Happiness

From Wikipedia, the free encyclopedia

Happiness is used in the context of mental or emotional states, including positive or pleasant emotions ranging from contentment to intense joy. It is also used in the context of life satisfaction, subjective well-being, eudaimonia, flourishing and well-being.

Since the 1960s, happiness research has been conducted in a wide variety of scientific disciplines, including gerontology, social psychology, clinical and medical research and happiness economics.

Definitions

'Happiness' is the subject of debate on usage and meaning, and on possible differences in understanding by culture.

The word is used in several related areas:

Happy children playing in water

• current experience, including (a) the feeling of an emotion (affect) such as pleasure or joy, or (b) a more general sense of 'emotional condition as a whole'. For instance Daniel Kahneman has defined happiness as "what I experience here and now". This usage is prevalent in dictionary definitions of happiness.
• appraisal of life satisfaction, such as of quality of life. For instance Ruut Veenhoven has defined happiness as "overall appreciation of one's life as-a-whole."
• subjective well-being, which includes measures of affect and of life satisfaction. For instance Sonja Lyubomirsky has described happiness as “the experience of joy, contentment, or positive well-being, combined with a sense that one's life is good, meaningful, and worthwhile.”
• eudaimonia, which is sometimes translated as flourishing.

These uses can give different results. For instance the correlation of income levels has been shown to be substantial with life satisfaction measures, but to be far weaker, at least above a certain threshold, with affect measures.

The implied meaning of the word may vary depending on context, qualifying happiness as a polyseme and a fuzzy concept.

Some users accept these issues, but continue to use the word because of it's convening power.

Philosophy

A smiling 95-year-old man from Pichilemu, Chile.

 

A butcher happily slicing meat.

In the Nicomachean Ethics, written in 350 BCE, Aristotle stated that happiness (also being well and doing well) is the only thing that humans desire for its own sake, unlike riches, honour, health or friendship. He observed that men sought riches, or honour, or health not only for their own sake but also in order to be happy. Note that eudaimonia, the term we translate as "happiness", is for Aristotle an activity rather than an emotion or a state. Thus understood, the happy life is the good life, that is, a life in which a person fulfills human nature in an excellent way. Specifically, Aristotle argues that the good life is the life of excellent rational activity. He arrives at this claim with the Function Argument. Basically, if it's right, every living thing has a function, that which it uniquely does. For humans, Aristotle contends, our function is to reason, since it is that alone that we uniquely do. And performing one's function well, or excellently, is good. Thus, according to Aristotle, the life of excellent rational activity is the happy life. Aristotle does not leave it at that, however. He argues that there is a second best life for those incapable of excellent rational activity. This second best life is the life of moral virtue.

Many ethicists make arguments for how humans should behave, either individually or collectively, based on the resulting happiness of such behavior. Utilitarians, such as John Stuart Mill and Jeremy Bentham, advocated the greatest happiness principle as a guide for ethical behavior.

Friedrich Nietzsche savagely critiqued the English Utilitarians' focus on attaining the greatest happiness, stating that "Man does not strive for happiness, only the Englishman does." Nietzsche meant that making happiness one's ultimate goal and the aim of one's existence, in his words "makes one contemptible." Nietzsche instead yearned for a culture that would set higher, more difficult goals than "mere happiness." He introduced the quasi-dystopic figure of the "last man" as a kind of thought experiment against the utilitarians and happiness-seekers. these small, "last men" who seek after only their own pleasure and health, avoiding all danger, exertion, difficulty, challenge, struggle are meant to seem contemptible to Nietzsche's reader. Nietzsche instead wants us to consider the value of what is difficult, what can only be earned through struggle, difficulty, pain and thus to come to see the affirmative value suffering and unhappiness truly play in creating everything of great worth in life, including all the highest achievements of human culture, not least of all philosophy.

Darrin McMahon claims that there has been a transition over time from emphasis on the happiness of virtue to the virtue of happiness.

Happiness may be said to be a relative concept; the source of happiness for one person might not be the source of happiness for another.

Not all cultures seek to maximise happiness, and some cultures are averse to happiness.

Religion

Eastern religions

Buddhism

Tibetan Buddhist monk

Happiness forms a central theme of Buddhist teachings. For ultimate freedom from suffering, the Noble Eightfold Path leads its practitioner to Nirvana, a state of everlasting peace. Ultimate happiness is only achieved by overcoming craving in all forms. More mundane forms of happiness, such as acquiring wealth and maintaining good friendships, are also recognized as worthy goals for lay people (see sukha). Buddhism also encourages the generation of loving kindness and compassion, the desire for the happiness and welfare of all beings.

Hinduism

In Advaita Vedanta, the ultimate goal of life is happiness, in the sense that duality between Atman and Brahman is transcended and one realizes oneself to be the Self in all.

Patanjali, author of the Yoga Sutras, wrote quite exhaustively on the psychological and ontological roots of bliss.

Confucianism

The Chinese Confucian thinker Mencius, who had sought to give advice to ruthless political leaders during China's Warring States period, was convinced that the mind played a mediating role between the "lesser self" (the physiological self) and the "greater self" (the moral self), and that getting the priorities right between these two would lead to sage-hood. He argued that if one did not feel satisfaction or pleasure in nourishing one's "vital force" with "righteous deeds", then that force would shrivel up (Mencius, 6A:15 2A:2). More specifically, he mentions the experience of intoxicating joy if one celebrates the practice of the great virtues, especially through music.

Abrahamic religions

Judaism

Happiness or simcha (Hebrew: שמחה‎) in Judaism is considered an important element in the service of God. The biblical verse "worship The Lord with gladness; come before him with joyful songs," (Psalm 100:2) stresses joy in the service of God. A popular teaching by Rabbi Nachman of Breslov, a 19th-century Chassidic Rabbi, is "Mitzvah Gedolah Le'hiyot Besimcha Tamid," it is a great mitzvah (commandment) to always be in a state of happiness. When a person is happy they are much more capable of serving God and going about their daily activities than when depressed or upset.

Roman Catholicism

The primary meaning of "happiness" in various European languages involves good fortune, chance or happening. The meaning in Greek philosophy, however, refers primarily to ethics.

In Catholicism, the ultimate end of human existence consists in felicity, Latin equivalent to the Greek eudaimonia, or "blessed happiness", described by the 13th-century philosopher-theologian Thomas Aquinas as a Beatific Vision of God's essence in the next life.

According to St. Augustine and Thomas Aquinas, man's last end is happiness: "all men agree in desiring the last end, which is happiness." However, where utilitarians focused on reasoning about consequences as the primary tool for reaching happiness, Aquinas agreed with Aristotle that happiness cannot be reached solely through reasoning about consequences of acts, but also requires a pursuit of good causes for acts, such as habits according to virtue. In turn, which habits and acts that normally lead to happiness is according to Aquinas caused by laws: natural law and divine law. These laws, in turn, were according to Aquinas caused by a first cause, or God.

According to Aquinas, happiness consists in an "operation of the speculative intellect": "Consequently happiness consists principally in such an operation, viz. in the contemplation of Divine things." And, "the last end cannot consist in the active life, which pertains to the practical intellect." So: "Therefore the last and perfect happiness, which we await in the life to come, consists entirely in contemplation. But imperfect happiness, such as can be had here, consists first and principally in contemplation, but secondarily, in an operation of the practical intellect directing human actions and passions."

Human complexities, like reason and cognition, can produce well-being or happiness, but such form is limited and transitory. In temporal life, the contemplation of God, the infinitely Beautiful, is the supreme delight of the will. Beatitudo, or perfect happiness, as complete well-being, is to be attained not in this life, but the next.

Islam

Al-Ghazali (1058–1111), the Muslim Sufi thinker, wrote "The Alchemy of Happiness", a manual of spiritual instruction throughout the Muslim world and widely practiced today.

Psychology

Happiness in its broad sense is the label for a family of pleasant emotional states, such as joy, amusement, satisfaction, gratification, euphoria, and triumph.

Happiness can be examined in experiential and evaluative contexts. Experiential well-being, or "objective happiness", is happiness measured in the moment via questions such as "How good or bad is your experience now?". In contrast, evaluative well-being asks questions such as "How good was your vacation?" and measures one's subjective thoughts and feelings about happiness in the past. Experiential well-being is less prone to errors in reconstructive memory, but the majority of literature on happiness refers to evaluative well-being. The two measures of happiness can be related by heuristics such as the peak-end rule.

Some commentators focus on the difference between the hedonistic tradition of seeking pleasant and avoiding unpleasant experiences, and the eudaimonic tradition of living life in a full and deeply satisfying way.

Theories on how to achieve happiness include "encountering unexpected positive events", "seeing a significant other", and "basking in the acceptance and praise of others". However others believe that happiness is not solely derived from external, momentary pleasures.

Theories

Maslow's hierarchy of needs

Maslow's hierarchy of needs is a pyramid depicting the levels of human needs, psychological, and physical. When a human being ascends the steps of the pyramid, he reaches self-actualization. Beyond the routine of needs fulfillment, Maslow envisioned moments of extraordinary experience, known as peak experiences, profound moments of love, understanding, happiness, or rapture, during which a person feels more whole, alive, self-sufficient, and yet a part of the world. This is similar to the flow concept of Mihály Csíkszentmihályi. Amitai Etzioni points out that Maslow's definition of human needs, even on the highest level, that of self-actualization, is self-centered (i.e. his view of satisfaction or what makes a person happy, does not include service to others or the common good—unless it enriches the self). As implied by its name, self-actualization is highly individualistic and reflects Maslow's premise that the self is “sovereign and inviolable” and entitled to “his or her own tastes, opinions, values, etc.”

Self-determination theory

Smiling woman from Vietnam

Self-determination theory relates intrinsic motivation to three needs: competence, autonomy, and relatedness.

Modernization and freedom of choice

Ronald Inglehart has traced cross-national differences in the level of happiness based on data from the World Values Survey. He finds that the extent to which a society allows free choice has a major impact on happiness. When basic needs are satisfied, the degree of happiness depends on economic and cultural factors that enable free choice in how people live their lives. Happiness also depends on religion in countries where free choice is constrained.

Positive psychology

Since 2000 the field of positive psychology has expanded drastically in terms of scientific publications, and has produced many different views on causes of happiness, and on factors that correlate with happiness. Numerous short-term self-help interventions have been developed and demonstrated to improve happiness.

Measurement of happiness

Several scales have been developed to measure happiness:

• The Subjective Happiness Scale (SHS) is a four-item scale, measuring global subjective happiness. The scale requires participants to use absolute ratings to characterize themselves as happy or unhappy individuals, as well as it asks to what extent they identify themselves with descriptions of happy and unhappy individuals.
• The Positive and Negative Affect Schedule (PANAS) is used to detect the relation between personality traits and positive or negative affects at this moment, today, the past few days, the past week, the past few weeks, the past year, and generally (on average). PANAS is a 20-item questionnaire, which uses a five-point Likert scale (1 = very slightly or not at all, 5 = extremely). A longer version with additional affect scales is available in a manual.
• The Satisfaction with Life Scale (SWLS) is a global cognitive assessment of life satisfaction developed by Ed Diener. The SWLS requires a person to use a seven-item scale to state their agreement or disagreement (1 = strongly disagree, 4 = neither agree nor disagree, 7 = strongly agree) with five statements about their life.

The UK began to measure national well being in 2012, following Bhutan, which already measured gross national happiness.

The 2012 World Happiness Report stated that in subjective well-being measures, the primary distinction is between cognitive life evaluations and emotional reports. Happiness is used in both life evaluation, as in “How happy are you with your life as a whole?”, and in emotional reports, as in “How happy are you now?,” and people seem able to use happiness as appropriate in these verbal contexts. Using these measures, the World Happiness Report identifies the countries with the highest levels of happiness.

Etzioni argues that happiness is the wrong metric, because it does not take into account that doing the right thing, what is moral, often does not produce happiness in the way this term is usually used.
Happiness has been found to be quite stable over time.

Relationship to physical characteristics

Even though no evidence of happiness causing improved physical health has been found, the topic is being researched by Laura Kubzansky, a professor at the Lee Kum Sheung Center for Health and Happiness at the Harvard T.H. Chan School of Public Health, Harvard University. A positive relationship has been suggested between the volume of gray matter in the right precuneus area of the brain and the subject's subjective happiness score.

Possible limits on happiness seeking

June Gruber suggests that seeking happiness can have negative effects, such as failure to meet over-high expectations, and instead advocates a more open stance to all emotions. Other research has analysed possible trade-offs between happiness and meaning in life. Not all cultures seek to maximise happiness.

Economic and political views

Newly commissioned officers celebrate their new positions by throwing their midshipmen covers into the air as part of the U.S. Naval Academy class of 2011 graduation and commissioning ceremony.

In politics, happiness as a guiding ideal is expressed in the United States Declaration of Independence of 1776, written by Thomas Jefferson, as the universal right to "the pursuit of happiness." This seems to suggest a subjective interpretation but one that nonetheless goes beyond emotions alone. In fact, this discussion is often based on the naive assumption that the word happiness meant the same thing in 1776 as it does today. In fact, happiness meant "prosperity, thriving, wellbeing" in the 18th century.

Common market health measures such as GDP and GNP have been used as a measure of successful policy. On average richer nations tend to be happier than poorer nations, but this effect seems to diminish with wealth. This has been explained by the fact that the dependency is not linear but logarithmic, i.e., the same percentual increase in the GNP produces the same increase in happiness for wealthy countries as for poor countries. Increasingly, academic economists and international economic organisations are arguing for and developing multi-dimensional dashboards which combine subjective and objective indicators to provide a more direct and explicit assessment of human wellbeing. Work by Paul Anand and colleagues helps to highlight the fact that there many different contributors to adult wellbeing, that happiness judgement reflect, in part, the presence of salient constraints, and that fairness, autonomy, community and engagement are key aspects of happiness and wellbeing throughout the life course.

Libertarian think tank Cato Institute claims that economic freedom correlates strongly with happiness preferably within the context of a western mixed economy, with free press and a democracy. According to certain standards, East European countries (ruled by Communist parties) were less happy than Western ones, even less happy than other equally poor countries.

However, much empirical research in the field of happiness economics, such as that by Benjamin Radcliff, professor of Political Science at the University of Notre Dame, supports the contention that (at least in democratic countries) life satisfaction is strongly and positively related to the social democratic model of a generous social safety net, pro-worker labor market regulations, and strong labor unions. Similarly, there is evidence that public policies that reduce poverty and support a strong middle class, such as a higher minimum wage, strongly affects average levels of well-being.

It has been argued that happiness measures could be used not as a replacement for more traditional measures, but as a supplement. According to professor Edward Glaeser, people constantly make choices that decrease their happiness, because they have also more important aims. Therefore, the government should not decrease the alternatives available for the citizen by patronizing them but let the citizen keep a maximal freedom of choice.

Good mental health and good relationships contribute more than income to happiness and governments should take these into account.

Contributing factors and research outcomes

Research on positive psychology, well-being, eudaimonia and happiness, and the theories of Diener, Ryff, Keyes, and Seligmann covers a broad range of levels and topics, including "the biological, personal, relational, institutional, cultural, and global dimensions of life."

Reward system

From Wikipedia, the free encyclopedia

Examples of primary rewards

Water Sex

Food Parental care

Addiction and dependence glossary

addiction – a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences addictive behavior – a behavior that is both rewarding and reinforcing addictive drug – a drug that is both rewarding and reinforcing dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose drug withdrawal – symptoms that occur upon cessation of repeated drug use physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens) psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia) reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach sensitization – an amplified response to a stimulus resulting from repeated exposure to it substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

The reward system is a group of neural structures responsible for incentive salience (i.e., motivation and "wanting", desire, or craving for a reward), associative learning (primarily positive reinforcement and classical conditioning), and positively-valenced emotions, particularly ones which involve pleasure as a core component (e.g., joy, euphoria and ecstasy). Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. In its description of a rewarding stimulus (i.e., "a reward"), a review on reward neuroscience noted, "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward." In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.

Primary rewards are a class of rewarding stimuli which facilitate the survival of one's self and offspring, and include homeostatic (e.g., palatable food) and reproductive (e.g., sexual contact and parental investment) rewards. Intrinsic rewards are unconditioned rewards that are attractive and motivate behavior because they are inherently pleasurable. Extrinsic rewards (e.g., money or seeing one's favorite sports team winning a game) are conditioned rewards that are attractive and motivate behavior, but are not inherently pleasurable. Extrinsic rewards derive their motivational value as a result of a learned association (i.e., conditioning) with intrinsic rewards. Extrinsic rewards may also elicit pleasure (e.g., euphoria from winning a lot of money in a lottery) after being classically conditioned with intrinsic rewards.

Survival for most animal species depends upon maximizing contact with beneficial stimuli and minimizing contact with harmful stimuli. Reward cognition serves to increase the likelihood of survival and reproduction by causing associative learning, eliciting approach and consummatory behavior, and triggering positively-valenced emotions. Thus, reward is a mechanism that evolved to help increase the adaptive fitness of animals.

Definition

In neuroscience, the reward system is a collection of brain structures and neural pathways that are responsible for reward-related cognition, including associative learning (primarily classical conditioning and operant reinforcement), incentive salience (i.e., motivation and "wanting", desire, or craving for a reward), and positively-valenced emotions, particularly emotions that involve pleasure (i.e., hedonic "liking").

Terms that are commonly used to describe behavior related to the "wanting" or desire component of reward include appetitive behavior, approach behavior, preparatory behavior, instrumental behavior, anticipatory behavior, and seeking. Terms that are commonly used to describe behavior related to the "liking" or pleasure component of reward include consummatory behavior and taking behavior.

The three primary functions of rewards are their capacity to:

1. produce associative learning (i.e., classical conditioning and operant reinforcement);
2. affect decision-making and induce approach behavior (via the assignment of motivational salience to rewarding stimuli);
3. elicit positively-valenced emotions, particularly pleasure.

Anatomy

The brain structures that compose the reward system are located primarily within the cortico-basal ganglia-thalamo-cortical loop; the basal ganglia portion of the loop drives activity within the reward system. Most of the pathways that connect structures within the reward system are glutamatergic interneurons, GABAergic medium spiny neurons (MSNs), and dopaminergic projection neurons, although other types of projection neurons contribute (e.g., orexinergic projection neurons). The reward system includes the ventral tegmental area, ventral striatum (i.e., the nucleus accumbens and olfactory tubercle), dorsal striatum (i.e., the caudate nucleus and putamen), substantia nigra (i.e., the pars compacta and pars reticulata), prefrontal cortex, anterior cingulate cortex, insular cortex, hippocampus, hypothalamus (particularly, the orexinergic nucleus in the lateral hypothalamus), thalamus (multiple nuclei), subthalamic nucleus, globus pallidus (both external and internal), ventral pallidum, parabrachial nucleus, amygdala, and the remainder of the extended amygdala. The dorsal raphe nucleus and cerebellum appear to modulate some forms of reward-related cognition (i.e., associative learning, motivational salience, and positive emotions) and behaviors as well. The laterodorsal tegmental nucleus (LTD), pedunculopontine nucleus (PPTg), and lateral habenula (LHb) (both directly and indirectly via the rostromedial tegmental nucleus) are also capable of inducing aversive salience and incentive salience through their projections to the ventral tegmental area (VTA). The LDT and PPTg both send glutaminergic projections to the VTA that synapse on dopaminergic neurons, both of which can produce incentive salience. The LHb sends glutaminergic projections, the majority of which synapse on GABAergic RMTg neurons that in turn drive inhibition of dopaminergic VTA neurons, although some LHb projections terminate on VTA interneurons. These LHb projections are activated both by aversive stimuli and by the absence of an expected reward, and excitation of the LHb can induce aversion.

Most of the dopamine pathways (i.e., neurons that use the neurotransmitter dopamine to communicate with other neurons) that project out of the ventral tegmental area are part of the reward system; in these pathways, dopamine acts on D1-like receptors or D2-like receptors to either stimulate (D1-like) or inhibit (D2-like) the production of cAMP. The GABAergic medium spiny neurons of the striatum are components of the reward system as well. The glutamatergic projection nuclei in the subthalamic nucleus, prefrontal cortex, hippocampus, thalamus, and amygdala connect to other parts of the reward system via glutamate pathways. The medial forebrain bundle, which is a set of many neural pathways that mediate brain stimulation reward (i.e., reward derived from direct electrochemical stimulation of the lateral hypothalamus), is also a component of the reward system.

Two theories exist with regard to the activity of the nucleus accumbens and the generation liking and wanting. The inhibition (or hyper­polar­ization) hypothesis proposes that the nucleus accumbens exerts tonic inhibitory effects on downstream structures such as the ventral pallidum, hypothalamus or ventral tegmental area, and that in inhibiting MSNs in the nucleus accumbens (NAcc), these structures are excited, "releasing" reward related behavior. While GABA receptor agonists are capable of eliciting both "liking" and "wanting" reactions in the nucleus accumbens, glutaminergic inputs from the basolateral amygdala, ventral hippocampus, and medial prefrontal cortex can drive incentive salience. Furthermore, while most studies find that NAcc neurons reduce firing in response to reward, a number of studies find the opposite response. This had led to the proposal of the disinhibition (or depolarization) hypothesis, that proposes that excitation or NAcc neurons, or at least certain subsets, drives reward related behavior.

After nearly 50 years of research on brain-stimulation reward, experts have certified that dozens of sites in the brain will maintain intracranial self-stimulation. Regions include the lateral hypothalamus and medial forebrain bundles, which are especially effective. Stimulation there activates fibers that form the ascending pathways; the ascending pathways include the mesolimbic dopamine pathway, which projects from the ventral tegmental area to the nucleus accumbens. There are several explanations as to why the mesolimbic dopamine pathway is central to circuits mediating reward. First, there is a marked increase in dopamine release from the mesolimbic pathway when animals engage in intracranial self-stimulation. Second, experiments consistently indicate that brain-stimulation reward stimulates the reinforcement of pathways that are normally activated by natural rewards, and drug reward or intracranial self-stimulation can exert more powerful activation of central reward mechanisms because they activate the reward center directly rather than through the peripheral nerves. Third, when animals are administered addictive drugs or engage in naturally rewarding behaviors, such as feeding or sexual activity, there is a marked release of dopamine within the nucleus accumbens. However, dopamine is not the only reward compound in the brain.

Pleasure centers

Pleasure is a component of reward, but not all rewards are pleasurable (e.g., money does not elicit pleasure unless this response is conditioned). Stimuli that are naturally pleasurable, and therefore attractive, are known as intrinsic rewards, whereas stimuli that are attractive and motivate approach behavior, but are not inherently pleasurable, are termed extrinsic rewards. Extrinsic rewards (e.g., money) are rewarding as a result of a learned association with an intrinsic reward. In other words, extrinsic rewards function as motivational magnets that elicit "wanting", but not "liking" reactions once they have been acquired.

The reward system contains pleasure centers or hedonic hotspots – i.e., brain structures that mediate pleasure or "liking" reactions from intrinsic rewards. As of October 2017, hedonic hotspots have been identified in subcompartments within the nucleus accumbens shell, ventral pallidum, parabrachial nucleus, orbitofrontal cortex (OFC), and insular cortex. The hotspot within the nucleus accumbens shell is located in the rostrodorsal quadrant of the medial shell, while the hedonic coldspot is located in a more posterior region. The posterior ventral pallidum also contains a hedonic hotspot, while the anterior ventral pallidum contains a hedonic coldspot. Microinjections of opioids, endocannabinoids, and orexin are capable of enhancing liking in these hotspots. The hedonic hotspots located in the anterior OFC and posterior insula have been demonstrated to respond to orexin and opioids, as has the overlapping hedonic coldspot in the anterior insula and posterior OFC. On the other hand, the parabrachial nucleus hotspot has only been demonstrated to respond to benzodiazepine receptor agonists.

Hedonic hotspots are functionally linked, in that activation of one hotspot results in the recruitment of the others, as indexed by the induced expression of c-Fos, an immediate early gene. Furthermore, inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense euphoria.

Wanting

Tuning of appetitive and defensive reactions in the nucleus accumbens shell. (Above) AMPA blockade requires D1 function in order to produce motivated behaviors, regardless of valence, and D2 function to produce defensive behaviors. GABA agonism, on the other hand, does not requires dopamine receptor function.(Below)The expansion of the anatomical regions that produce defensive behaviors under stress, and appetitive behaviors in the home environment produced by AMPA antagonism. This flexibility is less evident with GABA agonism.

 

Incentive salience is the "wanting" or "desire" attribute, which includes a motivational component, that is assigned to a rewarding stimulus by the nucleus accumbens shell (NAcc shell). The degree of dopamine neurotransmission into the NAcc shell from the mesolimbic pathway is highly correlated with the magnitude of incentive salience for rewarding stimuli.

Activation of the dorsorostral region of the nucleus accumbens correlates with increases in wanting without concurrent increases in liking. However, dopaminergic neurotransmission into the nucleus accumbens shell is responsible not only for appetitive motivational salience (i.e., incentive salience) towards rewarding stimuli, but also for aversive motivational salience, which directs behavior away from undesirable stimuli. In the dorsal striatum, activation of D1 expressing MSNs produces appetitive incentive salience, while activation of D2 expressing MSNs produces aversion. In the NAcc, such a dichotomy is not as clear cut, and activation of both D1 and D2 MSNs is sufficient to enhance motivation, likely via disinhibiting the VTA through inhibiting the ventral pallidum.

Robinson and Berridge's incentive-sensitization theory (1993) proposed that reward contains separable psychological components: wanting (incentive) and liking (pleasure). To explain increasing contact with a certain stimulus such as chocolate, there are two independent factors at work – our desire to have the chocolate (wanting) and the pleasure effect of the chocolate (liking). According to Robinson and Berridge, wanting and liking are two aspects of the same process, so rewards are usually wanted and liked to the same degree. However, wanting and liking also change independently under certain circumstances. For example, rats that do not eat after receiving dopamine (experiencing a loss of desire for food) act as though they still like food. In another example, activated self-stimulation electrodes in the lateral hypothalamus of rats increase appetite, but also cause more adverse reactions to tastes such as sugar and salt; apparently, the stimulation increases wanting but not liking. Such results demonstrate that our reward system includes independent processes of wanting and liking. The wanting component is thought to be controlled by dopaminergic pathways, whereas the liking component is thought to be controlled by opiate-benzodiazepine systems.

Animals vs. humans

Animals quickly learn to press a bar to obtain an injection of opiates directly into the midbrain tegmentum or the nucleus accumbens. The same animals do not work to obtain the opiates if the dopaminergic neurons of the mesolimbic pathway are inactivated. In this perspective, animals, like humans, engage in behaviors that increase dopamine release.

Kent Berridge, a researcher in affective neuroscience, found that sweet (liked ) and bitter (disliked ) tastes produced distinct orofacial expressions, and these expressions were similarly displayed by human newborns, orangutans, and rats. This was evidence that pleasure (specifically, liking) has objective features and was essentially the same across various animal species. Most neuroscience studies have shown that the more dopamine released by the reward, the more effective the reward is. This is called the hedonic impact, which can be changed by the effort for the reward and the reward itself. Berridge discovered that blocking dopamine systems did not seem to change the positive reaction to something sweet (as measured by facial expression). In other words, the hedonic impact did not change based on the amount of sugar. This discounted the conventional assumption that dopamine mediates pleasure. Even with more-intense dopamine alterations, the data seemed to remain constant.

Berridge developed the incentive salience hypothesis to address the wanting aspect of rewards. It explains the compulsive use of drugs by drug addicts even when the drug no longer produces euphoria, and the cravings experienced even after the individual has finished going through withdrawal. Some addicts respond to certain stimuli involving neural changes caused by drugs. This sensitization in the brain is similar to the effect of dopamine because wanting and liking reactions occur. Human and animal brains and behaviors experience similar changes regarding reward systems because these systems are so prominent.

Learning

Rewarding stimuli can drive learning in both the form of classical conditioning (Pavlovian conditioning) and operant conditioning (instrumental conditioning). In classical conditioning, a reward can act as an unconditioned stimulus that, when associated with the conditioned stimulus, causes the conditioned stimulus to elicit both musculoskeletal (in the form of simple approach and avoidance behaviors) and vegetative responses. In operant conditioning, a reward may act as a reinforcer in that it increases or supports actions that lead to itself. Learned behaviors may or may not be sensitive to the value of the outcomes they lead to; behaviors that are sensitive to the contingency of an outcome on the performance of an action as well as the outcome value are goal-directed, while elicited actions that are insensitive to contingency or value are called habits. This distinction is thought to reflected two forms of learning, model free and model based. Model free learning involves the simple caching and updating of values. In contrast, model based learning involves the storage and construction of an internal model of events that allows inference and flexible prediction. Although pavlovian conditioning is generally assumed to be model-free, the incentive salience assigned to a conditioned stimulus is flexible with regard to changes in internal motivational states.

Distinct neural systems are responsible for learning associations between stimuli and outcomes, actions and outcomes, and stimuli and responses. Although classical conditioning is not limited to the reward system, the enhancement of instrumental performance by stimuli (i.e., Pavlovian-instrumental transfer) requires the nucleus accumbens. Habitual and goal directed instrumental learning are dependent upon the lateral striatum and the medial striatum, respectively.

During instrumental learning, opposing changes in the ratio of AMPA to NMDA receptors and phosphorylated ERK occurs in the D₁-type and D₂-type MSNs that constitute the direct and indirect pathways, respectively. These changes in synaptic plasticity and the accompanying learning is dependent upon activation of striatal D1 and NMDA receptors. The intracellular cascade activated by D1 receptors involves the recruitment of protein kinase A, and through resulting phosphorylation of DARPP-32, the inhibition of phosphatases that deactivate ERK. NMDA receptors activate ERK through a different but interrelated Ras-Raf-MEK-ERK pathway. Alone NMDA mediated activation of ERK is self-limited, as NMDA activation also inhibits PKA mediated inhibition of ERK deactivating phosphatases. However, when D1 and NMDA cascades are co-activated, they work synergistically, and the resultant activation of ERK regulates synaptic plasticity in the form of spine restructuring, transport of AMPA receptors, regulation of CREB, and increasing cellular excitability via inhibiting Kv4.2.

History

Skinner box

The first clue to the presence of a reward system in the brain came with an accident discovery by James Olds and Peter Milner in 1954. They discovered that rats would perform behaviors such as pressing a bar, to administer a brief burst of electrical stimulation to specific sites in their brains. This phenomenon is called intracranial self-stimulation or brain stimulation reward. Typically, rats will press a lever hundreds or thousands of times per hour to obtain this brain stimulation, stopping only when they are exhausted. While trying to teach rats how to solve problems and run mazes, stimulation of certain regions of the brain where the stimulation was found seemed to give pleasure to the animals. They tried the same thing with humans and the results were similar. The explanation to why animals engage in a behavior that has no value to the survival of either themselves or their species is that the brain stimulation is activating the system underlying reward.

In a fundamental discovery made in 1954, researchers James Olds and Peter Milner found that low-voltage electrical stimulation of certain regions of the brain of the rat acted as a reward in teaching the animals to run mazes and solve problems. It seemed that stimulation of those parts of the brain gave the animals pleasure, and in later work humans reported pleasurable sensations from such stimulation. When rats were tested in Skinner boxes where they could stimulate the reward system by pressing a lever, the rats pressed for hours. Research in the next two decades established that dopamine is one of the main chemicals aiding neural signaling in these regions, and dopamine was suggested to be the brain's "pleasure chemical".

Ivan Pavlov was a psychologist who used the reward system to study classical conditioning. Pavlov used the reward system by rewarding dogs with food after they had heard a bell or another stimulus. Pavlov was rewarding the dogs so that the dogs associated food, the reward, with the bell, the stimulus. Edward L. Thorndike used the reward system to study operant conditioning. He began by putting cats in a puzzle box and placing food outside of the box so that the cat wanted to escape. The cats worked to get out of the puzzle box to get to the food. Although the cats ate the food after they escaped the box, Thorndike learned that the cats attempted to escape the box without the reward of food. Thorndike used the rewards of food and freedom to stimulate the reward system of the cats. Thorndike used this to see how the cats learned to escape the box.

Clinical significance

Addiction

ΔFosB (DeltaFosB) – a gene transcription factor – overexpression in the D1-type medium spiny neurons of the nucleus accumbens is the crucial common factor among virtually all forms of addiction (i.e., behavioral addictions and drug addictions) that induces addiction-related behavior and neural plasticity. In particular, ΔFosB promotes self-administration, reward sensitization, and reward cross-sensitization effects among specific addictive drugs and behaviors. Certain epigenetic modifications of histone protein tails (i.e., histone modifications) in specific regions of the brain are also known to play a crucial role in the molecular basis of addictions.

Addictive drugs and behaviors are rewarding and reinforcing (i.e., are addictive) due to their effects on the dopamine reward pathway.

The lateral hypothalamus and medial forebrain bundle has been the most-frequently-studied brain-stimulation reward site, particularly in studies of the effects of drugs on brain stimulation reward.^[64] The neurotransmitter system that has been most-clearly identified with the habit-forming actions of drugs-of-abuse is the mesolimbic dopamine system, with its efferent targets in the nucleus accumbens and its local GABAergic afferents. The reward-relevant actions of amphetamine and cocaine are in the dopaminergic synapses of the nucleus accumbens and perhaps the medial prefrontal cortex. Rats also learn to lever-press for cocaine injections into the medial prefrontal cortex, which works by increasing dopamine turnover in the nucleus accumbens. Nicotine infused directly into the nucleus accumbens also enhances local dopamine release, presumably by a presynaptic action on the dopaminergic terminals of this region. Nicotinic receptors localize to dopaminergic cell bodies and local nicotine injections increase dopaminergic cell firing that is critical for nicotinic reward. Some additional habit-forming drugs are also likely to decrease the output of medium spiny neurons as a consequence, despite activating dopaminergic projections. For opiates, the lowest-threshold site for reward effects involves actions on GABAergic neurons in the ventral tegmental area, a secondary site of opiate-rewarding actions on medium spiny output neurons of the nucleus accumbens. Thus GABAergic afferents to the mesolimbic dopamine neurons (primary substrate of opiate reward), the mesolimbic dopamine neurons themselves (primary substrate of psychomotor stimulant reward), and GABAergic efferents to the mesolimbic dopamine neurons (a secondary site of opiate reward) form the core of currently characterized drug-reward circuitry.

Motivation

Dysfunctional motivational salience appears in a number of psychiatric symptoms and disorders. Anhedonia, traditionally defined as a reduced capacity to feel pleasure, has been reexamined as reflecting blunted incentive salience, as most anhedonic populations exhibit intact “liking”. On the other end of the spectrum, heightened incentive salience that is narrowed for specific stimuli is characteristic of behavioral and drug addictions. In the case of fear or paranoia, dysfunction may lie in elevated aversive salience.

Neuroimaging studies across diagnoses associated with anhedonia have reported reduced activity in the OFC and ventral striatum. One meta analysis reported anhedonia was associated with reduced neural response to reward anticipation in the caudate nucleus, putamen, nucleus accumbens and medial prefrontal cortex (mPFC).

Mood Disorders

Depression is associated with reduced motivation, as assessed by willingness to expend effort for reward. These abnormalities have been tentatively linked to reduced activity in areas of the striatum, and while dopaminergic abnormalities are hypothesized to play a role, most studies probing dopamine function in depression have reported inconsistent results. Although postmortem and neuroimaging studies have found abnormalities in numerous regions of the reward system, few findings are consistently replicated. Some studies have reported reduced NAcc, hippocampus, medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC) activity, as well as elevated basolateral amygdala and subgenual cingulate cortex (sgACC) activity during tasks related to reward or positive stimuli. These neuroimaging abnormalities are complimented by little post mortem research, but what little research has been done suggests reduced excitatory synapses in the mPFC. Reduced activity in the mPFC during reward related tasks appears to be localized to more dorsal regions(i.e. the pregenual cingulate cortex), while the more ventral sgACC is hyperactive in depression.

Attempts to investigate underlying neural circuitry in animal models has also yielded conflicting results. Two paradigms are commonly used to simulate depression, chronic social defeat (CSDS), and chronic mild stress (CMS), although many exist. CSDS produces reduced preference for sucrose, reduced social interactions, and increased immobility in the forced swim test. CMS similarly reduces sucrose preference, and behavioral despair as assessed by tail suspension and forced swim tests. Animals susceptible to CSDS exhibit increased phasic VTA firing, and inhibition of VTA-NAcc projections attenuates behavioral deficits induced by CSDS. However, inhibition of VTA-mPFC projections exacerbates social withdrawal. On the other hand, CMS associated reductions in sucrose preference and immobility were attenuated and exacerbated by VTA excitation and inhibition, respectively. Although these differences may be attributable to different stimulation protocols or poor translational paradigms, variable results may also lie in the heterogenous functionality of reward related regions.

Optogenetic stimulation of the mPFC as a whole produces antidepressant effects. This effect appears localized to the rodent homologue of the pgACC (the prelimbic cortex), as stimulation of the rodent homologue of the sgACC (the infralimbic cortex) produces no behavioral effects. Furthermore, deep brain stimulation in the infralimbic cortex, which is thought to have an inhibitory effect, also produces an antidepressant effect. This finding is congruent with the observation that pharmacological inhibition of the infralimbic cortex attenuates depressive behaviors.

Schizophrenia

Schizophrenia is associated with deficits in motivation, commonly grouped under other negative symptoms such as reduced spontaneous speech. The experience of “liking” is frequently reported to be intact, both behaviorally and neurally, although results may be specific to certain stimuli, such as monetary rewards. Furthermore, implicit learning and simple reward related tasks are also intact in schizophrenia. Rather, deficits in the reward system present during reward related tasks that are cognitively complex. These deficits are associated with both abnormal striatal and OFC activity, as well as abnormalities in regions associated with cognitive functions such as the dorsolateral prefrontal cortex (dlPFC).

Orbitofrontal cortex

From Wikipedia, the free encyclopedia

Orbitofrontal cortex
Approximate location of the OFC shown on a sagittal MRI
Orbital surface of left frontal lobe.
Details
Part of	Frontal lobe
Identifiers
Latin	cortex orbitofrontalis
NeuroNames	91
NeuroLex ID	birnlex_1049
FMA	242003

The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 and 13; in humans it consists of Brodmann area 10, 11 and 47.

The OFC is considered anatomically synonymous with the ventromedial prefrontal cortex. Therefore, the region is distinguished due to the distinct neural connections and the distinct functions it performs. It is defined as the part of the prefrontal cortex that receives projections from the magnocellular, medial nucleus of the mediodorsal thalamus, and is thought to represent emotion and reward in decision making. It gets its name from its position immediately above the orbits in which the eyes are located. Considerable individual variability has been found in the OFC of humans. A related area is found in rodents.

Structure

The OFC is divided into multiple broad regions distinguished by cytoarchitecture, including brodmann area 47/12, brodmann area 11, brodmann area 14, brodmann area 13, and brodmann area 10. Four gyri are split by a complex of sulci that most frequently resembles a "H" or a "K" pattern. Extending along the rostro-caudal axis, two sulci, the lateral and orbital sulci, are usually connected by the transverse orbital suclus, which extends along a medial-lateral axis. Most medially, the medial orbital gyrus is separated from the gyrus rectus by the olfactory sulcus. Anteriorly, both the gyrus rectus and the medial part of the medial orbital gyrus consist of area 11(m), and posteriorly, area 14. The posterior orbital gyrus consists mostly of area 13, and is bordered medially and laterally by the anterior limbs of the medial and lateral orbital sulci. Area 11 makes up a large part of the OFC involving both the lateral parts of the medial orbital gyrus as well as the anterior orbital gyrus. The lateral orbital gyrus consists mostly of area 47/12. Most of the OFC is granular, although the caudal parts of area 13 and area 14 are agranular. These caudal regions, which sometimes includes parts of the insular cortex, responds primarily to unprocessed sensory cues.

Connections

The connectivity of the OFC varies somewhat along a rostral-caudal axis. The caudal OFC is more heavily interconnected with sensory regions, notably receiving direct input from the pyriform cortex. The caudal OFC is also the most heavily interconnected with the amygdala. Rostrally, the OFC receives fewer direct sensory projections, and is less connected with the amygdala, but it is interconnected with the lateral prefrontal cortex and parahippocampus. The connectivity of the OFC has also been conceptualized as being composed of two networks; an orbital network composed of most of the central parts of the OFC, including most of areas 47/12, 13, and 11; a medial network composed of the medial most and caudolateral regions of the OFC, as well as areas 24, 25 and 32 of the medial prefrontal cortex. The medial and orbital networks are sometimes referred to as the "visceromotor network" and the "sensory network", respectively.

Afferents

The OFC receives projections from multiple sensory modalities. The primary olfactory cortex, gustatory cortex, secondary somatosensory cortex, superior and inferior temporal gyrus(conveying visual information) all project to the OFC. Evidence for auditory inputs is weak, although the some neurons respond to auditory stimuli, indicating an indirect projection may exist. The OFC also receives input from the medial dorsal nucleus, insular cortex, entorhinal cortex, perirhinal cortex, hypothalamus, and amygdala.

Efferents

The orbitofrontal cortex is reciprocally connected with the perihinal and entorhinal cortices, the amygdala, the hypothalamus, and parts of the medial temporal lobe. In addition to these outputs, the OFC also projects to the striatum, including the nucleus accumbens, caudate nucleus, and ventral putamen, as well as regions of the midbrain including the periaqueductal grey, and ventral tegmental area. OFC inputs to the amygdala synapse on multiple targets, including two robust pathways to the basolateral amygdala and intercalated cells of the amygdala, as well as a weaker direct projection to the central nucleus of the amygdala.

Function

Multiple functions have been ascribed to the OFC including mediating context specific responding, encoding contingencies in a flexible manner, encoding value, encoding inferred value, inhibiting responses, learning changes in contingency, emotional appraisal, altering behavior through somatic markers, driving social behavior, and representing state spaces. While most of these theories explain certain aspects of electrophysiological observations and lesion related changes in behavior, they often fail to explain, or are contradicted by other findings. One proposal that explains the variety of OFC functions is that the OFC encodes state spaces, or the discrete configuration of internal and external characteristics associated with a situation and its contingencies For example the proposal that the OFC encodes economic value may be a reflection of the OFC encoding task state value. The representation of task states could also explain the proposal that the OFC acts as a flexible map of contingencies, as a switch in task state would enable the encoding of new contingencies in one state, with the preservation of old contingencies in a separate state, enabling switching contingencies when the old task state becomes relevant again. The representation of task states is supported by electrophysiological evidence demonstrating that the OFC responds to a diverse array of task features, and is capable of rapidly remapping during contingency shifts. The representation of task states may influence behavior through multiple potential mechanisms. For example, the OFC is necessary for ventral tegmental area (VTA) neurons to produce a dopaminergic reward prediction error, and the OFC may encode expectations for computation of RPEs in the VTA.

Specific functions have been ascribed to subregions of the OFC. The lateral OFC has been proposed to reflect potential choice value, enabling fictive(counterfactual) prediction errors to potentially mediate switching choices during reversal, extinction and devaluation. Optogenetic activation of the lOFC enhances goal directed over habitual behavior, possibly reflecting increased sensitivity to potential choices and therefore increased switching. The mOFC, on the other hand, has been proposed to reflect relative subjective value. In rodents, a similar function has been ascribed to the mOFC, encoding action value in a graded fashion, while the lOFC has been proposed to encode specific sensory features of outcomes. The lOFC has also been proposed to encode stimulus outcome associations, which are then compared by value in the mOFC. Meta analysis of neuroimaging studies in humans reveals that a medial-lateral valence gradient exists, with the medial OFC responding most often to reward, and the lateral OFC responding most often to punishment. A posterior-anterior abstractness gradient was also found, with the posterior OFC responding to more simple reward, and the anterior OFC responding more to abstract rewards. Similar results were reported in a meta analysis of studies on primary versus secondary rewards.

The OFC and basolteral amygdala (BLA) are highly interconnected, and their connectivity is necessary for devaluation tasks. Damage to either the BLA or the OFC before, but only the OFC after devaluation impairs performance. While the BLA only responds to cues predicting salient outcomes in a graded fashion in accordance with value, the OFC responds to both value and the specific sensory attributes of cue-outcome associations. While OFC neurons that, early in learning, respond to outcome receipt normally transfer their response to the onset of cues that predict the outcome, damage to the BLA impairs this form of learning.

The posterior orbitofrontal cortex (pOFC) is connected to the amygdala via multiple paths, that are capable of both upregulating and downregulating autonomic nervous system activity. Tentative evidence suggests that the neuromodulator dopamine plays a role in mediating the balance between the inhibitory and excitatory pathways, with a high dopamine state driving autonomic activity.

It has been suggested that the medial OFC is involved in making stimulus-reward associations and with the reinforcement of behavior, while the lateral OFC is involved in stimulus-outcome associations and the evaluation and possibly reversal of behavior. Activity in the lateral OFC is found, for example, when subjects encode new expectations about punishment and social reprisal.

The mid-anterior OFC has been found to consistently track subjective pleasure in neuroimaging studies. A hedonic hotspot has been discovered in the anterior OFC, which is capable of enhancing liking response to sucrose. The OFC is also capable of biasing the affective responses induced by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonism in the nucleus accumbens towards appetitive responses.

The OFC is capable of modulating aggressive behavior via a projections to interneurons in the amygdala that inhibit glutaminergic projections to the ventromedial hypothalamus.

Electrophysiology

Neurons in the OFC respond both to primary reinforcers, as well as cues that predict rewards across multiple sensory domains. The evidence for responses to visual, gustatory, somatosensory, and olfactory stimuli is robust, but evidence or auditory responses are weaker. In a subset of OFC neurons, neural responses to rewards or reward cues are modulated by individual preference and by internal motivational states such as hunger. A fraction of neurons that respond to sensory cues predicting a reward are selective for reward, and exhibit reversal behavior when cue outcome relationships are swapped. Neurons in the OFC also exhibit responses to the absence of an expected reward, and punishment. Another population of neurons exhibits responses to novel stimuli and can “remember” familiar stimuli for up to a day.

During cued reward or cued instrumental reward tasks, neurons in the OFC exhibit three general patterns of firing; firing in response to cues; firing before reward receipt; firing in response to reward receipt. In contrast to the medial prefrontal cortex and striatum, OFC neurons do not exhibit firing mediating by movement. The encoding of reward magnitude is also flexible, and takes into account the relative values of present rewards.

Humans

The human OFC is among the least-understood regions of the human brain; but it has been proposed that the OFC is involved in sensory integration, in representing the affective value of reinforcers, and in decision-making and expectation. In particular, the OFC seems to be important in signaling the expected rewards/punishments of an action given the particular details of a situation. In doing this, the brain is capable of comparing the expected reward/punishment with the actual delivery of reward/punishment, thus, making the OFC critical for adaptive learning. This is supported by research in humans, non-human primates, and rodents.

Psychiatric disorders

The orbitofrontal cortex has been implicated in schizophrenia, major depressive disorder, bipolar disorder, obsessive-compulsive disorder, addiction, post-traumatic stress disorder, and panic disorder. Although neuroimaging studies have provided evidence for dysfunction in a wide variety of psychiatric disorders, the enigmatic nature of the OFCs role in behavior complicates the understanding of its role in the pathophysiology of psychiatric disorders. The function of the OFC is not known, but its anatomical connections with the ventral striatum, amygdala, hypothalamus, hippocampus, and periaqueductal grey support a role in mediating reward and fear related behaviors.

Obsessive compulsive disorder

Meta analyses of neuroimaging studies in OCD report hyperactivity in areas generally considered to be part of the orbitofrontal segment of the cortico-basal ganglia-thalamo-cortical loop such as the caudate nucleus, thalamus and orbitofrontal cortex. OCD has been proposed to reflect a positive feedback loop due to mutual excitation of the OFC and subcortical structures. While the OFC is usually overactive during symptom provocation tasks, cognitive tasks usually elicit hypoactivity of the OFC; this may reflect a distinction between emotional and non emotional tasks, lateral and medial OFC, or simply just inconsistent methodologies.

Addiction

Animal models, and cell specific manipulations in relation to drug seeking behavior implicate dsyfunction of the OFC in addiction. Substance use disorders are associated with a variety of deficits related to flexible goal directed behavior and decision making. These deficits overlap with symptoms related to OFC lesions, and are also associated with reduced orbitofrontal grey matter, resting state hypometabolism, and blunted OFC activity during tasks involving decision making or goal directed behavior. In contrast to resting state and decision related activity, cues associated with drugs evoke robust OFC activity that correlates with craving. Rodent studies also demonstrate that lOFC to BLA projections are necessary for cue induced reinstatement of self administration. These findings are all congruent with the role that the OFC plays in encoding the outcomes associated with certain stimuli. The progression towards compulsive substance abuse may reflect a shift between model based decision making, where an internal model of future outcomes guides decisions, to model free learning, where decisions are based on reinforcement history. Model based learning involves the OFC and is flexible and goal directed, while model free learning is more rigid; as shift to more model free behavior due to dysfunction in the OFC, like that produced by drugs of misuse, could underlie drug seeking habits.

Behavioral disorders

Conduct disorder is associated with both structural abnormalities, and functional abnormalities during affective tasks. Abnormalities in OFC structure, activity, and functional connectivity have all been observed in association with aggression.

Affective Disorders

Neuroimaging studies have found abnormalities in the OFC in both MDD and bipolar disorder. Consistent with the medial/reward and lateral/punishment gradient found in neuroimaging studies, some neuroimaging studies have observed elevated lateral OFC activity in depression, as well as reduced interconnectivity of the medial OFC, and enhanced interconnectivity in the lateral OFC. Hypoactivity of the lateral OFC has been frequently observed in bipolar disorder, in particular during manic episodes.

Research

Imaging

Using functional magnetic resonance imaging (fMRI) to image the human OFC is a challenge, because this brain region is in proximity to the air-filled sinuses. This means that signal dropout, geometric distortion and susceptibility artifacts are common when using EPI at higher magnetic field strengths. Extra care is therefore recommended for obtaining a good signal from the orbitofrontal cortex, and a number of strategies have been devised, such as automatic shimming at high static magnetic field strengths.

Rodents

In rodents, the OFC is entirely agranular or dysgranular. The OFC is divided into ventrolateral (VLO), lateral (LO), medial (MO) and dorsolateral (DLO) regions. Using highly specific techniques to manipulate circuitry, such as optogenetics, the OFC has been implicated in OCD like behaviors.

Clinical significance

Damage

Destruction of the OFC through acquired brain injury typically leads to a pattern of disinhibited behaviour. Examples include swearing excessively, hypersexuality, poor social interaction, compulsive gambling, drug use (including alcohol and tobacco), and poor empathising ability. Disinhibited behaviour by patients with some forms of frontotemporal dementia is thought to be caused by degeneration of the OFC.

Disruption

When OFC connections are disrupted, a number of cognitive, behavioral, and emotional consequences may arise. Research supports that the main disorders associated with dysregulated OFC connectivity/circuitry center around decision-making, emotion regulation, and reward expectation. A recent multi-modal human neuroimaging study shows disrupted structural and functional connectivity of the OFC with the subcortical limbic structures (e.g., amygdala or hippocampus) and other frontal regions (e.g., dorsal prefrontal cortex or anterior cingulate cortex) correlates with abnormal OFC affect (e.g., fear) processing in clinically anxious adults.

One clear extension of problems with decision-making is drug addiction/substance dependence, which can result from disruption of the striato-thalamo-orbitofrontal circuit. Attention deficit hyperactivity disorder (ADHD) has also been implicated in dysfunction of neural reward circuitry controlling motivation, reward, and impulsivity, including OFC systems. Other disorders of executive functioning and impulse control may be affected by OFC circuitry dysregulation, such as obsessive–compulsive disorder and trichotillomania.
 
Some dementias are also associated with OFC connectivity disruptions. The behavioral variant of frontotemporal dementia is associated with neural atrophy patterns of white and gray matter projection fibers involved with OFC connectivity. Finally, some research suggests that later stages of Alzheimer’s Disease be impacted by altered connectivity of OFC systems.

Orbitofrontal epilepsy

Orbitofrontal epilepsy is rare, but does occur. The presentation of OFC epilepsy is fairly diverse, although common characteristics include being sleep related, automatisms, and hypermotor symptoms. One review reported that auras were generally not common or nonspecific, while another reported that OFC epilepsy was associated auras involving somatosensory phenomenon and fear.

Assessment

The visual discrimination test has two components. In the first component, "reversal learning", participants are presented with one of two pictures, A and B. They learn that they will be rewarded if they press a button when picture A is displayed, but punished if they press the button when picture B is displayed. Once this rule has been established, the rule swaps. In other words, now it is correct to press the button for picture B, not picture A. Most healthy participants pick up on this rule reversal almost immediately, but patients with OFC damage continue to respond to the original pattern of reinforcement, although they are now being punished for persevering with it. Rolls et al. noted that this pattern of behaviour is particularly unusual given that the patients reported that they understood the rule.

The second component of the test is "extinction". Again, participants learn to press the button for picture A but not picture B. However this time, instead of the rules reversing, the rule changes altogether. Now the participant will be punished for pressing the button in response to either picture. The correct response is not to press the button at all, but people with OFC dysfunction find it difficult to resist the temptation to press the button despite being punished for it.

The Iowa Gambling Task A simulation of real life decision-making, the Iowa gambling task is widely used in cognition and emotion research. Participants are presented with four virtual decks of cards on a computer screen. They are told that each time they choose a card they will win some game money. Every so often, however, when they choose a card they will lose some money. They are told that the aim of the game is to win as much money as possible. The task is meant to be opaque, that is, participants are not meant to consciously work out the rule, and they are supposed to choose cards based on their "gut reaction." Two of the decks are "bad decks", which means that, over a long enough time, they will make a net loss; the other two decks are "good decks" and will make a net gain over time.

Most healthy participants sample cards from each deck, and after about 40 or 50 selections are fairly good at sticking to the good decks. Patients with OFC dysfunction, however, continue to perseverate with the bad decks, sometimes even though they know that they are losing money overall. Concurrent measurement of galvanic skin response shows that healthy participants show a "stress" reaction to hovering over the bad decks after only 10 trials, long before conscious sensation that the decks are bad. By contrast, patients with OFC dysfunction never develop this physiological reaction to impending punishment. Bechara and his colleagues explain this in terms of the somatic marker hypothesis. The Iowa gambling task is currently being used by a number of research groups using fMRI to investigate which brain regions are activated by the task in healthy volunteers as well as clinical groups with conditions such as schizophrenia and obsessive compulsive disorder.

The faux pas test is a series of vignettes recounting a social occasion during which someone said something that should not have been said, or an awkward occurrence. The participant's task is to identify what was said that was awkward, why it was awkward, how people would have felt in reaction to the faux pas and to a factual control question. Although first designed for use in people on the autism spectrum, the test is also sensitive to patients with OFC dysfunction, who cannot judge when something socially awkward has happened despite appearing to understand the story perfectly well.