A Sleep Aid Without the Side Effects

Insomniacs desperate for some zzzs may one day have a safer way to get them. Scientists have developed a new sleep medication that has induced sleep in rodents and monkeys without apparently impairing cognition, a potentially dangerous side effect of common sleep aids. The discovery, which originated in work explaining narcolepsy, could lead to a new class of drugs that help people who don’t respond to other treatments.

Between 10% and 15% of Americans chronically struggle with getting to or staying asleep. Many of them turn to sleeping pills for relief, and most are prescribed drugs, such as zolpidem (Ambien) and eszopiclone (Lunesta), that slow down the brain by binding to receptors for GABA, a neurotransmitter that’s involved in mood, cognition, and muscle tone. But because the drugs target GABA indiscriminately, they can also impair cognition, causing amnesia, confusion, and other problems with learning and memory, along with a number of strange sleepwalking behaviors, including wandering, eating, and driving while asleep. This has led many researchers to seek out alternative mechanisms for inducing sleep.

Neuroscientist Jason Uslaner of Merck Research Laboratories in West Point, Pennsylvania, and colleagues decided to tap into the brain’s orexin system. Orexin (also known as hypocretin) is a protein that controls wakefulness and is missing in people with narcolepsy. Past studies successfully induced sleep by inhibiting orexin, but had not looked into its effects on cognition. The researchers developed a new orexin-inhibiting compound called DORA-22 and confirmed that it could induce sleep in rats and rhesus monkeys as effectively as the GABA-modulating drugs.

Then the researchers went about testing the drugs’ effects on the animals’ cognition. They measured the rats’ cognition and memory by assessing the rodents’ ability to recognize objects. They presented the rats with a new object—say, a cone or a sphere—that the rats then sniffed and explored. Then they took the object away for an hour. After that hour, the rats were exposed to a new object and the one they’d already gotten to know; if the rats remembered, they spent less time checking out the familiar object. With the primates, Uslaner’s team tested their ability to match colors on a touchscreen and to pay attention to and identify the origin of a flashing light. In all the cases, the researchers found the GABA-modulating sleeping pills caused both the rats and the primates to respond more slowly and less accurately. Monkeys taking the memory and attention tests, for example, were 20% less accurate on the highest dose of each of the GABA-modulating drugs. But DORA-22 had no such effect on cognition, the team reports today in Science Translational Medicine.

"We were very excited," Uslaner says. "Folks who take sleep medications need to be able to perform cognitive tasks when they awake, and this [compound] could help them do so without impairment."

Although DORA-22 has not yet been tested in humans, it holds tremendous promise for helping people suffering from sleep disorders, says Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California. “This study is encouraging and exciting, because there’s good reason to believe it would work differently from what we’ve used in the past,” says Mignot, who helped discover the link between orexin (or its absence) and narcolepsy. “Not every drug works for everyone, so it’s really, really good news to have a potential new drug on the horizon.”

Shift of Language Function to Right Hemisphere Impedes Post-Stroke Aphasia Recovery

In a study designed to differentiate why some stroke patients recover from aphasia and others do not, investigators have found that a compensatory reorganization of language function to right hemispheric brain regions bodes poorly for language recovery. Patients who recovered from aphasia showed a return to normal left-hemispheric language activation patterns. These results, which may open up new rehabilitation strategies, are available in the current issue of Restorative Neurology and Neuroscience.

“Overall, approximately 30% of patients with stroke suffer from various types of aphasia, with this deficit most common in stroke with left middle cerebral artery territory damage. Some of the affected patients recover to a certain degree in the months and years following the stroke. The recovery process is modulated by several known factors, but the degree of the contribution of brain areas unaffected by stroke to the recovery process is less clear,” says lead investigator Jerzy P. Szaflarski, MD, PhD, of the Departments of Neurology at the University of Alabama and University of Cincinnati Academic Health Center.

For the study, 27 right-handed adults who suffered from a left middle cerebral artery infarction at least one year prior to study enrollment were recruited. After language testing, 9 subjects were considered to have normal language ability while 18 were considered aphasic. Patients underwent a battery of language tests as well as a semantic decision/tone decision cognitive task during functional MRI (fMRI) in order to map language function. MRI scans were used to determine stroke volume.

The authors found that linguistic performance was better in those who had stronger left-hemispheric fMRI signals while performance was worse in those who had stronger signal-shifts to the right hemisphere. As expected, they also found a negative association between the size of the stroke and performance on some linguistic tests. Right cerebellar activation was also linked to better post-stroke language ability.

The authors say that while a shift to the non-dominant right hemisphere can restore language function in children who have experienced left-hemispheric injury or stroke, for adults such a shift may impede recovery. For adults, it is the left hemisphere that is necessary for language function preservation and/or recovery.

Avoid impulsive acts by imagining future benefits

Why is it so hard for some people to resist the least little temptation, while others seem to possess incredible patience, passing up immediate gratification for a greater long-term good?

The answer, suggests a new brain imaging study from Washington University in St. Louis, lies in how effective people are at feeling good right now about all the future benefits that may come from passing up a smaller immediate reward. Researchers found that activity in two regions of the brain distinguished impulsive and patient people.

“Activity in one part of the brain, the anterior prefrontal cortex, seems to show whether you’re getting pleasure from thinking about the future reward you are about to receive,” explains study co-author Todd Braver, PhD, professor of psychology in Arts & Sciences. “People can relate to this idea that when you know something good is coming, just that waiting can feel pleasurable.”

The study, which was published in the first issue of the Journal of Neuroscience this year, was designed to examine what happens in the brain as people wait for a reward, especially whether people characterized as “impulsive” would show different brain responses than those considered “patient.”

The lead author of the study was Koji Jimura, then a postdoctoral researcher in Braver’s Cognitive Control and Psychopathology Laboratory, and now a research associate professor at the Tokyo Institute of Technology, in Japan.

Unlike previous research on delayed gratification that had people choose between hypothetical rewards of money over long delays (e.g, $500 now or $1,000 a year from now), this Washington University study presented their participants with real rewards of squirts of juice that they chose to receive either immediately or after a delay of up to a minute.

“It’s kind of funny because we treated the people in our study like researchers that work with animals do, and we actually squirted juice into their mouths,” Braver says.

Results show that a brain region called the ventral striatum (VS) ramped up its activity in impulsive people as they got closer and closer to receiving their delayed reward. The VS activity of patient people, on the other hand, stayed more constant.

The researchers interpreted these different brain responses to mean that impulsive people initially did not find the prospect of waiting for a reward very appealing. However, as they approached the time they’d receive that reward, they became more excited and their VS reflected that excitement.

“This gradual increase may reflect impatience or excessive anticipation of the upcoming reward in impulsive individuals,” says Jimura. This was unlike patient people, who were likely content with waiting for the reward from the start, as no changes in VS activity were observed for them.

The most novel finding of the study concerned the anterior prefrontal cortex (aPFC). This is the part of the brain that helps you think about the future. Here, we found that the patient people heightened activity in the aPFC when they first started waiting for they reward, which then decreased as the time to receive the reward approached. Impulsive people didn’t show this brain activity pattern.

“The aPFC appears to allow you to create a mental simulation of the future. It helps you consider what it’ll be like getting the future reward. In this way, you can get access to the utility and satisfaction in the present,” says Braver.

By thinking about the future reward, patient people were able to gain what economists call “anticipatory utility.” While their reward was far away in time, they were giddy with anticipation in the present. Conversely, impulsive people weren’t thinking beyond the present and so did not feel pleasure when they were told they had to wait. Their excitement built only as they got closer to receiving their reward.

Overall this study suggests that people may be impulsive because they do not or cannot imagine the future, so they prefer rewards right away. This research could be useful for assessing the effects of clinical treatments for impulsivity problems, which can lead to issues such as problem gambling and substance abuse disorders. A similar brain imaging approach as was used in the Washington University study could allow clinicians to track the effects of an intervention on changes not only in impulsive behavior but also changes in patients’ brain responses.

“One possible treatment approach could be to enhance mental functions in aPFC, a brain region well-known to be associated with cognitive control,” says Jimura. By increasing cognitive control, impulsive patients could learn to reject their immediate impulses.

Impulsivity occurs not only in a clinical setting but also every day in our own lives. Applying his research to his personal life, Braver says, “When I’m successful at achieving long-term goals it’s from explicitly trying to activate that goal and imagining each decision as helping me achieve it, to keep me on track.” Perhaps adopting this strategy of focusing on the long-term could help us move past present distractions and move toward our future goals.

Brain cell signal network genes linked to schizophrenia risk in families

New genetic factors that predispose to schizophrenia have been uncovered in five families with several affected relatives. The psychiatric disorder can disrupt thinking, feeling, and acting, and blur the border between reality and imagination.

Dr. Debby W. Tsuang, professor of psychiatry and behavioral sciences, and Dr. Marshall S. Horwitz, professor of pathology, both at the University of Washington in Seattle, led the multi-institutional study. Tsuang is also a staff physician at the Puget Sound Veterans Administration Health Care System.

The results are published in the April 3 online edition of the JAMA Psychiatry.

Loss of brain nerve cell integrity occurs in schizophrenia, but scientists have not worked out the details of when and how this happens. In all five families in the present study, the researchers found rare variants in genes tied to the networking of certain signal receptors on nerve cells distributed throughout the brain. These N-methyl-D-aspartate, or NMDA, receptors are widespread molecular control towers in the brain. They regulate the release of chemical messages that influence the strength of brain cell connections and the ongoing remodeling of the networks.

These receptors respond to glutamate, one of the most common nerve-signaling chemicals in the brain, and they are also found on brain circuits that manage dopamine release. Dopamine is a nerve signal associated with reward-seeking, movement and emotions. Deficits in glutamate and dopamine function have both been implicated in schizophrenia but most of the medications that have been developed to treat schizophrenia have targeted dopamine receptors.

Tsuang and her groups’ discovery of gene variations that disturb N-methyl-D-aspartate receptor networking functions supports the hypothesis that decreased NMDA receptor-mediated nerve-signal transmissions contributes to some cases of schizophrenia.

Tsuang pointed out that several hallucinogenic drugs, such as ketamine and phencyclidine (PCP, or angel dust), block N-methyl-D-aspartate receptors and can produce symptoms similar to schizophrenia. These are the strongest evidence implicating these receptors in schizophrenia. The drugs sometimes induce psychosis and terrifying sensory detachment. Reports of such effects in recreational drug users fingered faulty NMDA receptor networks as suspects in schizophrenia.

In all five of their study families, Tsuang’s team detected rare protein-altering variants in one of three genes involved with the N-methyl-D-aspartate receptor network. One of the genes, GRM5, is directly linked with glutamate signaling. In the other two genes, the links are indirect and connected through other proteins synthesized in brain cells. One of these proteins, PPEF2, appears to affect the levels of certain brain nerve-cell signaling mediators, and the other altered protein, LRP1B, may compete with a normal protein for a binding spot on a subunit of the NMDA receptor.

These discoveries provide additional clues to the molecular disarray that might occur in the brain nerve cells of some patients with schizophrenia, and suggest new targets for therapy for certain patients. In a disease occurring in about 1 percent of the population, the picture of how and why schizophrenia arises in all these people is far from complete.

“Disorders like schizophrenia are likely to have many underlying causes,” Tsuang noted. She added that it might eventually make sense to divide schizophrenia into categories based, for example, on which biochemical pathways in the brain are disrupted. Treatments might be developed to correct the exact malfunctioning mechanisms underlying various forms of the disease.

Tsuang gave an example: Agents that stimulate N-methyl-D-aspartate receptor-mediated nerve-signal transmissions include glycine-site blockers and glycine-transport inhibitors have shown some encouraging results in pre-clinical drug trials, but mostly in adjunctive treatment in addition to standard antipsychotic therapy.

“But perhaps the data we have generated will help pharmaceutical companies target specific subunits of the NMDA receptors and pathways,” Tsuang said. She added, however, that effective treatments may lag by many years after these kinds of discoveries. Someday it may make sense to initiate such treatments in people at high genetic risk when early symptoms, such as apathy and lack of motivation, appear, and before brain dysfunction is severe.

Also, possessing the newly discovered gene mutations does not always mean that a person will become schizophrenic. In the recent family study, three of the five families had relatives with the protein-altering variants who did not have schizophrenia.

“This isn’t surprising,” Tsuang observed, “Given that schizophrenia is such a complex disorder, we would expect that not everyone who carries the variants would develop the disease.” In the future, researchers will be seeking what triggers the gene variants into causing problems, other mutations within affected individuals’ genetic profile that might promote or protect against disease, as well as non-genetic factors in the onset of the illness in genetically susceptible people.

The researchers also utilized a strategy and selected more distant relatives of affected individuals for genetic sequencing. Distant kin share, a smaller proportion of genes compared to closely related family members. For example,siblings typically on the average share about 50 percent of their genes whereas cousins on the average share 12.5 percent of their genes. The researhers also hypothesized that the causative mutation within each family would be the same variant.

This strategy helped the researchers decrease the number of genetic variants that were detected by sequencing and thereby concentrate only on the remaining strongest candidates. The researchers also filtered their results against the many publicly available sequencing databases. This allowed them to pick out genetic variants not seen in individuals without psychiatric illness.

According to Tsuang, the research team was excited by recent advances in technology enabled them to uncover unknown, rare genetic variants not previously found in large populations without psychiatric condition. The ability to rapidly sequence only those portions of the genome that code for proteins made this experiment possible.

The next step for the researchers will be to screen for the newly discovered genetic variants in a large sample of unrelated cases of schizophrenia compared to controls. They want to determine if the variants are statistically associated with the disease.

Hallucinations of musical notation: new paper for neurology journal Brain by Oliver Sacks

Professor of neurology, physician, and author Oliver Sacks M.D. has outlined case studies of hallucinations of musical notation, and commented on the neural basis of such hallucinations, in a new paper for the neurology journal Brain.

In this paper, Dr Sacks is building on work done by Dominic ffytche et al in 2000, which delineates more than a dozen types of hallucinations, particularly in relation to people with Charles Bonnet syndrome (a condition that causes patients with visual loss to have complex visual hallucinations). While ffytche believes that hallucinations of musical notation are rarer than some other types of visual hallucination, Sacks says that his own experience is different.

“Perhaps because I have investigated various musical syndromes,” writes Dr Sacks, “and people often write to me about these… I have seen or corresponded with a dozen or more people whose hallucinations include – and sometimes consist exclusively of – musical notation.”

Sacks goes on to detail eight fascinating case studies of people who have reported experiencing hallucinations of musical notation, including:

• A 77 year old woman with glaucoma who wrote of her “musical eyes”. She saw “music, lines, spaces, notes, clefs – in fact written music on everything [she] looked at.”

• A surgeon and pianist suffering from macular degeneration, who saw unreadable and unplayable music on a white background.

• A Sanskrit scholar who developed Parkinson’s disease in his 60s and later reported hallucinating ornately-written music, occurring with a Sanskrit script. “Despite the exotic nature of the script the result is still western music,” he said.

• A woman who reported seeing musical notation on her ceiling upon waking in the morning.

• A woman who said she wasn’t a musician, but would hallucinate when she had high fevers as a child. She said that the notes were “angry, and [she] felt unease. The lines and notes were out of control and at times in a ball.”

It is striking that, of Dr Sacks’ eight case studies, seven were gifted musicians. Sacks comments, “This is perhaps a coincidence, but it makes one wonder whether there is something about musical scores that is radically different from verbal texts.” Musical scores are far more visually complex than standard (English) text, with not just a variety of notes, but also many symbols that indicate how the notes should be played.

Dr Sacks also says that he has a mild form of Charles Bonnet syndrome himself, in which he sees a variety of simple forms whenever he gazes at a blank surface. “When I recently returned to playing the piano and to studying scores minutely, I began to ‘see’ showers of flat signs along with the letters and runes on blank surfaces.”

Another striking feature of these hallucinations is that – like text hallucinations – they are generally unreadable. They can seem playable at first, but on closer inspection it transpires that the music is often nonsensical or impossible to play, such as an example reported in one of the case studies: a melody line three or more octaves above middle C, and so may have half a dozen or more ledger lines above the treble staff.

Usually, the early visual system analyses forms and sends the information it has extracted to higher areas, where it gains coherence and meaning. Normally, in the act of perception, the entire visual system is engaged. Paradoxically, according to Sacks, “one may have to study disorders of the visual system to see how complex perceptual and cognitive processes are analysed and delegated to different levels… and hallucinations of musical notation can provide a very rich field of study here.”

Awake imaging device moves diagnostics field forward

A technology being developed at the Department of Energy’s Oak Ridge National Laboratory promises to provide clear images of the brains of children, the elderly and people with Parkinson’s and other diseases without the use of uncomfortable or intrusive restraints.

Awake imaging provides motion compensation reconstruction, which removes blur caused by motion, allowing physicians to get a transparent picture of the functioning brain without anesthetics that can mask conditions and alter test results. The use of anesthetics, patient restraints or both is not ideal because they can trigger brain activities that may alter the normal brain functions being studied.

With this new capability, researchers hope to better understand brain development in babies, pre-teens and teen-agers. In addition, they believe the technology will provide unprecedented insight into conditions such as autism, drug addictions, alcoholism, traumatic brain injuries and Alzheimer’s disease.

"With this work, we’re hoping to establish a new paradigm in noninvasive diagnostic imaging," said Justin Baba, a biomedical engineer who heads the ORNL development team.

The study, which was performed in collaboration with Thomas Jefferson National Accelerator Laboratory and Johns Hopkins University, utilized an awake imaging scanner and awake, unanesthetized, unrestrained mice that had been injected with a radiotracer known as DaTSCAN, provided by GE-Medical.

With awake imaging using DaTSCAN and other molecular probes, Baba and colleagues envision development of new, more effective therapies for a wide assortment of conditions and diseases while also contributing to pharmaceutical drug discovery, development and testing. The technology could also help with real-time stabilization and registration of targets during surgical intervention.

Baba noted that this technical accomplishment, detailed in a paper published in The Journal of Nuclear Medicine, has its origins in past DOE-supported research on biomedical imaging. The paper is titled “Conscious, Unrestrained Molecular Imaging of Mice with AwakeSPECT.” Jim Goddard of ORNL’s Measurement Science and Systems Engineering Division is a co-author.

While a working prototype scanner is located at Johns Hopkins School of Medicine, ORNL is pursuing commercialization of the technology.

Scientists Decode Dreams With Brain Scans

It used to be that what happened in your dreams was your own little secret. But today scientists report for the first time that they’ve successfully decoded details of people’s dreams using brain scans.

Before you reach for your tin hat, you should know that the scientists managed this feat only with the full cooperation of their research subjects, and they only decoded dreams after the fact, not in real time. The thought police won’t be busting you for renting bowling shoes from Saddam Hussein or whatever else you’ve been up to in your dreams.

All the same, the work is yet another impressive step for researchers interested in decoding mental states from brain activity, and it opens the door to a new way of studying dreaming, one of the most mysterious and fascinating aspects of the human experience.

In the first part of the new study, neuroscientist Yukiyasu Kamitani and colleagues at the Advanced Telecommunications Research Institute International in Kyoto, Japan monitored three young men as they tried to get some sleep inside an fMRI scanner while the machine monitored their brain activity. The researchers also monitored each volunteer’s brain activity with EEG electrodes, and when they saw an EEG signature indicative of dreaming, they woke him up to ask what he’d been dreaming about.

Technically speaking, this is what researchers call ”hypnagogic imagery,” the dream-like state that occurs as people fall asleep. In the interest of saving time, Kamitani and colleagues chose to study this type of imagery rather than the dreams that tend to occur during REM sleep later in the night. They woke up each subject at least 200 times over the course of several days to build up a database of dream reports.

In the second part of the experiment, Kamitani and colleagues developed a visual imagery decoder based on machine learning algorithms. They trained the decoder to classify patterns of brain activity recorded from the same three men while they were awake and watching a video montage of hundreds of images selected from several online databases. After the decoder for each person had been trained, the researchers could input a pattern of brain activity and have the decoder predict which image was most likely to have produced that pattern of brain activity.

But that much has been done before. Where Kamitani’s team went beyond previous work was in feeding the decoder patterns of brain activity collected while the subjects were dreaming. This enabled them to correctly identify objects the men had seen in their dreams, they report Apr. 4 in Science. Or rather, they could identify the type of object a subject had seen: it could predict that a man had dreamt about a car, not that he’d been cruising around in a Maserati. And the decoder only worked when the researchers gave it a pair of possible objects to chose from (whether it was a man or a chair, for example).

“Our dream decoding is still very primitive,” Kamitani said.

Decoding color, action, or emotion is also still beyond the scope of the technology, Kamitani says. Also, it only seems to work for imagery that occurred — at most — about 15 seconds before waking up.

Finally, the decoder is unique to each person. To decode the dreams of another person, the team would have to train up a new decoder by having that person view hundreds of images.

Even so, it’s remarkable that it works as well as it does, says neuroscientist Jack Gallant of the University of California, Berkeley and a pioneer of decoding mental states from brain scans. ”It took just a huge amount of non-glamorous work to do this, and they deserve big props for that,” Gallant said.

With refinements, Gallant says the method could be useful for studying the nature and function of dreams.

“There’s the classic question of when you dream are you actively generating these movies in your head, or is it that when you wake up you’re essentially confabulating it,” Gallant said. “What this shows you is there’s at least some correspondence between what the brain is doing during dreaming and what it’s doing when you’re awake.”

Kamitani is thinking about the possibilities too. ”One theory states that dreaming is for strengthening memory, but another theory states dreaming is for forgetting,” he said. “We could record the frequency of decoded dream contents for each memory item and see the correlation between the frequency and the memory performance.”

A “light switch” in the brain illuminates neural networks

Researchers from NTNU’s Kavli Institute of Systems Neuroscience are able to see which cells communicate with each other in the brain by flipping a neural light switch. The results of their efforts are presented in an article in the 5 April issue of Science magazine.

There are cells in your brain that recognize very specific places, and have that and nothing else as their job. These cells, called place cells, are found in an area behind your temple called the hippocampus. While these cells must be sent information from nearby cells to do their job, so far no one has been able to determine exactly what kind of cells work with place cells to craft the code they create for each location. Neurons come in many different types with specialized functions. Some respond to edges and borders, others to specific locations, others act like a compass and react to which way you turn your head.

Now, researchers at the Kavli Institute for Systems Neuroscience have developed a range of advanced techniques that enable them to identify which neurons communicate with each other at different times in the rat brain, and in doing so, create the animal’s sense of direction.

"A rat’s brain is the size of a grape. Inside there are about fifty million neurons that are connected together at a staggering 450 billion places (roughly)," explains Professor Edvard Moser, director of the Kavli Institute. "Inside this grape-sized brain are areas on each side that are smaller than a grape seed, where we know that memory and the sense of location reside. This is also where we find the neurons that respond to specific places, the place cells. But from which cells do these place cells get information?"

From spaghetti to light switches
The problem is, of course, that researchers cannot simply cut open the rat brain to see which cells have had contact. That would be the equivalent of taking a giant pile of cooked spaghetti, chopping it into little pieces, and then trying to figure out how the various spaghetti strands were tangled together before the pile was cut up.
A job like this requires the use of a completely different set of neural tools, which is where the “light switches” come into play.

Neurons share many similarities with electric cables when they send signals to each other. They send an electric current in one direction – from the “body” of the neuron and down a long arm, called the axon, which goes to another nerve cell next in line. Place cells thus get their small electric signals from a whole series of such arms.

So how do light switches play into all of this?

Viruses do the work
“What we did first was to give these nerve arms a harmless viral infection,” Moser says. “We designed a unique virus that does not cause disease, but that acts as a pathway for delivering genes to specific cells. The virus creeps into the neurons, crawls up against the electric current, and uses the nerve cell’s own factory to make the genetic recipe that we gave to the virus to carry.”

The genetic recipe enabled the cell to make the equivalent of a light switch. Our eyes actually contain the same kind of biological light switch, which allows us to see. The virus infection converts neurons that have previously existed only in darkness, deep inside the brain, to now be sensitive to light.

Then the researchers inserted optical fibres in the rat’s brain to transmit light to the place cells that had light switches in them. They also implanted thin microelectrodes down between the cells so they could detect the signals sent through the axons every time the light from the optical fibre was turned on.

"Now we had everything set up, with light switches installed in cells around the place cells, a lamp, and a way to record the activity," Moser said.

10,000 times
The researchers then turned the lights on and off more than ten thousand times in their rat lab partners, while they monitored and recorded the activity of hundreds of individual cells in the rats’ grape-sized brains. The researchers did this research while the rats ran around in a metre-square box, gathering treats. As the rats explored their box and found the treats, the researchers were able to use the light-sensitive cells to reveal how the rat’s brain created the map of where the rat had been.

When the researchers put together all the information afterwards they concluded that there is a whole range of different specialized cells that together provide place cells their information. The brain’s GPS – its sense of place – is created by signals from head direction cells, border cells, cells that have no known function in creating location points and grid cells. Place cells receive both information about the rat’s surroundings and landmarks, but also continuously update their own movement, which is actually independent on sensory input.

"The biggest mystery is the role that the cells that are not part of the sense of direction play. They send signals to place cells, but what do they actually do?" wonders Moser.

"We also wonder how the cells in the hippocampus are able to sort out the various signals they receive. Do they ‘listen’ to all of the cells equally effectively all the time, or are there some cells that get more time than others to ‘talk’ to place cells?"

Ability To ‘Think About Thinking’ Not Limited Only To Humans According to New Research

Humans’ closest animal relatives, chimpanzees, have the ability to “think about thinking” – what is called “metacognition,” according to new research by scientists at Georgia State University and the University at Buffalo.

Michael J. Beran and Bonnie M. Perdue of the Georgia State Language Research Center (LRC) and J. David Smith of the University at Buffalo conducted the research, published in the journal Psychological Science of the Association for Psychological Science.

“The demonstration of metacognition in nonhuman primates has important implications regarding the emergence of self-reflective mind during humans’ cognitive evolution,” the research team noted.

Metacognition is the ability to recognize one’s own cognitive states. For example, a game show contestant must make the decision to “phone a friend” or risk it all, dependent on how confident he or she is in knowing the answer.

“There has been an intense debate in the scientific literature in recent years over whether metacognition is unique to humans,” Beran said.

Chimpanzees at Georgia State’s LRC have been trained to use a language-like system of symbols to name things, giving researchers a unique way to query animals about their states of knowing or not knowing.

In the experiment, researchers tested the chimpanzees on a task that required them to use symbols to name what food was hidden in a location. If a piece of banana was hidden, the chimpanzees would report that fact and gain the food by touching the symbol for banana on their symbol keyboards.

But then, the researchers provided chimpanzees either with complete or incomplete information about the identity of the food rewards.

In some cases, the chimpanzees had already seen what item was available in the hidden location and could immediately name it by touching the correct symbol without going to look at the item in the hidden location to see what it was.

In other cases, the chimpanzees could not know what food item was in the hidden location, because either they had not seen any food yet on that trial, or because even if they had seen a food item, it may not have been the one moved to the hidden location.

In those cases, they should have first gone to look in the hidden location before trying to name any food.

In the end, chimpanzees named items immediately and directly when they knew what was there, but they sought out more information before naming when they did not already know.

The research team said, “This pattern of behavior reflects a controlled information-seeking capacity that serves to support intelligent responding, and it strongly suggests that our closest living relative has metacognitive abilities closely related to those of humans.”