First man to hear people before they speak

"I told my daughter her living room TV was out of sync. Then I noticed the kitchen telly was also dubbed badly. Suddenly I noticed that her voice was out of sync too. It wasn’t the TV, it was me."

Ever watched an old movie, only for the sound to go out of sync with the action? Now imagine every voice you hear sounds similarly off-kilter – even your own. That’s the world PH lives in. Soon after surgery for a heart problem, he began to notice that something wasn’t quite right.

"I was staying with my daughter and they like to have the television on in their house. I turned to my daughter and said ‘you ought to get a decent telly, one where the sound and programme are synchronised’. I gave a little chuckle. But they said ‘there’s nothing wrong with the TV’."

Puzzled, he went to the kitchen to make a cup of tea. “They’ve got another telly up on the wall and it was the same. I went into the lounge and I said to her ‘hey you’ve got two TVs that need sorting!’.”

That was when he started to notice that his daughter’s speech was out of time with her lip movements too. “It wasn’t the TV, it was me. It was happening in real life.”

PH is the first confirmed case of someone who hears people speak before registering the movement of their lips. His situation is giving unique insights into how our brains unify what we hear and see.

It’s unclear why PH’s problem started when it did – but it may have had something to do with having acute pericarditis, inflammation of the sac around the heart, or the surgery he had to treat it.

Brain scans after the timing problems appeared showed two lesions in areas thought to play a role in hearing, timing and movement. “Where these came from is anyone’s guess,” says PH. “They may have been there all my life or as a result of being in intensive care.”

Disconcerting delay

Several weeks later, PH realised that it wasn’t just other people who were out of sync: when he spoke, he registered his words before he felt his jaw make the movement. “It felt like a significant delay, it sort of snuck up on me. It was very disconcerting. At the time I didn’t know whether the delay was going to get bigger, but it seems to have stuck at about a quarter of a second.”

Light and sound travel at different speeds, so when someone speaks, visual and auditory inputs arrive at our eyes and ears at different times. The signals are then processed at different rates in the brain. Despite this, we normally perceive the events as happening simultaneously – but how the brain achieves this is unclear.

To investigate PH’s situation, Elliot Freeman at City University London and colleagues performed a temporal order judgement test. PH was shown clips of people talking and was asked whether the voice came before or after the lip movements. Sure enough, he said it came before, and to perceive them as synchronous the team had to play the voice about 200 milliseconds later than the lip movements.

The team then carried out a second, more objective test based on the McGurk illusion. This involves listening to one syllable while watching someone mouth another; the combination makes you perceive a third syllable.

Since PH hears people speaking before he sees their lips move, the team expected the illusion to work when they delayed the voice. So they were surprised to get the opposite result: presenting the voice 200 ms earlier than the lip movements triggered the illusion, suggesting that his brain was processing the sight before the sound in this particular task.

And it wasn’t only PH who gave these results. When 37 others were tested on both tasks, many showed a similar pattern, though none of the mismatches were noticeable in everyday life.

Many clocks

Freeman says this implies that the same event in the outside world is perceived by different parts of your brain as happening at different times. This suggests that, rather than one unified “now”, there are many clocks in the brain – two of which showed up in the tasks – and that all the clocks measure their individual “nows” relative to their average.

In PH’s case, one or more of these clocks has been significantly slowed – shifting his average – possibly as a result of the lesions. Freeman thinks PH’s timing discrepancies may be too large and have happened too suddenly for him to ignore or adapt to, resulting in him being aware of the asynchrony in everyday life. He may perceive just one of his clocks because it is the only one he has conscious access to, says Freeman.

PH says that in general he has learned to live with the sensory mismatch but admits he has trouble in noisy places or at large meetings. Since he hears himself speak before he feels his mouth move, does he ever feel like he’s not in control of his own voice? “No, I’m definitely sure it’s me that’s speaking,” he says, “it’s just a strange sensation.”

Help may be at hand: Freeman is looking for a way to slow down PH’s hearing so it matches what he is seeing. PH says he would be happy to trial a treatment, but he’s actually not that anxious to fix the problem. “It’s not life-threatening,” he says. “You learn to live with these things as you get older. I don’t expect my body to work perfectly.”

With Parents’ Help, Preschoolers Can Learn to Pay Attention

To Preserve Memory Into Old Age, Keep Your Brain Active!

A new study from Rush University Medical Center in Chicago claims reading and writing may preserve memory into old age. By keeping your brain active, says study author Robert S. Wilson, PhD, you’re able to slow the rate at which your memory decreases in later years.

This is not the first time researchers have arrived at such a conclusion, of course. Previous studies have also found keeping the brain active by reading, writing, completing crossword puzzles and more can essentially exercise the brain and keep it limber far into old age. One study also concluded that keeping television consumption to a minimal amount may also boost brain power over the years. Wilson’s study was recently published in the journal Neurology.

“Our study suggests that exercising your brain by taking part in activities such as these across a person’s lifetime, from childhood through old age, is important for brain health in old age,” said Wilson in a statement.

For his study, Wilson gathered nearly 300 people around the age of 80. He then gave them tests which were designed to measure both their memory and cognition each year until they passed away at an average age of 89. The same participants also answered questions about their past, such as whether they read books, did any writing, or engaged in any other mentally stimulating activities. The volunteers answered these questions for every part of their life, from childhood to adolescence, middle age and beyond.

When the participants passed away, their brains were then examined at an autopsy as Wilson’s team looked for physical evidence of dementia, such as lesions in the brain, tangles or plaques. After examining the brains of these volunteers and compiling the data from the questionnaires, Wilson’s team found those who had kept their minds active throughout their lives had a slower rate of memory decline than those who did not often participate in mentally challenging activities. Based on the amount of plaques and tangles in the brains, keeping your brain active is responsible for a 15 percent differential in memory decline.

The study also found the rate of memory decline was reduced by 32 percent in people who kept their brains active late in life. Those who were not mentally active had it much worse; their memories declined 48 percent faster than their actively reading and writing peers.

“Based on this, we shouldn’t underestimate the effects of everyday activities, such as reading and writing, on our children, ourselves and our parents or grandparents,” said Wilson.

And this news is hardly surprising. Doctors, teachers and parents have been admonishing children to turn off the television and pick up a book for years. There is no shortage of studies to back up their claims. A 2009 study, for example, found people who keep their brains active saw a 30 to 50 percent decrease in risk of developing memory loss. This study, conducted by doctors at the Mayo Clinic in Rochester, Minnesota observed people between the ages of 70 and 89 with and without diagnosed memory loss.

Those who were likely to read magazines or engage in other social activities were 40 percent less likely to develop memory loss than homebodies who did not read. Furthermore, those who spent less than seven hours a day watching television were 50 percent less likely to develop memory loss than those who planted themselves in front of the tube for long stretches of time.

Unique Epigenomic Code Identified During Human Brain Development

Changes in the epigenome, including chemical modifications of DNA, can act as an extra layer of information in the genome, and are thought to play a role in learning and memory, as well as in age-related cognitive decline. The results of a new study by scientists at the Salk Institute for Biological Studies show that the landscape of DNA methylation, a particular type of epigenomic modification, is highly dynamic in brain cells during the transition from birth to adulthood, helping to understand how information in the genomes of cells in the brain is controlled from fetal development to adulthood. The brain is much more complex than all other organs in the body and this discovery opens the door to a deeper understanding of how the intricate patterns of connectivity in the brain are formed.

“These results extend our knowledge of the unique role of DNA methylation in brain development and function,” says senior author Joseph R. Ecker, professor and director of Salk’s Genomic Analysis Laboratory and holder of the Salk International Council Chair in Genetics. “They offer a new framework for testing the role of the epigenome in healthy function and in pathological disruptions of neural circuits.”

A healthy brain is the product of a long process of development. The front-most part of our brain, called the frontal cortex, plays a key role in our ability to think, decide and act. The brain accomplishes all of this through the interaction of special cells such as neurons and glia. We know that these cells have distinct functions, but what gives these cells their individual identities? The answer lies in how each cell expresses the information contained in its DNA. Epigenomic modifications, such as DNA methylation, can control which genes are turned on or off without changing letters of the DNA alphabet (A-T-C-G), and thus help distinguish different cell types.

In this new study, published July 4 in Science, the scientists found that the patterns of DNA methylation undergo widespread reconfiguration in the frontal cortex of mouse and human brains during a time of development when synapses, or connections between nerve cells, are growing rapidly. The researchers identified the exact sites of DNA methylation throughout the genome in brains from infants through adults. They found that one form of DNA methylation is present in neurons and glia from birth. Strikingly, a second form of “non-CG” DNA methylation that is almost exclusive to neurons accumulates as the brain matures, becoming the dominant form of methylation in the genome of human neurons. These results help us to understand how the intricate DNA landscape of brain cells develops during the key stages of childhood.

The genetic code in DNA is made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). DNA methylation typically occurs at so-called CpG sites, where C (cytosine) sits next to G (guanine) in the DNA alphabet. About 80 to 90 percent of CpG sites are methylated in human DNA. Salk researchers previously discovered that in human embryonic stem cells and induced pluripotent stem cells, a type of artificially derived stem cell, DNA methylation can also occur when G does not follow C, hence “non-CG methylation.” Originally, they thought that this type of methylation disappeared when stem cells differentiate into specific tissue-types such as lung or fat cells. The current study finds this is not the case in the brain, where non-CG methylation appears after cells differentiate, usually during childhood and adolescence when the brain is maturing.

By sequencing the genomes of mouse and human brain tissue as well as neurons and glia (from the frontal cortex of the brain) during early postnatal, juvenile, adolescent and adult stages, the Salk team found that non-CG methylation accumulates in neurons through early childhood and adolescence, and becomes the dominant form of DNA methylation in mature human neurons. “This shows that the period during which the neural circuits of the brain mature is accompanied by a parallel process of large-scale reconfiguration of the neural epigenome,” says Ecker, who is a Howard Hughes Medical Institute and Gordon and Betty Moore Foundation investigator.

The study provides the first comprehensive maps of how DNA methylation patterns change in the mouse and human brain during development, forming a critical foundation to now explore whether changes in methylation patterns may be linked to human diseases, including psychiatric disorders. Recent studies have demonstrated a possible role for DNA methylation in schizophrenia, depression, suicide and bipolar disorder. “Our work will let us begin to ask more detailed questions about how changes in the epigenome sculpt the complex identities of brain cells through life,” says co-first author Eran Mukamel, from Salk’s Computational Neurobiology Laboratory.

“The human brain has been called the most complex system that we know of in the universe,” says Ryan Lister, co-corresponding author on the new paper, previously a postdoctoral fellow in Ecker’s laboratory at Salk and now a group leader at The University of Western Australia. “So perhaps we shouldn’t be so surprised that this complexity extends to the level of the brain epigenome. These unique features of DNA methylation that emerge during critical phases of brain development suggest the presence of previously unrecognized regulatory processes that may be critically involved in normal brain function and brain disorders.”

At present, there is consensus among neuroscientists that many mental disorders have a neurodevelopmental origin and arise from an interaction between genetic predisposition and environmental influences (for example, early-life stress or drug abuse), the outcome of which is altered activity of brain networks. The building and shaping of these brain networks requires a long maturation process in which central nervous system cell types (neurons and glia) need to fine-tune the way they express their genetic code.

“DNA methylation fulfills this role,” says study co-author Terrence J. Sejnowski, a Howard Hughes Medical Institute Investigator, holder of the Francis Crick Chair and head of Salk’s Computational Neurobiology Laboratory. “We found that patterns of methylation are dynamic during brain development, in particular for non-CG methylation during early childhood and adolescence, which changes the way that we think about normal brain function and dysfunction.”

By disrupting the transcriptional expression of neurons, adds co-corresponding author M. Margarita Behrens, a staff scientist in the Computational Neurobiology Laboratory, “the alterations of these methylation patterns will change the way in which networks are formed, which could, in turn, lead to the appearance of mental disorders later in life.”

Why do we gesticulate?

If you rely on hand gestures to get your point across, you can thank fish for that! Scientists have found that the evolution of the control of speech and hand movements can be traced back to the same place in the brain, which could explain why we use hand gestures when we are speaking.

Professor Andrew Bass (Cornell University), who will be presenting his work at the meeting of the Society for Experimental Biology on the 3rd July, said: “We have traced the evolutionary origins of the behavioural coupling between speech and hand movement back to a developmental compartment in the brain of fishes.”

"Pectoral appendages (fins and forelimbs) are mainly used for locomotion. However, pectoral appendages also function in social communication for the purposes of making sounds that we simply refer to as non-vocal sonic signals, and for gestural signalling."

Studies of early development in fishes show that neural networks in the brain controlling the more complex vocal and pectoral mechanisms of social signalling among birds and mammals have their ancestral origins in a single compartment of the hindbrain in fishes. This begins to explain the ancestral origins of the neural basis for the close coupling between vocal and pectoral/gestural signalling that is observed among many vertebrate groups, including humans.

Professor Bass said: “Coupling of vocal and pectoral-gestural circuitry starts to get at the evolutionary origins of the coupling between vocalization (speech) and gestural signalling (hand movements). This is all part of the perhaps even larger story of language evolution.”

Exercise reorganizes the brain to be more resilient to stress

Physical activity reorganizes the brain so that its response to stress is reduced and anxiety is less likely to interfere with normal brain function, according to a research team based at Princeton University.

The researchers report in the Journal of Neuroscience that when mice allowed to exercise regularly experienced a stressor — exposure to cold water — their brains exhibited a spike in the activity of neurons that shut off excitement in the ventral hippocampus, a brain region shown to regulate anxiety.

These findings potentially resolve a discrepancy in research related to the effect of exercise on the brain — namely that exercise reduces anxiety while also promoting the growth of new neurons in the ventral hippocampus. Because these young neurons are typically more excitable than their more mature counterparts, exercise should result in more anxiety, not less. The Princeton-led researchers, however, found that exercise also strengthens the mechanisms that prevent these brain cells from firing.

The impact of physical activity on the ventral hippocampus specifically has not been deeply explored, said senior author Elizabeth Gould, Princeton’s Dorman T. Warren Professor of Psychology. By doing so, members of Gould’s laboratory pinpointed brain cells and regions important to anxiety regulation that may help scientists better understand and treat human anxiety disorders, she said.

From an evolutionary standpoint, the research also shows that the brain can be extremely adaptive and tailor its own processes to an organism’s lifestyle or surroundings, Gould said. A higher likelihood of anxious behavior may have an adaptive advantage for less physically fit creatures. Anxiety often manifests itself in avoidant behavior and avoiding potentially dangerous situations would increase the likelihood of survival, particularly for those less capable of responding with a “fight or flight” reaction, she said.

"Understanding how the brain regulates anxious behavior gives us potential clues about helping people with anxiety disorders. It also tells us something about how the brain modifies itself to respond optimally to its own environment," said Gould, who also is a professor in the Princeton Neuroscience Institute.

The research was part of the graduate dissertation for first author Timothy Schoenfeld, now a postdoctoral fellow at the National Institute of Mental Health, as well as part of the senior thesis project of co-author Brian Hsueh, now an MD/Ph.D. student at Stanford University. The project also included co-authors Pedro Rada and Pedro Pieruzzini, both from the University of Los Andes in Venezuela.

For the experiments, one group of mice was given unlimited access to a running wheel and a second group had no running wheel. Natural runners, mice will dash up to 4 kilometers (about 2.5 miles) a night when given access to a running wheel, Gould said. After six weeks, the mice were exposed to cold water for a brief period of time.

The brains of active and sedentary mice behaved differently almost as soon as the stressor occurred, an analysis showed. In the neurons of sedentary mice only, the cold water spurred an increase in “immediate early genes,” or short-lived genes that are rapidly turned on when a neuron fires. The lack of these genes in the neurons of active mice suggested that their brain cells did not immediately leap into an excited state in response to the stressor.

Instead, the brain in a runner mouse showed every sign of controlling its reaction to an extent not observed in the brain of a sedentary mouse. There was a boost of activity in inhibitory neurons that are known to keep excitable neurons in check. At the same time, neurons in these mice released more of the neurotransmitter gamma-aminobutyric acid, or GABA, which tamps down neural excitement. The protein that packages GABA into little travel pods known as vesicles for release into the synapse also was present in higher amounts in runners.

The anxiety-reducing effect of exercise was canceled out when the researchers blocked the GABA receptor that calms neuron activity in the ventral hippocampus. The researchers used the chemical bicuculine, which is used in medical research to block GABA receptors and simulate the cellular activity underlying epilepsy. In this case, when applied to the ventral hippocampus, the chemical blocked the mollifying effects of GABA in active mice.

Researchers find new clue to cause of human narcolepsy

In 2000, researchers at the UCLA Center for Sleep Research published findings showing that people suffering from narcolepsy, a disorder characterized by uncontrollable periods of deep sleep, had 90 percent fewer neurons containing the neuropeptide hypocretin in their brains than healthy people. The study was the first to show a possible biological cause of the disorder.

Subsequent work by this group and others demonstrated that hypocretin is an arousing chemical that keeps us awake and elevates both mood and alertness; the death of hypocretin cells, the researchers said, helps explain the sleepiness of narcolepsy. But it has remained unclear what kills these cells.

Now the same UCLA team reports that an excess of another brain cell type — this one containing histamine — may be the cause of the loss of hypocretin cells in human narcoleptics.

UCLA professor of psychiatry Jerome Siegel and colleagues report in the current online edition of the journal Annals of Neurology that people with the disorder have nearly 65 percent more brain cells containing the chemical histamine. Their research suggests that this excess of histamine cells causes the loss of hypocretin cells in human narcoleptics.

Narcolepsy is a chronic disorder of the central nervous system characterized by the brain’s inability to control sleep–wake cycles. It causes sudden bouts of sleep and is often accompanied by cataplexy, an abrupt loss of voluntary muscle tone that can cause person to collapse. According to the National Institutes of Health, narcolepsy is thought to affect roughly one in every 3,000 Americans. Currently, there is no cure.

Histamine is a body chemical that works as part of the immune system to kill invading cells. When the immune system goes awry, histamine can act on a person’s eyes, nose, throat, lungs, skin or gastrointestinal tract, causing the symptoms of allergy that many people are familiar with. But histamine is also present in a type of brain cell.

For the study, researchers examined five narcoleptic brains and seven control brains from human cadavers. Prior to death, all the narcoleptics had been diagnosed by a sleep disorder center as having narcolepsy with cataplexy. These brains were also compared with the brains of three narcoleptic mouse models and to the brains of narcoleptic dogs.

The researchers found that the humans with narcolepsy had an average of 64 percent more histamine neurons. Interestingly, the team did not see an increased number of these cells in any of the animal models of narcolepsy.

"Humans and animals with narcolepsy share the same symptoms, but we did not see the histamine cell changes we saw in humans in the animal models we examined," said Siegel, who directs the Center for Sleep Research at the UCLA Semel Institute for Neuroscience and Human Behavior and is the senior author of the research. "We know that narcolepsy in the animal models is caused by engineered genetic changes that block hypocretin function. However, in humans, we did not know why the hypocretin cells die.

"Our current findings indicate that the increase of histamine cells that we see in human narcolepsy may cause the loss of hypocretin cells," he said.

The study results may also further our understanding of brain plasticity, Siegel noted. While scientists have known of the existence neurogenesis — the process by which the brain is populated with new neurons — it was thought to function mainly to replace existing cells that had died.

"This paper shows for the first time that neuronal numbers can increase greatly and not just serve as replacement cells," he said. "In the current example, this appears to be pathological with the destruction of hypocretin, but in other circumstances, it may underlie recovery and learning and open new routes to treatment of a number of neurological disorders."

Brain Sets Prices With Emotional Value

You might be falling in love with that new car, but you probably wouldn’t pay as much for it if you could resist the feeling.

Researchers at Duke University who study how the brain values things — a field called neuroeconomics — have found that your feelings about something and the value you put on it are calculated similarly in a specific area of the brain. 

The region is small area right between the eyes at the front of the brain. It’s called the ventromedial prefrontal cortex, or vmPFC for short. Scott Huettel, director of Duke’s Center for Interdisciplinary Decision Science, said scientists studying emotion and neuroeconomics had independently singled out this area of the brain in their research but neither group recognized that the other’s research was focused on it too.

Now, after a series of experiments in which subjects were asked to modify how they felt about something either positively or negatively, the Duke group is arguing that emotional and economic calculations are more closely related than brain scientists had realized. The study appears July 3 in the Journal of Neuroscience.

Earlier research by other groups had shown the vmPFC participates in calculating the value of rewards and that it is engaged by positive stimuli that aren’t really rewards, like a happy memory or a picture of a happy face. A separate line of studies had shown that this brain region also set values on little things like snacks. 

The vmPFC handles value tradeoffs such as ‘is that product worth parting with my hard-earned money?’ “This says that your emotions would enter into that tradeoff,” Huettel said. 

"The neuroscience fits with your intuitive understanding," said Amy Winecoff, a graduate student in psychology and neuroscience who led the research. "Emotions appear to be relying on the same value system."

In the Duke study, experimental subjects were first trained to do “reappraisal,” in which they could change their emotional response to a situation. “In reappraisal you reassess the meaning of an emotional stimulus, rather than trying to avoid the emotional stimulus or suppress your reaction to it,” Winecoff said. 

While the subjects’ brains were being scanned using functional MRI, they were shown images of evocative scenes and faces. After each image the subjects were told to either let their feelings flow or to practice reappraisal to change their thoughts. Then they were asked to rate how positive or negative they felt.

In the case of “an unregulated positive affect” — letting the good feelings flow — the vmPFC was shown to be working harder, which the researchers say could be used to predict how much value a person is putting on something. But when the subjects dampened their emotion responses to positive images, the vmPFC activation diminished, as if the images were less valuable to the subjects.  

"This changes our frame of reference for thinking about these things," Huettel said. He said advertisers have long been using emotional appeals to get people to value their products, "but they didn’t know why it worked."

Previous studies had focused only on reappraisal of negative emotions, but this time around the Duke scientists wanted to watch people reappraise both negative and positive responses. “We have kind of a skewed picture because this has only been done on the negative,” Winecoff said.

"It’s not the case that you never want to reappraise a positive emotion," said Huettel. But when buying a house or a car, it’s a good idea to dampen your infatuation down a bit, he added.