Neuroscience

ScienceDaily (May 7, 2012) — A Kansas State University graduate student is creating a schoolyard that can become a therapeutic landscape for children with autism.

Chelsey King, master’s student in landscape architecture, St. Peters, Mo., is working with Katie Kingery-Page, assistant professor of landscape architecture, to envision a place where elementary school children with autism could feel comfortable and included.

"My main goal was to provide different opportunities for children with autism to be able to interact in their environment without being segregated from the rest of the school," King said. "I didn’t want that separation to occur."

The schoolyard can be an inviting place for children with autism, King said, if it provides several aspects: clear boundaries, a variety of activities and activity level spaces, places where the child can go when overstimulated, opportunities for a variety of sensory input without being overwhelming and a variety of ways to foster communication between peers.

"The biggest issue with traditional schoolyards is that they are completely open but also busy and crowded in specific areas," King said. "This can be too overstimulating for a person with autism."

King researched ways that she could create an environment where children with autism would be able to interact with their surroundings and their peers, but where they could also get away from overstimulation until they felt more comfortable and could re-enter the activities.

"Through this research, I was able to determine that therapies and activities geared toward sensory stimulation, cognitive development, communication skills, and fine and gross motor skills — which traditionally occur in a classroom setting — could be integrated into the schoolyard," King said.

King designed her schoolyard with both traditional aspects — such as a central play area — and additional elements that would appeal to children with autism, including:

* A music garden where children can play with outdoor musical instruments to help with sensory aspects.

* An edible garden/greenhouse that allows hands-on interaction with nature and opportunities for horticulture therapy.

* A sensory playground, which uses different panels to help children build tolerances to difference sensory stimulation.

* A butterfly garden to encourage nature-oriented learning in a quiet place.

* A variety of alcoves, which provide children with a place to get away when they feel overwhelmed and want to regain control.

King created different signs and pictures boards around these schoolyard elements, so that it was easier for children and teachers to communicate about activities. She also designed a series of small hills around the central play areas so that children with autism could have a place to escape and watch the action around them.

"It is important to make the children feel included in the schoolyard without being overwhelmed," King said. "It helps if they have a place — such as a hill or an alcove — where they can step away from it and then rejoin the activity when they are ready.

King and Kingery-Page see the benefits of this type of schoolyard as an enriching learning environment for all children because it involves building sensory experience and communication.

"Most children spend seven to nine hours per weekday in school settings," Kingery-Page said. "Designing schoolyards that are educational, richly experiential, with potentially restorative nature contact for children should be a community concern."

The researchers collaborated with Jessica Wilkinson, a special education teacher who works with children with autism. King designed her schoolyard around Amanda Arnold Elementary School, which is the Manhattan school district’s magnet school for children with autism.

"Although there are no current plans to construct the schoolyard, designing for a real school allowed Chelsey to test principles synthesized from literature against the actual needs of an educational facility," Kingery-Page said. "Chelsey’s interaction with the school autism coordinator and school principal has grounded her research in the daily challenges of elementary education for students with autism."

Source: Science Daily

May 7, 2012

Many of us love massages, but imagine a massage so deep that tissues, organs and cells could also be ‘massaged’.

That’s exactly what Vibroacoustic Therapy, a low frequency sound massage, is clinically proven to do, and new research at U of T suggests that it may help people with debilitating diseases.

“It is basically stimulating the body with very low sound – like sitting on a subwoofer,” said Professor Lee Bartel of the Faculty of Music.  “But it requires special speakers that carry sound almost too low to hear in a way that changes it basically to something you feel instead of hear.”

Bartel and his team in the new Music and Health Research Collaboratory (MaHRC) are exploring the medical effects of low frequency sound and have shown that this therapy can play a key role in reducing the symptoms of Parkinson’s disease.

Vibroacoustic therapy (VAT) consists of low sound frequencies that are transmitted to the body and mind through special transducers that convert the sound to inner body massage. MaHRC associates Heidi Ahonen and Quincy Almeida treated two groups of Parkinson’s patients (20 with dominant tremor symptoms and 20 with slow/rigid movement symptoms) with five minutes of 30 Hz vibration.

Both groups showed improvements in all symptoms, including less rigidity and better walking speed with bigger steps and less tremor.

“There have been several studies using vibration from sound with Parkinson’s,” said Bartel   “It has been known for over 100 years that vibration (like riding in a wagon on cobblestones) helped relieve some symptoms. So the scientific study of the effect of low frequency sound was a natural connection. Also known is that 40 Hz brain waves seem to be carriers of information between the parts of the brain that control movement. So adding extra stimulation in that zone should help that communication and so assist in movement control.”

Bartel, Founding and Acting Director of MaHRC, says the goal of low frequency sound studies with Parkinson’s is to determine which approach is most effective, how much and how often treatment is needed, and whether medication can be reduced. Vibroacoustic Therapy frequencies, between 20 and 100 Hz or pulses per second, correspond to brainwave activities and function that are currently being explored in neuroscience. 

But the effects of Vibroacoustic Therapy extend beyond the brain. It also provides deep physical cellular stimulation to skin, muscles and joints, resulting in decreased pain and increased mobility. Like hand/mechanical massage, vibroacoustic therapy aids circulation, relaxes muscles, and feels good.

Bartel points to research that shows that “several medical conditions including Parkinson’s and neuralgic pain like fibromyalgia, may be related to a common brain mechanism – a brain rhythm disorientation between the inner brain and the outer cortex. Since the rhythmic pulses of music can drive and stabilize these, we speculate that low frequency sound might help in fibromyalgia as well as Parkinson’s.”

Bartel’s team is now looking at the role of vibroacoustic therapy as a treatment for patients with fibromyalgia.

“Although it is too early to form any conclusions, there is encouraging data indicating that treating fibromyalgia patients with doses of 40 Hz sound seems to reduce pain.” 

“It is truly an exciting time for music medicine – the idea of developing audioceuticals (prescribable sound) points to a whole new direction for music therapy, and the potential for MaHRC to lead in this is very exciting for me” said Bartel.      

Provided by University of Toronto

Source: medicalxpress.com

May 6, 2012

Gaining access to the inner workings of a neuron in the living brain offers a wealth of useful information: its patterns of electrical activity, its shape, even a profile of which genes are turned on at a given moment. However, achieving this entry is such a painstaking task that it is considered an art form; it is so difficult to learn that only a small number of labs in the world practice it.

Researchers at MIT and the Georgia Institute of Technology have developed a way to automate a process called whole-cell patch clamping, which involves bringing a tiny hollow glass pipette in contact with the cell membrane of a neuron, then opening up a small pore in the membrane to record the electrical activity within the cell. Credit: Sputnik Animation and MIT McGovern Institute

But that could soon change: Researchers at MIT and the Georgia Institute of Technology have developed a way to automate the process of finding and recording information from neurons in the living brain. The researchers have shown that a robotic arm guided by a cell-detecting computer algorithm can identify and record from neurons in the living mouse brain with better accuracy and speed than a human experimenter.

The new automated process eliminates the need for months of training and provides long-sought information about living cells’ activities. Using this technique, scientists could classify the thousands of different types of cells in the brain, map how they connect to each other, and figure out how diseased cells differ from normal cells.

The project is a collaboration between the labs of Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT, and Craig Forest, an assistant professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech.

"Our team has been interdisciplinary from the beginning, and this has enabled us to bring the principles of precision machine design to bear upon the study of the living brain," Forest says. His graduate student, Suhasa Kodandaramaiah, spent the past two years as a visiting student at MIT, and is the lead author of the study, which appears in the May 6 issue of Nature Methods.

The method could be particularly useful in studying brain disorders such as schizophrenia, Parkinson’s disease, autism and epilepsy, Boyden says. “In all these cases, a molecular description of a cell that is integrated with [its] electrical and circuit properties … has remained elusive,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research. “If we could really describe how diseases change molecules in specific cells within the living brain, it might enable better drug targets to be found.”

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May 6, 2012 

Brain networks may avoid traffic jams at their busiest intersections by communicating on different frequencies, researchers at Washington University School of Medicine in St. Louis, the University Medical Center at Hamburg-Eppendorf and the University of Tübingen have learned.

"Many neurological and psychiatric conditions are likely to involve problems with signaling in brain networks," says co-author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University. "Examining the temporal structure of brain activity from this perspective may be especially helpful in understanding psychiatric conditions like depression and schizophrenia, where structural markers are scarce."

The research will be published May 6 in Nature Neuroscience.

Scientists usually study brain networks — areas of the brain that regularly work together — using magnetic resonance imaging, which tracks blood flow. They assume that an increase in blood flow to part of the brain indicates increased activity in the brain cells of that region.

"Magnetic resonance imaging is a useful tool, but it does have limitations," Corbetta says. "It only allows us to track brain cell activity indirectly, and it is unable to track activity that occurs at frequencies greater than 0.1 hertz, or once every 10 seconds. We know that some signals in the brain can cycle as high as 500 hertz, or 500 times per second."

For the new study, conducted at the University Medical Center at Hamburg-Eppendorf, the researchers used a technique called magnetoencephalography (MEG) to analyze brain activity in 43 healthy volunteers. MEG detects very small changes in magnetic fields in the brain that are caused by many cells being active at once. It can detect these signals at rates up to 100 hertz.

"We found that different brain networks ticked at different frequencies, like clocks ticking at different speeds," says lead author Joerg Hipp, PhD, of the University Medical Center at Hamburg-Eppendorf and the University of Tübingen, both in Germany.

For example, networks that included the hippocampus, a brain area critical for memory formation, tended to be active at frequencies around 5 hertz. Networks constituting areas involved in the senses and movement were active between 32 hertz and 45 hertz. Many other brain networks were active at frequencies between eight and 32 hertz. These “time-dependent” networks resemble different airline route maps, overlapping but each ticking at a different rate.

"There have been a number of fMRI studies of depression and schizophrenia showing ‘spatial’ changes in the organization of brain networks," Corbettta says. "MEG studies provide a window into a much richer ‘temporal’ structure. In the future, this might offer new diagnostic tests or ways to monitor the efficacy of interventions in these debilitating mental conditions."

Provided by Washington University School of Medicine

Source: medicalxpress.com

ScienceDaily (May 4, 2012) — Researchers in Spain have found that at least some of the individuals claiming to see the so-called aura of people actually have the neuropsychological phenomenon known as “synesthesia” (specifically, “emotional synesthesia”). This might be a scientific explanation of their alleged ability.

New research suggests that at least some of the individuals claiming to see the so-called aura of people actually have the neuropsychological phenomenon known as “synesthesia” (specifically, “emotional synesthesia”). This might be a scientific explanation of their alleged ability. (Credit: © Nikki Zalewski / Fotolia)

In synesthetes, the brain regions responsible for the processing of each type of sensory stimuli are intensely interconnected. Synesthetes can see or taste a sound, feel a taste, or associate people or letters with a particular color.

The study was conducted by the University of Granada Department of Experimental Psychology Óscar Iborra, Luis Pastor and Emilio Gómez Milán, and has been published in the journal Consciousness and Cognition. This is the first time that a scientific explanation has been provided for the esoteric phenomenon of the aura, a supposed energy field of luminous radiation surrounding a person as a halo, which is imperceptible to most human beings.

In basic neurological terms, synesthesia is thought to be due to cross-wiring in the brain of some people (synesthetes); in other words, synesthetes present more synaptic connections than “normal” people. “These extra connections cause them to automatically establish associations between brain areas that are not normally interconnected,” professor Gómez Milán explains. New research suggests that many healers claiming to see the aura of people might have this condition.

The case of the "Santón de Baza"

One of the University of Granada researchers remarked that “not all ‘healers’ are synesthetes, but there is a higher prevalence of this phenomenon among them. The same occurs among painters and artists, for example.” To carry out this study, the researchers interviewed some synesthetes including a ‘healer’ from Granada, “Esteban Sánchez Casas,” known as"El Santón de Baza".

Many local people attribute “paranormal powers” to El Santón, because of his supposed ability to see the aura of people “but, in fact, it is a clear case of synesthesia,” the researchers explained. According to the researchers, El Santón has face-color synesthesia (the brain region responsible for face recognition is associated with the color-processing region); touch-mirror synesthesia (when the synesthete observes a person who is being touched or is experiencing pain, s/he experiences the same); high empathy (the ability to feel what other person is feeling), and schizotypy (certain personality traits in healthy people involving slight paranoia and delusions). “These capacities make synesthetes have the ability to make people feel understood, and provide them with special emotion and pain reading skills,” the researchers explain.

In the light of the results obtained, the researchers remarked on the significant “placebo effect” that healers have on people, “though some healers really have the ability to see people’s ‘auras’ and feel the pain in others due to synesthesia.” Some healers “have abilities and attitudes that make them believe in their ability to heal other people, but it is actually a case of self-deception, as synesthesia is not an extrasensory power, but a subjective and ‘adorned’ perception of reality,” the researchers state.

Source: Science Daily

May 5, 2012 

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure the communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside of the body using stem cell-derived neurons and muscle cells, and that the level of communication, or synaptic activity, between the cells could be accurately measured by stimulating motor neurons with an electrode and then measuring the transfer of electrical activity into the muscle cells to which the motor neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells, allowing the entry of calcium and other ions that cause them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons. That estimation could shed light on a variety of neurodegenerative diseasessuch as spinal muscular atrophy and amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in which the communication between motor neurons and muscle cells is thought to unravel, said study senior author Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4, 2012 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."

Novitch said the synaptic communication activity his team was able to create and measure using mouse embryonic stem cell-derived motor neurons and muscle cells looks very similar what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,. To do that, we had to first define an activity profile of normal synaptic communication," he said. "Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology, used mouse embryonic stem cells to create the motor neurons and previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

In less than a week, the neurons had reached out to the muscle cells and assembled the protein networks needed for synaptic communication, Novitch said.

To measure the connections between the cells, the scientists used a technique called dual patch clamp recording. Pipettes containing stimulating and recording electrodes are inserted into the membranes of the motor neurons and muscle cells, being careful not to injure them. With this method, they were able send an electrical current into the motor neurons and measure responses in the muscle cells, as well as visualize the muscular contractions.

"The in vitro system developed here might accordingly be expanded to assess the underlying cellular and molecular mechanisms that contribute to this decline in synaptic input to motor neurons," the study states. "Thus, in addition to their utility for helping to answer fundamental biological questions, these co-cultures have clear applications in addressing problems of medical significance."

Going forward, Novitch and his team hope to recreate and confirm the work using human stem cell-derived motor neurons and muscle cells and measure the synaptic communications with newly developed optical recording methods, which are less invasive than the patch clamp techniques used in this study.

Provided by University of California, Los Angeles

Source: medicalxpress.com

ScienceDaily (May 3, 2012) — Malfunctioning single proteins can cause disruptions in neuronal junctions leading to autistic forms of behavior. A current study, published in the scientific journal Nature, comes to this conclusion after examining genetically altered mice.

The study, in which scientists from Charité — Universitätsmedizin Berlin and the NeuroCure Cluster of Excellence contributed, thus supports the hypothesis that disruptions in neuronal junctions, i.e. synapses, could be the cause of the development of neuropsychiatric illnesses like autism. The international research team, that included scientists from Ulm University and the Institut Pasteur in Paris, ascribes a key role to the excitatory synapses. This finding could become an important step stone for future autism therapies.

Nerve cells communicate with each other via signal transmission to synaptic junctions. These junctions are stabilized through structural proteins, including the so-called ProSAP1/Shank2 protein. In order to understand the role that this protein has on synapses and ultimately in the development of autism, the researchers genetically modified mice and disabled the relevant protein. The choice of this protein was not arbitrary: In preparation for the current study, a number of the scientists involved found evidence that the mutation of this protein can lead to autism in humans. Various neuronal developmental disorders manifested through distinctive social and communicative behavioral features, as well as stereotyped behaviors are combined under the term of “autism.”

The absence of this structural protein in the mouse model also had visible implications: Animals with the mutated gene are hyperactive and demonstrate compulsive repetitions of particular features — like grooming, for example. In behavioral experiments, peculiarities in social and communicative interaction also become distinct. In the brains of the mice, researchers found noticeable mutations of synaptic junctions — specifically in excitatory synapses. When glutamate transmitters bind to glutamate receptors located at these junctions, the nerve cells become excitatory. If the mouse is lacking this structural protein, the transmitters increasingly find a related structural protein on the excitatory synapses, the ProSAP2/Shank3. This protein has also been implicated in the development of autism. At the same time, the composition of glutamate receptors mutates.

But what happens when this related structural protein in the mice is switched off? This is also examined in the study presented. The conclusion is that, in this case as well, mutations of the excitatory synapses occur. Obviously, both structural molecules alternate in fulfilling regular functions. “The study illustrates the significant role glutamatergic systems play in autism and thus contributes to understanding better synaptic changes in autism,” reports Stephanie Wegener, one of the participating scientists at Charité Berlin. The study is therefore an important part of the essential scientific foundation needed to develop possible therapies for autism.

Source: Science Daily

ScienceDaily (May 3, 2012) — The problems of living with bipolar have been well documented, but a new study by Lancaster University has captured the views of those who also report highly-valued, positive experiences of living with the condition.

Researchers at Lancaster’s Spectrum Centre, which is dedicated to the study of bipolar disorder, interviewed and recorded their views of ten people with a bipolar diagnosis, aged between 24 and 57. Participants in the study reported a number of perceived benefits to the condition ranging from to sharper senses to increased productivity.

The research was designed to explore growing evidence that some people with bipolar value their experiences and in some cases would prefer not to be without the condition.

Participants described a wide range of experiences and internal states that they believed they felt to a far greater intensity than those without the condition. These included increased perceptual sensitivity, creativity, focus and clarity of thought.

Some held (or had previously held) high functioning professional jobs or had been studying for higher level qualifications. They described in detail how they experienced times when tasks that are usually quite difficult or time consuming, would feel incredibly easy and the ability to achieve at a high level during these times was clearly immensely rewarding.

Others expressed the view that they felt ‘lucky’ or even ‘blessed’ to have the condition.

Alan, (not his real name) one of the interviewees, said: “It’s almost as if it opens up something in the brain that isn’t otherwise there, and I see colour much more vividly than I used to……So I think that my access to music and art are something for which I’m grateful to bipolar for enhancing. It’s almost as if it’s a magnifying glass that sits between that and myself.”

Researchers even found some people with bipolar reaped positive experiences from their lows such as greater empathy with the suffering of others.

Dr Fiona Lobban, who led the study, said: “Bipolar Disorder is generally seen as a severe and enduring mental illness with serious negative consequences for the people with this diagnosis and their friends and family. For some people this is very much the case. Research shows that long term unemployment rates are high, relationships are marred by high levels of burden on family and friends and quality of life is often poor. High rates of drug and alcohol misuse are reported for people with this diagnosis and suicide rates are twenty times that of the general population.

"However, despite all these factors researchers and clinicians are aware that that some aspects of bipolar experiences are also highly valued by some people. We wanted to find out what these positive experiences were.

"People were very keen to take part in this study and express views which some felt had to be hidden from the medical profession.

"It is really important that we learn more about the positives of bipolar as focusing only on negative aspects paints a very biased picture that perpetuates the view of bipolar as a wholly negative experience. If we fail to explore the positives of bipolar we also fail to understand the ambivalence of some people towards treatment."

Rita Long from Stockport was not part of the study but can identify with its findings. She was 40 when she was diagnosed with the condition but from her school days she was aware that she experienced the world differently to her twin sister.

"We were making Christmas cakes at school and I was so interested and excited by it and my sister says she remembers watching me and thinking, ‘I really wish I could get that excited about making a Christmas cake’. I noticed things, experienced them with a different level of intensity, we’d be on a walk and I’d be saying look at the colour of this, and my sister would be saying, ‘It’s just a berry’. Socially too, people with bipolar can be quite quick witted, humorous. Until much later in life I just presumed those things were part of my personality.

"I don’t want to underestimate how difficult the bad times can be that some people go through with bipolar but at the same time I feel very passionate about the positives. If we are going to move on as a society — in academia, in business, in entertainment — we need people who will push boundaries. People with bipolar can do that."

Source: Science Daily

ScienceDaily (May 3, 2012) — A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. (Credit: Photo courtesy of The Scripps Research Institute)

What genetic changes account for the vast behavioral differences between humans and other primates? Researchers so far have catalogued only a few, but now it seems that they can add a big one to the list. A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

Surprisingly, the added copy doesn’t augment the function of the original gene, SRGAP2, which makes neurons sprout connections to neighboring cells. Instead it interferes with that original function, effectively giving neurons more time to wire themselves into a bigger brain.

"This appears to be a major example of a genomic innovation that contributed to human evolution," said Franck Polleux, a professor at The Scripps Research Institute. "The finding that a duplicated gene can interact with the original copy also suggests a new way to think about how evolution occurs and might give us clues to human-specific developmental disorders such as autism and schizophrenia."

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ScienceDaily (May 3, 2012) — UCSF scientists have identified patterns of brain activity in the rat brain that play a role in the formation and recall of memories and decision-making. The discovery, which builds on the team’s previous findings, offers a path for studying learning, decision-making and post-traumatic stress syndrome.

Brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past. (Credit: © Oleg Kozlov / Fotolia)

The researchers previously identified patterns of brain activity in the rat hippocampus, a brain region critical for memory storage. The patterns sometimes represented where an animal was in space, and, at other times, represented fast-motion replays of places the animal had been, but no one knew whether these patterns indicated the process of memory formation and recollection.

In the journal Science this week (online May 3, 2012), the UCSF researchers demonstrated that the brain activity is critical for memory formation and recall. Moreover, they showed that the brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past.

"We think these memory-replay events are central to understanding how the brain retrieves past experiences and uses them to make decisions," said neuroscientist Loren Frank, PhD, a associate professor of physiology and a member of the Keck Center for Integrative Neuroscience at UCSF, who led the research with Shantanu Jadhav, PhD, a post-doctoral fellow. "They offer insight into how a past experience can have such a profound effect on how we think and feel."

The finding gives scientists a new way to investigate fundamental processes like learning and decision-making in animals and in people. It also may help shed light on memory disorders like post-traumatic stress disorder (PTSD), which is characterized by strong, disturbing and uncontrolled memories.

Without Links to the Past, Rats Face Indecision

Seeking to understand how the recall of specific memories in the brain guides our thinking, Frank and his colleagues built a system for detecting the underlying patterns of neuronal activity in rats. They fitted the animals with electrodes and built a system that enabled them to detect a specific pattern, called a sharp-wave ripple, in the hippocampus. Whenever they detected a ripple, they would send a small amount of electricity into another set of electrodes that would immediately interrupt the ripple event, in effect turning off all memory replay activity without otherwise affecting the brain.

The UCSF researchers knew that these sharp-wave ripples would be activated when the animals had to make choices about which direction to turn as they wended their way toward their reward: a few drops of sweetened condensed milk. These signals seem to be flashes of memory recall, said Frank, a rat’s past knowledge flooding back to inform it on what had happened in the past and where it might go in the future. Squashing the sharp-wave ripples, the UCSF team found, disrupted the recall and subverted the rat’s ability to correctly navigate the maze.

This shows, said Frank, that the sharp-wave ripples are critical for this type of memory recall. Through these brain waves, the rat reprocesses and replays old experiences in a fleeting instant — lessons from the past essential for shaping their perception of the present.

"We think these memory replay events are a fundamental constituent of memory retrieval and play a key role in human perspective and decision-making as well," he said. "These same events have been seen in memory tasks in humans, and now we know they are critical for memory in rats. We think that these fast-forward replays make up the individual elements of our own memories, which jump rapidly from event to event."

Next, the team wants to tease out information about how the rats actually use these memory replay events to make decisions and how amplifying or blocking specific replay events will change the way an animal learns and remembers. They also think that these events could be important for understanding memory problems, as when stressful memories intrude into daily life.

Source: Science Daily

May 3, 2012

Under some conditions, the brains of embryonic chicks appear to be awake well before those chicks are ready to hatch out of their eggs. That’s according to an imaging study published online on May 3 in Current Biology, a Cell Press publication, in which researchers woke chick embryos inside their eggs by playing loud, meaningful sounds to them. Playing meaningless sounds to the embryos wasn’t enough to rouse their brains.

This image shows an X-ray computed-tomography image of the chicken embryo skeleton inside an egg, which shows the developmental stage, together with a positron emission tomography image showing nervous system activity in the brain. Balaban et al., publishing in Current Biology, report the activity in chicken embryo brains is inversely related to behavioral activity, with different sleep-like states emerging for the first time. Playing meaningful sounds selectively induced patterns of embryonic brain activity similar to awake, post-hatching animals. Image 3D rendering by Carmen García-Villalba. Credit: Balaban et al. Current Biology

The findings may have implications not only for developing chicks and other animals, but also for prematurely born infants, the researchers say. Pediatricians have worried about the effects of stimulating brains that are still under construction, especially as modern medicine continues to push back the gestational age at which preemies can reliably survive.

"This work showed that embryo brains can function in a waking-like manner earlier than previously thought—well before birth," said Evan Balaban of McGill University. "Like adult brains, embryo brains also have neural circuitry that monitors the environment to selectively wake the brain up during important events."

That waking-like brain activity appears in a latent but inducible state during the final 20 percent of embryonic life, the researchers found. At that point, sleep-like brain activity patterns also emerge.

Before that major dividing line in development—for the first 80 percent of embryonic life— “embryos are in a state that is neither like sleep nor waking,” Balaban said. He suggests it may be useful to compare that state to what happens when people are comatose or under the influence of anesthesia.

This entire line of work was made possible by a new generation of molecular brain imagers developed by Balaban’s coauthors Juan-José Vaquero and Manuel Desco at the Universidad Carlos III in Madrid. Those state-of-the art machines can detect very small amounts of tracer molecules and pinpoint them to a tiny region of the brain (about 0.7 mm, or less than 3/100ths of an inch).

The researchers say they were surprised to capture waking-like activity before birth. And there were other surprises, too. The embryo brains they observed showed considerable variation in activity, for one.

Before the emergence of sleep and waking patterns of brain activity, the chick embryos in their study exhibited lots of spontaneous movement, even as their higher-brain regions remained inactive. Once the chicks reached that 80 percent mark in development, higher-brain regions began crackling with activity. At the same time, those physical movements ceased as the embryos entered a sleep-like state.

"The last 30 percent of fetal brain development is a more interesting time than we previously thought, because it’s when complex whole-brain functions that depend on coordination of widely separated brain areas first emerge," Balaban said. "Embryos begin to cycle through a variety of brain states and are even capable of showing waking-like brain activity."

That might explain instances of complex fetal and early neonatal learning. “It also raises questions about the longer-term developmental consequences that such brain activity may have, if it is induced before intrinsic brain wiring is sufficiently completed,” Balaban said, “for example, in babies born very prematurely. We are excited by the possibility that the techniques developed here can now be used to provide answers to these questions.”

Provided by Cell Press

Source: medicalxpress.com

ScienceDaily (May 2, 2012) — Results of a new study reported recently by psychology researcher Lisa Scott and colleagues at the University of Massachusetts Amherst confirm that although infants are born with equal abilities to tell apart people within multiple races, by age 9 months they are better at recognizing faces and emotional expressions of people within groups they interact with most.

For part of the UMass Amherst study of infants and recognition of individuals of other races, a net of recording sensors was placed on the infant’s head to record brain activity while they viewed own-race and other-race emotion faces (happy, sad) that either matched or did not match a corresponding emotion sound (laughing, crying). This measure helps researchers understand how the brain develops in response to experience during the first year of life. Lisa Scott is pictured adjusting the head net on an infant subject. (Credit: UMass Amherst)

The researchers found that by 9 months, infants show a decline in their ability to tell apart two faces within another race and to accurately match emotional sounds with emotional expressions of different-race individuals. This is the first investigation of this effect in infancy and supports other studies suggesting that emotion recognition is less accurate for other-race faces than own-race faces. Scott’s paper was singled out for special mention as the “Editor’s Choice” article in the May issue of Developmental Science.

This research suggests that throughout the first year of life, babies are developing highly specialized perceptual abilities in response to important people in their environment, such as family members. This focus of attention to familiar groups of people compared to unfamiliar groups is hypothesized to be the root of later difficulties some adults have in identifying and recognizing faces of other races.

This is similar to how babies learn language. Early in infancy babies do not know yet which sounds are meaningful in their native language, so they treat all sounds similarly. But as they learn the language spoken around them, their ability to tell apart sounds within other languages declines and their ability to differentiate sounds within their native language improves.

Scott says, “In addition to providing information critical for understanding how infants learn about the surrounding environment, the results of this research may serve as a guide for early education and interventions designed to reduce later racial prejudice and stereotyping” Scott states. “These results suggest that biases in face recognition and perception begin in preverbal infants, well before concepts about race are formed. It is important for us to understand the nature of these biases in order to reduce or eliminate them.”

For this study, each infant came to the lab with a parent for a one-hour session that included showing infants pictures of faces and having them listen to sounds while their looking time and brain activity were recorded. Forty-eight Caucasian infants with little to no previous experience with African-American or black individuals participated in this study.

Infants completed two tasks. The first was designed to assess their ability to tell the difference between two faces within their own race and two faces within another, unfamiliar, race. For the second task, a net of recording sensors was placed on the infant’s head to record brain activity while they viewed own-race and other-race emotion faces (happy, sad) that either matched or did not match a corresponding emotion sound (laughing, crying).

Consistent with previous reports, 5-month-old infants were found to equally tell apart faces from both races, whereas 9-month-old infants were better at telling apart two faces within their own race, Scott and colleagues report.

Further, measures of brain activity revealed differential neural processing of own-race compared to other-race emotional faces at 9 months. However, 5-month olds exhibited similar processing for both own- and other-race faces. In addition, infants were found to shift their processing of face-related emotion information from neural regions in the front of the brain to neural regions in the back of the brain from 5 to 9 months of age. This shift in neural processing helps researchers understand how the brain develops in response to experience during the first year of life.

Source: Science Daily

ScienceDaily (May 2, 2012) — A highly toxic beta-amyloid — a protein that exists in the brains of Alzheimer’s disease victims — has been found to greatly increase the toxicity of other more common and less toxic beta-amyloids, serving as a possible “trigger” for the advent and development of Alzheimer’s, researchers at the University of Virginia and German biotech company Probiodrug have discovered.

Pyroglutanylated beta-amyloid (green) accumulates in the brains of mice genetically engineered to overproduce it. The red cells are astrocytes, which invade brain regions where the amyloid is deposited and neurons die. The blue structures are nuclei of neurons and astrocytes. (Credit: University of Virginia)

The finding, reported in the May 2 online edition of the journal Nature, could lead to more effective treatments for Alzheimer’s. Already, Probiodrug AG, based in Halle, Germany has completed phase 1 clinical trials in Europe with a small molecule that inhibits an enzyme, glutaminyl cyclase, that catalyzes the formation of this hypertoxic version of beta-amyloid.

"This form of beta-amyloid, called pyroglutamylated (or pyroglu) beta-amyloid, is a real bad guy in Alzheimer’s disease," said principal investigator George Bloom, a U.Va. professor of biology and cell biology in the College of Arts & Sciences and School of Medicine, who is collaborating on the study with scientists at Probiodrug. "We’ve confirmed that it converts more abundant beta-amyloids into a form that is up to 100 times more toxic, making this a very dangerous killer of brain cells and an attractive target for drug therapy."

Bloom said the process is similar to various prion diseases, such as mad cow disease or chronic wasting disease, where a toxic protein can “infect” normal proteins that spread through the brain and ultimately destroy it.

In the case of Alzheimer’s, severe dementia occurs over the course of years prior to death.

"You might think of this pyroglu beta-amyloid as a seed that can further contaminate something that’s already bad into something much worse — it’s the trigger," Bloom said. Just as importantly, the hypertoxic mixtures that are seeded by pyroglu beta-amyloid exist as small aggregates, called oligomers, rather than as much larger fibers found in the amyloid plaques that are a signature feature of the Alzheimer’s brain.

And the trigger fires a “bullet,” as Bloom puts it. The bullet is a protein called tau that is stimulated by beta-amyloid to form toxic “tangles” in the brain that play a major role in the onset and development of Alzheimer’s. Using mice bred to have no tau genes, the researchers found that without the interaction of toxic beta-amyloids with tau, the Alzheimer’s cascade cannot begin. The pathway by which pyroglu beta-amyloid induces the tau-dependent death of neurons is now the target of further investigation to understand this important step in the early development of Alzheimer’s disease

"There are two matters of practical importance in our discovery," Bloom said. "One, is the new insights we have as to how Alzheimer’s might actually progress — the mechanisms which are important to understand if we are to try to prevent it from happening; and second, it provides a lead into how to design drugs that might prevent this kind of beta-amyloid from building up in the first place."

Said study co-author Hans-Ulrich Demuth, a biochemist and chief scientific officer at Probiodrug, “This publication further adds significant evidence to our hypothesis about the critical role pyroglu beta-amyloid plays in the initiation of Alzheimer’s Disease. For the first time we have found a clear link in the relationship between pyroglu beta-amyloid, oligomer formation and tau protein in neuronal toxicity.”

Bloom and his collaborators are now looking for other proteins that are needed for pyroglu beta-amyloid to become toxic. Any such proteins they discover are potential targets for the early diagnosis and/or treatment of Alzheimer’s disease.

Source: Science Daily

ScienceDaily (May 2, 2012) — A drug prescribed for Alzheimer’s disease does not ease clinically significant agitation in patients, according to a new study conducted by researchers from the U.K., U.S. and Norway. This is the first randomized controlled trial designed to assess the effectiveness of the drug (generic name memantine) for significant agitation in Alzheimer’s patients.

Previous studies suggested memantine could help reduce agitation and improve cognitive functions such as memory. Led by the University of East Anglia in the U.K., the new research found that while memantine does improve cognitive functioning and neuropsychiatric symptoms such as delusion, mood and anxiety, it is no more effective in reducing significant agitation than a placebo.

"Memantine is quite commonly prescribed for Alzheimer’s disease in the U.S. Despite the negative findings regarding agitation, this trial opens a door of hope," said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate professor of medicine at the Indiana University School of Medicine and associate director of the IU Center for Aging Research. "Memantine does appear to help with other behavioral and psychological symptoms of Alzheimer’s disease."

Dr. Boustani, a co-author of the study, is also the medical and research director of the Healthy Aging Brain Center at Wishard Health Services.

"Efficacy of memantine for agitation in Alzheimer’s dementia: a randomized double-blind placebo controlled trial"published in PLoS ONEon May 2. Authors of the study are from Indiana University; the University of East Anglia, University College London, University of Kent, Aston University, Oxleas National Health Service Foundation Trust and Kings College London, all in the U.K.; and the University of Stavanger in Norway.

An estimated 5.4 million Americans have Alzheimer’s disease according to the Alzheimer’s Association. Many are agitated. They may, for example, pace continually, become physically or verbally aggressive or scream persistently. In addition to harming quality of life for the patient, agitation places enormous strain on relationships with family members and care providers, and often results in institutionalization.

"People who have mild symptoms [of agitation] often respond to changes in the environment or psychological treatment, but these methods are impractical in severe agitation," said Chris Fox, M.D., of Norwich Medical School at University of East Anglia, who led the research. "Our findings regarding memantine are disappointing with respect to severe agitation — particularly as the alternative antipsychotic medications can have significant side effects such as increased rates of stroke and death. However, we hope our study will highlight the urgent need for investment in safe and effective new treatments for this growing disease."

The team of researchers studied 153 nursing home residents and hospital inpatients with severe Alzheimer’s from September 2007 to May 2010. All the study participants displayed significant agitation requiring clinical treatment. Half were given memantine, and half received a placebo. The researchers reported signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given memantine, but no statistically significant difference in terms of the severe agitation that was the primary focus of the study.

Memantine is approved by the U.S. Food and Drug Administration for Alzheimer’s disease. The trial was sponsored by East Kent Hospitals University National Health Service Foundation Trust in the U.K. The study was funded by Lundbeck, a manufacturer of memantine.

"This research suggests that even though memantine can have real benefits for people in the later stages of Alzheimer’s, it may not have all the answers," said Anne Corbett, research manager at the Alzheimer’s Society of the U.K., which was not involved in the research. "However, prescribers should not see the only alternative as being to hand out antipsychotics. These overprescribed drugs double the risk of death and treble the risk of stroke and should always be a last resort for people with dementia."

Source: Science Daily

ScienceDaily (May 2, 2012) — A new study suggests that eating foods that contain omega-3 fatty acids, such as fish, chicken, salad dressing and nuts, may be associated with lower blood levels of a protein related to Alzheimer’s disease and memory problems. The research is published in the May 2, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"While it’s not easy to measure the level of beta-amyloid deposits in the brain in this type of study, it is relatively easy to measure the levels of beta-amyloid in the blood, which, to a certain degree, relates to the level in the brain," said study author Nikolaos Scarmeas, MD, MS, with Columbia University Medical Center in New York and a member of the American Academy of Neurology.

For the study, 1,219 people older than age 65, free of dementia, provided information about their diet for an average of 1.2 years before their blood was tested for the beta-amyloid. Researchers looked specifically at 10 nutrients, including saturated fatty acids, omega-3 and omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D.

The study found that the more omega-3 fatty acids a person took in, the lower their blood beta-amyloid levels. Consuming one gram of omega-3 per day (equal to approximately half a fillet of salmon per week) more than the average omega-3 consumed by people in the study is associated with 20 to 30 percent lower blood beta-amyloid levels.

Other nutrients were not associated with plasma beta-amyloid levels. The results stayed the same after adjusting for age, education, gender, ethnicity, amount of calories consumed and whether a participant had the APOE gene, a risk factor for Alzheimer’s disease.

"Determining through further research whether omega-3 fatty acids or other nutrients relate to spinal fluid or brain beta-amyloid levels or levels of other Alzheimer’s disease related proteins can strengthen our confidence on beneficial effects of parts of our diet in preventing dementia," said Scarmeas.

Source: Science Daily

ScienceDaily (May 2, 2012) — The way we use our hands may determine how emotions are organized in our brains, according to a recent study published inPLoS ONE by psychologists Geoffrey Brookshire and Daniel Casasanto of The New School for Social Research in New York.

Motivation, the drive to approach or withdraw from physical and social stimuli, is a basic building block of human emotion. For decades, scientists have believed that approach motivation is computed mainly in the left hemisphere of the brain, and withdraw motivation in the right hemisphere. Brookshire and Casasanto’s study challenges this idea, showing that a well-established pattern of brain activity, found across dozens of studies in right-handers, completely reverses in left-handers.

The study used electroencepahlography (EEG) to compare activity in participants’ right and left hemispheres during rest. After having their brain waves measured, participants completed a survey measuring their level of approach motivation, a core aspect of our personalities. In right-handers, stronger approach motivation was associated with greater activity in the left hemisphere than the right, consistent with previous studies. Left-handers showed the opposite pattern: approach motivation was associated with greater activity in the right hemisphere than the left.

A New Link Between Motor Action and Emotion

Most cognitive functions do not reverse with handedness. Language, for example, is mainly in the left hemisphere for the majority of right- and left-handers. However, these results were not unexpected.

"We predicted this hemispheric reversal because we observed that people tend to use different hands to perform approach- and avoidance-related actions," says Casasanto. Approach actions are often performed with the dominant hand, and avoidance actions with the non-dominant hand.

"Approach motivation is computed by the hemisphere that controls the right hand in right-handers, and by the hemisphere that controls the left hand in left-handers," says Casasanto. "We don’t think this is a coincidence. Neural circuits for motivation may be functionally related to circuits that control hand actions — emotion may be built upon neural circuits for action, in evolutionary or developmental time."

The authors caution that these data show a correlation between emotional motivation and motor control, and that further studies are needed to establish a causal link.

Implications for the treatment of depression and anxiety disorders

To treat depression and anxiety disorders, brain stimulation is used to increase neural activity in the patient’s left hemisphere, long believed to the ‘approach hemisphere.” “Given what we show here,” says Brookshire, “this treatment, which helps right-handers, may be detrimental to left-handers — the exact opposite of what they need.” The discovery that approach motivation reverses with handedness may lead to safer, more effective neural therapies for left-handers, according to Brookshire, “it’s something we’re investigating now.”

Source: Science Daily

May 2, 2012 

The brain’s neurons are coupled together into vast and complex networks called circuits. Yet despite their complexity, these circuits are capable of displaying striking examples of collective behavior such as the phenomenon known as “neuronal avalanches,” brief bursts of activity in a group of interconnected neurons that set off a cascade of increasing excitation.

In a paper published in the American Institute of Physics’ journal Chaos, an international team of researchers from China, Hong Kong, and Australia explores connections between neuronal avalanches and a model of learning – a rule for how neurons “choose” to connect among themselves in response to stimuli. The learning model, called spike time-dependent plasticity, is based on observations of real behavior in the brain.

The researchers’ simulations reveal that the complex neuronal circuit obtained from the learning model would also be good at generating neuronal avalanches. This agreement between the model and a real, proven behavior of neurons suggests that the learning model is an accurate way to describe how the brain processes information.

The authors say their work could aid an understanding of how learning could lead to the formation of cortical structures in the brain, as well as why the resulting structures are so efficient at processing large amounts of information. “While [the finding] is entirely consistent with existing neurophysiology, our work is the first to provide this concrete link” between this particular learning rule and neuronal avalanches, says co-author Michael Small of the University of Western Australia. “It provides a simple, and therefore perhaps surprising, explanation for how a system as complex as the cortex can generate such striking collective behavior.”

Provided by American Institute of Physics

Source: medicalxpress.com

ScienceDaily (May 2, 2012) — Although the two disorders may seem dissimilar, epilepsy and psychosis are associated. Individuals with epilepsy are more likely to have schizophrenia, and a family history of epilepsy is a risk factor for psychosis. It is not known whether the converse is true, i.e., whether a family history of psychosis is a risk factor for epilepsy.

Multiple studies using varied investigative techniques have shown that patients with schizophrenia and patients with epilepsy show some similar structural brain and genetic abnormalities, suggesting they may share a common etiology.

To investigate this possibility, researchers conducted a population-based study of parents and their children born in Helsinki, Finland. Using data available in two Finnish national registers, the study included 9,653 families and 23,404 offspring.

Individuals with epilepsy had a 5.5-fold increase in the risk of having a psychotic disorder, a 6.3-fold increase in the risk of having bipolar disorder, and an 8.5-fold increase in the risk of having schizophrenia.

They also found that the association between epilepsy and psychosis clusters within families. Individuals with a parental history of epilepsy had a 2-fold increase in the risk of developing psychosis, compared to individuals without a parental history of epilepsy. Individuals with a parental history of psychosis had a 2.7-fold increase in the risk of having a diagnosis of epilepsy, compared to individuals without a parental history of psychosis.

There have been multiple theories regarding the link between epilepsy and psychosis, but most have been predicated on the idea that epilepsy has toxic effects on the brain. However, combined with prior genetic and neurodevelopmental evidence, these new findings suggest a much more complex association, which likely includes a shared genetic vulnerability.

"Our evidence that epilepsy and psychotic illness may cluster within some families indicates that these disorders may be more closely linked than previously thought. We hope that this epidemiological evidence may contribute to the on-going efforts to disentangle the complex pathways that lead to these serious illnesses," said Dr. Mary Clarke, first author of the study and lecturer at Royal College of Surgeons in Ireland.

Dr. John Krystal, Editor of Biological Psychiatry, commented: “We have long known that particular types of epilepsy were associated with psychosis. However, the finding that a parental history of psychosis is associated with an increased risk of epilepsy in the offspring strengthens the mechanistic link between the two conditions.”

Source: Science Daily

ScienceDaily (May 2, 2012) — Parkinson’s disease, a disorder which affects movement and cognition, affects over a million Americans, including actor Michael J. Fox, who first brought it to the attention of many TV-watching Americans. It’s characterized by a gradual loss of neurons that produce dopamine. Mutations in the gene known as DJ-1 lead to accelerated loss of dopaminergic neurons and result in the onset of Parkinson’s symptoms at a young age.

The ability to modify the activity of DJ-1 could change the progress of the disease, says Dr. Nirit Lev, a researcher at Tel Aviv University’s Sackler Faculty of Medicine and a movement disorders specialist at Rabin Medical Center. Working in collaboration with Profs. Dani Offen and Eldad Melamed, Dr. Lev has now developed a peptide which mimics DJ-1’s normal function, thereby protecting dopamine- producing neurons. What’s more, the peptide can be easily delivered by daily injections or absorbed into the skin through an adhesive patch.

Based on a short protein derived from DJ-1 itself, the peptide has been shown to freeze neurodegeneration in its tracks, reducing problems with mobility and leading to greater protection of neurons and higher dopamine levels in the brain. Dr. Lev says that this method, which has been published in a number of journals including the Journal of Neural Transmission, could be developed as a preventative therapy.

Guarding dopamine levels

As we age, we naturally lose dopamine-producing neurons. Parkinson’s patients experience a rapid loss of these neurons from the onset of the disease, leading to much more drastic deficiencies in dopamine than the average person. Preserving dopamine-producing neurons can mean the difference between living life as a Parkinson’s patient or aging normally, says Dr. Lev.

The researchers set out to develop a therapy based on the protective effects of DJ-1, using a short peptide based on the healthy version of DJ-1 itself as a vehicle. “We attached the DJ-1-related peptide to another peptide that would allow it to enter the cells, and be carried to the brain,” explains Dr. Lev.

In pre-clinical trials, the treatment was tested on mice utilizing well-established toxic and genetic models for Parkinson’s disease. From both a behavioral and biochemical standpoint, the mice that received the peptide treatment showed remarkable improvement. Symptoms such as mobility dysfunctions were reduced significantly, and researchers noted the preservation of dopamine-producing neurons and higher dopamine levels in the brain.

Preliminary tests indicate that the peptide is a viable treatment option. Though many peptides have a short life span and degrade quickly, this peptide does not. Additionally, it provides a safe treatment option because peptides are organic to the body itself.

Filling an urgent need

According to Dr. Lev, this peptide could fill a gap in the treatment of Parkinson’s disease. “Current treatments are lacking because they can only address symptoms — there is nothing that can change or halt the disease,” she says. “Until now, we have lacked tools for neuroprotection.”

The researchers also note the potential for the peptides to be used preventatively. In some cases, Parkinson’s can be diagnosed before motor symptoms begin with the help of brain scans, explains Dr. Lev, and patients who have a genetic link to the disease might opt for early testing. A preventative therapy could help many potential Parkinson’s patients live a normal life.

Source: Science Daily

ScienceDaily (May 1, 2012) — Vision and hearing are so crucial to our daily lives that any impairments usually become obvious to an affected person. Although a number of known genetic mutations can lead to hereditary defects in these senses, little is known about our sense of touch, where defects might be so subtle that they go unnoticed.

There are good reasons to suspect that hearing and touch might have a common genetic basis. Sound-sensing cells in the ear detect vibrations and transform them into electrical impulses. Likewise, nerves that lie just below the surface of the skin detect movement and changes in pressure, and generate impulses. The similarity suggests that the two systems might have a common evolutionary origin—they may depend on an overlapping set of molecules that transform motion into signals that can be transmitted along nerves to the brain. (Credit: © Vladimir Voronin / Fotolia)

People with good hearing also have a keen sense of touch; people with impaired hearing generally have an impaired sense of touch. Extensive data supporting this hypothesis was presented by Dr. Henning Frenzel and Professor Gary R. Lewin of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. The two researchers showed that both senses — hearing and touch — have a common genetic basis. In patients with Usher syndrome, a hereditary form of deafness accompanied by impaired vision, the researchers discovered a gene mutation that is also causative for the patients’ impaired touch sensitivity.

The examination was preceded by various studies, including studies with healthy identical and non-identical human twins. In total, the researchers assessed sensory function in 518 volunteers.

In all vertebrates, and consequently also in humans, hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. When we hear, sound waves trigger vibrations that stimulate the hair-like nerve endings in the cochlea in the inner ear. These then transform the mechanical stimuli into electrical signals, which are transmitted to the brain via the auditory nerve. When we touch something a similar process takes place: The mechanical stimulus — sliding the fingers over a rough or smooth surface, the perception of vibrations — is taken up via sensors in the skin, converted into an electrical stimulus and transmitted to the brain.

Twin study with 100 pairs of twins

In recent years about 70 genes have been identified in humans, mutations in which trigger hearing loss or deafness. “Surprisingly, no genes have been found that negatively influence the sense of touch,” Professor Lewin said. To see whether the sense of touch also has a hereditary component, the researchers first studied 100 pairs of twins — 66 pairs of monozygotic twins and 34 dizygotic pairs of twins. Monozygotic twins are genetically completely identical; dizygotic twins are genetically identical to 50 percent. The tests showed that the touch sensitivity of the subjects was determined to more than 50 percent by genes. Furthermore, hearing and touch tests showed that there is a correlation between the sense of hearing and touch.

The researchers therefore suspected that genes that influence the sense of hearing may also have an influence on the sense of touch. In a next step, they recruited test subjects at a school in Berlin for students with hearing impairments. There they assessed the touch sensitivity in a cohort of 39 young people who suffered from severe congenital hearing impairment. The researchers compared these findings with the data from their twin study and discovered that not all of the young people with hearing loss had impaired tactile acuity. “Strikingly, however, many of these young people did indeed have poor tactile acuity,” Professor Lewin explained.

The researchers decided it would take too much time to analyze which of the approximately 70 genes that adversely affect the sense of hearing may also negatively affect the sense of touch. Therefore, the researchers focused specifically on patients with the Usher syndrome, a hereditary form of hearing impairment, in which the patients progressively become blind. Usher syndrome patients have varying degrees of hearing impairment, and the disease is genetically very well studied. There are nine known Usher genes carrying mutations which cause the disease.

The researchers examined one cohort of patients in a special consultation at the Charité — Universitätsmedizin Berlin for Usher patients from all over Germany. A second cohort was recruited at the university hospital La Fe in Valencia, Spain. The studies revealed that not all patients with Usher-syndrome have poor tactile acuity and touch sensitivity. The researchers showed that only patients with Usher syndrome who have a mutation in the gene USH2A have poor touch sensitivity. This mutation is also responsible for the impaired hearing of 19 patients. The 29 Usher-syndrome patients in whom the mutation could not be detected had a normal sense of touch. The researchers thus demonstrated that there is a common genetic basis for the sense of hearing and touch. They suspect that even more genes will be discovered in the future that influence both mechanosensory traits.

Women hear better than men and have a finer sense of touch

The researchers discovered another interesting detail during their five-year study. “When women complain that their men are not really listening to them, there is some truth in that,” Professor Lewin said. “The studies with a total of 518 individuals including 295 women have actually shown that women hear better and they also have a finer sense of touch than men; in short woman hear and feel more than men!”

Source: Science Daily

ScienceDaily (May 1, 2012) — Slacker or go-getter? Everyone knows that people vary substantially in how hard they are willing to work, but the origin of these individual differences in the brain remains a mystery.

Slacker or go-getter? Everyone knows that people vary substantially in how hard they are willing to work, but the origin of these individual differences in the brain remained a mystery. Until now. (Credit: © Dana Heinemann / Fotolia)

Now the veil has been pushed back by a new brain imaging study that has found an individual’s willingness to work hard to earn money is strongly influenced by the chemistry in three specific areas of the brain. In addition to shedding new light on how the brain works, the research could have important implications for the treatment of attention-deficit disorder, depression, schizophrenia and other forms of mental illness characterized by decreased motivation.

The study was published May 2 in the Journal of Neuroscience and was performed by a team of Vanderbilt scientists including post-doctoral student Michael Treadway and Professor of Psychology David Zald.

Using a brain mapping technique called positron emission tomography (PETscan), the researchers found that “go-getters” who are willing to work hard for rewards had higher release of the neurotransmitter dopamine in areas of the brain known to play an important role in reward and motivation, the striatum and ventromedial prefrontal cortex. On the other hand, “slackers” who are less willing to work hard for a reward had high dopamine levels in another brain area that plays a role in emotion and risk perception, the anterior insula.

"Past studies in rats have shown that dopamine is crucial for reward motivation," said Treadway, "but this study provides new information about how dopamine determines individual differences in the behavior of human reward-seekers."

The role of dopamine in the anterior insula came as a complete surprise to the researchers. The finding was unexpected because it suggests that more dopamine in the insula is associated with a reduced desire to work, even when it means earning less money. The fact that dopamine can have opposing effects in different parts of the brain complicates the picture regarding the use of psychotropic medications that affect dopamine levels for the treatment of attention-deficit disorder, depression and schizophrenia because it calls into question the general assumption that these dopaminergic drugs have the same effect throughout the brain.

The study was conducted with 25 healthy volunteers (52 percent female) ranging in age from 18 to 29. To determine their willingness to work for a monetary reward, the participants were asked to perform a button-pushing task. First, they were asked to select either an easy or a hard button-pushing task. Easy tasks earned $1 while the reward for hard tasks ranged up to $4. Once they made their selection, they were told they had a high, medium or low probability of getting the reward. Individual tasks lasted for about 30 seconds and participants were asked to perform them repeatedly for about 20 minutes.

"At this point, we don’t have any data proving that this 20-minute snippet of behavior corresponds to an individual’s long-term achievement," said Zald, "but if it does measure a trait variable such as an individual’s willingness to expend effort to obtain long-term goals, it will be extremely valuable."

The research is part of a larger project designed to search for objective measures for depression and other psychological disorders where motivation is reduced. “Right now our diagnoses for these disorders is often fuzzy and based on subjective self-report of symptoms,” said Zald. “Imagine how valuable it would be if we had an objective test that could tell whether a patient was suffering from a deficit or abnormality in an underlying neural system. With objective measures we could treat the underlying conditions instead of the symptoms.”

Further research is needed to examine whether similar individual differences in dopamine levels help explain the altered motivation seen in forms of mental illness such as depression and addiction. Additional research is under way to examine how medications specifically impact these motivational systems.

Source: Science Daily

May 2, 2012

Collaborative research by groups headed by scientists Joan J. Guinovart and Marco Milán at the Institute for Research in Biomedicine (IRB Barcelona) has revealed conclusive evidence about the harmful effects of the accumulation of glucose chains (glycogen) in fly and mouse neurons.

This image shows a cerebellum sample from a healthy mouse. Credit: Jordi Duran (IRB Barcelona)

These two animal models will allow scientists to address the genes involved in this harmful process and to find pharmacological solutions that allow disintegration of the accumulations or limitation of glycogen production. Advances in this direction would make a significant contribution to investigation into Lafora progressive myoclonic epilepsy and other neurodegenerative diseases characterized by glycogen accumulation in neurons. The journal EMBO Molecular Medicine publishes the results of the study this week.

This image shows the same tissue (mouse cerebellum) after glycogen accumulation. Credit: Jordi Duran (IRB Barcelona)

"Our data clearly indicate that glycogen accumulation alone kills neurons and thus dramatically reduces lifespan", explains Guinovart, an expert in glycogen metabolism, group leader at IRB Barcelona, and senior professor at the University of Barcelona, "because the only thing we have manipulated in the neurons is their capacity to produce glycogen".

The inclusion of the Drosophila fly in the study provides in vivo confirmation of the theory in another animal model as these flies also show the same symptoms of degeneration as mice when glycogen accumulates in neurons. However, in addition the use of Drosophila will speed up obtaining genetic data and the screening of therapeutic molecules. “In a short time we will be able to perform a massive search for genes involved in the pathological process and to understand it better at the molecular level”, emphasizes Marco Milán, ICREA researcher at IRB Barcelona and a specialist inDrosophila. “But the flies will also be useful to identify pharmacological molecules that can cure”, he explains.

The IRB Barcelona teams are designing several experiments to identify the possible therapeutic targets that may be useful to prevent glycogen accumulation in neurons. In addition to the direct relation to Lafora epilepsy, a progressive degenerative disease that affects adolescents and has no cure, glycogen accumulation could be the main cause of other neurodegenerative illnesses such as Adult polyglucosan body disease and Andersen’s disease.

Provided by Institute for Research in Biomedicine (IRB Barcelona)

Source: medicalxpress.com

May 1, 2012

Scientists now have a better understanding of how precise memories are formed thanks to research led by Prof. Jean-Claude Lacaille of the University of Montreal’s Department of Physiology. “In terms of human applications, these findings could help us to better understand memory impairments in neurodegenerative disorders like Alzheimer’s disease,” Lacaille said.

The study looks at the cells in our brains, or neurons, and how they work together as a group to form memories. Chemical receptors at neuron interconnections called synapses enable these cells to form electrical networks that encode memories, and neurons are classified into two groups according to the type of chemical they produce: excitatory, who produce chemicals that increase communication between neurons, and inhibitory, who have the opposite effect, decreasing communication. “Scientists knew that inhibitory cells enable us to refine our memories, to make them specific to a precise set of information,” Lacaille explained. “Our findings explain for the first time how this happens at the molecular and cell levels.”

Many studies have been undertaken on excitatory neurons, but very little research has been done on inhibitory neurons, partly because they are very difficult to study. The scientists found that a factor called “CREB” plays a key role in adjusting gene expression and the strength of synapses in inhibitory neurons. Proteins are biochemical compounds encoded in our genes that enable cells to perform their various functions, and new proteins are necessary for memory formation. “We were able to study how synapses of inhibitory neurons taken from rats are modified in the 24 hours following the formation of a memory,” Lacaille said. “In the laboratory, we simulated the formation of a new memory by using chemicals. We then measured the electrical activity within the network of cells. In cells where we had removed CREB, we saw that the strength of the electrical connections was much weaker. Conversely, when we increased the presence of CREB, the connections were stronger.”

This new understanding of the chemical functioning of the brain may one day lead to new treatments for disorders like Alzheimer’s, as researchers will be able to look at these synaptic mechanisms and design drugs that target the chemicals involved. “We knew that problems with synapse modifications are amongst the roots of the cognitive symptoms suffered by the victims of neurodegenerative diseases,” Lacaille said. “These findings shine light on the neurobiological basis of their memory problems. However, we are unfortunately many years away from developing new treatments from this information.”

The findings were published in the Journal of Neuroscience on May 2, 2012. The researchers received funding from the Canadian Institutes of Health Research and the Fonds de recherche du Québec – Santé. Jean-Claude Lacaille is the Canada Research Chair in Cellular and Molecular Neurophysiology. Israeli Ran, recipient of a Fellowship of the Savoy Foundation, and Isabel Laplante contributed to this research. All three researchers were affiliated with the Department of Physiology and the Groupe de Recherche sur le Système Nerveux Central of the University of Montreal when the research was undertaken. The University of Montreal is officially known as Université de Montréal.

Provided by University of Montreal 

Source: medicalxpress.com

ScienceDaily (May 1, 2012) — Barrow Neurological Institute researchers Jorge Otero-Millan, Stephen Macknik, and Susana Martinez-Conde share the recent cover of the Journal of Neuroscience in a compelling study into why illusions trick our brains. Barrow is part of St. Joseph’s Hospital and Medical Center in Phoenix.

The study, led by Martinez-Conde’s laboratory, explores the neural bases of illusory motion in Akiyoshi Kitaoka’s striking visual illusion, known as the “Rotating Snakes.” Kitaoka is a Japanese psychology professor who specializes in visual illusions of geometric shapes and motion illusions.

The study shows that tiny eye movements and blinking can make a geometric drawing of “snakes” appear to dance. The results help explain the mystery of how the Rotating Snakes illusion tricks the brain.

"Visual illusions demonstrate the ways in which the brain creates a mental representation that differs from the physical world," says Martinez-Conde. "By studying illusions, we can learn the mechanisms by which the brain constructs our conscious experience of the world."

Earlier studies of the “Rotating Snakes” indicated the perception of motion was triggered by the eyes moving slowly across the illusion. But by tracking eye movements in eight volunteers, the vision neuroscientists found a different explanation: fast eye movements called “saccades,” some of which are microscopic and undetectable by the viewer, drive the illusory motion.

Participants lifted a button when the snakes seemed to swirl and pressed down the button when the snakes appeared still. Right before the snakes appeared to move, participants tended to produce blinks, saccades and/or microsaccades, and right before the snakes stopped, participants’ eyes tended to remain stable, Otero-Millan, Macknik, and Martinez-Conde report in the April 25th Journal of Neuroscience cover story.

"Studying the mismatch between perception and reality may lead to a deeper understanding of the mind," says Martinez-Conde. "The findings from our recent study may help us to understand the neural bases of motion perception, both in the normal brain, and in patients with brain lesions that affect the perception of motion. This research could aid in the design of neural prosthetics for patients with brain damage."

Source: Science Daily

ScienceDaily (May 1, 2012) — Scientists at Joslin Diabetes Center have identified a key mechanism of action for the TOR (target of rapamycin) protein kinase, a critical regulator of cell growth which plays a major role in illness and aging. This finding not only illuminates the physiology of aging but could lead to new treatments to increase lifespan and control age-related conditions, such as cancer, type 2 diabetes, and neurodegeneration.

Over the past decade, studies have shown that inhibiting TOR activity, which promotes cell growth by regulating protein synthesis, increases lifespan in a variety of species including flies and mice; in recent years research has focused on uncovering the precise mechanisms underlying this effect. The Joslin study, published in the May 2 issue of Cell Metabolism, reports that TOR has a direct impact on two master gene regulator proteins — SKN-1 and DAF-16 -which control genes that protect against environmental, metabolic and proteotoxic stress. The TOR kinase acts in two signaling pathways, TORC1 and TORC2. When TORC1 is inhibited, SKN-1 and DAF-16 are mobilized, leading to activation of protective genes that increase stress resistance and longevity. This new finding was demonstrated in experiments with C. elegans, a microscopic worm used as a model organism, but activation of protective genes was also observed in mice. Most findings in C. elegans have turned out to be applicable to mice and humans.

"We uncovered a critical mechanism in the relationship between TOR and aging and disease. There is a homeostatic relationship between protein synthesis and stress defenses: when protein synthesis is reduced, stress defenses increase," says lead author T. Keith Blackwell, MD, PhD, co-head of the Joslin Islet Cell & Regenerative Biology Section and Professor of Pathology at Harvard Medical School. The Blackwell lab studies the aging process and how it is influenced by insulin and other metabolic regulatory mechanisms.

TOR activity, which is essential for early development but can lead to age-related decline, is implicated in a variety of chronic diseases, including diabetes, cardiovascular disease, cancer and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. In diabetes, TOR has both positive and negative effects: It promotes beta cell growth and insulin production but inappropriate TORC1 activity leads to insulin resistance and beta cell demise, as well as fat accumulation. At the same time, insufficient TORC2 activity can lead to insulin resistance.

The new results on TOR and SKN-1 suggest that SKN-1 might have a positive effects in Type 2 diabetes: “Turning on this pathway could be important in defending against the effects of high glucose, and promoting beta cell health” says Blackwell.

In the study, TOR activity was inhibited by genetic interference and the TOR-inhibitor rapamycin, a naturally occurring compound which is used as an immunosuppressant in organ transplants, and has been shown to increase lifespan in mice. Using rapamycin or related drugs to treat diseases affected by TOR has been a subject of intense interest among scientists and clinicians. The study found that rapamycin inhibits both TORC1 and TORC2, which will interest scientists investigating rapamycin as a pharmaceutical. “We need to increase understanding of rapamycin and its effects on TOR activity to determine how targeting TOR or processes it controls can help treat diseases that involve TOR and derangement of metabolism. We also need to look at therapies that work on TORC1 and TORC2 independently,” said Blackwell. However, one caveat with TOR inhibition is that the kinase plays such a central role in the basic physiology of growing and dividing cells. The new results suggest that in some situations we might want to bypass TOR itself, and directly harness beneficial processes that are controlled by SKN-1 or DAF-16.

Future research will focus on gaining a deeper understanding of how TOR acts on beneficial defense pathways and affects aging and disease. “In science, we are always looking for ways to interfere with mechanisms that promote aging and disease in ways that are beneficial to people,” says Blackwell.

Source: Science Daily

May 1, 2012

You think your computer has a lot of memory … if you keep using your computer you may, too.

Combining mentally stimulating activities, such as using a computer, with moderate exercise decreases your odds of having memory loss more than computer use or exercise alone, a Mayo Clinic study shows. Previous studies have shown that exercising your body and your mind will help your memory but the new study, published in the May 2012 issue of Mayo Clinic Proceedings, reports a synergistic interaction between computer activities and moderate exercise in “protecting” the brain function in people better than 70 years old.

Researchers studies 926 people in Olmsted County, Minn., ages 70 to 93, who completed self-reported questionnaires on physical exercise, and computer use within one year prior of the date of interview. Moderate physical exercise was defined as brisk walking, hiking, aerobics, strength training, golfing without a golf cart, swimming, doubles tennis, yoga, martial arts, using exercise machines and weightlifting. Mentally stimulating activities included reading, crafts, computer use, playing games, playing music, group and social and artistic activities and watching less television. Of those activities the study singled out computer use because of its popularity, said study author Yonas E. Geda, M.D., MSc, a physician scientist with Mayo Clinic in Arizona.

"The aging of baby boomers is projected to lead to dramatic increases in the prevalence of dementia," Dr. Geda said. "As frequent computer use has becoming increasingly common among all age groups, it is important to examine how it relates to aging and dementia. Our study further adds to this discussion."

The study examined exercise, computer use and the relationship to neurological risks such as mild cognitive impairment, Dr. Geda says. Mild cognitive impairment is the intermediate stage between normal memory loss that comes with aging and early Alzheimer’s disease. Of the study participants who did not exercise and did not use a computer, 20.1 percent were cognitively normal and 37.6 percent showed signs of mild cognitive impairment. Of the participants who both exercise and use a computer, 36 percent were cognitively normal and 18.3 percent showed signs of MCI.

Dr. Geda expects that this study will lead to more research on this topic.

Provided by Mayo Clinic

Source: medicalxpress.com

ScienceDaily (Apr. 30, 2012) — Migraine pain sits at the upper end of the typical pain scale — an angry-red section often labeled “severe.” At this intensity, pain is debilitating. Yet many sufferers do not get relief from — or cannot tolerate — over-the-counter and commonly prescribed pain medications.

Migraine Therapy: Computer model of the distribution of electrical current in the brain’s pain network (sub-cortical and brainstem structures) during transcranial direct current stimulation (tDCS). (Credit: Image courtesy of City College of New York)

Recently, a team of researchers that includes Dr. Marom Bikson, associate professor of biomedical engineering in CCNY’s Grove School of Engineering, has shown that a brain stimulation technology can prevent migraine attacks from occurring. Their technique, using transcranial direct current stimulation (tDCS), applies a mild electrical current to the brain from electrodes attached to the scalp.

"We developed this technology and methodology in order to get the currents deep into the brain," said Bikson. The researchers aimed to tap into the so-called pain network, among other areas, a collection of interconnected brain regions involved in perceiving and regulating pain.

Professor Bikson and his colleagues, including Dr. Alexandre DaSilva at the University of Michigan School of Dentistry and Dr. Felipe Fregni at Harvard Medical School, found that the technology seems to reverse ingrained changes in the brain caused by chronic migraine, such as greater sensitivity to headache triggers.

Repeated sessions reduced the duration of attacks and decreased the pain intensity of migraines that did occur on average about 37 percent. The improvements accumulated over four weeks of treatment and they persisted.

In pilot studies, the effects lasted for months. The only side effect subjects reported was a mild tingling sensation during treatment. Professor Bikson expects that a patient could use the system every day to ward off attacks, or periodically, like a booster.

The team’s computational models show that tDCS delivers therapeutic current along the pain network through both upper (cortical) and deep brain structures. They will publish their results in the journal Headache.

Thirty-six million Americans suffer from migraine, according to the Migraine Research Foundation. Of these, 14 million of them experience chronic daily headaches. “The fact that people still suffer from migraines means that the existing treatments using electrical technology or chemistry are not working,” said Professor Bikson.

Existing brain stimulation technologies can help relieve a migraine already underway. But those afflicted with chronic migraine pain may suffer 15 or more attacks a month, making treatment a constant battle.

The other techniques also have drawbacks — from heavy, unwieldy equipment to serious side effects, such as seizures. Some only stimulate the upper layers of the brain. Others reach deep brain regions, but require brain surgery to implant the electrodes. The tDCS technology is safe, easy to use, and portable, Professor Bikson said. “You can walk around with it and keep it in your desk drawer or purse. This is definitely the first technology that operates on just a 9-volt battery and can be applied at home.” He envisions future units as small as an iPod.

The next step will be to scale up clinical trials to a larger study population. A market-ready version of the tDCS is still years away. “There’s something about migraine pain that’s particularly distressing,” noted Professor Bikson. “If it’s possible to help some people get just 30 percent better, that’s a very meaningful improvement in quality of life.”

Source: Science Daily

ScienceDaily (Apr. 30, 2012) — Researchers studying multiple sclerosis (MS) have long been looking for the specific molecules in the body that cause lesions in myelin, the fatty, insulating cells that sheathe the nerves. Nearly a decade ago, a group at Mayo Clinic found a new enzyme, called Kallikrein 6, that is present in abundance in MS lesions and blood samples and is associated with inflammation and demyelination in other neurodegenerative diseases. In a study published this month in Brain Pathology,the same group found that an antibody that neutralizes Kallikrein 6 is capable of staving off MS in mice.

"We were able to slow the course of disease through early chronic stages, both in the brain and spinal cord," says lead author Isobel Scarisbrick, Ph.D., of the Mayo Clinic Department of Physical Medicine and Rehabilitation.

Researchers looked at mice representing a viral model of MS. The model is based on the theory that infection with viral infection early in life results in an eventual abnormal immune response in the brain and spinal cord. One week after being infected with a virus, the mice showed elevated levels of Kallikrein 6 enzyme in the brain and spinal cord. However, when researchers treated mice to produce an antibody capable of blocking and neutralizing the enzyme, they saw a decrease in diseases effecting the brain and spinal cord, including demyelination. The Kallikrein 6 neutralizing antibody had reduced inflammatory white blood cells and slowed the depletion of myelin basic protein, a key component of the myelin sheath.

The findings in the MS model have implications for other conditions affecting the brain and spinal cord. The group has previously shown that the Kallikrein 6 enzyme, produced by immune cells, is elevated in spinal cord injury, while other studies have shown it to be elevated in animal models of stroke and patients with post-polio syndrome.

"These findings suggest Kallikrein 6 plays a role in the inflammatory and demyelinating processes that accompany many types of neurological conditions," says Dr. Scarisbrick. "In the early chronic stages of some neurological diseases, Kallikrein 6 may represent a good molecule to target with drugs capable of neutralizing its effects."

Source: Science Daily

ScienceDaily (Apr. 30, 2012) — UC Davis researchers have found novel compounds that disrupt the formation of amyloid, the clumps of protein in the brains of people with Alzheimer’s disease believed to be important in causing the disease’s characteristic mental decline. The so-called “spin-labeled fluorene compounds” are an important new target for researchers and physicians focused on diagnosing, treating and studying the disease.

The study was published April 30 in the online journal PLoS ONE.

"We have found these small molecules to have significant beneficial effects on cultured neurons, from protecting against toxic compounds that form in neurons to reducing inflammatory factors," said John C. Voss, professor of biochemistry and molecular medicine at the UC Davis School of Medicine and the principal investigator of the study. "As a result, they have great potential as a therapeutic agent to prevent or delay injury in individuals in the earliest stages of Alzheimer’s disease, before significant damage to the brain occurs."

Amyloid is an accumulation of proteins and peptides that are otherwise found naturally in the body. One component of amyloid − the amyloid beta (Aβ) peptide − is believed to be primarily responsible for destroying neurons in the brain. Fluorene compounds, which are small three-ringed molecules, originally were developed as imaging agents to detect amyloid with PET imaging. In addition to being excellent for detecting amyloid, fluorenes bind and destabilize Aβ peptide and thereby reduce amyloid formation, according to previous findings in mice by Lee-Way Jin, another study author and associate professor in the UC Davis MIND Institute and Department of Medical Pathology and Laboratory Medicine.

The current research studied the effects of fluorene compounds by attaching a special molecule to make their activity evident using electron paramagnetic resonance (EPR) spectroscopy. This technology allows researchers to observe very specific activities of molecules of interest because biological tissues do not emit signals detectable by EPR. Since Voss was interested in the activity of fluorenes, he added a nitroxide “spin label,” a chemical species with a unique signal that can be measured by EPR.

The group found that spin-labeled compounds disrupted Aβ peptide formation even more effectively than did non-labeled fluorenes. In addition, the antioxidant properties of the nitroxide, which scavenge reactive oxygen species known to damage neurons and increase inflammation, significantly contributed to the protective effects on neurons.

"The spin-labeled fluorenes demonstrated a number of extremely important qualities: They are excellent for detecting amyloid in imaging studies, they disrupt Aβ formation, and they reduce inflammation," said Voss. "This makes them potentially useful in the areas of research, diagnostics and treatment of Alzheimer’s disease."

Alzheimer’s disease is the most common form of dementia and affects some 5 million Americans. Current medications used to fight the disease usually have only small and temporary benefits, and commonly have many side effects.

A major obstacle in developing Alzheimer’s disease therapy is that most molecules will not cross the blood-brain barrier, so that potential treatments given orally or injected into the bloodstream cannot enter the brain where they are needed. Fluorene compounds are small molecules that have been shown to penetrate the brain well.

"We have brought together expertise from diverse fields to get to this point, and what was once a side interest has become a major focus," said Voss. "We are very excited and hopeful that these unique compounds can become extremely important."

Voss’ group next plans to study the safety of spin-labeled fluorene compounds as well as their efficacy for treating models of Alzheimer’s disease in small animals.

Source: Science Daily

April 30, 2012

A Northwestern University study that will be published in the Proceedings of the National Academy of Sciences (PNAS) provides the first biological evidence that bilinguals’ rich experience with language in essence “fine-tunes” their auditory nervous system and helps them juggle linguistic input in ways that enhance attention and working memory.

Northwestern bilingualism expert Viorica Marian teamed up with auditory neuroscientist Nina Kraus to investigate how bilingualism affects the brain. In particular, they looked at subcortical auditory regions that are bathed with input from cognitive brain areas. In extensive research, Kraus has already shown that lifelong music training enhances language processing, and an examination of subcortical auditory regions helped to tell that tale.

"For our first collaborative study, we asked if bilingualism could also promote experience-dependent changes in the fundamental encoding of sound in the brainstem — an evolutionarily ancient part of the brain," said Marian, professor of communication sciences in Northwestern’s School of Communication. The answer, according to their study, is a resounding yes.

The researchers found that the experience of bilingualism changes how the nervous system responds to sound. “People do crossword puzzles and other activities to keep their minds sharp,” Marian said. “But the advantages we’ve discovered in dual language speakers come automatically simply from knowing and using two languages. It seems that the benefits of bilingualism are particularly powerful and broad, and include attention, inhibition and encoding of sound.”

Co-authored by Kraus, Marian and researchers Jennifer Krizman, Anthony Shook and Erika Skoe, “Bilingualism and the Brain: Subcortical Indices of Enhanced Executive Function” underscores the pervasive impact of bilingualism on brain development. The article will appear in the April 30 issue of PNAS.

"Bilingualism serves as enrichment for the brain and has real consequences when it comes to executive function, specifically attention and working memory," said Kraus, Hugh Knowles Professor at Northwestern. In future studies, she and Marian will investigate whether these results can be achieved by learning a language later in life.

In the study, the researchers recorded the brainstem responses to complex sounds (cABR) in 23 bilingual English-and-Spanish-speaking teenagers and 25 English-only-speaking teens as they heard speech sounds in two conditions.

Under a quiet condition, the groups responded similarly. But against a backdrop of background noise, the bilingual brains were significantly better at encoding the fundamental frequency of speech sounds known to underlie pitch perception and grouping of auditory objects. This enhancement was linked with advantages in auditory attention.

"Through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound," Kraus explained.

"Bilinguals are natural jugglers," said Marian. "The bilingual juggles linguistic input and, it appears, automatically pays greater attention to relevant versus irrelevant sounds. Rather than promoting linguistic confusion, bilingualism promotes improved ‘inhibitory control,’ or the ability to pick out relevant speech sounds and ignore others."

The study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. “The bilingual’s enhanced experience with sound results in an auditory system that is highly efficient, flexible and focused in its automatic sound processing, especially in challenging or novel listening conditions,” Kraus added.

Provided by Northwestern University

Source: medicalxpress.com

ScienceDaily (Apr. 30, 2012) — University of Iowa biologists have advanced the knowledge of human neurodevelopmental disorders by finding that a lack of a particular group of cell adhesion molecules in the cerebral cortex — the outermost layer of the brain where language, thought and other higher functions take place — disrupts the formation of neural circuitry.

Reconstructions of single wildtype (left) and gamma-protocadherin mutant (right) cortical neurons are superimposed upon a low magnification view of fluorescently-labeled neurons in the corresponding animals. (Credit: Image courtesy of University of Iowa Health Care)

Andrew Garrett, former neuroscience graduate student and current postdoctoral fellow at the Jackson Laboratory, Bar Harbor, Maine; Dietmar Schreiner, former postdoctoral fellow currently at the University of Basel, Switzerland; Mark Lobas, current neuroscience graduate student; and Joshua A. Weiner, associate professor in the UI College of Liberal Arts and Sciences Department of Biology, published their findings in the April 26 issue of the journal Neuron.

Cell adhesion is the way in which cells “hold hands” — how one cell binds itself to another cell using specific molecules that protrude from cell membranes and bind each other together. The process is necessary to form all body tissues. The UI researchers studied a clustered family of 22 genes (gamma-protocadherins) that make such cellular hand-holding possible by encoding cell adhesion molecules.

In their previous work, they found that mice lacking the molecules exhibited death of neurons and loss of synapses in the spinal cord. So, they knew the gamma-protocadherins were important for neurons in the spinal cord, but not whether this was true in the cortex. However, in the current study, they found that an absence of the cell adhesion molecules had a significant and much different effect.

"We found that mice lacking the gamma-protocadherins in the cortex do not exhibit the severe loss of synapses and increased neuronal death that we observed in the spinal cord," says Weiner. "Instead, we found that the cortical neurons had severely reduced development of their dendrites, tree-like branched structures that receive input from other neurons.

"We discovered the reason for this: gamma-protocadherins normally inhibit a key signaling pathway within neurons that acts to reduce dendrite branching. In the absence of the gamma-protocadherins, this signaling pathway was hyperactive, leading to defective branching of cortical neuron dendrites," says Weiner.

In their previous work, the researchers showed that these molecules — the 22 distinct adhesion molecules, the gamma-protocadherins — are critical for the development of the animal, because when all of the genes are deleted from mice, they die shortly after birth with a variety of neurological defects including loss of connections (synapses) and excessive neuronal cell death in the spinal cord — an early-developing part of the nervous system.

Because those mutants die so young, the researchers could not assess a role for the gamma-protocadherins in the cerebral cortex. The reason is that the cortex develops only after birth. They used new genetic technologies to remove the gamma-protocadherins only from the cerebral cortex, which allowed the animals to survive to adulthood.

Weiner says that the latest research findings may help researchers to better understand the causes of various human developmental disorders.

"Human neurodevelopmental disorders such as autism, mental retardation, and schizophrenia all involve dysregulation of dendrite branching and synaptogenesis," he says. "Our identification of a large family of 22 cell adhesion molecules — which we previously showed interact with each other in very complex and specific ways — as new regulators of dendrite branching raises the question of whether specific interactions between distinct neuronal groups during development is important for the spreading of dendritic branches. If so, the gamma-protocadherins and/or the signaling pathways they regulate might be disrupted in a variety of human brain disorders."

Now that the researchers have shown that the gamma-protocadherin family, as a whole, is critical for dendrite branching, they plan to become more focused in their research. Next, they plan to ask whether specific interactions between individual members of the family are important for instructing neurons on the location and size of dendrite growth.

Source: Science Daily

April 30, 2012

Neuropathic pain, caused by nerve or tissue damage, is the culprit behind many cases of chronic pain. It can be the result of an accident or caused by a variety of medical conditions and diseases such as tumors, lupus, and diabetes. Typically resistant to common types of pain management including ibuprofen and even morphine, neuropathic pain can lead to lifelong disability for many sufferers.

Now a drug developed by Tel Aviv University researchers, known as BL-7050, is offering new hope to patients with neuropathic pain. Developed by Prof. Bernard Attali and Dr. Asher Peretz of TAU’s Department of Physiology and Pharmacology at the Sackler Faculty of Medicine, the medication inhibits the transmission of pain signals throughout the body. In both in-vitro and in-vivo experiments measuring electrical activity of neurons, the compound has been shown to prevent the hyper-excitability of neurons — protecting not only against neuropathic pain, but epileptic seizures as well.

The medication has been licensed by Ramot, TAU’s technology transfer company, for development and commercialization by BioLineRx, an Israeli biopharmaceutical development company.

Targeting potassium for pain control

According to Prof. Attali, the medication works by targeting a group of proteins which act as a channel for potassium. Potassium has a crucial role in the excitability of cells, specifically those in the nervous system and the heart. When potassium channels don’t function properly, cells are prone to hyper-excitability, leading to neurological and cardiovascular disorders such as epilepsy and arrhythmias. These are also the channels that convey pain signals caused by nerve or tissue damage, known as neuropathic pain.

With few treatment options available for neuropathic pain, Prof. Attali set out to develop a medication that could bind to and stabilize the body’s potassium channels, controlling their hyper-excitability and preventing the occurrence of pain by keeping the channels open for the outflow of potassium. This novel targeting approach has been recently reported in the journal PNAS.

Inducing calm in the neurons

Understanding the mechanism that controls these channels has been crucial to the development of the drug. By successfully controlling the excitability of the neurons, Prof. Attali believes that BL-7050 could bring relief to hundreds of millions of patients around the world who suffer from neuropathic pain. The medication will reach the first phase of clinical trials in the near future.

In pre-clinical trials, BL-7050 was tested in rats experiencing both epilepsy and neuropathic pain and was found to be efficient in protecting against both when taken as a pill. While on the medication, rats were no longer affected by stimuli that had previously caused pain. Measures in the electrical activities of neurons also revealed that the medication was able to induce “calm” in the neurons, inhibiting pain pathways.

Provided by Tel Aviv University

Source: medicalxpress.com

April 30, 2012

(Medical Xpress) — Scientists at the UCSF-affiliated Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson’s disease — and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson’s.

Now, in a paper published online today in Nature Neuroscience, Kreitzer, who is also an assistant professor of physiology at UCSF, and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson’s symptoms — and mark an important step in finding new treatments for those who suffer from addiction or depression.

“The physical symptoms that affect people with Parkinson’s — including tremors and rigidity of movement — are caused by an imbalance between two types of medium spiny neurons in the brain,” said Kreitzer, whose lab studies how Parkinson’s disease affects brain functions. “In this paper we showed that psychiatric disorders — specifically addiction and depression —might be caused by this same neural imbalance.”

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson’s, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson’s, but also in addiction and depression. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones—and that an imbalance in this process could lead to addictive or depressive behaviors.

Kreitzer and his team genetically modified two sets of mice so that they could control which specific type of MSN was activated. They placed mice one at a time in a box with two triggers — one that delivered a laser pulse to stimulate the neurons and one that did nothing. They then monitored which trigger each mouse preferred.

“The mice that had only dMSNs activated gravitated toward the laser trigger, pushing it again and again to get the stimulation — reminiscent of addictive behavior,” said Alexxai Kravitz, PhD, Gladstone postdoctoral fellow and a lead author of the paper. “But the mice that had only iMSNs activated did the opposite. Unlike their dMSN counterparts, the iMSN mice avoided the laser stimulation, which suggests that they found it unpleasant.” These findings reveal a precise relationship between the two MSN types and how behaviors are learned. They also show how an MSN imbalance can throw normal learning processes out of whack, potentially leading to addictive or depressive behavior.

“People with Parkinson’s disease often show signs of depression before the onset of significant movement problems, so it’s likely that the neural imbalance in Parkinson’s is also responsible for some behavioral changes associated with the disease,” said Kreitzer, who is also an assistant professor of physiology at UCSF.. “Future research could discover how MSNs are activated in those suffering from addiction or depression—and whether tweaking them could reduce their symptoms and improve their quality of life.

Graduate student Lynne Tye was also a lead author on this paper. Funding came from a variety of sources, including the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the National Institutes of Health.

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Provided by University of California, San Francisco 

Source: medicalxpress.com

April 30, 2012

Children with developmental delay or autism may have unrecognized epilepsy-like brain activity during sleep, report researchers at Boston Children’s Hospital. These nighttime electrical spikes, detectable only on EEGs, occur even in some children without known epilepsy and appear to result from early strokes or other early life injuries to the developing brain, the study found. Results were published online April 25 by the journal Neurology.

“Kids can have an almost normal EEG while awake, but may show increased spikes during sleep,” says lead investigator Tobias Loddenkemper, MD, a neurologist in the Epilepsy Center at Boston Children’s. “If nighttime spiking remains undiagnosed and untreated, it may interfere with learning and development. This has been frequently overlooked in the past.”

Based on their findings, the researchers suggest that sleep EEG monitoring should be considered more often in children not meeting developmental milestones, and that bedtime medications to suppress nighttime seizures may be beneficial if heightened brain electrical activity is found. In a preliminary treatment trial, such nighttime dosing before times of greatest spike or seizure activity has been found to be beneficial.

The study involved sleep EEG monitoring in 147 patients who were suspected of having excess brain electrical activity during sleep, based on loss of developmental milestones, and, in some cases, known seizures. All children had at least one brain MRI available for review. The EEGs and MRIs were read by physicians who did not know details of the patients’ history.

Of the 147 patients, seen at Boston Children’s over a 14-year period, 100 had prominent EEG spikes during sleep; the other 47 (controls) did not. Although there was no significant difference between groups in the percentage of patients with recognized seizures (78 percent of the “spike” group versus 64 percent of controls) or on most clinical measures, the “spike” group had significantly more patients with brain lesions on MRI (48 vs. 19 percent).

Children with EEG spikes were especially more likely than controls (14 vs. 2 percent) to have damage in the thalamus, the structure that relays sensory and motor signals to the cortex and regulates sleep and consciousness. The most common type of brain injury was early stroke (found in 14 vs. 0 percent, respectively).

The authors speculate that these early injuries disrupt circuit formation in the developing brain and lead to over-excitability – too much communication that is reflected in the EEG spikes and that may impinge on learning and development. “We know that children lose skills when these spikes appear,” says Loddenkemper. “These children lose out on a critical period of brain development and may never fully catch up later in life.”

Loddenkemper notes that up to 20 percent of children with heightened nighttime brain electrical activity do not have seizures or recognizable epilepsy. “Developmental delay may be the only clinical finding in some children,” he says. “Children at age 2 or 3, and sometimes older, may suddenly lose developmental milestones such as language, walking skills or fine motor movement.”

In the future, Loddenkemper and colleagues hope to conduct a prospective, multicenter trial in which they follow children with known early brain injury and monitor their nighttime EEG activity. They will then try different drugs to suppress nighttime spiking to see how the children’s long-term learning and development are affected.

Provided by Children’s Hospital Boston 

Source: medicalxpress.com

April 29, 2012

Why do some teenagers start smoking or experimenting with drugs—while others don’t?

Newly discovered networks in the brain, shown here in color, go a long way toward explaining why some teenagers are more likely to start experimenting with drugs and alcohol. Diminished activity in some of these networks, discovered by two scientists at the University of Vermont and their European colleagues, makes some teens more impulsive — and less able to inhibit urges to try alcohol, cigarettes and illegal drugs in early adolescence. Credit: Robert Whelan, University of Vermont, Nature Neuroscience, 2012

In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer.

Robert Whelan and Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive.

Their findings are presented in the journal Nature Neuroscience, published online April 29, 2012.

This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it.

"The differences in these networks seem to precede drug use," says Garavan, Whelan’s colleague in UVM’s psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study.

In a key finding, diminished activity in a network involving the “orbitofrontal cortex” is associated with experimentation with alcohol, cigarettes and illegal drugs in early adolescence.

"These networks are not working as well for some kids as for others," says Whelan, making them more impulsive.

Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, “yeah, gimme, gimme, gimme!” says Garavan, “and this other kid is saying, ‘no, I’m not going to do that.’”

Testing for lower function in this and other brain networks could, perhaps, be used by researchers someday as “a risk factor or biomarker for potential drug use,” Garavan says.

The researchers were also able to show that other newly discovered networks are connected with the symptoms of attention-deficit hyperactivity disorder. These ADHD networks are distinct from those associated with early drug use.

In recent years, there has been controversy and extensive media attention about the possible connection between ADHD and drug abuse. Both ADHD and early drug use are associated with poor inhibitory control—they’re problems that plague impulsive people.

But the new research shows that these seemingly related problems are regulated by different networks in the brain—even though both groups of teens can score poorly on tests of their “stop-signal reaction time,” a standard measure of overall inhibitory control used in this study and other similar ones. This strengthens the idea that risk of ADHD is not necessarily a full-blown risk for drug use as some recent studies suggest.

The impulsivity networks—connected areas of activity in the brain revealed by increased blood flow—begin to paint a more nuanced portrait of the neurobiology underlying the patchwork of attributes and behaviors that psychologists call impulsivity—as well as the capacity to put brakes on these impulses, a set of skills sometimes called inhibitory control.

Edythe London, Professor of Addiction Studies and Director of the UCLA Laboratory of Molecular Pharmacology, who was not part of the new study, described it as “outstanding,” noting that the work by Whelan and others “substantially advances our understanding of the neural circuitry that governs inhibitory control in the adolescent brain.”

Using a complex mathematical approach called factor analysis, Whelan and colleagues were able to fish out seven networks involved when impulses were successfully inhibited and six networks involved when inhibition failed—from the vast and chaotic actions of a teenage brain at work. These networks “light up,” Whelan says, in a functional MRI scanner during trials when the teenagers were asked to perform a repetitive task that involved pushing a button on a keyboard, but then were able to successfully stop—or inhibit—the act of pushing the button in mid-action. Those teens with better inhibitory control were able to succeed at this task faster.

But the underlying networks behind these tasks could not have been detectable in a “typical fMRI study of about 16 or 20 people,” says Whelan. “This study was orders of magnitude bigger, which lets us overcome much of the randomness and noise—and find the brain regions that actually vary together.”

"The take-home message is that impulsivity can be decomposed, broken down into different brain regions," says Garavan, "and the functioning of one region is related to ADHD symptoms, while the functioning of other regions is related to drug use.

The new study draws on the multi-year work of the IMAGEN Consortium, funded by the European Union, and headed by Prof. Gunter Schumann at the Institute of Psychiatry, King’s College London. IMAGEN, lead by a team of scientists across Europe, carried out neuroimaging, genetic and behavioral analyses in 2000 teenage volunteers in Ireland, England, France, and Germany and will be following them for several years, investigating the roots of risk-taking behavior and mental health in teenagers.

That teenagers push against boundaries—and sometimes take risks—is as predictable as the sunrise. It happens in all cultures and even across all mammal species: adolescence is a time to test limits and develop independence.

But death among teenagers in the industrialized world is largely caused by preventable or self-inflicted accidents that are often launched by impulsive risky behaviors, often associated with alcohol and drug use. Additionally, “addiction in the western world is our number one health problem,” says Garavan. “Think about alcohol, cigarettes or harder drugs and all the consequences that has in society for people’s health.” Understanding brain networks that put some teenagers at higher risk for starting to use them could have large implications for public health.

Provided by University of Vermont

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — In a new study, scientists at the University of Copenhagen show that a specific type of carbohydrate plays an important role in the intercellular signalling that controls the growth and development of the nervous system. In particular, defects in that carbohydrate may result in the uninhibited cell growth that characterizes the genetic disease neurofibromatosis and certain types of cancer.

Egghead to the right: Changes in cellular growth. (Credit: Klaus Qvortrup)

The results have just been published in the well-reputed journal PNAS.

Scientists from The Faculty of Health and Medical Sciences at the University of Copenhagen have put a special type of fruit fly under the microscope. The new research results turn the spotlight on a certain group of carbohydrates — the so-called glycolipids — and their influence on the cells’ complicated communication system. In the long term, this model study can shine new light on the disease neurofibromatosis for the benefit of patients the world over.

"The most important thing about our discovery right now is that we document a new function for carbohydrates in the communication between cells. We also show how disturbances in the signalling pathways cause changes in cellular growth. This is knowledge that cancer researchers can develop," says Ole Kjærulff, doctor and associate professor at the Department of Neuroscience and Pharmacology, who has conducted the study together with Dr. Katja Dahlgaard, and Hans Wandall, associate professor at the Copenhagen Center for Glycomics.

Sugar chains control cell growth

Glycolipids are compounds consisting of fats linked to long chains of sugar molecules. They are located in the cell membrane, where they serve various functions, such as protecting the cell or making it recognizable to the immune system.

"In the fruit fly model, if we prevent the sugar chains from lengthening, we can show that carbohydrate plays an important role in controlling the growth of normal cells. When the sugar chains are shortened, the tissue grows dramatically on account of increased cell division. In particular, it appears that the nervous system’s support cells — the glia cells — are influenced," explains Hans Wandall, associate professor.

Neurofibromatosis can cause deformity

The new results also influence our understanding of neurofibromatosis. This is a heritable disorder that results in unsightly tumours — so-called neurofibromas — in the nerves and skin. The disease affects approximately 20 people out of 100,000 and varies from mild to severe cases with decided deformities. The condition also affects the bones and often causes learning problems:

"When you get closer to an understanding of the mechanisms that result in a certain disease, naturally it is easier to influence the disease process in the form of drug development in the longer term. Neurofibromatosis is not a terminal disease, but it very much affects the life quality of the people who have it because the symptoms are so noticeable," explains Ole Kjærulff. Hans Wandall adds that the disease is also associated with certain types of cancer, particularly in the brain.

Source: Science Daily 

April 27, 2012

Aging may seem unavoidable, but that’s not necessarily so when it comes to the brain. So say researchers in the April 27th issue of the Cell Press journal Trends in Cognitive Sciences explaining that it is what you do in old age that matters more when it comes to maintaining a youthful brain not what you did earlier in life.

"Although some memory functions do tend to decline as we get older, several elderly show well preserved functioning and this is related to a well-preserved, youth-like brain," says Lars Nyberg of Umeå University in Sweden.

Education won’t save your brain — PhDs are as likely as high-school dropouts to experience memory loss with old age, the researchers say. Don’t count on your job either. Those with a complex or demanding career may enjoy a limited advantage, but those benefits quickly dwindle after retirement.

Engagement is the secret to success. Those who are socially, mentally and physically stimulated reliably show better cognitive performance with a brain that appears younger than its years.

"There is quite solid evidence that staying physically and mentally active is a way towards brain maintenance," Nyberg says.

The researchers say this new take on successful aging represents an important shift in focus for the field. Much attention in the past has gone instead to understanding ways in which the brain copes with or compensates for cognitive decline in aging. The research team now argues for the importance of avoiding those age-related brain changes in the first place. Genes play some role, but life choices and other environmental factors, especially in old age, are critical.

Elderly people generally do have more trouble remembering meetings or names, Nyberg says. But those memory losses often happen later than many often think, after the age of 60. Older people also continue to accumulate knowledge and to use what they know effectively, often to very old ages.

"Taken together, a wide range of findings provides converging evidence for marked heterogeneity in brain aging," the scientists write. "Critically, some older adults show little or no brain changes relative to younger adults, along with intact cognitive performance, which supports the notion of brain maintenance. In other words, maintaining a youthful brain, rather than responding to and compensating for changes, may be the key to successful memory aging."

Provided by Cell Press

Source: medicalxpress.com

April 27, 2012

(HealthDay) — Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Roger T. Staff, Ph.D., of the Aberdeen Royal Infirmary in the United Kingdom, and colleagues used magnetic resonance imaging of the brain to measure whole brain and hippocampal volume in 249 volunteers without dementia who were born in 1936. Childhood socioeconomic status history was recorded and mental ability at age 11 (recorded in 1947) was available for all participants.

After adjusting for mental ability at age 11 years, adult socioeconomic status, gender, and education, the researchers observed a significant association between childhood socioeconomic status and hippocampal volume.

"Early life socioeconomic conditions contribute to hippocampal volume in late adulthood independently of later life circumstances," the authors conclude. "These findings suggest that the capacity to compensate for age-related neuropathology (reserve) may well be established in early life."

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — Our genes control many aspects of who we are — from the colour of our hair to our vulnerability to certain diseases — but how are the genes, and consequently the proteins they make themselves controlled? Researchers have discovered a new group of molecules which control some of the fundamental processes behind memory function and may hold the key to developing new therapies for treating neurodegenerative diseases.

The mirror-miRNA (red) is expressed in hippocampal neurons, the nucleus is shown in blue. (Credit: Image courtesy of University of Bristol)

The research, led by academics from the University of Bristol’s Schools of Clinical Sciences, Biochemistry and Physiology & Pharmacology and published in the Journal of Biological Chemistry, has revealed a new group of molecules, called mirror-microRNAs.

MicroRNAs are non-coding genes that often reside within ‘junk DNA’ and regulate the levels and functions of multiple target proteins — responsible for controlling cellular processes in the brain. The study’s findings have shown that two microRNA genes with different functions can be produced from the same piece (sequence) of DNA — one is produced from the top strand and another from the bottom complementary ‘mirror’ strand.

Specifically, the research has shown that a single piece of human DNA gives rise to two fully processed microRNA genes that are expressed in the brain and have different and previously unknown functions. One microRNA is expressed in the parts of nerve cells that are known to control memory function and the other microRNA controls the processes that move protein cargos around nerve cells.

James Uney, Professor of Molecular Neuroscience in the University’s School of Clinical Sciences, said: “These findings are important as they show that very small changes in microRNA genes will have a dramatic effect on brain function and may influence our memory function or likelihood of developing neurodegenerative diseases. These findings also suggest that many more human mirror microRNAs will be found and that they could ultimately be used as treatments for human neurodegenerative diseases such as dementia.”

MicroRNAs can be seen as a novel regulatory layer within the genome, relying on the interaction between different RNA molecules. Through binding to messenger RNA (mRNA), they adjust the levels of proteins. Due to their small size, they are able to regulate many different RNAs. MicroRNAs have already been found throughout the double helix, lying in between genes or in areas of the code for a single gene that would normally be discarded. Such areas that were once considered “junk DNA” are now revealing a more complex and important role. In addition microRNAs can be produced in conjunction with their genes, within which they lie, or be controlled and produced entirely independently.

Helen Scott and Joanna Howarth, the lead authors on the study, added: “We have now found that both sides of the double helix can each produce a microRNA. These two microRNAs are almost a perfect mirror of each other, but due to slight differences in their sequence, they regulate different sets of protein producing RNAs, which will in turn affect different biological functions. Such mirror-miRNAs are likely to represent a new group of microRNAs with complex roles in coordinating gene expression, doubling the capacity of regulation.”

Source: Science Daily

ScienceDaily (Apr. 27, 2012) — Researchers at the Centre for Addiction and Mental Health (CAMH) led a study discovering a gene for a new form of intellectual disability, as well as how it likely affects cognitive development by disrupting neuron functioning.

CAMH Senior Scientist Dr. John Vincent and his team found a mutation in the gene NSUN2 among three sisters with intellectual disability, a finding to be published in the May issue of the American Journal of Human Genetics.

The discovery was made after mapping genes in a Pakistani family, in which three of seven siblings had intellectual disability as well as muscle weakness and walking difficulties, says Dr. Vincent, who heads the Molecular Neuropsychiatry and Development Laboratory in the Campbell Family Mental Health Research Institute at CAMH.

Intellectual disability is a condition in which individuals have limitations in their mental abilities and in functioning in daily life. It affects one to three per cent of the population, and is often caused by genetic mutations.

Another study in the same journal, submitted together with the CAMH-led research, also identified NSUN2 gene mutations in Iranian and Kurdish families with intellectual disability. As with the Pakistani family, first cousin marriages in these families carrying the mutations increased the likelihood of intellectual disability among their children, and enabled researchers to focus on areas to map genes.

"The combined results from these two studies mean that NSUN2 is among the most common causes of intellectual disability resulting from recessive genes," says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene from each parent to develop intellectual disability. This gene, located on chromosome 5p, encodes a type of protein called an RNA methyltransferase.

At the cellular level, the researchers found that the mutated protein was prevented from reaching its target area within the nucleus of a cell. As a result, it was unable to perform its normal role in cell division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K., showed which type of brain cells were likely to be most affected by this mutation. They are called Purkinje cells, a type of neuron that responds to the neurotransmitter GABA. Purkinje cells also control motor coordination, which were affected in the Pakistani family.

"We speculate that the muscle effects may result from the accumulation of the NSUN2 protein outside its target area in the nucleus," says Dr. Vincent.

To date, Dr. Vincent’s lab has identified five genes causing different forms of recessive intellectual disability.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — A new University of British Columbia study finds that analytic thinking can decrease religious belief, even in devout believers.

The statue “The Thinker,” by Auguste Rodin. (Credit: © Ignatius Wooster / Fotolia)

The study, which is published in the April 27 issue of Science, finds that thinking analytically increases disbelief among believers and skeptics alike, shedding important new light on the psychology of religious belief.

“Our goal was to explore the fundamental question of why people believe in a God to different degrees,” says lead author Will Gervais, a PhD student in UBC’s Dept. of Psychology. “A combination of complex factors influence matters of personal spirituality, and these new findings suggest that the cognitive system related to analytic thoughts is one factor that can influence disbelief.”

Researchers used problem-solving tasks and subtle experimental priming – including showing participants Rodin’s sculpture The Thinker or asking participants to complete questionnaires in hard-to-read fonts – to successfully produce “analytic” thinking. The researchers, who assessed participants’ belief levels using a variety of self-reported measures, found that religious belief decreased when participants engaged in analytic tasks, compared to participants who engaged in tasks that did not involve analytic thinking.

The findings, Gervais says, are based on a longstanding human psychology model of two distinct, but related cognitive systems to process information: an “intuitive” system that relies on mental shortcuts to yield fast and efficient responses, and a more “analytic” system that yields more deliberate, reasoned responses.

“Our study builds on previous research that links religious beliefs to ‘intuitive’ thinking,” says study co-author and Associate Prof. Ara Norenzayan, UBC Dept. of Psychology. “Our findings suggest that activating the ‘analytic’ cognitive system in the brain can undermine the ‘intuitive’ support for religious belief, at least temporarily.”

The study involved more than 650 participants in the U.S. and Canada. Gervais says future studies will explore whether the increase in religious disbelief is temporary or long-lasting, and how the findings apply to non-Western cultures.

Recent figures suggest that the majority of the world’s population believes in a God, however atheists and agnostics number in the hundreds of millions, says Norenzayan, a co-director of UBC’s Centre for Human Evolution, Cognition and Culture. Religious convictions are shaped by psychological and cultural factors and fluctuate across time and situations, he says.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — Scientists at the Gladstone Institutes have unraveled a process by which depletion of a specific protein in the brain contributes to the memory problems associated with Alzheimer’s disease. These findings provide insights into the disease’s development and may lead to new therapies that could benefit the millions of people worldwide suffering from Alzheimer’s and other devastating neurological disorders.

The study, led by Gladstone Investigator Jorge J. Palop, PhD, revealed that low levels of a protein, called Nav1.1, disrupt the electrical activity between brain cells. Such activity is crucial for healthy brain function and memory. Indeed, the researchers found that restoring Nav1.1 levels in mice that were genetically modified to mimic key aspects of Alzheimer’s disease (AD-mice) improved learning and memory functions and increased their lifespan. Their findings are featured on the cover of the April 27 issue of Cell, available online April 26.

"It is estimated that more than 30 million people worldwide suffer from Alzheimer’s disease and that number is expected to rise dramatically in the near future," said Lennart Mucke, MD, who directs neurological research at Gladstone, an independent and nonprofit biomedical-research organization. "This research improves our understanding of the biological processes that underlie cognitive dysfunction in this disease and could open the door for new therapeutic interventions."

The researchers’ findings suggest that Nav1.1 levels in special regulatory nerve cells called parvalbumin cells, or PV cells, are essential to generate healthy brain-wave activity — and that problems in this process contribute to cognitive decline in AD-mice and possibly in patients with Alzheimer’s.

In the brain, neurons form highly interconnected networks, using chemical and electrical signals to communicate with each other. The researchers investigated whether this communication between neurons is disrupted in AD-mice, and if so, how this may affect the symptoms of Alzheimer’s disease.

To study this, they performed electroencephalogram (EEG) recordings — a technique that detects abnormalities in the brain’s electrical waves such as those found in patients with epilepsy. They found that similar abnormalities emerged during periods of reduced gamma-wave oscillations — a type of brain wave that is crucial to regulating learning and memory.

"Like a conductor in an orchestra, PV cells regulate brain rhythms by precisely controlling excitatory brain activity," said Laure Verret, PhD, postdoctoral fellow and lead author. "We found that PV cells in patients with Alzheimer’s and in AD-mice have low levels of the protein Nav1.1 — likely contributing to PV cell dysfunction. As a consequence, AD-mice had abnormal brain rhythms. By restoring Nav1.1 levels, we were able to re-establish normal brain function."

Indeed, the scientists found that increasing Nav1.1 levels in PV cells improves brain wave activity, learning, memory and survival rates in AD-mice.

"Enhancing Nav1.1 activity, and consequently improving PV cell function, may help in the treatment of Alzheimer’s disease and other neurological disorders associated with gamma-wave alterations and cognitive impairments such as epilepsy, autism and schizophrenia," said Dr. Palop, who is also an assistant professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "These findings may allow us to develop therapies to help patients with these devastating diseases."

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — The ability to navigate using spatial cues was impaired in mice whose brains were minus a channel that delivers potassium — a finding that may have implications for humans with damage to the hippocampus, a brain structure critical to memory and learning, according to a Baylor University researcher.

Mice missing the channel also showed diminished learning ability in an experiment dealing with fear conditioning, said Joaquin Lugo, Ph.D., the lead author in the study and an assistant professor of psychology and neuroscience in Baylor’s College of Arts & Sciences. “By targeting chemical pathways that alter those potassium channels, we may eventually be able to apply the findings to humans and reverse some of the cognitive deficits in people with epilepsy and other neurological disorders,” Lugo said.

The research was done in Baylor College of Medicine Intellectual and Developmental Disabilities Research Center Mouse Neurobehavior Core in Houston during Lugo’s time as a researcher there.

The findings are published online in the journal Learning & Memory.

The channel, called Kv4.2, delivers potassium, which aids neuron function in the brain’s hippocampus. The hippocampus forms memory for long-term storage in the brain. Potassium also helps to regulate excitability.

Individuals who have epilepsy sometimes exhibit altered or missing Kv.4.2 channels or similar types of channels.

In the experiment investigating navigation, “knockout” mice — those without the channel — were tested in a water maze four feet in diameter and 12 inches deep, with eight trials daily — each lasting about a minute — over four days, he said. Their performance was compared with that of normal mice.

Both groups responded to visual cues — colored symbols — in learning their way around the maze, but the knockout mice did not respond as well as the normal mice in terms of spatial cues — hidden platforms in the water.

"When the mice don’t have this channel, it hurts their ability to learn," Lugo said. In a separate experiment examining fear conditioning, both knockout mice and normal mice were placed in a cage, and researchers sounded a tone before giving the mice a mild electric shock. In repeated trials, both groups began to freeze upon hearing the tone as they anticipated a shock. But the normal mice also reacted to the context — being placed in the cage — while the mice who did not have the Kv4.2 channel reacted only to the tone. The research was funded by the Epilepsy Foundation and the National Institutes of Health.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience (NIN-KNAW) have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on April 25 in the journal Neuron. Their study may be significant in developing treatments of neurodevelopmental disorders.

Two inhibitory synapses (yellow) disappear from the process of a nerve-cell (red) during learning. (Credit: Image courtesy of Netherlands Institute for Neuroscience)

Ability to learn

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills — walking, talking, hearing and seeing — early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Disappearing inhibitors

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Regulating the information network

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Hope

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders — for example epilepsy, but also autism and schizophrenia — may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Source: Science Daily

April 26, 2012

They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on Wednesday in the prestigious journal Neuron. Their study may be significant in the treatment of neurodevelopmental disorders such as epilepsy, autism and schizophrenia.

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills – walking, talking, hearing and seeing – early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders – for example epilepsy, but also autism and schizophrenia – may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Provided by Royal Netherlands Academy of Arts and Sciences

Source: medicalxpress.com

April 26, 2012

What happens at the level of individual neurons while we learn? This question intrigued the neuroscientist Daniel Huber, who recently arrived at the Department of Basic Neuroscience at the University of Geneva. During his stay in the United States, he and his team tried to unravel the network mechanisms underlying learning and memory at the level of the cerebral cortex.

What’s the role of individual neurons in behavior? Do they always participate in the same functions? How do their responses evolve during learning?” asks the professor. One way to address these questions is to follow the activity of a large set of neurons while the subject learns a novel task. The goal is to link the behavioral changes with the changes in neuronal representations.

It’s currently impossible to follow the activity of a large number of individual neurons in humans, but the team of researchers quickly realized that mice are excellent subjects for such studies. “We were surprised by capacities of these small rodents. They learn novel associations quickly and are able to focus for hours on complex behavioral tasks. However, it is important to keep them motivated by rewarding them accordingly. They are very similar to us in that way.”

The behavioral task of the mice consisted in sampling the area in front of their snout with their whiskers to search for a small object. The object was presented either within reach and out of reach of their whiskers. Each time the object was detected with the whiskers, the mouse had to respond by licking to a reward spout. The correct choices were rewarded with a drop of liquid. “In this task different sensory and motor circuits have to interact in order to establish a novel association, leading to better and better performance”.

Remained the problem of how to follow the activity of the large number of neurons across many days of learning. The researchers replaced a small part of the bone overlying motor cortex with a tiny glass window. The neurons underneath the window were genetically modified to express a fluorescent marker which changes its intensity according to the activity of the neurons. This window into the brain allowed the researches around Daniel Huber to use two-photon microscopy to record the activity of the same set of 500 neurons during days of learning. 

"We then correlated the activity of the individual neurons with the different actions of the mouse, such as moving the whiskers, touching the object or licking at the right moment. It’s like synchronizing the soundtrack with the images in a movie" adds the neuroscientist. The researchers analyzed this data using a series of computational approaches to establish a link between the neuronal activity and the different sensory and motor features of the task. This allowed them to build algorithmic models that can predict different motor outputs by solely monitoring the neuronal activity. Decoding the neuronal activity allowed the researchers then to construct functional maps of the recorded neurons and quantify each neuron’s link with the different aspects of the behavior.

These functional maps revealed several fundamental findings: “Although the movements of the whiskers became more and more precise and targeted to search for the object during the learning, their relative neuronal representation remained relatively stable. In contrast, the representation of licking to respond and collect the rewards became more and more pronounced”. Taken together, only selected aspects of the learned behavior induced changes it the neuronal representation in the cortex. The scientists also found that different sensory and motor representations are spatially intermingled in the rodent brain.

Other analysis revealed that individual neurons remain stably linked to a given behavioral function, but they have a flexibility to remain silent on a given day. This functional stability despite a flexibility to join (or not) a given representation was actually suggested by different theoretical work on learning.

"If these characteristics are limited to the motor cortex or if these are more general rules that are apply across the cerebral cortex remains open" says Daniel Huber. That in fact this is one of the questions we are currently investigating in my lab in Geneva".

Provided by University of Geneva

Source: medicalxpress.com

April 26, 2012 by Stuart Mason Dambrot

(Medical Xpress) — Remarkably, cortical maps show that neurons in the primary visual cortex have specific preferences for the location and orientation of a given visual field stimulus – but how these maps develop and what function they play in visual processing remains a mystery. Evidence suggests that the retinotopic map is established by molecular gradients, but little is known about how orientation maps are wired. One hypothesis: at their inception, these orientation maps are seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics. Recently, scientists in the Departments of Neurobiology and Psychology at the University of California, Los Angeles have shown that this proposed mechanism predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map, and have confirmed this prediction in the tree shrew primary visual cortex. The researchers say their findings support the idea that spatially structured retinal input may provide a blueprint of sorts for the early development of cortical maps and receptive fields – and that the same may hold true for other senses as well.

Moiré interference of retinal mosaics predicts a link between retinotopic and orientation maps. (A) (Upper) Two hexagonal lattices representing ON- (red) and OFF-center (blue) ganglion cell receptive fields/ (Lower) A cortical cell with input dominated by a dipole has a receptive field with side-by-side subregions of opposite sign and can be tuned for orientation. (B) (Upper) The orientation of dipoles in the interference pattern, indicated by the orientation of short line segments, changes over space, generating a blueprint for an orientation map. (Lower) The organization of orientation preferences around negative (Left) and positive (Right) singularities. Image Courtesy PNAS, doi: 10.1073/pnas.1118926109

Professor of Neurobiology and Psychology Dario L. Ringach articulates the primary elements of showing that the hypothesis that orientation maps are initially seeded by the spatial interference of ON- and OFF-center retinal receptive field mosaics corresponds to a mechanism that predicts a link between the layout of orientation preferences around singularities of different signs and the cardinal axes of the retinotopic map. “The cerebral cortex of higher mammals contains diverse maps,” he tells Medical Xpress, “where information about sensory input or motor planning is laid out systematically across the surface of a given cortical area. Some scientists have postulated that these computational maps are key to cortical function. However, we still do not know exactly what role cortical maps play in normal sensory and motor processes.” Their importance, he stresses, is that understanding how cortical maps are wired during development, and what types of pathology may arise from their faulty wiring, are fundamental questions of brain function.

Ringach also notes that neurons in primary visual cortex are selective to the orientation of a stimulus in visual space, and their preference changes systematically across the cortical surface in a periodic fashion. “We know these maps are present at the earliest stages of life,” he continues, “and do not require normal sensory experience to develop – but how do they wire themselves? We’ve postulated that the initial structure of these maps is biased by the spatial organization of the periphery.” In the visual system this is represented by the signals the retina within the eye conveys to the brain.

The researchers’ model postulates that at each location in the visual field, the input from the retina constraints the range of orientation preferences that the cortex can implement at that location. “We show that, given what is known about the organization of retinal signals, that such constraints would be quasi-periodic, thereby potentially providing the blueprint for an orientation map in the cortex.” One prediction of this theory is that groups of neurons preferring the same orientation should be arranged on an approximate hexagonal lattice on the cortical surface – a prediction the researchers confirmed in a previous study¹. 

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