Posts tagged nucleus accumbens
Articles and news from the latest research reports.
(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)
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.
Deep Brain Stimulation for Obsessive-Compulsive Disorder Releases Dopamine in the Brain
Some have characterized dopamine as the elixir of pleasure because so many rewarding stimuli – food, drugs, sex, exercise – trigger its release in the brain. However, more than a decade of research indicates that when drug use becomes compulsive, the related dopamine release becomes deficient in the striatum, a brain region that is involved in reward and behavioral control.
New research now published in Biological Psychiatry from the Academic Medical Center in Amsterdam suggests that dopamine release is increased in obsessive-compulsive disorder (OCD) and may be normalized by the therapeutic application of deep brain stimulation (DBS).
To conduct the study, the authors recruited clinically stable outpatients with OCD who had been receiving DBS therapy for greater than one year. The patients then underwent three single photon emission computerized tomography (SPECT) imaging scans to measure dopamine availability in the brain.
In order to evaluate the effect of DBS, these scans were conducted during chronic DBS, 8 days after DBS had been discontinued, and then after DBS was resumed. Designing the study in this manner also allowed the researchers to measure the relationship between dopamine availability and symptoms.
During the chronic DBS phase, patients showed increased striatal dopamine release compared to healthy volunteers. When DBS was turned off, patients showed worsening of symptoms and reduced dopamine release, which was reversed within one hour by the resumption of DBS. This observation suggests that enhancing striatal dopamine signaling may have some therapeutic effects for treatment-resistant symptoms of OCD.
First author Dr. Martijn Figee further explained, “DBS of the nucleus accumbens decreased central dopamine D2 receptor binding potential indicative of DBS-induced dopamine release. As dopamine is important for reward-motivated behaviors, these changes may explain why DBS is able to restore healthy behavior in patients suffering from OCD, but potentially other disorders involving compulsive behaviors, such as eating disorders or addiction.”
The patients selected for participation in this study had previously been non-responsive to traditional pharmacological therapies that target the dopamine system. These findings suggest that the effectiveness of DBS for OCD may be related to its ability to compensate for an underlying dysfunction of the dopaminergic system. The DBS-related stimulatory increase in dopamine appears to aid patients by improving their control over obsessive-compulsive behaviors.
“It is exciting to see circuit-based DBS linked to molecular brain imaging. This is a strategy that may shed light into the mechanisms through which this treatment can produce positive clinical change,” said Dr. John Krystal, Editor of Biological Psychiatry.
He also noted, “It would be interesting to know whether the patients who do respond to dopamine-blocking antipsychotic medications commonly prescribed for OCD symptoms have a different underlying disturbance in dopamine function than the patients enrolled in this study who failed to respond to these medications. Nonetheless, the findings of this study raise the possibility that some deficits in dopamine signaling in the brain that might be targeted by novel treatments may prevent adequate response to conventional treatments for this disorder.”
(Image: © Thom Graves)
Genetic Pre-Disposition Toward Exercise and Mental Development May be Linked
University of Missouri researchers have previously shown that a genetic pre-disposition to be more or less motivated to exercise exists. In a new study, Frank Booth, a professor in the MU College of Veterinary Medicine, has found a potential link between the genetic pre-disposition for high levels of exercise motivation and the speed at which mental maturation occurs.
For his study, Booth selectively bred rats that exhibited traits of either extreme activity or extreme laziness. Booth then put the rats in cages with running wheels and measured how much each rat willingly ran on their wheels during a six-day period. He then bred the top 26 runners with each other and bred the 26 rats that ran the least with each other. They repeated this process through 10 generations and found that the line of running rats chose to run 10 times more than the line of “lazy” rats.
Booth studied the brains of the rats and found much higher levels of neural maturation in the brains of the active rats than in the brains of the lazy rats.
“We looked at the part of the brain known as the ‘grand central station,’ or the hub where the brain is constantly sending and receiving signals,” Booth said. “We found a big difference between the amount of molecules present in the brains of active rats compared to the brains of lazy rats. This suggests that the active rats were experiencing faster development of neural pathways than the lazy rats.”
Booth says these findings may suggest a link between the genes responsible for exercise motivation and the genes responsible for mental development. He also says this research hints that exercising at a young age could help develop more neural pathways for motivation to be physically active.
“This study illustrates a potentially important link between exercise and the development of these neural pathways,” Booth said. “Ultimately, this could show the benefits of exercise for mental development in humans, especially young children with constantly growing brains.”
(Source: munews.missouri.edu)
Casual marijuana use linked to brain abnormalities in students
Young adults who used marijuana only recreationally showed significant abnormalities in two key brain regions that are important in emotion and motivation, scientists report. The study was a collaboration between Northwestern Medicine® and Massachusetts General Hospital/Harvard Medical School.
This is the first study to show casual use of marijuana is related to major brain changes. It showed the degree of brain abnormalities in these regions is directly related to the number of joints a person smoked per week. The more joints a person smoked, the more abnormal the shape, volume and density of the brain regions.
"This study raises a strong challenge to the idea that casual marijuana use isn’t associated with bad consequences," said corresponding and co-senior study author Hans Breiter, M.D. He is a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital.
"Some of these people only used marijuana to get high once or twice a week," Breiter said. "People think a little recreational use shouldn’t cause a problem, if someone is doing OK with work or school. Our data directly says this is not the case."
The study will be published April 16 in the Journal of Neuroscience.
Scientists examined the nucleus accumbens and the amygdala — key regions for emotion and motivation, and associated with addiction — in the brains of casual marijuana users and non-users. Researchers analyzed three measures: volume, shape and density of grey matter (i.e., where most cells are located in brain tissue) to obtain a comprehensive view of how each region was affected.
Both these regions in recreational pot users were abnormally altered for at least two of these structural measures. The degree of those alterations was directly related to how much marijuana the subjects used.
Of particular note, the nucleus acccumbens was abnormally large, and its alteration in size, shape and density was directly related to how many joints an individual smoked.
"One unique strength of this study is that we looked at the nucleus accumbens in three different ways to get a detailed and consistent picture of the problem," said lead author Jodi Gilman, a researcher in the Massachusetts General Center for Addiction Medicine and an instructor in psychology at Harvard Medical School. "It allows a more nuanced picture of the results."
Examining the three different measures also was important because no single measure is the gold standard. Some abnormalities may be more detectable using one type of neuroimaging analysis method than another. Breiter said the three measures provide a multidimensional view when integrated together for evaluating the effects of marijuana on the brain.
"These are core, fundamental structures of the brain," said co-senior study author Anne Blood, director of the Mood and Motor Control Laboratory at Massachusetts General and assistant professor of psychiatry at Harvard Medical School. "They form the basis for how you assess positive and negative features about things in the environment and make decisions about them."
Through different methods of neuroimaging, scientists examined the brains of young adults, ages 18 to 25, from Boston-area colleges; 20 who smoked marijuana and 20 who didn’t. Each group had nine males and 11 females. The users underwent a psychiatric interview to confirm they were not dependent on marijuana. They did not meet criteria for abuse of any other illegal drugs during their lifetime.
The changes in brain structures indicate the marijuana users’ brains are adapting to low-level exposure to marijuana, the scientists said.
The study results fit with animal studies that show when rats are given tetrahydrocannabinol (THC) their brains rewire and form many new connections. THC is the mind-altering ingredient found in marijuana.
"It may be that we’re seeing a type of drug learning in the brain," Gilman said. "We think when people are in the process of becoming addicted, their brains form these new connections."
In animals, these new connections indicate the brain is adapting to the unnatural level of reward and stimulation from marijuana. These connections make other natural rewards less satisfying.
"Drugs of abuse can cause more dopamine release than natural rewards like food, sex and social interaction," Gilman said. "In those you also get a burst of dopamine but not as much as in many drugs of abuse. That is why drugs take on so much salience, and everything else loses its importance."
The brain changes suggest that structural changes to the brain are an important early result of casual drug use, Breiter said. “Further work, including longitudinal studies, is needed to determine if these findings can be linked to animal studies showing marijuana can be a gateway drug for stronger substances,” he noted.
Because the study was retrospective, researchers did not know the THC content of the marijuana, which can range from 5 to 9 percent or even higher in the currently available drug. The THC content is much higher today than the marijuana during the 1960s and 1970s, which was often about 1 to 3 percent, Gilman said.
Marijuana is the most commonly used illicit drug in the U.S. with an estimated 15.2 million users, the study reports, based on the National Survey on Drug Use and Health in 2008. The drug’s use is increasing among adolescents and young adults, partially due to society’s changing beliefs about cannabis use and its legal status.
A recent Northwestern study showed chronic use of marijuana was linked to brain abnormalities. “With the findings of these two papers,” Breiter said, “I’ve developed a severe worry about whether we should be allowing anybody under age 30 to use pot unless they have a terminal illness and need it for pain.”
(Source: eurekalert.org)
(Image caption: A cross-section of mouse brain in the nucleus accumbens, a region of the brain known to be involved in reward and motivation, taken by a fluorescence microscope. Blue corresponds to cell nuclei, and green to fluorescence emitted by a green-fluorescent protein (NdT: the original incorrectly states “green fluorescente protein”) that identifies neurons having received the virus that can genetically abolish the expression of lipoprotein lipase protein. Credit: ©Serge Luquet, CNRS/Université Paris Diderot)
Obesity: are lipids hard drugs for the brain?
Why can we get up for a piece of chocolate, but never because we fancy a carrot? Serge Luquet’s team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) has demonstrated part of the answer: triglycerides, fatty substances from food, may act in our brains directly on the reward circuit, the same circuit that is involved in drug addiction. These results, published on April 15, 2014 in Molecular Psychiatry, show a strong link in mice between fluctuations in triglyceride concentration and brain reward development. Identifying the action of nutritional lipids on motivation and the search for pleasure in dietary intake will help us better understand the causes of some compulsive behaviors and obesity.
Though the act of eating responds to a biological need, it is also an essential cultural and social function in our modern societies. Meals are generally associated with a strong notion of pleasure, a feeling that pushes us towards food. Sometimes this is dangerous: 2.8 million people worldwide die from the consequences of obesity each year. Fundamentally, obesity is caused by imbalance between calories consumed and expended. A sedentary life combined with an abundance of sugary, fatty foods provides fertile ground for this disease.
The body uses sugars and fats as energy sources. The brain only consumes glucose. So why do we find an enzyme that can decompose triglycerides, lipids that come in particular from food, at its core, at the heart of the reward mechanism? A team at the “Biologie Fonctionnelle et Adaptative” laboratory (CNRS/Université Paris Diderot) led by Serge Luquet, a CNRS researcher, has tackled this fundamental question.
If they have the choice, normal behavior in mice is to prefer a high-fat diet to simpler foods. To simulate the action of a good meal, researchers have developed an approach that allows small quantities of lipids to be injected directly into the brains of mice. They observed that an infusion of triglycerides in the brain reduces the animal’s motivation to press a lever to obtain a food reward. It also reduces physical activity by half. What is more, an “infused” mouse balances its diet between the two food sources offered (high-fat foods and simpler foods).
To ensure that it is indeed the lipids injected that change the mice’s behavior, these Parisian scientists made sure that the lipids could not be detected by the animal’s brain any longer. They managed to remove the specific enzyme for triglycerides by silencing its coding gene, but only at the heart of the reward mechanism. The animal then shows increased motivation to obtain a reward, and if given the choice, consumes much richer food than average. This work echoes the previous work by their colleagues: reducing this enzyme in the hippocampus causes obesity.
Paradoxically, with obesity, blood (and therefore brain) triglyceride levels are higher than average. So obesity is often associated with overconsumption of sugary, fatty foods. The researchers explain this: with long-lasting high exposure to triglycerides, mice always display lower locomotor activity. By contrast, food rewards are still attractive! The ideal conditions for weight gain are therefore in place. At high triglyceride contents, the brain adapts to obtain its reward, similar to the mechanisms observed when people consume drugs.
This work, financed in particular by CNRS and ANR, indicate for the first time that triglycerides from food may act as hard drugs in the brain, on the reward system, controlling the motivational and pleasureseeking component of food intake.
Ketamine acts as antidepressant by boosting serotonin
Ketamine is a potent anesthetic employed in human and veterinary medicine, and sometimes used illegally as a recreational drug. The drug is also a promising candidate for the fast treatment of depression in patients who do not respond to other medications. New research from the RIKEN Center for Life Science Technologies in Japan demonstrates using PET imaging studies on macaque monkeys that ketamine increases the activity of serotoninergic neurons in the brain areas regulating motivation. The researchers conclude that ketamine’s action on serotonin, often called the “feel-good neurotransmitter”, may explain its antidepressant action in humans.
The study, published today in the journal Translational Psychiatry demonstrates that Positron Emission Tomography (PET) molecular imaging studies may be useful in the diagnosis of major depressive disorder in humans, as well as the development of new antidepressants.
Ketamine has recently been shown to have an antidepressant action with short onset and long-term duration in patients suffering from treatment-resistant major depressive disorder, who do not respond to standard medications such as serotonin reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants. However, the mechanisms underlying ketamine’s action on the depressive brain have remained unclear.
To understand the effects of ketamine on the serotonergic system in the brain, Dr. Hajime Yamanaka and Dr. Hirotaka Onoe, who has pioneered PET imaging on conscious non-human primates, together with an international team, performed a PET study on rhesus monkeys.
The team performed PET imaging studies on four rhesus monkeys with two tracer molecules related to serotonin (5-HT) that bind highly selectively to the serotonin 1B receptor 5-HT1B and the serotonin transporter SERT.
From the analysis of the 3 dimensional images generated by the PET scans, the researchers could infer that ketamine induces an increase in the binding of serotonin to its receptor 5-HT1B in the nucleus accumbens and the ventral pallidum, but a decrease in binding to its transporter SERT in these brain regions. The nucleus accumbens and the ventral pallidum are brain regions associated with motivation and both have been shown to be involved in depression.
In addition, the researchers demonstrate that treatment with NBQX, a drug known to block the anti-depressive effect of ketamine in rodents by selectively blocking the glutamate AMPA receptor, cancels the action of ketamine on 5-HT1B but not on SERT binding.
Taken together, these findings indicate that ketamine may act as an antidepressant by increasing the expression of postsynaptic 5-HT1B receptors, and that this process is mediated by the glutamate AMPA receptor.
Silencing Synapses: Research Team Finds Hope for Pharmacological Solution to Cocaine Addiction
Imagine kicking a cocaine addiction by simply popping a pill that alters the way your brain processes chemical addiction. New research from the University of Pittsburgh suggests that a method of biologically manipulating certain neurocircuits could lead to a pharmacological approach that would weaken post-withdrawal cocaine cravings. The findings have been published in Nature Neuroscience.
Researchers led by Pitt neuroscience professor Yan Dong used rat models to examine the effects of cocaine addiction and withdrawal on nerve cells in the nucleus accumbens, a small region in the brain that is commonly associated with reward, emotion, motivation, and addiction. Specifically, they investigated the roles of synapses—the structures at the ends of nerve cells that relay signals.
When an individual uses cocaine, some immature synapses are generated, which are called “silent synapses” because they send few signals under normal physiological conditions. After that individual quits using cocaine, these “silent synapses” go through a maturation phase and acquire the ability to send signals. Once they can send signals, the synapses will send craving signals for cocaine if the individual is exposed to cues that previously led him or her to use the drug.
The researchers hypothesized that if they could reverse the maturation of the synapses, the synapses would remain silent, thus rendering them unable to send craving signals. They examined a chemical receptor known as CP-AMPAR that is essential for the maturation of the synapses. In their experiments, the synapses reverted to their silent states when the receptor was removed.
“Reversing the maturation process prevents the intensification process of cocaine craving,” said Dong, the study’s corresponding author and assistant professor of neuroscience in Pitt’s Kenneth P. Dietrich School of Arts and Sciences. “We are now developing strategies to maintain the ‘reversal’ effects. Our goal is to develop biological and pharmacological strategies to produce long-lasting de-maturation of cocaine-generated silent synapses.”
(Source: news.pitt.edu)
Predicting Who Will Have Chronic Pain
Abnormalities in brain axons predispose people to chronic back pain after injury
Abnormalities in the structure of the brain predispose people to develop chronic pain after a lower back injury, according to new Northwestern Medicine® research. The findings could lead to changes in the way physicians treat patients’ pain.
Most scientists and clinicians have assumed chronic back pain stems from the site of the original injury.
“We’ve found the pain is triggered by these irregularities in the brain,” said A. Vania Apkarian, senior author of the study and a professor of physiology at Northwestern University Feinberg School of Medicine. “We’ve shown abnormalities in brain structure connections may be enough to push someone to develop chronic pain once they have an injury.”
Based on MRI brain scans of people who had a new lower back injury, Northwestern scientists could predict with about 85 percent accuracy which patients’ pain would persist. The predictor was a specific irregularity or marker the scientists identified in the axons, pathways in the brain’s white matter that connect brain cells so they can communicate with each other.
The findings provide a new view of treating chronic pain, which affects nearly 100 million Americans and costs up to $635 billion a year to treat.
“We think the people who are vulnerable need to be treated aggressively with medication early on to prevent their pain from becoming chronic,” Apkarian said. “Last year, we showed people who take medication early on had a better chance of recovering. Medication does help.” Apkarian also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The research, funded by the National Institutes of Health, was published Sept. 16 in the journal Pain.
Brain abnormalities have been observed in other long-term chronic pain conditions. Apkarian’s study is the first to show brain structure abnormalities are a marker of a predisposition to the chronic pain, not a result of living with it.
The lead author of the study is Ali Mansour, M.D., formerly a postdoctoral fellow in Apkarian’s lab.
Apkarian’s research focuses on the relationship between chronic pain and the brain. One of his previous studies showed chronic pain patients lose gray matter volume over time.
Chronic pain is one of the most expensive health care conditions in the U.S. and takes an enormous toll on quality of life, yet there still is not a scientifically validated therapy for the condition. Lower back pain represents 28 percent of all causes of pain in the U.S.; about 23 percent of these patients suffer long-term pain.
The abnormalities identified in the study were found in multiple white matter axon bundles, some surrounding the nucleus accumbens and medial prefrontal cortex, two brain regions involved in processing emotion and pain. Last year, the Apkarian group showed that the physiological properties of these two regions identify which patients will persist with back pain. The new results identify a pre-existing culprit for these physiological responses to the injury.
“The brain abnormalities exist in the general population, but only those people with a back injury go on to develop the chronic pain,” Apkarian said.
For the study, Apkarian and his colleagues scanned the brains of 46 people who had an episode of lower back pain for at least four weeks and had not experienced any pain for at least one year before that. Their pain had to be rated at least five out of 10 on a pain scale for them to be included in the study.
Scientists followed the patients for a year, scanning their brains at the onset of study and one year later. After a year about half of them had improved, regardless of whether they took anything to treat the pain, and half of them continued to have pain. Those with the persistent pain had the same structural abnormalities in their white matter at the onset of the injury and after one year.
“The abnormality makes them vulnerable and predisposes them to enhanced emotional learning that then amplifies the pain and makes it more emotionally significant,” Apkarian said.
“Pain is becoming an enormous burden on the public,” said Linda Porter, the pain policy advisor at National Institute of Neurological Disorders and Stroke (NINDS) and a leader of the National Institutes of Health (NIH) Pain Consortium. “The U.S. government recently outlined steps to reduce the future burden of pain through broad-ranging efforts, including enhanced research. This study is a good example of the kind of innovative research we hope will reduce chronic pain, which affects a huge portion of the population.”
(Image: Shutterstock)
'Love hormone' may play wider role in social interaction than previously thought
Researchers at the Stanford University School of Medicine have shown that oxytocin — often referred to as “the love hormone” because of its importance in the formation and maintenance of strong mother-child and sexual attachments — is involved in a broader range of social interactions than previously understood.
The discovery may have implications for neurological disorders such as autism, as well as for scientific conceptions of our evolutionary heritage.
Scientists estimate that the advent of social living preceded the emergence of pair living by 35 million years. The new study suggests that oxytocin’s role in one-on-one bonding probably evolved from an existing, broader affinity for group living.
Oxytocin is the focus of intense scrutiny for its apparent roles in establishing trust between people, and has been administered to children with autism spectrum disorders in clinical trials. The new study, published Sept. 12 in Nature, pinpoints a unique way in which oxytocin alters activity in a part of the brain that is crucial to experiencing the pleasant sensation neuroscientists call “reward.” The findings not only provide validity for ongoing trials of oxytocin in autistic patients, but also suggest possible new treatments for neuropsychiatric conditions in which social activity is impaired.
"People with autism-spectrum disorders may not experience the normal reward the rest of us all get from being with our friends," said Robert Malenka, MD, PhD, the study’s senior author. "For them, social interactions can be downright painful. So we asked, what in the brain makes you enjoy hanging out with your buddies?"
Some genetic evidence suggests the awkward social interaction that is a hallmark of autism-spectrum disorders may be at least in part oxytocin-related. Certain variations in the gene that encodes the oxytocin receptor — a cell-surface protein that senses the substance’s presence — are associated with increased autism risk.
Malenka, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences, has spent the better part of two decades studying the reward system — a network of interconnected brain regions responsible for our sensation of pleasure in response to a variety of activities such as finding or eating food when we’re hungry, sleeping when we’re tired, having sex or acquiring a mate, or, in a pathological twist, taking addictive drugs. The reward system has evolved to reinforce behaviors that promote our survival, he said.
For this study, Malenka and lead author Gül Dölen, MD, PhD, a postdoctoral scholar in his group with over 10 years of autism-research expertise, teamed up to untangle the complicated neurophysiological underpinnings of oxytocin’s role in social interactions. They focused on biochemical events taking place in a brain region called the nucleus accumbens, known for its centrality to the reward system.
In the 1970s, biologists learned that in prairie voles, which mate for life, the nucleus accumbens is replete with oxytocin receptors. Disrupting the binding of oxytocin to these receptors impaired prairie voles’ monogamous behavior. In many other species that are not monogamous by nature, such as mountain voles and common mice, the nucleus accumbens appeared to lack those receptors.
"From this observation sprang a dogma that pair bonding is a special type of social behavior tied to the presence of oxytocin receptors in the nucleus accumbens. But what’s driving the more common group behaviors that all mammals engage in — cooperation, altruism or just playing around — remained mysterious, since these oxytocin receptors were supposedly absent in the nucleus accumbens of most social animals," said Dölen.
The new discovery shows that mice do indeed have oxytocin receptors at a key location in the nucleus accumbens and, importantly, that blocking oxytocin’s activity there significantly diminishes these animals’ appetite for socializing. Dölen, Malenka and their Stanford colleagues also identified, for the first time, the nerve tract that secretes oxytocin in the region, and they pinpointed the effects of oxytocin release on other nerve tracts projecting to this area.
Mice can squeak, but they can’t talk, Malenka noted. “You can’t ask a mouse, ‘Hey, did hanging out with your buddies a while ago make you happier?’” So, to explore the social-interaction effects of oxytocin activity in the nucleus accumbens, the investigators used a standard measure called the conditioned place preference test.
"It’s very simple," Malenka said. "You like to hang out in places where you had fun, and avoid places where you didn’t. We give the mice a ‘house’ made of two rooms separated by a door they can walk through at any time. But first, we let them spend 24 hours in one room with their littermates, followed by 24 hours in the other room all by themselves. On the third day we put the two rooms together to make the house, give them complete freedom to go back and forth through the door and log the amount of time they spend in each room."
Mice normally prefer to spend time in the room that reminds them of the good times they enjoyed in the company of their buddies. But that preference vanished when oxytocin activity in their nucleus accumbens was blocked. Interestingly, only social activity appeared to be affected. There was no difference, for example, in the mice’s general propensity to move around. And when the researchers trained the mice to prefer one room over the other by giving them cocaine (which mice love) only when they went into one room, blocking oxytocin activity didn’t stop the mice from picking the cocaine den.
In an extensive series of sophisticated, highly technical experiments, Dölen, Malenka and their teammates located the oxytocin receptors in the murine nucleus accumbens. These receptors lie not on nucleus accumbens nerve cells that carry signals forward to numerous other reward-system nodes but, instead, at the tips of nerve cells forming a tract from a brain region called the dorsal Raphe, which projects to the nucleus accumbens. The dorsal Raphe secretes another important substance, serotonin, triggering changes in nucleus accumbens activity. In fact, popular antidepressants such as Prozac, Paxil and Zoloft belong to a class of drugs called serotonin-reuptake inhibitors that increase available amounts of serotonin in brain regions, including the nucleus accumbens.
As the Stanford team found, oxytocin acting at the nucleus accumbens wasn’t simply squirted into general circulation, as hormones typically are, but was secreted at this spot by another nerve tract originating in the hypothalamus, a multifunction midbrain structure. Oxytocin released by this tract binds to receptors on the dorsal Raphe projections to the nucleus accumbens, in turn liberating serotonin in this key node of the brain’s reward circuitry. The serotonin causes changes in the activity of yet other nerve tracts terminating at the nucleus accumbens, ultimately resulting in altered nucleus accumbens activity — and a happy feeling.
"There are at least 14 different subtypes of serotonin receptor," said Dölen. "We’ve identified one in particular as being important for social reward. Drugs that selectively act on this receptor aren’t clinically available yet, but our study may encourage researchers to start looking at drugs that target it for the treatment of diseases such as autism, where social interactions are impaired."
Malenka and Dölen said they think their findings in mice are highly likely to generalize to humans because the brain’s reward circuitry has been so carefully conserved over the course of hundreds of millions of years of evolution. This extensive cross-species similarity probably stems from pleasure’s absolutely essential role in reinforcing behavior likely to boost an individual’s chance of survival and procreation.
(Source: med.stanford.edu)
Study Shows that Intensity of Facebook Use Can Be Predicted by Reward-related Activity in the Brain
Neuroscientists at Freie Universität Berlin show a link between reward activity in the brain due to discovering one has a good reputation and social media use
A person’s intensity of Facebook use can be predicted by activity in the nucleus accumbens, a reward-related area of the brain, according to a new study published by neuroscientists in the Languages of Emotion Cluster of Excellence at Freie Universität Berlin. Dr. Dar Meshi and his colleagues conducted this first ever study to relate brain activity (functional MRI) to social media use. The study was published in the latest issue of the open-access journal Frontiers in Human Neuroscience.
The researchers focused on the nucleus accumbens, a small but critical structure located deep in the center of the brain, because previous research has shown that rewards —including food, money, sex, and gains in reputation — are processed in this region.
“As human beings, we evolved to care about our reputation. In today’s world, one way we’re able to manage our reputation is by using social media websites like Facebook,” says Dar Meshi, lead author of the paper. Facebook is the world’s largest social media channel with 1.2 billion monthly active users. It was used in the study because interactions on the website are carried out in view of the user’s friends or public and can affect their reputation. For example, Facebook consists of users “liking” posted information. This approval is positive social feedback, and can be considered related to their reputation.
All 31 participants completed the Facebook Intensity Scale to determine how many friends each participant had, how many minutes they each spent on Facebook, and general thoughts. The participants were selected to vary widely in their Facebook Intensity Scale scores.
First, the subjects participated in a video interview. Next, the brain activity of the subjects was recorded, by using functional magnetic resonance imaging, in different situations. In the scanner, subjects were told whether people who supposedly viewed the video interview thought highly of them, and subjects also found out whether people thought highly of another person. They also performed a card task to win money.
Results showed that participants who received positive feedback about themselves produced stronger activation of the nucleus accumbens than when they saw the positive feedback that another person received. The strength of this difference corresponded to participants’ reported intensity of Facebook use. But the nucleus accumbens response to monetary reward did not predict Facebook use.
“Our study reveals that the processing of social gains in reputation in the left nucleus accumbens predicts the intensity of Facebook use across individuals,” says Meshi. “These findings expand upon our present knowledge of nucleus accumbens function as it relates to complex human behavior.”
Regarding the potential for social media addiction and the effects of social media on education quality, these results may provide important motivation for clinical research and for further research on learning. As Meshi says, “Our findings relating individual social media use to the individual response of the brain’s reward system may also be relevant for both educational and clinical research in the future.” The authors point out, however, that their results do not determine if positive social feedback drives people to interact on social media, or if sustained use of social media changes the way positive social feedback is processed by the brain.