A Brain Bank Halloween horror: A weakness of the mind

The term ‘haunting’ is generally applied to cases involving recurrent phenomena, of a supposedly paranormal nature, that are associated with particular places. Approaches to understanding hauntings can be divided into two categories: those that attempt to explain the manifestations ‘naturalistically’ (e.g. non-paranormal explanations), and those that employ paranormal concepts such as telepathy or the laying down of a ‘psychic trace’. – Peter A. McCue (2002)

“You know it’s all a load of b******s, just tricks of the mind….that’s why ghosts only come out at night,” I splurged as we sped along the A6. Miranda just laughed.

It was the weekend after Halloween and as a ‘bit of fun’ we had decided to drive across to Bakewell, enjoy the scenery, have a bite to eat, then, at twilight, wander down to the infamous ‘Shady Lane’. The Lane is said to be narrow and heavily wooded in parts; from all accounts a pretty creepy place to visit at any time of the day. However, according to legends the real horror comes at twilight. It is said that a procession of 12 headless men walk this lane in the failing light carrying an empty coffin. Apparently, if you are unlucky enough to catching a glimpse of these grisly coffin bearers it represents an omen of your imminent death.

I shuffled uncomfortably in my seat. Planning the trip had seemed like a bit of a laugh, something a bit different, a bit ‘hands on’ to do for Halloween and being scientists we knew it was all rubbish…didn’t we. However, I still couldn’t shake the feeling of unease.

As the bleak November countryside rushed past the window I turned to Miranda and, trying to add a sarcastic inflection to my voice, asked, “Do you think we’ll see anything?”. “I guess it depends if it’s our time or not,” she replied with a giggle, then after a pause added, “you’re not getting nervous are you?”.

“About what?” I replied, “The scary headless ghosts? Ha, there are enough real things to worry about without adding ghosts and goblins to the list. You know I have a presentation to give on Monday, now that’s scary”. She smiled and I turned back to the window.

The truth was however, that even though my logical brain knew that there was no real evidence behind the stories, just tall tales and folklore, I couldn’t shake the nagging doubt of the ‘what-if’s. That and, being a neuroscientist, I knew how amazingly deceptive the mind can be. Apparently most ghostly sightings and paranormal experiences can be explained away by tricks of the mind; states of heightened fear, tiredness, low light, even the obscure phenomena of ‘infrasound‘ can all trick us into experiencing things which just aren’t there. Yes I’d been researching it; but, despite my scepticism, after reading numerous ‘eye-witness accounts’ of experiences on Shady Lane my mind was primed for something paranormal.

It was about twelve o’clock when we eventually pulled into a small local car park. The clouds, which had been threatening a downpour since the start of our journey, finally made good on their threat and as we stepped out of the car the heavens opened. Pulling our hoods tight, we rushed for the nearest restaurant, fish and chips, no complaints there. I felt myself relax slightly as the familiar sounds and smells of the restaurant washed over me. After all, what reason did I have to be tense, this was just a normal day.

File:John Henry Fuseli - The Nightmare.JPG“Have you ever seen a ghost?” Miranda asked as we sat down.

“No,” I replied, “I tend to have a good relationship with the paranormal, I leave it alone and it leaves me. But actually,” I ventured, “…I do get sleep paralysis! Since I know what it is, it doesn’t scare me but I read that it’s responsible for a fair number of apparent ghost sightings”. Intrigued, Miranda leant in, “I’ve never heard of it before…..what is it?” she asked.

I decided to opt for a simple explanation, “It’s kinda the opposite of sleep walking. It’s when your mind wakes up, but your body stays paralysed. You feel like you’re awake, but you’re still mentally in a more suggestive ‘dreamy’ state. Since you can’t move or open your eyes your mind can play tricks….I often hear footsteps and sometimes feel like there’s someone or something in the room, often it feels like something is sitting on top of me”.

“Like a perverted ghost,” Miranda joked.

“Yeah, something like that,” I replied, “It’s relatively common, and can be explained scientifically, but before people knew what it was many thought they were experiencing a ghostly presence holding them down. It’s spooky stuff if you don’t know what you’re dealing with!”. Miranda looked genuinely concerned, “It sounds horrible,” she muttered.

“Yeah, but I guess it’s just an example of how complicated our minds are,” I said, “We’re all exposed to some pretty strange ideas in life, like ghosts and boogy men. I guess there are times, when you’re tired, or feeling scared, that your mind can wander; you know, create things which aren’t really there from its own imagination or fears… like your own internal horror movie ”.

I paused for a minute. The conversation had shifted and I wondered whom I was trying to convince with my rant. Perhaps, if I can recognise the reality behind these nocturnal horrors, I had no reason to be scared of Shady Lane? The logic is no different…“Are you ready to order?” chimed the waitress, snapping me back to reality with a jolt. Miranda glanced over, obviously noticing me jump at the unexpected intrusion. “You sure you’re OK?” she quizzed.

“Yeah, I’m fine, just got side-tracked” I smiled, and we ordered our meals.

As the day drew on the rain subsided and we decided to explore the town. Wandering round the shops we discussed more of our own personal ghostly experiences, debunking myths as we went, until eventually I started to wonder what I was so concerned about. Ghosts and ghouls are all in the mind; as long as you’re strong and can control your own fears you have nothing to worry about. With the acquisition of this new personal bravado I began to feel better prepared for our evening’s escapades.

It wasn’t long before the light began to wane and I soon found myself taken from the comfort of the busy shopping centre back to the car. The lane was a few miles outside Bakewell close to the village of Little Longstone. Our plan was to park up at The Packhorse Inn, a local pub in the village, then walk the rest of the journey to the lane, returning after dark for a well-deserved drink.

By the time we arrived at the pub the rain had started again, not a downpour this time, but rather a homogeneous haze, the kind of rain which manages to get you wet within minutes no matter how hard you try to avoid it. “Picked a great day for it,” I groaned.

“Well, it is November in the Peaks, what do you expect?” replied Miranda, then adding quietly, “You know if you’d rather stay here, have a drink and some food – I don’t mind”. For the first time that day I sensed a wavering in her resolve. Miranda was by far the most sensible and down-to-earth of my friends, to recognise the shudder of anxiety in her voice was particularly unusual. I’m not sure why, but something about her uncertainty spurred me on, giving me confidence… now I was the brave one!

“Ha, we can’t leave without even seeing the lane, Matt said we would chicken out, you don’t want to prove him right do you? He’ll never let us live it down,” I replied, grabbing my waterproofs from the boot of the car. “Lets do this!”

Ahead over two fields, then turn left on the Monsal Trail. Just before the railway bridge turn left up the steps then, at the top, turn right over the bridge.

We followed the directions I printed from the internet and soon found ourselves standing at the opening to the Lane. The ground was loose under our feet and a combination of the rain and waning light made it hard to see too far ahead. Miranda turned to me, “So you’re sure about this? You have been a bit off today you know”. I glanced back at her, trying to conceal the pleasure I suddenly felt over her uncertainly, “Don’t be silly,” I said with a cheeky grin, “I’m fine, lets go”.

Overcome with a sudden childish sense of accomplishment and mastery over my fears I began to run down the path. “Catch me if you can, slow coach,” I shouted as I sped around a bend.

Giggling to myself over how silly and unwarranted my earlier fears had been I slowed to catch my breath. The path was particularly narrow at this point and overhung by an unusually thick canopy considering the time of year, bloomin’ global warming. I squinted ahead through the gathering gloom, it looked as if further along another path joined the lane. Most likely the entrance to Thornbridge Hall. I glanced back to see if Miranda had caught up with me. I could just make out something moving in the distance, perhaps a flash of pink, could it be her coat? I was about to shout to her when something drew my attention, halting the words before they left my mouth. A shuffle, definitely the sound of movement coming from towards the turning. I spun around to try and glimpse the cause of the noise, but the path ahead looked deserted. Then it came again, the crunch of wet leaves underfoot, under a number of feet. My bravado all but gone, I felt my heart begin to race. If I could just get back to Miranda, get her attention, I’d be OK. But my legs wouldn’t move and my voice wouldn’t come. Cemented to the spot I stared helplessly ahead. Then they came, hazy at first and obscured by the rain, but certainly there. They were people, a group of them, moving slowly down the lane. I couldn’t see their faces, perhaps they were wearing hoods – or were they just headless? I felt faint.

Just as the last of my strength drained away and I felt the sudden pressure on my knees as I slid to the floor something else moved. Faster and smaller than the figures it appeared from between them, rushing towards me. Closing my eyes in panic I quietly prepared for the end.

Warm and wet, something landed on my chest, breathing heavily against my face and…licking… “Toby….Toby….what are you doing? Leave her alone,” a man shouted. “Are you all right luv’?”. I opened my eyes. There standing in front of me was a group of ramblers, with their hoods pulled tight against the rain and a large chocolate Labrador staring happily at me and panting. The dog’s owner looked concerned and offered me his hand. “I’m so sorry, Toby can be such a handful, he just loves people, but he doesn’t know his own strength”. My mind raced as I tried to make sense of what just happened. I reached for his hand and soon found myself lifted back to my feet. Miranda, having just caught up to me put her hand on my shoulder. “What on earth happened? Are you OK?”.

“I’m really sorry,” interrupted a young woman wearing a purple rain coat, perhaps the wife of the man who helped me up. “It’s our dog Toby, he got excited and knocked her over”. Sensing Miranda was about to jump to my defence I finally found my voice. “I’m fine really, no damage done, I have dogs too, so it’s no problem”. The woman smiled at me, “It’s getting late you know, where are you both heading?”.

“Back to the Packhorse Inn, in Little Longstone,” interrupted Miranda before I had time to speak.

“Ah so are we,” the woman replied. “How about we go together?”. Miranda caught my eye and I nodded feebly.

“It’s not like you to be floored by a dog,” she whispered as we started back towards the Inn.

“I’ll tell you all about it over a drink,” I muttered hoarsely and continued on ahead.

It had taken some time, but as we walked out of Shady Lane I began to piece the experience together in my mind. Perhaps I was more fallible than I imagined. I sighed, it seems no one is immune to fear. The group were chatting loudly amongst themselves “Did you hear the story about this lane? Apparently it’s haunted!”. “What a load of rubbish, you don’t believe in that kind of stuff do you?”. I turned to join in the conversation, but was interrupted by a sudden overpowering smell of incense, which vanished almost as quickly as it had appeared. “Did you just….” I turned to Miranda.

“Did I just what?” she replied.

I shook my head “Oh nothing, nothing, lets just get back”….

Story by: Sarah Werefox

The science behind the myths: Are there clinical explanations for vampires, zombies or werewolves?

When people don’t understand how something works, they often come up with their own explanations. For example, when ancient societies didn’t understand where lightning came from, they attributed it to an angry god. Thus the myth of the lightning god was born.

This tendency of humans to create their own explanations for unusual phenomena may have led to the invention of mythological creatures such as those now seen dominating fantasy writing and films. From a scientific point of view, it is interesting to investigate the source of these myths. How did they come about and why did they become so popular?

With Halloween approaching, I have decided to dedicate a blog entry to the potential ‘scientific’ explanations behind some of our favourite and most enduring mythological creatures: vampires,  zombies and werewolves!


Vampires have always been amongst the most popular mythological creatures, from the tales of Bram Stoker to more modern incarnations like those in Buffy the Vampire Slayer and Twilight. However, in case you have been living in a cave and these have all bypassed you, here is a brief overview of the vampire legend: vampires are generally believed to be human beings who, in life, were bitten by another vampire and then return after death to feed on the blood of other humans. Vampires are generally assumed to never die naturally but, depending on which adaptation you read, can be killed by exposure to sunlight, garlic, holy water or direct penetration through the heart with a wooden stake. Vampires are now a pretty popular part of modern culture, but how could the myth have first come about?

Although few scientific papers exist on this topic the internet is rife with debate and appears to point to several different medical conditions:

Probably the most popular theory of the origin of the vampire is the disease porphyria:  as explained by this article in Scientific American. Porphyria is actually a term for several diseases which are all caused by irregularities in production of heme, a chemical in blood. Some forms of this condition, such as cutaneous erythropoietic porphyria (CEP), lead to deposition of toxins in the skin. Sufferers are often sensitive to light since light activates these toxins. When active, toxins eat away at the skin causing disfigurement, including erosion of the lips and gums. These factors could have led to the corpse-like, fanged appearance that we associate with vampires and their dislike of sunlight. Interestingly, people who suffer from porphyria also have an intolerance to foods that have a high sulphur content…such as garlic.

Mycobacterium tuberculosis

Another possible explanation for vampires is tuberculosis (TB). This is a lung disease caused by the bacterium Mycobacterium tuberculosis. The reason this disease has been suggested as the origin of the vampire myth is because victims turn very pale, often avoid the sunlight and cough up blood. This is actually due to the disease damaging the lungs, but it’s easy to see how it could be misinterpreted as someone having recently drunk blood. According to this study, the vampire myth may also have arisen from the fact that TB spreads rapidly and easily from person to person. The infectious nature of this disease may have led to the belief that the vampire rises from the dead to feed on his loved ones, causing them to suffer the same symptoms.

An intriguing alternative explanation is Catalepsy. This is a disease of the central nervous system leading to a slowing of the heart and breathing rate, with sufferers often seizing up completely. These symptoms may have led people to mistakenly believe the sufferer to be dead. Therefore, since these individuals were perceived to have risen from the dead, it is easy to see how this disorder could be linked to paranormal mythology.


Ah, the zombie apocalypse, ever a popular scenario in films and books. Some organisations, such as the Centers for Disease Control in the USA even run “zombie apocalypse” days so you can prepare for what to do when the end is nigh.

Zombies are usually defined as people who were once human, but have been altered in some way so they no longer have a sense of self. Usually the sufferers have died and then been re-animated with a surprising taste for human brains. Zombies pursue this delicacy relentlessly. Often, anything that has had its free will removed and is bending to the will of others is also referred to as a “zombie”.

The zombie myth is believed to have originated in Haiti. There are many examples in Haitian and voodoo folklore of corpses which have been re-animated and used as slaves by sorcerers. The existence of zombies was explored scientifically in 1982 by Dr. Wade Davis after a man, Clairvius Narcisse, claimed to have been brought back to life by a sorcerer. Dr. Davis examined samples of the “zombie powder” which the sorcerer allegedly used to create his zombies. He found that the powder contained several toxins, including tetrodotoxin, which is found in pufferfish. Dr. Davis theorised that the tetrodotoxin caused paralysis and a death-like appearance in the sufferer, but that this state would eventually wear off, giving the illusion that the victim had been raised from the dead. He wrote two books on the subject, called Passage of Darkness and The Serpent and the Rainbow (the latter of which was used as the basis for a horror film). However, some sources do not believe that Davis’s work is scientifically valid due to the fact that the tetrodotoxin level in the “zombie powder” were actually found to be quite low. There was also some speculation that Davis’ work could have been plagued with murky ethics following reports of alleged grave-robbing.

Film depictions of the zombie apocalypse usually hint that it is rapidly spread by a pathogen such as a bacteria or virus. This may have some root in real life, as there are a number of known pathogens that are suspected of causing behavioural changes. As explained in this blog by fellow Brain Bank-er Sarah the parasite Toxoplasma gondii can control the behaviour of rats. The rats behave in a “zombie-like” manner, going against their natural instincts to actively seek out cats – the parasite’s true target. There have been some suggestions that toxoplasma gondii can affect the behaviour of humans too, making men more jealous and women more ‘warm hearted’. If T. gondii or similar parasites are ever able to affect humans in a way that modifies their behaviour to extremes well … hello, zombie apocalypse! (In the interests of not scaring you too much, I should point out that this scenario is very, very, unlikely).

However, there are other ways of creating a Zombie. Scarily, some current scientific techniques may one day be capable of creating ‘zombies’! Scientists are now capable of controlling some aspects of behaviour in certain laboratory animals using targeted laser light to activate groups of genetically modified neurons, this technique is known as optogenetics (for more detail see this post by fellow Brain Bank-er Natasha). This notion of behavioural control of ‘loss of free will’ is spookily similar to the depictions of some of the mindless zombies seen in popular culture. However, the ultimate aim of this technology is much less sinister, it is actually being used to investigate how the nervous system works and how problems may be corrected when things go wrong.


Werewolves appear to be having a mini media renaissance, thanks to Professor Lupin from the Harry Potter books and all of Team Jacob. Legend has it that werewolves spend most their time in human form but then, on the full moon, transform into a giant man-eating wolf with no human conscience. The werewolf usually turns back into a human at sunrise, with no recollection of their wolfish activities.

Lycanthropy, the clinical name given to werewolves in fiction, is actually a real medical term referring to someone who is under the delusion that they are a wolf.

Some medical theories concerning the origin of werewolves were explored in the book Why do Men have Nipples? by Billy Goldberg and Mark Leyner. One of these is once again based around porphyria, the same disease with links to the vampire myth. Some sufferers of cutaneous porphyria exhibit the canine “fang” look caused by the erosion of the gums. Also, following exposure to light, the healing blisters on sufferers’ skin often grow a fine layer of hair.

Someone suffering from congenital hypertrichosis universalis

The authors also speculate that the disease congenital hypertrichosis universalis could be a cause of the werewolf myth as this also causes excessive hair growth across the whole body. However, this disease is extremely rare so may not be prevalent enough to have bred such a popular myth.

Another possible reason behind the werewolf myth is the disease rabies. Rabies most famously affects dogs, but can also be transmitted to other animals. Its most characteristic feature is foaming at the mouth but it also causes hydrophobia (fear of water), aggressiveness, hallucinations and delirium. If an infected animal bites a human, they will suffer from similar symptoms. Possibly, in the past, someone noticed that a human bitten by a rabid dog took on the same characteristics and thought that the person was literally becoming a very aggressive dog or wolf.  However, rabies doesn’t explain the all-over hairiness or link to the lunar cycle most people associate with werewolves, particularly as, if you believe Noel Coward, sufferers of rabies famously come out in the midday sun.

According to howstuffworks.com, the idea of men turning into wolves has been  a part of folklore since ancient times, but was popularised by the 1941 film The Wolf Man. It is therefore possible that the myth of werewolves, unlike vampires and zombies, has been shaped more by popular culture than medical science.

My boyfriend suggested that being a woman may also be an origin for the werewolf myth. He decided to point out that women tend to get a bit aggressive at certain times once a month. This suggestion was met with a stony silence and being made to pay for dinner (I think it may have been a full moon).

So, there is no clear scientific explanation for these myths, but the subjects continue to fascinate and intrigue us. More and more films and books are being produced which revolve around these mythical horrors, often meaning that the origins of the myths become further buried as authors and film-makers add new characteristics and traits (However, that doesn’t make unearthing the science behind these enduring and popular creatures any less interesting). As you can see from some of the articles here, scientists are using the popularity of these myths, especially zombies, to raise awareness of very real and potentially dangerous situations such as the rapid spreading of a deadly disease. Since these stories can be used both to entertain and educate, keep the tales coming!

Post by: Louise Walking Dead

‘Working out’ the answer to MS-induced fatigue

With 2012 being the year of the Olympics, many of us will have noticed the various campaigns pushing us to get out and get fit. We receive regular updates on the benefits of exercise to our health and have become increasingly familiar with phrases like ‘30 minutes a day’ and ‘at least 3 times a week.’ Now, there is growing evidence to suggest that regular physical activity may also benefit Multiple Sclerosis (MS) sufferers – lessening their fatigue, aiding walking mobility and improving their quality of life.

MS is one of the most common neurological disorders affecting young adults today. Approximately 250 million people from around the world currently suffer from this disease; including some well-known faces from the Olympic sporting community itself. Some may recall the 4-times Olympic Gold medallist, Betty Cuthbert for instance, who was diagnosed with MS back in her thirties.

MS is a chronic autoimmune disease, where the bodies own immune system targets and damages the sufferers nervous tissue. The disease specifically targets the fatty covering which surrounds most nerve fibres (called myelin). Myelin is necessary for nerve cells to communicate efficiently over long distances, meaning that nerve fibres of MS sufferers are significantly less efficient at sending messages around the body. As a result, MS sufferers present with a range of symptoms, depending on where the damage is located, including fatigue, muscle weakness and reduced mobility.

Quite understandably, MS sufferers therefore tend to be less active than the general population. Approximately 75-95% of patients with MS report fatigue as their most common symptom, with at least half of suffers classifying it as being the most troublesome. To date no medicines have been approved by drug licensing bodies to treat MS-related fatigue. A number of studies trialling exercise therapy in MS sufferers, however, have yielded promising results…

A few years back in 2009, two independent research groups reviewed the use of physical activity to treat MS-associated fatigue and mobility problems. Maria Garrett and Susan Coote, based at Limerick University’s department of Physiotherapy, reviewed 19 related studies which took place between 2004 and 2008. Whilst Robert Motl and Erin Snook from the University of Illinois, drew evidence from 22 further studies spanning a period of more than 40 years. The type of exercise both groups were interested in consisted of regular and supervised exercise regimes which progressed in intensity over several weeks.

Crucially, the main conclusions that both Garrett’s and Motl’s groups drew from their assessments were that formal exercise programmes can have a positive impact on fatigue and walking mobility in patients with MS. In addition, no harmful effects or exacerbation to symptoms were seen in any of the studies, and patients generally felt their quality of life was improved by the therapy.

Despite a few limitations (such as small sample size), which may have biased the studies, both research groups believed that there was sufficient merit in these findings to justify further research into the area. In their discussions, Garrett and Motl both recommend the development of longer, larger and more controlled trials involving the use of exercise therapy on patients with MS. Unfortunately, while it seems this research may be well worth carrying out, no such studies have yet appeared.

However, just this year Robert Motl from the University of Illinois headed a pilot study on exercise intervention for MS. This research, published in the March 2012 edition of the Journal of Neurologic Physical Therapy, investigated the effects of an 8-week exercise programme on 13 patients with MS. This regime involved a mixture of aerobic, resistance and balance-based exercises supervised by an experienced physiotherapist. Promisingly, all the patients involved in this trial reported improvements in their walking mobility. Objective measures showing increased walking speeds also supported patient feedback. Looking at these results, one would certainly hope this trial will be a precursor to research on a larger scale.

So perhaps this year, MS sufferers could actually benefit from ‘jumping on the Olympic bandwagon’ to get active and exercise. After all, research so far has implied no harmful effects of using exercise therapy for patients with MS. Not to mention the small but promising number of trials, we have discussed here, which indicate that physical activity may in fact aid fatigue and walking mobility in suffers. Given such evidence, healthcare professionals may also look towards encouraging a change in the behaviour of their MS patients.

Meanwhile, I for one will certainly have my fingers crossed with the hope that Motl’s study is a sign that further and larger-scale research into this area is now on its way…

Post by: Megan Barrett


Why do you play?

File:Diablo III cover.pngIn July of this year, an 18-year old boy died in an Internet Cafe in Taiwan, after supposedly playing the video game ‘Diablo 3’ for 40-hours straight. Over the past decade, video gaming has become a controversial topic of escalating media attention. What was traditionally seen as a harmless pastime for children is now revealing a darker side, resulting in some devastating consequences. Namely, a worldwide increase in the number of diagnosed cases of gaming addiction. In an attempt to understand this problem neuroscientists are investigating what makes gaming addicts disrupt their sleep patterns, neglect personal hygiene and in some cases, push their bodies into cardiac arrest all for the sake of winning a game!

Some research suggests that gaming addicts may have a pre-existing tendency towards making bad decisions. One study investigated this in gamers who excessively played the online role-playing game, World of Warcraft. It was observed that in many decision making tasks, these gamers would persistently show a preference towards choices that would grant them instant reward, but would most likely be disadvantageous in the long run.

But what neural mechanisms underlie the ability to become so obsessed with a virtual world that addicts are able to discard even their most basic survival instincts? In 2009 a study used specialised imaging techniques to observed what happened in the brain when an individual experienced the urge to game. The researchers identified a number of key regions which they argued drove self-destructive behaviours in gamers. High activity was observed in the dorso-lateral prefrontal cortex (DLPC). An area which uses sensory information (i.e. what you see, hear and feel when playing the game) and memory about past experiences to maintain cravings by reinforcing positive expectations. Another active area was a structure called the caudate nucleus. This was identified as the region of the brain which allows the gaming urge to develop into a habit eventually becoming a routine which can be difficult to disrupt.

Significant evidence also indicates that video gaming triggers activation of the ‘dopamine reward system’. Dopamine is a neurotransmitter (a chemical that acts as a signal between brain cells) that has an important role in motivation towards rewarding behaviours. Scientists at the University of Michigan found that stimulating dopamine-containing brain cells led rats to develop strong cravings for particular rewarding behaviours. This research suggests that, in some individuals, a slight imbalance or over activity in this chemical pathway could cause the obsessive craving feelings that eventually lead to a gaming addiction.

A combination of these different processes may explain why, in some cases, we lose control after exposure to cues that remind us of the exciting and rewarding feelings that have been defined by our past experiences with a game.

One particularly interesting finding is that much of the research addressing the neural mechanisms behind gaming addiction, seem to overlap with those associated with drug dependency. For example, the DLPC is also activated in craving behaviour in cocaine, alcohol and nicotine addicts. Suggesting that the DLPC may have an important role in reinforcing craving-induced behaviours across all addictions.

So how does a gaming addiction turn lethal? For the most recent victim in Taiwan; he had been sitting in the same position for such a long time that a blood clot formed which eventually preventing blood from flowing to his heart leading to organ failure. However, another more general pitfall of prolonged game play is a sustained elevation in heart rate and blood pressure caused by the excitement and adrenaline rush associated with the act of gaming. If your blood pressure remains disproportionately high for long phases, the body’s energy expenditure is dramatically altered, hence why 40 hours sitting in front of a screen could kill you.

File:MK7 snapshot10.pngWhile I can’t pretend that I haven’t spent many mindless hours playing Mario Kart, I think that everyone, in particular young people, should be aware of the very real consequences that can result from long-term immersion in a virtual world. Indeed, due to the overlaps between gaming and other addictions, could it be time to treat gaming addictions as seriously as we do substance abuse?

Post by: Isabelle Abbey-Vital

Solving the Stem Cell Problem: A Nobel Prize-winning discovery

An important part a scientist’s work is being aware of the ethical issues surrounding their research and the implications these have on the wider community. Some scientists dedicate their careers to resolving these ethical issues. The winners of the 2012 Nobel Prize in Physiology or Medicine, John Gurdon and Shinya Yamanaka, have pioneered a method which hopefully represents a big step towards solving the ethical issues involved in the use of Stem Cells.

The Stem Cell Problem

Imagine that there was a potential cure for illnesses such as Alzheimer’s, heart disease, spinal cord injuries, or any number of others. Then assume that in order to achieve this, an unborn embryo has to be destroyed. What would you do? This dilemma is at the heart of the Stem Cell Problem.

Embryonic Stem Cell’s (ES) are used in a number of areas of research. The use of these cells is controversial since they are taken from human embryos, initially created for In Vitro Fertilisation (IVF) but not implanted, these ‘spare’ embryos are then donated to scientific research. Unfortunately, during the course of the research the embryo is destroyed; a fact which has led some organisations, such as the Catholic Church, to claim that research using ES cells is tantamount to murder.

The reason ES cells are so important to medical research is that certain properties, only possessed by these young cells, makes them ideal for therapeutic manipulations. Mature cells in the human body are highly specialised towards their function, whether this is in the blood, liver, brain or elsewhere. However, stem cells are immature cells which have yet to develop into their final specialised form. When required, the stem cell is stimulated by certain factors in its environment and eventually develops into a specific mature cell type, for example a blood cell. This means that an embryonic stem cell has the potential to become any cell in the body, given the right environment! ES cells are also able to replicate themselves many times over, unlike specialised adult cells. Therefore these cells are invaluable to scientists investigating cell behaviour and methods for regenerating damaged tissue. The therapeutic uses for stem cells range from understanding cancer to regenerating tissue in a whole number of degenerative disorders.

The 2012 Nobel Prize in Physiology and Medicine was recently awarded to two researchers who made extraordinary advances in cell reprogramming. Their pioneering work has given scientists a clearer understanding of how cells function and also provided a method of obtaining stem cells from adult tissue. Thus, potentially solving the ethical issues surrounding the use of ES cells in research.

Cell Reprogramming

One of the Nobel Prize recipients is Sir John Gurdon of the University of Cambridge. In 1962, Gurdon transferred a nucleus (the part of the cell which contains DNA) from an adult frog cell into a frog egg cell. The egg developed into a normal tadpole, showing that DNA from a specialised adult cell could be reprogrammed to function in a developing embryo. This was a landmark discovery since, up until this point, it was thought that adult cells “lost” certain components of their DNA so could not function as part of a developing cell. Gurdon’s work showed that this wasn’t the case proving that mature differentiated cells contain a full compliment of DNA; it’s just that some of the DNA in mature cells is inactive. This also showed that mature adult DNA can be reverted to a previous immature form. The work opened the door for many other scientific breakthroughs, including the cloning of Dolly the Sheep in 1996.

Shinya Yamanaka, the second Nobel recipient, built on Gurdon’s work reprogramming mature adult cells back to an immature form. Yamanaka developed a line of cells called induced Pluripotent Stem Cells (iPSCs). He and his colleagues adjusted the expression of certain components within adult cells, enabling them to revert back to their young, stem-cell, form. These reprogrammed cells had similar characteristics to embryonic stem cells, including the ability to mature into a variety of different cell types. Yamanaka then used the same technique with human adult cells, reverting them to a state similar to an ES cell, further developing his concept to be used in the study of human cells and diseases. As they display many of the important properties found in ES cells, iPSCs could potentially be used as a replacement for ES cells, thus eliminating the controversy surrounding the use of embryonic cells in research.

Stem Cells in Organ Transplants

The potential of iPSCs doesn’t stop at replacing ES cells. They could also herald a major advance in the science behind organ transplantation. Since, ES cells can both regenerate themselves several times over and become any cell type, their use in the replacement of damaged tissue is now being studied. Meaning it may soon be possible for patients to receive transplants composed of reprogrammed cells (iPSC’s) from their own bodies. This would solve the major problem of transplant rejection from donated tissues, caused by the recipient’s body recognising the donated organ as foreign. In theory, an iPSC-derived tissue would not be rejected as it would be made from the patient’s own cells.

Problem Solved?

As a cell biologist, I may be slightly biased, but I think many scientists (especially biologists) would agree that the work undertaken by Gurdon, Yamanaka and their colleagues is incredibly exciting. It represents a great leap forward in our understanding of how cells work and new ways of studying them in a controversy-free environment.

So, does this Nobel prize-winning work signal a solution to the Stem Cell Problem? Alas, no. It is unclear whether iPSCs and ES cells are equivalent on the molecular level, casting doubt on the likelihood of iPSCs being able to completely replace ES cells in research. Another problem, as with many newly discovered techniques, is that the long-term effects of these technologies are unknown. For example, there are concerns that cells derived from any form of stem cells have a tendency to become cancerous. There has also been a surprising report that iPSCs still produce an immune response when transplanted in mice, which would lead to transplant rejection.

So, unfortunately we still don’t have a comprehensive solution to the Stem Cell Problem. However, this does not detract in any way from the discoveries of Gurdon, Yamanaka and their colleagues, and there is no doubt that their innovation, expertise and skills should have been rewarded by the Nobel Prize. Only time will tell just how much more useful their discoveries will be.

Post by: Louise Walker

For more information on the properties and use of stem cells: http://stemcells.nih.gov/

Can neural implants hotwire damaged brain circuits?

Scientists from North Carolina have developed and implemented a neural implant designed to improve higher-order brain processing- providing hope that one day such implants may be developed to alleviate symptoms of cognitive impairments such as Alzheimer’s.

The brain: the final frontier. Neuroscientists around the world are working painstakingly to uncover the mysteries of the brain and ultimately find ways to reinstate functionality lost through damage or disease. One area of research offering such promise is the field of neural prostheses. At a basic level this work endeavors to repair faulty neural connections by interfacing the brain with computer technology. Significant advances have been made in connecting the human brain with the outside world through sensory and motor prostheses (for example the artificial retina). However, the task of restoring or improving cognitive function has yielded very different problems to those addressed in the development of sensory and motor interfaces.

To restore cognitive function, a neural implant must gather data from one area of the brain, process this information correctly and then deliver the resulting signal to another brain region, bypassing any damaged tissue. This process necessitates an understanding of how different brain regions communicate with each other and how this communication is modified as it travels through the brain in the form of electrochemical impulses. Although this is certainly not an easy task, if successful, this research will have a profound impact on the quality of life throughout society, offering promise for people suffering from a range of disorders including Alzheimer’s, stroke and various other forms of brain trauma and degeneration.

Implant in prefrontal cortex (pink circle): Implant records activity in layers 2/3 and layer 5 (blue) and stimulates in layer 5 (red)

Sam Deadwyler and his team at Wake Forest University School of Medicine in Winston-Salem, North Carolina have recently taken an important step toward making cognitive enhancement via neural prostheses a reality. This group is the first to study the effect of brain implants on decision-making in behaving primates. Their work focused on an area of the brain known to be involved in decision-making; the prefrontal cortex. The structure of this region is well-known and can be separated into a number of layers, each containing different types of brain cell. These cells form connections between layers, passing information through the structure. The team developed an implant which could span a number of these layers. This implant was positioned to record activity simultaneously from both layer2/3 and layer 5 and to deliver custom-designed stimulation to layer 5 cells.

The first task faced by the team was to understand how cellular activity changed when the monkey made either a correct or incorrect decision. To achieve this, the group monitored activity across the implant as the monkeys performed a memory task (choosing a familiar image from a group of unfamiliar images). The team focused on cellular recordings taken just prior to the point when the animals made their choice: the decision period. After observing a number of trials, they found that they could predict how cells would respond to both correct and incorrect decisions. This meant that the scientists were able to ‘decode’ the language of the cells and predict what choice would be made before the animal actually made it!

Now that the group knew what a correct response looked like they were able to write a pretty complicated algorithm to mimic this activity and replay it to cells in layer 5. Amazingly they found that animals stimulated with this artificial activity pattern performed significantly better on the task than animals receiving no stimulation. Indeed, in some of the harder tasks (ones using more images) the animals improved both their speed and accuracy, in some cases improving their average performance by 10-20%. This improvement was also dependent on the stimulation provided. For example an improvement would only be seen if a monkey was provided with a ‘correct’ stimulation pattern calculated from its own data, but not when the experimenters used patterns taken from other animals or arbitrary patterns.

The next question was: if this stimulation could improve performance in normal animals, could it also recover the ability to make correct decisions in animals with specific impairments? This is an important question, since the ultimate medical goal for these implants would be to restore lost functionality. To answer this question the team used a drug that they knew reduces connectivity in the prefrontal cortex and impairs decision-making: cocaine. Monkeys given cocaine performed poorly on the task, being on average 10% worse than their sober counterparts. The team was able to monitor layer 2/3 activity in these animals and judge when an incorrect decision was about to be made, then replace the incorrect activity with their own simulated correct firing pattern. This intervention not only restored normal function but actually raised the cocaine-treated animals performance scores even higher than non-treated animals.

Nope I still don't understand this...

It can’t be denied that from both a technical and medical standpoint, these findings are amazing. However, I believe there are still a number of hurdles to be cleared before we see this technology implemented in patients suffering from cognitive deficits. Many cognitive disorders, such as Alzheimer’s, involve widespread damage incorporating a large number of higher-level processing areas. It is therefore an absolute requirement that we first understand exactly how information is processed in these systems, before we attempt to bypass or repair them. Although this implant certainly improved performance, it relies significantly upon mimicking what is known to be a correct response rather than understanding how the system works. This reminds me of my primary school recorder lessons, where I learned to play by watching where other pupils put their fingers instead of learning to read the sheet music. The end result may be similar, but you can go much further and make fewer mistakes if you fully understand the system! Therefore I think the ‘take home’ message from this study is; we have made some promising progress towards improving cognition through neural implantation, however if we ultimately want to treat widespread neural damage we still need to get a better grip on how these systems function before we move toward treatment.

Post by Sarah Fox