Posts tagged orbitofrontal cortex
Articles and news from the latest research reports.
Missing “brake in the brain” can trigger anxiety states
Fear, at the right level, can increase alertness and protect against dangers. Disproportionate fear, on the other hand, can disrupt the sensory perception, be disabling, reduce happiness and therefore become a danger in itself. Anxiety disorders are therefore a psychiatric condition that should not be underestimated. In these disorders, the fear is so strong that there is tremendous psychological strain and living a normal life appears to be impossible. Researchers at the MedUni Vienna have now found a possible explanation as to how social phobias and fear can be triggered in the brain: a missing inhibitory connection or missing “brake” in the brain.
Inside the brain, the amygdala and the orbitofrontal cortex in the frontal lobe form an important control circuit for regulating the emotions. This control circuit is termed the brain’s emotional control centre. Whereas in healthy subjects, this circuit has “negative feedback” and “calmness” was identified, scientists used functional magnetic resonance imaging (MRI) on people with social phobias and found the opposite to be true: an important inhibitory connection is different in these patients, which may explain why they are unable to control their fears.
In collaboration with the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna, the research team lead by Christian Windischberger was also able to discover through its recent study at the MedUni Vienna’s High Field MR Centre of Excellence how the areas of the brain that are involved with processing emotions are able to influence each other.
The study participants were shown a series of “emotional faces” while undergoing functional magnetic resonance imaging. fMRI is a non-invasive method which uses radio waves and magnetic fields to measure changes in the levels of oxygen in the blood and therefore neuronal activity in individual regions of the brain. An analysis method developed at University College London was used to provide new perspectives on the data obtained.
Breaking the circle of fear
When emotional facial expressions were shown - from laughing to crying, from happiness to anger - neuronal activity was triggered in the brain. The result: on a purely external basis, the test subjects looked no different, but the healthy subjects were kept calm thanks to their automatic “brake”, despite the emotional nature of the images. For the social phobics, on the other hand, the photographs put their brains into “overdrive”, triggering very strong neuronal activity. This was demonstrated very clearly using the new analysis method: “We have the opportunity not only to localise brain activity and compare it between groups, but we can now also make statements regarding functional connections within the brain. In psychiatric conditions especially, we can assume that there are not complete failures of these connections going on, but rather imbalances in complex regulatory processes,” says Ronald Sladky, the study’s primary author.
This better understanding of the neuronal mechanisms involved will now be used to develop new approaches to treatment. The aim is to understand what effect medications and psycho-therapeutic support have on the networks involved in order to help patients break out of their circles of fear.
(Source: meduniwien.ac.at)
A neurological basis for the lack of empathy in psychopaths
When individuals with psychopathy imagine others in pain, brain areas necessary for feeling empathy and concern for others fail to become active and be connected to other important regions involved in affective processing and decision-making, reports a study published in the open-access journal Frontiers in Human Neuroscience.
Psychopathy is a personality disorder characterized by a lack of empathy and remorse, shallow affect, glibness, manipulation and callousness. Previous research indicates that the rate of psychopathy in prisons is around 23%, greater than the average population which is around 1%.
To better understand the neurological basis of empathy dysfunction in psychopaths, neuroscientists used functional magnetic resonance imaging (fMRI) on the brains of 121 inmates of a medium-security prison in the USA.
Participants were shown visual scenarios illustrating physical pain, such as a finger caught between a door, or a toe caught under a heavy object. They were by turns invited to imagine that this accident happened to themselves, or somebody else. They were also shown control images that did not depict any painful situation, for example a hand on a doorknob.
Participants were assessed with the widely used PCL-R, a diagnostic tool to identify their degree of psychopathic tendencies. Based on this assessment, the participants were then divided in three groups of approximately 40 individuals each: highly, moderately, and weakly psychopathic.
When highly psychopathic participants imagined pain to themselves, they showed a typical neural response within the brain regions involved in empathy for pain, including the anterior insula, the anterior midcingulate cortex, somatosensory cortex, and the right amygdala. The increase in brain activity in these regions was unusually pronounced, suggesting that psychopathic people are sensitive to the thought of pain.
But when participants imagined pain to others, these regions failed to become active in high psychopaths. Moreover, psychopaths showed an increased response in the ventral striatum, an area known to be involved in pleasure, when imagining others in pain.
This atypical activation combined with a negative functional connectivity between the insula and the ventromedial prefrontal cortex may suggest that individuals with high scores on psychopathy actually enjoyed imagining pain inflicted on others and did not care for them. The ventromedial prefrontal cortex is a region that plays a critical role in empathetic decision-making, such as caring for the wellbeing of others.
Taken together, this atypical pattern of activation and effective connectivity associated with perspective taking manipulations may inform intervention programs in a domain where therapeutic pessimism is more the rule than the exception. Altered connectivity may constitute novel targets for intervention. Imagining oneself in pain or in distress may trigger a stronger affective reaction than imagining what another person would feel, and this could be used with some psychopaths in cognitive-behavior therapies as a kick-starting technique, write the authors.
Brain size may signal risk of developing an eating disorder
New research indicates that teens with anorexia nervosa have bigger brains than teens that do not have the eating disorder. That is according to a study by researchers at the University of Colorado’s School of Medicine that examined a group of adolescents with anorexia nervosa and a group without. They found that girls with anorexia nervosa had a larger insula, a part of the brain that is active when we taste food, and a larger orbitofrontal cortex, a part of the brain that tells a person when to stop eating.
Guido Frank, MD, assistant professor of psychiatry and neuroscience at CU School of Medicine, and his colleagues report that the bigger brain may be the reason people with anorexia are able to starve themselves. Similar results in children with anorexia nervosa and in adults who had recovered from the disease, raise the possibility that insula and orbitofrontal cortex brain size could predispose a person to develop eating disorders.
"While eating disorders are often triggered by the environment, there are most likely biological mechanisms that have to come together for an individual to develop an eating disorder such as anorexia nervosa," Frank says.
The researchers recruited 19 adolescent girls with anorexia nervosa and 22 in a control group and used magnetic resonance imaging (MRI) to study brain volumes. Individuals with anorexia nervosa showed greater left orbitofrontal, right insular, and bilateral temporal cortex gray matter compared to the control group. In individuals with anorexia nervosa, orbitofrontal gray matter volume related negatively with sweet tastes. An additional comparison of this study group with adults with anorexia nervosa and a healthy control group supported greater orbitofrontal cortex and insula volumes in the disorder across this age group as well.
The medial orbitofrontal cortex has been associated with signaling when we feel satiated by a certain type of food (so called “sensory specific satiety”). This study suggests that larger volume in this brain area could be a trait across eating disorders that promotes these individuals to stop eating faster than in healthy individuals, before eating enough.
The right insula is a region that processes taste, as well as integrates body perception and this could contribute to the perception of being fat despite being underweight.
This study is complementary to another that found adults with anorexia and individuals who had recovered from this illness also had differences in brain size, previously published in the American Journal of Psychiatry.
(Source: eurekalert.org)
This is your brain on Vivaldi and Beatles
Listening to music activates large networks in the brain, but different kinds of music are processed differently. A team of researchers from Finland, Denmark and the UK has developed a new method for studying music processing in the brain during a realistic listening situation. Using a combination of brain imaging and computer modeling, they found areas in the auditory, motor, and limbic regions to be activated during free listening to music. They were furthermore able to pinpoint differences in the processing between vocal and instrumental music. The new method helps us to understand better the complex brain dynamics of brain networks and the processing of lyrics in music. The study was published in the journal NeuroImage.
Using functional magnetic resonance imaging (fMRI), the research team, led by Dr. Vinoo Alluri from the University of Jyväskylä, Finland, recorded the brain responses of individuals while they were listening to music from different genres, including pieces by Antonio Vivaldi, Miles Davis, Booker T. & the M.G.’s, The Shadows, Astor Piazzolla, and The Beatles. Following this, they analyzed the musical content of the pieces using sophisticated computer algorithms to extract musical features related to timbre, rhythm and tonality. Using a novel cross-validation method, they subsequently located activated brain areas that were common across the different musical stimuli.
The study revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions were activated by all musical pieces. Notable, areas in the medial orbitofrontal region and the anterior cingulate cortex, which are relevant for self-referential appraisal and aesthetic judgments, were found to be activated during the listening. A further interesting finding was that vocal and instrumental music were processed differently. In particular, the presence of lyrics was found to shift the processing of musical features towards the right auditory cortex, which suggests a left-hemispheric dominance in the processing of the lyrics. This result is in line with previous research, but now for the first time observed during continuous listening to music.
"The new method provides a powerful means to predict brain responses to music, speech, and soundscapes across a variety of contexts", says Dr. Vinoo Alluri.
Switching between habitual and goal-directed actions — a ‘2 in 1’ system in our brain
"Pressing the button of the lift at your work place, or apartment building is an automatic action – a habit. You don’t even really look at the different buttons; your hand is almost reaching out and pressing on its own. But what happens when you use the lift in a new place? In this case, your hand doesn’t know the way, you have to locate the buttons, find the right one, and only then your hand can press a button. Here, pushing the button is a goal-directed action." It is with this example that Rui Costa, principal investigator at the Champalimaud Neuroscience Programme (CNP), explains how critical it is to be able to shift between habits and goal-direct actions, in a fast and accurate way, in everyday life.
To unravel the circuit that underlies this capacity, the capacity to “break habits”, was the goal of this study, carried out by Christina Gremel and Rui Costa, at NIAAA, National Institutes of Health, USA and the Champalimaud Foundation, in Portugal, that is published today (Date) in Nature Communications.
"We developed a task where mice would shift between making the same action in a goal-directed or habitual manner. We could then, for the first time, directly examine brain areas controlling the capacity to break habits," explains the study’s lead author Christina Gremel from NIAAA. Evidence from previous studies has shown that two neighbouring regions of the brain are necessary for these different functions – the dorsal medial striatum is necessary for goal-directed actions and the dorsal lateral striatum is necessary for habitual actions. What was not known, and this new study reveals, is that a third region, the orbital frontal cortex (OFC), is critical for shifting between these two types of actions. As explained by Rui Costa, "when neurons in the OFC were inhibited, the generation of goal-directed actions was disrupted, while activation of these neurons, by means of a technique called optogenetics, selectively increased goal-directed actions."
For Costa, the results of this study suggest “something quite extraordinary – the same neural circuits function in a dynamic way, enabling the learning of automatic and goal-directed actions in parallel.”
These results have important implications for understanding neuropsychiatric disorders where the balance between habits and goal-directed actions is disrupted, such as obsessive-compulsive disorder.
The neural bases of behaviour, and their connection to neuropsychiatric disorders, are at the core of ongoing work by neuroscientists and clinicians at the Champalimaud Foundation.
(Source: eurekalert.org)
Brain discovery could help schizophrenics
The discovery of brain impairment in mice may eventually lead to better therapies for people with schizophrenia and major depression.
Studying rodents that have a gene associated with mental illness, Michigan State University neuroscientist Alexander Johnson and colleagues found a link between a specific area of the prefrontal cortex, and learning and behavioral deficits.
While much work needs to be done, the discovery is a major step toward better understanding mental illness. While antipsychotic drugs can treat hallucinations related to schizophrenia, there essentially is no treatment for other symptoms such as lack of motivation or anhedonia, the inability to experience pleasure.
“This study may well suggest that if we start targeting these brain-behavior mechanisms in people with mental illness, it may help to alleviate some of the cognitive and motivational symptoms, which to date remain largely untreated with current drug therapies,” said Johnson, MSU assistant professor of psychology.
The study is published in the Proceedings of the National Academy of Sciences.
Schizophrenia, a disabling brain disorder marked by paranoia and hearing voices that aren’t there, affects some 2.4 million Americans and runs in families, according to the National Institute of Mental Health.
The researchers conducted a series of experiments with two groups of mice – those with the gene associated with mental illness and those without the gene (or the control group).
In one experiment, related to cognition, the mice were presented with tasty food when they responded on one side of a conditioning box. After repeated feedings, the food was switched to the other side of the box. The mice with the mental illness gene had a much more difficult time learning to adapt to the new side.
In another experiment, related to motivation, the mice had to respond an increasing number of times each time they wanted food. By the end of the three-hour session, all mice with the mental illness gene stopped responding for food, while half of the control group continued on.
Johnson said the deficiencies may suggest a problem in the prefrontal cortex area known as the orbitofrontal cortex, and that further research should target this area.
The brain’s response to sweets may indicate risk for development of alcoholism
Several human and animal studies have shown a relationship between a preference for highly sweet tastes and alcohol use disorders. Furthermore, the brain mechanisms of sweet-taste responses may share common neural pathways with responses to alcohol and other drugs. A new study using functional magnetic resonance imaging (fMRI) has found that recent drinking is related to the orbitofrontal-region brain response to an intensely sweet stimulus, a brain response that may serve as an important phenotype, or observable characteristic, of alcoholism risk.
Results will be published in the December 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"It has long-been known that animals bred to prefer alcohol also drink considerably greater quantities of sweetened water than do animals without this selective breeding for alcohol preference," explained David A. Kareken, deputy director of the Indiana Alcohol Research Center, a professor in the department of neurology at Indiana University School of Medicine, and corresponding author for the study. "More recently, it has become clear that animals bred to prefer the artificial sweetener, saccharin, also drink more alcohol. Although the data in humans are somewhat more variable, some studies do show that alcoholics, or even non-alcoholics with a family history of alcoholism, have a preference for unusually sweet tastes. Thus, while the precise reasons remain unclear, there does seem to be significant evidence suggesting some link between the rewarding properties of both sweet tastes and alcohol."
Kareken added that this is the first study to examine the extent to which regions of the brain’s reward system, as they respond to an intensely sweet taste, are related to human drinking patterns.
Kareken and his colleagues recruited 16 (12 males, 4 females) right-handed, non-treatment seeking, healthy volunteers with a mean age of 26 years from the community. All participants underwent a taste test using a range of sucrose concentrations, and their blood oxygen dependent (BOLD) activation was measured during an fMRI scan while receiving small squirts of either water or an intensely sweet mixture of sugar in water. All were asked about their drinking patterns.
"Our study was designed to determine which brain areas responded to sweet taste – as compared to plain water – and the extent to which these brain responses were related to subjects’ binge-drinking patterns, the number of alcoholic drinks subjects consumed per day when drinking," explained Kareken.
"In addition to ‘activating’ the brain’s gustatory or taste circuits, the sugared water also activated key elements of what neuroscientists consider to be part of the brain’s reward system, including the ventral striatum, amygdala, and parts of the orbitofrontal cortex – the inferior frontal lobe surface just above the eyes – that respond to ingested rewards," Kareken said. "We refer to these as ‘primary’ rewards, being distinct from secondary rewards, like money, which can be used to obtain primary rewards."
What the researchers found was that the response to this intensely sweet taste in the left orbitofrontal area correlated significantly with subjects’ drinking patterns.
"Specifically, the trend was such that those who drank more alcohol on drinking days had stronger left orbitofrontal responses to the intensely sweet water," said Kareken. "Subjects’ subjectively rated liking of the sweetened water also contributed to this relationship, so that both the brain response itself, as well as liking of the sugared water, collectively correlated with drinking behavior."
While previous human and animal research has noted this association between preferences for both sweet tastes and alcohol intoxication, Kareken believes that this is the first study to examine the human brain mechanism behind this association.
"While much more research needs to be done to truly understand the commonalities between sweet-liking and alcoholism, and while alcoholism itself is likely the product of several mechanisms, our findings may implicate a particular brain region that is more generally involved in coding for the value of ‘primary’ rewards such as pleasures," he said. "In a more practical sense, the findings are compelling evidence that the brain response to an intensely sweet taste may be used in future research to test for differences in the reward circuits of those at risk for alcoholism. This may be particularly useful since alcohol itself is not an easy drug to work with in this kind of human imaging, and since alcohol exposure is not ethically appropriate for use in all at-risk subjects, or in subjects trying to abstain from drinking."
(Source: eurekalert.org)
New research uncovers the neural mechanism underlying drug cravings
Addiction may result from abnormal brain circuitry in the frontal cortex, the part of the brain that controls decision-making. Researchers from the RIKEN Center for Molecular Imaging Science in Japan collaborating with colleagues from the Montreal Neurological Institute of McGill University in Canada report today that the lateral and orbital regions of the frontal cortex interact during the response to a drug-related cue and that aberrant interaction between the two frontal regions may underlie addiction. Their results are published today in the journal Proceedings of the National Academy of Sciences of the USA.
Cues such as the sight of drugs can induce cravings and lead to drug-seeking behaviors and drug use. But cravings are also influenced by other factors, such as drug availability and self-control. To investigate the neural mechanisms involved in cue-induced cravings the researchers studied the brain activity of a group of 10 smokers, following exposure to cigarette cues under two different conditions of cigarette availability. In one experiment cigarettes were available immediately and in the other they were not. The researchers combined a technique called transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI).
The results demonstrate that in smokers the orbitofrontal cortex (OFC) tracks the level of craving while the dorsolateral prefrontal cortex (DPFC) is responsible for integrating drug cues and drug availability. Moreover, the DPFC has the ability to suppress activity in the OFC when the cigarette is unavailable. When the DPFC was inactivated using TMS, both craving and craving-related signals in the OFC became independent of drug availability.
The authors of the study conclude that the DLPFC incorporates drug cues and knowledge on drug availability to modulate the value signals it transmits to the OFC, where this information is transformed into drug-seeking action.
"We demonstrate that in smokers, cravings build up in the OFC upon processing of cigarette cues and availability by the DFPC. What is surprising is that this is a neural circuit involved in decision making and self-control, that normally guides individuals to optimal behaviors in daily life." Explains Dr. Hayashi, from RIKEN, who designed and conducted the fMRI and TMS experiments.
"This research uncovers the brain circuitry responsible for self-control during reward-seeking choices. It is also consistent with the view that drug addiction is a pathology of decision making." According to Dr. Alain Dagher, a neurologist at the Montreal Neurological Institute.
These findings will help understand the neural basis of addiction and may contribute to a therapeutic approach for addiction.
(Image: New Jersey Addiction Assistance)
Childhood trauma leaves its mark on the brain
EPFL scientists have found that childhood trauma leaves a lasting imprint on the brain – a structural change that is related to a predisposition to violence.
It is well known that violent individuals are often themselves the victims of psychological trauma experienced in childhood. Some of these individuals also exhibit alterations in their orbitofrontal cortex. But is there a connection between these physical changes in the brain and a psychologically traumatic childhood? Can one’s experiences modify the physical structure of the brain?
An EPFL team led by Professor Carmen Sandi, member of the National Centers for Competence in Research SYNAPSY, has demonstrated for the first time a correlation between psychological trauma and specific changes in the brain that are related to aggressive behavior. In rats, the experience of pre-adolescent trauma led to aggressive behavior accompanied by structural and functional changes in the brain – the same changes that have been observed in violent human beings. In other words, psychological wounds inflicted in childhood leave a lasting biological trace that persists in the adult brain. The team’s findings have been published in the January 15 edition of the journal Translational Psychiatry.
“This research shows that people exposed to trauma in childhood don’t only suffer psychologically, but their brain also gets altered,” explains Sandi, who is head of EPFL’s Laboratory of Behavioral Genetics and director of the Brain Mind Institute. “This adds an additional dimension to the consequences of abuse, and obviously has scientific, therapeutic and social implications.”
Remarkable results
The researchers were able to unravel the biological foundations of violence using a cohort of male rats that were exposed to psychologically stressful situations when young. After observing that these experiences led to aggressive behavior when the rats reached adulthood, they examined what was happening in the animals’ brains to see if the traumatic period had left a lasting mark.
“In a challenging social situation, the orbitofrontal cortex of a healthy individual is activated in order to inhibit aggressive impulses and to maintain normal interactions,” explains Sandi. “But in the rats we studied, we noticed that there was very little activation of the orbitofrontal cortex. This, in turn, reduces their ability to moderate their negative impulses. This reduced activation is accompanied by the overactivation of the amygdala, a region of the brain that’s involved in emotional reactions.” Other researchers who have studied the brains of violent human individuals have observed the same deficit in orbitofrontal activation and the same concomitant reduced inhibition of aggressive impulses. “It’s remarkable; we didn’t expect to find this level of similarity,” says Sandi.
Antidepressants and cerebral plasticity
The scientists also measured changes in the expression of certain genes in the brain. The neurobiologists focused on genes known to be involved in aggressive behavior for which there are polymorphisms (genetic variants) that predispose carriers to an aggressive attitude. They looked at whether the psychological stress experienced by the rats caused a modification in these genes’ expression. “We found that the level of MAOA gene expression increased in the prefrontal cortex,” says Sandi. This alteration was linked to an epigenetic change; in other words, the traumatic experience ended up causing a long-term modification of this gene’s expression.
Finally, the researchers tried to see if an MAOA gene inhibitor, in this case an antidepressant, could reverse the increase in aggressive behavior induced by the juvenile stress. The treatment was effective. The team will now concentrate its efforts on trying to better understand these mechanisms, and explore whether a treatment could possibly reverse these changes in the brain, and above all, to shed light on whether some people are more vulnerable than others depending on their genetic makeup. “This research could also reveal the possible ability of antidepressants – an ability that’s increasingly being suspected – to renew cerebral plasticity,” says the professor.
Study pinpoints brain area’s role in learning
An area of the brain called the orbitofrontal cortex is responsible for decisions made on the spur of the moment, but not those made based on prior experience or habit, according to a new basic science study from substance abuse researchers at the University of Maryland School of Medicine and the National Institute on Drug Abuse (NIDA). Scientists had previously believed that the area of the brain was responsible for both types of behavior and decision-making. The distinction is critical to understanding the neurobiology of decision-making, particularly with regard to substance abuse. The study was published online in the journal Science.
Scientists have assumed that the orbitofrontal cortex plays a role in “value-based” decision-making, when a person compares options and weights consequences and rewards to choose best alternative. The Science study shows that this area of the brain is involved in decision-making only when the value must be inferred or computed rapidly or hastily. If the value has been “cached” or pre-computed, like a habit, then the orbitofrontal cortex is not necessary.
The same is true for learning — if a person infers an outcome but it does not happen, the resulting error can drive learning. The study shows that the orbitofrontal cortex is necessary for the inferred value that is used for this type of learning.
"Our research showed that damage to the orbitofrontal cortex may decrease a person’s ability to use prior experience to make good decisions on the fly," says lead author Joshua Jones, Ph.D., a postdoctoral researcher at the University of Maryland School of Medicine and a research scientist at NIDA, part of the National Institutes of Health. "The person isn’t able to consider the whole continuum of the decision — the mind’s map of how choices play out further down the road. Instead, the person is going to regress to habitual behavior, gravitating toward the choice that provides the most value in its immediate reward."
The study enhances scientists’ understanding of how the brain works in healthy and unhealthy individuals, according to the researchers.
"This discovery has general implications in understanding how the brain processes information to help us make good decisions and to learn from our mistakes," says senior author Geoffrey Schoenbaum, M.D., Ph.D., adjunct professor at the University of Maryland School of Medicine and senior investigator and chief of the Cellular Neurobiology Research Branch at NIDA. "Understanding more about the orbitofrontal cortex also is important for understanding disorders such as addiction that seem to involve maladaptive decision-making and learning. Cocaine in particular seems to have long-lasting effects on the orbitofrontal cortex. One aspect of this work, which we are pursuing, is that perhaps some of the problems that characterize addiction are the result of drug-induced changes in this area of the brain."
(Image: iStock)
