Neuroscience

Researchers at the University of Copenhagen have found that a protein, known for causing cancer cells to spread around the body, is also one of the molecules that trigger repair processes in the brain. These findings are the subject of a paper, published this week in Nature Communications. They point the way to new avenues of research into degenerative brain diseases like Alzheimer’s.

How to repair brain injuries is a fundamental question facing brain researchers. Scientists have been familiar with the protein S100A4 for some time as a factor in metastasis, or how cancer spreads. However it’s the first time the protein has been shown to play a role in brain protection and repair.

“This protein is not normally in the brain, only when there’s trauma or degeneration. When we deleted the protein in mice we discovered that their brains were less protected and able to resist injury. We also discovered that S100A4 works by activating signalling pathways inside neurons,” says Postdoc Oksana Dmytriyeva, who worked on the research in a team at the Protein Laboratory in the Department of Neuroscience and Pharmacology at the University of Copenhagen.

The villain turns out to be the hero

This research stands on the shoulders of many years of work on S100A4 in its deadlier role in cancer progression. The discovery represents a significant development for the new Neuro-Oncology Group that moved to the University of Copenhagen’s Protein Laboratory Group from the Danish Cancer Society in October.

“We were surprised to find this protein in this role, as we thought it was purely a cancer protein. We are very excited about it and we’re looking forward to continuing our research in a practical direction. We hope that the findings will eventually benefit people who need treatment for neurodegenerative disorders like Alzheimer’s disease, although obviously we have a long way to go before we get to that point,” says Oksana Dmytriyeva.

A team of cognitive neuroscientists has identified the areas of the brain responsible for processing specific words meanings, bringing us one step closer to developing multilingual mind reading machines.

Presenting the findings at the Society for the Neurobiology of Language Conference in San Sebastián, Spain, Joao Correia of Maastricht University explained that his team decided to answer one central question: “how do we represent the meaning of words independent of the language we are listening to?”

Past studies have focused on identifying areas of the brain that generate and hear general terms or feelings. However, if we can locate where the actual concept of a word — which transcends language — is processed, we would be able to read the mind of any individual. The recent case of 39-year-old Scott Routley letting doctors know he is not in pain, just by thinking, is a prime example of where this could be extremely effective in the future. After not responding to any stimulation for more than a decade, Routley was thought to be in a persistent vegetative state. However, by studying fMRI scans in real time neurologists could identify that Routley was in fact responding to their questions — they asked him to think about playing tennis or walking around at home to indicate yes or no. These two actions are processed in different areas of the brain, so answers could be extracted by reading scans. With Correia’s approach, we would need no signifier for yes or no — we could go straight to the source where the processing of the meaning of positive and negative takes place; the “hub”, as he puts it.

"This fMRI study investigates the neural network of speech processing responsible for transforming sound to meaning, by exploring the semantic similarities between bilingual wordpairs," explains an abstract of the study. To achieve this, they needed bilingual volunteers, so worked with eight Dutch candidates all fluent in English. First off, the team monitored the volunteers’ neural activity while saying the words "bull", "horse", "shark" and "duck" in English. All the words chosen had one syllable, were from a similar group and were probably learnt round the same period — this ensured that any differences would specifically relate to meaning. Different brain activity patterns appeared in the left anterior temporal cortex, and each of these were then fed into an algorithm so it would be able to flag up when one of the words was uttered again.

The hypothesis was, if the algorithm could still correctly identify the words when they were spoken in Dutch, these patterns would hold the key to where the word concepts are derived. The algorithm did exactly that. It demonstrates that words are encoded in the same way in the brain, regardless of language.

There is one pretty major drawback to the process, which quashes any visions of a full-on real-time mind translation machine hitting stores anytime soon — the neural activity patterns differed slightly from person to person. Our neurons learn and identify in unique ways, and understanding these pathway patterns through machine learning would be a long process. “You would have to scan a person as they thought their way through a dictionary,” said Matt Davis of the MRC Cognition and Brain Sciences Unit in Cambridge. It would be difficult to translate a mind now without this concept map. However, we are only at the beginning of this line of study, and an algorithm could potentially be devised to aggregate hundreds of neural activity patterns to help indicate what the brain activity of an individual unable to communicate represents.

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published November 7 in the Journal of Neuroscience.

“We showed for the first time that embryonic stem cells that we’ve programmed to become neurons can integrate into existing brain circuits and fire patterns of electrical activity that are critical for consciousness and neural network activity,” said Stuart A. Lipton, M.D., Ph.D., senior author of the study. Lipton is director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

The trick turned out to be light. Lipton and his team—including Juan Piña-Crespo, Ph.D., D.V.M., Maria Talantova, M.D., Ph.D., and other colleagues at Sanford-Burnham and Stanford University—transplanted human stem cell-derived neurons into a rodent hippocampus, the brain’s information-processing center. Then they specifically activated the transplanted neurons with optogenetic stimulation, a relatively new technique that combines light and genetics to precisely control cellular behavior in living tissues or animals.

To determine if the newly transplanted, light-stimulated human neurons were actually working, Lipton and his team measured high-frequency oscillations in existing neurons at a distance from the transplanted ones. They found that the transplanted neurons triggered the existing neurons to fire high-frequency oscillations. Faster neuronal oscillations are usually better—they’re associated with enhanced performance in sensory-motor and cognitive tasks.

To sum it up, the transplanted human neurons not only conducted electrical impulses, they also roused neighboring neuronal networks into firing—at roughly the same rate they would in a normal, functioning hippocampus.

The therapeutic outlook for this technology looks promising. “Based on these results, we might be able to restore brain activity—and thus restore motor and cognitive function—by transplanting easily manipulated neuronal cells derived from embryonic stem cells,” Lipton said.

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.