Neuroscience

Neuroscientists studying the link between poor sleep and schizophrenia have found that irregular sleep patterns and desynchronised brain activity during sleep could trigger some of the disease’s symptoms. The findings, published in the journal Neuron, suggest that these prolonged disturbances might be a cause and not just a consequence of the disorder’s debilitating effects.

The possible link between poor sleep and schizophrenia prompted the research team, led by scientists from the University of Bristol, the Lilly Centre for Cognitive Neuroscience and funded by the Medical Research Council (MRC), to explore the impact of irregular sleep patterns on the brain by recording electrical brain activity in multiple brain regions during sleep.

For many people, sleep deprivation can affect mood, concentration and stress levels. In extreme cases, prolonged sleep deprivation can induce hallucinations, memory loss and confusion all of which are also symptoms associated with schizophrenia.

Dr Ullrich Bartsch, one of the study’s researchers, said: “Sleep disturbances are well-documented in the disease, though often regarded as side effects and poorly understood in terms of their potential to actually trigger its symptoms.”

Using a rat model of the disease, the team’s recordings showed desynchronisation of the waves of activity which normally travel from the front to the back of the brain during deep sleep. In particular the information flow between the hippocampus — involved in memory formation, and the frontal cortex — involved in decision-making, appeared to be disrupted. The team’s findings reported distinct irregular sleep patterns very similar to those observed in schizophrenia patients.

Dr Matt Jones, the lead researcher from the University’s School of Physiology and Pharmacology, added: “Decoupling of brain regions involved in memory formation and decision-making during wakefulness are already implicated in schizophrenia, but decoupling during sleep provides a new mechanistic explanation for the cognitive deficits observed in both the animal model and patients: sleep disturbances might be a cause, not just a consequence of schizophrenia. In fact, abnormal sleep patterns may trigger abnormal brain activity in a range of conditions.”

Cognitive deficits — reduced short term memory and attention span, are typically resistant to medication in patients. The findings from this study provide new angles for neurocognitive therapy in schizophrenia and related psychiatric diseases.

Scientists have taken a step forward in helping to solve one of life’s greatest mysteries - what makes us human?

Image: Irish Wildcat

An international team of researchers have discovered a new gene that helps explain how humans evolved from apes. Scientists say the gene - calledmiR-941 - appears to have played a crucial role in human brain development and may shed light on how we learned to use tools and language. Researchers say it is the first time that a new gene - carried only by humans and not by apes - has been shown to have a specific function within the human body.

Unique finding

A team at the University of Edinburgh compared the human genome to 11 other species of mammals, including chimpanzees, gorillas, mouse and rat, to find the differences between them. The results, published in Nature Communications, showed that the gene - miR-941 - is unique to humans. The researchers say that it emerged between six and one million years ago, after humans had evolved from apes. The gene is highly active in two areas of the brain that control our decision making and language abilities. The study suggests it could have a role in the advanced brain functions that make us human.

Startling results

It is known that most differences between species occur as a result of changes to existing genes, or the duplication and deletion of genes. But scientists say this gene emerged fully functional out of non-coding genetic material, previously termed “junk DNA”, in a startlingly brief interval of evolutionary time. Until now, it has been remarkably difficult to see this process in action. Researcher Dr Martin Taylor, who led the study at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, said the results were fascinating.

This new molecule sprang from nowhere at a time when our species was undergoing dramatic changes: living longer, walking upright, learning how to use tools and how to communicate. We’re now hopeful that we will find more new genes that help show what makes us human. -Dr Martin Taylor (Programme leader, Biomedical Systems Analysis)

A gene that confers a higher risk for dementia in old age could also promote better-than-average memory and verbal skills in youth, according to a new University of Sussex-led study.

Neuroscientists tested the cognitive abilities of those with a particular gene variant, known as ‘APOE e4’, found in approximately 25 per cent of the population, against those without it. They also looked at the brain structure and brain activities of both groups during the tasks.

They found that young people with the e4 variant performed better in attention tests (one involving episodic memory of words, the other requiring participants to spot number sequences), which correlated with increased task-related brain activation as detected by MRI scans. The researchers also noticed subtle differences in the white matter of the brains of those with the variant.

Lead researcher Professor Jennifer Rusted said: “Earlier studies suggested that those with the e4 variant outperform those without it in tasks such as memory, speed of processing, mental arithmetic and verbal fluency.

But it is also well-established that this gene is a risk factor for Alzheimer’s disease. The suggestion is that while this confers cognitive advantages in early life, leading to higher achievement, it may also increase susceptibility to memory failure as we enter old age.

“Our study is the first to show that subtle differences in the structure and activation of the brain during cognitive tasks in APOE e4 carriers are linked to their cognitive performance. It is possible that the brain over-activations that we see in youth have negative effects over the longer term and contribute to a kind of ‘burnout’ in older adulthood.”

‘APOE e4 polymorphism in young adults is associated with improved attention andindexed by distinct neural signatures’, by Professor Jennifer Rusted, Dr Simon Evans and Dr Sarah King in the School of Psychology, Dr Nick Dowell and Professor Paul Tofts in the Clinical Imaging Sciences Centre at the Brighton and Sussex Medical School (BSMS), and Dr Najo Tabet in the BSMS Institute of Postgraduate Medicine, is published in NeuroImage.

A new Northwestern University study shows the power of language in infants’ ability to understand the intentions of others.

As the babies watched intently, an experimenter produced an unusual behavior—she used her forehead to turn on a light. But how did babies interpret this behavior? Did they see it as an intentional act, as something worthy of imitating? Or did they see it as a fluke? To answer this question, the experimenter gave 14-month-old infants an opportunity to play with the light themselves.

The results, based on two experiments, show that introducing a novel word for the impending novel event had a powerful effect on the infants’ tendency to imitate the behavior. Infants were more likely to imitate behavior, however unconventional, if it had been named, than if it remained unnamed, the study shows.

When the experimenter announced her unusual behavior (“I’m going to blick the light”), infants imitated her. But when she did not provide a name, they did not follow suit.

This revealed that infants as young as 14 months of age coordinate their insights about human behavior and their intuitions about human language in the service of discovering which behaviors, observed in others, are ones to imitate.

"This work shows, for the first time, that even for infants who have only just begun to ‘crack the language code,’ language promotes culturally-shared knowledge and actions – naturally, generatively and apparently effortlessly," said Sandra R. Waxman, co-author of the study and the Louis W. Menk Professor of Psychology at Northwestern.

"This is the first demonstration of how infants’ keen observational skills, when augmented by human language, heighten their acuity for ‘reading’ the underlying intentions of their ‘tutors’ (adults) and foster infants’ imitation of adults’ actions."

Waxman said absent language and its power in conveying meaning, infants don’t imitate these “strange” actions.

"This means that human language provides infants with a powerful key: it unlocks for them a broader world of social intentions," Waxman said. "We know that language, and especially the shared meaning within a linguistic community, is one of the most powerful conduits of the cultural knowledge that we humans transmit across generations."

The unconscious brain may not be able to ace an SAT test, but new research suggests that it can handle more complex language processing and arithmetic tasks than anyone has previously believed. According to these findings, just published in the Proceedings of the National Academy of Sciences, we may be blithely unaware of all the hard work the unconscious brain is doing.

In their experiments, researchers from Hebrew University in Israel used a cutting-edge “masking” technique to keep their test subjects from consciously perceiving certain stimuli. With this technique, known as continuous flash suppression, the researchers show a rapidly changing series of colorful patterns to just one of the subject’s eyes. The bright patterns dominate the subject’s awareness to such an extent that when researchers show less flashy material to the other eye (like words or equations), it takes several seconds before the brain consciously registers it. 

This masking technique is “a game changer in the study of the unconscious,” the scientists write, “because unlike all previous methods, it gives unconscious processes ample time to engage with and operate on subliminal stimuli.”

To study the unconscious brain’s ability to process language, the researchers subliminally showed the subject short phrases that made variable amounts of sense: For example, subjects might see the phrase “I ironed coffee” or “I ironed clothes.” The researchers gradually turned up the contrast between the phrase and its background, and measured how long it took for the phrase to “pop” into the subject’s conscious awareness. As the nonsensical phrases popped sooner, the researchers hypothesize that the unconscious brain processed the sentence, found it surprising and odd, and quickly passed it along to the conscious brain for further examination.

To determine the unconscious brain’s mathematical abilities, the researchers presented a simple subtraction or addition equation (for example, “9 − 3 − 4 = “) to a subject, but took it away before it could pop into consciousness. Then they stopped the masking pattern and displayed a single number, asking the viewer to pronounce the number as soon as it registered. When the number was the answer to the subtraction equation (for example, “2”), the subject was quicker to pronounce it. The researchers argue that the viewer was “primed” to respond to that number because the unconscious brain had solved the equation. Oddly, they didn’t find the same clear effect with easier addition equations.

Research may prompt new investigations into white matter’s role in psychiatric disorders as well as connections between mood and myelin diseases, like MS

Animals that are socially isolated for prolonged periods make less myelin in the region of the brain responsible for complex emotional and cognitive behavior, researchers at the University at Buffalo and Mt. Sinai School of Medicine report in Nature Neuroscience online.

The research sheds new light on brain plasticity, the brain’s ability to adapt to environmental changes. It reveals that neurons aren’t the only brain structures that undergo changes in response to an individual’s environment and experience, according to one of the paper’s lead authors, Karen Dietz, PhD, research scientist in the Department of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences.

Dietz did the work while a postdoctoral researcher at Mt. Sinai School of Medicine; Jia Liu, PhD, a Mt. Sinai postdoctoral researcher, is the other lead author.

The paper notes that changes in the brain’s white matter, or myelin, have been seen before in psychiatric disorders, and demyelinating disorders have also had an association with depression. Recently, myelin changes were also seen in very young animals or adolescents responding to environmental changes.

"This research reveals for the first time a role for myelin in adult psychiatric disorders," Dietz says. "It demonstrates that plasticity in the brain is not restricted to neurons, but actively occurs in glial cells, such as the oligodendrocytes, which produce myelin."

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Eye experts and scientists at the University of Southampton have discovered specific cells in the eye which could lead to a new procedure to treat and cure blinding eye conditions.

Led by Professor Andrew Lotery, the study found that cells called corneal limbal stromal cells, taken from the front surface of the eye have stem cell properties and could be cultured to create retinal cells.

This could lead to new treatments for eye conditions such as retinitis pigmentosa or wet age-related macular degeneration, a condition which is a common cause of loss of vision in older people and will affect around one in three people in the UK by age 70.

Furthermore the research, published in the British Journal for Ophthalmology, suggests that using corneal limbus cells would be beneficial in humans as it would avoid complications with rejection or contamination because the cells taken from the eye would be returned to the same patient.

Professor Lotery, who is also a Consultant Ophthalmologist at Southampton General Hospital, comments: “This is an important step for our research into the prevention and treatment of eye conditions and blindness.

“We were able to characterize the corneal limbal stromal cells found on the front surface of the eye and identify the precise layer in the cornea that they came from. We were then successful in culturing them in a dish to take on some of the properties of retinal cells. We are now investigating whether these cells could be taken from the front of the eye and be used to replace diseased cells in the back of the eye in the retina. If successful this would open up new and efficient ways of treating people who have blinding eye conditions.”

This is a promising discovery as the corneal limbus is one of the most accessible regions of the human eye and it represents 90 per cent of the thickness of the front eye wall. Therefore cells could be easily obtainable from this area with little risk to the patient’s eye and sight. However Professor Lotery says more research is needed to develop this approach before they are used in patients.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have defined the molecular structure of an enzyme as it interacts with several proteins involved in outcomes that can influence neurodegenerative disease and insulin resistance. The enzymes in question, which play a critical role in nerve cell (neuron) survival, are among the most prized targets for drugs to treat brain disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

The study was published online ahead of print on November 8, 2012, by the journal Structure.

The new study reveals the structure of a class of enzymes called c-jun-N-terminal kinases (JNK) when bound to three peptides from different protein families; JNK is an important contributor to stress-induced apoptosis (cell death), and several studies in animal models have shown that JNK inhibition protects against neurodegeneration.

"Our findings have long-range implications for drug discovery," said TSRI Professor Philip LoGrasso, who, along with TSRI Associate Professor Kendall Nettles, led the study. "Knowing the structure of JNK bound to these proteins will allow us to make novel substrate competitive inhibitors for this enzyme with even greater specificity and hopefully less toxicity."

The scientists used what they called structure class analysis, looking at groups of structures, which revealed subtle differences not apparent looking at them individually.

"From a structural point of view, these different proteins appear to be very similar, but the biochemistry shows that the results of their binding to JNK were very different," he said.

LoGrasso and his colleagues were responsible for creating and solving the crystal structures of the three peptides (JIP1, SAB, and ATF-2) with JNK3 using a technique called x-ray crystallography, while Nettles handled much of the data analysis.

All three peptides have important effects, LoGrasso said, inducing two distinct inhibitory mechanisms—one where the peptide caused the activation loop to bind directly in the ATP pocket, and another with allosteric control (that is, using a location on the protein other than the active site). Because JNK signaling needs to be tightly controlled, even small changes in it can alter a cell’s fate.

"Solving the crystal structures of these three bound peptides gives us a clearer idea of how we can block each of these mechanisms related to cell death and survival," LoGrasso said. "You have to know their structure to know how to deal with them."

Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.

Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer’s disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.

Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer’s and stroke, and especially following traumatic brain injury.

Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published recently in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.

Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn’t die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.

What’s next? Xu and colleagues are now probing appoptosin’s function in mouse models. They’re also looking for new therapies that target the protein.

“Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer’s, we’re now searching for small molecules that modulate appoptosin expression or activity. We’ll then determine whether these compounds may be potential drugs for Alzheimer’s or other neurodegenerative diseases,” Xu explains.

Putting a stop to runaway appoptosin won’t be easy, though. That’s because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. “Too much of anything is bad, but so is too little,” Xu says.

New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It’s an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person’s risk for Alzheimer’s and Parkinson’s diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury “one of the signature injuries of troops wounded in Afghanistan and Iraq.”