Posts tagged neuroscience

In comparing amounts of things — be it the grains of sand on a beach, or the size of a sea gull flock inhabiting it — humans use a part of the brain that is organized topographically, researchers have finally shown. In other words, the neurons that work to make this “numerosity” assessment are laid out in a shape that allows those most closely related to communicate and interact over the shortest possible distance.

This layout, referred to as a topographical map, is characteristic of all primary senses — sight, hearing, touch, smell and taste — and scientists have long assumed that numerosity, while not a primary sense (but perceived similarly to one), might be characterized by such a map, too.

But they have not been able to find it, which has caused some doubt in the field as to whether a map for numerosity exists.

Now, however, Utrecht University’s Benjamin Harvey, along with his colleagues, have sussed out signals that illustrate the hypothesized numerosity map is real.

Numerosity, it is important to note, is distinct from symbolic numbers. “We use symbolic numbers to represent numerosity and other aspects of magnitude, but the symbol itself is only a representation,” Harvey said. He went on to explain that numerosity selectivity in the brain is derived from visual processing of image features, where symbolic number selectivity is derived by recognizing the shapes of numerals, written words, and linguistic sounds that represent numbers. “This latter task relies on very different parts of the brain that specialize in written and spoken language.”

Understanding whether the brain’s processing of numerosity and symbolic numbers is related, as we might be tempted to think, is just one area that will be better informed by Harvey’s new map.

To uncover it, he and his colleagues asked eight adult study participants to look at patterns of dots that varied in number over time, all the while analysing the neural response properties in a numerosity-linked part of their brain using high-field fMRI (functional magnetic resonance imaging). Use of this advanced neuroimaging method allowed them to scan the subjects for far fewer hours per sitting than would have been required with a less powerful scanning technology.

With the fMRI data that resulted, Harvey and his team used population receptive field modelling, which aims to measure neural response as directly and quantitatively as possible. “This was the key to our success,” Harvey said. It allowed the researchers to model the human fMRI response properties they observed following results of recordings from macaque neurons, in which numerosity experiments had been conducted more extensively.

Their efforts revealed a topographical layout of numerosity in the human brain; the small quantities of dots the participants observed were encoded by neurons in one part of the brain, and the larger quantities, in another.

This finding demonstrates that topography can emerge not just for lower-level cognitive functions, like the primary senses, but for higher-level cognitive functions, too.

"We are very excited that association cortex can produce emergent topographic structures," Harvey said.

Because scientists know a great deal about topographical maps (and have the tools to probe them), the work of Harvey et al. may help scientists better analyse the neural computation underlying number processing.

"We believe this will lead to a much more complete understanding of humans’ unique numerical and mathematical skills," Harvey said.

Having heard from others in the field about the difficulty associated with the hunt for a topographical map of numerosity, Harvey and colleagues were surprised to obtain the results they did.

They also found the variations between their subjects interesting.

"Every individual brain is a complex and very different system," Harvey explained. "I was very surprised then that the map we report is in such a consistent location between our subjects, and that numerosity preferences always increased in the same direction along the cortex."

"On the other hand," he continued, "the extent of individual differences … is also striking." Harvey explained that understanding the consequences of these differences for their subjects’ perception or task performance will require further study.

(Source: eurekalert.org)

Details of destructive neuronal pathway should help improve drug therapies

Alzheimer’s disease affects more than 26 million people worldwide. It is predicted to skyrocket as boomers age—nearly 106 million people are projected to have the disease by 2050. Fortunately, scientists are making progress towards therapies. A collaboration among several research entities, including the Salk Institute and the Sanford-Burnham Medical Research Institute, has defined a key mechanism behind the disease’s progress, giving hope that a newly modified Alzheimer’s drug will be effective.

In a previous study in 2009, Stephen F. Heinemann, a professor in Salk’s Molecular Neurobiology Laboratory, found that a nicotinic receptor called Alpha7 may help trigger Alzheimer’s disease. “Previous studies exposed a possible interaction between Alpha-7 nicotinic receptors (α7Rs) with amyloid beta, the toxic protein found in the disease’s hallmark plaques,” says Gustavo Dziewczapolski, a staff researcher in Heinemann’s lab. “We showed for the first time, in vivo, that the binding of this two proteins, α7Rs and amyloid beta, provoke detrimental effects in mice similar to the symptoms observed in Alzheimer’s disease .”

Their experiments, published in The Journal of Neuroscience, with Dziewczapolski as first author, consisted in testing Alzheimer’s disease-induced mice with and without the gene for α7Rs. They found that while both types of mice developed plaques, only the ones with α7Rs showed the impairments associated with Alzheimer’s.

But that still left a key question: Why was the pairing deleterious?

In a recent paper in the Proceedings of the National Academy of Sciences, Heinemann and Dziewczapolski here at Salk with Juan Piña-Crespo, Sara Sanz-Blasco, Stuart A. Lipton of the Sanford-Burnham Medical Research Institute and their collaborators announced they had found the answer in unexpected interactions among neurons and other brain cells.

Neurons communicate by sending electrical and chemical signals to each other across gaps called synapses. The biochemical mix at synapses resembles a major airport on a holiday weekend—it’s crowded, complicated and exquisitely sensitive to increases and decreases in traffic. One of these signaling chemicals is glutamate, an excitatory neurotransmitter, which is essential for learning and storing memories. In the right balance, glutamate is part of the normal functioning of neuronal synapses. But neurons are not the only cells in the brain capable of releasing glutamate. Astrocytes, once thought to be merely cellular glue between neurons, also release this neurotransmitter.

In this new understanding of Alzheimer’s disease, there is a cellular signaling cascade, in which amyloid beta stimulates the alpha 7 nicotine receptors, which trigger astrocytes to release additional glutamate into the synapse, overwhelming it with excitatory (“go”) signals.

This release in turn activates another set of receptors outside of the synapse, called extrasynaptic-N-methyl-D-aspartate receptors (eNMDARs) that depress synaptic activity. Unfortunately, the eNMDARs seem to overly depress synaptic function, leading to the memory loss and confusion associated with Alzheimer’s.

Now that the team has finally determined the steps in this destructive pathway, the good news is that a drug developed by the Lipton’s Laboratory called NitroMemantine, a modification of the earlier Alzheimer’s medication, Memantine, may block the entry of eNMDARs into the cascade.

"Thanks to the joint effort of our colleagues and collaborators, we seem to finally have a clear mechanistic link between a key target of the amyloid beta in the brain, the Alpha7 nicotinic receptors, triggering downstream harmful effects associated with the initiation and progression of Alzheimer’s disease," says Dziewczapolski. "This is a clear demonstration of the value of basic biomedical research. Drug development cannot proceed without knowing the details of interactions at the molecular and cellular level. Our research revealed two potential targets, α7Rs and eNMDARs, for future disease-modifying therapeutics, which Dr. Heinemann and I both hope will translate in a better treatment for Alzheimer’s patients."

(Source: salk.edu)

University of Tübingen neuroscientists show that monkeys can decide to call out or keep silent

“Should I say something or not?” Human beings are not alone in pondering this dilemma – animals also face decisions when they communicate by voice. University of Tübingen neurobiologists Dr. Steffen Hage and Professor Andreas Nieder have now demonstrated that nerve cells in the brain signal the targeted initiation of calls – forming the basis of voluntary vocal expression. Their results are published in “Nature Communications.”

When we speak, we use the sounds we make for a specific purpose – we intentionally say what we think, or consciously withhold information. Animals, however, usually make sounds according to what they feel at that moment. Even our closest relations among the primates make sounds as a reflex based on their mood. Now, Tübingen neuroscientists have shown that rhesus monkeys are able to call (or be silent) on command. They can instrumentalize the sounds they make in a targeted way, an important behavioral ability which we also use to put language to a purpose.

To find out how the neural cells in the brain catalyse the production of controled vocal noises, the researchers taught rhesus monkeys to call out quickly when a spot appeared on a computer screen. While the monkeys solved puzzles, measurements taken in their prefrontal cortex revealed astonishing reactions in the cells there. The nerve cells became active whenever the monkey saw the spot of light which was the instruction to call out. But if the monkey simply called out spontaneously, these nerve cells were not activated. The cells therefore did not signaled for just any vocalisation – only for calls that the monkey actively decided to make.

The results published in “Nature Communications” provide valuable insights into the neurobiological foundations of vocalization. “We want to understand the physiological mechanisms in the brain which lead to the voluntary production of calls,” says Dr. Steffen Hage of the Institute for Neurobiology, “because it played a key role in the evolution of human ability to use speech.” The study offers important indicators of the function of part of the brain which in humans has developed into one of the central locations for controlling speech. “Disorders in this part of the human brain lead to severe speech disorders or even complete loss of speech in the patient,” Professor Andreas Nieder explains. The results – giving insights into how the production of sound is initiated – may help us better understand speech disorders.

(Source: uni-tuebingen.de)

Researchers at Johns Hopkins and the National Institutes of Health have identified a compound that dramatically bolsters learning and memory when given to mice with a Down syndrome-like condition on the day of birth. As they report in the Sept. 4 issue of Science Translational Medicine, the single-dose treatment appears to enable the cerebellum of the rodents’ brains to grow to a normal size.

The scientists caution that use of the compound, a small molecule known as a sonic hedgehog pathway agonist, has not been proven safe to try in people with Down syndrome, but say their experiments hold promise for developing drugs like it.

“Most people with Down syndrome have a cerebellum that’s about 60 percent of the normal size,” says Roger Reeves, Ph.D., a professor in the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine. “We treated the Down syndrome-like mice with a compound we thought might normalize the cerebellum’s growth, and it worked beautifully. What we didn’t expect were the effects on learning and memory, which are generally controlled by the hippocampus, not the cerebellum.”

Reeves has devoted his career to studying Down syndrome, a condition that occurs when people have three, rather than the usual two, copies of chromosome 21. As a result of this “trisomy,” people with Down syndrome have extra copies of the more than 300 genes housed on that chromosome, which leads to intellectual disabilities, distinctive facial features and sometimes heart problems and other health effects. Since the condition involves so many genes, developing treatments for it is a formidable challenge, Reeves says.

For the current experiments, Reeves and his colleagues used mice that were genetically engineered to have extra copies of about half of the genes found on human chromosome 21.
The mice have many characteristics similar to those of people with Down syndrome, including relatively small cerebellums and difficulty learning and remembering how to navigate through a familiar space. (In the case of the mice, this was tested by tracking how readily the animals located a platform while swimming in a so-called water maze.)
Based on previous experiments on how Down syndrome affects brain development, the researchers tried supercharging a biochemical chain of events known as the sonic hedgehog pathway that triggers growth and development. They used a compound — a sonic hedgehog pathway agonist — that could do just that.

The compound was injected into the Down syndrome-like mice just once, on the day of birth, while their cerebellums were still developing. “We were able to completely normalize growth of the cerebellum through adulthood with that single injection,” Reeves says.

But the research team went beyond measuring the cerebellums, looking for changes in behavior, too. “Making the animals, synthesizing the compound and guessing the right dose were so difficult and time-consuming that we wanted to get as much data out of the experiment as we could,” Reeves says. The team tested the treated mice against untreated Down syndrome-like mice and normal mice in a variety of ways, and found that the treated mice did just as well as the normal ones on the water maze test.

Reeves says further research is needed to learn why exactly the treatment works, because their examination of certain cells in the hippocampus known to be involved in learning and affected by Down syndrome appeared unchanged by the sonic hedgehog agonist treatment. One idea is that the treatment improved learning by strengthening communication between the cerebellum and the hippocampus, he says.

As for the compound’s potential to become a human drug, the problem, Reeves says, is that altering an important biological chain of events like sonic hedgehog would likely have many unintended effects throughout the body, such as raising the risk of cancer by triggering inappropriate growth. But now that the team has seen the potential of this strategy, they will look for more targeted ways to safely harness the power of sonic hedgehog in the cerebellum. Even if his team succeeds in developing a clinically useful drug, however, Reeves cautions that it wouldn’t constitute a “cure” for the learning and memory-related effects of Down syndrome. “Down syndrome is very complex, and nobody thinks there’s going to be a silver bullet that normalizes cognition,” he says. “Multiple approaches will be needed.”

(Source: newswise.com)

Our sense of touch can contribute to our ability to perceive faces, according to new research published in Psychological Science, a journal of the Association for Psychological Science.

“In daily life, we usually recognize faces through sight and almost never explore them through touch,” says lead researcher Kazumichi Matsumiya of Tohoku University in Japan. “But we use information from multiple sensory modalities in order to perceive many everyday non-face objects and events, such as speech perception or object recognition — these new findings suggest that even face processing is essentially multisensory.”

In a series of studies, Matsumiya took advantage of a phenomenon called the “face aftereffect” to investigate whether our visual system responds to nonvisual signals for processing faces. Inthe face aftereffect, we adapt to a face with a particular expression — happiness, for example — which causes us to perceive a subsequent neutral face as having the opposite facial expression (i.e., sadness).

Matsumiya hypothesized that if the visual system really does respond to signals from another modality, then we should see evidence for face aftereffects from one modality to the other. So, adaptation to a face that is explored by touch should produce visual face aftereffects.

To test this, Matsumiya had participants explore face masks concealed below a mirror by touching them. After this adaptation period, the participants were visually presented with a series of faces that had varying expressions and were asked to classify the faces as happy or sad. The visual faces and the masks were created from the same exemplar.

In line with his hypothesis, Matsumiya found that participants’ experiences exploring the face masks by touch shifted their perception of the faces presented visually compared to participants who had no adaptation period, such that the visual faces were perceived as having the opposite facial expression.

Further experiments ruled out other explanations for the results, including the possibility that the face aftereffects emerged because participants were intentionally imagining visual faces during the adaptation period.

And a fourth experiment revealed that the aftereffect also works the other way: Visual stimuli can influence how we perceive a face through touch.

According to Matsumiya, current views on face processing assume that the visual system only receives facial signals from the visual modality — but these experiments suggest that face perception is truly crossmodal.

“These findings suggest that facial information may be coded in a shared representation between vision and haptics in the brain,” notes Matsumiya, suggesting that these findings may have implications for enhancing vision and telecommunication in the development of aids for the visually impaired.