Posts tagged striatum

Posts tagged striatum
The pleasure of learning new words
From our very first years, we are intrinsically motivated to learn new words and their meanings. First language acquisition occurs within a permanent emotional interaction between parents and children. However, the exact mechanism behind the human drive to acquire communicative linguistic skills is yet to be established.
In a study published in the journal Current Biology, researchers from the University of Barcelona (UB), the Bellvitge Biomedical Research Institute (IDIBELL) and the Otto von Guericke University Magdeburg (Germany) have experimentally proved that human adult word learning exhibit activation not only of cortical language regions but also of the ventral striatum, a core region of reward processing. Results confirm that the motivation to learn is preserved throughout the lifespan, helping adults to acquire a second language.
Researchers determined that the reward region that is activated is the same that answers to a wide range of stimuli, including food, sex, drugs or game. “The main objective of the study was to know to what extent language learning activates subcortical reward and motivational systems”, explains Pablo Ripollés, PhD student at UB-IDIBELL and first author of the article. “Moreover, the fact that language could be favoured by this type of circuitries is an interesting hypothesis from an evolutionary point of view”, points out the expert.
According to Antoni Rodríguez Fornells, UB lecturer and ICREA researcher at IDIBELL, “the language region has been traditionally located at an apparently encapsulated cortical structure which has never been related to reward circuitries, which are considered much older from an evolutionary perspective”. “The study —he adds— questions whether language only comes from cortical evolution or structured mechanisms and suggests that emotions may influence language acquisition processes”.
Motivation for learning a second language
By using diffusion tensor imaging, UB-IDIBELL researchers reconstructed the white matter pathways that link brain regions in each participant. Experts were able to correlate the number of new words learnt by each person during the experiment with a low myelin index, a measure of structure integrity. Results proved that subjects who presented higher myelin concentrations in the structures that carry information to the ventral striatum —in other words, those that are best connected to the reward area— were able to learn more words.
“Results provide a neural substrate of the influence that reward and motivation circuitries may have in learning words from context”, affirms Josep Marco Pallarès, UB-IDIBELL researcher. The activation of these circuitries during word learning suggests future research lines aimed at stimulating reward regions to improve language learning in patients with linguistic problems.
The fact that non-linguistic subcortical mechanisms, which are much older from an evolutionary perspective, work together with language cortical regions —which appeared latter— suggests new language theories trying to explain how reward mechanisms have influenced and supported one of our primal urges: the desire to acquire language and to communicate.
Experiment with words and gambling
Researchers carried out an experiment with thirty-six adults who participated in two magnetic resonance sessions. On the first one, functional magnetic resonance was used to measure participants’ brain activity while they perform two different tasks. This technique enables to detect accurately what brain regions are active while a person is performing a certain activity. In the first task, participants must learn the meaning of some new words from context in two different sentences. For instance, subjects saw on a screen the sentences: “Every Sunday the grandmother went to the jedin” and “The man was buried in the jedin”. Considering both sentences, participants could learn that the word jedin means “graveyard”. Then, participants completed two runs of a standard-event-related money gambling task.
The experiment revealed that when subjects inferred and memorized the meaning of a new word, brain activity in the ventral striatum was increased. Indeed, the same ventral striatum activation was observed when earning money in gambling. Therefore, to learn the meaning of a new word activates reward and motivational circuitries like in gambling activities. Moreover, it was observed that word learning produce an increase of brain activity synchronization between the ventral striatum and cortical language regions.
Eating habits, body fat related to differences in brain chemistry
People who are obese may be more susceptible to environmental food cues than their lean counterparts due to differences in brain chemistry that make eating more habitual and less rewarding, according to a National Institutes of Health study published in Molecular Psychiatry.
Researchers at the NIH Clinical Center found that, when examining 43 men and women with varying amounts of body fat, obese participants tended to have greater dopamine activity in the habit-forming region of the brain than lean counterparts, and less activity in the region controlling reward. Those differences could potentially make the obese people more drawn to overeat in response to food triggers and simultaneously making food less rewarding to them. A chemical messenger in the brain, dopamine influences reward, motivation and habit formation.
"While we cannot say whether obesity is a cause or an effect of these patterns of dopamine activity, eating based on unconscious habits rather than conscious choices could make it harder to achieve and maintain a healthy weight, especially when appetizing food cues are practically everywhere," said Kevin D. Hall, Ph.D., lead author and a senior investigator at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH. "This means that triggers such as the smell of popcorn at a movie theater or a commercial for a favorite food may have a stronger pull for an obese person – and a stronger reaction from their brain chemistry – than for a lean person exposed to the same trigger."
Study participants followed the same eating, sleeping and activity schedule. Tendency to overeat in response to triggers in the environment was determined from a detailed questionnaire. Positron emission tomography (PET) scans evaluated the sites in the brain where dopamine was able to act.
According to the Centers for Disease Control and Prevention, more than one-third of U.S. adults are obese. Obesity-related conditions include heart disease, type 2 diabetes and certain types of cancer, some of the leading causes of preventable death.
"These findings point to the complexity of obesity and contribute to our understanding of how people with varying amounts of body fat process information about food," said NIDDK Director Griffin P. Rodgers, M.D. "Accounting for differences in brain activity and related behaviors has the potential to inform the design of effective weight-loss programs."
The study did not demonstrate cause and effect among habit formation, reward, dopamine activity, eating behavior and obesity. Future research will examine dopamine activity and eating behavior in people over time as they change their diets, physical activity, and their weight.
Reacting to Personal Setbacks: Do You Bounce Back or Give Up?
Sometimes when people get upsetting news – such as a failing exam grade or a negative job review – they decide instantly to do better the next time. In other situations that are equally disappointing, the same people may feel inclined to just give up.
How can similar setbacks produce such different reactions? It may come down to how much control we feel we have over what happened, according to new research from Rutgers University-Newark. The study, published in the journal Neuron, also finds that when these setbacks occur, the level of control we perceive may even determine which of two distinct parts of the brain will handle the crisis.
“Think of the student who failed an exam,” says Jamil Bhanji, a postdoctoral fellow at Rutgers and one of the study’s co-authors. “They might feel they wouldn’t have failed if they had studied harder, studied differently – something under their control.” That student, Bhanji says, resolves to try new study habits and work hard toward acing the next exam. Functional magnetic resonance imaging (fMRI) used in the study showed activity in a part of the brain called the ventral striatum – which has been shown to guide goals based on prior experiences.
A different student might have failed the same test, but believes it happened because the questions were unfair or the professor was mean, things that he could not control. The negative emotions produced by this uncontrollable setback may cause the student to drop the course.
Overcoming those negative emotions and refocusing on doing well in the class may require a more complicated thought process. In cases like this, fMRI revealed that activity in the ventromedial prefrontal cortex (vmPFC), a part of the brain that regulates emotions in more flexible ways, is necessary to promote persistence.
Mauricio Delgado, an associate professor of psychology at Rutgers’ Newark College of Arts and Sciences and the study’s other co-author, says people whose jobs include delivering bad news should pay attention to these results, because their actions might influence how the news is received.
“You may deliver the news to the student – no sugar coating, here’s your setback,” says Delgado. “But then you make an offer – ‘would you like to review those study habits with me? I’d be happy to do it.’ This puts the student in a situation where they may experience control and be more likely to improve the next time.” This approach, Delgado says, may be far more constructive than curtly delivering a bad grade.
Bhanji says lessons from the study may even guide certain people toward giving up too soon on careers where they could do well. “We wonder why there are fewer women and minorities in the sciences, for example,” he explains. “Maybe in cases like that it’s fair to say there are things we can do to promote reactions to negative feedback that encourage persistence.”
That is not to say everyone should persist. “There are times,” Delgado adds, “when you should not be persistent with your goals. That’s where the striatal system in the brain, which can be a source of more habitual responses, may be a detriment. You keep thinking ‘I can do it, I can do it.’ But maybe you shouldn’t do it. During these times, interpreting the setback more flexibly, via the vmPFC, may be more helpful.”
As research continues, adds Bhanji, important areas to explore will include “figuring out when it’s worth continuing to keep trying and when it’s not.”

The striatum acts as hub for multisensory integration
A new study from Karolinska Institutet provides insight on how the brain processes external input such as touch, vision or sound from different sources and sides of the body, in order to select and generate adequate movements. The findings, which are presented in the journal Neuron, show that the striatum acts as a sensory ‘hub’ integrating various types of sensory information, with specialised functional roles for the different neuron types.
“The striatum is the main input structure in the basal ganglia, and is typically associated with motor function”, says Principal Investigator Gilad Silberberg at the Department of Neuroscience. “Our study focuses on its role in processing sensory input. This is important knowledge, since the striatum is implicated in numerous diseases and disorders, including Parkinson’s disease, Huntington’s disease, ADHD and Tourette syndrome.”
The striatum is the largest structure in a collection of brain nuclei called the basal ganglia, which are located at the base of the forebrain. It is involved in motor learning, planning and execution as well as selecting our actions out of all possible choices, based on the expected reward by the dopamine system. Most research performed in the striatum is focused on the motor aspects of its function, largely due to the devastating motor symptoms of the related diseases.
However, in order to select the correct actions, and generate proper motor activity it is essential to continuously process sensory information, often arriving from different sources, different sides of the body and from different sensory modalities, such as tactile (touch), visual, auditory, and olfactory. This integration of sensory information is in fact a fundamental function of our nervous system.
Patch-clamp recordings
In the current study, researchers Gilad Silberberg and Ramon Reig show that individual striatal neurons integrate sensory input from both sides of the body, and that a subpopulation of these neurons process sensory input from different modalities; touch, light and vision. The team used intracellular patch-clamp recordings from single neurons in the mouse striatum to show their responses to whisker stimulation from both sides as well as responses to visual stimulation. Neurons responding to both visual and tactile stimuli were located in a specific medial region of the striatum.
“We also showed that neurons of different types integrate sensory inputs in a different manner, suggesting that they have specific roles in the processing of such sensory information in the striatal network”, says Gilad Silberberg.
(Image: Shutterstock)
(Image caption: This is the happiness equation, where t is the trial number, w0 is a constant term, other weights w capture the influence of different event types, 0 ≤ γ ≤ 1 is a forgetting factor that makes events in more recent trials more influential than those in earlier trials, CRj is the CR if chosen instead of a gamble on trial j, EVj is the EV of a gamble (average reward for the gamble) if chosen on trial j, and RPEj is the RPE on trial j contingent on choice of the gamble. The RPE is equal to the reward received minus the expectation in that trial EVj. If the CR was chosen, then EVj = 0 and RPEj = 0; if the gamble was chosen, then CRj = 0. The variables in the equation are quantities that the neuromodulator dopamine has been associated with in previous neuroscience studies. Credit: Robb Rutledge, UCL)
The happiness of over 18,000 people worldwide has been predicted by a mathematical equation developed by researchers at UCL, with results showing that moment-to-moment happiness reflects not just how well things are going, but whether things are going better than expected.
The new equation accurately predicts exactly how happy people will say they are from moment to moment based on recent events, such as the rewards they receive and the expectations they have during a decision-making task. Scientists found that overall wealth accumulated during the experiment was not a good predictor of happiness. Instead, moment-to-moment happiness depended on the recent history of rewards and expectations. These expectations depended, for example, on whether the available options could lead to good or bad outcomes.
The study, published in the Proceedings of the National Academy of Sciences, investigated the relationship between happiness and reward, and the neural processes that lead to feelings that are central to our conscious experience, such as happiness. Before now, it was known that life events affect an individual’s happiness but not exactly how happy people will be from moment to moment as they make decisions and receive outcomes resulting from those decisions, something the new equation can predict.
Scientists believe that quantifying subjective states mathematically could help doctors better understand mood disorders, by seeing how self-reported feelings fluctuate in response to events like small wins and losses in a smartphone game. A better understanding of how mood is determined by life events and circumstances, and how that differs in people suffering from mood disorders, will hopefully lead to more effective treatments.
Research examining how and why happiness changes from moment to moment in individuals could also assist governments who deploy population measures of wellbeing to inform policy, by providing quantitative insight into what the collected information means. This is especially relevant to the UK following the launch of the National Wellbeing Programme in 2010 and subsequent annual reports by the Office for National Statistics on ‘Measuring National Wellbeing’.
For the study, 26 subjects completed a decision-making task in which their choices led to monetary gains and losses, and they were repeatedly asked to answer the question ‘how happy are you right now?’. The participant’s neural activity was also measured during the task using functional MRI and from these data, scientists built a computational model in which self-reported happiness was related to recent rewards and expectations. The model was then tested on 18,420 participants in the game ‘What makes me happy?’ in a smartphone app developed at UCL called 'The Great Brain Experiment'. Scientists were surprised to find that the same equation could be used to predict how happy subjects would be while they played the smartphone game, even though subjects could win only points and not money.
Lead author of the study, Dr Robb Rutledge (UCL Wellcome Trust Centre for Neuroimaging and the new Max Planck UCL Centre for Computational Psychiatry and Ageing), said: “We expected to see that recent rewards would affect moment-to-moment happiness but were surprised to find just how important expectations are in determining happiness. In real-world situations, the rewards associated with life decisions such as starting a new job or getting married are often not realised for a long time, and our results suggest expectations related to these decisions, good and bad, have a big effect on happiness.
"Life is full of expectations - it would be difficult to make good decisions without knowing, for example, which restaurant you like better. It is often said that you will be happier if your expectations are lower. We find that there is some truth to this: lower expectations make it more likely that an outcome will exceed those expectations and have a positive impact on happiness. However, expectations also affect happiness even before we learn the outcome of a decision. If you have plans to meet a friend at your favourite restaurant, those positive expectations may increase your happiness as soon as you make the plan. The new equation captures these different effects of expectations and allows happiness to be predicted based on the combined effects of many past events.
"It’s great that the data from the large and varied population using The Great Brain Experiment smartphone app shows that the same happiness equation applies to thousands people worldwide playing our game, as with our much smaller laboratory-based experiments which demonstrate the tremendous value of this approach for studying human well-being on a large scale."
The team used functional MRI to demonstrate that neural signals during decisions and outcomes in the task in an area of the brain called the striatum can be used to predict changes in moment-to-moment happiness. The striatum has a lot of connections with dopamine neurons, and signals in this brain area are thought to depend at least partially on dopamine. These results raise the possibility that dopamine may play a role in determining happiness.
Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, describes a way that brain chemistry may make some people notice food more easily, which can tempt overeating even in people who are not overweight. Dopamine activity in the striatum, an area of the brain sensitive to food reward, was linked to how quickly men noticed a food picture hidden among neutral pictures. In turn, the men who quickly noticed food pictures also ate more.
From rodent research it is clear that dopamine action in the striatum motivates eating, and this goes awry in obesity. “We do know that in human obesity the striatal dopamine system is affected, but interesting enough we know little about the striatal dopamine system of young, healthy individuals and how it relates to the motivation to eat” says Susanne la Fleur from the Academic Medical Center in Amsterdam, who directed the study linking dopamine, attention to food, and eating.
Ordinarily the burst of dopamine during a rewarding activity is eventually stopped when it is re-absorbed into the cells it came from. That re-uptake process requires a brain chemical called “dopamine transporter” (DAT). Lower DAT means dopamine is reabsorbed more slowly, causing it to keep acting on the brain. The researchers scanned brains of healthy, non-obese young men to determine available DAT. The men completed a computerized visual attention task to see how quickly they could detect food pictures among neutral pictures. Subjects were also asked to report food intake during 7 days.
The researchers found that the men with lower DAT, which means higher dopamine activity, showed a stronger visual attention bias towards food, detecting food pictures more quickly. “We could speculate that in healthy humans dopamine does motivate eating, however although we did observe a correlation between striatal dopamine transporter binding and the visual attention bias for food; and between visual attention bias for food and actual food intake, we did not observe a correlation between striatal dopamine transporter binding and actual food intake. Thus, a factor in addition to dopamine must be involved in going from being motivated to actual eating”, la Fleur concluded.
(Source: eurekalert.org)
Brain’s dynamic duel underlies win-win choices
People choosing between two or more equally positive outcomes experience paradoxical feelings of pleasure and anxiety, feelings associated with activity in different regions of the brain, according to research led by Amitai Shenhav, an associate research scholar at the Princeton Neuroscience Institute at Princeton University.
In one experiment, 42 people rated the desirability of more than 300 products using an auction-like procedure. Then they looked at images of paired products with different or similar values and were asked to choose between them. Their brain activity was scanned using functional magnetic resonance imaging (fMRI). After the scan, participants reported their feelings before and during each choice. They received one of their choices at the end of the study.
Choices between two highly valued items (high-high), such as a digital camera and a camcorder, were associated with the most positive feelings and the greatest anxiety, compared with choices between items of low value (low-low), like a desk lamp and a water bottle, or between items of different values (low-high). Functional MRI scans showed activity in two regions of the brain, the striatum and the prefrontal cortex, both known to be involved in decision-making. Interestingly, lower parts of both regions were more active when subjects felt excited about being offered the choice, while activity in upper parts was strongly tied to feelings of anxiety.
This evidence that parallel brain circuits are associated with opposing emotional reactions helps to answer a puzzling question, according to Shenhav: “Why isn’t our positivity quelled by our anxiety, or our anxiety quelled by the fact that we’re getting this really good thing at the end? This suggests that it’s because these circuits evolved for two different reasons,” he said. “One of them is about evaluating the thing we’re going to get, and the other is about guiding our actions and working out how difficult the choice will be.”
The study, “Neural correlates of dueling affective reactions to win-win choices,” was published July 14 in the Proceedings of the National Academy of Sciences. Shenhav conducted the research as a graduate student at Harvard University, along with Professor of Psychology and Neuroscience Randy Buckner, the study’s senior author.
A second fMRI experiment showed that the same patterns of emotional reactions and brain activity persisted even when the participants were told before each choice how similarly they had valued the items. Their anxiety didn’t abate, despite knowing how little they stood to lose by making a “wrong” choice. In a third experiment, Shenhav and Buckner tested whether giving people more than two choices increased their levels of anxiety. Indeed, they found that providing six options led to higher levels of anxiety than two options, particularly when all six of the options were highly valued items. But positive feelings about being presented with the choice were similar for two or six options.
This suggests that the anxiety stems from the conflict of making the decision, rather than the opportunity cost of the choice — an economic concept that refers to the lost value of the second-best option. The opportunity cost should be the same, regardless of the number of choices. In addition, subjects in this final study were given an unlimited amount of time to make a decision, compared with 1.5 seconds in the first two studies. The results showed that time pressure was not the main source of anxiety during the choices.
At the end of each study, participants had a surprise opportunity to reverse their earlier choices. Higher activity in a part of the brain called the anterior cingulate cortex around the time of an initial choice predicted whether that decision would later be reversed. Previous work has shown that this brain region is involved in assessing how conflicted an individual feels over a particular choice; this result suggests that some choices may have continued to elicit conflict after the participant made a decision, Shenhav said. The researchers also found that people who reported more anxiety in their daily lives were more likely to change their minds.
This work could explain why ostensibly positive options can evoke a mixture of positive and negative responses, which are not explained by purely economic analyses of choice. “Rationally, there’s no reason why when you put one good thing with another good thing, you should feel worse about the situation,” said Brian Knutson, an associate professor of psychology and neuroscience at Stanford University, who is familiar with the work but was not involved in it. “The neuroimaging tells us that these different mechanisms are fighting with each other,” he said. “Understanding that dynamic can help us understand why decisions that we think should make us feel better can actually make us feel worse.”
According to Shenhav, this research could shed light on the neural processes that can make more momentous choices so paralyzing for some people — for instance, deciding where to go to college or which job offer to take. But he admits that even more trivial decisions can be tough for him. “I probably experience more win-win choice anxiety than the average person,” he said. “I’m even terrible at choosing where to eat dinner.”
Choice bias: A quirky byproduct of learning from reward
The price of learning from rewarding choices may be just a touch of self-delusion, according to a new study in Neuron.
The research by Brown University brain scientists links a fundamental problem in neuroscience called “credit assignment” — how the brain reinforces learning only in the exact circuits that caused the rewarding choice — to an oft-observed quirk of behavior called “choice bias” – we value the rewards we choose more than equivalent rewards we don’t choose. The researchers used computational modeling and behavioral and genetic experiments to discover evidence that choice bias is essentially a byproduct of credit assignment.
“We weren’t looking to explain anything about choice bias to start off with,” said lead author Jeffrey Cockburn, a graduate student in the research group of senior author Michael Frank, associate professor of cognitive, linguistic, and psychological sciences. “This just happened to be the behavioral phenomenon we thought would emerge out of this credit assignment model.”
So the next time a friend raves about the movie he chose and is less enthusiastic about the just-as-good one that you chose, you might be able to chalk it up to his basic learning circuitry and a genetic difference that affects it.
Modeled mechanism
The model, developed by Frank, Cockburn, and co-author Anne Collins, a postdoctoral researcher, was based on prior research on the function of the striatum, a part of the brain’s basal ganglia (BG) that is principally involved in representing reward values of actions and picking one. “An interaction between three key BG regions moderates that decision-making process. When a rewarding choice has been made, the substantia nigra pars compacta (SNc) releases dopamine into the striatum to reinforce connections between cortex and striatum, so that rewarded actions are more likely to be repeated. But how does the SNc reinforce just the circuits that made the right call? The authors proposed a mechanism by which another part of the subtantia nigra, the SNr, detects when actions are worth choosing and then simultaneously amplifies any dopamine signal coming from the SNc.”
“The novel part here is that we have proposed a mechanism by which the BG can detect when it has selected an action and should therefore amplify the dopamine reinforcing event specifically at that time,” Frank said. “When the SNr decides that striatal valuation signals are strong enough for one action, it releases the brakes not only on downstream structures that allow actions to be executed, but also on the SNc dopamine system, so any unexpected rewards are amplified.”
Specifically, dopamine provides reinforcement by enhancing the responsiveness of connections between cells so that a circuit can more easily repeat its rewarding behavior in the future. But along with that process of reinforcing the action of choosing, the value placed on the resulting reward becomes elevated compared to rewards not experienced this way.
Experimental evidence
That prediction seemed intriguing, but it still had to be tested. The authors identified both behavioral and genetic tests that would be telling.
They recruited 80 people at Brown and elsewhere in Providence to play a behavioral game and to donate some saliva for genetic testing.
The game first presented the subjects pictures of arbitrary Japanese characters that would have different probabilities of rewards if chosen ranging from a 20 percent to 80 percent chance of winning a point or losing a point. For some characters, the player could choose a character to discover its resulting reward or penalty, whereas for others, its result was simply given to them. After that learning phase, the subjects were then presented the characters in pairs and instructed to pick the one they thought had the highest chance of winning based on what they had learned.
The researchers built the game so that for every character a player could choose, there was an equally rewarding one that had merely been given to them. On average, players showed a clear choice bias in that they were more likely to prefer rewarding characters that they had chosen over equally rewarding characters they had been given.
Notably, they exhibited no choice bias between unrewarding characters suggesting that choice bias emerges only in relation to reward, one of the key predictions of their model. But they wanted to test further whether the impact of reward on choice bias was related to the proposed biological mechanism, that striatal dopaminergic learning is enhanced to chosen rewards.
The genetic tests focused on single-letter differences in a gene called DARPP-32, which governs how well cells in the striatum respond to the reinforcing influence of dopamine.
People with one version of the gene have been shown in previous research to be less able to learn from rewards, while people with other versions were less driven by reward in learning.
“The reason why this gene is interesting is because we know something about the biology of what it does and where it is expressed in the brain,” Frank said. “It’s predominant in the striatum and specifically affects synaptic plasticity induced by dopamine signaling. It’s related to the imbalance by which you learn from really good things or not so good things.
“The logic was if the mechanism that we think describes this choice bias and credit assignment problem is accurate then that gene should predict the impact of how good something was on this choice bias phenomenon,” he said.
Indeed, that’s what the data showed. People with the form of the gene that predisposed them to be responsive to big rewards also showed more choice bias from the most strongly rewarded characters. Interestingly, the other people also showed choice bias, but more strongly for those characters that were more mediocre. This pattern was mirrored by the authors’ model when it simulated the effects of DARPP-32 on reward learning imbalances from positive vs. negative outcomes.
For some people, the plums are sweeter if they picked them.
(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.
A study group at the Medical University of Vienna’s Centre for Brain Research has investigated the function of an intracellular dopamine pump in Parkinson’s patients compared to a healthy test group. It turned out that this pump is less effective at pumping out dopamine and storing it in the brain cells of Parkinson’s sufferers. If dopamine is not stored correctly, however, it can cause self-destruction of the affected nerve cells.

In the brain, dopamine mediates the exchange of information between different neurons and, to help it do this, it is continuously reformed at the contact points between the corresponding nerve cells. It is stored in structures known as vesicles (intracellular bubbles) and it is released when required. In people with Parkinson’s disease, the death of these nerve cells causes a lack of dopamine, and this in turn causes the familiar movement problems such as motor retardation, stiffness of the muscles and tremors.
More than 50 years ago, in the Institute of Pharmacology at the University of Vienna (now the MedUni Vienna), Herbert Ehringer and Oleh Hornykiewicz discovered that Parkinson’s disease is caused by a lack of dopamine in certain regions of the brain. This discovery enabled Hornykiewicz to introduce the amino acid L-DOPA into the treatment of Parkinson’s to substitute the dopamine and make the symptoms of the condition manageable for years.
The reasons for the death of nerve cells in Parkinson’s disease are not yet fully understood, however, which is why it is still not possible to prevent the disease from developing. Nevertheless, dopamine itself, if it is not stored correctly in vesicles, can cause self-destruction of the affected nerve cells.
Now, a further step forward has been taken in the research into the causes of this disease: a study at the MedUni Vienna’s Centre for Brain Research, led by Christian Pifl and the now 87-year-old Oleh Hornykiewicz, compared the brains of deceased Parkinson’s patients with those of a neurologically healthy control group. For the first time, it was possible to prepare the dopamine-storing vesicles from the brains so that their ability to store dopamine by pumping it in could be measured in quantitative terms.
It turned out that the pumps in the vesicles of Parkinson’s sufferers pumped the dopamine out less efficiently. “This pump deficiency and the associated reduction in dopamine storage capacity of the Parkinson’s vesicles could lead to dopamine collecting in the nerve cells, developing its toxic effect and destroying the nerve cells,” explains Christian Pifl.
(Source: meduniwien.ac.at)