Posts tagged neuroscience
Articles and news from the latest research reports.
Brain waves encode rules for behavior
One of the biggest puzzles in neuroscience is how our brains encode thoughts, such as perceptions and memories, at the cellular level. Some evidence suggests that ensembles of neurons represent each unique piece of information, but no one knows just what these ensembles look like, or how they form.
A new study from researchers at MIT and Boston University (BU) sheds light on how neural ensembles form thoughts and support the flexibility to change one’s mind. The research team, led by Earl Miller, the Picower Professor of Neuroscience at MIT, identified groups of neurons that encode specific behavioral rules by oscillating in synchrony with each other.
The results suggest that the nature of conscious thought may be rhythmic, according to the researchers, who published their findings in the Nov. 21 issue of Neuron.
“As we talk, thoughts float in and out of our heads. Those are all ensembles forming and then reconfiguring to something else. It’s been a mystery how the brain does this,” says Miller, who is also a member of MIT’s Picower Institute for Learning and Memory. “That’s the fundamental problem that we’re talking about — the very nature of thought itself.”
Researchers at Emory University School of Medicine have discovered that dozens of adults with an elevated need for sleep have a substance in their cerebrospinal fluid that acts like a sleeping pill.
The results are scheduled for publication online Wednesday by the journal Science Translational Medicine.
Some members of this patient population appear to have a distinct, disabling sleep disorder called “primary hypersomnia,” which is separate from better-known conditions such as sleep apnea or narcolepsy. They regularly sleep more than 70 hours per week and have difficulties awakening. When awake, they still have reaction times comparable to someone who has been awake all night. Their sleepiness often interferes with work or school attendance, and conventional treatments such as stimulants bring little relief.
"These individuals report feeling as if they’re walking around in a fog — physically, but not mentally awake," says lead author David Rye, professor of neurology at Emory University School of Medicine and director of research for Emory Healthcare’s Program in Sleep. "When encountering excessive sleepiness in a patient, we typically think it’s caused by an impairment in the brain’s wake systems and treat it with stimulant medications. However, in these patients, the situation is more akin to attempting to drive a car with the parking brake engaged. Our thinking needs to shift from pushing the accelerator harder, to releasing the brake."
In a clinical study with seven patients who remained sleepy despite above-ordinary sleep amounts and treatment with stimulants, Emory researchers showed that treatment with the drug flumazenil can restore alertness, although flumazenil’s effectiveness was not uniform for all seven. Alertness was gauged through the psychomotor vigilance test, a measurement of reaction time.
Neural interaction in periods of silence
While in deep dreamless sleep, our hippocampus sends messages to our cortex and changes its plasticity, possibly transferring recently acquired knowledge to long-term memory. But how exactly is this done? Scientists from the Max Planck Institute for Biological Cybernetics have now developed a novel multimodal methodology called “neural event-triggered functional magnetic resonance imaging” (NET-fMRI) and presented the very first results obtained using it in experiments with both anesthetized and awake, behaving monkeys. The new methodology uses multiple-contact electrodes in combination with functional magnetic resonance imaging (fMRI) of the entire brain to map widespread networks of neurons that are activated by local, structure-specific neural events.
New hope for understanding autism spectrum disorders
Researchers from McGill University and the University of Montreal have identified a crucial link between protein synthesis and autism spectrum disorders (ASD), which can bolster new therapeutic avenues. Regulation of protein synthesis, also termed mRNA translation, is the process by which cells manufacture proteins.
This mechanism is involved in all aspects of cell and organism function. A new study in mice has found that abnormally high synthesis of a group of neuronal proteins called neuroligins results in symptoms similar to those diagnosed in ASD. The study also reveals that autism-like behaviors can be rectified in adult mice with compounds inhibiting protein synthesis, or with gene-therapy targeting neuroligins. Their results are published in the journal Nature.
Autism spectrum disorders (ASD) encompass a wide array of neurodevelopmental diseases that affect three areas of behaviour: social interactions, communication and repetitive interests or behaviors. According to the U.S.-based Centers for Disease Control and Prevention, 1 in 88 children suffer from ASD, and the disorder is reported to occur in all racial, ethnic, and socioeconomic groups. ASDs are almost five times more common among boys (1 in 54) than among girls (1 in 252).
“My lab is dedicated to elucidating the role of dysregulated protein synthesis in cancer etiology. However, our team was surprised to discover that similar mechanisms may be implicated in the development of ASD”, explained Prof. Nahum Sonenberg, from McGill’s Dept. of Biochemistry, Faculty of Medicine, and the Goodman Cancer Research Centre. “We used a mouse model in which a key gene controlling initiation of protein synthesis was deleted. In these mice, production of neuroligins was increased. Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain and essential for the maintenance of the balance in the transmission of information from neuron to neuron.”
“Since the discovery of neuroligin mutations in individuals with ASD in 2003, the precise molecular mechanisms implicated remain unknown,” said Christos Gkogkas, a postdoctoral fellow at McGill and lead author. “Our work is the first to link translational control of neuroligins with altered synaptic function and autism-like behaviors in mice. The key is that we achieved reversal of ASD-like symptoms in adult mice. Firstly, we used compounds, which were previously developed for cancer treatment, to reduce protein synthesis. Secondly, we used non-replicating viruses as vehicles to put a break on exaggerated synthesis of neuroligins.”
Computer modeling played an important role in this research. “By using a new sophisticated computer algorithm that we specially developed to answer Dr. Sonenberg’s questions, we identified the unique structures of mRNAs of the neuroligins that could be responsible for their specific regulation,” explained Prof. François Major, of the University of Montreal’s Institute for Research in Immunology and Cancer and Department of Computer Science.
The researchers found that dysregulated synthesis of neuroligins augments synaptic activity, resulting in an imbalance between excitation and inhibition in single brain cells, opening up exciting new avenues for research that may unlock the secrets of autism.
“The autistic behaviours in mice were prevented by selectively reducing the synthesis of one type of neuroligin and reversing the changes in synaptic excitation in cells,” explained Prof. Jean-Claude Lacaille at the University of Montreal’s Groupe de Recherche sur le Système Nerveux Central and Department of Physiology. “In short, we manipulated mechanisms in brain cells and observed how they influence the behaviour of the animal.” The researchers were also able to reverse changes in inhibition and augment autistic behaviors by manipulating a second neuroligin. “The fact that the balance can be affected suggests that there could be a potential for pharmacological intervention by targeting these mechanisms,” Lacaille concluded.
(Source: nouvelles.umontreal.ca)
Fetuses yawn in the womb, according to new research
We know that unborn babies hiccup, swallow and stretch in the womb but new observational research concludes that they also yawn.
The 4D scans of 15 healthy fetuses, by Durham and Lancaster Universities, also suggest that yawning is a developmental process which could potentially give doctors another index of a fetus’ health.
While some researchers have suggested that fetuses yawn, others have disagreed and claim it is simple mouth opening.
But the new research clearly distinguished ‘yawning’ from ‘non-yawn mouth opening’ based on the duration of mouth opening. The researchers did this by using the 4D video footage to closely examine all events where a mouth stretch occurred in the fetus.
Using their newly developed criteria, the research team found that over half of the mouth openings observed in the study were classed as yawns.
The study was carried out on eight female and seven male foetuses from 24 to 36 weeks gestation. The researchers found that yawning declined from 28 weeks and that there was no significant difference between boys and girls in yawning frequency.
Although the function and importance of yawning is still unknown, the study findings suggest that yawning could be linked to fetal development, and as such could provide a further medical indication of the health of the unborn baby.
MRI shows brain disruption in patients with post-concussion syndrome
MRI shows changes in the brains of people with post-concussion syndrome (PCS), according to a new study published online in the journal Radiology. Researchers hope the results point the way to improved detection and treatment for the disorder.
PCS affects approximately 20 percent to 30 percent of people who suffer mild traumatic brain injury (MTBI)—defined by the World Health Organization as a traumatic event causing brief loss of consciousness and/or transient memory dysfunction or disorientation. Symptoms of PCS include headache, poor concentration and memory difficulty.
Conventional neuroimaging cannot distinguish which MTBI patients will develop PCS.
"Conventional imaging with CT or MRI is pretty much normal in MTBI patients, even though some go on to develop symptoms, including severe cognitive problems," said Yulin Ge, M.D., associate professor, Department of Radiology at the NYU School of Medicine in New York City. "We want to try to better understand why and how these symptoms arise."
Dr. Ge’s study used MRI to look at the brain during its resting state, or the state when it is not engaged in a specific task, such as when the mind wanders or while daydreaming. The resting state is thought to involve connections among a number of regions, with the default mode network (DMN) playing a particularly important role.
"Baseline DMN is very important for information processing and maintenance," Dr. Ge said.
Alterations in DMN have been found in several psychiatric disorders, including Alzheimer’s disease, autism and schizophrenia, but little is known about DMN connectivity changes in MTBI.
For the new study, Dr. Ge and colleagues used resting-state functional MRI to compare 23 MTBI patients who had post-traumatic symptoms within two months of the injury and 18 age-matched healthy controls. Resting state MRI detects distinct changes in baseline oxygen level fluctuations associated with brain functional networks between patients with MTBI and control patients.
The MRI results showed that communication and information integration in the brain were disrupted among key DMN structures after mild head injury, and that the brain tapped into different neural resources to compensate for the impaired function.
"We found decreased functional connectivity in the posterior network of the brain and increased connectivity in the anterior component, probably due to functional compensation in patients with PCS," Dr. Ge said. "The reduced posterior connectivity correlated positively with neurocognitive dysfunction."
Dr. Ge and the other researchers hope to recruit additional MTBI patients for further studies with an eye toward developing a biomarker to monitor disease progression and recovery as well as treatment effects.
"We want to do studies to look at the changes in the network over time and correlate these functional changes with structural changes in the brain," he said. "This could give us hints on treatments to bring back cognitive function."
(Source: medicalxpress.com)
Scientists at Mainz University identify inhibitor of myelin formation in the central nervous system
Scientists at the Mainz University Medical Center have discovered another molecule that plays an important role in regulating myelin formation in the central nervous system. Myelin promotes the conduction of nerve cell impulses by forming a sheath around their projections, the so-called axons, at specific locations – acting like the plastic insulation around a power cord. The research team, led by Dr. Robin White of the Institute of Physiology and Pathophysiology at the University Medical Center of Johannes Gutenberg University Mainz, recently published their findings in the prestigious journal EMBO reports.
Complex organisms have evolved a technique known as saltatory conduction of impulses to enable nerve cells to transmit information over large distances more efficiently. This is possible because the specialized nerve cell axonal projections involved in conducting impulses are coated at specific intervals with myelin, which acts as an insulating layer. In the central nervous system, myelin develops when oligodendrocytes, which are a type of brain cell, repeatedly wrap their cellular processes around the axons of nerve cells forming a compact stack of cell membranes, a so-called myelin sheath. A myelin sheath not only has a high lipid content but also contains two main proteins, the synthesis of which needs to be carefully regulated.
The current study analyzed the synthesis of myelin basic protein (MBP), a substance which is essential for the formation and stabilization of myelin membranes. In common with all proteins, MBP is generated in a two-stage process originating from basic genetic material in the form of DNA. First, DNA is converted to mRNA, which, in turn, serves as a template for the actual synthesis of MBP. During myelin formation, the synthesis of MBP in oligodendrocytes is suppressed until distinct signals from nerve cells initiate myelination at specific “production sites”. To date, the mechanisms involved in the suppression of MBP synthesis over relatively long periods of time have not been understood. This is where the current work of the Mainz scientists comes in, as they were able to identify a molecule that is responsible for the suppression of MBP synthesis.
"This molecule, called sncRNA715, binds to MBP mRNA, thus preventing MBP synthesis," explains Dr. Robin White. "Our research findings show that levels of sncRNA715 and MBP inversely correlate during myelin formation and that it is possible to influence the extent of MBP production in oligodendrocytes by artificially modifying levels of sncRNA715. This indicates that the recently discovered molecule is a significant factor in the regulation of MBP synthesis."
Understanding the molecular basis for myelin formation is essential with regard to various neurological illnesses that involve a loss of the protective myelin layer. For example, it is still unclear why oligodendrocytes lose their ability to repair the damage to myelin in the progress of multiple sclerosis (MS). “Interestingly, in collaboration with our Dutch colleagues, we have been able to identify a correlation between levels of sncRNA715 and MBP in the brain tissue of MS patients,” Robin White continues. “In contrast with unaffected areas of the brain in which the myelin structure appears normal, there are higher levels of sncRNA715 in affected areas in which myelin formation is impaired. Our findings may help to provide a molecular explanation for myelination failures in illnesses such as multiple sclerosis.”
(Source: uni-mainz.de)
Researchers find decline in availability and use of key treatment for depression
Electroconvulsive therapy (ECT) is considered the most effective treatment option for patients with severe depression who cannot find symptom relief through antidepressant medications or psychotherapy. In a new study, researchers at Butler Hospital and Bradley Hospital in Rhode Island found a sharp decline in the availability and use of ECT in general hospitals across the U.S. The findings were published online in the journal Biological Psychiatry on October 10, 2012.
The researchers analyzed data from a nationally representative survey of US general hospitals, the Nationwide Inpatient Sample (NIS), conducted annually by the Agency for Healthcare Research and Quality (AHRQ). They took information from between five and eight million patient discharge records at 1,000 hospitals nationwide between the years 1993 through 2009 and found that the annual number of hospital stays in which ECT was administered fell 43 percent over the 17 year period, from more than 1.2 million to 720,000. Researchers also found a dramatic decline in the percentage of hospitals conducting ECT, from 55 percent to 35 percent of facilities with a psychiatric unit. The percentage of inpatients with severe, recurrent major depression treated in hospitals conducting ECT fell from 71 to 45 percent. But for depressed patients treated in hospitals that conduct ECT, the proportion who received the procedure remained stable.
"The data strongly support the impression that psychiatric units in general hospitals are discontinuing use of ECT and that this is driving the decline in the number of severely depressed inpatients receiving the procedure," said Brady Case, MD, an assistant professor of psychiatry and human behavior at Brown University and director of the Health Services Research Program at Bradley Hospital. "Growing pressures to avoid the inpatient treatment costs and length of stay associated with ECT may be one factor associated with this trend. We didn’t have information on provider and patient attitudes, but as facilities cease conducting ECT, we can expect that fewer clinicians and inpatients are exposed to the option, reinforcing the turn away from ECT." Researchers also note the FDA approval of new treatment alternatives, like vagus nerve stimulation and transcranial magnetic stimulation, as possible influences.
Discovery of molecular pathway of Alzheimer’s disease reveals new drug targets
The discovery of the molecular pathway that drives the changes seen in the brains of Alzheimer’s patients is reported today, revealing new targets for drug discovery that could be exploited to combat the disease. The study gives the most detailed understanding yet of the complex processes leading to Alzheimer’s.
Alzheimer’s disease is associated with plaques made up of deposits of a molecule called amyloid between brain cells, which leads to the formation of tangles of twisted fibres made from a molecule called tau, found inside the brain cells. This causes the death of brain cells which is thought to bring about the symptoms of memory loss and dementia. Although it has been accepted for over twenty years that the progression of disease is driven by amyloid and results in abnormal changes in tau, the exact mechanisms of disease remain somewhat of a mystery.
Recent genome wide association studies have identified the gene for a molecule called clusterin as a susceptibility factor for late-onset Alzheimer’s disease. Levels of clusterin are also known to be elevated in blood in patients with Alzheimer’s from an early stage in the disease so the researchers wanted to find out what role it might play in the progression of disease.
The team, led by researchers at King’s College London’s Institute of Psychiatry, looked first in mouse brain cells grown in the laboratory and found that the presence of amyloid alters the amount of clusterin in these cells. Clusterin then acts to switch on a signalling pathway that drives the changes in tau that are associated with the formation of tangles inside the cells, another hallmark of the disease. When this signalling pathway was chronically switched on in a mouse model of the disease, the researchers observed an increase in tangle formation and evidence of cognitive defects.
The study, published in the journal Molecular Psychiatry, also looked in humans and detected the signature of clusterin activation in the brains of Alzheimer’s patients but not in the brains of patients with other forms of dementia.
Dr Richard Killick from King’s College London’s Institute of Psychiatry said: “This is the first time we’ve been able to connect the molecular mechanisms behind the formation of amyloid plaques in the brain with the formation of tangles inside the brain cells, two of the defining features of Alzheimer’s disease. Our research has given the most detailed picture yet of how the disease progresses and we hope it will offer leads for the development of new treatments.”
The signalling pathway that is turned on by clusterin is called DKK1-WNT. It involves interactions between a number of different molecules that could prove to be useful targets for the development of new drugs.
Current treatments for Alzheimer’s are focused on alleviating the symptoms and there is no therapy that can prevent the progression of disease.
Professor Simon Lovestone, also from King’s College London’s Institute of Psychiatry, who led the study, said: “We have shown that we can block the toxic effects of amyloid when we stop this signalling pathway in brain cells grown in the lab. We believe that if we could block its activity in the brains of Alzheimer’s patients too, we may have an opportunity to halt the disease in man. Indeed, we have already begun our own drug development programme to do just that and are at the stage where potential compounds are coming back to us for further testing.”
The DKK1-WNT pathways has also been implicated in some human cancers and although there is no evidence for a direct link, the findings from this study mean that there could be an opportunity to make advances in Alzheimer’s research by capitalising on knowledge that is being gained from cancer research, the authors suggest.
Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, which helped fund this study, said: “We will see more and more people affected by Alzheimer’s disease as our population ages. This study gives us a much-needed additional insight to the complex biology that contributes to the development of Alzheimer’s, which is vital if we are to develop new treatments that are so urgently needed.”
(Source: eurekalert.org)
Research shows diabetes drug improves memory
An FDA-approved drug initially used to treat insulin resistance in diabetics has shown promise as a way to improve cognitive performance in some people with Alzheimer’s disease.
Working with genetically engineered mice designed to serve as models for Alzheimer’s, University of Texas Medical Branch at Galveston researchers found that treatment with the anti-insulin-resistance drug rosiglitazone enhanced learning and memory as well as normalized insulin resistance. The scientists believe that the drug produced the response by reducing the negative influence of Alzheimer’s on the behavior of a key brain-signaling molecule.
The molecule, called extracellular signal-regulated kinase (ERK), becomes hyperactive both in the brains of Alzheimer’s patients and in the mice at a disease stage corresponding to mild cognitive impairment in human Alzheimer’s. This excessive activity leads to improper synaptic transmission between neurons, interfering with learning and memory.
Rosiglitazone brings ERK back into line by activating what’s known as the peroxisome proliferator-activated receptor gamma (PPARγ) pathway, which interacts with genes that respond to both PPARγ and ERK.
“Using this drug appears to restore the neuronal signaling required for proper cognitive function,” said UTMB professor Larry Denner, the lead author of a paper describing this work now online (posted Nov. 21) in the Journal of Neuroscience. “It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer’s patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer’s.”