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A method for imaging the brain that has largely been confined to neuroscience labs may now find its place as a proper tool for medical diagnosis.

Oxford University scientists have come up with a new approach that turns functional magnetic resonance imaging (fMRI) from something that produces pictures of changes in brain activity into a full numerical measure of how the brain is working.

Doctors may be able to use this new MRI approach to provide a lot more clinically useful information about patients coming in with strokes, brain injuries or a variety of other conditions.

Functional MRI is a tremendously successful research method for imaging the brain. The pictures it produces of the working brain are now pretty familiar, with different regions of the brain ‘lighting up’ while those being scanned do different tasks, and it has taught us a lot about the organisation of the working brain in health and disease.

However, the technique only captures relative changes in the MRI signal. And what is more, the MRI signal reflects a complex mix of different physiological processes going on in the brain, such as changes in blood flow and brain cells burning up the oxygen they get from the blood. That is: fMRI is very much an indirect indicator of brain activity, not a pure measurement technique able to put a value on specific brain processes.

‘MRI is great for localising which areas of the brain are activated during different stimuli and so helping us to understand how the brain works as a whole,’ explains Dr Daniel Bulte of Oxford's Centre for Functional Magnetic Imaging of the Brain (FMRIB), who led the work. ‘However the images we produce are just that, pictures. They are not measurements.’

The scientists at FMRIB have countered this by introducing a new approach to MRI scanning. They report their work in the journal NeuroImage.

Patients lie in the MRI scanner and breathe air through a mask or nose tubes. By simply varying the proportion of carbon dioxide and oxygen the patients breathe through the mask, the scientists show it is possible to use the MRI signal to measure blood flow, blood volume, oxygen use and brain metabolism across the whole brain.

‘By making some slight changes to the air breathed by a patient in the scanner we can produce beautiful images of brain physiology that actually correspond to real measurements,’ says Daniel. ‘During the scan the subject would spend short periods breathing a little extra oxygen than normal and short periods breathing a little extra carbon dioxide. The subject would not notice either of these as the changes are quite subtle compared to normal air.’

The measurements are comparable to those obtained with another more complex medical technique called Oxygen-15 positron emission tomography, or ¹⁵O-PET. However, the MRI approach would have a number of advantages and – importantly – wouldn’t expose patients to the radioactive labels used in PET.

‘The problem with ¹⁵O-PET is that it is very, very expensive, there are very few places in the world that can do it, the scans take a long time, and it requires giving the patient a significant dose of radiation,’ says Daniel. ‘Our MRI method takes less than 20 minutes to perform, could be run on any modern clinical MRI scanner, is very cheap and uses no drugs or injections, and exposes the patient to no ionising radiation.’

Daniel adds that it could be a real boon in hospitals: ‘At the moment most stroke patients get a CT scan when they arrive at the hospital, and very few get an MRI. The main reason for this is that MRI is much more expensive than CT, and the imaging techniques currently available do not provide enough diagnostic information to be sufficiently useful for most patients. Thus the diagnoses and treatments are arrived upon with very little detailed information about what is actually going on in the patient's brain.

‘A scan such as this one could potentially be used to provide emergency room staff with much more information about a variety of different diseases and injuries, improving the outcomes for the patients, and saving time and money. We hope to start trialling the scans with patients with a range of different diseases later this year.’

The study was funded by the EPSRC, MRC, Wellcome Trust, Dunhill Medical Trust and the NIHR Oxford Biomedical Research Centre. 

They may have looked more like a green carpet than a forest but the first land plants really did change the world.

New research led by scientists from Oxford University and Exeter University has shown that the invasion of the land by plants in the Ordovician Period (488-443 million years ago) cooled the climate and triggered a series of ice ages.

I asked Liam Dolan of Oxford University’s Department of Plant Sciences, one of the leaders of the research reported today in Nature Geoscience, about the work and what it reveals about yesterday’s - and tomorrow’s - climate:

OxSciBlog: What sort of plants were there during the Ordovician?
Liam Dolan: The fossil record tells us that the first plants to grow on land appeared sometime before 475 million years ago during the Ordovician Period.

We only have fossilised remains of small fragments of plants but we don’t know how the bits fit together – a bit like a jigsaw puzzle with a lot of the bits missing. It is safe to say that these plants were very small and probably looked like liverworts and mosses - their closest living relatives.

OSB: How did the climate change during this period?
LD: Climate changed dramatically during the late Ordovician Period. It changed from a climate that was warmer than today (with no ice) into an ice age. Ice ages are pretty rare in Earth history and what gave rise to the Ordovician glaciation has always been a mystery.

OSB: How did you test whether plants triggered this change?
LD: While increasing the amount of carbon dioxide causes global warming, removing carbon dioxide from the atmosphere causes global cooling. One of the dominant mechanisms for removing carbon dioxide from the atmosphere is silicate weathering: the chemical reaction between silicate minerals of rocks and carbon dioxide in the atmosphere.

We tested the hypothesis that non-vascular plants (mosses) increase rates of silicate weathering. To our amazement we found that these simple plants did in fact increase the weathering of silicate minerals. We then incorporated these measurements of silicate weathering rates into computer models of Ordovician Period climate.

When we re-ran the models with our new data, we discovered that the appearance of the first land plants in the Ordovician plants would have caused a dramatic decrease in atmospheric carbon dioxide which would have brought about climate cooling and contributed to the initiation of the late Ordovician ice age. 

OSB: What do your results reveal about how plants influence climate?
LD: We know that plants play a critical role in climate systems by pulling carbon dioxide out of the atmosphere in two ways: Firstly, plants carry out photosynthesis, which converts carbon dioxide into plant biomass that store carbon. Secondly, plants increase rates of silicate weathering, the chemical reaction that breaks down rocks, and in so doing removes carbon dioxide from the atmosphere.

We knew that the dramatic cooling of the planet between 300 and 200 million years ago was the result of the evolution of large plants with large rooting systems that caused huge changes in both of these processes. In the results we published today we showed that the appearance of the first land plants had an effect much earlier - 100 million years earlier.

For me the most important take home message is that the invasion of the land by plants - a pivotal time in the history of the planet - brought about huge climate changes. It should also remind us that the removal of large areas of the world’s vegetation, which act as carbon stores, will increase atmospheric carbon dioxide levels and cause dramatic climate change.

OSB: What can they tell us about plants and climate change today?
LD: Our discovery emphasizes that plants have a central regulatory role in the control of climate: they did yesterday, they do today and they certainly will in the future. This study warns us that if we continue destroy the Earth’s vegetation, by felling forests and draining wet lands, we will suffer dramatic climate change: the opposite of an ice-age. That’s called global warming.

Professor Liam Dolan is based at Oxford's Department of Plant Sciences.

The idea of a simple, cheap and widely available device that could boost brain function sounds too good to be true.

Yet promising results in the lab with emerging ‘brain stimulation’ techniques, though still very preliminary, have prompted Oxford neuroscientists to team up with leading ethicists at the University to consider the issues the new technology could raise. They spoke to Radio 4's Today programme this morning.

Recent research in Oxford and elsewhere has shown that one type of brain stimulation in particular, called transcranial direct current stimulation or TDCS, can be used to improve language and maths abilities, memory, problem solving, attention, even movement.

Critically, this is not just helping to restore function in those with impaired abilities. TDCS can be used to enhance healthy people’s mental capacities. Indeed, most of the research so far has been carried out in healthy adults.

TDCS uses electrodes placed on the outside of the head to pass tiny currents across regions of the brain for 20 minutes or so. The currents of 1–2 mA make it easier for neurons in these brain regions to fire. It is thought that this enhances the making and strengthening of connections involved in learning and memory.

The technique is painless, all indications at the moment are that it is safe, and the effects can last over the long term.

Dr Roi Cohen Kadosh, who has carried out brain stimulation studies at the Department of Experimental Psychology, very definitely has a vision for how TDCS could be used in the future: ‘I can see a time when people plug a simple device into an iPad so that their brain is stimulated when they are doing their homework, learning French or taking up the piano,’ he says.

The growing number of positive results in early-stage studies, led the neuroscientists Dr Cohen Kadosh and Dr Jacinta O’Shea to talk to Professor Neil Levy, Dr Nick Shea and Professor Julian Savulescu in the Oxford Centre for Neuroethics about what ethical issues there may be in future widespread use of TDCS to boost abilities in healthy people.

The researchers outline the issues in a short paper in the journal Current Biology, and indicate the research that is now necessary to address some of the potential concerns.

‘We ask: should we use brain stimulation to enhance cognition, and what are the risks?’ explains Roi. ‘Our aim was to look at whether it gives rise to new ethical issues, issues that will increasingly need to be thought about in our field but also by policymakers and the public.’

‘This research cuts to core of humanity: the capacity to learn,’ says Professor Julian Savulescu. ‘The capacity to learn varies across people, across ages and with illness. This kind of technology enables people to get more out of the work they put into learning something.’
 
He adds: ‘This is a first step down the path of maximizing human potential. It is a very exciting development but we need to control the release of the genie. Although this looks like a simple external device, it acts by affecting the brain. That could have very good effects, but unpredictable side effects.’

One of the most obvious uses of brain stimulation techniques is in children as an educational or learning aid. The researchers believe that their use in children would be warranted, and that we should begin research to understand how TDCS might be used in children.

Roi notes that: ‘Parents will often send their child to piano lessons or to football lessons, wanting them to do well.’ He considers that providing people with ways of fulfilling their potential is not a bad thing.

The researchers consider whether brain stimulation could be thought of as cheating, with the idea that we can get extra cognitive abilities for no effort. Here they offer a resounding ‘No’.

The technique seems to boost the learning process in conjunction with standard education or training. There is no free ride here – people still need to work at learning a new skill or language themselves. ‘It won’t be possible to go to sleep at night with the electrodes on, wake up the next day and pass all your exams,’ says Roi.

They also look at access to this technology, and will it further benefit the well off. But they suggest the TDCS kit is simple and cheap enough to be available to all in schools.

‘This technology overcomes some standard objections to enhancement: It is not a set of cheat notes,’ says Julian. ‘You require effort and hard work to learn. It is just that you get more out of your effort. And because it is cheap, low tech, easily affordable, it could be widely available. This addresses the objection that it will introduce inequality and unfairness. It could be available and should be available to all, if it is safe and effective.’
 
The researchers’ concern is more that the technology is such that people could assemble all the components needed at home reasonably simply. Roi clearly says that this is not warranted yet with our limited current knowledge about the technique’s use: ‘The message should very much be “Don’t try this at home”.’

While there have been some ethical discussions in the past of using some drugs to boost concentration or attention, the researchers explain that TDCS is different and needs to be considered separately.

For example, drugs in general are prescribed for use by one person, ingested and taken internally, and with limits on dose. There are no such in-built limits with brain stimulation, and it may not feel as serious as taking a drug because it is an externally applied treatment – though its effects may be as strong.

‘Once you have a brain stimulation device, you can use it as often as you want and there are no limits on who uses it,’ Roi points out.

But at the current time, most of the TDCS work that has been done is preliminary, small-scale and in the lab. There are no clear guidelines for its use as yet, as research is still establishing the optimal ways of using TDCS for different areas of cognition.

The researchers are concerned that in this gap, some people could step in to offer TDCS to vulnerable patients or parents desperate to advance their children before the technique is fully understood.

The researchers also identify a number of outstanding questions:
Are there downsides to boosting capacity in one area of cognitive ability? Do other mental abilities lose out?
The developing brain in children is different to adults. With most research having been in adults, the use of TDCS in children becomes a pressing question.
And are the benefits seen in the lab clinically relevant: can TDCS lead to improvements that matter in normal daily life?

Julian says: ‘At this stage, we need more research to understand better the risks and benefits, in specific populations, in real life. Any regulation should prevent misuse and abuse, but facilitate good research. This kind of technology could be as important as the internet and computing. Those are external cognitive enhancements. This is basic fundamental cognitive enhancement.’
 
The researchers conclude the exciting potential of TDCS requires that this research be done and all these ethical questions considered.

‘Enhancing cognitive abilities, or our ability to learn, is not a bad thing to do. There is no problem with that, as far as we see, as long as there are no side effects,’ says Roi.

‘What is the ethical way forward? More research before deployment,’ says Julian. ‘It is promising but not proven at this stage.’

For BBC science correspondent Tom Feilden's take, see here. 

The researchers are funded by the Wellcome Trust, Australian Research Council, the Oxford Martin School and the Royal Society.

If you’re enjoying BBC Two’s Stargazing Live then you’ll want to join in the astronomical fun at Stargazing Oxford this Saturday, 21 January.

The free public event, running 2pm-10pm at Oxford University’s Department of Physics, aims to offer space-related activities for all ages.

Kids can learn to make cardboard telescopes, satellites, and a working spectrograph out of a cereal box – to discover how the light from distant stars can tell us what they’re made of.

There’ll also be the chance to observe the night sky through a range of telescopes and learn tips for star-gazing at home from amateur astronomy groups and Oxford scientists.

Other highlights include an inflatable planetarium, getting hands-on with a collection of meteorites, talks exploring topics such as simulating the universe, the shape of galaxies, and the weather on other planets.

There’s even space-inspired art on display, in the form of ‘darkmatter’, a unique and exhilarating work by installation artist Marion Yorston, and you can see the latest images from today’s best telescopes, plus models of tomorrow’s telescopes – SKA and E-ELT – that, when completed, will be the largest in the world.

You’ll find updates on preparations for the event on the Astro Blog, but there’s no need to book in advance just drop-in to the party, held at the Denys Wilkinson Building, on the day.

Pop psychology assertions about left-brain/right-brain differences are pretty much tosh. Our personalities are not dominated by a battle between the creative skills residing in one half of the brain competing with the hard reasoning in the other.

But that’s not to say there aren’t any differences between the left and right sides of our brains. There are some anatomical details that differ between the opposite hemispheres of the brain. Language appears to be localised more to networks in the left brain, and differences in the brain can be seen according to whether we are right-handed or left-handed.

Understanding the detail of these left-right differences – how they occur and how they underlie the processing going on in our brains – is tricky, though.

A research group based at Oxford and Cambridge universities led by Professor Ole Paulsen has been using some of the latest, most precise neuroscience techniques to get a handle on this problem.

The scientists studied recently discovered asymmetries among nerve cells involved in learning and memory processes in the mouse brain. Their findings were published in Nature Neuroscience.

These particular nerve cells, or neurons, are found in the mouse hippocampus, part of the brain intimately involved in memory.

Neurons in one part of the hippocampus have different numbers of brain-chemical-responding proteins according to whether they are contacted by the left or right side of another region of the hippocampus.

The question is whether this finding of a molecular left-brain/right-brain difference is important: does it play any role in learning and memory?

Standard lab techniques for probing neurons and working out what’s going on tend to use electric currents to stimulate the nerves to fire. But such approaches would not be fine enough or accurate enough to pinpoint differences according to whether signals came from the left or right side of the hippocampus.

So the researchers used laser light and gene technology to gain extra control and be able to define exactly which neurons were being stimulated to fire. The technique, known as optogenetics, was pioneered by Professor Gero Miesenböck at Oxford.

‘It enables us to be far more precise about which cells are being activated. We really gain control over what’s happening in a cell,’ explains Oxford DPhil student Olivia Shipton.

Olivia and her colleagues used this approach to stimulate only the key neurons on the left side of the hippocampus, or alternatively only the neurons on the right.

They then measured what this did in the neurons receiving these connections. They reasoned that if the left-right asymmetry in the hippocampus is important, there may be differences according to which side of the brain the signals came from.

They found that signals coming from the left hippocampus led to a strengthening of long-term electrical connections between neurons. This strengthening of connections is a widely accepted model of learning and memory in the brain.

‘It is thought to be associated with how we lay down new memories,’ says Olivia.

In contrast, there were no such changes with signals coming from the right hippocampus.

‘There was a striking difference. It suggests that the left and right hippocampus in the mouse have distinct functions in learning and memory processes,’ says Olivia.

She adds that it’s possible to speculate that the right hippocampus may provide a constant signal or context against which new learning could be compared through the left side.

The group now want to explore if this functional difference between the left and right sides of the hippocampus is important in guiding the learning of mice.

They believe it should be possible to use the same techniques to control which sides of the hippocampus fire and whether this affects a mouse’s spatial memory as it learns how to navigate mazes.