neurosciencestuff:

This is Your Brain on Drugs

Funded by a $1 million award from the Keck Foundation, biomedical researchers at UCSB will strive to find out who could be more vulnerable to addiction

We’ve all heard the term “addictive personality,” and many of us know individuals who are consistently more likely to take the extra drink or pill that puts them over the edge. But the specific balance of neurochemicals in the brain that spurs him or her to overdo it is still something of a mystery.

“There’s not really a lot we know about specific molecules that are linked to vulnerability to addiction,” said Tod Kippin, a neuroscientist at UC Santa Barbara who studies cocaine addiction. In a general sense, it is understood that animals — humans included — take substances to derive that pleasurable rush of dopamine, the neurochemical linked with the reward center of the brain. But, according to Kippin, that dopamine rush underlies virtually any type of reward animals seek, including the kinds of urges we need to have in order to survive or propagate, such as food, sex or water. Therefore, therapies that deal with that reward system have not been particularly successful in treating addiction.

However, thanks to a collaboration between UCSB researchers Kippin; Tom Soh, professor of mechanical engineering and of materials; and Kevin Plaxco, professor of chemistry and biochemistry — and funding from a $1 million grant from the W. M. Keck Foundation — the neurochemistry of addiction could become a lot less mysterious and a lot more specific. Their study, “Continuous, Real-Time Measurement of Psychoactive Molecules in the Brain,” could, in time, lead to more effective therapies for those who are particularly inclined toward addictive behaviors.

“The main purpose is to try to identify individuals that would be vulnerable to drug addiction based on their initial neurochemistry,” said Kippin. “The idea is that if we can identify phenotypes — observable characteristics — that are vulnerable to addiction and then understand how drugs change the neurochemistry related to that phenotype, we’ll be in a better position to develop therapeutics to help people with that addiction.”

To identify these addiction-prone neurochemical profiles, the researchers will rely on technology they recently developed, a biosensor that can track the concentration of specific molecules in vivo, in real time. One early incarnation of this device was called MEDIC (Microfluidic Electrochemical Detector for In vivo Concentrations). Through artificial DNA strands called aptamers, MEDIC could indicate the concentration of target molecules in the bloodstream. 

“Specifically, the DNA molecules are modified so that when they bind their specific target molecule they begin to transfer electrons to an underlying electrode, producing an easily measurable current,” said Plaxco. Prior to the Keck award, the team had shown that this technology could be used to measure specific drugs continuously and in real time in blood drawn from a subject via a catheter. With Keck funding, “the team is hoping to make the leap to measurements performed directly in vivo. That is, directly in the brains of test subjects,” said Plaxco.

For this study, the technology would be modified for use in the brain tissue of awake, ambulatory animals, whose neurochemical profiles would be measured continuously and in real time. The subjects would then be allowed to self-dose with cocaine, while the levels of the drug in their brain are monitored. Also monitored are concomitant changes in the animal’s neurochemistry or drug-seeking (or other) behaviors.

“The key aspect of it is understanding the timing of the neurochemical release,” said Kippin. “What are the changes in neurochemistry that causes the animals to take the drug versus those that immediately follow consumption of the drug?”

Among techniques for achieving this goal, a single existing technology allows scientists to monitor more than one target molecule at a time (e.g., a drug, a metabolite, and a neurotransmitter). However, Kippin noted, it provides an average of one data point about every 20 minutes, which is far slower than the time course of drug-taking behaviors and much less than the sub-second timescale over which the brain responds to drugs. With the implantable biosensor the team has proposed, it would be possible not only to track how the concentration of neurochemicals shift in relation to addictive behavior in real time, but also to simultaneously monitor the concentrations of several different molecules.

“One of our hypotheses about what makes someone vulnerable to addiction is the metabolism of a drug to other active molecules so that they may end up with a more powerful, more rewarding pharmacological state than someone with a different metabolic profile,” Kippin said. “It’s not enough to understand the levels of the compound that is administered; we have to understand all the other compounds that are produced and how they’re working together.”

The implantable biosensor technology also has the potential to go beyond cocaine and shed light on addictions to other substances such as methamphetamines or alcohol. It also could explore behavioral impulses behind obesity, or investigate how memory works, which could lead to further understanding of diseases such as Alzheimers.

(Reblogged from neurosciencestuff)

How neuro cells turn cancerous

neurosciencestuff:

Scientists from the Sloan-Kettering Institute for Cancer Research in New York with the help of  Plymouth University Peninsula Schools of Medicine and Dentistry have completed research which for the first time brings us nearer to understanding how some cells in the brain and nervous system become cancerous.

image

The results of their study are published in the prestigious journal Cancer Cell.

The research team led by Sloan-Kettering researchers studied a tumour suppressor called Merlin. 

The results of the study have identified a new  mechanism whereby Merlin suppresses tumours, and that the mechanism operates within the nucleus. The research team has discovered that unsuppressed tumour cells increase via a core signalling system, the hippo pathway, and they have identified the route and method by which this signalling occurs.

By identifying the signalling system and understanding how, when present, Merlin suppresses it, the way is open for research into drug therapies which may suppress the signalling in a similar way to Merlin. 

Tumour suppressors exist in cells to prevent abnormal cell division in our bodies. The loss of Merlin leads to tumours in many cell types within our nervous systems. There are two copies of a tumour suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin can be caused by random loss of both copies in a single cell, causing sporadic tumours, or by inheriting one abnormal copy and losing the second copy throughout our lifetime as is seen in the inherited condition of neurofibromatosis type 2 (NF2). 

No effective therapy for these tumours exists, other than repeated invasive surgery aiming at a single tumour at a time and which is unlikely to eradicate the full extent of the tumours, or radiotherapy.

Professor Oliver Hanemann, Director of the Institute of Translational and Stratified Medicine at Plymouth University Peninsula Schools of Medicine and Dentistry, and who led the Plymouth aspect of the study, commented:

“We have known for some time that the loss of the tumour suppressor Merlin resulted in the development of nervous system tumours, and we have come tantalisingly close to understanding how this occurs. Our joint study with colleagues at the Sloan-Kettering Institute for Cancer Research shows for the first time how this mechanism works. By understanding the mechanism, we can use this knowledge to develop effective drug therapies – in some cases adapting existing drugs – to treat patients for whom current therapies are limited and potentially devastating.”

(Reblogged from neurosciencestuff)

neurosciencestuff:

Seeing the inner workings of the brain made easier by new technique

Last year Karl Deisseroth, a Stanford professor of bioengineering and of psychiatry and behavioral sciences, announced a new way of peering into a brain – removed from the body – that provided spectacular fly-through views of its inner connections. Since then laboratories around the world have begun using the technique, called CLARITY, with some success, to better understand the brain’s wiring.

However, Deisseroth said that with two technological fixes CLARITY could be even more broadly adopted. The first problem was that laboratories were not set up to reliably carry out the CLARITY process. Second, the most commonly available microscopy methods were not designed to image the whole transparent brain. “There have been a number of remarkable results described using CLARITY,” Deisseroth said, “but we needed to address these two distinct challenges to make the technology easier to use.”

In a Nature Protocols paper published June 19, Deisseroth presented solutions to both of those bottlenecks. “These transform CLARITY, making the overall process much easier and the data collection much faster,” he said. He and his co-authors, including postdoctoral fellows Raju Tomer and Li Ye and graduate student Brian Hsueh, anticipate that even more scientists will now be able to take advantage of the technique to better understand the brain at a fundamental level, and also to probe the origins of brain diseases.

This paper may be the first to be published with support of the White House BRAIN Initiative, announced last year with the ambitious goal of mapping the brain’s trillions of nerve connections and understanding how signals zip through those interconnected cells to control our thoughts, memories, movement and everything else that makes us us.

"This work shares the spirit of the BRAIN Initiative goal of building new technologies to understand the brain – including the human brain," said Deisseroth, who is also a Stanford Bio-X affiliated faculty member.

Eliminating fat

When you look at the brain, what you see is the fatty outer covering of the nerve cells within, which blocks microscopes from taking images of the intricate connections between deep brain cells. The idea behind CLARITY was to eliminate that fatty covering while keeping the brain intact, complete with all its intricate inner wiring.

The way Deisseroth and his team eliminated the fat was to build a gel within the intact brain that held all the structures and proteins in place. They then used an electric field to pull out the fat layer that had been dissolved in an electrically charged detergent, leaving behind all the brain’s structures embedded in the firm water-based gel, or hydrogel. This is called electrophoretic CLARITY.

The electric field aspect was a challenge for some labs. “About half the people who tried it got it working right away,” Deisseroth said, “but others had problems with the voltage damaging tissue.” Deisseroth said that this kind of challenge is normal when introducing new technologies. When he first introduced optogenetics, which allows scientists to control individual nerves using light, a similar proportion of labs were not initially set up to easily implement the new technology, and ran into challenges.

To help expand the use of CLARITY, the team devised an alternate way of pulling out the fat from the hydrogel-embedded brain – a technique they call passive CLARITY. It takes a little longer, but still removes all the fat, is much easier and does not pose a risk to the tissue. “Electrophoretic CLARITY is important for cases where speed is critical, and for some tissues,” said Deisseroth, who is also the D.H. Chen Professor. “But passive CLARITY is a crucial advance for the community, especially for neuroscience.” Passive CLARITY requires nothing more than some chemicals, a warm bath and time.

Many groups have begun to apply CLARITY to probe brains donated from people who had diseases like epilepsy or autism, which might have left clues in the brain to help scientists understand and eventually treat the disease. But scientists, including Deisseroth, had been wary of trying electrophoretic CLARTY on these valuable clinical samples with even a very low risk of damage. “It’s a rare and precious donated sample, you don’t want to have a chance of damage or error,” Deisseroth said. “Now the risk issue is addressed, and on top of that you can get the data very rapidly.”

Fast CLARITY imaging in color

The second advance had to do this rapidity of data collection. In studying any cells, scientists often make use of probes that will go into the cell or tissue, latch onto a particular molecule, then glow green, blue, yellow or other colors in response to particular wavelengths of light. This is what produces the colorful cellular images that are so common in biology research. Using CLARITY, these colorful structures become visible throughout the entire brain, since no fat remains to block the light.

But here’s the hitch. Those probes stop working, or get bleached, after they’ve been exposed to too much light. That’s fine if a scientist is just taking a picture of a small cellular structure, which takes little time. But to get a high-resolution image of an entire brain, the whole tissue is bathed in light throughout the time it takes to image it point by point. This approach bleaches out the probes before the entire brain can be imaged at high resolution.

The second advance of the new paper addresses this issue, making it easier to image the entire brain without bleaching the probes. “We can now scan an entire plane at one time instead of a point,” Deisseroth said. “That buys you a couple orders of magnitude of time, and also efficiently delivers light only to where the imaging is happening.” The technique is called light sheet microscopy and has been around for a while, but previously didn’t have high enough resolution to see the fine details of cellular structures. “We advanced traditional light sheet microscopy for CLARITY, and can now see fine wiring structures deep within an intact adult brain,” Deisseroth said. His lab built their own microscope, but the procedures are described in the paper, and the key components are commercially available. Additionally, Deisseroth’s lab provides free training courses in CLARITY, modeled after his optogenetics courses, to help disseminate the techniques.

Brain imaging to help soldiers

The BRAIN Initiative is being funded through several government agencies including the Defense Advanced Research Projects Agency (DARPA), which funded Deisseroth’s work through its new Neuro-FAST program. Deisseroth said that like the National Institute of Mental Health (NIMH, another major funder of the new paper), DARPA “is interested in deepening our understanding of brain circuits in intact and injured brains to inform the development of better therapies.” The new methods Deisseroth and his team developed will accelerate both human- and animal-model CLARITY; as CLARITY becomes more widely used, it will continue to help reveal how those inner circuits are structured in normal and diseased brains, and perhaps point to possible therapies.

Other arms of the BRAIN Initiative are funded through the National Science Foundation (NSF) and the National Institutes of Health (NIH). A working group for the NIH arm was co-led by William Newsome, professor of neurobiology and director of the Stanford Neurosciences Institute, and also included Deisseroth and Mark Schnitzer, associate professor of biology and of applied physics. That group recently recommended a $4.5 billion investment in the BRAIN Initiative over the next 12 years, which NIH Director Francis Collins approved earlier this month.

In addition to funding by DARPA and NIMH, the work was funded by the NSF, the National Institute on Drug Abuse, the Simons Foundation and the Wiegers Family Fund.

(Reblogged from science666)

neurosciencestuff:

(Image caption: The light grey coil on the left is a conventional, commercially available TMS coil. The black coil on the right is the new, innovative version designed to fit a smaller non-human primate’s cranium and work with the neural monitoring device. Credit: Photo courtesy of Warren Grill.)

Watching Individual Neurons Respond to Magnetic Therapy

Engineers and neuroscientists at Duke University have developed a method to measure the response of an individual neuron to transcranial magnetic stimulation (TMS) of the brain. The advance will help researchers understand the underlying physiological effects of TMS — a procedure used to treat psychiatric disorders — and optimize its use as a therapeutic treatment.

TMS uses magnetic fields created by electric currents running through a wire coil to induce neural activity in the brain. With the flip of a switch, researchers can cause a hand to move or influence behavior. The technique has long been used in conjunction with other treatments in the hopes of improving treatment for conditions including depression and substance abuse.

While studies have demonstrated the efficacy of TMS, the technique’s physiological mechanisms have long been lost in a “black box.” Researchers know what goes into the treatment and the results that come out, but do not understand what’s happening in between.

Part of the reason for this mystery lies in the difficulty of measuring neural responses during the procedure; the comparatively tiny activity of a single neuron is lost in the tidal wave of current being generated by TMS. But the new study demonstrates a way to remove the proverbial haystack.

The results were published online June 29 in Nature Neuroscience.

“Nobody really knows what TMS is doing inside the brain, and given that lack of information, it has been very hard to interpret the outcomes of studies or to make therapies more effective,” said Warren Grill, professor of biomedical engineering, electrical and computer engineering, and neurobiology at Duke. “We set out to try to understand what’s happening inside that black box by recording activity from single neurons during the delivery of TMS in a non-human primate. Conceptually, it was a very simple goal. But technically, it turned out to be very challenging.”

First, Grill and his colleagues in the Duke Institute for Brain Sciences (DIBS) engineered new hardware that could separate the TMS current from the neural response, which is thousands of times smaller. Once that was achieved, however, they discovered that their recording instrument was doing more than simply recording.

The TMS magnetic field was creating an electric current through the electrode measuring the neuron, raising the possibility that this current, instead of the TMS, was causing the neural response. The team had to characterize this current and make it small enough to ignore.

Finally, the researchers had to account for vibrations caused by the large current passing through the TMS device’s small coil of wire — a design problem in and of itself, because the typical TMS coil is too large for a non-human primate’s head. Because the coil is physically connected to the skull, the vibration was jostling the measurement electrode.

The researchers were able to compensate for each artifact, however, and see for the first time into the black box of TMS. They successfully recorded the action potentials of an individual neuron moments after TMS pulses and observed changes in its activity that significantly differed from activity following placebo treatments.

Grill worked with Angel Peterchev, assistant professor in psychiatry and behavioral science, biomedical engineering, and electrical and computer engineering, on the design of the coil. The team also included Michael Platt, director of DIBS and professor of neurobiology, and Mark Sommer, a professor of biomedical engineering.

They demonstrated that the technique could be recreated in different labs. “So, any modern lab working with non-human primates and electrophysiology can use this same approach in their studies,” said Grill.

The researchers hope that many others will take their method and use it to reveal the effects TMS has on neurons. Once a basic understanding is gained of how TMS interacts with neurons on an individual scale, its effects could be amplified and the therapeutic benefits of TMS increased.

“Studies with TMS have all been empirical,” said Grill. “You could look at the effects and change the coil, frequency, duration or many other variables. Now we can begin to understand the physiological effects of TMS and carefully craft protocols rather than relying on trial and error. I think that is where the real power of this research is going to come from.”

(Reblogged from neurosciencestuff)

neurosciencestuff:

The Social Psychology of Nerve Cells

The functional organization of the central nervous system depends upon a precise architecture and connectivity of distinct types of neurons. Multiple cell types are present within any brain structure, but the rules governing their positioning, and the molecular mechanisms mediating those rules, have been relatively unexplored.

A new study by UC Santa Barbara researchers demonstrates that a particular neuron, the cholinergic amacrine cell, creates a “personal space” in much the same way that people distance themselves from one another in an elevator. In addition, the study, published in the Proceedings of the National Academy of Sciences, shows that this feature is heritable and identifies a genetic contributor to it, pituitary tumor-transforming gene 1 (Pttg1).

Patrick Keeley, a postdoctoral scholar in Benjamin Reese’s laboratory at UCSB’s Neuroscience Research Institute, has been using the retina as a model system for exploring such principles of developmental neurobiology. The retina is ideal because this portion of the central nervous system lends itself to such spatial analysis. 

“Populations of neurons in the retina are laid out in single strata within this layered structure, lending themselves to accurate quantitation and statistical analysis,” explained Keeley. “Rather than being distributed as regular lattices of nerve cells, populations in the retina appear to abide by a simple rule, that of minimizing proximity to other cells of the same type. We would like to understand how such populations create and maintain such spacing behavior.”

To address this, Keeley and colleagues quantified the regularity in the population of a particular type of amacrine cell in the mouse retina. They did so in 26 genetically distinct strains of mice and found that every strain exhibited this same self-spacing behavior but that some strains did so more efficiently than others. Amacrine cells are retinal interneurons that form connections between other neurons and regulate bipolar cell output.

“The regularity in the patterning of these amacrine cells showed little variation within each strain, while showing conspicuous variation between the strains, indicating a heritable component to this trait,” said Keeley.

“This itself was something of a surprise, given that the patterning in such populations has an apparently stochastic quality to it,” said Reese, a professor in the Department of Psychological and Brain Sciences. Stochastic systems are random and are analyzed, at least in part, using probability theory.

This strain variation in the regularity of this cellular patterning showed a significant linkage to a location in the genome on chromosome 11, where the researchers identified Pttg1, previously unknown to play any role in the retina.

Working in collaboration with colleagues at the University of Tennessee Health Science Center in Memphis, Keeley’s team demonstrated that the expression of this gene varies across the 26 strains of mice and that there was a positive correlation between gene expression and regularity. They then identified a mutation in this gene that itself correlated with expression levels and with regularity. Working with colleagues at Cedars-Sinai Medical Center in Los Angeles, the team also demonstrated directly that this mutation controlled gene expression.   

“Pttg1 has diverse functions, being an oncogene for pituitary tumors, and is known to have regulatory functions orchestrating gene expression elsewhere in the body,” explained Keeley. “Within this class of retinal neurons, it should be regulating the way in which cells integrate signals from their immediate neighbors, translating that information to position the cell farthest from those neighbors.” Future studies should decipher the genetic network controlled by Pttg1 that mediates such nerve-cell spacing.

(Reblogged from neurosciencestuff)

neurosciencestuff:

Blocking brain’s ‘internal marijuana’ may trigger early Alzheimer’s deficits

A new study led by investigators at the Stanford University School of Medicine has implicated the blocking of endocannabinoids — signaling substances that are the brain’s internal versions of the psychoactive chemicals in marijuana and hashish — in the early pathology of Alzheimer’s disease.

A substance called A-beta — strongly suspected to play a key role in Alzheimer’s because it’s the chief constituent of the hallmark clumps dotting the brains of people with Alzheimer’s — may, in the disease’s earliest stages, impair learning and memory by blocking the natural, beneficial action of endocannabinoids in the brain, the study demonstrates. The Stanford group is now trying to figure out the molecular details of how and where this interference occurs. Pinning down those details could pave the path to new drugs to stave off the defects in learning ability and memory that characterize Alzheimer’s.

In the study, published June 18 in Neuron, researchers analyzed A-beta’s effects on a brain structure known as the hippocampus. In all mammals, this midbrain structure serves as a combination GPS system and memory-filing assistant, along with other duties.

“The hippocampus tells us where we are in space at any given time,” said Daniel Madison, PhD, associate professor of molecular and cellular physiology and the study’s senior author. “It also processes new experiences so that our memories of them can be stored in other parts of the brain. It’s the filing secretary, not the filing cabinet.”

Surprise finding

Applying electrophysiological techniques to brain slices from rats, Madison and his associates examined a key hippocampal circuit, one of whose chief elements is a class of nerve cells called pyramidal cells. They wanted to see how the circuit’s different elements reacted to small amounts of A-beta, which is produced throughout the body but whose normal physiological functions have until now been ill-defined.

A surprise finding by Madison’s group suggests that in small, physiologically normal concentrations, A-beta tamps down a signal-boosting process that under certain conditions increases the odds that pyramidal nerve cells will transmit information they’ve received to other nerve cells down the line.

When incoming signals to the pyramidal tract build to high intensity, pyramidal cells adapt by becoming more inclined to fire than they normally are. This phenomenon, which neuroscientists call plasticity, is thought to underpin learning and memory. It ensures that volleys of high-intensity input — such as might accompany falling into a hole, burning one’s finger with a match, suddenly remembering where you buried the treasure or learning for the first time how to spell “cat” — are firmly stored in the brain’s memory vaults and more accessible to retrieval.

These intense bursts of incoming signals are the exception, not the rule. Pyramidal nerve cells constantly receive random beeps and burps from upstream nerve cells — effectively, noise in a highly complex, electrochemical signaling system. This calls for some quality control. Pyramidal cells are encouraged to ignore mere noise by another set of “wet blanket” nerve cells called interneurons. Like the proverbial spouse reading a newspaper at the kitchen table, interneurons continuously discourage pyramidal cells’ transmission of impulses to downstream nerve cells by steadily secreting an inhibitory substance — the molecular equivalent of yawning, eye-rolling and oft-muttered suggestions that this or that chatter is really not worth repeating to the world at large, so why not just shut up.

Passing along the message

But when the news is particularly significant, pyramidal cells squirt out their own “no, this is important, you shut up!” chemical — endocannabinoids — which bind to specialized receptors on the hippocampal interneurons, temporarily suppressing them and allowing impulses to continue coursing along the pyramidal cells to their follow-on peers.

A-beta is known to impair pyramidal-cell plasticity. But Madison’s research team showed for the first time how it does so. Small clusters consisting of just a few A-beta molecules render the interneuron’s endocannabinoid receptors powerless, leaving inhibition intact even in the face of important news and thus squashing plasticity.

While small A-beta clusters have been known for a decade to be toxic to nerve cells, this toxicity requires relatively long-term exposure, said Madison. The endocannabinoid-nullifying effect the new study revealed is much more transient. A possible physiological role for A-beta in the normal, healthy brain, he said, is that of supplying that organ’s sophisticated circuits with yet another, beneficial layer of discretion in processing information. Madison thinks this normal, everyday A-beta mechanism run wild may represent an entry point to the progressive and destructive stages of Alzheimer’s disease.

Exactly how A-beta blocks endocannabinoids’ action is not yet known. But, Madison’s group demonstrated, A-beta doesn’t stop them from reaching and binding to their receptors on interneurons. Rather, it interferes with something that binding ordinarily generates. (By analogy, turning the key in your car’s ignition switch won’t do much good if your battery is dead.)

Madison said it would be wildly off the mark to assume that, just because A-beta interferes with a valuable neurophysiological process mediated by endocannabinoids, smoking pot would be a great way to counter or prevent A-beta’s nefarious effects on memory and learning ability. Smoking or ingesting marijuana results in long-acting inhibition of interneurons by the herb’s active chemical, tetrahydrocannabinol. That is vastly different from short-acting endocannabinoid bursts precisely timed to occur only when a signal is truly worthy of attention.

“Endocannabinoids in the brain are very transient and act only when important inputs come in,” said Madison, who is also a member of the interdisciplinary Stanford Bio-X institute. “Exposure to marijuana over minutes or hours is different: more like enhancing everything indiscriminately, so you lose the filtering effect. It’s like listening to five radio stations at once.”

Besides, flooding the brain with external cannabinoids induces tolerance — it may reduce the number of endocannabinoid receptors on interneurons, impeding endocannabinoids’ ability to do their crucial job of opening the gates of learning and memory.

(Reblogged from neurosciencestuff)

neurosciencestuff:

Hippocampal activity during music listening exposes the memory-boosting power of music

For the first time the hippocampus—a brain structure crucial for creating long-lasting memories—has been observed to be active in response to recurring musical phrases while listening to music. Thus, the hippocampal involvement in long-term memory may be less specific than previously thought, indicating that short and long-term memory processes may depend on each other after all.

The study was conducted at the University of Jyväskylä and the AMI Center of Aalto University, by a group of researchers led by Academy Professor Petri Toiviainen, the Finnish Centre for Interdisciplinary Music Research (CIMR) at the University of Jyväskylä, and Dr. Elvira Brattico, Aalto University and the University of Helsinki. Results of the study were published in Cortex, a journal devoted to the study of the nervous system and behaviour.

“Our study basically shows an increase of activity in the medial temporal lobe areas—best known for being essential for long term memory—when musical motifs in the piece were repeated. This means that the lobe areas are engaged in the short-term recognition of musical phrases,” explains Iballa Burunat, the leading author of the study. Dr. Brattico adds: “Importantly, this hadn’t been observed before in music neuroscience.”

A fundamental highlight of the study is the use of a setting that is more natural than those traditionally employed in neuroscience: the participants’ only task was to attentively listen to an Argentinian tango from beginning to end. This kind of music provides well-defined, salient musical motifs that are easy to follow. They can be used to study recognition processes in the brain without having to resort to sound created in a lab. By using this more realistic approach, the researchers were able to identify brain areas involved in motif tracking without having to rely on the participants’ ability to self-report, which would have constrained the study of brain processes.

“We think that our novel method allowed us to uncover this phenomenon. In other words, the identified areas may also be related to the formation of a more permanent memory trace of a musical piece, enabled precisely by the very use of a real-life stimulus (the recording of a live performance) in a realistic situation where participants just listen to the music as their brain responses are recorded,” Iballa Burunat goes on to explain. Listening to the music from beginning to end may have imprinted the participants with a long lasting memory of the tune. This might not be expected were the participants exposed to a simpler stimulus in controlled conditions, as is the case in most studies in music and memory.

Although a real-life setting may be sufficient to trigger the involvement of the hippocampus, another explanation could lie in music’s capacity to elicit emotions. “We cannot ignore music’s emotional power which is thought to be crucial for the mnemonic power of music as to how and what we remember. There is evidence on the robust integration of music, memory and emotion—take for instance autobiographical memories. So it wouldn’t be surprising that the emotional content of the music may well have been a factor in triggering these limbic responses,” she continues. This makes sense, since the chosen musical piece by Astor Piazzolla was a tribute to his father after his sudden death, and so the main purpose of the piece was to be of a deeply emotional nature”. Certainly, the hippocampus—as part of the limbic system—is connected to neural circuitry involved in emotional behavior, and ongoing research suggests that emotional events seem to be more memorable than neutral ones. The authors emphasize that these results should motivate similar approaches to study verbal or visual short term memory by tracking the themes or repetitive structures of a given stimulus. Moreover, the study has implications for neurodegenerative diseases associated with hippocampal atrophy, like Alzheimer’s. “Music may positively affect patients if used wisely to stimulate their hippocampi, and thus their memory system,” Academy Professor Petri Toiviainen indicates. A better understanding of the link between music and memory could have widespread repercussions, leading to novel interventions to rehabilitate or improve the life quality of patients with neurodegenerative conditions.

(Reblogged from neurosciencestuff)

neurosciencestuff:

Study examines how brain ‘reboots’ itself to consciousness after anesthesia

One of the great mysteries of anesthesia is how patients can be temporarily rendered completely unresponsive during surgery and then wake up again, with all their memories and skills intact.

A new study by Dr. Andrew Hudson, an assistant professor of anesthesiology at the David Geffen School of Medicine at UCLA, and colleagues provides important clues about the processes used by structurally normal brains to navigate from unconsciousness back to consciousness. Their findings are currently available in the early online edition of Proceedings of the National Academy of Sciences.

Previous research has shown that the anesthetized brain is not “silent” under surgical levels of anesthesia but experiences certain patterns of activity, and it spontaneously changes its activity patterns over time, Hudson said.

For the current study, the research team recorded the brain’s electrical activity in a rodent model that had been administered the inhaled anesthesia isoflurane by placing electrodes in several brain areas associated with arousal and consciousness. They then slowly decreased the amount of anesthesia, as is done with patients in the operating room, monitoring how the electrical activity in the brain changed and looking for common activity patterns across all the study subjects.

The researchers found that the brain activity occurred in discrete clumps, or clusters, and that the brain did not jump between all of the clusters uniformly.

A small number of activity patterns consistently occurred in the anesthetized rodents, Hudson noted. The patterns depended on how much anesthesia the subject was receiving, and the brain would jump spontaneously from one activity pattern to another. A few activity patterns served as “hubs” on the way back to consciousness, connecting activity patterns consistent with deeper anesthesia to those observed under lighter anesthesia.

"Recovery from anesthesia, is not simply the result of the anesthetic ‘wearing off’ but also of the brain finding its way back through a maze of possible activity states to those that allow conscious experience," Hudson said. "Put simply, the brain reboots itself."

The study suggests a new way to think about the human brain under anesthesia and could encourage physicians to reexamine how they approach monitoring anesthesia in the operating room. Additionally, if the results are applicable to other disorders of consciousness — such as coma or minimally conscious states — doctors may be better able to predict functional recovery from brain injuries by looking at the spontaneously occurring jumps in brain activity.

In addition, this work provides some constraints for theories about how the brain leads to consciousness itself, Hudson said.

Going forward, the UCLA researchers will test other anesthetic agents to determine if they produce similar characteristic brain activity patterns with “hub” states. They also hope to better characterize how the brain jumps between patterns.

(Reblogged from neurosciencestuff)

arachnofiend:

lieutenantbites:

thank you science

this fly housefly is still high on the list of my favorite things

(Source: weirdinternet)

(Reblogged from slimydad)

neurosciencestuff:

(Image caption: Brain scans show high activity in the medial prefrontal cortex (top) and striatum (bottom) while playing a competitive game. UC Berkeley and UIUC researchers have now found genetic variations in dopamine-regulating genes in the prefrontal cortex and striatum associated with differences in belief learning and reinforcement learning, respectively. Credit: Ming Hsu)

Your genes affect your betting behavior

Investors and gamblers take note: your betting decisions and strategy are determined, in part, by your genes.

Researchers from the University of California, Berkeley, National University of Singapore and University of Illinois at Urbana-Champaign (UIUC) have shown that betting decisions in a simple competitive game are influenced by the specific variants of dopamine-regulating genes in a person’s brain.

Dopamine is a neurotransmitter – a chemical released by brain cells to signal other brain cells – that is a key part of the brain’s reward and pleasure-seeking system. Dopamine deficiency leads to Parkinson’s disease, while disruption of the dopamine network is linked to numerous psychiatric and neurodegenerative disorders, including schizophrenia, depression and dementia.

While previous studies have shown the important role of the neurotransmitter dopamine in social interactions, this is the first study tying these interactions to specific genes that govern dopamine functioning.

“This study shows that genes influence complex social behavior, in this case strategic behavior,” said study leader Ming Hsu, an assistant professor of marketing in UC Berkeley’s Haas School of Business and a member of the Helen Wills Neuroscience Institute. “We now have some clues about the neural mechanisms through which our genes affect behavior.”

The implications for business are potentially vast but unclear, Hsu said, though one possibility is training workforces to be more strategic. But the findings could significantly affect our understanding of diseases involving dopamine, such as schizophrenia, as well as disorders of social interaction, such as autism.

“When people talk about dopamine dysfunction, schizophrenia is one of the first diseases that come to mind,” Hsu said, noting that the disease involves a very complex pattern of social and decision making deficits. “To the degree that we can better understand ubiquitous social interactions in strategic settings, it may help us understand how to characterize and eventually treat the social deficits that are symptoms of diseases like schizophrenia.”

Hsu, UIUC graduate student Eric Set and their colleagues, including Richard P. Ebstein and Soo Hong Chew from the National University of Singapore, will publish their findings the week of June 16 in the online early edition of the Proceedings of the National Academy of Sciences.

Two brain areas involved in competition

Hsu established two years ago that when people engage in competitive social interactions, such as betting games, they primarily call upon two areas of the brain: the medial prefrontal cortex, which is the executive part of the brain, and the striatum, which deals with motivation and is crucial for learning to acquire rewards. Functional magnetic resonance imaging (fMRI) scans showed that people playing these games displayed intense activity in these areas.

“If you think of the brain as a computing machine, these are areas that take inputs, crank them through an algorithm, and translate them into behavioral outputs,” Hsu said. “What is really interesting about these areas is that both are innervated by neurons that use dopamine.”

Hsu and Set of UIUC’s Department of Economics wanted to determine which genes involved in regulating dopamine concentrations in these brain areas were associated with strategic thinking, so they enlisted as subjects a group of 217 undergraduates at the National University of Singapore, all of whom had had their genomes scanned for some 700,000 genetic variants. The researchers focused on only 143 variants within 12 genes involved in regulating dopamine. Some of the 12 are primarily involved in regulating dopamine in the prefrontal cortex, while others primarily regulate dopamine in the striatum.

The competition was a game called patent race, commonly used by social scientists to study social interactions. It involves one person betting, via computer, with an anonymous opponent.

“We know from brain imaging studies that when people compete against one another, they actually engage in two distinct types of learning processes,” Set said, referring to Hsu’s 2012 study. “One type involves learning purely from the consequences of your own actions, called reinforcement learning. The other is a bit more sophisticated, called belief learning, where people try to make a mental model of the other players, in order to anticipate and respond to their actions.”

Trial-and-error learning vs belief learning

Using a mathematical model of brain function during competitive social interactions, Hsu and Set correlated performance in reinforcement learning and belief learning with different variants or mutations of the 12 dopamine-related genes, and discovered a distinct difference.

They found that differences in belief learning – the degree to which players were able to anticipate and respond to the actions of others, or to imagine what their competitor is thinking and respond strategically – was associated with variation in three genes which primarily affect dopamine functioning in the medial prefrontal cortex.

In contrast, differences in trial-and-error reinforcement learning – how quickly they forget past experiences and how quickly they change strategy – was associated with variation in two genes that primarily affect striatal dopamine.

Hsu said that the findings correlate well with previous brain studies showing that the prefrontal cortex is involved in belief learning, while the striatum is involved in reinforcement learning.

“We were surprised by the degree of overlap, but it hints at the power of studying the neural and genetic levels under a single mathematical framework, which is only beginning in this area,” he said.

Hsu is currently collaborating with other scientists to correlate career achievements in older adults with genes and performance on competitive games, to see which brain regions and types of learning are most important for different kinds of success in life.

(Reblogged from neurosciencestuff)