Posts tagged neuroscience

April 11, 2012

The discovery, using state-of-the-art informatics tools, increases the likelihood that it will be possible to predict much of the fundamental structure and function of the brain without having to measure every aspect of it. That in turn makes the Holy Grail of modelling the brain in silico — the goal of the proposed Human Brain Project — a more realistic, less Herculean, prospect.

“It is the door that opens to a world of predictive biology,” says Henry Markram. Credit: EPFL

"It is the door that opens to a world of predictive biology," says Henry Markram, the senior author on the study, which is published this week in PLoS ONE.

Within a cortical column, the basic processing unit of the mammalian brain, there are roughly 300 different neuronal types. These types are defined both by their anatomical structure and by their electrical properties, and their electrical properties are in turn defined by the combination of ion channels they present—the tiny pores in their cell membranes through which electrical current passes, which make communication between neurons possible.

Scientists would like to be able to predict, based on a minimal set of experimental data, which combination of ion channels a neuron presents. They know that genes are often expressed together, perhaps because two genes share a common promoter—the stretch of DNA that allows a gene to be transcribed and, ultimately, translated into a functioning protein—or because one gene modifies the activity of another. The expression of certain gene combinations is therefore informative about a neuron’s characteristics, and Georges Khazen and co-workers hypothesised that they could extract rules from gene expression patterns to predict those characteristics.

They took a dataset that Prof Markram and others had collected a few years ago, in which they recorded the expression of 26 genes encoding ion channels in different neuronal types from the rat brain. They also had data classifying those types according to a neuron’s morphology, its electrophysiological properties and its position within the six, anatomically distinct layers of the cortex. They found that, based on the classification data alone, they could predict those previously measured ion channel patterns with 78 per cent accuracy. And when they added in a subset of data about the ion channels to the classification data, as input to their data-mining programme, they were able to boost that accuracy to 87 per cent for the more commonly occurring neuronal types.

"This shows that it is possible to mine rules from a subset of data and use them to complete the dataset informatically," says one of the study’s authors, Felix Schürmann. "Using the methods we have developed, it may not be necessary to measure every single aspect of the behaviour you’re interested in." Once the rules have been validated in similar but independently collected datasets, for example, they could be used to predict the entire complement of ion channels presented by a given neuron, based simply on data about that neuron’s morphology, its electrical behaviour and a few key genes that it expresses.

Researchers could also use such rules to explore the roles of different genes in regulating transcription processes. And importantly, if rules exist for ion channels, they are also likely to exist for other aspects of brain organisation. For example, the researchers believe it will be possible to predict where synapses are likely to form in neuronal networks, based on information about the ratio of neuronal types in that network. Knowledge of such rules could therefore usher in a new era of predictive biology, and accelerate progress towards understanding and modelling the brain.

Provided by Ecole Polytechnique Federale de Lausanne

Source: medicalxpress.com

April 10, 2012

Scientists report that they have mapped the physical architecture of intelligence in the brain. Theirs is one of the largest and most comprehensive analyses so far of the brain structures vital to general intelligence and to specific aspects of intellectual functioning, such as verbal comprehension and working memory.

A new study found that specific structures, primarily on the left side of the brain, are vital to general intelligence and executive function (the ability to regulate and control behavior). Brain regions that are associated with general intelligence and executive function are shown in color, with red indicating common areas, orange indicating regions specific to general intelligence, and yellow indicating areas specific to executive function. Credit: Aron Barbey

Their study, published in Brain: A Journal of Neurology, is unique in that it enlisted an extraordinary pool of volunteer participants: 182 Vietnam veterans with highly localized brain damage from penetrating head injuries.

"It’s a significant challenge to find patients (for research) who have brain damage, and even further, it’s very hard to find patients who have focal brain damage," said University of Illinois neuroscience professor Aron Barbey, who led the study. Brain damage – from stroke, for example – often impairs multiple brain areas, he said, complicating the task of identifying the cognitive contributions of specific brain structures.

But the very focal brain injuries analyzed in the study allowed the researchers “to draw inferences about how specific brain structures are necessary for performance,” Barbey said. “By studying how damage to particular brain regions produces specific forms of cognitive impairment, we can map the architecture of the mind, identifying brain structures that are critically important for specific intellectual abilities.”

The researchers took CT scans of the participants’ brains and administered an extensive battery of cognitive tests. They pooled the CT data to produce a collective map of the cortex, which they divided into more than 3,000 three-dimensional units called voxels. By analyzing multiple patients with damage to a particular voxel or cluster of voxels and comparing their cognitive abilities with those of patients in whom the same structures were intact, the researchers were able to identify brain regions essential to specific cognitive functions, and those structures that contribute significantly to intelligence.

"We found that general intelligence depends on a remarkably circumscribed neural system," Barbey said. "Several brain regions, and the connections between them, were most important for general intelligence."

These structures are located primarily within the left prefrontal cortex (behind the forehead), left temporal cortex (behind the ear) and left parietal cortex (at the top rear of the head) and in “white matter association tracts” that connect them. (Watch a video about the findings.)

The researchers also found that brain regions for planning, self-control and other aspects of executive function overlap to a significant extent with regions vital to general intelligence.

The study provides new evidence that intelligence relies not on one brain region or even the brain as a whole, Barbey said, but involves specific brain areas working together in a coordinated fashion.

"In fact, the particular regions and connections we found support an emerging body of neuroscience evidence indicating that intelligence depends on the brain’s ability to integrate information from verbal, visual, spatial and executive processes," he said.

The findings will “open the door to further investigations into the biological basis of intelligence, exploring how the brain, genes, nutrition and the environment together interact to shape the development and continued evolution of the remarkable intellectual abilities that make us human,” Barbey said.

Provided by University of Illinois at Urbana-Champaign

Source: medicalxpress.com

April 9, 2012 by Stuart Mason Dambrot      

(Medical Xpress) — The link between dreaming and rapid eye movement (REM) sleep are well understood – but the fact that consciousness is reduced during nonrapid eye movement (NREM) sleep is not. Recently, scientists in the Cyclotron Research Centre at the University of Liège, in Liège, Belgium, and the Institut National de la Santé et de la Recherche Médicale at the Université Pierre et Marie Curie in Paris, and the Functional Neuroimaging Unit at the Montreal Geriatrics Institute, investigated NREM sleep with the hypothesis that this phenomenon is associated with increased modularity of the brain’s functional activity during these periods. Using functional clustering – which estimates how integration is hierarchically organized within and across the constituent parts of a system they found that while in NREM sleep, hierarchically-organized large-scale neural networks were disaggregated into smaller independent modules. The researchers concluded that this difference could reduce the ability of the brain to integrate information, thereby accounting for the decreased consciousness experienced during NREM sleep.

(A) The six networks extracted during wakefulness. (B) Levels of brain hierarchical integration. (C) Increases in functional clustering ratio in the brain and the six networks (all significant with a probability >0.95). Networks: dATT, dorsal attentional; DM, default mode; EC, executive control; MOT, sensorimotor; SAL, salience; VIS, visual. Copyright © PNAS, doi: 10.1073/pnas.111113310

Led by Pierre Maquet at the Cyclotron Research Centre and Habib Benali at the Institut National de la Santé et de la Recherche Médicale, the team faced a fundamental challenge in framing their research. Maquet first notes that there is currently no consensus on what consciousness really is, let alone how it arises.

“For many years,” he explains to Medical Xpress, “Giulio Tononi put forward the hypothesis that consciousness is related to the ability of the brain to integrate information. Our objective was simply to test this hypothesis, using novel tools allowing for the computation of information exchange within the brain and a set of EEG/fMRI data recorded in the same individuals during wakefulness and deep NREM sleep.” The latter state, he adds, is arguably the condition associated with the most reduce conscious content in normal human volunteers.

Maquet notes that the team used methods devised by Benali. “These allow us to measure the hierarchical organization of integration – i.e., information. The data itself,” he continues, “were acquired in Liège. Conducting simultaneous EEG/fMRI recordings in sleeping volunteers is not that easy.” Moreover, he notes, in practice, their findings are only one small step toward a better understanding of consciousness – and, for that matter, unconsciousness.

“The results were rather unexpected in that the amount of information exchanged in the brain actually increased during sleep. However, the patterns of exchange between regions were different than during wakefulness. Essentially, there was an increased information exchange within small clusters of mainly homologous brain areas whereas communication between clusters significantly decreased during sleep.” Thus, he points out, the data support their hypothesis.

The team has already defined the next steps in their research, says Maquet, who acknowledges that fMRI suffers from a rather sluggish signal. “The next step is to apply the methods to EEG, which has a much better time resolution.” He also states that it might it be possible to transition to in silico modeling, and that there are attempts in this direction in some laboratories.

A key advantage of the team’s approach was relying on functional clustering rather than so-called total integration in neural network analysis. “This is a big question,” states Maquet. “We don’t know what is the information exchanged within clusters, and I don’t see any technique that could currently answer this question in humans. More generally,” he adds, “it is thought that NREM sleep is regulated by the homeostasis of synaptic strength, and perhaps by neuronal energy metabolism.” These assumptions, he concludes, are being studied in animal models.

Source: medicalxpress.com

April 9, 2012

The part of the brain we use when engaging in egalitarian behavior may also be linked to a larger sense of morality, researchers have found. Their conclusions, which offer scientific support for Adam Smith’s theories of morality, are based on experimental research published in the latest issue of the Proceedings of the National Academy of Sciences.

The study, coming seven months after the start of the Occupy Wall Street Movement, which has been aimed at addressing income inequality, was conducted by researchers from: New York University’s Wilf Family Department of Politics; the University of Toronto; the University of California, San Diego; the University of California, Davis; and the University of Nebraska, Lincoln.

Previous scholarship has established that two areas of the brain are active when we behave in an egalitarian manner—the ventromedial prefrontal cortex (vmPFC) and the insular cortex, which are two neurological regions previously shown to be related to social preferences such as altruism, reciprocity, fairness, and aversion to inequality. Less clear, however, is how these parts of the brain may also be connected to egalitarian behavior in a group setting.

To explore this possibility, the researchers conducted an experiment in which individuals played a game to gauge brain activity in decision-making. In the “random income game” participants in a group are randomly assigned a level of income and the group is assigned to one of three income distributions. Subjects are shown the income of all members of their group, including their own, on a computer screen. Individuals are then asked if they wish to pay a cost in order to increase or decrease the incomes of group members. Subjects are told they may keep the money they don’t give away to the others shown on their screen, so there is a strong incentive not to part with any of the money already allocated to them. Nonetheless, the researchers found that the study’s subjects frequently sought to reallocate resources so the money was more equally distributed among the group members.

During this period, the researchers gauged the subjects’ neurological activity through functional magnetic resonance imaging (fMRI). As shown in previous studies, the researchers found significant activity in the brain’s vmPFC and insular cortex.

But to get at a more detailed understanding of neurological activity during these behaviors, they also examined whether activations in these areas were associated with two additional measures of egalitarian preferences elicited outside of the fMRI. As part of a survey, subjects were asked their level of agreement or disagreement to six questions, which included: “Our society should do whatever is necessary to make sure that everyone has an equal opportunity to succeed” and “This country would be better off if we worried less about how equal people are.” In addition, subjects completed a series of decision-making tasks asking them to split money with another anonymous person. The choices individuals make in this task are a measure of egalitarian behavior.

The researchers found that these two measures of egalitarian preferences were significantly associated with activations in the insular cortex, but not with the vmPFC.

This particular result is a potentially profound one as the insular cortex is also the part of the brain that processes the relationship of the individual with respect to her or his environment. In other words, egalitarian behavior may not exist in isolation, neurologically speaking, but, rather, be part of a larger process that stems from altruism and a sense of the larger social good.

Adam Smith, in The Theory of Moral Sentiments, expressed this perspective in his 18th-century essay.

"Adam Smith contended that moral sentiments like egalitarianism derived from a ‘fellow-feeling’ that would increase with our level of sympathy for others, predicting not merely aversion to inequity, but also our propensity to engage in egalitarian behaviors," the researchers wrote. "The evidence here supports such an interpretation—our results suggest that it is the brain mechanisms involved in experiencing the emotional and social states of self and others that appear to be driving egalitarian behaviors. This conclusion is consistent with a broader view of the insular cortex as a neural substrate that processes the relationship of the individual with respect to his or her environment."

Provided by New York University 

Source: medicalxpress.com

April 5th, 2012

Discovery of key link between circadian rhythms and metabolism may lead to new therapies for sleep disorders and diabetes.

The discovery of a major gear in the biological clock that tells the body when to sleep and metabolize food may lead to new drugs to treat sleep problems and metabolic disorders, including diabetes.

Scientists at the Salk Institute for Biological Studies, led by Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, showed that two cellular switches found on the nucleus of mouse cells, known as REV-ERB-α and REV-ERB-β, are essential for maintaining normal sleeping and eating cycles and for metabolism of nutrients from food.

The findings, reported March 29 in Nature, describe a powerful link between circadian rhythms and metabolism and suggest a new avenue for treating disorders of both systems, including jet lag, sleep disorders, obesity and diabetes.

“This fundamentally changes our knowledge about the workings of the circadian clock and how it orchestrates our sleep-wake cycles, when we eat and even the times our bodies metabolize nutrients,” says Evans. “Nuclear receptors can be targeted with drugs, which suggests we might be able to target REV-ERB-α and β to treat disorders of sleep and metabolism.”

Nurses, emergency personnel and others who work shifts that alter the normal 24-hour cycle of waking and sleeping are at much higher risk for a number of diseases, including metabolic disorders such as diabetes. To address this, scientists are trying to understand precisely how the biological clock works and uncover possible targets for drugs that could adjust the circadian rhythm in people with sleep disorders and circadian-associated metabolic disorders.

In mammals, the circadian timing system is orchestrated by a central clock in the brain and subsidiary clocks in most other organs. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior.

Scientists knew that two genes, BMAL1 and CLOCK, worked together at the core of the clock’s molecular machinery to activate the network of circadian genes. In this way, BMAL1 acts like the accelerator on a car, activating genes to rev up our physiology each morning so that we are alert, hungry and physically active.

Prior to this work REV-ERB-α and β were thought to play only a minor role in these cycles, possibly working together to slow CLOCK-BMAL1 activity to make minor adjustments to keep the clock running on time.

However, genetic studies of two genes with similar functions can be very difficult and thus the real importance of REV-ERB-α and β remained mysterious.

The Salk scientists got around this hurdle by developing mice in which both genes could be turned off in the liver at any point by giving them an estrogen derivative called tamoxifen. Now mice could develop normally to adulthood, at which point the scientists could turn off REV-ERB-α and REV-ERB-β in their livers—an organ crucial to maintaining the correct balance of sugar and fat in blood—to see what effects it had on circadian rhythms and metabolism.

“When we turned off both receptors, the animal’s biological clocks went haywire,” says Han Cho, first author on the paper and a postdoctoral researcher in Evan’s laboratory. “The mice started running on their exercise wheels when they should have been resting. This suggested REV-ERB-α and REV-ERB-β aren’t an auxiliary system that makes minor adjustments, but an integral part of the clock’s core mechanism. Without them, the clock can’t function properly.”

Digging more deeply into the clockworks, the Salk scientists mapped out the genes that the REV-ERBs control to keep the body operating on the right schedule, finding that they overlap with hundreds of the same genes controlled by CLOCK and BMAL1. This and other findings suggested that the REV-ERBs, act as a break on the genes BMAL1 activates.

“We thought that the core of the clock was an accelerator, and that all REV-ERB-α and REV-ERB-β did was to pull the foot off that pedal,” says Evans. “What we’ve shown is that these receptors act directly as a break to slow clock activity. Now we’ve got a accelerator and a break, each equally important in creating the daily rhythm of the clock.”

The scientists also found that the REV-ERBs control the activity of hundreds of genes involved metabolism, including those responsible for controlling levels of fats and bile. The mice in which REV-ERB-α and REV-ERB-β were turned off had high levels of fat and sugar in their blood—common problems in people with metabolic disorders.

“This explains how our cellular metabolism is tied to daylight cycles determined by the movements of the sun and the earth,” says Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory and co-author on the paper. “Now we want to find ways of leveraging this mechanism to fix a person’s metabolic rhythms when they are disrupted by travel, shift work or sleep disorders.”

Source: Neuroscience News

April 5th, 2012

Yale researchers show in detail how three genes within human embryonic stem cells regulate development, a finding that increases understanding of how to grow these cells for therapeutic purposes.

This process, described in the April 6 issue of the journal Cell Stem Cell, is different in humans than in mice, highlighting the importance of research using human embryonic stem cells.

“It is difficult to deduce from the mouse how these cells work in humans,” said Natalia Ivanova, assistant professor of genetics in the Yale Stem Cell Center and senior author of the study. “Human networks organize themselves quite differently.”

Embryonic stem cells form soon after conception and are special because each cell can become any type of cell in the body. Cells become increasingly specialized as development progresses, losing the ability to become other cell types — except for the renewal of a few new stem cells. Scientists want to understand the processes of self-renewal and differentiation in order to treat a host of diseases characterized by damaged cells such as Parkinson’s disease, spinal cord injury, heart disease, and Alzheimer’s.

Scientists have identified three genes active in early development — Nanog, Oct 4, and Sox 2 — as essential to maintaining the stem cell’s ability to self-renew and prevent premature differentiation into the “wrong” type of cells. Because of restrictions on the use of human embryonic stem cells, much of the investigation into how these genes work has been done in mice.

The new study shows that human embryonic cells operate in fundamentally different ways in humans than in mouse cells. In humans, for instance, Nanog pairs with Oct 4 to regulate differentiation of so-called neuro-ectoderm cells, a lineage that gives rise to neurons and other central nervous system cells. Sox 2, by contrast, inhibits the differentiation of mesoderm — a lineage that gives rise to muscles and many other tissue types. Oct 4 cooperates with the other genes and is crucial in the regulation of all four early cell lineages: ectoderm, mesoderm, and endoderm — which gives rise to gut and glands such as liver and pancreas — as well as the creation of new stem cells. The self-renewal of stem cells has been implicated in several forms of cancer.

Ivanova stresses that many other genes must be involved in regulation of these early developmental changes, and her lab is investigating that question now.

Source: Neuroscience News

April 4, 2012

Brain pacemakers have a long-term effect in patients with the most severe depression. This has now been proven by scientists from the Bonn University Medical Center. Eleven patients took part in the study over a period of two to five years. A lasting reduction in symptoms of more than 50 percent was seen in nearly half of the subjects. The results are now being presented in the current edition of the journal Neuropsychopharmacology.

People with severe depression are constantly despondent, lacking in drive, withdrawn and no longer feel joy. Most suffer from anxiety and the desire to take their own life. Approximately one out of every five people in Germany suffers from depression in the course of his/her life – sometimes resulting in suicide. People with depression are frequently treated with psychotherapy and medication. “However, many patients are not helped by any therapy,” says Prof. Dr. Thomas E. Schläpfer from the Bonn University Medical Center for Psychiatry and Psychotherapy. “Many spend more than ten years in bed – not because they are tired, but because they have no drive at all and they are unable to get up.”

One possible alternative is “deep brain stimulation,” in which electrodes are implanted in the patient’s brain. The target point is the nucleus accumbens - an area of the brain known as the gratification center. There, a weak electrical current stimulates the nerve cells. Brain pacemakers of this type are often used today by neurosurgeons and neurologists to treat ongoing muscle tremors in Parkinson’s disease.

A 2009 study proved an antidepressive effect

In 2009, the Bonn scientists were able to establish that brain pacemakers also demonstrate an effect in the most severely depressed patients. Ten subjects who underwent implantation of electrodes in the nucleus accumbens all experienced relief of symptoms. Half of the subjects had a particularly noticeable response to the stimulation by the electrodes.

"In the current study, we investigated whether these effects last over the long term or whether the effects of the deep brain stimulation gradually weaken in patients," says Prof. Schläpfer. There are always relapses in the case of psychotherapy or drug treatment. Many patients had already undergone up to 60 treatments with psychotherapy, medications and electroconvulsive therapy, to no avail. "By contrast, in the case of deep brain stimulation, the clinical improvement continues steadily for many years." The scientists observed a total of eleven patients over a period of two to five years. "Those who initially responded to the deep brain stimulation are still responding to it even today," says the Bonn psychiatrist, summarizing the results. During the study, one patient committed suicide. "That is very unfortunate," says Prof. Schläpfer. "However, this cannot always be prevented in the case of patients with very severe depression."

he current study shows that the positive effects last for years

Even after a short amount of time, the study participants demonstrated an improvement in symptoms. “The intensity of the anxiety symptoms decreased and the subjects’ drive improved,” reports the psychiatrist. “After many years of illness, some were even able to work again.” With the current publication, the scientists have now demonstrated that the positive effects do not decrease over a longer period of time. “An improvement in symptoms was recorded for all subjects; for nearly half of the subjects, the extent of the symptoms was more than 50 percent below that of the baseline, even years after the start of treatment,” says Prof. Schläpfer. “There were no serious adverse effects of the therapy recorded.”

The long-term effect is now confirmed with the current study. How precisely the electrical stimulation is able to alter the function of the nucleus accumbens is not yet known. “Research is still needed in this area,” says Prof. Schläpfer. “Using imaging techniques, it was proven that the electrodes actually activate the nucleus accumbens.” The deep brain stimulation method may signify hope for people who suffer from the most severe forms of depressive diseases. “However, it will still take quite a bit of time before this therapeutic method becomes a part of standard clinical practice,” says the Bonn scientist.

Provided by University of Bonn 

Source: medicalxpress.com

April 4, 2012

Awakening from anesthesia is often associated with an initial phase of delirious struggle before the full restoration of awareness and orientation to one’s surroundings. Scientists now know why this may occur: primitive consciousness emerges first. Using brain imaging techniques in healthy volunteers, a team of scientists led by Adjunct Professor Harry Scheinin, M.D. from the University of Turku, Finland in collaboration with investigators from the University of California, Irvine, have now imaged the process of returning consciousness after general anesthesia. The emergence of consciousness was found to be associated with activations of deep, primitive brain structures rather than the evolutionary younger neocortex.

This image shows one returning from oblivion — imaging the neural core of consciousness. Positron emission tomography (PET) findings show that the emergence of consciousness after anesthesia is associated with activation of deep, phylogenetically old brain structures rather than the neocortex. Left: Sagittal (top) and axial (bottom) sections show activation in the anterior cingulate cortex (i), thalamus (ii) and the brainstem (iii) locus coeruleus/parabrachial area overlaid on magnetic resonance image (MRI) slices. Right: Cortical renderings show no evident activations. Credit: Turku PET Center

These results may represent an important step forward in the scientific explanation of human consciousness.

"We expected to see the outer bits of brain, the cerebral cortex (often thought to be the seat of higher human consciousness), would turn back on when consciousness was restored following anesthesia. Surprisingly, that is not what the images showed us. In fact, the central core structures of the more primitive brain structures including the thalamus and parts of the limbic system appeared to become functional first, suggesting that a foundational primitive conscious state must be restored before higher order conscious activity can occur" Scheinin said.

Twenty young healthy volunteers were put under anesthesia in a brain scanner using either dexme-detomidine or propofol anesthetic drugs. The subjects were then woken up while brain activity pictures were being taken. Dexmedetomidine is used as a sedative in the intensive care unit setting and propofol is widely used for induction and maintenance of general anesthesia. Dexmedetomidineinduced unconsciousness has a close resemblance to normal physiological sleep, as it can be reversed with mild physical stimulation or loud voices without requiring any change in the dosing of the drug. This unique property was critical to the study design, as it enabled the investigators to separate the brain activity changes associated with the changing level of consciousness from the drugrelated effects on the brain. The staterelated changes in brain activity were imaged with positron emission tomography (PET).

The emergence of consciousness, as assessed with a motor response to a spoken command, was associated with the activation of a core network involving subcortical and limbic regions that became functionally coupled with parts of frontal and inferior parietal cortices upon awakening from dexme-detomidine-induced unconsciousness. This network thus enabled the subjective awareness of the external world and the capacity to behaviorally express the contents of consciousness through voluntary responses.

Interestingly, the same deep brain structures, i.e. the brain stem, thalamus, hypothalamus and the anterior cingulate cortex, were activated also upon emergence from propofol anesthesia, suggesting a common, drugindependent mechanism of arousal. For both drugs, activations seen upon regaining consciousness were thus mostly localized in deep, phylogenetically old brain structures rather than in the neocortex.

The researchers speculate that because current depth-of-anesthesia monitoring technology is based on cortical electroencephalography (EEG) measurement (i.e., measuring electrical signals on the sur-face of the scalp that arise from the brain’s cortical surface), their results help to explain why these devices fail in differentiating the conscious and unconscious states and why patient awareness during general anesthesia may not always be detected. The results presented here also add to the current understanding of anesthesia mechanisms and form the foundation for developing more reliable depth-of-anesthesia technology.

The anesthetized brain provides new views into the emergence of consciousness. Anesthetic agents are clinically useful for their remarkable property of being able to manipulate the state of consciousness. When given a sufficient dose of an anesthetic, a person will lose the precious but mysterious capacity of being aware of one’s own self and the surrounding world, and will sink into a state of oblivion. Conversely, when the dose is lightened or wears off, the brain almost magically recreates a subjective sense of being as experience and awareness returns. The ultimate nature of consciousness remains a mystery, but anesthesia offers a unique window for imaging internal brain activity when the subjective phenomenon of consciousness first vanishes and then re-emerges. This study was designed to give the clearest picture so far of the internal brain processes involved in this phenomenon.

The results may also have broader implications. The demonstration of which brain mechanisms are involved in the emergence of the conscious state is an important step forward in the scientific explanation of consciousness. Yet, much harder questions remain. How and why do these neural mechanisms create the subjective feeling of being, the awareness of self and environment the state of being conscious?

Provided by Academy of Finland

Source: medicalxpress.com

ScienceDaily (Apr. 4, 2012) — University of Oregon scientists collaborating with an Oregon company that synthesizes antisense Morpholinos for genetic research have developed a UV light-activated on-off switch for the vital gene-blocking molecule. Based on initial testing in zebra-fish embryos, the enhanced molecule promises to deliver new insights for developmental biologists and brain researchers.

The seven-member team describes the advancement in an open-access paper published in the May issue of the journal Development. UO neuroscientist Philip Washbourne, a professor of biology, says the paper is a “proof-of-concept” on an idea he began discussing with scientists at Gene Tools LLC in Philomath, Ore., about four years ago. Gene Tools was founded in the 1980s by James Summerton, who first invented Morpholino oligos. The company holds the exclusive license to distribute these molecules to researchers around the world.

Morpholinos are short-chain, artificially produced oligomers that bind to RNA in cells and block protein synthesis. For a decade, biologists have used them in zebra fish, mice and African clawed toads to study development, but they remained in the active, or on, position. Gene Tools created and introduced a light-sensitive linker, allowing researchers to control the molecule — even leaving one on in one cell and off in an adjacent cell — with a pinpoint UV laser beam.

Researchers in Washbourne’s lab — led by neuroscience research associate Alexandra Tallafuss — were challenged to give the new molecules a test run. They applied them to their work in zebra fish. “Now we can turn them on and off,” Washbourne said. “You can insert them and then manipulate them to learn just when a gene is important, and we learned two things right away.”

Researchers have known that if a gene known as “no tail” is blocked in development, zebra fish fail to grow tails. They now know that the no-tail gene does not need to produce protein for tail formation until about 10 hours, or very late, into an embryo’s development.

Secondly, the researchers looked at the gene sox10, which is vital in the formation of neural crest cells, which give rise to dorsal root ganglion cells — neurons that migrate out of the spinal cord — and pigment cells. “Again, we found that sox10 is not needed as early in development as theorized,” Washbourne said.

"These light-sensitive molecules significantly expand the power and precision of molecular genetic studies in zebrafish," said Robert Riddle, a program director at the National Institute of Neurological Disorders and Stroke (NINDS). "Researchers from many fields will be able to use these tools to explore the function of different genes in embryonic regions, specific cell types and at precise times in an animal’s lifespan."

The NINDS and National Institute of Child Health and Human Development, both at the National Institutes of Health, supported the research through grants to Washbourne and Eisen.

"This successful collaboration between our scientists and this Oregon-based company shows that commercial innovation can come quickly by jointly addressing common needs," said Kimberly Andrews Espy, vice president for research and innovation at the UO. "This is a remarkable example of turning a concept into a working tool that likely will benefit many researchers around the world."

Source: Science Daily