Synchronized brain waves enable rapid learning

The human mind can rapidly absorb and analyze new information as it flits from thought to thought. These quickly changing brain states may be encoded by synchronization of brain waves across different brain regions, according to a new study from MIT neuroscientists.

The researchers found that as monkeys learn to categorize different patterns of dots, two brain areas involved in learning — the prefrontal cortex and the striatum — synchronize their brain waves to form new communication circuits.

“We’re seeing direct evidence for the interactions between these two systems during learning, which hasn’t been seen before. Category-learning results in new functional circuits between these two areas, and these functional circuits are rhythm-based, which is key because that’s a relatively new concept in systems neuroscience,” says Earl Miller, the Picower Professor of Neuroscience at MIT and senior author of the study, which appears in the June 12 issue of Neuron.

There are millions of neurons in the brain, each producing its own electrical signals. These combined signals generate oscillations known as brain waves, which can be measured by electroencephalography (EEG). The research team focused on EEG patterns from the prefrontal cortex —the seat of the brain’s executive control system — and the striatum, which controls habit formation.

The phenomenon of brain-wave synchronization likely precedes the changes in synapses, or connections between neurons, believed to underlie learning and long-term memory formation, Miller says. That process, known as synaptic plasticity, is too time-consuming to account for the human mind’s flexibility, he believes.

“If you can change your thoughts from moment to moment, you can’t be doing it by constantly making new connections and breaking them apart in your brain. Plasticity doesn’t happen on that kind of time scale,” says Miller, who is a member of MIT’s Picower Institute for Learning and Memory. “There’s got to be some way of dynamically establishing circuits to correspond to the thoughts we’re having in this moment, and then if we change our minds a moment later, those circuits break apart somehow. We think synchronized brain waves may be the way the brain does it.”

The paper’s lead author is former Picower Institute postdoc Evan Antzoulatos, who is now at the University of California at Davis.

Humming together

Miller’s lab has previously shown that during category-learning, neurons in the striatum become active early, followed by slower activation of neurons in the prefrontal cortex. “The striatum learns very simple things really quickly, and then its output trains the prefrontal cortex to gradually pick up on the bigger picture,” Miller says. “The striatum learns the pieces of the puzzle, and then the prefrontal cortex puts the pieces of the puzzle together.”

In the new study, the researchers wanted to investigate whether this activity pattern actually reflects communication between the prefrontal cortex and striatum, or if each region is working independently. To do this, they measured EEG signals as monkeys learned to assign patterns of dots into one of two categories.

At first, the animals were shown just two different examples, or “exemplars,” from each category. After each round, the number of exemplars was doubled. In the early stages, the animals could simply memorize which exemplars belonged to each category. However, the number of exemplars eventually became too large for the animals to memorize all of them, and they began to learn the general traits that characterized each category.

By the end of the experiment, when the researchers were showing 256 novel exemplars, the monkeys were able to categorize all of them correctly.

As the monkeys shifted from rote memorization to learning the categories, the researchers saw a corresponding shift in EEG patterns. Brain waves known as “beta bands,” produced independently by the prefrontal cortex and the striatum, began to synchronize with each other. This suggests that a communication circuit is forming between the two regions, Miller says.

“There is some unknown mechanism that allows these resonance patterns to form, and these circuits start humming together,” he says. “That humming may then foster subsequent long-term plasticity changes in the brain, so real anatomical circuits can form. But the first thing that happens is they start humming together.”

A little later, as an animal nailed down the two categories, two separate circuits formed between the striatum and prefrontal cortex, each corresponding to one of the categories.

“This is the first paper that provides data suggesting that coupling in the beta-band between prefrontal cortex and striatum may play a key role in category-formation. In addition to revealing a novel mechanism involved in category-learning, the results also contribute to better understanding of the significance of coupled beta-band oscillations in the brain,” says Andreas Engel, a professor of physiology at the University Medical Center Hamburg-Eppendorf in Germany.

“Expanding your knowledge”

Previous studies have shown that during cognitively demanding tasks, there is increased synchrony between the frontal cortex and visual cortex, but Miller’s lab is the first to show specific patterns of synchrony linked to specific thoughts.

Miller and Antzoulatos also showed that once the prefrontal cortex learns the categories and sends them to the striatum, they undergo further modification as new information comes in, allowing more expansive learning to take place. This iteration can occur over and over.

“That’s how you get the open-ended nature of human thought. You keep expanding your knowledge,” Miller says. “The prefrontal cortex learning the categories isn’t the end of the game. The cortex is learning these new categories and then forming circuits that can send the categories down to the striatum as if it’s just brand-new material for the brain to elaborate on.”

In follow-up studies, the researchers are now looking at how the brain learns more abstract categories, and how activity in the striatum and prefrontal cortex might reflect that type of abstraction.

Neural reward response may demonstrate why quitting smoking is harder for some

For some cigarette smokers, strategies to aid quitting work well, while for many others no method seems to work. Researchers have now identified an aspect of brain activity that helps to predict the effectiveness of a reward-based strategy as motivation to quit smoking.

The researchers observed the brains of nicotine-deprived smokers with functional magnetic resonance imaging (fMRI) and found that those who exhibited the weakest response to rewards were also the least willing to refrain from smoking, even when offered money to do so.

"We believe that our findings may help to explain why some smokers find it so difficult to quit smoking," said Stephen J. Wilson, assistant professor of psychology, Penn State. "Namely, potential sources of reinforcement for giving up smoking — for example, the prospect of saving money or improving health — may hold less value for some individuals and, accordingly, have less impact on their behavior."

The researchers recruited 44 smokers to examine striatal response to monetary reward in those expecting to smoke and in those who were not, and the subsequent willingness of the smokers to forego a cigarette in an effort to earn more money.

"The striatum is part of the so-called reward system in the brain," said Wilson. "It is the area of the brain that is important for motivation and goal-directed behavior — functions highly relevant to addiction."

The participants, who were between the ages of 18 and 45, all reported that they smoked at least 10 cigarettes per day for the past 12 months. They were instructed to abstain from smoking and from using any products containing nicotine for 12 hours prior to arriving for the experiment.

Each participant spent time in an fMRI scanner while playing a card-guessing game with the potential to win money. The participants were informed that they would have to wait approximately two hours, until the experiment was over, to smoke a cigarette. Partway through the card-guessing task, half of the participants were informed that there had been a mistake, and they would be allowed to smoke during a 50-minute break that would occur in another 16 minutes.

However, when the time came for the cigarette break, the participant was told that for every 5 minutes he or she did not smoke, he or she would receive $1 — with the potential to earn up to $10.

Wilson and his colleagues reported in a recent issue of Cognitive, Affective and Behavioral Neuroscience that they found that smokers who could not resist the temptation to smoke also showed weaker responses in the ventral striatum when offered monetary rewards while in the fMRI.

"Our results suggest that it may be possible to identify individuals prospectively by measuring how their brains respond to rewards, an observation that has significant conceptual and clinical implications," said Wilson. "For example, particularly ‘at-risk’ smokers could potentially be identified prior to a quit attempt and be provided with special interventions designed to increase their chances for success."

Does porn affect the brain? Scientists urge more study

Researchers found less grey matter in the brains of men who watched large amounts of sexually explicit material, according to a new study.

The research, which appeared Wednesday in the journal JAMA Psychiatry, could not determine if porn actually caused the brain to shrink however, and the authors called for additional study on the topic.

"Future studies should investigate the effects of pornography longitudinally or expose naive participants to pornography and investigate the causal effects over time," said researchers at the Max Planck Institute for Human Development in Berlin, Germany.

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The science behind rewards and punishment

In a neuroimaging study, a UQ psychologist has examined whether having allegiances with someone can affect feelings of empathy when punishing and rewarding others.

An international team of researchers, including Dr Pascal Molenberghs from UQ’s School of Psychology, mapped the brain activity while volunteers where giving electroshocks or money to members within or outside their group.

Dr Molenberghs said the research was a first of its kind and demonstrated that different neural responses were involved when delivering rewards or punishment to others.

“When we reward others we activate similar brain areas as when we receive rewards ourselves,” he said.

“However, these areas become more active when we reward members from our own group.

“Previous research has shown that we prefer to give more money to people from our own group, now we can actually show that this is associated with increased activation in reward-related brain areas, which is really exciting.

“The brain responses for punishing others directly revealed a different pattern of activation, one that was typically associated with receiving and seeing others in pain,” Dr Molenberghs said.

The study also found that personality traits influenced activity in these punishment-related brain areas.

People who did not care as much about others, showed less activation in these areas when shocking others, especially when they were shocking out-group members.

Co-author Professor Jean Decety, from the University of Chicago, said the results provided important insights into why some people don’t care as much when hurting others.

“Empathy and sympathy are necessary abilities to understand the potential consequences decisions will have on the feelings and emotions of others, even if the recipients of those decisions belong to a different group,” he said.

(Image caption: A series of three MRI images (top row) shows how dopamine concentrations change over time in the brain’s ventral striatum. Photocollage: Christine Daniloff/MIT, with images courtesy of the researchers)

Delving deep into the brain

MRI sensor allows neuroscientists to map neural activity with molecular precision

Launched in 2013, the national BRAIN Initiative aims to revolutionize our understanding of cognition by mapping the activity of every neuron in the human brain, revealing how brain circuits interact to create memories, learn new skills, and interpret the world around us.

Before that can happen, neuroscientists need new tools that will let them probe the brain more deeply and in greater detail, says Alan Jasanoff, an MIT associate professor of biological engineering. “There’s a general recognition that in order to understand the brain’s processes in comprehensive detail, we need ways to monitor neural function deep in the brain with spatial, temporal, and functional precision,” he says.

Jasanoff and colleagues have now taken a step toward that goal: They have established a technique that allows them to track neural communication in the brain over time, using magnetic resonance imaging (MRI) along with a specialized molecular sensor. This is the first time anyone has been able to map neural signals with high precision over large brain regions in living animals, offering a new window on brain function, says Jasanoff, who is also an associate member of MIT’s McGovern Institute for Brain Research.

His team used this molecular imaging approach, described in the May 1 online edition of Science, to study the neurotransmitter dopamine in a region called the ventral striatum, which is involved in motivation, reward, and reinforcement of behavior. In future studies, Jasanoff plans to combine dopamine imaging with functional MRI techniques that measure overall brain activity to gain a better understanding of how dopamine levels influence neural circuitry.

“We want to be able to relate dopamine signaling to other neural processes that are going on,” Jasanoff says. “We can look at different types of stimuli and try to understand what dopamine is doing in different brain regions and relate it to other measures of brain function.”

Tracking dopamine

Dopamine is one of many neurotransmitters that help neurons to communicate with each other over short distances. Much of the brain’s dopamine is produced by a structure called the ventral tegmental area (VTA). This dopamine travels through the mesolimbic pathway to the ventral striatum, where it combines with sensory information from other parts of the brain to reinforce behavior and help the brain learn new tasks and motor functions. This circuit also plays a major role in addiction.

To track dopamine’s role in neural communication, the researchers used an MRI sensor they had previously designed, consisting of an iron-containing protein that acts as a weak magnet. When the sensor binds to dopamine, its magnetic interactions with the surrounding tissue weaken, which dims the tissue’s MRI signal. This allows the researchers to see where in the brain dopamine is being released. The researchers also developed an algorithm that lets them calculate the precise amount of dopamine present in each fraction of a cubic millimeter of the ventral striatum.

After delivering the MRI sensor to the ventral striatum of rats, Jasanoff’s team electrically stimulated the mesolimbic pathway and was able to detect exactly where in the ventral striatum dopamine was released. An area known as the nucleus accumbens core, known to be one of the main targets of dopamine from the VTA, showed the highest levels. The researchers also saw that some dopamine is released in neighboring regions such as the ventral pallidum, which regulates motivation and emotions, and parts of the thalamus, which relays sensory and motor signals in the brain.

Each dopamine stimulation lasted for 16 seconds and the researchers took an MRI image every eight seconds, allowing them to track how dopamine levels changed as the neurotransmitter was released from cells and then disappeared. “We could divide up the map into different regions of interest and determine dynamics separately for each of those regions,” Jasanoff says.

He and his colleagues plan to build on this work by expanding their studies to other parts of the brain, including the areas most affected by Parkinson’s disease, which is caused by the death of dopamine-generating cells. Jasanoff’s lab is also working on sensors to track other neurotransmitters, allowing them to study interactions between neurotransmitters during different tasks.

Scientists Hunt Down Origin of Huntington’s Disease in the Brain and Provide Insights to Help Deliver Therapy

The gene mutation that causes Huntington’s disease appears in every cell in the body, yet kills only two types of brain cells. Why? UCLA scientists used a unique approach to switch the gene off in individual brain regions and zero in on those that play a role in causing the disease in mice.

Published in the April 28 online edition of Nature Medicine, the research sheds light on where Huntington’s starts in the brain. It also suggests new targets and routes for therapeutic drugs to slow the devastating disease, which strikes an estimated 35,000 Americans.

“From day one of conception, the mutant gene that causes Huntington’s appears everywhere in the body, including every cell in the brain,” explained X. William Yang, professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA. “Before we can develop effective strategies to treat the disorder, we need to first identify where it starts and how it ravages the brain.”

Huntington’s disease is passed from parent to child through a mutation in a gene called huntingtin. Scientists blame a genetic “stutter” — a repetitive stretch of DNA at one end of the altered gene—for the cell death and brain atrophy that progressively deprives patients of their ability to move, speak, eat and think clearly. No cure exists, and people with aggressive cases may die in as little as 10 years.

Huntington’s disease targets cells in two brain regions for destruction: the cortex and the striatum. Far more neurons die in the striatum—a cerebral region named after its striped layers of gray and white matter. But it’s unclear whether cortical neurons play a role in the disease, including striatal neurons’ malfunction and death.

Yang’s team used a unique approach to uncover where the mutant gene wreaks the most damage in the brain.

In 2008, Yang collaborated with co-first author Michelle Gray, a former UCLA postdoctoral researcher now at the University of Alabama, to engineer a mouse model for Huntington’s disease. The scientists inserted the entire human huntintin gene, including the stutter, into the mouse genome. As the animals’ brains atrophied, the mice developed motor and psychiatric-like problems similar to the human patients.

In the current study, Yang and Nan Wang, co-first author and UCLA postdoctoral researcher, took the model one step further. They integrated a “genetic scissors” that snipped off the stutter and shut down the defective gene—first in the cortical neurons, then the striatal neurons and finally in both sets of cells. In each case, they measured how the mutant gene influenced disease development in the cells and affected the animals’ brain atrophy, motor and psychiatric-like symptoms.

“The genetic scissors gave us the power to study the role of any cell type in Huntington’s,” said Wang. “We were surprised to learn that cortical neurons play a key role in initiating aspects of the disease in the brain.”

The UCLA team discovered that reducing huntingtin in the cortex partially improved the animals’ symptoms. More importantly, shutting down mutant huntingtin in both the cortical and striatal neurons—while leaving it untouched in the rest of the brain— corrected every symptom they measured in the mice, including motor and psychiatric-like behavioral impairment and brain atrophy.

“We have evidence that the gene mutation highjacks communication between the cortical and striatal neurons,” explained Yang. “Reducing the defective gene in the cortex normalized this communication and helped lessen the disease’s impact on the striatum.”

“Our research helps to shed lights on an age-old question in the field,” he added. “Where does Huntington’s disease start? Equally important, our findings provide crucial insights on where to target therapies to reduce mutant gene levels in the brain—we should target both cortical and striatal neurons.”

Some of the current experimental therapies can be delivered only to limited brain areas, because their properties do not allow them to broadly spread in the brain.

The UCLA team’s next step will be to study how mutant huntingtin affects cortical and striatal neurons’ function and communication, and to identify therapeutic targets that may normalize cellular miscommunication to help slow progression of the disease.

Scientists Identify Critical New Protein Complex Involved in Learning and Memory

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified a protein complex that plays a critical but previously unknown role in learning and memory formation.

The study, which showed a novel role for a protein known as RGS7, was published April 22, 2014 in the journal eLife, a publisher supported by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

“This is a critical building block that regulates a fundamental process—memory,” said Kirill Martemyanov, a TSRI associate professor who led the study. “Now that we know about this important new player, it offers a unique therapeutic window if we can find a way to enhance its function.”

The team looked at RGS7 in the hippocampus, a small part of the brain that helps turn short-term memory in long-term memory.

The scientists found the RGS7 protein works in concert with another protein, R7BP, to regulate a key signaling cascade that is increasingly seen as a critical to cognitive development. The cascade involves the neurotransmitter GABA, which binds to the GABA_b receptor and opens inhibitory channels known as GIRKs in the cell membrane. This process ultimately makes it more difficult for a nerve cell to fire.

This process turned out to be critical to normal functioning, as the research showed mice lacking RGS7 exhibited deficits in learning and memory.

Martemyanov believes the findings could ultimately have broad therapeutic application. “GIRK channels are implicated in a range of neuropsychiatric conditions, including drug addiction and Down’s syndrome, that result from a disproportionate increase in neuronal inhibition as a result of greater mobilization of these channels,” he said. ^“Now that we know the identity of the critical modulator of GIRK channels we can try to find a way to increase its power with the hopes of reducing the inhibitory overdrive, and that might potentially alleviate some of the  disruptions seen in Down’s syndrome. It is possible that similar strategies might apply for dealing with addiction, where adaptations in the GABAb-GIRK pathway play a significant role.”

Targeting the RGS7 protein could allow for better therapeutic outcomes with fewer side effects because it allows for fine tuning of the signaling, according to Olga Ostrovskaya, the first author of the study and a member of Martemyanov’s lab, who sees many ways to follow up on the findings.

“We’re looking into how RGS7 is involved in neural circuitry and functions tied to the striatum, another part of the brain responsible for procedural memory, mood disorders, motivation and addiction,” Ostrovskaya said. “We may uncover the RGS7 regulation of other signaling complexes that may be very different from those in hippocampus.”

Promise of a bonus counter-productive in brains with high dopamine levels

Some people perform better and others worse when promised a high bonus. Brain researcher Esther Aarts of the Donders Institute in Nijmegen has demonstrated for the first time that the amount of dopamine in the brain plays a role in this regard. The journal Psychological Science will publish the results on February 13.

It has been known for some time that not everyone performs better after being promised a bonus. Scientists have published contradictory results regarding the cause. The study by Esther Aarts now shows that the differences can be explained by differences in the level of dopamine in the brain. People with a high level of dopamine in a specific brain region – the striatum – perform worse after a being promised a bonus, and people with a low level of dopamine in the same area perform better. Aarts used a PET (Positron Emission Tomography) scanner to examine the amount of dopamine in the brains of subjects. She conducted this research in Berkeley, California (USA), where she worked as a post-doctoral researcher for two years.

Overdose of dopamine
The promise of a bonus provides an additional spurt of the ‘motivation substance’ dopamine in the brain. ‘For people who usually have high levels of dopamine, the promise of a bonus causes a type of dopamine overdose in the striatum’, explains Aarts. ‘Our test subjects were asked to perform a task that required considerable concentration. An overdose of dopamine makes this difficult. People who usually have less dopamine are less likely to have an overdose of dopamine, and they therefore perform better after being promised a bonus.’

Concentration desired
Test subjects performed a computer task that elicited conflicting reactions, therefore requiring considerable concentration: an arrow appears on the screen, pointing either left or right. The word ‘left’ or ‘right’ is written in the middle of the arrow. Subjects were asked to ignore the direction indicated by the arrow and mention only the direction described by the word. For half of the attempts, a bonus of 15 cents was promised for a correct answer. In the other half, the subjects received only 1 cent for each correct answer. People who usually have a high level of dopamine performed better in the low-pay condition than they did in the high-pay condition. The reverse was observed for people with low levels of dopamine: they performed better with high rewards than they did with low rewards.

Flexibility or focus
‘This knowledge could make it possible to apply bonuses more effectively, but it would require observing the standard dopamine levels of people, as well as the nature of the task that they must perform’, reports Aarts. ‘It makes quite a difference whether the task is flexible and creative or whether it requires a great deal of focus. Our research shows how people perform on tasks that require considerable focus’. Given the high cost of PET scans, Aarts is now looking for easier ways of measuring dopamine levels. ‘I hope to be able to relate dopamine levels to scores on questionnaires. In the future, this might eliminate the need for PET scans for determining the quantity of dopamine in the brain’.

This is how your brain tells time

Did you make it to work on time this morning? Go ahead and thank the traffic gods, but also take a moment to thank your brain. The brain’s impressively accurate internal clock allows us to detect the passage of time, a skill essential for many critical daily functions. Without the ability to track elapsed time, our morning shower could continue indefinitely. Without that nagging feeling to remind us we’ve been driving too long, we might easily miss our exit.

But how does the brain generate this finely tuned mental clock? Neuroscientists believe that we have distinct neural systems for processing different types of time, for example, to maintain a circadian rhythm, to control the timing of fine body movements, and for conscious awareness of time passage. Until recently, most neuroscientists believed that this latter type of temporal processing – the kind that alerts you when you’ve lingered over breakfast for too long – is supported by a single brain system. However, emerging research indicates that the model of a single neural clock might be too simplistic. A new study, recently published in the Journal of Neuroscience by neuroscientists at the University of California, Irvine, reveals that the brain may in fact have a second method for sensing elapsed time. What’s more, the authors propose that this second internal clock not only works in parallel with our primary neural clock, but may even compete with it.

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Drug Reduces Brain Changes, Motor Deficits Associated With Huntington’s Disease

A drug that acts like a growth-promoting protein in the brain reduces degeneration and motor deficits associated with Huntington’s disease in two mouse models of the disorder, according to a study appearing November 27 in The Journal of Neuroscience. The findings add to a growing body of evidence that protecting or boosting neurotrophins — the molecules that support the survival and function of nerve cells — may slow the progression of Huntington’s disease and other neurodegenerative disorders.

Huntington’s disease is a brain disorder characterized by the emergence of decreased motor, cognitive, and psychiatric abilities, most commonly appearing in the mid-30s and 40s. The disease is caused by a genetic mutation that leads to abnormal clumps of protein in the brain, eventually resulting in the atrophy and death of nerve cells. While there are drugs to alleviate some symptoms of the disease, there are currently no therapies to delay the onset or slow its progression.

Previous studies of people with Huntington’s disease point to a link between low levels of a neurotrophin called brain-derived neurotrophic factor (BDNF) and symptoms of the disorder. In the current study, Frank Longo, MD, PhD, and others at Stanford University, tested LM22A-4, a drug that specifically binds to and activates the BDNF receptor TrkB on nerve cells, in mice that model the disorder. They found LM22A-4 reduces abnormal protein accumulation, delays nerve cell degeneration, and improves motor skills in the animals. The findings support other recent rodent studies that showed drugs that enhance the action of BDNF can reduce brain changes and symptoms of Huntington’s disease.

“These results strongly suggest that drugs that act, in part, like BDNF could be effective therapeutics for treating Huntington’s disease and other neurodegenerative conditions,” Longo said. 

How quickly the symptoms of Huntington’s disease progress in people vary greatly. Longo’s group examined the effects of LM22A-4 treatment in mice that were predisposed to develop symptoms of Huntington’s disease rapidly (within weeks) or gradually (within months). LM22A-4 treatment reduced the accumulation of abnormal proteins in the striatum and cortex — brain regions affected in Huntington’s disease. Motor behaviors (downward climbing and grip strength) also improved in the mice that received LM22A-4 treatments daily. “The search for treatments that slow the progression of neurodegenerative diseases has gradually shifted from ameliorating symptoms to finding agents that reduce the progression of the disease,” said Gary Lynch, PhD, who studies neurodegeneration at the University of California, Irvine, and was not involved with this study. “Given that this drug is clinically plausible, these results open up exciting possibilities for treating a devastating neurodegenerative disease,” he added.