidence of differences in brain structure that may affect connections and signaling between brain regions. These disruptions in brain connectivity can give rise to functional abnormalities characteristic of neuropsychological disorders such as autism.

Emily Larson Dennis, Neda Jahanshad, Jeffrey D Rudie, Jesse A Brown, Kori Johnson, Katie McMahon, Greig de Zubicaray, Grant Montgomery, Nicholas Martin, Margaret Wright, Susan Bookheimer, Mirella Dapretto, Arthur Toga, Paul Thompson. Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2. Brain Connectivity, 2012; 120229030236004 DOI: 10.1089/brain.2011.0064

Source: Science Daily

ScienceDaily (Mar. 21, 2012) — Why does inhaling anesthetics cause unconsciousness? New insights into this century-and-a-half-old question may spring from research performed at the National Institute of Standards and Technology (NIST). Scientists from NIST and the National Institutes of Health have found hints that anesthesia may affect the organization of fat molecules, or lipids, in a cell’s outer membrane — potentially altering the ability to send signals along nerve cell membranes.

"A better fundamental understanding of inhaled anesthetics could allow us to design better ones with fewer side effects," says Hirsh Nanda, a scientist at the NIST Center for Neutron Research (NCNR). "How these chemicals work in the body is a scientific mystery that stretches back to the Civil War."

At the turn of the 20th century, doctors suspected inhaled anesthetics had some effect on cell membranes, an animal cell’s outer boundary. Despite considerable investigation, however, no one was able to demonstrate that anesthetics produced changes in the physical properties of membranes large enough to cause anesthesia. But eventually, understanding of membrane function grew more refined as scientists learned more about ion channels.

Ion channels — large proteins embedded in the relatively small lipid molecules forming the membrane — are responsible for conducting electrical impulses along nerve cells in the brain and throughout our body. By a few decades ago, the prevailing theory held that inhaled anesthetics directly interacted with these protein channels, affecting their behavior in some fashion. But no one could find a single type of ion channel that reacted to anesthetics in a way pivotal enough to settle the matter, and the question remained open.

"That’s where we picked up the thread," says Nanda. "We had been looking at how different types of lipid molecules affect ion channels."

While a cell membrane is a highly fluid film made of many different kinds of lipid molecules, the region immediately surrounding an ion channel often consists of a single type of lipids that form a sort of “raft” that is more ordered and less fluid then the rest of the membrane. When the team heard other researchers had found that disrupting these lipid rafts could affect a channel’s function, they put to work their own previous experience working with the channels.

"We decided to test whether inhaled anesthetics could have an effect on rafts in model cell membranes," Nanda says. "No one had thought to ask the question before."

Using the NCNR’s neutron and X-ray diffraction devices as their microscope, the team explored how a model cell membrane responded to two chemicals — inhaled anesthetic, and another that has many of the same chemical properties as anesthetic but does not cause unconsciousness. Their finding showed a distinct difference in the way the lipid rafts responded: Exposing the membranes to an anesthetic caused the rafts to grow disorderly, freely mixing its lipids with the surrounding membrane, but the second chemical had a dramatically smaller effect.

While Nanda says the discovery does not answer the question definitively, he and his co-authors are following up with other experiments that could clarify the issue. “We feel the discovery has opened up an entirely new line of inquiry into this very old puzzle,” he says.

Source: Science Daily

March 21, 2012

Scientists from Germany discovered new functions of brain regions that are responsible for seeing movement.

When observing a fly buzzing around the room, we should have the impression that it is not the fly, but rather the space that lies behind it that is moving. After all, the fly is always fixed in our central point of view. But how does the brain convey the impression of a fly in motion in a motionless field? With the help of functional magnetic resonance imaging (fMRI) scientists from the Werner Reichardt Centre for Integrative Neuroscience and the Max Planck Institute for Biological Cybernetics in Tübingen have identified two areas of the brain that compare the movements of the eye with the visual movements cast onto the retina so as to correctly perceive objects in motion.

The two areas of the brain that are particularly good at reacting to external movements, even during eye movements, are known as V3A and V6. They are located in the upper half in the posterior part of the brain. Area V3A shows a high degree of integration: it reacts to movements around us regardless of whether or not we follow the moving object with our eyes. But the area does not react to visual movements on the retina when eye movements produce them. Area V6 has similar characteristics. In addition, it can perform these functions when we are moving forwards. The calculations the brain has to perform are more complicated in this case: the three-dimensional, expanding forward movement is superimposed onto the two-dimensional lateral movements that are caused by eye movements.

The scientists Elvira Fischer and Andreas Bartels from the Werner Reichardt Centre for Integrative Neuroscience and the Max Planck Institute for Biological Cybernetics have investigated these areas with the help of functional magnetic resonance imaging (fMRI). fMRI is a procedure that can measure brain activity based on local changes in blood flow and oxygen consumption. Participants in the study were shown various visual scenarios whilst undergoing fMRI scanning. For example, they had to follow a small dot with their eyes while it moved across a screen from one side to the other. The patterned background was either stationary or moved at varying speeds, sometimes slower, faster or at the same speed as the dot. Sometimes the dot was stationary while only the background moved. In a total of six experiments the scientists measured brain activity in more than a dozen different scenarios. From this they have been able to discover that V3A and V6, unlike other visual areas in the brain, have a pronounced ability to compare eye movements with the visual signals on the retina. “I am especially fascinated by V3A because it reacts so strongly and selectively to movements in our surroundings. It sounds trivial, but it is an astonishing capability of the brain”, explains Andreas Bartels, project leader of the study.

Whether it is ourselves who move or something else in our surroundings is a problem about which we seldom think, since at the subconscious level our brain constantly calculates and corrects our visual impression. Indeed, patients who have lost this ability to integrate movements in their surroundings with their eye movements can no longer recognize what it is that ultimately is moving: the surroundings or themselves. Every time they move their eyes these patients feel dizzy. Studies such as this bring us one step closer to an understanding of the causes of such illnesses.

Provided by Max-Planck-Gesellschaft

Source: medicalxpress.com

March 21, 2012

Amateurs have a new tool for conducting simple neuroscience experiments in their own garage: the SpikerBox.

As reported in the Mar. 21 issue of the open access journal PLoS ONE, the SpikerBox lets users amplify and listen to neurons’ electrical activity – like those in a cockroach leg or cricket torso – and is appropriate for use in middle or high school educational programs, or by amateurs.

The work was a project from Backyard Brains, a start-up company focused on developing neuroscience educational resources. In the paper, the authors, Timothy Marzullo and Gregory Gage, describe a sample experiment using a cockroach leg stuck with two needles and monitoring the electrical signals. They also provide instructions for using the SpikerBox to answer specific experimental questions, like how neurons carry information about touch, how the brain tells muscles to move, and how drugs affect neurons, and an online portal provides further instructional materials. These are just a few examples of the many ways this tool can be used.

"Our mission is to lower the barrier-to-entry for students interested in learning about the brain. We hope our manuscript finds its way into the hands of high school teachers around the world", says Dr. Marzullo.

Provided by Public Library of Science

Source: medicalxpress.com

March 21, 2012

(Medical Xpress) — People who lose their sight at a later stage in life have a greater spatial awareness than if they were born blind, according to scientists at Queen Mary, University of London.

The study, published in the journal Neuroscience and Biobehavioral Reviews, examined research which looked at the spatial skills of sighted and blind people and found that some spatial tasks need visual experience.

Co-author on the study, Dr. Michael Proulx from Queen Mary’s School of Biological and Chemical Sciences, said: “Numerous studies have tested how humans use vision for knowing the spatial locations of things yet few have examined the other senses and whether people with a visual impairment use the same strategies.

“In reviewing research already available, we found visual experience is necessary for the brain to develop the ability to process multisensory information. We use vision and the other senses to create a mental map of where objects are in relation to other objects and the environment.

“Our findings suggest that there is a sensitive period during which visual experience is necessary for the brain to develop those neurons that can represent the world in this way.”

Lead author Dr. Achille Pasqualotto, also from Queen Mary’s School of Biological and Chemical Sciences, said: “Blindness reveals how well humans can function using the remaining senses, even in a world designed by sighted people for sighted people.

“The brain develops spatial abilities that relate an object’s location to the individual. This makes sense given that a visually impaired person does not see objects at a distance in an environment, but instead acquires their location by personally approaching and identifying them.”

The team is building on their findings now by testing sighted and blind people on a variety of spatial tasks that will explicitly test these findings.

They hope this research will not only reveal the psychological and neural basis for spatial cognition, but also translate into better services for blind persons, such as the development of better navigational tools.

Dr. Proulx said: “We are actively recruiting blind people to participate in our research and we are particularly keen to involve people who have been blind since birth, yet people who lost vision later in life would be welcome to contact us too.”

Provided by Queen Mary, University of London

Source: medicalxpress.com

March 21, 2012

Research at the University of Calgary’s Hotchkiss Brain Institute (HBI) has demonstrated the novel expression of an ion channel in Purkinje cells – specialized neurons in the cerebellum, the area of the brain responsible for movement. Ray W. Turner, PhD, Professor in the Department of Cell Biology & Anatomy and PhD student Jordan Engbers and colleagues published this finding in the January edition of the journal Proceedings of the National Academy of Sciences (PNAS).

This research identifies for the first time that an ion channel called KCa3.1 that was not previously believed to be expressed in the brain is actually present in Purkinje cells. In addition, these researchers demonstrate the mechanism by which this ion channel allows Purkinje cells to filter sensory input in order to coordinate the body’s movements.

The discovery was unexpected, as Engbers explains, “we didn’t specifically go looking for this channel. A lot of time was spent trying to identify the source for an electrical current that we were observing and we finally found ourselves asking ‘what evidence is there that KCa3.1 isn’t in the brain?’ So we ran some tests and all the pieces really fell into place.”

In the cerebellum, sensory input activates neurons called Purkinje cells that have to filter the information and respond only to relevant inputs to produce an appropriate movement response. Although this function of Purkinje cells has been well documented, Engbers and Turner take our understanding a step further by demonstrating that the KCa3.1 ion channel plays a key part in this process - acting as a gatekeeper to filter the enormous amount of incoming information.

As Turner explains, “these cells receive hundreds of thousands of signals every second from the body’s sensory systems. KCa3.1 then allows the cells to filter out the background noise and respond to only the three or four inputs that are particularly relevant”.

Engbers further describes the mechanism by which KCa3.1 filters out the unwanted information, “these channels are activated by an influx of calcium, which generates an inhibitory influence until the correct input is detected. Once the appropriate input is detected, the Purkinje cell responds with a burst of nerve impulses, which in turn initiates the proper motor response.”

This research fills a substantial gap in understanding how neurons in the cerebellum process information. Engbers and Turner expect that continued research will identify KCa3.1 in other areas of the brain and that it will be responsible for several still unexplained phenomena observed in neuronal recordings.

"What we have found will help us understand how the cerebellum functions normally. Now that we have shown the scientific community this new information, we expect that it will become clear that KCa3.1 plays a much wider role in brain function," says Engbers.

Provided by University of Calgary 

Source: medicalxpress.com

March 21, 2012

Researchers at Weill Cornell Medical College have developed a computer program that has tracked the manner in which different forms of dementia spread within a human brain. They say their mathematic model can be used to predict where and approximately when an individual patient’s brain will suffer from the spread, neuron to neuron, of “prion-like” toxic proteins — a process they say underlies all forms of dementia.

Their findings, published in the March 22 issue of Neuron, could help patients and their families confirm a diagnosis of dementia and prepare in advance for future cognitive declines over time. In the future — in an era where targeted drugs against dementia exist — the program might also help physicians identify suitable brain targets for therapeutic intervention, says the study’s lead researcher, Ashish Raj, Ph.D., an assistant professor of computer science in radiology at Weill Cornell Medical College.

"Think of it as a weather radar system, which shows you a video of weather patterns in your area over the next 48 hours," says Dr. Raj. "Our model, when applied to the baseline magnetic resonance imaging scan of an individual brain, can similarly produce a future map of degeneration in that person over the next few years or decades.

"This could allow neurologists to predict what the patient’s neuroanatomic and associated cognitive state will be at any given point in the future. They could tell whether and when the patient will develop speech impediments, memory loss, behavioral peculiarities, and so on," he says. "Knowledge of what the future holds will allow patients to make informed choices regarding their lifestyle and therapeutic interventions.

"At some point we will gain the ability to target and improve the health of specific brain regions and nerve fiber tracts," Dr. Raj says. "At that point, a good prediction of a subject’s future anatomic state can help identify promising target regions for this intervention. Early detection will be key to preventing and managing dementia." 

Tracking the Flow of Proteins

The computational model, which Dr. Raj developed, is the latest, and one of the most significant, validations of the idea that dementia is caused by proteins that spread through the brain along networks of neurons. It extends findings that were widely reported in February that Alzheimer’s disease starts in a particular brain region, but spreads further via misfolded, toxic “tau” proteins. Those studies, by researchers at Columbia University Medical Center and Massachusetts General Hospital, were conducted in mouse models and focused only on Alzheimer’s disease.

In this study, Dr. Raj details how he developed the mathematical model of the flow of toxic proteins, and then demonstrates that it correctly predicted the patterns of degeneration that results in a number of different forms of dementia.

He says his model is predicated on the recent understanding that all known forms of dementia are accompanied by, and likely caused by, abnormal or “misfolded” proteins. Proteins have a defined shape, depending on their specific function — but proteins that become misshapen can produce unwanted toxic effects. One example is tau, which is found in a misfolded state in the brains of both Alzheimer’s patients and patients with frontal temporal dementia (FTD). Other proteins, such as TDP43 and ubiquitin, are also found in FTD, and alpha synuclein is found in Parkinson’s disease.

These proteins are called “prion-like” because misfolded, or diseased, proteins induce the misfolding of other proteins they touch down a specific neuronal pathway. Prion diseases (such as mad cow disease) that involve transmission of misfolded proteins are thought to be infectious between people. “There is no evidence that Alzheimer’s or other dementias are contagious in that way, which is why their transmission is called prion-like.”

Simple Explanation for Clinically Observed Patterns of Dementia

Dr. Raj calls his model of trans-neuronal spread of misfolded proteins “very simple.” It models the same process by which any gas diffuses in air, except that in the case of dementias the diffusion process occurs along connected neural fiber tracts in the brain.

"This is a common process by which any disease-causing protein can result in a variety of dementias," he says.

The model identifies the neural sub-networks in the brain into which misfolded proteins will collect before moving on to other brain areas that are connected by networks of neurons. In the process the proteins alter normal functioning of all brain areas they visit.

"What is new and really quite remarkable is the network diffusion model itself, which acts on the normal brain connectivity network and manages to reproduce many known aspects of whole brain disease patterns in dementias," Dr. Raj says. "This provides a very simple explanation for why different dementias appear to target specific areas of the brain."

In the study, he was able to match patterns from the diffusion model, which traced protein disbursal in a healthy brain, to the patterns of brain atrophy observed in patients with either Alzheimer’s disease or FTD. This degeneration was measured using MRI and other tools that could quantify the amount of brain volume loss experienced in each region of the patient’s brain. Co-author Amy Kuceyeski, Ph.D., a postdoctoral fellow who works with Dr. Raj, helped analyze brain volume measurements in the diseased brains.

"Our study demonstrates that such a spreading mechanism leads directly to the observed patterns of atrophy one sees in various dementias," Dr. Raj says. "While the classic patterns of dementia are well known, this is the first model to relate brain network properties to the patterns and explain them in a deterministic and predictive manner."

Provided by New York- Presbyterian Hospital

Source: medicalxpress.com

March 21, 2012

Alzheimer’s disease and other forms of dementia may spread within nerve networks in the brain by moving directly between connected neurons, instead of in other ways proposed by scientists, such as by propagating in all directions, according to researchers who report the finding in the March 22 edition of the journal Neuron.

Led by neurologist and MacArthur Foundation “genius award” recipient William Seeley, MD, from the UCSF Memory and Aging Center, and post-doctoral fellow Helen Juan Zhou, PhD, now a faculty member at Duke-NUS Graduate Medical School in Singapore, the researchers concluded that a nerve region’s connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to the spread of disease in some of the most common forms of dementia, including Alzheimer’s disease.

The finding, based on new magnetic resonance imaging research (MRI), raises hopes that physicians may be able to use MRI to predict the course of dementias – depending on where within an affected network degenerative damage is first discovered – and that researchers may use these predicted outcomes to determine whether a new treatment is working. Network modeling combined with functional MRI might serve as an intermediate biomarker to gauge drug efficacy in clinical trials before behavioral changes become measurable, according to Seeley.

"Our next goal is to further develop methods to predict disease progression, using these models to create a template for how disease will progress in the brain of an affected individual," Seeley said. "Already this work suggests that if we know the wiring diagram in a healthy brain, we can predict where the disease is going to go next. Once we can predict how the network will change over time we can predict how the patient’s behavior will change over time and we can monitor whether a potential therapy is working."

The new evidence suggests that different kinds of dementias spread from neuron to neuron in similar ways, even though they act on different brain networks, according to Seeley. Seeley’s previous work and earlier clinical and anatomical studies showed that the patterns of damage in the dementias are linked to particular networks of nerve cells, but until now scientists have found it difficult to evaluate in humans their ideas about how this neurodegeneration occurs.

In the current study, the researchers modeled not only the normal nerve network that can be affected by Alzheimer’s disease, but also those networks affected by frontotemporal dementia (FTD) and related disorders, a class of degenerative brain diseases identified by their devastating impact on social behaviors or language skills.

The scientists mapped brain connectedness in 12 healthy people. Then they used data from patients with the five different diseases to map and compare specific regions within the networks that are damaged by the different dementias.

"For each dementia, we looked at four ideas that scientists often bring up to explain how dementia might target brain networks," Seeley said. "The different proposed mechanisms lead to different predictions about how a region’s place in the healthy network affects its vulnerability to disease."

In the “nodal stress” hypothesis, small regions within the brain that serve as hubs to carry heavy signaling traffic would undergo wear and tear that gives rise to or worsens disease. In the “trophic failure” mechanism, breakdowns in connectivity would disrupt transport through the network of growth factors needed to maintain neurons. In the “shared vulnerability” mechanism, specific genes or proteins common to neurons in a network would make them more susceptible to disease. But predictions from the “trans-neuronal spread” mechanism model best fit the network connectivity maps constructed by the researchers.

"The trans-neuronal spread model predicts that the more closely connected a region is to the node of disease onset – which we call the epicenter – then the more vulnerable that region will be once the disease begins to spread," Seeley said. "It’s as if the disease is emanating from a point of origin, but it can reach any given target faster if there is a stronger connection."

The scientists tracked and analyzed linkages within nerve networks that the dementias target. They used a technique called functional connectivity MRI to measure and spatially represent activity in specific regions of key networks in the brains of the healthy subjects. The MRI readout allowed the researchers to model each region within the network as a distinct but interconnected node. They ranked the nodes that most consistently fired together as being the most closely connected.

Across the five diseases investigated in the study, trans-neuronal spread was the proposed mechanism for which the data best matched the predictions. Previous studies of animals and cells in the laboratory also support the idea that disease-related proteins can spread from an affected neuron to other neurons via intercellular connections.

For more than three decades researchers have been noticing that regions affected by Alzheimer’s disease are connected by axons that branch between and connect neurons, Seeley said. Trans-neuronal spread is a proven hallmark of certain rare neurodegenerative diseases – such as Creutzfeldt-Jakob disease – that are propagated by misfolded cell-surface proteins called prions, which induce neighboring proteins to change shape, aggregate and wreak havoc.

While Alzheimer’s disease and FTD are not considered infectious, abnormal protein structures also are implicated in these common dementias. Recent experiments in which researchers transplanted post-mortem, human brain extracts from dementia patients into genetically modified mice have resulted in disease, Seeley said, “But it is difficult to explore these ideas in humans, and we wanted to begin to bridge this knowledge gap.”

Provided by University of California - San Francisco

Source: medicalxpress.com 

March 21, 2012

What characterizes many people with depression, schizophrenia and some other mental illnesses is anhedonia: an inability to gain pleasure from normally pleasurable experiences.

This image shows VTA dopamine neurons (in red) and VTA GABA fibers (in green). Credit: Stuber Lab, UNC-Chapel Hill.

Exactly why this happens is unclear. But new research led by neuroscientists at the University of North Carolina at Chapel Hill School of Medicine may have literally shined a light on the answer, one that could lead to the discovery of new mental health therapies. A report of the study appears March 22 in the journal Neuron.

The study used a combination of genetic engineering and laser technology to manipulate the wiring of a specific population of brain cells deep in a portion of a midbrain area that’s known to promote behavioral responses to reward.

"For many years it’s been known that dopamine neurons in the ventral midbrain, the ventral tegmental area, or VTA, are involved in reward processing and motivation. For example, they’re activated during exposure to drugs of abuse and to naturally rewarding experiences," said study lead author Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and Molecular Physiology, and the UNC Neuroscience Center.

"The major focus in our lab is to determine what other sorts of neural circuits or genetically defined neural populations might be modulating the activity of those neurons, whether it’s increasing or decreasing their activity," Stuber said. "In our study we found that activation of the nearby VTA GABAergic neurons directly inhibit the function of dopamine neurons, which is something that’s never been shown before."

In the past, researchers have tried to get a glimpse into the inner workings of the brain using electrical stimulation or drugs, but those techniques couldn’t quickly and specifically change only one type of cell or one type of connection. But optogenetics, a technique that emerged about six years ago, can. 

In this study, the scientists used a transgenic animal with a foreign gene that has been inserted into its genome to express a bacterial enzyme that can cause DNA recombination only in GABA neurons and not dopamine cells. Using a gene transfer method developed at UNC and with the animal anesthetized, the Stuber team transferred light-sensitive proteins called “opsins” – derived from algae or bacteria that need light to grow – into the VTA, targeting GABA cells. The presence of these foreign opsins in GABA neurons allows researchers to excite or inhibit them by pumping light from a laser into brain tissue.

The animals were then tested in different reward situations, simple tasks in which they were trained to associate a cue with a sugar water reward from a bottle or were given the opportunity to drink the reward by “free licking,” where they could drink as much as they want.

Then, via optical fibers, the researchers shined laser beams onto the genetically manipulated GABA neurons, activating them for 5 seconds during the cue period followed by reward. And on another day, they activated the neurons during reward consumption, when the animals were actively engaged in drinking the sugar water.

"And what we saw when we activated the cells during the cue period, or reward anticipation, it didn’t do anything to the behavioral response at all; they showed no difference compared to non-stimulated animals," Stuber explained.

"And when they were actively engaging with the sucrose, we did see we could disrupt their reward consumption when we activated those cells. They immediately disengaged from drinking, stopped drinking the sucrose solution. And when the stimulus stopped, they would then return back and continue to drink it again."

During the “free licking” sessions, optical stimulation of GABA neurons resulted in disruption of sucrose consumption. The animals stopped drinking.

Using sophisticated electrophysiology and cell chemistry measures, the study team could monitor the activity of the GABA and dopamine neurons. They found a direct link between GABA activation and dopamine suppression.

"So basically, it appears that these GABA neurons located in the VTA are just microns away from dopamine and are negative regulators of dopamine function," Stuber proposes.

"When they become active, their basic job is to suppress dopamine release. A dysfunction in these GABA neurons might potentially underlie different aspects of neuropsychiatric illness, such as depression. Thus, we could think of them as a new physiological target for various aspects of neuropsychiatric diseases."

Provided by University of North Carolina School of Medicine

March 21, 2012

Investigators at the Stanford University School of Medicine have shown that removing a matched set of molecules that typically help to regulate the brain’s capacity for forming and eliminating connections between nerve cells could substantially aid recovery from stroke even days after the event. In experiments with mice, the scientists demonstrated that when these molecules are not present, the mice’s ability to recover from induced strokes improved significantly.

Importantly, these beneficial effects grew over the course of a full week post-stroke, suggesting that, in the future, treatments such as drugs designed to reproduce the effects in humans might work even if given as much as several days after a stroke occurs. The only currently available stroke treatment — tissue plasminogen activator, or tPA — must be given within a few hours of a stroke to be effective, and patients’ brains must first be scanned to determine whether this treatment is appropriate. Moreover, while tPA limits the initial damage caused by a stroke, it doesn’t help the brain restore or replace lost connections between nerve cells, which is essential to recovery.

The mice in the study had been genetically bioengineered to lack certain molecules that one of the Stanford researchers had previously shown to play a major role in modulating the ease with which key nerve-cell connections are made, strengthened, weakened or destroyed in the brain. The molecules in question include “K” and “D,” two of the 50 or so members of the so-called MHC class-1 complex, which plays a key role in the function of the immune system. Alternatively, when a receptor called PirB, which binds to these MHC molecules, is not present, the same improved outcome from stroke happens — significant, because receptors make good drug targets.

Read More →

March 20, 2012

A personality profile marked by overly gregarious yet anxious behavior is rooted in abnormal development of a circuit hub buried deep in the front center of the brain, say scientists at the National Institutes of Health. They used three different types of brain imaging to pinpoint the suspect brain area in people with Williams syndrome, a rare genetic disorder characterized by these behaviors. Matching the scans to scores on a personality rating scale revealed that the more an individual with Williams syndrome showed these personality/temperament traits, the more abnormalities there were in the brain structure, called the insula.

The severity of abnormalities in insula (red structure near bottom of brain), gray matter volume (left) and brain activity (right) predicted the extent of aberrant personality traits in Williams syndrome patients — as reflected in their scores (red dots) on personality rating scales (WSPP). Credit: Karen Berman, M.D., NIMH Clinical Brain Disorders Branch

"Scans of the brain’s tissue composition, wiring, and activity produced converging evidence of genetically-caused abnormalities in the structure and function of the front part of the insula and in its connectivity to other brain areas in the circuit," explained Karen Berman, M.D., of the NIH’s National Institute of Mental Health (NIMH).

Berman, Drs. Mbemda Jabbi, Shane Kippenham, and colleagues, report on their imaging study in Williams syndrome online in the journal Proceedings of the National Academy of Sciences.

"This line of research offers insight into how genes help to shape brain circuitry that regulates complex behaviors – such as the way a person responds to others – and thus holds promise for unraveling brain mechanisms in other disorders of social behavior," said NIMH Director Thomas R. Insel, M.D.

Long distance connections, white matter, between the insula and other parts of the brain are aberrant in Williams syndrome. Neuronal fibers of normal controls (left) extend further than those of Williams syndrome patients (right). Picture shows diffusion tensor imaging data from each patient superimposed on anatomical MRI of the median patient. Credit: Karen Berman, M.D., NIMH Clinical Brain Disorders Branch

Read More →

March 19th, 2012

Stowers researchers present a new model for how the brain is organized to process odor information.

Glomeruli in the olfactory bulb (shown in green), the first waystation for incoming olfactory signals, plays an important role in the processing and identification of smells. Image adapted from press release image courtesy of Limei Ma, Stowers Institute for Medical Research.

Just like a road atlas faithfully maps real-world locations, our brain maps many aspects of our physical world: Sensory inputs from our fingers are mapped next to each other in the somatosensory cortex; the auditory system is organized by sound frequency; and the various tastes are signaled in different parts of the gustatory cortex.

The olfactory system was believed to map similarly, where groups of chemically related odorants – amines, ketones, or esters, for example – register with clusters of cells that are laid out next to each other. When researchers at the Stowers Institute for Medical Research traced individual odor molecules’ signal deep into the brain, they found evidence that this “chemotopic” hypothesis of olfaction is insufficient, paving the way for a new model of how the sense of smell works, and how it came about.

“When we mapped the individual chemical features of different odorants, they mapped all over the olfactory bulb, which processes incoming olfactory information,” says Associate Investigator C. Ron Yu, PhD, who led the study published in this week’s online edition of the Proceedings of the National Academy of Sciences. “From the animal’s perspective that makes perfect sense. The chemical structure of an odor molecule is not what’s important to them. They really just want to learn about their environment and associate olfactory information with food or other relevant information.”

The brain receives information about odors from olfactory receptors, which are embedded in the membrane of sensory neurons in the nasal cavity. Any time an odor molecule interacts with a receptor, an electrical signal travels to so-called glomeruli in the olfactory bulb. Each glomerulus receives input from olfactory receptor neurons expressing only one type of olfactory receptor. The overall glomerular activation patterns within the olfactory bulb are thought to represent specific odors.

Read More →

March 19, 2012

Cerebral edemas are accumulations of fluid into the intra- or extracellular spaces of the brain and it can result from several factors such as stroke or head trauma, among others.

Cerebral edema is a serious problem in neurology. While in other organs swelling does not lead to an urgent situation, in the brain it leads to coma and death. Although there are therapeutic solutions such as surgery, more effective treatments are needed.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy (affects the white matter) of genetic origin. MLC can be considered as a model of chronic edema, as patients suffering from birth a high accumulation of water.

A study of the pathophysiology of this rare disease has uncovered one mechanism that destabilizes the homeostatic balance of brain cells causing edema. This study is published in the latest issue of the journal Neuron. The journal accompanies the paper with a commentary of the editor and an explanatory video on its website.

[Video]

Researchers from IDIBELL, the University of Barcelona (UB) and CIBERER (Spanish Network Research Centre on Rare Diseases) have found that one function of the protein GlialCAM, which is genetically altered in patients with MLC, is to regulate the activity of the channel that allows the passage of chloride ions between brain cells to regulate ion and fluid balance.

When this protein is lacked, the channel is not working properly and the fluid builds up in the brain glial cells forming edema.

Raul Estevez, director of this work, and Virginia Nunes, a partner of the study, believe that the importance of this finding is twofold. “On one hand”, explains Virginia Nunes, “it allows us to better understand the pathophysiology of this disease minority” and “on the other hand”, Raul Estevez continues, “we have identified a mechanism that can open doors to treatments based on the activation of this channel to restore homeostatic balance and perhaps treat brain edema in general.”

Both researchers agree to say that this case demonstrates that the investigation of a rare disease that affects a small proportion of the population can serve as a model to identify mechanisms to think of new treatments for common diseases.

MLC Leukodistophy

Megalencephalic Leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy that appears during the first year of life, characterized by macrocephaly (oversized head). A few years later, it appears a slow neurological deterioration with ataxia (lack of motor coordination) and spasms. Magnetic resonance techniques revealed inflammation of the cerebral white matter and subcortical cysts, particularly in the anterior temporal regions.

In the 75% of MLC patients it has been identified mutations in the gene MLC1, which cause the disease. Virginia Nunes and Raul Estevez have recently identified a second gene causing MLC, named GlialCAM.

In the present study they have been identified precisely a GlialCAM protein as an ion channel subunit chloride that allows its entering and exiting the brain so that the cells can regulate the homeostatic balance.

Provided by IDIBELL-Bellvitge Biomedical Research Institute

Source: medicalxpress.com

March 19, 2012

University of Alberta led research may have discovered how memories are encoded in our brains.

Scientists understand memory to exist as strengthened synaptic connections among neurons. However components of synaptic membranes are relatively short-lived and frequently re-cycled while memories can last a lifetime.

Based on this information, U of A physicist and lead researcher Jack Tuszynski, his graduate student Travis Craddock and University of Arizona professor Stuart Hameroff investigated the molecular mechanism of memory encoding in neurons.

The team looked into structures at the cytoskeletal level of brain structure. They found components that fit together and were capable of creating the information processing and storage capacity that the brain needs to form and retain memory.

The practical implications of understanding the mechanism of memory encoding are enormous.

"This could open up amazing new possibilities of dealing with memory loss problems, interfacing our brains with hybrid devices to augment and ‘refresh’ our memories," says Tuszynski. "More importantly, it could lead to new therapeutic and preventive ways of dealing with neurological diseases such as Alzheimer’s and dementia, whose incidence is growing very rapidly these days."

Provided by University of Alberta

Source: medicalxpress.com

March 19, 2012

Patients with relapsing onset Multiple Sclerosis (MS) who consumed alcohol, wine, coffee and fish on a regular basis took four to seven years longer to reach the point where they needed a walking aid than people who never consumed them. However the study, published in the April issue of the European Journal of Neurology, did not observe the same patterns in patients with progressive onset MS.

The authors say that the findings suggest that different mechanisms might be involved in how disability progresses in relapsing and progressive onset MS.

Researchers asked patients registered with the Flemish MS Society to take part in a survey, which included questions on themselves, their MS and their current consumption of alcohol, wine, coffee, tea, fish and cigarettes.

The 1,372 patients who agreed to take part were also asked to indicate whether they had reached stage six on the zero to ten stage Expanded Disability Status Scale (EDSS) and, if so, when this had happened.

"MS is a chronic, often disabling disease that attacks the central nervous system" explains lead author Dr Marie D’hooghe from the National MS Center at Melsbroek, Belgium. "The clinical symptoms, progression of disability and severity of MS are unpredictable and vary from one person to another.

"Two major MS onset types can be distinguished. Progressive onset MS is characterised by a gradual worsening of neurological function from the beginning, whereas patients with relapsing onset MS patients experience clearly defined attacks of worsening neurologic function with partial or full remission.

Read More →

March 19, 2012

An antioxidant combination of vitamin E, vitamin C and α-lipoic acid (E/C/ALA) was not associated with changes in some cerebrospinal fluid biomarkers related to Alzheimer disease in a randomized controlled trial, according to a study published Online First by Archives of Neurology.

Oxidative damage in the brain is associated with aging and is widespread in Alzheimer disease (AD) patients. Some observational studies have suggested that an antioxidant-rich diet may reduce the risk of AD, but antioxidant randomized clinical trials in AD have had mixed results, the authors write in their study background.

Douglas R. Galasko, M.D., of the University of California, San Diego, and colleagues examined changes in cerebrospinal fluid (CSF) biomarkers related to Alzheimer disease and oxidative stress, cognition and function.

The study included 78 patients from the Alzheimer’s Disease Cooperative Study (ADCS) Antioxidant Biomarker study who were divided into one of three groups: 800 IU/per day of vitamin E (α-tocopherol) plus 500 mg/per day of vitamin C plus 900 mg/per day of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q (CoQ) three times a day; or placebo. Sixty-six patients provided serial CSF specimens adequate for biochemical analyses during the 16-week trial.

"The combination of E/C/ALA did not affect CSF biomarkers related to Αβ, tau or P-tau (which are related to AD)," the authors comment.

The E/C/ALA group did see a lowering of CSF F2-isoprostane levels suggesting a reduction of oxidative stress in the brain, the results indicate. However, the treatment raised caution about faster cognitive decline as assessed by the Mini-Mental State Examination (MMSE).

"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD. The more rapid MMSE score decline raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered," the authors conclude.

The authors also note the results indicate that while CoQ was safe and well tolerated in patients, the absence of a biomarker signal in CSF suggests that CoQ, at the tested dose, does not improve indices of oxidative stress or neurodegeneration.

"These results do not support further clinical trial development of CoQ in AD," the researchers conclude.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

ScienceDaily (Mar. 19, 2012) — Researchers from Chalmers and the University of Gothenburg have shown that nanocellulose stimulates the formation of neural networks. This is the first step toward creating a three-dimensional model of the brain. Such a model could elevate brain research to totally new levels, with regard to Alzheimer’s disease and Parkinson’s disease, for example.

Nerve cells growing on a three-dimensional nanocellulose scaffold. One of the applications the research group would like to study is destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. Synapses are the connections between nerve cells. In the image, the functioning synapses are yellow and the red spots show where synapses have been destroyed. (Credit: Illustration: Philip Krantz, Chalmers)

Over a period of two years the research group has been trying to get human nerve cells to grow on nanocellulose.

"This has been a great challenge," says Paul Gatenholm, Professor of Biopolymer Technology at Chalmers.‟Until recently the cells were dying after a while, since we weren’t able to get them to adhere to the scaffold. But after many experiments we discovered a method to get them to attach to the scaffold by making it more positively charged. Now we have a stable method for cultivating nerve cells on nanocellulose."

When the nerve cells finally attached to the scaffold they began to develop and generate contacts with one another, so-called synapses. A neural network of hundreds of cells was produced. The researchers can now use electrical impulses and chemical signal substances to generate nerve impulses, that spread through the network in much the same way as they do in the brain. They can also study how nerve cells react with other molecules, such as pharmaceuticals.

The researchers are trying to develop ‟artificial brains,” which may open entirely new possibilities in brain research and health care, and eventually may lead to the development of biocomputers. Initially the group wants to investigate destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. For example, they would like to cultivate nerve cells and study how cells react to the patients’ spinal fluid.

In the future this method may be useful for testing various pharmaceutical candidates that could slow down the destruction of synapses. In addition, it could provide a better alternative to experiments on animals within the field of brain research in general.

The ability to cultivate nerve cells on nanocellulose is an important step ahead since there are many advantages to the material.

‟Pores can be created in nanocellulose, which allows nerve cells to grow in a three-dimensional matrix. This makes it extra comfortable for the cells and creates a realistic cultivation environment that is more like a real brain compared with a three-dimensional cell cultivation well,” says Paul Gatenholm.

Paul Gatenholm says that there are a number of new biomedical applications for nanocellulose. He is currently also leading other projects that use the material, for example a project where researchers are using nanocellulose to develop cartilage to create artificial outer ears. His research group has previously developed artificial blood vessels made of nanocellulose, which are being evaluated in pre-clinical studies.

Research on new application areas for nanocellulose is of major strategic significance for Sweden. Several projects are financed by the Knut and Alice Wallenberg Foundation and being conducted in collaboration between Chalmers and KTH within the Wallenberg Wood Science Center, WWSC.

Facts about nanocellulose: Nanocellulose is a material that consists of nanosized cellulose fibers. Typical dimensions are widths of 5 to 20 nanometers and lengths of up to 2,000 nanometers. Nanocellulose can be produced by bacteria that spin a close-meshed structure of cellulose fibers. It can also be isolated from wood pulp through processing in a high-pressure homogenizer.

Source: Science Daily

March 16, 2012 By Anne Trafton 

Alan Jasanoff. Credit: Allegra Boverman

After finishing his PhD in molecular biophysics, Alan Jasanoff decided to veer away from that field and try looking into some of the biggest questions in neuroscience: How do we perceive things? What happens in our brains when we make decisions?

After a few months, however, he realized that he didn’t have the tools he wanted to use — so he decided to start making his own.

Jasanoff, who recently earned tenure in MIT’s Department of Biological Engineering, now specializes in developing novel brain-imaging agents that can reveal information more detailed than other human brain-imaging techniques such as fMRI and PET, and more comprehensive than traditional neuroscience measurements such as microscopy and electrode recordings. With the new tools, he is also beginning to explore some of the fundamental questions that first drew him into neuroscience.

Neuroscientists commonly use fMRI, which measures blood flow in the brain, as a proxy for neural activity. In the past several years, Jasanoff has developed sensors that can be used with fMRI to image brain activity more directly, by measuring levels of neurotransmitters (the chemicals that carry messages between neurons) and calcium, which enters neurons when they fire.

Using those sensors, Jasanoff has started exploring how positive reinforcement influences behavior and decision making in animals. His work could also be applicable to fields outside of neuroscience, because intracellular signaling molecules such as calcium “are really ubiquitous — not just in neuronal signaling but signaling throughout the body, during development, immune-cell activity and so on,” says Jasanoff, who is an associate member of MIT’s McGovern Institute for Brain Research and an associate professor of biological engineering, nuclear science and engineering, and brain and cognitive sciences.

[Video]

Read More →

March 16, 2012

Distinct patterns of activity— which may indicate a predisposition to care for infants — appear in the brains of adults who view an image of an infant face — even when the child is not theirs, according to a study by researchers at the National Institutes of Health and in Germany, Italy, and Japan.

Seeing images of infant faces appeared to activate in the adult’s brains circuits that reflect preparation for movement and speech as well as feelings of reward.

The findings raise the possibility that studying this activity will yield insights into care giving behavior, but also in cases of child neglect or abuse.

"These adults have no children of their own. Yet images of a baby’s face triggered what we think might be a deeply embedded response to reach out and care for that child," said senior author Marc H. Bornstein, Ph.D., head of the Child and Family Research Section of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NIH institute that collaborated on the study.

While the researchers recorded participants’ brain activity, the participants did not speak or move. Yet their brain activity was typical of patterns preceding such actions as picking up or talking to an infant, the researchers explained. The activity pattern could represent a biological impulse that governs adults’ interactions with small children.

Read More →

March 15th, 2012

Researchers have identified the first gene mutation associated with a chronic and often fatal form of neuroblastoma that typically strikes adolescents and young adults. The finding provides the first clue about the genetic basis of the long-recognized but poorly understood link between treatment outcome and age at diagnosis.

The study involved 104 infants, children and young adults with advanced neuroblastoma, a cancer of the sympathetic nervous system. Investigators discovered the ATRX gene was mutated only in patients age 5 and older. The alterations occurred most often in patients age 12 and older. These older patients were also more likely than their younger counterparts to have a chronic form of neuroblastoma and die years after their disease is diagnosed.

The findings suggest that ATRX mutations might represent a new subtype of neuroblastoma that is more common in older children and young adults. The work is from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project (PCGP). The study appears in the March 14 edition of the Journal of the American Medical Association.

If validated, the results may change the way doctors think about this cancer, said co-author Richard Wilson, PhD, director of The Genome Institute at Washington University School of Medicine in St. Louis.

“This suggests we may need to think about different treatment strategies for patients depending on whether or not they have the ATRX mutation,” he says.

Neuroblastoma accounts for 7 percent to 10 percent of all childhood cancers and about 15 percent of pediatric cancer deaths. In about 50 percent of patients, the disease has already spread when the cancer is discovered.

Read More →

March 15, 2012

In Batten disease, a rare but fatal neurodegenerative disorder in infants and children, proteins (shown in pink) accumulate in the brain and contribute to mental decline, paralysis and seizures. In mice with the infantile form of the disease, combination treatment with gene therapy and bone marrow transplantation reduced the buildup of proteins, dramatically increasing life span and improving motor function. Credit: Mark Sands, Ph.D

Infants with Batten disease, a rare but fatal neurological disorder, appear healthy at birth. But within a few short years, the illness takes a heavy toll, leaving children blind, speechless and paralyzed. Most die by age 5.

There are no effective treatments for the disease, which can also strike older children. And several therapeutic approaches, evaluated in mouse models and in young children, have produced disappointing results.

But now, working in mice with the infantile form of Batten disease, scientists at Washington University School of Medicine in St. Louis and Kings College London have discovered dramatic improvements in life span and motor function by treating the animals with gene therapy and bone marrow transplants.

The results are surprising, the researchers say, because the combination therapy is far more effective than either treatment alone. Gene therapy was moderately effective in the mice, and bone marrow transplants provided no benefit, but together the two treatments created a striking synergy.

The research is online in the Annals of Neurology.

Read More →

ScienceDaily (Mar. 15, 2012) — Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner?

Odds are, you’re not going to make it all the way through this article without thinking about something else. In fact, studies have found that our minds are wandering half the time, drifting off to thoughts unrelated to what we’re doing — did I remember to turn off the light? What should I have for dinner? (Credit: © Yuri Arcurs / Fotolia)

A new study investigating the mental processes underlying a wandering mind reports a role for working memory, a sort of a mental workspace that allows you to juggle multiple thoughts simultaneously.

Imagine you see your neighbor upon arriving home one day and schedule a lunch date. On your way to add it to your calendar, you stop to turn off the drippy faucet, feed the cat, and add milk to your grocery list. The capacity that allows you to retain the lunch information through those unrelated tasks is working memory.

The new study, published online March 14 in the journal Psychological Science by Daniel Levinson and Richard Davidson at the University of Wisconsin-Madison and Jonathan Smallwood at the Max Planck Institute for Human Cognitive and Brain Science, reports that a person’s working memory capacity relates to the tendency of their mind to wander during a routine assignment. Lead author Levinson is a graduate student with Davidson, a professor of psychology and psychiatry, in the Center for Investigating Healthy Minds at the UW-Madison Waisman Center.

Read More →

ScienceDaily (Mar. 14, 2012) — The meal is pushed way, untouched. Loss of appetite can be a fleeting queasiness or continue to the point of emaciation. While it’s felt in the gut, more is going on inside the head.

New findings are emerging about brain and body messaging pathways that lead to loss of appetite, and the systems in place to avoid starvation.

Today, scientists report in Nature about a brain circuit that mediates the loss of appetite in mice. The researchers also discovered potential therapeutic targets within the pathway. Their experimental results may be valuable for developing new treatments for a variety of eating disorders. These include unrelenting nausea, food aversions, and anorexia nervosa, a condition in which a person no longer wants to eat enough to maintain a normal weight.

The senior author of the paper is Dr. Richard D. Palmiter, University of Washington professor of biochemistry and an investigator with the Howard Hughes Medical Institute. His co-authors are Dr. Qi Wu, formerly of the UW and now at the Eagles Diabetes Research Center and Department of Pharmacology at Carver College of Medicine, University of Iowa, and Dr. Michael S. Clark of the UW Department of Psychiatry and Behavioral Sciences. Palmiter is known for co-developing the first transgenic mice in the 1980s with Dr. Ralph Brinster at the University of Pennsylvania. His more recent studies are of chemicals that nerve cells use to communicate with each other, their roles in mouse brain development and function, and their relation to behavior.

Read More →

ScienceDaily (Mar. 14, 2012) — The difficulties that many women describe as memory problems when menopause approaches are real, according to a study published recently  in the journal Menopause, the journal of the North American Menopause Society.

The findings won’t come as a surprise to the millions of women who have had bouts of forgetfulness or who describe struggles with “brain fog” in their late 40s and 50s. But the results of the study, by scientists at the University of Rochester Medical Center and the University of Illinois at Chicago who gave women a rigorous battery of cognitive tests, validate their experiences and provide some clues to what is happening in the brain as women hit menopause.

"The most important thing to realize is that there really are some cognitive changes that occur during this phase in a woman’s life," said Miriam Weber, Ph.D., the neuropsychologist at the University of Rochester Medical Center who led the study. "If a woman approaching menopause feels she is having memory problems, no one should brush it off or attribute it to a jam-packed schedule. She can find comfort in knowing that there are new research findings that support her experience. She can view her experience as normal."

The study is one of only a handful to analyze in detail a woman’s brain function during menopause and to compare those findings to the woman’s own reports of memory or cognitive difficulties.

Read More →

ScienceDaily (Mar. 14, 2012) — People with symptoms suggesting rapid eye movement sleep behavior disorder, or RBD, have twice the risk of developing mild cognitive impairment (MCI) or Parkinson’s disease within four years of diagnosis with the sleep problem, compared with people without the disorder, a Mayo Clinic study has found.

The researchers published their findings recently in the Annals of Neurology.

One of the hallmarks of rapid eye movement (REM) sleep is a state of paralysis. In contrast, people with rapid eye movement sleep behavior disorder, appear to act out their dreams when they are in REM sleep. Researchers used the Mayo Sleep Questionnaire to diagnose probable RBD in people who were otherwise neurologically normal. Approximately 34 percent of people diagnosed with probable RBD developed MCI or Parkinson’s disease within four years of entering the study, a rate 2.2 times greater than those with normal rapid eye movement sleep.

"Understanding that certain patients are at greater risk for MCI or Parkinson’s disease will allow for early intervention, which is vital in the case of such disorders that destroy brain cells. Although we are still searching for effective treatments, our best chance of success is to identify and treat these disorders early, before cell death," says co-author Brad Boeve, M.D., a Mayo Clinic neurologist.

Previous studies of Mayo Clinic patients have shown that an estimated 45 percent of people who suffer from RBD will develop a neurodegenerative syndrome such as mild cognitive impairment or Parkinson’s disease within five years of diagnosis.

RBD, MCI and Parkinson’s Disease

"This study is the first to quantify the risk associated with probable RBD in average people, not clinical patients, and it shows that we can predict the onset of some neurodegenerative disorders simply by asking a few critical questions," says lead author Brendon P. Boot, M.D., a behavioral neurologist. Dr. Boot was at Mayo Clinic when the study was conducted. He is now at Harvard University.

• MCI is an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. It involves problems with memory, language, thinking and judgment that are greater than typical age-related changes.
• An estimated 500,000 Americans suffer from Parkinson’s disease, which is characterized by tremor or shakiness, stiffness of the limbs and trunk, slowness of movement, and impaired balance and coordination. 

Source: Science Daily

ScienceDaily (Mar. 14, 2012) — How are 100 billion cells created, each with specific duties? The human brain is evidence that nature can achieve this. Researchers at Linköping University in Sweden have now taken a step closer to solving this mystery.

The magenta-colored structures are nerve cells that use odourant receptor 47b, which senses pheromones. Expression of this receptor is controlled by the transcription factor E93. When E93 is removed, the neurons lose their ability to fulfill their task do detect pheromones, as evidenced by the deactivation of the fluorescent proteins (image to the right). The glowing, green cells, that use olfactory receptor 92a, are not affected because they are controlled by other transcription factors. (Credit: Image courtesy of Linkoeping Universitet)

"Knowledge about the mechanisms that diversify neurons and keep them diverse is necessary in order to cultivate and replace nerve cells in the future," says Mattias Alenius, Assistant Professor of Neuroscience, who has published his research breakthrough in the current issue of the journal PLoS Biology.

Alenius and his research team at the Department of Experimental and Clinical Medicine seek the answer to this pivotal question from a smaller perspective: the fruit fly’s olfactory system.

The humble fly’s olfactory system consists of 1200 olfactory neurons (humans have six million) divided into 34 groups. Each group responds to a particular set of odours, since all the neurons of the group use only one of the olfactory receptors present in the fly’s antennas. Together, the receptors provide the fly with the ability to distinguish between thousands of odours: one olfactory receptor — one neuron group, simple yet complex.

Alenius and his colleagues are the first to go through all of the fruit fly’s 753 gene regulatory genes, called transcription factors. They have identified a set of seven that, in different combinations, are required to create each of the 34 neuron groups in the antenna. A surprising finding is that most transcription factors perform two tasks simultaneously: they can activate odorant receptors’ expression; while at the same time turning off others in the same cell.

Alenius explains, “This is one of the many tricks that are useful to know for the future if you want to make and cultivate each of the many thousands of nerve cell groups that make up our brains.”

Source: Science Daily