viernes, 29 de abril de 2011

Red dots signal the location of electrical impulses generated within this grid cell, which are needed for the brain to store information about the rat

Red dots signal the location of electrical impulses generated within this grid cell, which are needed for the brain to store information about the rat's physical environment.

Biologists at UC San Diego have discovered that electrical oscillations in the brain, long thought to play a role in organizing cognitive functions such as memory, are critically important for the brain to store the information that allows us to navigate through our physical environment.

The scientists report in the April 29 issue of the journal Science that neurons called "grid cells" that create maps of the external environment in one portion of our brain require precisely timed electrical oscillations in order to function properly from another part of the brain that serves as a kind of neural pacemaker.

Their discovery has important implications for understanding the underlying causes of neurological diseases such as Alzheimer's disease and for restoring memory in areas of the brain that are necessary for orientation.

"This work is the first to demonstrate that oscillatory activity has a well-defined function in brain areas that store memories," says Stefan Leutgeb, an assistant professor of biology at UCSD who headed the team of researchers.

Scientists have long known that among the first brain areas to degenerate in Alzheimer's disease, leading to symptoms such as memory loss and disorientation, are the hippocampus and the nearby entorhinal cortex, important structures for the formation of memory. Those two regions of the brain contain three types of neurons that contribute to the formation of spatial memories and the spatial information in episodic memories from our life experiences.

These three types of neurons provide an internal GPS system to the brain. For example, one type of neuron, called "place cells," generates electrical activity only when an animal is at a certain position, while another type, called "head direction cells," acts like a compass. A third class of neurons, called "grid cells," provides grid-like patterns for the brain to store memories of physical dimensions of the external environment. The most striking feature about these cells is that their electrical activity is distributed at equidistant, periodic locations within each cell (shown in the figure). Grid cells were discovered by Norwegian scientists in rats in 2005, but in 2010 researchers in London detected groups of cells in human entorhinal cortex that share the same characteristics.

Leutgeb and his team of UCSD biologists—postdoctoral researcher Julie Koenig, undergraduate student Ashley Linder and Jill Leutgeb, an assistant professor of biology—were motivated to understand the function of electrical oscillations in the brain, which are routinely measured in clinical settings to diagnose neurological disorders.

Leutgeb's group demonstrated that neurons called grid cells in the entorhinal cortex that create maps of the external environment require precisely timed electrical oscillatory input signals from a neural pacemaker in the subcortex of the brain to function properly.

"Our findings represent a major milestone in understanding memory processing, and they will guide efforts to restore memory function when cells in the entorhinal cortex are damaged," says Stefan Leutgeb.

A group of scientists from Boston University reports related findings in a companion paper in the same April 29th issue of Science.

The UCSD researchers monitored the electrical activity of grid cells in rats that explored a small four-foot by four-foot enclosure. Grid cells, located in the entorhinal cortex just adjacent to the hippocampus, maintain an internal representation of the external environment. This representation is a grid-like map made of repeating equilateral triangles that tile the space in a hexagonal pattern. As an animal navigates through its environment, a given grid cell becomes active when the animal's position coincides with any of the vertices within the grid.

The scientists silenced the oscillatory input by manipulating a small group of pacemaker cells in the brain and observed a significant deterioration of the grid cells' maps of the environment.

Surprisingly, silencing the oscillatory input did not disrupt brain signals that indicate precise location (provided by place cells) and the compass signal (provided by head direction cells).

"It has been thought that the hippocampus is under control of the entorhinal cortex, so there was the assumption that grid cells would have a very large impact on place cells. We are surprised at how the function of place cells is maintained in the face of significant disruption in grid cell function," says Leutgeb.

"This important result shows that, in general, you can eliminate a substantial amount of incoming information to a brain circuit without that brain circuit losing a majority of its functionality," he adds. "The implication of this finding is that restoring memory function does not require that we exactly reassemble damaged neural circuitry, rather we can regain function by preserving or restoring key components."

"Our findings are a major step towards identifying these key components in an effort to preserve memory function in aging individuals and in patients with neurodegenerative diseases," he says.

Provided by University of California - San Diego

jueves, 28 de abril de 2011

Neurorobotics reveals brain mechanisms of self-consciousness

Neurorobotics reveals brain mechanisms of self-consciousness
April 27th, 2011 in Neuroscience

A new study uses creative engineering to unravel brain mechanisms associated with one of the most fundamental subjective human feelings: self-consciousness. The research, published by Cell Press in the April 28 issue of the journal Neuron, identifies a brain region called the temporo-parietal junction (TPJ) as being critical for the feeling of being an entity localized at a particular position in space and for perceiving the world from this position and perspective.

Recent theories of self-consciousness highlight the importance of integrating many different sensory and motor signals, but it is not clear how this type of integration induces subjective states such as self-location ("Where am I in space?") and the first-person perspective ("From where do I perceive the world?"). Studies of neurological patients reporting out-of-body experiences have provided some evidence that brain damage interfering with the integration of multisensory body information may lead to pathological changes of the first-person perspective and self-location. However, it is still not known how to examine brain mechanisms associated with self-consciousness.

"Recent behavioral and physiological work, using video-projection and various visuo-tactile conflicts showed that self-location can be manipulated in healthy participants," explains senior study author, Dr. Olaf Blanke, from the Ecole Polytechnique Fédérale de Lausanne in Switzerland. "However, so far these experimental findings and techniques do not allow for the induction of changes in the first-person perspective and have not been integrated with neuroimaging, probably because the experimental set-ups require participants to sit, stand, or move. This makes it very difficult to apply and film the visuo-tactile conflicts on the participant's body during standard brain imaging techniques."

Making use of inventive neuroimaging-compatible robotic technology that was developed by Dr. Gassert's group at the Swiss Federal Institute of Technology in Zurich, Dr. Blanke and colleagues studied healthy subjects and employed specific bodily conflicts that induced changes in self-location and first-person perspective while simultaneously monitoring brain activity with functional magnetic resonance imaging. They observed that TPJ activity reflected experimental changes in self-location and first-person perspective. The researchers also completed a large study of neurological patients with out-of-body experiences and found that brain damage was localized to the TPJ.

"Our results illustrate the power of merging technologies from engineering with those of neuroimaging and cognitive science for the understanding of the nature of one of the greatest mysteries of the human mind: self-consciousness and its neural mechanisms," concludes Dr. Blanke. "Our findings on experimentally and pathologically induced altered states of self-consciousness present a powerful new research technology and reveal that TPJ activity reflects one of the most fundamental subjective feelings of humans: the feeling that 'I' am an entity that is localized at a position in space and that 'I' perceive the world from here."

More information: Ionta et al.: “Multisensory Mechanisms in Temporo-Parietal Cortex Support Self-Location and First-Person Perspective.”

Provided by Cell Press

"Neurorobotics reveals brain mechanisms of self-consciousness." April 27th, 2011.

miércoles, 20 de abril de 2011

New study examines brain processes behind facial recognition

New study examines brain processes behind facial recognition
April 18th, 2011 in Medicine & Health / Neuroscience

When you think you see a face in the clouds or in the moon, you may wonder why it never seems to be upside down.

It turns out the answer to this seemingly minor detail is that your brain has been wired not to.

Using tests of visual perception and functional magnetic resonance imaging (fMRI), Lars Strother and colleagues at The University of Western Ontario's world-renowned Centre for Brain & Mind recently measured activity in two regions of the brain well known for facial recognition and found they were highly sensitive to the orientation of people's faces.

The team had participants look at faces that had been camouflaged and either held upright or turned upside down. They found that right-side up faces were easier to see – and activated the face areas in the brain more strongly – thus demonstrating that our brains are specialized to understand this orientation.

The surprise came when they found this bias in brain activity also applies to pictures of animals.

Like faces, animals are biological visual forms that have a typical upright orientation. In the study, published in the current issue of the journal PLoS ONE, Strother and his colleagues propose that the human visual system allows us to see familiar objects – not just faces – more easily when viewed in the familiar upright orientation.

They also demonstrated this bias can be found in the neural activity of those brain areas involved with the most basic steps in visual processing, when visual inputs from the eyes first reach the brain.

In future research, the team hopes to chase down how this bias is set up in these early visual areas of the brain – and what this tells us about how brain circuits can be modified by knowledge and experience.

Provided by University of Western Ontario

sábado, 2 de abril de 2011

Skywalker ensures optimal communication between neurons

Skywalker ensures optimal communication between neurons
April 1st, 2011 in Medicine & Health / Neuroscience

Patrik Verstreken (VIB/K.U.Leuven, Belgium) has discovered the mechanism that ensures neurons can continue to send the right signals for long consecutive periods - a process that is disrupted in neurological diseases such as Parkinson's. Verstreken and his colleagues discovered that an enzyme called Skywalker controls the subtle balance in communication.

"I hope that unraveling the way Skywalker works will not only teach us more about the way neurons communicate with each other but will also lead to new diagnostics and therapies for neurological diseases such as Parkinson's," says Verstreken.

Communication between brain cells

Brain disorders take a major toll on society. More than 8% of the population in the West depends on analgesics. Twenty per cent suffers from a mental disturbance and the number of people suffering from the effects of neurological diseases is estimated at 1 billion. Many of these problems are caused by the disruption of communication between brain cells. Hence, finding a solution depends on understanding this communication in the smallest details.

Communication between brain cells occurs at the synapses, where an electrical signal is passed via a vesicle (a small membrane-enclosed sac with signaling substances). The vesicle releases the signaling substances, thus activating another brain cell.

An eye for the proper balance

The vesicles are reused several times. This results in the gradual degradation of the proteins they need for carrying out their function properly, which in turn affects the release of signaling substances. How the vesicles are kept operational during this recycling process was a mystery until now. Most types of cells have incorporated an extra step into this recycling process via special cell compartments called endosomes. In the endosomes, vesicle proteins are sorted to ensure optimal functioning of the recycled vesicles.

However, it was not clear whether this extra step was relevant for vesicle recycling in brain cells. Various studies seemed to demonstrate that it was in fact missing in brain cells.

Skywalker regulates communication between brain cells

Patrik Verstreken and his colleagues have now discovered an enzyme, christened Skywalker, which regulates this extra step. The VIB researchers tested fruit flies unable to produce Skywalker. In these so-called sky flies, they noticed that broken-down proteins from the vesicles were more easily replaced, and that many more signaling substances were released than in the synapses of normal fruit flies. In other words, a lack of Skywalker increases the signal between two brain cells, resulting in overstressed flies.

But the discovery that inhibition of Skywalker leads to a stronger signal between brain cells offers possibilities for the fight against neurological diseases such as Parkinson's. In the early stages of these diseases, the signals between brain cells are too weak. Verstreken wants to study this further, but realizes that it will be an enormous challenge to find ways to maintain the subtle balance that ensures optimal communication.

More information: Loss of Skywalker reveals synaptic endosomes as sorting stations for synaptic vesicle proteins, Uytterhoeven et al., Cell.

Provided by Flanders Institute for Biotechnology

viernes, 1 de abril de 2011

Brain scientists offer medical educators tips on the neurobiology of learning

Brain scientists offer medical educators tips on the neurobiology of learning
March 30th, 2011 in Medicine & Health / Neuroscience

Everyone would like MDs to have the best education – and to absorb what they are taught. The lead article in the April 4 issue of the journal Academic Medicine* connects research on how the brain learns to how to incorporate this understanding into real world education, particularly the education of doctors.

"Repetition, reward, and visualization are tried and true teaching strategies. Now, knowing what is happening in the brain will enhance teaching and learning," said Michael J. Friedlander, executive director of the Virginia Tech Carilion Research Institute and professor of biological sciences and of biomedical engineering and science at Virginia Tech. He is the lead author on the article, "What can medical education learn from the neurobiology of learning?"

Friedlander collaborated on the article with Dr. Linda Andrews, senior associate dean for medical education, Baylor College of Medicine; Elizabeth G. Armstrong, director of Harvard Macy Institute, Harvard Medical School; Dr. Carol Aschenbrenner, executive vice president of the Association of American Medical Colleges; Dr. Joseph S. Kass, chief of neurology and director of the Stroke Center at Ben Taub Hospital and assistant professor of neurology, Center for Ethics and Health Policy, Baylor College of Medicine; Dr. Paul Ogden, associate dean for educational program development, Texas A&M Health Sciences Center and College of Medicine; Dr. Richard Schwartzstein, director of the Harvard Medical School Academy; and Dr. Tom Viggiano, the associate dean for faculty affairs, professor of medical education and medicine, and the Barbara Woodward Lips professor at Mayo Medical School.

The research

In the past 50 years, behavioral approaches combined with functional brain imaging and computational neuroscience have revealed strategies employed by mammals' brains to acquire, store, and retrieve information. In addition to molecular and cellular approaches to describe the workings of the underlying hardware changes that occur in the brain during learning and the formation of memories, there has also been progress in higher-order, human-based studies of cognition, including learning and memory. Scientists have used functional magnetic resonance imaging (fMRI) of the living brain combined with computational modeling to elucidate the strategies employed and the underlying biological processes.

The research has shown how learning leads to functional and structural changes in the cellular networks including the chemical communication points or synapses between neurons at a variety of sites throughout the central nervous system. The functional changes in the effectiveness of communication between individual neurons and within networks of neurons are accompanied by substantial changes in the structural circuitry of the brain, once thought to be hard-wired in adults.

"One of the most exciting advances, as a result of optical imaging of the living brain, is the demonstration that there is growth, retraction, and modifying connectivity between neurons," said Friedlander. "We have also seen that the mature brain can generate new neurons, although, this research is so new that the functional implications of these new neurons and their potential contribution to learning and memory formation remain to be determined," he said.

The recommendations

The most effective delivery of the best possible care requires identifying and assigning levels of importance to the biological components of learning. Here are 10 key aspects of learning based on decades of research by many scientists that the article's authors believe can be incorporated into effective teaching.

Medical curricula often employ compressed coverage over limited time frames of a great amount of material. Learning theory and the neurobiology of learning and memory suggest that going deeper is more likely to result in better retention and depth of understanding. With repetition, many components of the neural processes become more efficient, requiring less energy and leaving higher-order pathways available for additional cognitive processing. However, repetitions must be appropriately spaced.

Reward and reinforcement:
Reward is a key component of learning at all stages of life. "The brain's intrinsic reward system – self-congratulations with the realization of success -- plays a major role in reinforcement of learned behaviors," Friedlander said. "An important factor is the realization that accomplishing an immediate goal and a successful step toward a future goal can be equally rewarding."

In the case of medical students, there are considerable rewards ahead of them in addition to the more immediate rewards of the satisfaction of understanding medicine. The students who derive joy from learning as they proceed through their medical education may have a greater chance of using the brain's capacity to provide reward signals on an ongoing basis, facilitating their learning process.

Visualization and mental rehearsal are real biological processes with associated patterned activation of neural circuitry in sensory, motor, executive, and decision-making pathways in the brain. Internally generated activity in the brain from thoughts, visualization, memories, and emotions should be able to contribute to the learning process.

Active engagement:
There is considerable neurobiological evidence that functional changes in neural circuitry that are associated with learning occur best when the learner is actively engaged.. Learners' having multiple opportunities to assume the role of teacher also invoke neural motivation and reward pathways -- and another major biological component of the learning process: stress.

Although the consequences of stress are generally considered undesirable, there is evidence that the molecular signals associated with stress can enhance synaptic activity involved in the formation of memory. However, particularly high levels of stress can have opposite effects. The small, interactive teaching format may be judiciously employed to moderately engage the stress system.

Patterns of neuronal activity during sleep reinforce the day's events. Research suggests that it is important to have appropriate downtime between intense problem-solving sessions. Downtime permits consolidation away from the formal teaching process.

Multitasking is a distraction from learning, unless all of the tasks are relevant to the material being taught. The challenge is to integrate information from multiple sources, such as a lecture and a hand-held device.

Individual learning styles:
Neural responses of different individuals vary, which is the rationale for embracing multiple learning styles to provide opportunities for all learners to be most effectively reached.

Active involvement:
Doing is learning. And success at doing and learning builds confidence.

Revisiting information and concepts using multimedia:
Addressing the same information using different sensory processes, such as seeing and hearing, enhances the learning process, potentially bringing more neural hardware to bear to process and store information.

The researchers recommend that medical students be taught the underlying neurobiological principles that shape their learning experiences. "By appealing not only to students' capacity to derive pleasure from learning about medicine but also to their intellectual capacity for understanding the rationale for the educational process selected … real motivation can be engendered. … They become more effective communicators and enhance their patients' success at learning the information they need for managing their own health and treatments as well."

More information: *"What Can Medical Education Learn From the Neurobiology of Learning?" by Michael J. Friedlander, PhD; Linda Andrews, MD; Elizabeth G. Armstrong, PhD; Carol Aschenbrenner, MD; Joseph S. Kass, MD; Paul Ogden, MD; Richard Schwartzstein, MD; and Thomas R. Viggiano, MD, MEd. Academic Medicine, Vol. 86, No. 4 / April 2011

Provided by Virginia Tech