In a lab at Stanford University, a mouse is showing signs of depression. For around 10 weeks, it has experienced a series of irritations, from bouts without food or water, to erratic sleep patterns. Now, its motivation is low—when picked up by the tail, it makes few attempts to escape, and it doesn’t try to explore new spaces. It’s also less willing to sip from a sugary liquid– a sign that it gets less pleasure from normally pleasurable activities. It is never easy to assess the mental health of an animal, but this mouse is clearly showing some of the classic symptoms of depression.
But not for long.
Earlier, Kay Tye and Julie Mirzabekov altered the mouse so that a flash of light can activate a small part of its brain—the ventral tegmental area (VTA), near the bottom of the brain and close to the midline. A burst of light, and the mouse’s behaviour changes almost instantly. It struggles when held aloft, it explores open areas, and it regains its sweet tooth. A burst of light, and its symptoms disappear.
But on the other side of the country, at the Mount Sinai School of Medicine, Dipesh Chaudhury and Jessica Walsh are doing the same thing to completely different effect. Their mice have been altered in a similar way, so that light can also switch on their VTA neurons. But these rodents have endured a shorter but more intense form of stress—10 days of being placed in cages with dominant, aggressive rivals. Because of the resulting attacks, some of them have developed depressive symptoms. Others are more resilient. But when Chaudhury and Walsh flashed the VTAs of these mice, resilient individuals transformed into susceptible ones.
Both studies used the same methods to trigger neurons in the same part of the brain… and got completely different effects. In Tye and Mirzabekov’s experiment, depressed mice resumed their normal behaviour. In Chaudhury and Walsh’s study, the resilient mice showed more depressed symptoms.
That’s how my latest piece for Nature News starts. It’s obviously a cute result, but there’s some serious and intriguing science underlying it. These twin rewarding activities – sex and drinking – are linked by a chemical called neuropeptide F (NPF), which acts as a sort of currency of reward in the brain.
The study suggests that NPF is part of a system that acts like a ‘reward-thermostat’. If flies aren’t getting rewarding feelings from sex, their levels of NPF fall, and this compels them to get their kicks elsewhere, such as in a boozy meal.
Mammals also have a counterpart of NPF, known as NPY, which may play a similar role. It’s depleted in the brains of people who attempt suicide or suffer from PTSD, and some clinical trials are testing it as a way of dealing with addictions or mood disorders.
RM had his first out-of-body experience at the age of 16. Now, at the age of 55, he has had more than he can count. They usually happen just before he falls asleep; for ten minutes, he feels like he is floating above his body, looking down on himself. If the same thing happens when he’s awake, it’s a far less tranquil story. The sense of displacement is stronger – his real body feels like a marionette, while he feels like a puppeteer. His feelings of elevation soon change into religious delusions, in which he imagines himself talking to angels and demons. Psychotic episodes follow. After four or five days, RM is hospitalised.
This has happened between 15 to 20 times, ever since RM was first diagnosed with schizophrenia at the age of 23. He hears voices, and he suffers from hallucinations and delusions. Despite these problems, he managed to hold down a job as a reporter until 2002 and more recently, he has been working in restaurants and volunteering as an archivist. Then, about a year ago, he took part in a study that seems to have changed his life.
For large swathes of the brain, the neurons we’re born with are the ones we’re stuck with. But a few small areas, such as the hippocampus, create new neurons throughout our lives, through a process known as neurogenesis. This production line may be important for learning and memory. But it has particularly piqued the interest of scientists because of the seductive but controversial idea that it could protect against depression, anxiety and other mood disorders.
Now, by studying mice, Jason Snyder from the National Institute of Mental Health has found some of the strongest evidence yet for a connection between neurogenesis and depression (or, at least, mouse behaviours that resemble depression). He found that the new neurons help to buffer the brains of mice against stress. Without them, the rodents become more susceptible to stress hormones and they behave in unusual ways that are reminiscent of depressive symptoms in humans.
This is an updated version of one of my favourite stories from last year, edited to include a sequel study that develops and expands on the first one.
You’ve just been in a horrific car crash. You’re unharmed but the vividness of the experience – the sight of a looming car, the crunching of metal, the overwhelming panic – has left you a bit traumatised. You want something to help take the edge off and fortunately a doctor is on hand to prescribe you with… Tetris.
Yes, that Tetris. According to Emily Holmes from the University of Oxford, the classic video game of falling coloured blocks could prevent people who have suffered through a traumatic experience from developing full-blown post-traumatic stress disorder (PTSD). As ideas go, it’s practically the definition of quirky, but there is scientific method behind the madness.
Every traumatic experience flips a mental hourglass that runs out in about six hours. After that time, memories of the original event become firmly etched in the brain, greatly increasing the odds that the person will experience the vivid, distressing flashbacks that are the hallmark of PTSD. But the brain, powerful though it is, only has so much processing power available for laying down such memories. If something can be done soon enough to interfere with this process, the symptoms of PTSD could potentially be prevented.
Tetris, it seems, makes an ideal choice for that. To position its rotating blocks, players need good “visuospatial skills” – they need to see, focus on, and act upon the positions of different objects, all at high speed. These are the same sort of mental abilities that provide the foundations for flashback images.
This article is reposted from the old WordPress incarnation of Not Exactly Rocket Science.
Attention-deficit hyperactivity disorder is the most common developmental disorder in children, affecting anywhere between 3-5% of the world’s school-going population. As the name suggests, kids with ADHD are hyperactive and easily distracted; they are also forgetful and find it difficult to control their own impulses.
While some evidence has suggested that ADHD brains develop in fundamentally different ways to typical ones, other results have argued that they are just the result of a delay in the normal timetable for development.
Now, Philip Shaw, Judith Rapaport and others from the National Institute of Mental Health have found new evidence to support the second theory. When some parts of the brain stick to their normal timetable for development, while others lag behind, ADHD is the result.
The idea isn’t new; earlier studies have found that children with ADHD have similar brain activity to slightly younger children without the condition. Rapaport’s own group had previously found that the brain’s four lobes developed in very much the same way, regardless of whether children had ADHD or not.
But looking at the size of entire lobes is a blunt measure that, at best, provides a rough overview. To get an sharper picture, they used magnetic resonance imaging to measure the brains of 447 children of different ages, often at more than one point in time.
At over 40,000 parts of the brain, they noted the thickness of the child’s cerebral cortex, the brain’s outer layer, where its most complex functions like memory, language and consciousness are thought to lie. Half of the children had ADHD and using these measurements, Shaw could work out how their cortex differed from typical children as they grew up.
People infected with the bird flu virus – influenza A subtype H5N1 – go through the usual symptoms of fever, aching muscles and cough. The virus is so virulent that 60% of infected humans have died. But according to a study in mice, the infection could also take a more inconspicuous toll on the brain, causing the sorts of damage that could increase the risk of diseases like Parkinson’s and Alzheimer’s many years after the virus has been cleared.
The link between influenza and Parkinson’s disease is hardly old but certainly controversial. Previous studies have found no traces of flu genetic material in Parkinson’s patients, but one of the strongest pieces of evidence for a link comes from analysing an outbreak of von Economo disease following the 1918 flu pandemic.
To date, 433 people have been infected with H5N1, and a few cases have shown problems with their nervous system, running the gamut from inflammation of the brain to coma. For the survivors, it’s too early to say if their brief time with the virus could lead to neurological problems later on in life. Instead, Haeman Jang from St Jude’s Children’s Research Hospital turned to mice for answers.
He clearly showed that the H5N1 virus can infect mouse neurons within a few days, where it causes certain proteins to gather in the sorts of clumps that are so strongly associated with neurodegenerative disease. It kills off important cells, triggers symptoms reminiscent of Parkinson’s like tremors, and even stimulates an over-the-top immune response that lasted for months after the original infection was cleared.
Jang thinks that this long-lasting immune response may be how the virus leads to a higher risk of chronic diseases long after it has left its host. It’s a hit-and-run strategy, where the initial infection paves the way for something else to come along later on in life and make a “second hit”. According to this model, the flu virus doesn’t directly cause Parkinson’s or related diseases, but it primes the neurons for other things that do. This could also explain why scientists have been unable to detect influenza RNA in Parkinson’s patients.
For all appearances, this looks like the skull of any human child. But there are two very special things about it. The first is that its owner was clearly deformed; its asymmetrical skull is a sign of a medical condition called craniosynostosis
that’s associated with mental retardation. The second is that the skull is about half a million years old. It belonged to a child who lived in the Middle Pleistocene period.
The skull was uncovered in Atapuerca, Spain by Ana Gracia, who has named it Cranium 14. It’s a small specimen but it contains enough evidence to suggest that the deformity was present from birth and that the child was about 5-8 years old. The remains of 28 other humans have been recovered from the same site and none of them had any signs of deformity.
These facts strongly suggest that prehistoric humans cared for children with physical and mental deformities that would almost have certainly prevented them from caring for themselves. Without such assistance, it’s unlikely that the child would have survived that long.
For any animal, it pays to be able to spot other animals in order to find mates and companions and to avoid predators. Fortunately, many animals move in a distinct way, combining great flexibility with the constraints of a rigid skeleton – that sets them apart from inanimate objects like speeding trains or flying balls. The ability to detect this “biological motion” is incredibly important. Chicks have it. Cats have it. Even two-day-old babies have it. But autistic children do not.
Ami Klim from Yale has found that two-year-old children with autism lack normal preferences for natural movements. This difference could explain many of the problems that they face in interacting with other people because the ability to perceive biological motion – from gestures to facial expressions – is very important for our social lives.
Indeed, the parts of the brain involved in spotting them overlap with those that are involved in understanding the expressions on people’s faces or noticing where they are looking. Even the sounds of human motion can activate parts of the brain that usually only fire in response to sights.
You can appreciate the importance of this “biological motion” by looking at “point-light” animations, where a few points of light placed at key joints can simulate a moving animal. Just fifteen dots can simulate a human walker. They can even depict someone male or female, happy or sad, nervous or relaxed. Movement is the key – any single frame looks like a random collection of dots but once they move in time, the brain amazingly extracts an image from them.
But Klim found that autistic children don’t have any inclination toward point-light animations depicting natural movement. Instead, they were attracted to those where sounds and movements were synchronised – a feature that normal children tend to ignore. Again, this may explain why autistic children tend to avoid looking at people’s eyes, preferring instead to focus on their mouths.
Alim created a series of point-light animations used the type of motion-capture technology used by special effects technicians and video game designers. He filmed adults playing children’s games like “peek-a-boo” and “pat-a-cake” and converted their bodies into mere spots of light. He then showed two animations side-by-side to 76 children, of whom 21 had autism, 16 were developing slowly but were not autistic, and 39 were developing normally.
Alzheimer’s disease is the most common form of dementia in the world, affecting more than 26 million people. Creutzfeld-Jacob disease (CJD), another affliction is far less common, but both conditions share many of the same qualities. They are fatal within a few years of diagnosis, they are incurable and they involved the crippling degeneration of the brain’s neurons. Now, a group of Yale researchers have discovered that the two diseases are also linked by a pair of critical proteins.
Look into the brain of someone with Alzheimer’s disease and you will see large, insoluble “plaques” sitting between nerve cells. They consist of a protein fragment (or “peptide”) called amyloid-beta, accumulating in its thousands. These plaques are a hallmark of the disease, but even before they have formed, amyloid-beta peptides have already begun to cluster in small soluble groups. Even at this stage, they can impair memory, degrading the connections between separate neurons.
Juha Lauren wanted to work out how exactly clusters of amyloid-beta wreak havoc in neurons before they form plaques. In particular, he was after the identity of its molecular accomplices. Many proteins work their will in a cell by attaching to other proteins called receptors. To see if amyloid-beta does the same, Lauren’s team went fishing for receptors.
They created a synthetic version of the amyloid-beta peptide and connected it to a molecule called biotin – these were their hooks. Lauren lowered them into a massive pool of different proteins found in the brains of mice; if one of those was a receptor for amyloid-beta, it should take the bait and stick to it. As a rod, he used beads covered in a molecule called avidin, which sticks very strongly to biotin. The beads attracted biotin, which was stuck to amyloid-beta, which was in turn bound to its receptor.
From hundreds of thousands of proteins, their fishing trips pulled out just one that stuck to amyloid-beta, and it’s a familiar one – the prion protein. Incorrectly folded versions of this protein (PrPSC) are the culprits behind diseases like CJD, mad cow disease and scrapie. And now it seems that the normal, correctly folded version (PrPC) plays a role in Alzheimer’s disease too, by acting as the receptor for amyloid-beta. It’s the accomplice through which amyloid-beta clusters work their damaging effects on neurons.