How the Brain Remembers Pleasure: Implications for Addiction

How the Brain Remembers Pleasure: Implications for Addiction

  8:46:00 PM    Science Lover

---

Key details of the way nerve cells in the brain remember pleasure are revealed in a study by University of Alabama at Birmingham (UAB) researchers published today in the journal Nature Neuroscience. The molecular events that form such "reward memories" appear to differ from those created by drug addiction, despite the popular theory that addiction hijacks normal reward pathways.

Brain activity (artist's rendering). 
(Credit: © James Steidl / Fotolia)

Brain circuits have evolved to encourage behaviors proven to help our species survive by attaching pleasure to them. Eating rich food tastes good because it delivers energy and sex is desirable because it creates offspring. The same systems also connect in our mind's environmental cues with actual pleasures to form reward memories.

This study in rats supports the idea that the mammalian brain features several memory types, each using different circuits, with memories accessed and integrated as needed. Ancient memory types include those that remind us what to fear, what to seek out (reward), how to move (motor memory) and navigate (place memory). More recent developments enable us to remember the year Columbus sailed and our wedding day.

"We believe reward memory may serve as a good model for understanding the molecular mechanisms behind many types of learning and memory," said David Sweatt, Ph.D., chair of the UAB Department of Neurobiology, director of the Evelyn F. McKnight Brain Institute at UAB and corresponding author for the study. "Our results provide a leap in the field's understanding of reward-learning mechanisms and promise to guide future attempts to solve related problems such as addiction and criminal behavior."

The study is the first to illustrate that reward memories are created by chemical changes that influence known memory-related genes in nerve cells within a brain region called the ventral tegmental area, or VTA. Experiments that blocked those chemical changes -- a mix of DNA methylation and demethylation -- in the VTA prevented rats from forming new reward memories.

Methylation is the attachment of a methyl group (one carbon and three hydrogens) to a DNA chain at certain spots (cytosine bases). When methylation occurs near a gene or inside a gene sequence, it generally is thought to turn the gene off and its removal is thought to turn the gene on. This back-and-forth change affects gene expression without changing the code we inherit from our parents. Operating outside the genetic machinery proper, epigenetic changes enable each cell type to do its unique job and to react to its environment.

Furthermore, a stem cell in the womb that becomes bone or liver cells must "remember" its specialized nature and pass that identity to its descendants as they divide and multiply to form organs. This process requires genetic memory, which largely is driven by methylation. Note, most nerve cells do not divide and multiply as do other cells. They can't, according to one theory, because they put their epigenetic mechanisms to work making actual memories.

Natural pleasure versus addiction

The brain's pleasure center is known to proceed through nerve cells that signal using the neurochemical dopamine and generally is located in the VTA. Dopaminergic neurons exhibit a "remarkable capacity" to pass on pleasure signals. Unfortunately, the evolutionary processes that attached pleasure to advantageous behaviors also accidentally reinforced bad ones.

Addiction to all four major classes of abused drugs -- psychostimulants, opiates, ethanol and nicotine -- has been linked to increased dopamine transmission in the same parts of the brain associated with normal reward processing. Cues that predict both normal reward and effects of cocaine or alcohol also make dopamine nerve cells fire as do the experiences they recall. That had led to idea that drug addiction must take over normal reward-memory nerve pathways.

Along those lines, past research has argued that dopamine-producing neurons in the VTA -- and in a region that receives downstream dopamine signals from the VTA called the nucleus accumbens (NAC) -- both were involved in natural reward and drug-addiction-based memory formation. While that may true to some extent, this study revealed that blocking methylation in the VTA with a drug stopped the ability of rats to attach rewarding experiences to remembered cues but doing so in the NAC did not.

"We observed an important distinction, not in circuitry, but instead in the epigenetic regulation of that circuitry between natural reward responses and those that occur downstream with drugs of abuse or psychiatric illness," said Jeremy Day, Ph.D., a post-doctoral scholar in Sweatt's lab and first author for this study. "Although drug experiences may co-opt normal reward mechanisms to some extent, our results suggest they also may engage entirely separate epigenetic mechanisms that contribute only to addiction and that may explain its strength."

To investigate the molecular and epigenetic changes in the VTA, researchers took their cue from 19th century Russian physiologist Ivan Pavlov, who was the first to study the phenomenon of conditioning. By ringing a bell each day before giving his dogs food, Pavlov soon found that the dogs would salivate at the sound of the bell.

In this study, rats were trained to associate a sound tone with the availability of sugar pellets in their feed ports. This same animal model has been used to make most discoveries about how human dopamine neurons work since the 1990s, and most approved drugs that affect the dopamine system (e.g. L-Dopa for Parkinson's) were tested in it before being cleared for human trials.

To separate the effects of memory-related brain changes from those arising from the pleasure of the eating itself, the rats were separated into three groups. Rats in the "CS+" rats got sugar pellets each time they heard a sound cue. The "CS-" group heard the sound the same number of times and received as many sugar pellets -- but never together. A third tone-only group heard the sounds but never received sugar rewards.

Rats that always received sugar with the sound cue were found to poke their feed ports with their noses at least twice as often during this cue as control rats after three, 25-sound-cue sessions. Nose pokes are an established measure of the degree to which a rat has come to associate a cue with the memory of a tasty treat.

The team found that those CS+ rats (sugar paired with sound) that were better at forming reward memories had significantly higher expression of the genes Egr1 and Fos than control rats These genes are known to regulate memory in other brain regions by fine-tuning the signaling capacity of the connections between nerve cells. In a series of experiments, the team next revealed the methylation and demethylation pattern that drove the changes in gene expression seen as memories formed.

The study demonstrated that reward-related experiences caused both types of DNA methylation known to regulate gene expression.

One type involves attaching methyl groups to pieces of DNA called promoters, which reside immediately upstream of individual gene sequences (between genes), that tell the machinery that follows genetic instructions to "start reading here." The attachment of a methyl group to a promoter generally interferes with this and silences a nearby gene. However, ancient organisms such as plants and insects have less methylation between their genes, and more of it within the coding regions of the genes themselves (within gene bodies). Such gene-body methylation has been shown to encourage rather than silence gene expression.

Specifically, the team reported that two sites in the promoter for Egr1 gene were demethylated during reward experiences and, to a greater degree, in rats that associated the sugar with the sound cue. Conversely, spots within the gene body of both Egr1 and Fos underwent methylation as reward memories formed.

"When designing therapeutic treatments for psychiatric illness, addictions or memory disorders, you must profoundly understand the function of the biological systems you're working with," Day said. "Our field has learned from experience that attempts to treat addiction with something that globally impairs normal reward perception or reward memories do not succeed. Our study suggests the possibility that future treatments could dial down drug addiction or mental illness without affecting normal rewards."

Along with Sweatt and Day, authors for the study were Daniel Childs, Mikael Guzman-Karlsson, Mercy Kibe, Jerome Moulden, Esther Song and Absar Tahir within the Department of Neurobiology and the Evelyn F. McKnight Brain Institute at University of Alabama at Birmingham. This work is supported by the National Institute on Drug Abuse (DA029419), the National Institute on Mental Health (MH091122 and MH057014), and the Evelyn F. McKnight Brain Research Foundation.

Read More

Eating less keeps the brain young

Eating less keeps the brain young

  10:13:00 AM    Science Lover

---

Overeating may cause brain aging while eating less turns on a molecule that helps the brain stay young.

A team of Italian researchers at the Catholic University of Sacred Heart in Rome have discovered that this molecule, called CREB1, is triggered by "caloric restriction" (low caloric diet) in the brain of mice. They found that CREB1 activates many genes linked to longevity and to the proper functioning of the brain.

This work was led by Giovambattista Pani, researcher at the Institute of General Pathology, Faculty of Medicine at the Catholic University of Sacred Heart in Rome, directed by Professor Achille Cittadini, in collaboration with Professor Claudio Grassi of the Institute of Human Physiology. The research appears this week in the Proceedings of the National Academy of Sciences (PNAS).

"Our hope is to find a way to activate CREB1, for example through new drugs, so to keep the brain young without the need of a strict diet," Dr Pani said.

Caloric restriction means the animals can only eat up to 70 percent of the food they consume normally, and is a known experimental way to extend life, as seen in many experimental models. Typically, caloric-restricted mice do not become obese and don't develop diabetes; moreover they show greater cognitive performance and memory, are less aggressive. Furthermore they do not develop, if not much later, Alzheimer's disease and with less severe symptoms than in overfed animals.

Many studies suggest that obesity is bad for our brain, slows it down, causes early brain aging, making it susceptible to diseases typical of older people as the Alzheimer's and Parkinson's. In contrast, caloric restriction keeps the brain young. Nevertheless, the precise molecular mechanism behind the positive effects of an hypocaloric diet on the brain remained unknown till now.

The Italian team discovered that CREB1 is the molecule activated by caloric restriction and that it mediates the beneficial effects of the diet on the brain by turning on another group of molecules linked to longevity, the "sirtuins". This finding is consistent with the fact that CREB1 is known to regulate important brain functions as memory, learning and anxiety control, and its activity is reduced or physiologically compromised by aging.

Moreover, Italian researchers have discovered that the action of CREB1 can be dramatically increased by simply reducing caloric intake, and have shown that CREB is absolutely essential to make caloric restriction work on the brain. In fact, if mice lack CREB1 the benefits of caloric restriction on the brain (improving memory, etc.) disappeear. So the animals without CREB1 show the same brain disabilities typical of overfed and/or old animals.

"Thus, our findings identify for the first time an important mediator of the effects of diet on the brain," Dr. Pani said. "This discovery has important implications to develop future therapies to keep our brain young and prevent brain degeneration and the aging process. In addition, our study shed light on the correlation among metabolic diseases as diabetes and obesity and the decline in cognitive activities."

Provided by Catholic University of Rome

Read More

How brains benefit from meditation

How brains benefit from meditation

  10:05:00 AM    Science Lover

---

Experienced meditators seem to be able switch off areas of the brain associated with daydreaming as well as psychiatric disorders such as autism and schizophrenia, according to a new brain imaging study by Yale researchers.

Experienced meditators seem to switch off areas of the brain
associated with wandering thoughts, anxiety and some
psychiatric disorders such as schizophrenia. Researchers
used fMRI scans to determine how the brains of meditators
differed from subjects who were not meditating. The areas
shaded in blue highlight areas of decreased activity in the
brains of meditators. Credit: courtesy of yale

Meditation's ability to help people stay focused on the moment has been associated with increased happiness levels, said Judson A. Brewer, assistant professor of psychiatry and lead author of the study published the week of Nov. 21 in the Proceedings of the National Academy of Sciences. Understanding how meditation works will aid investigation into a host of diseases, he said.

"Meditation has been shown to help in variety of health problems, such as helping people quit smoking, cope with cancer, and even prevent psoriasis," Brewer said.

The Yale team conducted functional magnetic resonance imaging scans on both experienced and novice meditators as they practiced three different meditation techniques.

They found that experienced meditators had decreased activity in areas of the brain called the default mode network, which has been implicated in lapses of attention and disorders such as anxiety, attention deficit and hyperactivity disorder, and even the buildup of beta amyloid plaques in Alzheimer's disease. The decrease in activity in this network, consisting of the medial prefrontal and posterior cingulate cortex, was seen in experienced meditators regardless of the type of meditation they were doing.

The scans also showed that when the default mode network was active, brain regions associated with self-monitoring and cognitive control were co-activated in experienced meditators but not novices. This may indicate that meditators are constantly monitoring and suppressing the emergence of "me" thoughts, or mind-wandering. In pathological forms, these states are associated with diseases such as autism and schizophrenia.

The meditators did this both during meditation, and also when just resting — not being told to do anything in particular. This may indicate that meditators have developed a "new" default mode in which there is more present-centered awareness, and less "self"-centered, say the researchers. "Meditation's ability to help people stay in the moment has been part of philosophical and contemplative practices for thousands of years," Brewer said. "Conversely, the hallmarks of many forms of mental illness is a preoccupation with one's own thoughts, a condition meditation seems to affect. This gives us some nice cues as to the neural mechanisms of how it might be working clinically."

Read More

Mimicking the Brain -- In Silicon: New Computer Chip Models How Neurons Communicate With Each Other at Synapses

Mimicking the Brain -- In Silicon: New Computer Chip Models How Neurons Communicate With Each Other at Synapses

  1:39:00 PM    Science Lover

---

For decades, scientists have dreamed of building computer systems that could replicate the human BRAIN's talent for learning new tasks.

Researchers have taken a major step toward that goal by designing a computer chip that mimics how the brain's neurons adapt in response to new information. (Credit: MIT)

MIT researchers have now taken a major step toward that goal by designing a computer chip that mimics how the brain's neurons adapt in response to new information. This phenomenon, known as plasticity, is believed to underlie many brain functions, including learning and memory.

With about 400 transistors, the silicon chip can simulate the activity of a single brain synapse -- a connection between two neurons that allows information to flow from one to the other. The researchers anticipate this chip will help neuroscientists learn much more about how the brain works, and could also be used in neural prosthetic devices such as artificial retinas, says Chi-Sang Poon, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology.

Poon is the senior author of a paper describing the chip in the Proceedings of the National Academy of Sciences the week of Nov. 14. Guy Rachmuth, a former postdoc in Poon's lab, is lead author of the paper. Other authors are Mark Bear, the Picower Professor of Neuroscience at MIT, and Harel Shouval of the University of Texas Medical School.

Modeling synapses

There are about 100 billion neurons in the brain, each of which forms synapses with many other neurons. A synapse is the gap between two neurons (known as the presynaptic and postsynaptic neurons). The presynaptic neuron releases neurotransmitters, such as glutamate and GABA, which bind to receptors on the postsynaptic cell membrane, activating ion channels. Opening and closing those channels changes the cell's electrical potential. If the potential changes dramatically enough, the cell fires an electrical impulse called an action potential.

All of this synaptic activity depends on the ion channels, which control the flow of charged atoms such as sodium, potassium and calcium. Those channels are also key to two processes known as long-term potentiation (LTP) and long-term depression (LTD), which strengthen and weaken synapses, respectively.

The MIT researchers designed their computer chip so that the transistors could mimic the activity of different ion channels. While most chips operate in a binary, on/off mode, current flows through the transistors on the new brain chip in analog, not digital, fashion. A gradient of electrical potential drives current to flow through the transistors just as ions flow through ion channels in a cell.

"We can tweak the parameters of the circuit to match specific ion channels," Poon says. "We now have a way to capture each and every ionic process that's going on in a neuron."

Previously, researchers had built circuits that could simulate the firing of an action potential, but not all of the circumstances that produce the potentials. "If you really want to mimic brain function realistically, you have to do more than just spiking. You have to capture the intracellular processes that are ion channel-based," Poon says.

The new chip represents a "significant advance in the efforts to incorporate what we know about the biology of neurons and synaptic plasticity onto CMOS [complementary metal-oxide-semiconductor] chips," says Dean Buonomano, a professor of neurobiology at the University of California at Los Angeles, adding that "the level of biological realism is impressive.

The MIT researchers plan to use their chip to build systems to model specific neural functions, such as the visual processing system. Such systems could be much faster than digital computers. Even on high-capacity computer systems, it takes hours or days to simulate a simple brain circuit. With the analog chip system, the simulation is even faster than the biological system itself.

Another potential application is building chips that can interface with biological systems. This could be useful in enabling communication between neural prosthetic devices such as artificial retinas and the brain. Further down the road, these chips could also become building blocks for artificial intelligence devices, Poon says.

Debate resolved

The MIT researchers have already used their chip to propose a resolution to a longstanding debate over how LTD occurs.

One theory holds that LTD and LTP depend on the frequency of action potentials stimulated in the postsynaptic cell, while a more recent theory suggests that they depend on the timing of the action potentials' arrival at the synapse.

Both require the involvement of ion channels known as NMDA receptors, which detect postsynaptic activation. Recently, it has been theorized that both models could be unified if there were a second type of receptor involved in detecting that activity. One candidate for that second receptor is the endo-cannabinoid receptor.

Endo-cannabinoids, similar in structure to marijuana, are produced in the brain and are involved in many functions, including appetite, pain sensation and memory. Some neuroscientists had theorized that endo-cannabinoids produced in the postsynaptic cell are released into the synapse, where they activate presynaptic endo-cannabinoid receptors. If NMDA receptors are active at the same time, LTD occurs.

When the researchers included on their chip transistors that model endo-cannabinoid receptors, they were able to accurately simulate both LTD and LTP. Although previous experiments supported this theory, until now, "nobody had put all this together and demonstrated computationally that indeed this works, and this is how it works," Poon says.

Read More

Speaking and Understanding Speech Share the Same Parts of the Brain

Speaking and Understanding Speech Share the Same Parts of the Brain

  9:13:00 AM    Science Lover

---

The brain has two big tasks related to speech: making it and understanding it. Psychologists and others who study the brain have debated whether these are really two separate tasks or whether they both use the same regions of the brain. Now, a new study, published in the August issue of Psychological Science, a journal of the Association for Psychological Science, finds that speaking and understanding speech share the same parts of the brain, with one difference: we don't need the brain regions that control the movements of lips, teeth, and so on to understand speech.

New research finds that speaking and understanding 
speech share the same parts of the brain. 
(Credit: © Artsem Martysiuk / Fotolia)

Most studies of how speech works in the brain focuses on comprehension. That's mostly because it's easier to image the brains of people who are listening quietly; talking makes the head move, which is a problem when you're measuring the brain. But now, the Donders Institute at the Radboud University Nijmegen, where the study was conducted, has developed technology that allows recording from a moving brain.

Laura Menenti, a Postdoctoral Research Associate at the University of Glasgow, co-wrote the paper along with Peter Hagoort of Radboud University Nijmegen and the Max Planck Institute for Psycholinguistics, Sarah Gierhan and Katrien Segaert. Menenti was initially interested in how the brain produces grammatical sentences and wanted to track the process of producing a sentence in its entirety; looking not only at its grammatical structure but also at its meaning. "What made this particularly exciting to us was that no one had managed to perform such a study before, meaning that we could explore an almost completely new topic," says Menenti.




The authors used functional MRI technology to measure brain activity in people who were either listening to sentences or speaking sentences. The other problem with measuring brain activity in people who are speaking is that you have to get them to say the right kind of sentence. The authors accomplished this with a picture of an action -- a man strangling a woman, say -- with one person colored green and one colored red to indicate their order in the sentence. This prompted people to say either "The man is strangling the woman" or "The woman is strangled by the man." (The experiments were all carried out in Dutch.)

From this, the researchers were able to tell where in the brain three different speech tasks (computing meaning, coming up with the words, and building a grammatical sentence) -- were taking place. They found that the same areas were activated for each of these tasks in people who were speaking and people who were listening to sentences. However, although some studies have suggested that while people are listening to speech, they silently articulate the words in order to understand them, the authors found no involvement of motor regions when people were listening.

According to Menenti, though the study was largely designed to answer a specific theoretical question, it also points towards some useful avenues for treatment of people with language-related problems. It suggests that while it sometimes seems that people with comprehension problems may have intact production, and vice versa, this may not necessarily be the case. According to Menenti, "Our data suggest that these problems would be expected to always at least partly coincide. On the other, our data confirm the idea that many different processes in the language system, such as understanding meaning or grammar, can at least partly, be damaged independently of each other."

Read More

Researchers can predict future actions from human brain activity

Researchers can predict future actions from human brain activity

  2:42:00 AM    Science Lover

---

Bringing the real world into the brain scanner, researchers at The University of Western Ontario from The Centre for Brain and Mind can now determine the action a person was planning, mere moments before that action is actually executed.

A volunteer completes tasks while in the functional magnetic
imaging (fMRI) machine. This research project focuses
on understanding how the human brain plans actions.

The findings were published this week in the prestigious Journal of Neuroscience, in the paper, "Decoding Action Intentions from Preparatory Brain Activity in Human Parieto-Frontal Networks."



"This is a considerable step forward in our understanding of how the human brain plans actions," says Jason Gallivan, a Western Neuroscience PhD student, who was the first author on the paper.

University of Western Ontario researchers Jody Culham and Jason Gallivan describe how they can use a fMRI to determine the action a person was planning, mere moments before that action is actually executed. Credit: The University of Western Ontario

Over the course of the one-year study, human subjects had their brain activity scanned using functional magnetic resonance imaging (fMRI) while they performed one of three hand movements: grasping the top of an object, grasping the bottom of the object, or simply reaching out and touching the object. The team found that by using the signals from many brain regions, they could predict, better than chance, which of the actions the volunteer was merely intending to do, seconds later.

"Neuroimaging allows us to look at how action planning unfolds within human brain areas without having to insert electrodes directly into the human brain. This is obviously far less intrusive," explains Western Psychology professor Jody Culham, who was the paper's senior author.

Gallivan says the new findings could also have important clinical implications: "Being able to predict a human's desired movements using brain signals takes us one step closer to using those signals to control prosthetic limbs in movement-impaired patient populations, like those who suffer from spinal cord injuries or locked-in syndrome."

                    Brain timecourse video of subject's fMRI image during experiment

Provided by University of Western Ontario

Read More

Study brings brain-like computing a step closer to reality

Study brings brain-like computing a step closer to reality

  9:56:00 AM    Science Lover

---

The development of 'brain-like' computers has taken a major step forward today with the publication of research led by the University of Exeter.

Published in the journal Advanced Materials and funded by the Engineering and Physical Sciences Research Council, the study involved the first ever demonstration of simultaneous information processing and storage using phase-change materials. This new technique could revolutionise computing by making computers faster and more energy-efficient, as well as making them more closely resemble biological systems.

Computers currently deal with processing and memory separately, resulting in a speed and power 'bottleneck' caused by the need to continually move data around. This is totally unlike anything in biology, for example in human brains, where no real distinction is made between memory and computation. To perform these two functions simultaneously the University of Exeter research team used phase-change materials, a kind of semi-conductor that exhibits remarkable properties.

Their study demonstrates conclusively that phase-change materials can store and process information simultaneously. It also shows experimentally for the first time that they can perform general-purpose computing operations, such as addition, subtraction, multiplication and division. More strikingly perhaps it shows that phase-change materials can be used to make artificial neurons and synapses. This means that an artificial system made entirely from phase-change devices could potentially learn and process information in a similar way to our own brains.



Lead author Professor David Wright of the University of Exeter said: "Our findings have major implications for the development of entirely new forms of computing, including 'brain-like' computers. We have uncovered a technique for potentially developing new forms of 'brain-like' computer systems that could learn, adapt and change over time. This is something that researchers have been striving for over many years."

This study focused on the performance of a single phase-change cell. The next stage in Exeter's research will be to build systems of interconnected cells that can learn to perform simple tasks, such as identification of certain objects and patterns.


More information: Arithmetic and Biologically-Inspired Computing Using Phase-Change Materials, DOI: 10.1002/adma.201101060

Abstract

Phase-change materials offer a promising route for the practical realisation of new forms of general-purpose and ‘brain-like’ computers. An experimental proof-of-principle of such remakable capabilities is presented that includes (i) the reliable execution by a phase-change ‘processor’ of the four basic arithmetic functions of addition, subtraction, multiplication and division, (ii) the demonstration of an ‘integrate and fire’ hardware neuron using a single phase-change cell and (iii) the expostion of synaptic-like functionality via the ‘memflector’, an optical analogue of the memristor.

Provided by University of Exeter

Read More

Scientists Turn Memories Off and On With Flip of Switch

Scientists Turn Memories Off and On With Flip of Switch

  8:10:00 PM    Science Lover

---

Scientists have developed a way to turn memories on and off -- literally with the flip of a switch. Using an electronic system that duplicates the neural signals associated with memory, they managed to replicate the brain function in rats associated with long-term learned behavior, even when the rats had been drugged to forget.

In the experiment, the researchers had rats learn a task, 
pressing one lever rather than another to receive a reward. 
Using embedded electrical probes, the experimental research 
team recorded changes in the rat's brain activity between 
the two major internal divisions of the hippocampus, known 
as subregions CA3 and CA1. The experimenters then blocked 
the normal neural interactions between the two areas using 
pharmacological agents. The previously trained rats then 
no long displayed the long-term learned behavior. But long-
term memory capability returned to the pharmacologically 
blocked rats when the team activated the electronic device 
programmed to duplicate the memory-encoding function. 
(Credit: USC Viterbi School of Engineering)

"Flip the switch on, and the rats remember. Flip it off, and the rats forget," said Theodore Berger of the USC Viterbi School of Engineering's Department of Biomedical Engineering.

Berger is the lead author of an article that will be published in the Journal of Neural Engineering. His team worked with scientists from Wake Forest University in the study, building on recent advances in our understanding of the brain area known as the hippocampus and its role in learning.



In the experiment, the researchers had rats learn a task, pressing one lever rather than another to receive a reward. Using embedded electrical probes, the experimental research team, led by Sam A. Deadwyler of the Wake Forest Department of Physiology and Pharmacology, recorded changes in the rat's brain activity between the two major internal divisions of the hippocampus, known as subregions CA3 and CA1. During the learning process, the hippocampus converts short-term memory into long-term memory, the researchers prior work has shown.

"No hippocampus," says Berger, "no long-term memory, but still short-term memory." CA3 and CA1 interact to create long-term memory, prior research has shown.

In a dramatic demonstration, the experimenters blocked the normal neural interactions between the two areas using pharmacological agents. The previously trained rats then no longer displayed the long-term learned behavior.

"The rats still showed that they knew 'when you press left first, then press right next time, and vice-versa,'" Berger said. "And they still knew in general to press levers for water, but they could only remember whether they had pressed left or right for 5-10 seconds."

Using a model created by the prosthetics research team led by Berger, the teams then went further and developed an artificial hippocampal system that could duplicate the pattern of interaction between CA3-CA1 interactions.

Long-term memory capability returned to the pharmacologically blocked rats when the team activated the electronic device programmed to duplicate the memory-encoding function.

In addition, the researchers went on to show that if a prosthetic device and its associated electrodes were implanted in animals with a normal, functioning hippocampus, the device could actually strengthen the memory being generated internally in the brain and enhance the memory capability of normal rats.

"These integrated experimental modeling studies show for the first time that with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time identification and manipulation of the encoding process can restore and even enhance cognitive mnemonic processes," says the paper.

Next steps, according to Berger and Deadwyler, will be attempts to duplicate the rat results in primates (monkeys), with the aim of eventually creating prostheses that might help the human victims of Alzheimer's disease, stroke or injury recover function.

The paper is entitled "A Cortical Neural Prosthesis for Restoring and Enhancing Memory." Besides Deadwyler and Berger, the other authors are, from USC, BME Professor Vasilis Z. Marmarelis and Research Assistant Professor Dong Song, and from Wake Forest, Associate Professor Robert E. Hampson and Post-Doctoral Fellow Anushka Goonawardena.

Berger, who holds the David Packard Chair in Engineering, is the Director of the USC Center for Neural Engineering, Associate Director of the National Science Foundation Biomimetic MicroElectronic Systems Engineering Research Center, and a Fellow of the IEEE, the AAAS, and the AIMBE

"A Cortical Neural Prosthesis for Restoring and Enhancing Memory." (Berger et al 2011 J. Neural Eng. 8 046017)

Read More

3-D movie shows, for the first time, what happens in the brain as it loses consciousness

3-D movie shows, for the first time, what happens in the brain as it loses consciousness

  3:20:00 AM    Science Lover

---

For the first time researchers have been able to watch what happens to the brain as it loses consciousness. Using sophisticated imaging equipment they have constructed a 3-D movie of the brain as it changes while an anaesthetic drug takes effect.

Brian Pollard, Professor of Anaesthesia at The University of Manchester (UK), will tell the European Anaesthesiology Congress in Amsterdam that the real-time 3-D images seemed to show that losing consciousness involves a change in electrical activity deep within the brain, changing the activity of certain groups of nerve cells (neurons) and hindering communication between different parts of the brain.

He said the findings appear to support a hypothesis put forward by Professor Susan Greenfield, of the University of Oxford, about the nature of consciousness itself. Prof Greenfield suggests consciousness is formed by different groups of brain cells (neural assemblies), which work efficiently together, or not, depending on the available sensory stimulations, and that consciousness is not an all-or-none state but more like a dimmer switch, changing according to growth, mood or drugs. When someone is anaesthetised it appears that small neural assemblies either work less well together or inhibit communication with other neural assemblies.

"Our findings suggest that unconsciousness may be the increase of inhibitory assemblies across the brain's cortex. These findings lend support to Greenfield's hypothesis of neural assemblies forming consciousness," said Prof Pollard.

The team use an entirely new imaging method called "functional electrical impedance tomography by evoked response" (fEITER *), which enables high speed imaging and monitoring of electrical activity deep within the brain and is designed to enable researchers to measure brain function.

The new device was developed by a multidisciplinary team drawn from the Schools of Medicine and Electrical and Electronic Engineering at The University of Manchester (UK) led by Professor Hugh McCann and with support from a Wellcome Trust Translation Award.

The machine itself is a portable, light-weight monitor, which can fit on a small trolley. It has 32 electrodes that are fitted around the patient's head. A small, high-frequency electric current (too small to be felt or have any effect) is passed between two of the electrodes, and the voltages between other pairs of electrodes are measured in a process that takes less than one thousandth of a second.

An "electronic scan" is thus carried out and the machine does this whole procedure 100 times a second. By measuring the resistance to current flow (electrical impedance), a cross sectional image of the changing electrical conductivity within the brain is constructed. This is thought to reflect the amount of electrical activity in different parts of the brain. The speed of the response of fEITER is such that the evoked response of the brain to external stimuli, such as an anaesthetic drug, can be captured in rapid succession as different parts of the brain respond, thus tracking the brain's processing activity.

"We have looked at 20 healthy volunteers and are now looking at 20 anaesthetised patients scheduled for surgery," said Prof Pollard. "We are able to see 3-D images of the brain's conductivity change, and those where the patient is becoming anaesthetised are most interesting."

"We have been able to see a real time loss of consciousness in anatomically distinct regions of the brain for the first time. We are currently working on trying to interpret the changes that we have observed. We still do not know exactly what happens within the brain as unconsciousness occurs, but this is another step in the direction of understanding the brain and its functions."

The team at Manchester is one of many worldwide teams investigating electrical impedance tomography (EIT), but this is its first application to anaesthesia. Prof Pollard said that a huge amount of research still needed to be done to fully understand the role EIT could play in medicine.

"If its power can be harnessed, then it has the potential to make a huge impact on many areas of imaging in medicine. It should help us to better understand anaesthesia, sedation and unconsciousness, although its place in medicine is more likely to be in diagnosing changes to the brain that occur as a result of, for example, head injury, stroke and dementia.

"The biggest hurdle is working out what we are seeing and exactly what it means, and this will be an ongoing challenge," he concluded.

Provided by European Society of Anaesthesiology

Read More

Brain Performs Near Optimal Visual Search

Brain Performs Near Optimal Visual Search

  12:46:00 AM    Science Lover

---

In the wild, mammals survive because they can see and evade predators lurking in the shadowy bushes.

Transportation Security Administration screeners can 
pick out dangerous objects in an image of our messy 
and stuffed suitcases. This ability to recognize target 
objects surrounded by distracters is one of the 
remarkable functions of our nervous system. 
(Credit: © Daniel Schmid / Fotolia)

That ability translates to the human world. Transportation Security Administration screeners can pick out dangerous objects in an image of our messy and stuffed suitcases. We get out of the house every morning because we find our car keys on that cluttered shelf next to the door.

This ability to recognize target objects surrounded by distracters is one of the remarkable functions of our nervous system.

"Visual search is an important task for the brain. Surprisingly, even in a complex task like detecting an object in a scene with distracters, we find that people's performance is near optimal. That means that the brain manages to do the best possible job given the available information," said Dr. Wei Ji Ma, assistant professor of neuroscience at Baylor College of Medicine. A report on research by him and colleagues from other institutions appears online in the journal Nature Neuroscience.

Recognizing the target is more than figuring out each individual object.

"Target detection involves integrating information from multiple locations," said Ma. "Many objects might look like the target for which you are searching. It is a cognitive judgment as well as a visual one."

One factor that must be taken into account is reliability of the information.

"We study that in particular," said Ma. "If you are a detective, you weight different pieces of information based on the reliability of the source. Similarly, the brain has to weight different pieces of visual information."

In his study, he and his colleagues used computer screens to show subjects sets of lines that might or might not contain a line oriented in a particular way. To manipulate reliability, they randomly varied the contrast of each line, making the target easier or more difficult to detect. Each screen was shown for only a fraction of a second, making the search task very difficult.

"We found that even in this complex task, people came close to being optimal in detecting the target," he said. "That means that humans can in a split second integrate information across space while taking into account the reliability of that information. That is important in our daily lives."

The task was deliberately made very hard so that people made mistakes, he said, but their answers were as good as they could be given the noise that is inherent to visual observations.

In the second part of their study, they determined that this ability might rely on groups (populations) of neurons that respond differently to different line orientations. Using such populations, they were able to construct a neural network that could weight information by the appropriate reliability.

They simulated this task on the computer and reproduced the behavior of human subjects, giving credence to their argument that the task requires populations of neurons.

"The visual system is automatically and subconsciously doing complex tasks," said Ma. "People see objects and how they relate to one another. We don't just see with our eyes. We see with our brains. Our eyes are the camera, but the process of interpreting the image in our brains is seeing."

The next question is when does a visual task become so complex that the human brain fails to be optimal?

Others who took part in this research include Ronald van den Berg, a postdoc in Ma's lab, Vidhya Navalpakkam of the California Institute of Technology in Pasadena, Jeffrey M. Beck of University College London, and Alexandre Pouget of the University of Rochester in Rochester, New York.

Funding for this work came from the National Eye Institute, the National Science Foundation, the Gatsby Charitable Foundation, the Netherlands Organisation for Scientific Research, the U.S. Department of Defense's Multidisciplinary University Research Initiative (MURI), the National Institute on Drug Abuse and the James S. McDonnell Foundation.

Read More

Cells Send Signals Via Membrane Nanotubes

Cells Send Signals Via Membrane Nanotubes

  8:30:00 PM    Science Lover

---

Most of the body's cells communicate with each other by sending electrical signals through nano-thin membrane tubes. A sensational Norwegian research discovery may help to explain how cells cooperate to develop tissue in the embryo and how wounds heal.

Here a cell has coupled with another cell by growing 
a long nanotube which enables it to exchange 
electrical signals. (Credit: UiB)

For nearly ten years, researchers have known that cells can "grow" ultra-thin tubes named tunnelling nanotubes (TNTs) between one another. These nanotubes -- the length of two to three cells and just 1/500th the thickness of a human hair -- are connections that develop between nearly all cell types to form a communication channel different from any previously known mechanisms.

In 2010, Dr. Xiang Wang and Professor Hans-Hermann Gerdes -- colleagues at the University of Bergen's Department of Biomedicine -- discovered that electrical signals were being passed through nanotubes from one cell to another at high speed (roughly 1-2 m/sec). Their research receives funding under the Research Council's large-scale research programme Nanotechnology and New Materials (NANOMAT).

The breakthrough

In their key experiment, Dr Wang used fluorescent dye that changes in intensity as the electric potential of the cell membrane changes. When two cells connected by forming a nanotube, he poked into one of them with a microinjection needle to depolarise that cell's membrane potential. This caused the fluorescent indicator on the cell membrane to light up like a firework, and it was soon followed by a similar light display in the cell on the other end of the nanotube.

The breakthrough discovery began with an experiment demonstrating intercellular transmission of electrical signals via nanotubes in 2007. The researchers then carried out similar trials with a number of other cell types, observing similar occurrences.

"We confirmed that this is a common phenomenon between cells," explains Professor Gerdes. "Still, this characteristic is not in every cell type."

The experiment was replicated a number of times to obtain statistically reliable data. The electrophysiology group at the University of Bergen took precise conductivity measurements of the cell systems to determine the strength of the electrical coupling. In autumn 2010 the results were published in Proceedings of the National Academy of Sciences (PNAS).

Short lifespan

Intercellular nanotubes are far from permanent. Most of them last only a few minutes. This means the researchers cannot predict where and when the cells will form nanotube connections.

"It is truly painstaking work," says Professor Gerdes. "You may sit there examining cells for hours through a microscope without seeing a single tube. If you are lucky, however, you catch sight of a nanotube being created and can film the event."

To raise the likelihood of finding nanotubes, the researchers developed a micro-matrix consisting of thousands of points and bridges on a plate surface. Smaller than a postage stamp, the plate is covered by a nano-structured material to which the cells adhere. The researchers place one cell onto each point and hope that nanotubes will form along the bridges between the points. The camera is focused on these bridges.

Once the nanotubes have been established, the researchers manipulate the cells at specified times; meanwhile the microscope is programmed to photograph, say, 50 preselected points every five minutes. The team can thus obtain data about many nanotube connections in a short time.

How do cells do this?
Dr. Wang quickly discovered that the mere presence of a nanotube was not sufficient to transmit an electrical signal. There had to be another mechanism involved as well.

Many cells form tiny membrane pores with each other called gap junctions, which are made up of ring-shaped proteins. Back in the 1960s it was discovered that directly adjacent cells could exchange electrical impulses through these gap junctions. What Dr Wang found was that one end of the nanotube was always connected to cells by a gap junctions before it transmitted its electrical impulses.

He also found that in some coupled cells voltage-gated calcium channels were involved in the forwarding of the incoming signals. When the electrical signal being sent through the nanotube reaches the membrane of the receiving cell, the membrane surface is depolarised, opening the calcium channel and allowing calcium -- a vital ion in cell signalling -- to enter.

"In other words," explains Professor Gerdes, "there are two components: a nanotube and a gap junction. The nanotube grows out from one cell and connects to the other cell through a gap junction. Only then can the two cells be coupled electrically."

Controls embryonic cells?

Now the scientists are seeking answers as to why the cells send signals to each other in this way.

"It's quite possible that the discovery of nanotubes will give us new insight into intercellular communication," asserts Professor Gerdes. "The process could explain how cells are coordinated during embryo growth. In that phase cells travel long distances -- yet they demonstrate a kind of collective behaviour, and move together like a flock of birds can."

Nanotubes may also be a factor in explaining cell movement associated with wound healing, since cells move toward a wound in order to close it. We already know that electrical signals are somehow involved in this process; scientists can only speculate as to whether nanotubes are involved here as well, stresses Professor Gerdes.

Perhaps brain cells, too?

In terms of electronic signal processing, the human brain surpasses all other organs. If this same signalling mechanism proves to be present in human brain cells, it could add a new dimension to understanding how the brain functions. Communication channels involving synapses and dendrites that are already identified differ widely from nanotubes.

The Bergen-based neuroscientists see this research as an opportunity to formulate better explanations for phenomena related to consciousness and electrical connections in the brain. In the project "Cell-to-cell communication: Mechanism of tunnelling nanotube formation and function," they are now studying precisely how nanotube mechanisms function in brain cells.

Professor Gerdes is currently conducting research at the European Molecular Biology Laboratory in Heidelberg. By studying the electrical connections in vivo he hopes to figure out how the mechanisms work in live subjects. The results could enhance understanding of diseases that occur when cell mechanisms fail to function properly.

Read More

Neurorobotics Reveals Brain Mechanisms of Self-Consciousness

Neurorobotics Reveals Brain Mechanisms of Self-Consciousness

  12:57:00 AM    Science Lover

---

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 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.

A new study uses creative engineering to unravel brain 
mechanisms associated with one of the most fundamental 
subjective human feelings: self-consciousness. The research 
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. 
(Credit: © paul prescott / Fotolia)

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."

Read More