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The Neuroscience of Sleep and Circadian Rhythms in Adolescent Learning

November 20, 2014

By Dr. Christopher-James Harvey


At its simplest, sleep is driven by two broad systems working symbiotically: sleep/wake homeostasis and biological circadian rhythms. Sleep/wake homeostasis tells us that the need for sleep is accumulating as we progress throughout the day, and helps us to maintain sleep throughout the night to make sure that the ‘sleep debt’ we have built up throughout the day is repaid.


If this homeostatic system existed alone then we would all start the day feeling fresh and progressively get drowsier as the day went on. This is not the case: we have peaks and troughs in our tiredness/alertness throughout the day. This rhythm is driven by our internal circadian biology: our biological clock. In adults we naturally feel more tired between 13:00-15:00 and our strongest sleep-drive is at around 02:00-04:00. The intensity of tiredness during the circadian-lows will vary depending on how much sleep we have had the night before, as will the intensity of the alertness: if we are sleep deprived we will feel more tired during the natural dips and less alert during the natural highs. In this way sleep homeostasis informs circadian rhythms. Of course, as with anything in nature, there is natural variation in these rhythms from person to person but as a general rule these patterns are pretty consistent.


The circadian rhythm is driven by the suprachiasmatic nucleus (SCN), a part of our brains, which receives light signals from the optic nerve. In the morning, when it begins to get light, the SCN tells us it is time to be awake. The SCN then signals the onset of various processes, such as increasing body temperature and the production of certain hormones, such as cortisol which, amongst other functions, increases blood sugar, to provide an increase in energy levels. Other hormones, such as melatonin, are suppressed. Melatonin is involved in the onset of sleep and sleep maintenance. Melatonin levels typically remain low during the day and high during the night, increasing as we approach sleep.

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Education and Neuroscience

October 9, 2014

With new findings from neuroscience catching the headlines every day, surely we can tap into these results to improve our education system? The Education and Neuroscience Initiative hopes to address this question – this joint programme of work between the Wellcome Trust and the Education Endowment Foundation (EEF) aims to: build research and expertise at the interface between neuroscience and education; support the responsible transfer of technologies, resources and practices based upon neuroscience into education; and help teachers to be able to make informed choices based upon the best available evidence. In this post we explain why we are embarking on this work, share some of the learning we’ve gained in the process, and we invite a wider conversation on this topic.

Why are we doing this?

A vital reason to get this research off the ground is because teachers are already adapting their practice due to their interest in neuroscience, but have a weak evidence base to do so. A survey of teachers and parents we carried out in 2013 was consistent with previous research showing educators’ enthusiasm and appetite for increasing their understanding of how the brain learns and changing their teaching methods in response. Unfortunately a plethora of ‘brain-based’ programmes and publications, many of which are not based on real science let alone systematically tested, are pretty much all that is readily available to meet this demand. In many cases teachers were potentially wasting time and effort on programmes and pedagogies which were unsubstantiated. At its worst, teachers can be vulnerable to unscrupulous entrepreneurs who used pseudo-science to promote unevaluated, and sometimes expensive, educational approaches.

Many neuroscientists have emphasised the potential of their research to improve education, yet it is rare for their findings to be translated into testable and practical interventions. We wanted to help stimulate exploration of how neuroscience research could be translated into beneficial interventions and to test these ideas so that we know what does and does not work.

We do recognize that a lack of common language and different expertise can hinder neuroscientists and educators working together, but we are hopeful that bringing in other collaborators, such as psychologists and cognitive or sports scientists, will help bridge the divide. One of the aims of this Initiative is to help grow this interdisciplinary area of research and perhaps stimulate further funding in this area – watch this space!

The funding round

A central part of the Initiative has been the multi-million pound joint funding round with the EEF, launched in January 2014. It was a challenge to define the criteria for the research call to achieve our desired aims. We wanted to test interventions or teaching practices that were informed by neuroscience, and that already had some pilot data or evidence of raising attainment of pupils aged 5-16 (with a particular focus on disadvantaged learners to meet the EEF’s core purposes). In addition, interventions had to be practical, affordable and scalable so that those shown to be effective could be easily used by other schools.

We were delighted to receive nearly 90 applications from universities, schools, charities and other educational organisations on a very broad range of topics. It was encouraging to see diverse collaborations, and in some instances scientists applying their research to answer educational questions for the first time. We are most grateful to all the education and neuroscience experts who helped us in the shortlisting, peer review and interview process – your expertise and input were invaluable.

Today we are excited to be announcing the six successful projects which will investigate the effectiveness of a range of interventions and changes to teaching practices which have been based upon, or informed by neuroscience. In addition to the attainment measures that will be collected, some of the teams will also be collecting additional physiological and neurological measurements to build the evidence about what is happening in the bodies and brains of the children in the studies. In the coming months we will post blogs from each of the teams to give a greater insight into their proposed research questions.

In adopting the EEF’s approach to educational research, each of the project teams have been paired with an independent evaluator and the two teams will be working collaboratively to modify the trial designs from the initial applications and develop appropriate evaluation methodologies. As a research funder, it was really interesting to be involved in using this unusual model – most researchers typically evaluate their own work. The conversations and discussions in working up the collaborative project designs and evaluations have been fascinating.

What’s next?

The funded projects will be starting to recruit schools to take part in the trials in the near future. We hope that many schools will be keen to be part of such exciting research. It is important to remember that we will not know the extent to which the interventions are effective, if at all, until the final evaluation reports when the research is complete – so please be patient.

We are about to embark on another element of this initiative in which we will be trying to help teachers to successfully navigate the minefield of neuromyths, and instead access robust research to build their professional knowledge to inform their practice.

Neurogenesis: state of the field and implications for education

May 12, 2014

By Lisa M. Saksida, Reader in Cognitive Neuroscience, University of Cambridge. 

Nearly everything that we do has an impact on our brains. Changes in our behaviour and in our environment can lead to structural and functional alterations in our brains. These changes can happen at a number of different levels, from molecular and cellular changes that happen as a result of learning, up to the reorganization of entire cortical areas as a result of injury. This process is sometimes called experience-dependent plasticity, and it occurs at all ages, although the degree of plasticity is relatively high in childhood and decreases over the course of our lifetime. Neuroplasticity is what allows us to learn, to remember, to adapt and to modify our actions on the basis of experience.

One specific aspect of neuroplasticity that has received much attention over the past two decades is adult neurogenesis – the notion that new neurons can be produced in an adult brain. Until the mid-1960s it was firmly believed that neurogenesis in mammals ends in the period just after birth. Technological developments in the 1990s led to an ongoing period of intensive research in this area, and it is now well-established that every day thousands of new neurons are produced in the adult mammalian brain (Cameron and McKay, 2001; Spalding et al., 2013). Many of these new neurons are produced within a region of the brain called the hippocampus, which has long been established as being critical for learning and memory processes.

Although the process of neurogenesis has been well-studied, it is only very recently that the specific functional or behavioural consequences of neurogenesis have been considered. Increased neurogenesis generally correlates with better memory, as might be expected when the part of the brain associated with learning and memory is increased in volume. But what is the specific role of these new neurons in learning and memory?

There are several theories, but the largest body of evidence so far (although it is still very preliminary) supports the idea that new neurons in the hippocampus are important for a memory process known as “pattern separation” (Clelland et al., 2009) . In contrast to our usual notion of memory as the ability to retain information over time, pattern separation at the behavioural level refers to the ability to keep memories distinct and resistant to confusion. Imagine you are asked to remember where you parked your car this morning, yesterday morning and the day before. This task is difficult not because you need to remember something that happened a long time ago– it is easy to remember much of what happened three days ago – but because the similar memories of parking your car in the same car park over three consecutive mornings are so easily mixed up.

One very interesting aspect of neurogenesis is that it is highly responsive to environmental influences, some of which are described below. A number of simple factors have been shown to enhance neurogenesis. Less research has been done on the specific knock-on effects of increased neurogenesis on cognition, but some promising initial studies have been performed.

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Educational Neuroscience: Implications for deaf children

March 31, 2014

By Mairéad MacSweeney, Wellcome Trust Senior Research Fellow at the UCL Institute of Cognitive Neuroscience.


I work with people who are born severely or profoundly deaf in order to inform our understanding of how the brain processes language. People born deaf can provide a unique insight into how the brain processes language. This is because the vast majority of the population are born hearing, and hear spoken language even before they are born, while still in the womb. They are always surrounded by it. But for a child who is born profoundly deaf, the situation is very different.   By definition they have incomplete access to spoken language. In addition some deaf children may access a purely visual language – in this country – British Sign Language. We can look at language development and brain development in these children to gain unique insights into how language is processed in the absence of sound. I look at sign language processing and also spoken language processing in the form of lip-reading and reading.

Reading forms a major part of my current research. Deaf children find it incredibly difficult to learn to read, because when we read we read a spoken language written on the page and deaf children have impoverished access to spoken language. Although deafness is not a learning disability – most deaf children have normal non-verbal IQs – a typical deaf child will have a reading age of 10-11 years old when they leave school aged 16. This has major consequences for their educational and vocational attainment.

A major skill in developing reading accuracy is learning how to map the written letters onto the correct sounds. This is what phonics training is all about – mapping sounds to letters or letter combinations. Broader language skills are also very important to reading comprehension, such as semantics (the meaning of words) and syntactic structure (how words are put together to form sentences).

Some deaf children do become very good readers. If we can understand how they achieve this, despite the fact that they can’t hear the language that they are reading, then this can give us insights into how we might be able to better teach all deaf children. More broadly, an understanding of how important hearing spoken language is for learning to read has the potential to inform our understanding of reading in hearing children too, not just deaf children.

For example, one of the core deficits in hearing children with dyslexia is that they have poor phonological awareness skills, such as knowing that “chair” rhymes with “bear,” or that “split” without the “l” is “spit.” One of the main theories of dyslexia in hearing children is that they have some kind of low-level auditory processing deficit. With deaf children we can look at a group who have very little or no auditory input, and look at the impact of that on their reading.

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Attention and Motivation

February 3, 2014

Cognitive Neuroscience of Attention and Motivation

By Masud Husain, Wellcome Trust Principal Fellow, University of Oxford.    

Recent developments in the neuroscience of attention and motivation have moved forward at a rapid pace. We now understand a great deal about the brain systems, networks and neurotransmitters that underpin the deployment of attention and human motivation, two fundamental processes that are widely considered to play key roles in learning and educational outcome. However, application of these findings to education and improved performance is still in its infancy.

Neurofeedback is perhaps the technique which is closest to being used in educational settings. In this relatively new approach students are given real-time feedback on their own neurological state. This is typically achieved by visualising brainwaves using electroencephalography (EEG; Gruzelier, 2013), although neurofeedback has also been attempted with real-time functional magnetic resonance imaging (Weiskopf, 2012) in adults. It is proposed that by monitoring their brain activity through the use of neurofeedback, students are able to train their brains to produce specific patterns of activity that are optimal for learning (Enriquez-Geppert et al., 2013).

Several studies and, more recently, randomized trials have been conducted using  EEG in children with attention deficit hyperactivity disorder (ADHD) (Loo, et al, 2012Lofthouse, et al, 2012Moriyama, et al, 2012Gevensleben, et al, 2012). One recent six month study has even reported that neurofeedback outperformed standard drug treatment (methylphenidate) for ADHD in terms of academic outcome (Meisel, et al, 2013).

Other potential interventions include transcranial magnetic stimulation (TMS) (Demirtas­‐Tatlidede, et al, 2013), transcranial direct current stimulation (tDCS) (Kuo, et al, 2013) and cognitive enhancement using drugs (Husain & Mehta, 2011). The use of these techniques to enhance cognitive function has been explored, to varying extents, in adults. For example, tDCS has been reported to improve numerical abilities in adults (Cohen Kadosh, et al, 2010) but the use of such techniques in children, in particular, raises both safety and ethical issues (Cohen Kadosh, et al, 2012).  Similarly, studies of cognitive enhancement using drugs in adults have shown signs that the individuals most likely to benefit are those who have the lowest performance (Husain & Mehta, 2011), but these studies have not been systematically tested. For most drugs, the long-­term safety profile and effects on cognition have not been established in children.

In order for techniques to be translated effectively into the classroom, to become useful and safe, they need much further testing, considering both ethical and safety issues. Obtaining regulatory and ethics committee permissions for such studies would not be straightforward, but a case could be made, particularly if there is an unmet need, for instance, for students with different types of learning disability.

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Neuromodulation: could it improve education?

January 23, 2014

By Roi Cohen Kadosh, Wellcome Research Career Development Fellow, University of Oxford. 

Harnessing neuroplasticity for education using neuromodulation

I like movies. One of my favourite scenes is in “The Matrix” where the hero, Neo (no relationship to the cortex), took a short nap while a plug was inserted into the socket at the back of his head. A few seconds later, Neo woke up and said, “I know Kung Fu!” What a lovely idea! It would be much easier to learn maths, languages, and just to upload all the articles and books that I have not yet been able to read. Unfortunately, this remains as science fiction, and depending on the subject or type of learning it can take days, months, and even years of intensive labour. In the case of those with learning difficulties, such efforts do not improve their performance as they may in other people. My aim is not to invent a machine like the one Neo used, but to make a smaller step by examining the possibility of modulating neuronal activity in the brain whilst people are learning a skill and subsequently using it. Still, to the non-expert reader, it does sound like science fiction, and one of the questions that I was asked four years ago during my interview at the Wellcome Trust was if this idea is indeed feasible. In this blog I introduce the neuroscientific principles of the technique that I use in my research and describe the progress so far. I also discuss the work that still needs to be done in our efforts to improve the speed and quality of learning, and thus, educational achievements.

Stimulating the Brain using Electricity: A shocking idea?

The first association that comes to mind when electricity and brain stimulation are mentioned is electroconvulsive therapy (ECT) in which strong electrical current is induced in anaesthetised psychiatric patients for therapeutic effect. This is not what we are doing. Rather, my lab is using a technique called transcranial electrical stimulation (tES), in which we apply a small electrical current (for example, 1milliAmp, or one thousandth of an Ampere) to the scalp to modulate neuronal activity during training in order to enhance learning and high-level cognitive functions. The current is generated from a low power source, such as two AA batteries, and is delivered to the scalp using one or more electrodes.

Our research is supported by more basic research in neuroscience, in which animal studies have shown that low electrical currents can affect neuronal excitability and make it either easier or harder for neurons to fire (Bindmann, et al., 1964). More recently, research has shown that this is safe and effective in humans (Paulus, 2013Cohen Kadosh, 2013). By employing mostly basic tasks that have little to do with education, this early research has shown that it is possible, for instance, to aid finger movements (Nitsche & Paulus, 2000) or help the brain to detect motion more accurately (Antal, et al., 2004).

Animal studies have shown that this low level of electricity can enhance the secretion of a growth factor (brain-derived neurotrophic factor) which is crucial for synaptic learning (Fritsch, et al., 2010). Furthermore, in humans, the modulatory effect of tES affects regional levels of neurochemicals (gamma-aminobutyric acid and glutamate) that are involved in learning, memory, and neuroplasticity (the brain’s ability to change in response to new experiences or learning; Stagg, et al., 2009). In line with these findings, some studies have shown that tES in combination with training can improve motor skills acquisition (Reis, et al., 2009).

This research led to a great deal of hope for rehabilitative applications of tES, mainly in rehabilitation of those with acquired neurological damage, such as stroke patients, or degenerative illnesses (Cohen Kadosh, 2013). However, I envisage that this tool can be used to improve educational outcomes, such as learning of maths, or other functions that are critical for optimum educational outcome, such as literacy, working memory or attention (Kraus & Cohen Kadosh, 2013; Cohen Kadosh, et al., 2013).

Such an approach—to modulate neuronal excitability whilst people are learning, inducing physiological changes and harnessing neuroplasticity—is, in my view, one of the most exciting synergies between neuroscience and education. We are not only examining the neural correlates of learning or cognitive skills, but rather we are affecting the brain to increase learning outcomes in a given cognitive area. In the next section, I will describe some results from my lab, which focus mainly on one of the most sophisticated human abilities: mathematical cognition.

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Adolescent brain development

January 22, 2014

By Sarah-Jayne Blakemore, Royal Society Research Fellow and Professor of Cognitive Neuroscience at UCL. 

1. Adolescent brain development: What have we learned in the past 15 years?

Until about 15 years ago it was assumed that the vast majority of brain development takes place in the first few years of life. Up until that point, scientists did not have the technology to look inside the living, developing human brain. In the past decade, mainly due to advances in brain imaging technologies, in particular magnetic resonance imaging (MRI), neuroscientists have started to scan the living human brain at all ages, in order to track development changes in the brain’s structure – its organisation, including how much grey matter it contains – and also how it functions, across the lifespan. Many groups around the world are working in this area, and we now have a rich and detailed picture of how the living human brain develops. This picture has significantly changed the way we think about human brain development, by revealing that development does not stop in childhood, but continues throughout adolescence and well into adulthood.

Adolescence is defined as the period of life that starts with the biological changes of puberty and ends at the point at which an individual attains a stable, independent role in society. There are clearly large cultural differences in the age range associated with adolescence, and yet there are reports of adolescent-typical behaviour, such as heightened risk-taking and peer influence, in many very different cultures. There are also similarities in descriptions of adolescents throughout history. For example, in The Winter’s Tale Shakespeare portrayed adolescents as follows:

I would there were no age between 16 and three and twenty, or that youth would sleep out  the rest; for there is nothing in the between but getting wenches with child, wronging the ancientry, stealing, fighting.

Thus, almost 400 years ago, Shakespeare painted a similar picture of adolescents as we do now, and we are trying to understand this kind of adolescent-typical behaviour in terms of the underlying changes in the brain that characterise this period of life. One of the brain regions that undergoes the most striking and prolonged changes during adolescence is the prefrontal cortex. This is the part of the brain at the very front, and is involved in a wide variety of high level cognitive functions, including decision-making and planning, inhibiting inappropriate behaviour, stopping you taking risks, social interaction and self-awareness.

One of the main findings is that grey matter, which contains brain cell bodies and connections between cells in the prefrontal cortex, increases in volume during childhood, peaks in early adolescence and then starts to decrease in adolescence, and this decline continues throughout the twenties. So, the prefrontal cortex loses grey matter during adolescence. It has been proposed that this decline in grey matter volume partly reflects an important neurodevelopmental process: the loss of connections between brain cells (synapses) during development. This process, which is known as synaptic pruning, partly depends on the environment in that connections that are used are strengthened; connections that aren’t used are lost – they are pruned away. Synaptic pruning fine tunes brain tissue according partly to the environment. You can think of it as a bit like pruning a rose bush. You prune the weaker branches in order for the remaining branches to grow stronger. This is happening throughout adolescence in several cortical regions, including the prefrontal cortex.

A second line of inquiry involves scanning the brain using functional MRI (fMRI) to track changes in brain activity with age. Many fMRI studies have shown that brain activity associated with tasks such as decision-making, planning, inhibiting a response and reasoning, changes across adolescence.  For example, in my research group, we are particularly interested in the social brain – that is the network of brain regions that is used to understand other people. We bring adolescents into the lab to have a brain scan, and while they are being scanned we give them tasks that involve thinking about other people’s emotions, thoughts and feelings. Studies from our lab and from other labs shows consistently higher levels of activity in a social brain region called the medial prefrontal cortex in adolescents when they carry out social tasks that require understanding irony, thinking about social emotions such as guilt or embarrassment, or thinking about someone else’s intentions, for example. The different levels of activity within regions of the social brain might be because adolescents and adults use a different cognitive strategy (mental approach) to make social decisions. This is a hypothesis currently under investigation.

In order to look at cognitive approaches to social cognition, we carry out behavioural studies with adolescents, and we and other labs are finding that the ability to understand other people, for example to take another person’s perspective to guide decisions, is still developing in adolescence. At the same time, many studies have shown that the ability to plan and delay gratification is still developing during this period of life. Another area of adolescent research is risk-taking. It is well documented that teenagers tend to take risks, especially when they are with their peers. There appears to be a drive towards seeking the approval of peers, and becoming independent from one’s parents, in adolescence. Even adolescent rats and mice take more risks immediately after puberty than before puberty or in adulthood. One proposal that attempts to explain why risk-taking peaks in adolescence is to do with the brain’s limbic system – this is the brain system that gives us a rewarding feeling when we taking a risk. There is some evidence that in adolescence the limbic system is particularly sensitive to this rewarding feeling. And at the same time, the prefrontal cortex – which stops us taking risks and acting on impulse – is still developing.

Read more…

Education and neuroscience: An expert review

January 7, 2014


By Moheb Costandi

Our understanding of how the brain works has advanced rapidly in the past few decades, and there is now more public interest in neuroscience than at any time in the past. We have reached the point at which neuroscience has the potential to inform classroom practice and improve children’s educational outcomes – consequently there has been a significant increase in so-called “brain-based” classroom interventions which purport to do so.

At the same time, research suggests that myths and misconceptions about the brain are  prevalent among schoolteachers, and that those who are enthusiastic about the potential applications of neuroscience on teaching practice find it difficult to distinguish between pseudoscientific claims and scientific facts. Indeed, a recent survey by the Wellcome Trust found that many teachers use or have used educational activities which they believe to be based upon neuroscience but which rarely have a sound basis in the science – nor have they been systematically proven to improve performance. Teachers are clearly eager to improve their practice, but are trying to do so before the educational applications of neuroscience have been fully developed and tested.

As well as providing approximately £90 million per year in funding for neuroscience research, the Wellcome Trust is committed to improving science education and has funded a number of education and engagement projects about neuroscience in the past. One focus of the Trust’s 2010-2020 Education Strategy is to examine the ways in which brain research is being used to inform teaching and learning and, where possible, to develop further investigations into the strength of the evidence and how it can support and improve the quality of education.

To this end, the Trust’s education team has commissioned an expert review that examines the interface between neuroscience and education. Researchers, each with expertise in an area of brain research that has the potential to be applied to educational practice, were asked to: examine the readiness of their field to shape education; make judgements about whether or not their field is likely to yield testable and fruitful educational interventions; and provide recommendations about how it would be best to approach funding the testing of such interventions.

The review consists of a series of articles written by the contributing researchers. Selected summaries of these will be published on this ThInk blog over the coming weeks, covering a wide range of topics, from brain stimulation to neurogenesis and learning. The review was not intended to be exhaustive, but to help the Wellcome Trust decide on its next action in this area. For instance, research into circadian rhythms – that is, your body’s biological clock – is not covered in the review, but has already been tested in some schools and provides an interesting example of how neuroscience might improve educational outcomes. Circadian rhythms change dramatically during puberty and adolescents experience a delay of approximately two hours in their sleep/wake cycle as a result. In practical terms, this means that the school day starts too early for most adolescents, at a time when pupils are reaching the end of the sleep phase of their cycle. It follows that starting the school day an hour or two later would be beneficial, because timing the start of school with the onset of the wake phase of the cycle would optimise pupils’ potential for learning.

Circadian neuroscience researcher Russell Foster is one of the biggest advocates of this approach, which has recently been implemented in a UK school, although not in a way which allowed controlled assessment of its impact. It has, however, been tested in the US. In 1997, seven high schools in and around the Minneapolis area shifted their start times from 7.15 to 8.40am on the basis of these findings, and the first longitudinal study has shown that later start times had significant benefits, including improved attendance rates and less fatigue and sleeping in class.

To complement the Wellcome Trust’s work, the Education Endowment Foundation, with which the Trust has been partnering in this initiative, commissioned a review of the educational literature to identify other areas of research that could potentially be applied in the classroom. Conducted by Paul Howard-Jones, the review examines the available evidence about education initiatives that are, or purport to be, informed by neuroscience, and was guided by questions considering the validity of the alleged scientific basis of the educational concepts and approaches and the quality of evidence for impact.

Together the views of expert neuroscientists and the understanding of current practice from teachers themselves, as well as the educational literature review, have convinced the Wellcome Trust and the Education Endowment Foundation to embark on a new funding initiative – Education and Neuroscience. This £6 million one-off scheme aims to develop, evaluate and communicate the impact of education interventions grounded in neuroscience research. Do check back or sign-up for updates to read more of the expert opinions that helped to shape this work over the coming weeks.

Is it okay to use smart drugs?

May 20, 2013

C0021281 Tablets

In the past 5 years or so, there has been a huge increase in lifestyle use of prescription drugs that can enhance cognitive function in various ways. These so-called “smart drugs” include the stimulants methylphenidate (better known by its trade name, Ritalin), which is used to treat attention deficit hyperactivity disorder, and modafinil (also known as Provigil), used as a treatment for narcolepsy.

Off-label use of smart drugs is particularly prevalent among students, who face increasing pressure to improve their academic performance. They therefore take these drugs in an effort to focus their attention for longer periods of time and boost their overall productivity.

According to a 2008 survey conducted by the journal Nature, the use of smart drugs is increasing among academics, too. One in five of the approximately 1,600 researchers who responded to the survey said that they had used smart drugs – with Ritalin being the most popular – to focus their attention, memory or concentration.

Is it okay to boost brain function in this way? The question has divided the scientific community. Some researchers say ‘no’ for safety reasons: we still don’t know the consequences of taking smart drugs for long periods of time, and youngsters are particularly at risk because their brains continue to develop well into early adulthood. And the ease with which anyone can buy smart drugs online also raises concern.

Some object to cognitive enhancement on ethical grounds: it may increase the inequalities already present in society, because not everyone could afford to buy the drugs. And what about those who object because they think it would give an unfair advantage? Would they feel pressured into popping brain-boosting pills just to keep up with the others?

Others say that enhancement is not a dirty word, that more research should be done, and that the public should work together with scientists and policy makers to regulate the use of smart drugs. They emphasize the potential benefits that cognitive enhancement could bring to society. Recent research shows, for example, that smart drugs can improve the performance of sleep-deprived surgeons and nightshift workers. The U.S., British, French and Chinese military forces now use Modafinil routinely to combat fatigue in troops, and the drug has also been shown to improve some aspects of cognitive function in psychiatric patients.

Last year, the Wellcome Trust commissioned the second wave of its Monitor Survey, which was designed to assess the UK general public’s level of awareness and attitude toward this controversial issue. This is the most representative such survey to date, and included responses from nearly 1,400 adults and 400 young people aged 14-18.

The results show that opinion is similarly divided: About one-third of adults and young people said that long-term use of smart drugs to improve focus, memory or attention, or occasional use to improve exam performance or something similar, was acceptable, while about one-third said that it was unacceptable.

The results also suggest that the use of smart drugs is less widespread among the general public than within universities, with only 29 adults (or 2% of the total sample) and 9 young people (or 1%) saying that they had ever taken prescription medications for that purpose.

What’s your opinion? Join the debate using the Wellcome Trust’s Big Picture app.

Exposure to stress hormones in the womb linked to mood disorders

May 15, 2013

ResearchBlogging.orgPregnancyStress hormones released by a pregnant mother can cause the placenta to shrink and can directly affect the developing brain of the foetus. Now, researchers have identified the mechanism through which stress may damage an unborn child in the womb. An enzyme in the placenta of the mother and the brain of the foetus acts as a barrier to protect the unborn baby from chemicals released in times of stress. But during periods of prolonged stress – such as anxiety and depression or due to a traumatic event such as abuse – levels of the hormones can soar and are believed to overwhelm the protective barrier, resulting in a host of problems. The damage may make the child more likely to develop mood disorders such as depression, anxiety, and even schizophrenia.

Professor Megan Holmes of the University of Edinburgh has been looking into the mechanisms involved. She identified that an enzyme in the mother and baby, called 11-β HSD2, works by mopping up stress hormones called glucocorticoids (GCCs) and converting them to their inactive form. Using pregnant mice genetically engineered to lack the enzyme, her team showed that the increased exposure to GCCs (like cortisol) resulted in smaller pups, which went on to exhibit the signs of mood disorders. The mothers also had smaller placentas which meant a reduced flow of nutrients to pups in the womb – which could directly contribute to their mental condition.

When the team blocked the enzyme in the brains of the developing pups, but left the enzyme barrier in the placenta, the baby mice still showed some signs of damage. This indicates that both sites, the placenta and the foetal brain, play a role. The team are looking to see if one of the two sites has an overriding effect, although it’s thought to be a combination of the two.

This enzyme barrier is crucial during pregnancy as it maintains the difference between the relatively high levels of stress hormones in the mother and the low levels in the foetus. If too much GCC reaches the foetus it can affect the development of growing tissues. For instance, if the developing brain is exposed to cortisol it can cause the young cells to stop dividing and to start maturing instead. Although this is a key step in the normal developmental process, if it happens too early things can go wrong and it can result in faulty wiring of the brain. “The neurons may not be in right place yet and may be differentiating too soon” says Holmes.

But Holmes’ work suggests that stress exposure doesn’t just impact the brain in the womb, it can have an effect in adolescence too. Puberty is another key point in the timeline of the brain’s development, as it’s when existing connections and networks are strengthened or weakened. It’s a time when the brain is particularly sensitive to environmental factors, including stress.

In experiments, adolescent rats were conditioned to associate a flashing light with an electric shock and then had their brains scanned using functional MRI (fMRI). When they were shown the cue of a flashing light their emotional fear pathways were activated. In rats that had been stressed, the amygdala – the part of the brain which deals with fear and emotion – was overactive compared with rats that hadn’t been stressed. This indicated that the way in which the brain processed emotional stimuli had been changed.

The results suggest that the early teenage years are another critical period in the brain’s development in which stress could have an impact on the network of connections. The rewiring of emotional response pathways in the brain could result in long-term problems with mood disorders and emotional behaviour.

Presenting these findings at the British Neuroscience Association’s Festival of Neuroscience conference in London last month, Professor Holmes said that she hopes to use the animal models to uncover more about the pathways involved and to find more accessible targets for treatment. “We think this a really good translational model, so we can do the same tests or comparative tests to what are done in patient populations.”

It’s not all just mice and rats either, the damaging effect of stress hormones on the developing brain has demonstrated in human studies. Trials showed that the children of women who suffered from anxiety or depression during the pregnancy were more likely to develop the mood disorders themselves. In a telephone interview, Professor Vivette Glover, of Imperial College London, explained to me that in pregnant mothers with anxiety, production of the enzyme 11-β HSD2 decreases and this could expose the unborn baby to more cortisol. “The first thing is to look after pregnant women better,” said Glover. Although whether or not it’s a case for drug treatment isn‘t clear at this stage, “it’s an interesting idea”, she added.

Although genetic predisposition and environmental factors play a strong role in influencing the risk of developing mood disorders, this research hints at the potential for early therapeutic intervention. Currently, targeting 11-β HSD2 directly for drug treatment is difficult, so clinical trials may not be on the horizon just yet. “At the moment our intention is to use our models to see exactly which pathways are changing through development,” said Holmes, “and to try and find an alternative target that’s more easily targetable therapeutically.”


  • Holmes M (2013). Perinatal programming of stress-related behaviour by glucocorticoids. Abstract presented at BNA 2013, London.
  • O’Donnell, K., Bugge Jensen, A., Freeman, L., Khalife, N., O’Connor, T., & Glover, V. (2012). Maternal prenatal anxiety and downregulation of placental 11β-HSD2 Psychoneuroendocrinology, 37 (6), 818-826 DOI: 10.1016/j.psyneuen.2011.09.014
  • Giedd, J., Blumenthal, J., Jeffries, N., Castellanos, F., Liu, H., Zijdenbos, A., Paus, T., Evans, A., & Rapoport, J. (1999). Brain development during childhood and adolescence: a longitudinal MRI study Nature Neuroscience, 2 (10), 861-863 DOI: 10.1038/13158

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