Subfields of psychology

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Subfields_of_psychology 

Psychology encompasses a vast domain, and includes many different approaches to the study of mental processes and behavior. Below are the major areas of inquiry that taken together constitute psychology. A comprehensive list of the sub-fields and areas within psychology can be found at the list of psychology topics and list of psychology disciplines.

Divisions

Abnormal

Main article: Abnormal psychology

Abnormal psychology is the study of abnormal behavior in order to describe, predict, explain, and change abnormal patterns of functioning. Abnormal psychology studies the nature of psychopathology and its causes, and this knowledge is applied in clinical psychology to treat patients with psychological disorders.

It can be difficult to draw the line between normal and abnormal behaviors. In general, abnormal behaviors must be maladaptive and cause an individual significant discomfort in order to be of clinical and research interest. According to the DSM-IV-TR, behaviors may be considered abnormal if they are associated with disability, personal distress, the violation of social norms, or dysfunction.

Anomalistic

Main article: Anomalistic psychology

Anomalistic psychology is the study of human behaviour and experience connected with what is often called the paranormal, without the assumption that there is anything paranormal involved. Researchers involved with anomalistic psychology try to provide plausible non-paranormal accounts, supported by empirical evidence, of how psychological and physical factors might combine to give the impression of paranormal activity when there had been none. Apart from deception or self-deception such explanations might involve cognitive biases, anomalous psychological states, dissociative states, hallucinations, personality factors, developmental issues and the nature of memory. A notable researcher in the field of anomalistic psychology is the British psychologist Chris French who set up the Anomalistic Psychology Research Unit (APRU) in the Department of Psychology at Goldsmiths, University of London.

Behavioral Genetics

Main article: Behavioral genetics

Behavioural genetics uses genetically informative designs to understand the nature and origins of individual differences in behavior. In focusing on the causes of individual differences, behavioral genetics is distinct from evolutionary psychology, which tends to focus on human universals. Behavioral genetics has thus been associated strongly with the diathesis stress model of psychopathology as well as the nature/nurture debate. Behavioral genetics research was pioneered by Francis Galton and his seminal work in family studies and twin studies after falling out of favor during the eugenics movement during the first part of the 20th century up until World War II. A resurgence of behavioral genetics research began in the 1960s and rose into prominence in the 1980s and beyond. During this time twin study and adoption studies were conducted on a wide array of behavioral traits, including personality, cognitive ability, psychiatric illness, medical illness, and many others. The general conclusion of this large body of work is that every behavioral and medical trait, and indeed measures of the environment is heritable to some moderate degree. Taking advantage of the Human Genome Project more recent work in behavioral genetics uses recent technologies in array-based genotyping, genome sequencing, and other omics to measure genetic variants directly. These genetic variants can then be tested for association with behavioral traits and disorders, for example through genome-wide association studies. This approach to understanding the genetic influences on behavior have seen recent successes in, for example, schizophrenia. Psychiatric genetics is a subfield of behavioral genetics.

Biological

Main articles: Biological psychology, Neuropsychology, Physiological psychology, Behavioral neuroscience, and Cognitive neuroscience

 

MRI depicting the human brain. The arrow indicates the position of the hypothalamus.

Biological psychology is the scientific study of the biological substrates of behavior and mental states. Seeing all behavior as intertwined with the nervous system, biological psychologists feel it is sensible to study how the brain functions in order to understand behavior. This is the approach taken in behavioral neuroscience, cognitive neuroscience, and neuropsychology. Neuropsychology is the branch of psychology that aims to understand how the structure and function of the brain relate to specific behavioral and psychological processes. Neuropsychology is particularly concerned with the understanding of brain injury in an attempt to work out normal psychological function. Cognitive neuroscientists often use neuroimaging tools, which can help them to observe which areas of the brain are active during a particular task.

Clinical

Main article: Clinical psychology

Clinical psychology includes the study and application of psychology for the purpose of understanding, preventing, and relieving psychologically-based distress or dysfunction and to promote subjective well-being and personal development. Central to its practice are psychological assessment and psychotherapy, although clinical psychologists may also engage in research, teaching, consultation, forensic testimony, and program development and administration. Some clinical psychologists may focus on the clinical management of patients with brain injury—this area is known as clinical neuropsychology. In many countries clinical psychology is a regulated mental health profession.

The work performed by clinical psychologists tends to be influenced by various therapeutic approaches, all of which involve a formal relationship between professional and client (usually an individual, couple, family, or small group). The various therapeutic approaches and practices are associated with different theoretical perspectives and employ different procedures intended to form a therapeutic alliance, explore the nature of psychological problems, and encourage new ways of thinking, feeling, or behaving. Four major theoretical perspectives are psychodynamic, cognitive behavioral, existential-humanistic, and systems or family therapy. There has been a growing movement to integrate the various therapeutic approaches, especially with an increased understanding of issues regarding culture, gender, spirituality, and sexual-orientation. With the advent of more robust research findings regarding psychotherapy, there is evidence that most of the major therapies are about of equal effectiveness, with the key common element being a strong therapeutic alliance. Because of this, more training programs and psychologists are now adopting an eclectic therapeutic orientation.

Cognitive

Main article: Cognitive psychology

Cognitive psychology studies cognition, the mental processes underlying mental activity. Perception, learning, problem solving, reasoning, thinking, memory, attention, language and emotion are areas of research. Classical cognitive psychology is associated with a school of thought known as cognitivism, whose adherents argue for an information processing model of mental function, informed by functionalism and experimental psychology.

On a broader level, cognitive science is an interdisciplinary enterprise of cognitive psychologists, cognitive neuroscientists, researchers in artificial intelligence, linguists, human–computer interaction, computational neuroscience, logicians and social scientists. Computational models are sometimes used to simulate phenomena of interest. Computational models provide a tool for studying the functional organization of the mind whereas neuroscience provides measures of brain activity.

Community

Main article: Community psychology

Community psychology deals with the relationships of the individual to communities and the wider society. Community psychologists seek to understand the quality of life of individuals, communities, and society. Their aim is to enhance quality of life through collaborative research and action.

Community psychology makes use of various perspectives within and outside of psychology to address issues of communities, the relationships within them, and people's attitudes about them. Through collaborative research and action, community psychologists (practitioners and researchers) seek to understand and to enhance quality of life for individuals, communities, and society. Community psychology takes a public health approach and focuses on prevention and early intervention as a means to solve problems in addition to treatment. Rappaport (1977) discusses the perspective of community psychology as an ecological perspective with the person-environment fit being the focus of study and action instead of attempting to change the person or the environment when an individual is seen as having a problem.

Comparative

Main article: Comparative psychology

Comparative psychology refers to the study of the behavior and mental life of animals other than human beings. It is related to disciplines outside of psychology that study animal behavior such as ethology. Although the field of psychology is primarily concerned with humans the behavior and mental processes of animals is also an important part of psychological research. This being either as a subject in its own right (e.g., animal cognition and ethology) or with strong emphasis about evolutionary links, and somewhat more controversially, as a way of gaining an insight into human psychology. This is achieved by means of comparison or via animal models of emotional and behavior systems as seen in neuroscience of psychology (e.g., affective neuroscience and social neuroscience).

Consulting

Main article: Consulting psychology

Consulting psychology includes the application of psychology to consulting contexts at the individual, group and organizational levels. The field specializes in assessment and intervention, particularly in business and organizational applications but also is concerned with the consulting process used to assess and facilitate change in any area of psychology. Lowman (2002) provides an overview of the field, including the relevance of individual, group and organizational levels to consulting psychologists.

Counseling

Main article: Counseling psychology

Counseling psychology seeks to facilitate personal and interpersonal functioning across the lifespan with a focus on emotional, social, vocational, educational, health-related, developmental, and organizational concerns. Counselors are primarily clinicians, using psychotherapy and other interventions in order to treat clients. Traditionally, counseling psychology has focused more on normal developmental issues and everyday stress rather than psychopathology, but this distinction has softened over time. Counseling psychologists are employed in a variety of settings, including universities, hospitals, schools, governmental organizations, businesses, private practice, and community mental health centers.

Cyber

Main article: Cyberpsychology

Cyberpsychology is the study of the psychological processes related to, and underlying, technologically interconnected human behavior. Cyberpsychologists use psychological theory and research to explain online behaviour, and to investigate how connected technologies influence how we think, feel and behave. Areas in cyberpsychology include the psychology of online dating and relationships, online learning, online working, online gaming, online shopping, online gambling, online crime, online media (including social media), virtual reality, augmented reality and online entertainment. Cyberpsychology is a recognised subfield of psychology that has a dedicated section within the British Psychological Society (BPS).

Developmental

Main article: Developmental psychology

Mainly focusing on the development of the human mind through the life span, developmental psychology seeks to understand how people come to perceive, understand, and act within the world and how these processes change as they age. This may focus on intellectual, cognitive, neural, social, or moral development. Researchers who study children use a number of unique research methods to make observations in natural settings or to engage them in experimental tasks. Such tasks often resemble specially designed games and activities that are both enjoyable for the child and scientifically useful, and researchers have even devised clever methods to study the mental processes of small infants. In addition to studying children, developmental psychologists also study aging and processes throughout the life span, especially at other times of rapid change (such as adolescence and old age). Developmental psychologists draw on the full range of theorists in scientific psychology to inform their research.

Differential

Main article: Differential psychology

Differential psychology studies the ways in which individuals differ in their behavior and the processes that underlie it.

Educational

Main article: Educational psychology

Educational psychology is the study of how humans learn in educational settings, the effectiveness of educational interventions, the psychology of teaching, and the social psychology of schools as organizations. The work of child psychologists such as Lev Vygotsky, Jean Piaget and Jerome Bruner has been influential in creating teaching methods and educational practices. Educational psychology is often included in teacher education programs, at least in North America, Australia, and New Zealand.

Environmental

Main article: Environmental psychology

Environmental psychology is an interdisciplinary field focused on the interplay between humans and their surroundings. The field defines the term environment broadly, encompassing natural environments, social settings, built environments, learning environments, and informational environments. Since its conception, the field has been committed to the development of a discipline that is both value oriented and problem oriented, prioritizing research aiming at solving complex environmental problems in the pursuit of individual well-being within a larger society.

Evolutionary

Main article: Evolutionary psychology

Evolutionary psychology explores the evolutionary roots of mental and behavioral patterns, and posits that common patterns may have emerged because they were highly adaptive for humans in the environments of their evolutionary past—even if some of these patterns are maladaptive in today's environments. Fields closely related to evolutionary psychology are animal behavioral ecology, human behavioral ecology, dual inheritance theory, and sociobiology. Evolutionary psychology is distinct from, although related to, behavioral genetics. Memetics, founded by Richard Dawkins, is a related but competing field that proposes that cultural evolution can occur in a Darwinian sense but independently of Mendelian mechanisms; it therefore examines the ways in which thoughts, or memes, may evolve independently of genes.

Forensic

Main article: Forensic psychology

Forensic psychology applies psychology to legal cases, covering a broad range of practices including the clinical evaluations of defendants, reports to judges and attorneys, and courtroom testimony on given issues. Forensic psychologists are appointed by the court or hired by attorneys to evaluate defendants' competency to stand trial, competency to be executed, sanity, and need for involuntary commitment. Forensic psychologists provide sentencing recommendations, evaluate sex offenders and treatments, and provide recommendations to the court through written reports and testimony. Many of the questions the court asks the forensic psychologist go ultimately to legal issues, although a psychologist cannot answer legal questions. For example, there is no definition of sanity in psychology. Rather, sanity is a legal definition that varies from place to place throughout the world. Therefore, a prime qualification of a forensic psychologist is an intimate understanding of the law, especially criminal law.

Health

Main article: Health psychology

Health psychology is the application of psychological theory and research to health, illness and health care. Whereas clinical psychology focuses on mental health and neurological illness, health psychology is concerned with the psychology of a much wider range of health-related behavior including healthy eating, the doctor-patient relationship, a patient's understanding of health information, and beliefs about illness. Health psychologists may be involved in public health campaigns, examining the impact of illness or health policy on quality of life and in research into the psychological impact of health and social care.

Industrial-Organizational

Main article: Industrial and organizational psychology

Industrial and organizational psychology (I-O) applies psychological concepts and methods to optimize human potential in the workplace. Personnel psychology, a subfield of I-O psychology, applies the methods and principles of psychology in selecting and evaluating workers. I-O psychology's other subfield, organizational psychology, examines the effects of work environments and management styles on worker motivation, job satisfaction, and productivity.

Legal

Main article: Legal psychology

Legal psychology is a research-oriented field populated with researchers from several different areas within psychology (although social and cognitive psychologists are typical). Legal psychologists explore such topics as jury decision-making, eyewitness memory, scientific evidence, and legal policy. The term "legal psychology" has only recently come into use, and typically refers to any non-clinical law-related research.

Moral

Main article: Moral psychology

Moral psychology is an interdisciplinary field of research focusing on moral values, judgment, behavior, and other topics at the intersection of ethics and psychology.

Media

Main article: Media psychology

Media psychology seeks an understanding of the relationships between mediated communication and the thoughts, feelings, and behaviors of the senders and recipients of the communication. For instance, a media psychologist might determine that depressed individuals are especially likely to watch television.

Occupational Health

Main article: Occupational health psychology

Occupational health psychology (OHP) is a discipline that emerged from health psychology, industrial/organizational psychology, and occupational health. OHP is concerned with identifying psychosocial characteristics of workplaces that give rise to problems in physical (e.g., cardiovascular disease) and mental health (e.g., depression). OHP has investigated such psychosocial characteristics of workplaces as workers' decision latitude and supervisors' supportiveness. OHP also concerns itself with interventions that can prevent or ameliorate work-related health problems. Such interventions have important, beneficial implications for the economic success of organizations. Other research areas of concern to OHP include workplace violence, unemployment, and workplace safety. Two exemplary OHP journals are the Journal of Occupational Health Psychology and Work & Stress. Two prominent OHP professional organizations are the European Academy of Occupational Health Psychology and the Society for Occupational Health Psychology.

Personality

Main article: Personality psychology

Personality psychology studies enduring patterns of behavior, thought, and emotion in individuals, commonly referred to as personality. Theories of personality vary across different psychological schools and orientations. They carry different assumptions about such issues as the role of the unconscious and the importance of childhood experience. According to Freud, personality is based on the dynamic interactions of the ego, superego, and id. Trait theorists, in contrast, attempt to analyze personality in terms of a discrete number of key traits by the statistical method of factor analysis. The number of proposed traits has varied widely. An early model proposed by Hans Eysenck suggested that there are three traits that comprise human personality: extraversion-introversion, neuroticism, and psychoticism. Raymond Cattell proposed a theory of 16 personality factors. The Big Five personality traits, proposed by Lewis Goldberg, currently has strong support among trait theorists.

Quantitative

Main article: Quantitative psychology

Quantitative psychology involves the application of mathematical and statistical modeling in psychological research, and the development of statistical methods for analyzing and explaining behavioral data. The term "Quantitative psychology" is relatively new and little used (only recently have Ph.D. programs in quantitative psychology been formed), and it loosely covers the longer standing subfields psychometrics and mathematical psychology.

Psychometrics is the field of psychology concerned with the theory and technique of psychological measurement, which includes the measurement of knowledge, abilities, attitudes, and personality traits. Measurement of these phenomena is difficult, and much research has been developed to define and analyze such phenomena. Psychometric research typically involves two major research tasks, namely: (i) the construction of instruments and procedures for measurement; and (ii) the development and refinement of theoretical approaches to measurement.

Mathematical psychology is the subdiscipline that is concerned with the development of psychological theory in relation with mathematics and statistics. Basic topics in mathematical psychology include measurement theory and mathematical learning theory as well as the modeling and analysis of mental and motor processes. Psychometrics is more associated with educational psychology, personality, and clinical psychology. Mathematical psychology is more closely related to psychonomics/experimental and cognitive, and physiological psychology and (cognitive) neuroscience.

Religion/Spirituality

Main article: Psychology of religion

Psychology of religion and spirituality is the psychological study of religious and spiritual experiences, beliefs, activities, and feelings. This subfield has existed since modern psychology's early days, and is the focus of Division 36 of the American Psychological Association. William James (1842–1910) is regarded by most psychologists of religion/spirituality as the founder of the field, and his Varieties of Religious Experience is considered to be a classic work in the field. Since 2008, the American Psychological Association has published a journal dedicated to this subfield, entitled the Psychology of Religion and Spirituality. In recent decades, scholars have increasingly conceptualized religion as a way of living, rather than merely a belief system or institution. Religion and spirituality are commonly viewed as distinct but overlapping constructs. Surveys indicate that large majorities of US adults consider religion and/or spirituality to be very important in their lives. Scientific and psychological interest in the psychology of religion/spirituality has increased substantially in recent decades. The American Psychological Association now publishes many books on the topic of religion/spirituality. The Association's publications include the recent (2013) two-volume Handbook of Psychology, Religion, and Spirituality, with Volume One focusing on theory, and Volume Two focusing on applications.

School

Main article: School psychology

School psychology combines principles from educational psychology and clinical psychology to understand and treat students with learning disabilities; to foster the intellectual growth of "gifted" students; to facilitate prosocial behaviors in adolescents; and otherwise to promote safe, supportive, and effective learning environments. School psychologists are trained in educational and behavioral assessment, intervention, prevention, and consultation, and many have extensive training in research. Currently, school psychology is the only field in which a professional can be called a "psychologist" without a doctoral degree, with the National Association of School Psychologists (NASP) recognizing the specialist degree as the entry level. This is a matter of controversy as the APA does not recognize anything below a doctorate as the entry level for a psychologist. Specialist-level school psychologists, who typically receive three years of graduate training, function almost exclusively within school systems, while those at the doctoral-level are found in a number of other settings as well, including universities, hospitals and private practice.

Social

Main article: Social psychology (psychology)

 

Social psychology studies the nature and causes of social behavior.

Social psychology is the study of social behavior and mental processes, with an emphasis on how humans think about each other and how they relate to each other. Social psychologists are especially interested in how people react to social situations. They study such topics as the influence of others on an individual's behavior (e.g. conformity, persuasion), and the formation of beliefs, attitudes, and stereotypes about other people. Social cognition fuses elements of social and cognitive psychology in order to understand how people process, remember, and distort social information. The study of group dynamics reveals information about the nature and potential optimization of leadership, communication, and other phenomena that emerge at least at the microsocial level. In recent years, many social psychologists have become increasingly interested in implicit measures, mediational models, and the interaction of both person and social variables in accounting for behavior.

Olanzapine

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Olanzapine 

 

Olanzapine

Clinical data
Trade names	Zyprexa, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601213
License data	EU EMA: by INN US DailyMed: Olanzapine US FDA: Olanzapine
Pregnancy category	AU: C
Routes of administration	By mouth, intramuscular injection
Drug class	Atypical antipsychotic
ATC code	N05AH03 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only NZ: Prescription medicine UK: POM (Prescription only) US: ℞-only EU: Rx-only
Pharmacokinetic data
Bioavailability	60-65%
Protein binding	93%
Metabolism	Liver (direct glucuronidation and CYP1A2 mediated oxidation)
Elimination half-life	33 hours, 51.8 hours (elderly)
Excretion	Urine (57%; 7% as unchanged drug), faeces (30%)
Identifiers

IUPAC name
CAS Number	132539-06-1
PubChem CID	4585
IUPHAR/BPS	47
DrugBank	DB00334
ChemSpider	10442212
UNII	N7U69T4SZR
KEGG	D00454
ChEBI	CHEBI:7735
ChEMBL	ChEMBL715
CompTox Dashboard (EPA)	DTXSID9023388
ECHA InfoCard	100.125.320
Chemical and physical data
Formula	C17H20N4S
Molar mass	312.44 g·mol−1
3D model (JSmol)	Interactive image
Melting point	195 °C (383 °F)
Solubility in water	Practically insoluble in water mg/mL (20 °C)

Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

Common side effects include weight gain, movement disorders, dizziness, feeling tired, constipation, and dry mouth. Other side effects include low blood pressure with standing, allergic reactions, neuroleptic malignant syndrome, high blood sugar, seizures, and tardive dyskinesia. In older people with dementia, its use increases the risk of death. Use in the later part of pregnancy may result in a movement disorder in the baby for some time after birth. Although how it works is not entirely clear, it blocks dopamine and serotonin receptors.

Olanzapine was patented in 1991 and approved for medical use in the United States in 1996. It is available as a generic medication. In 2020, it was the 164th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Lilly also markets olanzapine in a fixed-dose combination with fluoxetine as olanzapine/fluoxetine (Symbyax).

Medical uses

It is approved by FDA for the following indications:

• schizophrenia
• Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder.
• Adjunct to valproate, carbamazepine or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder
• combination olanzapine/fluoxetine for the treatment of depressive episodes associated with bipolar I disorder.

In United Kingdom and Australia it is approved for schizophrenia, moderate to severe manic episodes, alone, or in combination with lithium or valproate and the short-term treatment of acute manic episodes associated with Bipolar I Disorder.

Schizophrenia

The first-line psychiatric treatment for schizophrenia is antipsychotic medication. Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early-onset schizophrenia. The usefulness of maintenance therapy, however, is difficult to determine, as more than half of people in trials quit before the 6-week completion date. Treatment with olanzapine (like clozapine) may result in increased weight gain and increased glucose and cholesterol levels when compared to most other second-generation antipsychotic drugs used to treat schizophrenia.

Bipolar disorder

Olanzapine is recommended by the National Institute for Health and Care Excellence as a first-line therapy for the treatment of acute mania in bipolar disorder. Other recommended first-line treatments are aripiprazole, haloperidol, quetiapine, and risperidone. It is recommended in combination with fluoxetine as a first-line therapy for acute bipolar depression, and as a second-line treatment by itself for the maintenance treatment of bipolar disorder.

The Network for Mood and Anxiety Treatments recommends olanzapine as a first-line maintenance treatment in bipolar disorder and the combination of olanzapine with fluoxetine as second-line treatment for bipolar depression.

A review on the efficacy of olanzapine as maintenance therapy in patients with bipolar disorder was published by Dando & Tohen in 2006. A 2014 meta-analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis.

Other uses

Olanzapine may be useful in promoting weight gain in underweight adult outpatients with anorexia nervosa. However, no improvement of psychological symptoms was noted.

Olanzapine has been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and has since been used in the treatment of a range of mood and anxiety disorders. Olanzapine is no less effective than lithium or valproate and more effective than placebo in treating bipolar disorder. It has also been used for Tourette syndrome and stuttering.

Olanzapine has been studied for the treatment of hyperactivity, aggressive behavior, and repetitive behaviors in autism.

Olanzapine is frequently prescribed off-label for the treatment of insomnia, including difficulty falling asleep and staying asleep, even though such use is not recommended. The daytime sedation experienced with olanzapine is generally comparable to quetiapine and lurasidone, which is a frequent complaint in clinical trials. In some cases, the sedation due to olanzapine impaired the ability of people to wake up at a consistent time every day. Some evidence of efficacy for treating insomnia is seen; however, side effects such as dyslipidemia and neutropenia, which may possibly be observed even at low doses, outweigh any potential benefits for insomnia that is not due to an underlying mental health condition.

Olanzapine has been recommended to be used in antiemetic regimens in people receiving chemotherapy that has a high risk for vomiting.

Specific populations

Pregnancy and lactation

Olanzapine is associated with the highest placental exposure of any atypical antipsychotic. Despite this, the available evidence suggests it is safe during pregnancy, although the evidence is insufficiently strong to say anything with a high degree of confidence. Olanzapine is associated with weight gain, which according to recent studies, may put olanzapine-treated patients' offspring at a heightened risk for neural tube defects (e.g. spina bifida). Breastfeeding in women taking olanzapine is advised against because olanzapine is secreted in breast milk, with one study finding that the exposure to the infant is about 1.8% that of the mother.

Elderly

Citing an increased risk of stroke, in 2004, the Committee on the Safety of Medicines in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis. A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors. Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to aripiprazole and risperidone.

Adverse effects

See also: List of adverse effects of olanzapine

The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in blood-lipid and blood-sugar profiles (see section metabolic effects). A 2013 meta-analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74. Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine, but may include tremors and muscle rigidity.

Aripiprazole, asenapine, clozapine, quetiapine and olanzapine, in comparison to other antipsychotic drugs, are less frequently associated with hyperprolactinaemia. Although these drugs can cause transient or sustained hyperprolactinaemia, the risk is much lower. Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia. Although olanzapine causes an early dose-related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. A rise in prolactin is seen in about half of patients on olanzapine compared to over 90% of those taking risperidone, and enduring increases were less frequent in those taking olanzapine.

It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe hypotension, sick sinus syndrome, and unstable angina.

Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce nontrivial high blood sugar in people with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur.

Other side effects include galactorrhea, amenorrhea, gynecomastia, and erectile dysfunction (impotence).

Drug-induced OCD

Main article: Obsessive–compulsive disorder § Drug-induced OCD

Many different types of medication can create or induce pure obsessive-compulsive disorder (OCD) in patients who have never had symptoms before. A new chapter about OCD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013) now specifically includes drug-induced OCD.

Metabolic effects

The US Food and Drug Administration (FDA) requires all atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs' ability to induce weight gain, although some reports have been made of metabolic changes in the absence of weight gain. Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures. The effect is dose dependent in humans and animal models of olanzapine-induced metabolic side effects. There are some case reports of olanzapine-induced diabetic ketoacidosis. Olanzapine may decrease insulin sensitivity, though one 3-week study seems to refute this. It may also increase triglyceride levels.

Despite weight gain, a large multicenter, randomized National Institute of Mental Health study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs. One small, open-label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain, but this has not been substantiated in a blinded experimental setting.

Post-injection delirium/sedation syndrome

Postinjection delirium/sedation syndrome (PDSS) is a rare syndrome that is specific to the long-acting injectable formulation of olanzapine, olanzapine pamoate. The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second-generation, long-acting antipsychotics (e.g. paliperidone palmitate), which do not appear to carry the same risk. PDSS is characterized by symptoms of delirium (e.g. confusion, difficulty speaking, and uncoordinated movements) and sedation. Most people with PDSS exhibit both delirium and sedation (83%). Although less specific to PDSS, a majority of cases (67%) involved a feeling of general discomfort. PDSS may occur due to accidental injection and absorption of olanzapine pamoate into the bloodstream, where it can act more rapidly, as opposed to slowly distributing out from muscle tissue. Using the proper, intramuscular-injection technique for olanzapine pamoate helps to decrease the risk of PDSS, though it does not eliminate it entirely. This is why the FDA advises that people who are injected with olanzapine pamoate be watched for 3 hours after administration, in the event that PDSS occurs.

Animal toxicology

Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals.

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly, vertigo, numbness, or muscle pains may occur. Symptoms generally resolve after a short time.

Tentative evidence indicates that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely, tardive dyskinesia can occur when the medication is stopped.

Overdose

Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness, and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg. Fatalities generally have occurred with olanzapine plasma concentrations greater than 1000 ng/mL post mortem, with concentrations up to 5200 ng/mL recorded (though this might represent confounding by dead tissue, which may release olanzapine into the blood upon death). No specific antidote for olanzapine overdose is known, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case. Olanzapine is considered moderately toxic in overdose, more toxic than quetiapine, aripiprazole, and the SSRIs, and less toxic than the monoamine oxidase inhibitors and tricyclic antidepressants.

Interactions

Drugs or agents that increase the activity of the enzyme CYP1A2, notably tobacco smoke, may significantly increase hepatic first-pass clearance of olanzapine; conversely, drugs that inhibit CYP1A2 activity (examples: ciprofloxacin, fluvoxamine) may reduce olanzapine clearance. Carbamazepine, a known enzyme inducer, has decreased the concentration/dose ration of olanzapine by 33% compared to olanzapine alone. Another enzyme inducer, ritonavir, has also been shown to decrease the body's exposure to olanzapine, due to its induction of the enzymes CYP1A2 and uridine 5'-diphospho-glucuronosyltransferase (UGT). Probenecid increases the total exposure (area under the curve) and maximum plasma concentration of olanzapine. Although olanzapine's metabolism includes the minor metabolic pathway of CYP2D6, the presence of the CYP2D6 inhibitor fluoxetine does not have a clinically significant effect on olanzapine's clearance.

Pharmacology

Pharmacodynamics

See also: Atypical antipsychotic § Pharmacodynamics, and Antipsychotic § Comparison of medications

Olanzapine was first discovered while searching for a chemical analog of clozapine that would not require hematological monitoring. Investigation on a series of thiophene isosteres on 1 of the phenyl rings in clozapine, a thienobenzodiazepine analog (olanzapine) was discovered.

Olanzapine has a higher affinity for 5-HT_2A serotonin receptors than D₂ dopamine receptors, which is a common property of most atypical antipsychotics, aside from the benzamide antipsychotics such as amisulpride along with the nonbenzamides aripiprazole, brexpiprazole, blonanserin, cariprazine, melperone, and perospirone.

In one study D2 receptor occupancy was 60% with low-dose olanzapine (5 mg/day) and occupancy with high dose at 83% (20 mg/day). In the usual clinical dose range of 10–20 mg/day, D2 receptor occupancy varied from 71% to 80%.

Olanzapine occupancy at 5-HT_2A receptor are high at all doses (5 mg to 20 mg). It is reported that 5 mg dose of olanzapine produced a mean occupancy of 85% at 5 mg, 88% at 10 mg, and 93% at 20 mg dose.

Olanzapine had the highest affinity of any second-generation antipsychotic towards the P-glycoprotein in one in vitro study. P-glycoprotein transports a myriad of drugs across a number of different biological membranes (found in numerous body systems) including the blood–brain barrier (a semipermeable membrane that filters the contents of blood prior to it reaching the brain); P-GP inhibition could mean that less brain exposure to olanzapine results from this interaction with the P-glycoprotein. A relatively large quantity of commonly encountered foods and medications inhibit P-GP, and pharmaceuticals fairly commonly are either substrates of P-GP, or inhibit its action; both substrates and inhibitors of P-GP effectively increase the permeability of the blood–brain barrier to P-GP substrates and subsequently increase the central activity of the substrate, while reducing the local effects on the GI tract. The mediation of olanzapine in the central nervous system by P-GP means that any other substance or drug that interacts with P-GP increases the risk for toxic accumulations of both olanzapine and the other drug.

Olanzapine is a potent antagonist of the muscarinic M₃ receptor, which may underlie its diabetogenic side effects. Additionally, it also exhibits a relatively low affinity for serotonin 5-HT₁, GABA_A, beta-adrenergic receptors, and benzodiazepine binding sites.

Although antagonistic effects of olanzapine at 5-HT2c alone is not associated with weight gain, olanzapine antagonism at histaminergic H1, and muscarinic M3 receptors have been implicated in weight gain.

The mode of action of olanzapine's antipsychotic activity is unknown. It may involve antagonism of dopamine and serotonin receptors. Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia (TD), and with therapeutic effects. Antagonism of muscarinic acetylcholine receptors is associated with anticholinergic side effects such as dry mouth and constipation; in addition, it may suppress or reduce the emergence of extrapyramidal effects for the duration of treatment, but it offers no protection against the development of TD. In common with other second-generation (atypical) antipsychotics, olanzapine poses a relatively low risk of extrapyramidal side effects including TD, due to its higher affinity for the 5HT_2A receptor over the D₂ receptor.

Antagonizing H₁ histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT_2C and dopamine D₂ receptors have also been associated with weight gain and appetite stimulation.

Pharmacokinetics

Metabolism

Olanzapine is metabolized by the cytochrome P450 (CYP) system; principally by isozyme 1A2 (CYP1A2) and to a lesser extent by CYP2D6. By these mechanisms, more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect. Clearance of olanzapine appears to vary by sex; women have roughly 25% lower clearance than men. Clearance of olanzapine also varies by race; in self-identified African Americans or Blacks, olanzapine's clearance was 26% higher. A difference in the clearance is not apparent between individuals identifying as Caucasian, Chinese, or Japanese. Routine, pharmacokinetic monitoring of olanzapine plasma levels is generally unwarranted, though unusual circumstances (e.g. the presence of drug–drug interactions) or a desire to determine if patients are taking their medicine may prompt its use.

Chemistry

Olanzapine is unusual in having four well-characterised crystalline polymorphs and many hydrated forms.

Chemical synthesis

The preparation of olanzapine was first disclosed in a series of patents from Eli Lilly & Co. in the 1990s. In the final two steps, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile was reduced with stannous chloride in ethanol to give the substituted thienobenzodiazepine ring system, and this was treated with methylpiperazine in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug.

Society and culture

Zyprexa (olanzapine) 10 mg tablets (AU)

Regulatory status

Olanzapine is approved by the US FDA for:

• Treatment—in combination with fluoxetine—of depressive episodes associated with bipolar disorder (December 2003).

• Long-term treatment of bipolar I disorder (January 2004).
• Long-term treatment—in combination with fluoxetine—of resistant depression (March 2009)
• Oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or sodium valproate)
• Intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults
• Oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults
• Treatment of the manifestations of psychotic disorders (September 1996 – March 2000).

• Short-term treatment of acute manic episodes associated with bipolar I disorder (March 2000)
• Short-term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders (March 2000)
• Maintaining treatment response in schizophrenic patients who had been stable for about eight weeks and were then followed for a period of up to eight months (November 2000)

The drug became generic in 2011. Sales of Zyprexa in 2008 were $2.2 billion in the US and $4.7 billion worldwide.

Controversy and litigation

Eli Lilly has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa, as well as by various governmental entities, insurance companies, and others. Lilly produced a large number of documents as part of the discovery phase of this litigation, which started in 2004; the documents were ruled to be confidential by a judge and placed under seal, and later themselves became the subject of litigation.

In 2006, Lilly paid $700 million to settle around 8,000 of these lawsuits, and in early 2007, Lilly settled around 18,000 suits for $500 million, which brought the total Lilly had paid to settle suits related to the drug to $1.2 billion.

A December 2006 New York Times article based on leaked company documents concluded that the company had engaged in a deliberate effort to downplay olanzapine's side effects. The company denied these allegations and stated that the article had been based on cherry-picked documents. The documents were provided to the Times by Jim Gottstein, a lawyer who represented mentally ill patients, who obtained them from a doctor, David Egilman, who was serving as an expert consultant on the case. After the documents were leaked to online peer-to-peer, file-sharing networks by Will Hall and others in the psychiatric survivors movement, who obtained copies, in 2007 Lilly filed a protection order to stop the dissemination of some of the documents, which Judge Jack B. Weinstein of the Brooklyn Federal District Court granted. Judge Weinstein also criticized the New York Times reporter, Gottstein, and Egilman in the ruling. The Times of London also received the documents and reported that as early as 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales. On October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose."

Lilly had threatened Egilman with criminal contempt charges regarding the documents he took and provided to reporters; in September 2007, he agreed to pay Lilly $100,000 in return for the company's agreement to drop the threat of charges.

In September 2008, Judge Weinstein issued an order to make public Lilly's internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors.

In March 2008, Lilly settled a suit with the state of Alaska, and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state consumer protection laws.

In 2009, Eli Lilly pleaded guilty to a US federal criminal misdemeanor charge of illegally marketing Zyprexa for off-label use and agreed to pay $1.4 billion. The settlement announcement stated "Eli Lilly admits that between September 1999 and March 31, 2001, the company promoted Zyprexa in elderly populations as treatment for dementia, including Alzheimer's dementia. Eli Lilly has agreed to pay a $515 million criminal fine and to forfeit an additional $100 million in assets."

The outcomes described here, and their legal ramifications, were fueled by motions and appeals that were not resolved until 2010. In 2021, Gottstein summarized this tangle of legal activities, and their impact on the political landscape of psychiatry and antipsychiatry in the US, in The Zyprexa Papers.

Trade names

Olanzapine is generic and available under many trade names worldwide.

Dosage forms

Olanzapine is marketed in a number of countries, with tablets ranging from 2.5 to 20 mg. Zyprexa (and generic olanzapine) is available as an orally disintegrating "wafer", which rapidly dissolves in saliva. It is also available in 10-mg vials for intramuscular injection.

Research

Olanzapine has been studied as an antiemetic, particularly for the control of chemotherapy-induced nausea and vomiting (CINV).

In general, olanzapine appears to be about as effective as aprepitant for the prevention of CINV, though some concerns remain for its use in this population. For example, concomitant use of metoclopramide or haloperidol increases the risk for extrapyramidal symptoms. Otherwise, olanzapine appears to be fairly well tolerated for this indication, with somnolence being the most common side effect.

Olanzapine has been considered as part of an early psychosis approach for schizophrenia. The Prevention through Risk Identification, Management, and Education study, funded by the National Institute of Mental Health and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with prodromal schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo. In this study, patients receiving olanzapine did not have a significantly lower risk of progressing to psychosis (16.1% vs 37.9%). Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.

Computational neuroscience

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Computational_neuroscience

Computational neuroscience (also known as theoretical neuroscience or mathematical neuroscience) is a branch of neuroscience which employs mathematical models, computer simulations, theoretical analysis and abstractions of the brain to understand the principles that govern the development, structure, physiology and cognitive abilities of the nervous system.

Computational neuroscience employs computational simulations to validate and solve mathematical models, and so can be seen as a sub-field of theoretical neuroscience; however, the two fields are often synonymous. The term mathematical neuroscience is also used sometimes, to stress the quantitative nature of the field.

Computational neuroscience focuses on the description of biologically plausible neurons (and neural systems) and their physiology and dynamics, and it is therefore not directly concerned with biologically unrealistic models used in connectionism, control theory, cybernetics, quantitative psychology, machine learning, artificial neural networks, artificial intelligence and computational learning theory; although mutual inspiration exists and sometimes there is no strict limit between fields, with model abstraction in computational neuroscience depending on research scope and the granularity at which biological entities are analyzed.

Models in theoretical neuroscience are aimed at capturing the essential features of the biological system at multiple spatial-temporal scales, from membrane currents, and chemical coupling via network oscillations, columnar and topographic architecture, nuclei, all the way up to psychological faculties like memory, learning and behavior. These computational models frame hypotheses that can be directly tested by biological or psychological experiments.

History

The term 'computational neuroscience' was introduced by Eric L. Schwartz, who organized a conference, held in 1985 in Carmel, California, at the request of the Systems Development Foundation to provide a summary of the current status of a field which until that point was referred to by a variety of names, such as neural modeling, brain theory and neural networks. The proceedings of this definitional meeting were published in 1990 as the book Computational Neuroscience. The first of the annual open international meetings focused on Computational Neuroscience was organized by James M. Bower and John Miller in San Francisco, California in 1989. The first graduate educational program in computational neuroscience was organized as the Computational and Neural Systems Ph.D. program at the California Institute of Technology in 1985.

The early historical roots of the field can be traced to the work of people including Louis Lapicque, Hodgkin & Huxley, Hubel and Wiesel, and David Marr. Lapicque introduced the integrate and fire model of the neuron in a seminal article published in 1907, a model still popular for artificial neural networks studies because of its simplicity (see a recent review).

About 40 years later, Hodgkin and Huxley developed the voltage clamp and created the first biophysical model of the action potential. Hubel and Wiesel discovered that neurons in the primary visual cortex, the first cortical area to process information coming from the retina, have oriented receptive fields and are organized in columns. David Marr's work focused on the interactions between neurons, suggesting computational approaches to the study of how functional groups of neurons within the hippocampus and neocortex interact, store, process, and transmit information. Computational modeling of biophysically realistic neurons and dendrites began with the work of Wilfrid Rall, with the first multicompartmental model using cable theory.

Major topics

Research in computational neuroscience can be roughly categorized into several lines of inquiry. Most computational neuroscientists collaborate closely with experimentalists in analyzing novel data and synthesizing new models of biological phenomena.

Single-neuron modeling

Main article: Biological neuron models

Even a single neuron has complex biophysical characteristics and can perform computations (e.g.). Hodgkin and Huxley's original model only employed two voltage-sensitive currents (Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse under certain conditions through the axolemma), the fast-acting sodium and the inward-rectifying potassium. Though successful in predicting the timing and qualitative features of the action potential, it nevertheless failed to predict a number of important features such as adaptation and shunting. Scientists now believe that there are a wide variety of voltage-sensitive currents, and the implications of the differing dynamics, modulations, and sensitivity of these currents is an important topic of computational neuroscience.

The computational functions of complex dendrites are also under intense investigation. There is a large body of literature regarding how different currents interact with geometric properties of neurons.

Some models are also tracking biochemical pathways at very small scales such as dendritic spines or synaptic clefts.

There are many software packages, such as GENESIS and NEURON, that allow rapid and systematic in silico modeling of realistic neurons. Blue Brain, a project founded by Henry Markram from the École Polytechnique Fédérale de Lausanne, aims to construct a biophysically detailed simulation of a cortical column on the Blue Gene supercomputer.

Modeling the richness of biophysical properties on the single-neuron scale can supply mechanisms that serve as the building blocks for network dynamics. However, detailed neuron descriptions are computationally expensive and this computing cost can limit the pursuit of realistic network investigations, where many neurons need to be simulated. As a result, researchers that study large neural circuits typically represent each neuron and synapse with an artificially simple model, ignoring much of the biological detail. Hence there is a drive to produce simplified neuron models that can retain significant biological fidelity at a low computational overhead. Algorithms have been developed to produce faithful, faster running, simplified surrogate neuron models from computationally expensive, detailed neuron models.

Modeling Neuron-glia interactions

Glial cells participate significantly to the regulation of neuronal activity at a cellular but also at a network level. Modeling this interaction allows to clarify the potassium cycle, so important for maintaining homeostatis and to prevent epileptic seizures. Modeling reveals the role of glial protrusions that can penetrate in some cases the synaptic cleft to interfere with the synpatic transmission and thus control synaptic communication.

Development, axonal patterning, and guidance

Computational neuroscience aims to address a wide array of questions. How do axons and dendrites form during development? How do axons know where to target and how to reach these targets? How do neurons migrate to the proper position in the central and peripheral systems? How do synapses form? We know from molecular biology that distinct parts of the nervous system release distinct chemical cues, from growth factors to hormones that modulate and influence the growth and development of functional connections between neurons.

Theoretical investigations into the formation and patterning of synaptic connection and morphology are still nascent. One hypothesis that has recently garnered some attention is the minimal wiring hypothesis, which postulates that the formation of axons and dendrites effectively minimizes resource allocation while maintaining maximal information storage.

Sensory processing

Early models on sensory processing understood within a theoretical framework are credited to Horace Barlow. Somewhat similar to the minimal wiring hypothesis described in the preceding section, Barlow understood the processing of the early sensory systems to be a form of efficient coding, where the neurons encoded information which minimized the number of spikes. Experimental and computational work have since supported this hypothesis in one form or another. For the example of visual processing, efficient coding is manifested in the forms of efficient spatial coding, color coding, temporal/motion coding, stereo coding, and combinations of them.

Further along the visual pathway, even the efficiently coded visual information is too much for the capacity of the information bottleneck, the visual attentional bottleneck. A subsequent theory, V1 Saliency Hypothesis (V1SH), has been developed on exogenous attentional selection of a fraction of visual input for further processing, guided by a bottom-up saliency map in the primary visual cortex.

Current research in sensory processing is divided among a biophysical modelling of different subsystems and a more theoretical modelling of perception. Current models of perception have suggested that the brain performs some form of Bayesian inference and integration of different sensory information in generating our perception of the physical world.

Motor control

Many models of the way the brain controls movement have been developed. This includes models of processing in the brain such as the cerebellum's role for error correction, skill learning in motor cortex and the basal ganglia, or the control of the vestibulo ocular reflex. This also includes many normative models, such as those of the Bayesian or optimal control flavor which are built on the idea that the brain efficiently solves its problems.

Memory and synaptic plasticity

Main article: Synaptic plasticity

Earlier models of memory are primarily based on the postulates of Hebbian learning. Biologically relevant models such as Hopfield net have been developed to address the properties of associative (also known as "content-addressable") style of memory that occur in biological systems. These attempts are primarily focusing on the formation of medium- and long-term memory, localizing in the hippocampus. Models of working memory, relying on theories of network oscillations and persistent activity, have been built to capture some features of the prefrontal cortex in context-related memory. Additional models look at the close relationship between the basal ganglia and the prefrontal cortex and how that contributes to working memory.

One of the major problems in neurophysiological memory is how it is maintained and changed through multiple time scales. Unstable synapses are easy to train but also prone to stochastic disruption. Stable synapses forget less easily, but they are also harder to consolidate. One recent computational hypothesis involves cascades of plasticity that allow synapses to function at multiple time scales. Stereochemically detailed models of the acetylcholine receptor-based synapse with the Monte Carlo method, working at the time scale of microseconds, have been built. It is likely that computational tools will contribute greatly to our understanding of how synapses function and change in relation to external stimulus in the coming decades.

Behaviors of networks

Biological neurons are connected to each other in a complex, recurrent fashion. These connections are, unlike most artificial neural networks, sparse and usually specific. It is not known how information is transmitted through such sparsely connected networks, although specific areas of the brain, such as the visual cortex, are understood in some detail. It is also unknown what the computational functions of these specific connectivity patterns are, if any.

The interactions of neurons in a small network can be often reduced to simple models such as the Ising model. The statistical mechanics of such simple systems are well-characterized theoretically. Some recent evidence suggests that dynamics of arbitrary neuronal networks can be reduced to pairwise interactions. It is not known, however, whether such descriptive dynamics impart any important computational function. With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test the new theories regarding neuronal networks.

In some cases the complex interactions between inhibitory and excitatory neurons can be simplified using mean-field theory, which gives rise to the population model of neural networks. While many neurotheorists prefer such models with reduced complexity, others argue that uncovering structural-functional relations depends on including as much neuronal and network structure as possible. Models of this type are typically built in large simulation platforms like GENESIS or NEURON. There have been some attempts to provide unified methods that bridge and integrate these levels of complexity.

Visual attention, identification, and categorization

Visual attention can be described as a set of mechanisms that limit some processing to a subset of incoming stimuli. Attentional mechanisms shape what we see and what we can act upon. They allow for concurrent selection of some (preferably, relevant) information and inhibition of other information. In order to have a more concrete specification of the mechanism underlying visual attention and the binding of features, a number of computational models have been proposed aiming to explain psychophysical findings. In general, all models postulate the existence of a saliency or priority map for registering the potentially interesting areas of the retinal input, and a gating mechanism for reducing the amount of incoming visual information, so that the limited computational resources of the brain can handle it. An example theory that is being extensively tested behaviorally and physiologically is the V1 Saliency Hypothesis that a bottom-up saliency map is created in the primary visual cortex to guide attention exogenously. Computational neuroscience provides a mathematical framework for studying the mechanisms involved in brain function and allows complete simulation and prediction of neuropsychological syndromes.

Cognition, discrimination, and learning

Computational modeling of higher cognitive functions has only recently begun. Experimental data comes primarily from single-unit recording in primates. The frontal lobe and parietal lobe function as integrators of information from multiple sensory modalities. There are some tentative ideas regarding how simple mutually inhibitory functional circuits in these areas may carry out biologically relevant computation.

The brain seems to be able to discriminate and adapt particularly well in certain contexts. For instance, human beings seem to have an enormous capacity for memorizing and recognizing faces. One of the key goals of computational neuroscience is to dissect how biological systems carry out these complex computations efficiently and potentially replicate these processes in building intelligent machines.

The brain's large-scale organizational principles are illuminated by many fields, including biology, psychology, and clinical practice. Integrative neuroscience attempts to consolidate these observations through unified descriptive models and databases of behavioral measures and recordings. These are the bases for some quantitative modeling of large-scale brain activity.

The Computational Representational Understanding of Mind (CRUM) is another attempt at modeling human cognition through simulated processes like acquired rule-based systems in decision making and the manipulation of visual representations in decision making.

Consciousness

One of the ultimate goals of psychology/neuroscience is to be able to explain the everyday experience of conscious life. Francis Crick, Giulio Tononi and Christof Koch made some attempts to formulate consistent frameworks for future work in neural correlates of consciousness (NCC), though much of the work in this field remains speculative. Specifically, Crick cautioned the field of neuroscience to not approach topics that are traditionally left to philosophy and religion.

Computational clinical neuroscience

Computational clinical neuroscience is a field that brings together experts in neuroscience, neurology, psychiatry, decision sciences and computational modeling to quantitatively define and investigate problems in neurological and psychiatric diseases, and to train scientists and clinicians that wish to apply these models to diagnosis and treatment.

Predictive computational neuroscience

Predictive computational neuroscience is a recent field that combines signal processing, neuroscience, clinical data and machine learning to predict the brain during coma or anesthesia. For example, it is possible to anticipate deep brain states using the EEG signal. These states can be used to anticipate hypnotic concentration to administrate to the patient.

Computational Psychiatry

Computational psychiatry is a new emerging field that brings together experts in machine learning, neuroscience, neurology, psychiatry, psychology to provide an understanding of psychiatric disorders.

Technology

Neuromorphic computing

Main article: Neuromorphic engineering

A neuromorphic computer/chip is any device that uses physical artificial neurons (made from silicon) to do computations (See: neuromorphic computing, physical neural network). One of the advantages of using a physical model computer such as this is that it takes the computational load of the processor (in the sense that the structural and some of the functional elements don't have to be programmed since they are in hardware). In recent times, neuromorphic technology has been used to build supercomputers which are used in international neuroscience collaborations. Examples include the Human Brain Project SpiNNaker supercomputer and the BrainScaleS computer.