Adrian Owen has found a way to use brain scans to communicate with people previously written off as unreachable. Now, he is fighting to take his methods to the clinic.

Adrian Owen still gets animated when he talks about patient 23. The patient was only 24 years old when his life was devastated by a car accident. Alive but unresponsive, he had been languishing in what neurologists refer to as a vegetative state for five years, when Owen, a neuro-scientist then at the University of Cambridge, UK, and his colleagues at the University of Liège in Belgium, put him into a functional magnetic resonance imaging (fMRI) machine and started asking him questions.

Incredibly, he provided answers. A change in blood flow to certain parts of the man’s injured brain convinced Owen that patient 23 was conscious and able to communicate. It was the first time that anyone had exchanged information with someone in a vegetative state.

Patients in these states have emerged from a coma and seem awake. Some parts of their brains function, and they may be able to grind their teeth, grimace or make random eye movements. They also have sleep–wake cycles. But they show no awareness of their surroundings, and doctors have assumed that the parts of the brain needed for cognition, perception, memory and intention are fundamentally damaged. They are usually written off as lost.

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ScienceDaily (June 15, 2012) — People make complex judgements about a person from looking at their face that are based on a range of factors beyond simply their race and gender, according to findings of new research funded by the Economic and Social Research Council (ESRC).

The findings question a long-held belief that people immediately put a person they meet into a limited number of social categories such as: female or male; Asian, Black, Latino or White; and young or old.

Dr Kimberly Quinn at the University of Birmingham found that people ‘see’ faces in a multiple of ways. This could have wider importance in understanding stereotyping and discrimination because it has implications on whether and how people categorise others.

Categorisation is not done purely on the physical features of the face in front of us, but depends on other information as well, including whether the person is already known and whether the person is believed to share other important identities with us.

"How we perceive faces is not just a reflection of what’s in those faces," Dr Quinn said. "We are not objective; we bring our current goals and past knowledge to every new encounter. And this happens really quickly — within a couple of hundred milliseconds of seeing the face."

Dr Quinn and her colleagues explored social categories such as sex, race and age; physical attributes such as attractiveness; personality traits such as trustworthiness; and emotional states such as anger, sadness and happiness.

She found that although social categories are used to gather information on faces, these can be easily undermined. This research found that we reject simple stereotypes when something about the situation alerts us to the fact the stereotype does not tell the whole story. If we take, for example, a racial group and the corresponding stereotype of members of that group as unintelligent, seeing a person in that group playing an intellectual game such as chess would tell us to cancel out the stereotype.

In order to investigate the causes, mechanisms, and results of social categorisation, Dr Quinn used techniques from cognitive psychology and neuroscience to investigate how people process faces. The research was designed to provide insight into when and why people categorise others according to social group membership.

Their findings differ from previous research that adopted a ‘dual process’ approach and assumed people initially categorised faces based on factors such as gender, race or age before determining whether to stereotype them or to see them as unique individuals.

Dr Quinn’s findings were more consistent with a single process that initially focuses on ‘coarse’ information that is easy to detect, and then immediately starts to include more fine-grained processing as time elapses. This model allows for either categorisation or more individuated processing to emerge, and does not assume that categorisation always comes before recognising unique identities — thereby allowing for more diverse outcomes than previously thought.

Further information: http://www.esrc.ac.uk/my-esrc/grants/RES-061-23-0130/read

Source: Science Daily

ScienceDaily (June 15, 2012) — Researchers at The University of Nottingham have identified three sets of genetic markers that could potentially pave the way for new diagnostic tools for a deadly type of brain tumour that mainly targets children.

The study, published in the latest edition of the journal Lancet Oncology, was led by Professor Richard Grundy at the University’s Children’s Brain Tumour Research Centre and Dr Suzanne Miller, a post doctoral research fellow in the Centre.

It focuses on a rare and aggressive cancer called Central Nervous System primitive neuro-ectodermal brain tumours. Patients with CNS PNET have a very poor prognosis and current treatments, including high dose chemotherapy and cranio-spinal radiotherapy are relatively unsuccessful and have severe lifelong side-effects. This is particularly the case in very young children.

Despite the need for new and more effective treatments, little research has been done to examine the underlying causes of CNS PNET, partly due to their rarity. The Nottingham study aimed to identify molecular markers as a first step to improving the treatments and therapies available to fight the cancer.

The Nottingham team collaborated with researchers at the Hospital for Sick Kids in Toronto, Canada, to perform an International study collecting 142 CNS PNET samples from 20 institutions in nine countries.

Professor Richard Grundy said: “Following our earlier research we realised that an international effort was needed to bring sufficient numbers of cases together to make the breakthrough we needed to better understand this disease or indeed diseases identified in our study. The next step is to translate this knowledge into improving treatments.”

By studying the genetics of the tumours, they discovered that instead of one cancer, the tumours have three sub-types featuring distinct genetic abnormalities and leading to different outcomes for patients.

They found that each group had its own genetic signature through subtle differences in the way they expressed two genetic markers, LIN28 and OLIG2.

When compared with clinical factors including age, survival and metastases (the spread of the tumours through the body), they discovered that group 1 tumours (primitive neural) were found most often in the youngest patients and had the poorest survival rates. Patients with group 3 tumours had the highest incidence of metastases at diagnosis.

Ultimately, the research has identified the two genetic markers LIN28 and OLIG2 as a promising basis for more effective tools for diagnosing and predicting outcomes for young patients with these types of brain tumours.

The research was funded by the Canadian Institute of Health Research, the Brainchild/Sick Kids Foundation and the Samantha Dickson Brain Tumour Trust.

Chief Executive of Samantha Dickson Brain Tumour Trust, Sarah Lindsell, said: “As the UK’s leading brain tumour charity, and the largest dedicated funder of brain tumour research, we are delighted that our investment has led to such significant success. It is great to see that understanding of these tumours is improving — this is desperately needed given the poor outcomes for children with this tumour. Samantha Dickson Brain Tumour Trust is proud to have been instrumental in this work.”

Source: Science Daily

ScienceDaily (June 15, 2012) — A study recently published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism (JCEM) suggests that vitamin D — when taken with calcium — can reduce the rate of mortality in seniors, therefore providing a possible means of increasing life expectancy.

During the last decade, there has been increasing recognition of the potential health effects of vitamin D. It is well known that calcium with vitamin D supplements reduces the risk of fractures. The present study assessed mortality among patients randomized to either vitamin D alone or vitamin D with calcium. The findings from the study found that the reduced mortality was not due to a lower number of fractures, but represents a beneficial effect beyond the reduced fracture risk.

"This is the largest study ever performed on effects of calcium and vitamin D on mortality," said Lars Rejnmark, PhD, of Aarhus University Hospital in Denmark and lead author of the study. "Our results showed reduced mortality in elderly patients using vitamin D supplements in combination with calcium, but these results were not found in patients on vitamin D alone."

In this study, researchers used pooled data from eight randomized controlled trials with more than 1,000 participants each. The patient data set was composed of nearly 90 percent women, with a median age of 70 years. During the three-year study, death was reduced by 9 percent in those treated with vitamin D with calcium.

"Some studies have suggested calcium (with or without vitamin D) supplements can have adverse effects on cardiovascular health," said Rejnmark. "Although our study does not rule out such effects, we found that calcium with vitamin D supplementation to elderly participants is overall not harmful to survival, and may have beneficial effects on general health."

Source: Science Daily

ScienceDaily (June 15, 2012) — Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.

BPA is a human-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.

"We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression," said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. "Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations."

In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.

"BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies," said Rissman. "It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health."

Source: Science Daily

June 15, 2012

The research led by Newcastle University’s Dr Mark Cunningham and Professor Miles Whittington and supported by the Dr Hadwen Trust for Humane Research, indicates a novel electrical bio-marker in humans.

The brain produces electrical rhythms and using EEG - electrodes on the scalp - researchers were able to monitor the brain patterns in patients with epilepsy. Both in patients and in brain tissue samples the team were able to witness an abnormal brain wave noticeable due to its rapidly increasing frequency over time.

Comparing these to a musical ‘glissando’, an upwards glide from one pitch to another, the team found that this brain rhythm is unique to humans and they believe it could be related to epilepsy.

Dr Cunningham, senior lecturer in Neuronal Dynamics at Newcastle University said: “We were able to examine EEG collected from patients with drug resistant epilepsy who were continually monitored over a two week period. During that time we noticed patterns of electrical activity with rapidly increasing frequency, just like glissandi, emerging in the lead-up to an epileptic seizure.”

"We are in the early days of the work and we want to investigate this in a larger group of patients but it may offer a promising insight into when a seizure is going to start."

Professor Whittington added: “Classical composers such as Gustav Mahler are famous for using notes of rapidly increasing pitch – called glissando - to convey intense expressions of anticipation. Similarly we identified glissando-like patterns of brain electrical activity generated in anticipation of seizures in patients with epilepsy.”

The team recorded electrical activity taken from patients in Newcastle and Glasgow with the help of collaborators Dr Roderick Duncan and Dr Aline Russell and worked in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital part of the Newcastle Hospitals NHS Foundation Trust.

Having received permission from patients to use brain tissue removed during an operation to cure their seizures, the team were able to observe and study in great detail glissando discharges in slices of this human epileptic tissue maintained in the lab.

Publishing in Epilepsia online, the team discovered that glissandi are highly indicative of pathology associated with human epilepsy and, unlike other forms of epileptic activity studied previously, are extremely difficult to reproduce in normal, non-epileptic brain tissue. The team worked with Professor Roger Traub at the IBM Watson Research Centre in New York to provide predictions using highly detailed computational models. By manipulating the chemical conditions surrounding human epileptic brain tissue according to these predictions, they discovered that glissandi did not require any of the conventional chemical connections between nerve cells thought to underlie most brain functions. Instead, glissandi were generated by a combination of large changes in the pH of the tissue, specific electrical properties of certain types of nerve cell and, most importantly, direct electrical connections between these nerve cells.

"This work also suggests that given the lengths one has to go to reproduce this experimentally in rodents that the glissandi may be a unique feature of the human epileptic brain," explains Dr Cunningham.

Dr Kailah Eglington, Chief Executive of the Dr Hadwen Trust, said: “Of all human brain disorders, epilepsy research ranks as one that currently employs substantial numbers of laboratory animals worldwide.

"Dr Cunningham’s work at Newcastle University aims to address the shortcomings of existing animal-based research by removing animals from the equation and addressing the issue directly in humans."

Provided by Newcastle University

Source: medicalxpress.com

June 15, 2012

The first large non-commercial study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS) shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.

The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from the Peninsula College of Medicine and Dentistry (PCMD), Plymouth University. The study was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership, the Multiple Sclerosis Society and the Multiple Sclerosis Trust.

The preliminary results of CUPID are to be presented by lead researcher Professor John Zajicek at the Association of British Neurologists’ Annual Meeting in Brighton on Tuesday 29th May.

CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).

Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding. One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is that of slow progression.

As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis will continue for several months. The CUPID study will therefore provide important information about conducting further large scale clinical trials in MS.

Professor John Zajicek, Professor of Clinical Neuroscience at PCMD, Plymouth University, said: “To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be ‘neuroprotective’. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective.”

He added: “Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS.”

Dr Doug Brown, Head of Biomedical Research at the MS Society, said: “There are currently no treatments for people with progressive MS to slow or stop the worsening of disability. The MS Society is committed to supporting research in this area and this was an important study for us to fund. While this study sadly suggests THC is ineffective at slowing the course of progressive MS, we will not stop our search for effective treatments. We are encouraged by the possibility shown by this study that THC may have potential benefits for some people with MS and we welcome further investigation in this area.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012 By Angela Herring

Object manip­u­la­tion or tool use is almost a uniquely human trait, said Dagmar Sternad, director of Northeastern’s Action Lab, a research group inter­ested in move­ment coor­di­na­tion. “Not only does it require cer­tain cog­ni­tive abil­i­ties but also dis­tinct motor abilities.”

Professor Dagmar Sternad and postdoctoral researcher C.J. Hasson show that we subconsciously adjust our “safety margin” when we move a dynamic object like a cup of coffee based on the amount of variability in the situation. Credit: John Guillemin

Simply moving one’s own body, for instance by directing a hand toward a coffee cup, requires the orga­ni­za­tion of var­ious phys­i­o­log­ical sys­tems including the cen­tral and periph­eral ner­vous sys­tems and the mus­cu­loskeletal system.

Once the hand grasps and picks up the cup, the ques­tions become even more com­pli­cated. What if the cup is filled with liquid? At this point, the com­plexity of the con­trol problem bal­loons — the pres­ence of the liquid intro­duces non­linear fluid dynamics with the risk of a spill because of the inherent vari­ability in one’s movement.

Sternad, a pro­fessor of , biology, elec­trical and com­puter engi­neering and physics and post­doc­toral researcher C.J. Hasson are inter­ested in how we adapt our move­ment strate­gies when inter­acting with dynamic objects in the environment.

In a recent paper pub­lished in the Journal of Neu­ro­phys­i­ology, Hasson and Sternad explored the ques­tion by looking at the everyday task of manip­u­lating a cup of coffee. They show that how we adapt our move­ment strate­gies is directly related to the amount of vari­ability and reli­a­bility in our sur­round­ings and ourselves.

“Because we’re humans and not machines, we’re noisy and vari­able,” said Hasson. “We can’t expect that a move­ment will unfold exactly as we planned it.”

For the study, 18 healthy par­tic­i­pants vis­ited the Action Lab to play a video game, wherein they attempted to move a vir­tual cup filled with vir­tual liquid across a large video screen. Instead of a normal video-game con­troller, sub­jects moved the vir­tual cup by grasping a manip­u­landum — a large robotic arm. Sim­ilar to the real-life sce­nario, the robot sim­u­lated the forces one would feel from the weight of the object and the sloshing of the liquid in the cup.

They asked par­tic­i­pants to move the cup across the screen within a com­fort­able time of two sec­onds, a task for which there is an infi­nite number of pos­si­bil­i­ties. You could move fast for one second and slow for one second, slow for a half second and then fast for one and a half sec­onds. The team hypoth­e­sized that par­tic­i­pants would nat­u­rally adapt a safe move­ment strategy with prac­tice — and they did.

But the most intriguing result, said Hasson, was that the size of each participant’s safety margin —or how close they let the liquid get to the edge of the cup — could be pre­dicted by how vari­able they were in their move­ments. Those with more vari­ability tended to adapt a “safer” strategy with a larger safety margin.

“If you have a large safety margin and I move with a small margin, the ques­tion is, ‘Why am I more risky than you?’” Hasson said. “Well, you may find that I am much more con­sis­tent in my move­ments, so I don’t need a big safety margin. If you’re more vari­able, you need a larger safety margin.”

The results have impli­ca­tions in assessing elderly patients and patients of motor dis­or­ders such as cere­bral palsy. “If vari­ability deter­mines the move­ments that you do, maybe that’s an inter­ven­tion point,” said Sternad.

Provided by Northeastern University

Source: medicalxpress.com

June 15, 2012

Researchers from the Peninsula College of Medicine and Dentistry, University of Exeter, in collaboration with colleagues from Rutgers University, Newark and University College London, have furthered understanding of the mechanism by which the cells that insulate the nerve cells in the peripheral nervous system, Schwann cells, protect and repair damage caused by trauma and disease.

The findings of the study, published on-line by the Journal of Neuroscience and supported by the Wellcome Trust, are exciting in that they point to future therapies for the repair and improvement of damage to the peripheral nervous system.

The peripheral nervous system is the part of the nervous system outside the brain and the spinal cord. It regulates almost every aspect of our bodily function, carrying sensory information that allows us to feel the sun on our face and motor information, that allows us to move. It also controls the functions of all the organs of the body.

Damage can occur through trauma: it can occur in diabetic neuropathy (suffered by almost half of those with diabetes) and patients with common inherited conditions such as Charcot-Marie-Tooth (CMT) disease. There can be a wide range of symptoms, from loss of sensation in the hands and feet to problems with digestion, blood pressure regulation, sexual function and bladder control.

Schwann cells provide the insulation, or myelin sheath, for the nerve cells that carry electrical impulses to and from the spinal cord. Schwann cells, because of their plasticity, are able to revert back to an immature ‘repair’ cell to repair damage to the peripheral nervous system. The level of repair is remarkably good but incomplete repair, perhaps after the severance of a nerve, may lead to long-term loss of function and pain.

The ability of Schwann cells to demyelinate can make them susceptible to the disease process seen in conditions such as CMT. CMT affects one in 2500people, so is a comparatively common inherited disease of the nervous system. Mutations in the many different genes in CMT can cause cycles of repair and re-insulation (re-myelination) which lead to long-term damage and the death of both Schwann and nerve cells. There is currently no therapy for CMT and patients experience increased sensory and motor problems which may lead to permanent disability.

The research team believes that its work to understand the ability of Schwann cells to revert back to an immature state and stimulate repair will lead to therapies to improve damage from severe trauma and break the cycle of damage caused by CMT. They also believe that there may also be potential to improve repair in cases of diabetic neuropathy.

They have identified a DNA binding protein, cJun, as a key player in the plasticity that allows a Schwann cell to revert back to the active repair state. cJun may be activated by a number of pathways that convey signals from the surface of the Schwann cell to the nucleus. One such pathway, the p38 Mitogen Activated Protein Kinase Pathway, appears to play a vital role: it is activated after PNS damage and may promote the process of repair; conversely it may be abnormally activated in demyelinating diseases such as CMT.

Professor David Parkinson, Associate Professor in Neuroscience, Peninsula College of Medicine and Dentistry, University of Exeter, said: “The findings of our research are exciting because we have pinpointed and are understanding the mechanism by which our bodies can repair damage to the peripheral nervous system. With further investigation, this could well lead to therapies to repair nerve damage from trauma and mitigate the damage which relates to common illnesses, such as CMT.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012

Whether or not a neuron transmits an electrical impulse is a function of many factors. European research is using a heady mixture of techniques – molecular, microscopy and electrophysiological – to identify the necessary input for nerve transmission in the cortex.

Credit: Thinkstock

In the central nervous system (CNS), a nerve cell or neuron has a ‘forest’ of elaborate dendritic trees arising from the cell body. These literally receive many thousands of synapses (junctions that allow transmission of a signal) at positions around the tree. These inputs then are able to generate an impulse, or ‘spike’, known as an action potential at the initial part of the axon.

Previous research has confirmed that an activated synapse will generate an electric signal as a result of neurotransmitters released from pre-synaptic axons. Electrical recordings from the neocortex have confirmed that, in line with the cable theory prediction, that modulation of potential at the dendrite is highly distance-dependent from the cell body or soma.

The ‘Information processing in distal dendrites of neocortical layer 5 pyramidal neurons’ (Channelrhodopsin) project aimed to shed more light on how more distal sites in the ‘tree’ influence the action potential of the post-synaptic neuron. Furthermore, they investigated exactly how dendritic spikes can be generated, another issue about which there is little information so far.

Recent research has highlighted the importance of activation of N-methyl-D-aspartate (NMDA) receptors to bring about the production of a signal that will proceed to the soma and then result in a spike. There is also indirect evidence that interneurons targeting dendrites can control level of dendrite excitability.

Channelrhodopsin scientists simultaneously recorded the pre- and post-synaptic electrical recordings of identified interneurons and a special type of neuron, pyramidal cells that are primary excitation units in the mammalian cortex.

The project team first characterised the different types of inhibitory neuron deep in the cortex in layer 5 at apical tuft dendrites. The researchers then showed that a special type of inhibitory interneuron in the outer layer of the neocortex can suppress dendritic spiking in layer 5.

Project results show that a superficial inhibitory neuron can impact information processing in a specific pyramidal neuron. The research will have massive implications for neuroscience and help to unravel the integrative operations of CNS neurons.

Provided by CORDIS

Source: medicalxpress.com