Behavioural genetics

From Wikipedia, the free encyclopedia

Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates genetic and environmental influences, using research designs that allow removal of the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans (typically using twin and family studies), as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research (e.g., knockout mice) and in human studies (e.g., genome-wide association studies), leading to new scientific discoveries.

Findings from behavioural genetic research have broadly impacted modern understanding of the role of genetic and environmental influences on behaviour. These include evidence that nearly all researched behaviors are under a significant degree of genetic influence, and that influence tends to increase as individuals develop into adulthood. Further, most researched human behaviours are influenced by a very large number of genes and the individual effects of these genes are very small. Environmental influences also play a strong role, but they tend to make family members more different from one another, not more similar. Despite progress on these findings, the field continues to wrestle with unrealistic statistical and scientific assumptions.

History

Farmers with wheat and cattle - Ancient Egyptian art 1,422 BCE displaying domesticated animals.

Selective breeding and the domestication of animals is perhaps the earliest evidence that humans considered the idea that individual differences in behaviour could be due to natural causes. Plato and Aristotle each speculated on the basis and mechanisms of inheritance of behavioural characteristics. Plato, for example, argued in The Republic that selective breeding among the citizenry to encourage the development of some traits and discourage others, what today might be called eugenics, was to be encouraged in the pursuit of an ideal society. Behavioural genetic concepts also existed during the English renaissance, where William Shakespeare perhaps first coined the terms "nature" versus "nurture" in The Tempest, where he wrote in Act IV, Scene I, that Caliban was "A devil, a born devil, on whose nature Nurture can never stick".

Modern-day behavioural genetics began with Sir Francis Galton, a nineteenth-century intellectual and cousin of Charles Darwin. Galton was a polymath who studied many subjects, including the heritability of human abilities and mental characteristics. One of Galton's investigations involved a large pedigree study of social and intellectual achievement in the English upper class. In 1869, 10 years after Darwin's On the Origin of Species, Galton published his results in Hereditary Genius. In this work, Galton found that the rate of "eminence" was highest among close relatives of eminent individuals, and decreased as the degree of relationship to eminent individuals decreased. While Galton could not rule out the role of environmental influences on eminence, a fact which he acknowledged, the study served to initiate an important debate about the relative roles of genes and environment on behavioural characteristics. Through his work, Galton also "introduced multivariate analysis and paved the way towards modern Bayesian statistics" that are used throughout the sciences—launching what has been dubbed the "Statistical Enlightenment".

Galton in his later years

The field of behavioural genetics, as founded by Galton, was ultimately undermined by another of Galton's intellectual contributions, the founding of the eugenics movement in 20th century society. The primary idea behind eugenics was to use selective breeding combined with knowledge about the inheritance of behaviour to improve the human species. The eugenics movement was subsequently discredited by scientific corruption and genocidal actions in Nazi Germany. Behavioural genetics was thereby discredited through its association to eugenics. The field once again gained status as a distinct scientific discipline through the publication of early texts on behavioural genetics, such as Calvin S. Hall's 1951 book chapter on behavioural genetics, in which he introduced the term "psychogenetics", which enjoyed some limited popularity in the 1960s and 1970s. However, it eventually disappeared from usage in favour of "behaviour genetics".

The start of behavior genetics as a well-identified field was marked by the publication in 1960 of the book Behavior Genetics by John L. Fuller and William Robert (Bob) Thompson. It is widely accepted now that many if not most behaviours in animals and humans are under significant genetic influence, although the extent of genetic influence for any particular trait can differ widely. A decade later, in February 1970, the first issue of the journal Behavior Genetics was published and in 1972 the Behavior Genetics Association was formed with Theodosius Dobzhansky elected as the association's first president. The field has since grown and diversified, touching many scientific disciplines.

Methods

The primary goal of behavioural genetics is to investigate the nature and origins of individual differences in behaviour. A wide variety of different methodological approaches are used in behavioral genetic research, only a few of which are outlined below.

Animal studies

Animal behavior genetic studies are considered more reliable than are studies on humans, because animal experiments allow for more variables to be manipulated in the laboratory. In animal research selection experiments have often been employed. For example, laboratory house mice have been bred for open-field behaviour, thermoregulatory nesting, and voluntary wheel-running behaviour. A range of methods in these designs are covered on those pages.

Behavioural geneticists using model organisms employ a range of molecular techniques to alter, insert, or delete genes. These techniques include knockouts, floxing, gene knockdown, or genome editing using methods like CRISPR-Cas9. These techniques allow behavioural geneticists different levels of control in the model organism's genome, to evaluate the molecular, physiological, or behavioural outcome of genetic changes. Animals commonly used as model organisms in behavioral genetics include mice, zebra fish, and the nematode species C. elegans.

Twin and family studies

Pedigree chart showing an inheritance pattern consistent with autosomal dominant transmission. Behavioural geneticists have used pedigree studies to investigate the genetic and environmental basis of behaviour.

Some research designs used in behavioural genetic research are variations on family designs (also known as pedigree designs), including twin studies and adoption studies. Quantitative genetic modelling of individuals with known genetic relationships (e.g., parent-child, sibling, dizygotic and monozygotic twins) allows one to estimate to what extent genes and environment contribute to phenotypic differences among individuals. The basic intuition of the twin study is that monozygotic twins share 100% of their genome and dizygotic twins share, on average, 50% of their segregating genome. Thus, differences between the two members of a monozygotic twin pair can only be due to differences in their environment, whereas dizygotic twins will differ from one another due to environment as well as genes. Under this simplistic model, if dizygotic twins differ more than monozygotic twins it can only be attributable to genetic influences. An important assumption of the twin model is the equal environment assumption that monozygotic twins have the same shared environmental experiences as dizygotic twins. If, for example, monozygotic twins tend to have more similar experiences than dizygotic twins—and these experiences themselves are not genetically mediated through gene-environment correlation mechanisms—then monozygotic twins will tend to be more similar to one another than dizygotic twins for reasons that have nothing to do with genes.

Twin studies of monozygotic and dizygotic twins use a biometrical formulation to describe the influences on twin similarity and to infer heritability. The formulation rests on the basic observation that the variance in a phenotype is due to two sources, genes and environment. More formally, ${\displaystyle Var(P)=g+(g\times \epsilon )+\epsilon }$, where ${\displaystyle P}$ is the phenotype, ${\displaystyle g}$ is the effect of genes, ${\displaystyle \epsilon }$ is the effect of the environment, and ${\displaystyle (g\times \epsilon )}$ is a gene by environment interaction. The ${\displaystyle g}$ term can be expanded to include additive (${\displaystyle a^{2}}$), dominance (${\displaystyle d^{2}}$), and epistatic (${\displaystyle i^{2}}$) genetic effects. Similarly, the environmental term ${\displaystyle \epsilon }$ can be expanded to include shared environment (${\displaystyle c^{2}}$) and non-shared environment (${\displaystyle e^{2}}$), which includes any measurement error. Dropping the gene by environment interaction for simplicity (typical in twin studies) and fully decomposing the ${\displaystyle g}$ and ${\displaystyle \epsilon }$ terms, we now have ${\displaystyle Var(P)=(a^{2}+d^{2}+i^{2})+(c^{2}+e^{2})}$. Twin research then models the similarity in monozygotic twins and dizogotic twins using simplified forms of this decomposition, shown in the table.

Decomposing the genetic and environmental contributions to twin similarity.

Type of relationship	Full decomposition	Falconer's decomposition
Perfect similarity between siblings	${\displaystyle 1.0=a^{2}+d^{2}+i^{2}+c^{2}+e^{2}}$	${\displaystyle 1.0=a^{2}+c^{2}+e^{2}}$
Monozygotic twin correlation(${\displaystyle r_{MZ}}$)	${\displaystyle r_{MZ}=a^{2}+d^{2}+i^{2}+c^{2}}$	${\displaystyle r_{MZ}=a^{2}+c^{2}}$
Dizygotic twin correlation (${\displaystyle r_{DZ}}$)	${\displaystyle r_{DZ}={\frac {1}{2}}a^{2}+{\frac {1}{4}}d^{2}+(k)i^{2}+c^{2}}$	${\displaystyle r_{DZ}={\frac {1}{2}}a^{2}+c^{2}}$
Where ${\displaystyle k}$ is an unknown (probably very small) quantity.

The simplified Falconer formulation can then be used to derive estimates of ${\displaystyle a^{2}}$, ${\displaystyle c^{2}}$, and ${\displaystyle e^{2}}$. Rearranging and substituting the ${\displaystyle r_{MZ}}$ and ${\displaystyle r_{DZ}}$ equations one can obtain an estimate of the additive genetic variance, or heritability, ${\displaystyle a^{2}=2(r_{MZ}-r_{DZ})}$, the non-shared environmental effect ${\displaystyle e^{2}=1-r_{MZ}}$ and, finally, the shared environmental effect ${\displaystyle c^{2}=r_{MZ}-a^{2}}$. The Falconer formulation is presented here to illustrate how the twin model works. Modern approaches use maximum likelihood to estimate the genetic and environmental variance components.

Measured genetic variants

The Human Genome Project has allowed scientists to directly genotype the sequence of human DNA nucleotides. Once genotyped, genetic variants can be tested for association with a behavioural phenotype, such as mental disorder, cognitive ability, personality, and so on.

• Candidate Genes. One popular approach has been to test for association candidate genes with behavioural phenotypes, where the candidate gene is selected based on some a priori theory about biological mechanisms involved in the manifestation of a behavioural trait or phenotype. In general, such studies have proven difficult to broadly replicate and there has been concern raised that the false positive rate in this type of research is high.
• Genome-wide association studies. In genome-wide association studies, researchers test the relationship of millions of genetic polymorphisms with behavioural phenotypes across the genome. This approach to genetic association studies is largely atheoretical, and typically not guided by a particular biological hypothesis regarding the phenotype. Genetic association findings for behavioural traits and psychiatric disorders have been found to be highly polygenic (involving many small genetic effects).
• SNP heritability and co-heritability. Recently, researchers have begun to use similarity between classically unrelated people at their measured single nucleotide polymorphisms (SNPs) to estimate genetic variation or covariation that is tagged by SNPs, using mixed effects models implemented in software such as Genome-wide complex trait analysis (GCTA). To do this, researchers find the average genetic relatedness over all SNPs between all individuals in a (typically large) sample, and use Haseman-Elston regression or restricted maximum likelihood to estimate the genetic variation that is "tagged" by, or predicted by, the SNPs. The proportion of phenotypic variation that is accounted for by the genetic relatedness has been called "SNP heritability". Intuitively, SNP heritability increases to the degree that phenotypic similarity is predicted by genetic similarity at measured SNPs, and is expected to be lower than the true narrow-sense heritability to the degree that measured SNPs fail to tag (typically rare) causal variants. The value of this method is that it is an independent way to estimate heritability that does not require the same assumptions as those in twin and family studies, and that it gives insight into the allelic frequency spectrum of the causal variants underlying trait variation.

Quasi-experimental designs

Some behavioural genetic designs are useful not to understand genetic influences on behaviour, but to control for genetic influences to test environmentally-mediated influences on behaviour. Such behavioural genetic designs may be considered a subset of natural experiments, quasi-experiments that attempt to take advantage of naturally occurring situations that mimic true experiments by providing some control over an independent variable. Natural experiments can be particularly useful when experiments are infeasible, due to practical or ethical limitations.

A general limitation of observational studies is that the relative influences of genes and environment are confounded. A simple demonstration of this fact is that measures of 'environmental' influence are heritable. Thus, observing a correlation between an environmental risk factor and a health outcome is not necessarily evidence for environmental influence on the health outcome. Similarly, in observational studies of parent-child behavioural transmission, for example, it is impossible to know if the transmission is due to genetic or environmental influences, due to the problem of passive gene-environment correlation. The simple observation that the children of parents who use drugs are more likely to use drugs as adults does not indicate why the children are more likely to use drugs when they grow up. It could be because the children are modelling their parents' behaviour. Equally plausible, it could be that the children inherited drug-use-predisposing genes from their parent, which put them at increased risk for drug use as adults regardless of their parents' behaviour. Adoption studies, which parse the relative effects of rearing environment and genetic inheritance, find a small to negligible effect of rearing environment on smoking, alcohol, and marijuana use in adopted children, but a larger effect of rearing environment on harder drug use.

Other behavioural genetic designs include discordant twin studies, children of twins designs, and Mendelian randomization.

General findings

There are many broad conclusions to be drawn from behavioural genetic research about the nature and origins of behaviour. Three major conclusions include: 1) all behavioural traits and disorders are influenced by genes; 2) environmental influences tend to make members of the same family more different, rather than more similar; and 3) the influence of genes tends to increase in relative importance as individuals age.

Genetic influences on behaviour are pervasive

It is clear from multiple lines of evidence that all researched behavioural traits and disorders are influenced by genes; that is, they are heritable. The single largest source of evidence comes from twin studies, where it is routinely observed that monozygotic (identical) twins are more similar to one another than are same-sex dizygotic (fraternal) twins.

The conclusion that genetic influences are pervasive has also been observed in research designs that do not depend on the assumptions of the twin method. Adoption studies show that adoptees are routinely more similar to their biological relatives than their adoptive relatives for a wide variety of traits and disorders. In the Minnesota Study of Twins Reared Apart, monozygotic twins separated shortly after birth were reunited in adulthood. These adopted, reared-apart twins were as similar to one another as were twins reared together on a wide range of measures including general cognitive ability, personality, religious attitudes, and vocational interests, among others. Approaches using genome-wide genotyping have allowed researchers to measure genetic relatedness between individuals and estimate heritability based on millions of genetic variants. Methods exist to test whether the extent of genetic similarity (aka, relatedness) between nominally unrelated individuals (individuals who are not close or even distant relatives) is associated with phenotypic similarity. Such methods do not rely on the same assumptions as twin or adoption studies, and routinely find evidence for heritability of behavioural traits and disorders.

Nature of environmental influence

Just as all researched human behavioural phenotypes are influenced by genes (i.e., are heritable), all such phenotypes are also influenced by the environment. The basic fact that monozygotic twins are genetically identical but are never perfectly concordant for psychiatric disorder or perfectly correlated for behavioural traits, indicates that the environment shapes human behaviour.

The nature of this environmental influence, however, is such that it tends to make individuals in the same family more different from one another, not more similar to one another. That is, estimates of shared environmental effects (${\displaystyle c^{2}}$) in human studies are small, negligible, or zero for the vast majority of behavioural traits and psychiatric disorders, whereas estimates of non-shared environmental effects (${\displaystyle e^{2}}$) are moderate to large. From twin studies ${\displaystyle c^{2}}$ is typically estimated at 0 because the correlation (${\displaystyle r_{MZ}}$) between monozygotic twins is at least twice the correlation (${\displaystyle r_{DZ}}$) for dizygotic twins. When using the Falconer variance decomposition (${\displaystyle 1.0=a^{2}+c^{2}+e^{2}}$) this difference between monozygotic and dizygotic twin similarity results in an estimated ${\displaystyle c^{2}=0}$. It is important to note that the Falconer decomposition is simplistic. It removes the possible influence of dominance and epistatic effects which, if present, will tend to make monozygotic twins more similar than dizygotic twins and mask the influence of shared environmental effects. This is a limitation of the twin design for estimating ${\displaystyle c^{2}}$. However, the general conclusion that shared environmental effects are negligible does not rest on twin studies alone. Adoption research also fails to find large (${\displaystyle c^{2}}$) components; that is, adoptive parents and their adopted children tend to show much less resemblance to one another than the adopted child and his or her non-rearing biological parent. In studies of adoptive families with at least one biological child and one adopted child, the sibling resemblance also tends be nearly zero for most traits that have been studied.

Similarity in twins and adoptees indicates a small role for shared environment in personality.

The figure provides an example from personality research, where twin and adoption studies converge on the conclusion of zero to small influences of shared environment on broad personality traits measured by the Multidimensional Personality Questionnaire including positive emotionality, negative emotionality, and constraint.

Given the conclusion that all researched behavioural traits and psychiatric disorders are heritable, biological siblings will always tend to be more similar to one another than will adopted siblings. However, for some traits, especially when measured during adolescence, adopted siblings do show some significant similarity (e.g., correlations of .20) to one another. Traits that have been demonstrated to have significant shared environmental influences include internalizing and externalizing psychopathology, substance use and dependence, and intelligence.

Nature of genetic influence

Genetic effects on human behavioural outcomes can be described in multiple ways. One way to describe the effect is in terms of how much variance in the behaviour can be accounted for by alleles in the genetic variant, otherwise known as the coefficient of determination or ${\displaystyle R^{2}}$. An intuitive way to think about ${\displaystyle R^{2}}$ is that it describes the extent to which the genetic variant makes individuals, who harbour different alleles, different from one another on the behavioural outcome. A complementary way to describe effects of individual genetic variants is in how much change one expects on the behavioural outcome given a change in the number of risk alleles an individual harbours, often denoted by the Greek letter ${\displaystyle \beta }$ (denoting the slope in a regression equation), or, in the case of binary disease outcomes by the odds ratio ${\displaystyle OR}$ of disease given allele status. Note the difference: ${\displaystyle R^{2}}$ describes the population-level effect of alleles within a genetic variant; ${\displaystyle \beta }$ or ${\displaystyle OR}$ describe the effect of having a risk allele on the individual who harbours it, relative to an individual who does not harbour a risk allele.

When described on the ${\displaystyle R^{2}}$ metric, the effects of individual genetic variants on complex human behavioural traits and disorders are vanishingly small, with each variant accounting for ${\displaystyle R^{2}<0 .3="" annotation="">$ of variation in the phenotype. This fact has been discovered primarily through genome-wide association studies of complex behavioural phenotypes, including results on substance use, personality, fertility, schizophrenia, depression, and endophenotypes including brain structure and function. There are a small handful of replicated and robustly studied exceptions to this rule, including the effect of APOE on Alzheimer's disease, and CHRNA5 on smoking behaviour, and ALDH2 (in individuals of East Asian ancestry) on alcohol use.

On the other hand, when assessing effects according to the ${\displaystyle \beta }$ metric, there are a large number of genetic variants that have very large effects on complex behavioural phenotypes. The risk alleles within such variants are exceedingly rare, such that their large behavioural effects impact only a small number of individuals. Thus, when assessed at a population level using the ${\displaystyle R^{2}}$ metric, they account for only a small amount of the differences in risk between individuals in the population. Examples include variants within APP that result in familial forms of severe early onset Alzheimer's disease but affect only relatively few individuals. Compare this to risk alleles within APOE, which pose much smaller risk compared to APP, but are far more common and therefore affect a much greater proportion of the population.

Finally, there are classical behavioural disorders that are genetically simple in their etiology, such as Huntington's disease. Huntington's is caused by a single autosomal dominant variant in the HTT gene, which is the only variant that accounts for any differences among individuals in their risk for developing the disease, assuming they live long enough. In the case of genetically simple and rare diseases such as Huntington's, the variant ${\displaystyle R^{2}}$ and the ${\displaystyle OR}$ are simultaneously large.

Criticisms and controversies

Behavioural genetic research and findings have at times been controversial. Some of this controversy has arisen because behavioural genetic findings can challenge societal beliefs about the nature of human behaviour and abilities. Major areas of controversy have included genetic research on topics such as racial differences, intelligence, violence, and human sexuality. Other controversies have arisen due to misunderstandings of behavioural genetic research, whether by the lay public or the researchers themselves. The notion of heritability is easily misunderstood to imply causality. When behavioral genetics researchers say that a behavior is X% heritable, that does not mean that genetics causes up to X% of the behavior. Instead, heritability is a statement about population level correlations.

Perhaps the most controversial subject has been on race and genetics, where fringe research groups have claimed that observed racial differences on a behavioral trait are a product of racial differences in allele frequencies. Such claims are made most frequently to differences between White and Black racial groups. These are complicated issues that are extremely difficult to resolve due to the confounding of the racial group and environmental experience, such as discrimination and oppression. Indeed, race is a social construct that is not very useful for genetic research. Instead, geneticists use concepts such as ancestry, which is more rigorously defined. For example, a so-called "Black" race may include all individuals of relatively recent African descent ("recent" because all humans are descended from African ancestors). However, there is more genetic diversity in Africa than the rest of the world combined, so speaking of a "Black" race is without a precise genetic meaning.

Qualitative research has fostered arguments that behavioural genetics is an ungovernable field without scientific norms or consensus, which fosters controversy. The argument continues that this state of affairs has led to controversies including race and IQ, instances where variation within a single gene was found to very strongly influence a controversial phenotype (e.g., the "gay gene" controversy), and others. This argument, made by Aaron Panofsky in his book Misbehaving Science, further states that because of the persistence of controversy in behavior genetics and the failure of disputes to be resolved, behavior genetics does not conform to the standards of good science.

The scientific assumptions on which parts of behavioral genetic research are based have also been criticized as flawed. Genome wide association studies are often implemented with simplifying statistical assumptions, such as additivity, which may be statistically robust but unrealistic. Critics further contend that, in humans, behavior genetics represents a misguided form of genetic reductionism based on inaccurate interpretations of seriously flawed statistical analyses. Studies comparing monozygotic (MZ) and dizygotic (DZ) twins assume that environmental influences will be the same in both types of twins, but this assumption may also be unrealistic. In reality MZ twins are treated more alike than DZ twins, which itself may be an example of evocative gene-environment correlation, suggesting that one's genes influence their treatment by others. It is also not possible in twin studies to completely eliminate effects of the shared womb environment, although studies comparing twins who experience monochorionic and dichorionic environments in utero do exist, and indicate limited impact. Studies of twins separated in early life include children who were separated not at birth but part way through childhood. The effect of early rearing environment can therefore be evaluated to some extent in such a study, by comparing twin similarity for those twins separated early and those separated later.

Behavioral neuroscience

From Wikipedia, the free encyclopedia

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology is the application of the principles of biology to the study of physiological, genetic, and developmental mechanisms of behavior in humans and other animals.

History

Behavioral neuroscience as a scientific discipline emerged from a variety of scientific and philosophical traditions in the 18th and 19th centuries. In philosophy, people like René Descartes proposed physical models to explain animal and human behavior. Descartes, for example, suggested that the pineal gland, a midline unpaired structure in the brain of many organisms, was the point of contact between mind and body. Descartes also elaborated on a theory in which the pneumatics of bodily fluids could explain reflexes and other motor behavior. This theory was inspired by moving statues in a garden in Paris.

Other philosophers also helped give birth to psychology. One of the earliest textbooks in the new field, The Principles of Psychology by William James, argues that the scientific study of psychology should be grounded in an understanding of biology:

Bodily experiences, therefore, and more particularly brain-experiences, must take a place amongst those conditions of the mental life of which Psychology need take account. The spiritualist and the associationist must both be 'cerebralists,' to the extent at least of admitting that certain peculiarities in the way of working of their own favorite principles are explicable only by the fact that the brain laws are a codeterminant of their result.

Our first conclusion, then, is that a certain amount of brain-physiology must be presupposed or included in Psychology.

The emergence of both psychology and behavioral neuroscience as legitimate sciences can be traced from the emergence of physiology from anatomy, particularly neuroanatomy. Physiologists conducted experiments on living organisms, a practice that was distrusted by the dominant anatomists of the 18th and 19th centuries. The influential work of Claude Bernard, Charles Bell, and William Harvey helped to convince the scientific community that reliable data could be obtained from living subjects.

Even before the 18th and 19th century, behavioral neuroscience was beginning to take form as far back as 1700 B.C. The question that seems to continually arise is what is the connection between the mind and body. The debate is formally referred to as the mind-body problem. There are two major schools of thought that attempt to resolve the mind–body problem; monism and dualism. Plato and Aristotle are two of several philosophers who participated in this debate. Plato believed that the brain was where all mental thought and processes happened. In contrast, Aristotle believed that the brain served the purpose of cooling down the emotions derived from the heart. The mind-body problem was a stepping stone toward attempting to understand the connection between the mind and body.
Another debate arose about was localization of function or functional specialization versus equipotentiality which played a significant role in the development in behavioral neuroscience. As a result of localization of function research, many famous people found within psychology have come to various different conclusions. Wilder Penfield was able to develop a map of the cerebral cortex through studying epileptic patients along with Rassmussen. Research on localization of function has led behavioral neuroscientist to a better understanding of which parts of the brain control behavior. This is best exemplified through the case study of Phineas Gage.

The term "psychobiology" has been used in a variety of contexts, emphasizing the importance of biology, which is the discipline that studies organic, neural and cellular modifications in behavior, plasticity in neuroscience, and biological diseases in all aspects, in addition, biology focuses and analyzes behavior and all the subjects it is concerned about, from a scientific point of view. In this context, psychology helps as a complementary, but important discipline in the neurobiological sciences. The role of psychology in this questions is that of a social tool that backs up the main or strongest biological science. The term "psychobiology" was first used in its modern sense by Knight Dunlap in his book An Outline of Psychobiology (1914). Dunlap also was the founder and editor-in-chief of the journal Psychobiology. In the announcement of that journal, Dunlap writes that the journal will publish research "...bearing on the interconnection of mental and physiological functions", which describes the field of behavioral neuroscience even in its modern sense.

Relationship to other fields of psychology and biology

In many cases, humans may serve as experimental subjects in behavioral neuroscience experiments; however, a great deal of the experimental literature in behavioral neuroscience comes from the study of non-human species, most frequently rats, mice, and monkeys. As a result, a critical assumption in behavioral neuroscience is that organisms share biological and behavioral similarities, enough to permit extrapolations across species. This allies behavioral neuroscience closely with comparative psychology, evolutionary psychology, evolutionary biology, and neurobiology. Behavioral neuroscience also has paradigmatic and methodological similarities to neuropsychology, which relies heavily on the study of the behavior of humans with nervous system dysfunction (i.e., a non-experimentally based biological manipulation).

Synonyms for behavioral neuroscience include biopsychology, biological psychology, and psychobiology. Physiological psychology is a subfield of behavioral neuroscience, with an appropriately narrower definition

Research methods

The distinguishing characteristic of a behavioral neuroscience experiment is that either the independent variable of the experiment is biological, or some dependent variable is biological. In other words, the nervous system of the organism under study is permanently or temporarily altered, or some aspect of the nervous system is measured (usually to be related to a behavioral variable).

Disabling or decreasing neural function

• Lesions – A classic method in which a brain-region of interest is naturally or intentionally destroyed to observe any resulting changes such as degraded or enhanced performance on some behavioral measure. Lesions can be placed with relatively high accuracy "Thanks to a variety of brain 'atlases' which provide a map of brain regions in 3-dimensional "stereotactic coordinates.
  • Surgical lesions – Neural tissue is destroyed by removing it surgically.
  • Electrolytic lesions – Neural tissue is destroyed through the application of electrical shock trauma.
  • Chemical lesions – Neural tissue is destroyed by the infusion of a neurotoxin.
  • Temporary lesions – Neural tissue is temporarily disabled by cooling or by the use of anesthetics such as tetrodotoxin.
• Transcranial magnetic stimulation – A new technique usually used with human subjects in which a magnetic coil applied to the scalp causes unsystematic electrical activity in nearby cortical neurons which can be experimentally analyzed as a functional lesion.
• Synthetic ligand injection – A receptor activated solely by a synthetic ligand (RASSL) or Designer Receptor Exclusively Activated by Designer Drugs (DREADD), permits spatial and temporal control of G protein signaling in vivo. These systems utilize G protein-coupled receptors (GPCR) engineered to respond exclusively to synthetic small molecules ligands, like clozapine N-oxide (CNO), and not to their natural ligand(s). RASSL's represent a GPCR-based chemogenetic tool. These synthetic ligands upon activation can decrease neural function by G-protein activation. This can with Potassium attenuating neural activity.
• Psychopharmacological manipulations – A chemical receptor antagonist induces neural activity by interfering with neurotransmission. Antagonists can be delivered systemically (such as by intravenous injection) or locally (intracerebrally) during a surgical procedure into the ventricles or into specific brain structures. For example, NMDA antagonist AP5 has been shown to inhibit the initiation of long term potentiation of excitatory synaptic transmission (in rodent fear conditioning) which is believed to be a vital mechanism in learning and memory.
• Optogenetic inhibition – A light activated inhibitory protein is expressed in cells of interest. Powerful millisecond timescale neuronal inhibition is instigated upon stimulation by the appropriate frequency of light delivered via fiber optics or implanted LEDs in the case of vertebrates, or via external illumination for small, sufficiently translucent invertebrates. Bacterial Halorhodopsins or Proton pumps are the two classes of proteins used for inhibitory optogenetics, achieving inhibition by increasing cytoplasmic levels of halides (Cl⁻) or decreasing the cytoplasmic concentration of protons, respectively.

Enhancing neural function

• Electrical stimulation – A classic method in which neural activity is enhanced by application of a small electric current (too small to cause significant cell death).
• Psychopharmacological manipulations – A chemical receptor agonist facilitates neural activity by enhancing or replacing endogenous neurotransmitters. Agonists can be delivered systemically (such as by intravenous injection) or locally (intracerebrally) during a surgical procedure.
• Synthetic Ligand Injection – Likewise, G_q-DREADDs can be used to modulate cellular function by innervation of brain regions such as Hippocampus. This innervation results in the amplification of γ-rhythms, which increases motor activity.
• Transcranial magnetic stimulation – In some cases (for example, studies of motor cortex), this technique can be analyzed as having a stimulatory effect (rather than as a functional lesion).
• Optogenetic excitation – A light activated excitatory protein is expressed in select cells. Channelrhodopsin-2 (ChR2), a light activated cation channel, was the first bacterial opsin shown to excite neurons in response to light, though a number of new excitatory optogenetic tools have now been generated by improving and imparting novel properties to ChR2.

Measuring neural activity

• Optical techniques – Optical methods for recording neuronal activity rely on methods that modify the optical properties of neurons in response to the cellular events associated with action potentials or neurotransmitter release.
  • Voltage sensitive dyes (VSDs) were among the earliest method for optically detecting action potentials. VSDs commonly become fluorescent in response to a neuron's change in voltage, rendering individual action potentials detectable. Genetically encoded voltage sensitive fluorescent proteins have also been developed.
  • Calcium imaging relies on dyes or genetically encoded proteins that fluoresce upon binding to the calcium that is transiently present during an action potential.
  • Synapto-pHluorin is a technique that relies on a fusion protein that combines a synaptic vesicle membrane protein and a pH sensitive fluorescent protein. Upon synaptic vesicle release, the chimeric protein is exposed to the higher pH of the synaptic cleft, causing a measurable change in fluorescence.
• Single-unit recording – A method whereby an electrode is introduced into the brain of a living animal to detect electrical activity that is generated by the neurons adjacent to the electrode tip. Normally this is performed with sedated animals but sometimes it is performed on awake animals engaged in a behavioral event, such as a thirsty rat whisking a particular sandpaper grade previously paired with water in order to measure the corresponding patterns of neuronal firing at the decision point.
• Multielectrode recording – The use of a bundle of fine electrodes to record the simultaneous activity of up to hundreds of neurons.
• fMRI – Functional magnetic resonance imaging, a technique most frequently applied on human subjects, in which changes in cerebral blood flow can be detected in an MRI apparatus and are taken to indicate relative activity of larger scale brain regions (i.e., on the order of hundreds of thousands of neurons).
• PET - Positron Emission Tomography detects particles called photons using a 3-D nuclear medicine examination. These particles are emitted by injections of radioisotopes such as fluorine. PET imaging reveal the pathological processes which predict anatomic changes making it important for detecting, diagnosing and characterising many pathologies.
• Electroencephalography – Or EEG; and the derivative technique of event-related potentials, in which scalp electrodes monitor the average activity of neurons in the cortex (again, used most frequently with human subjects). This technique uses different types of electrodes for recording systems such as needle electrodes and saline-based electrodes. EEG allows for the investigation of mental disorders, sleep disorders and physiology. It can monitor brain development and cognitive engagement.
• Functional neuroanatomy – A more complex counterpart of phrenology. The expression of some anatomical marker is taken to reflect neural activity. For example, the expression of immediate early genes is thought to be caused by vigorous neural activity. Likewise, the injection of 2-deoxyglucose prior to some behavioral task can be followed by anatomical localization of that chemical; it is taken up by neurons that are electrically active.
• MEG – Magnetoencephalography shows the functioning of the human brain through the measurement of electromagnetic activity. Measuring the magnetic fields created by the electric current flowing within the neurons identifies brain activity associated with various human functions in real time, with millimeter spatial accuracy. Clinicians can noninvasively obtain data to help them assess neurological disorders and plan surgical treatments.

Genetic techniques

• QTL mapping – The influence of a gene in some behavior can be statistically inferred by studying inbred strains of some species, most commonly mice. The recent sequencing of the genome of many species, most notably mice, has facilitated this technique.
• Selective breeding – Organisms, often mice, may be bred selectively among inbred strains to create a recombinant congenic strain. This might be done to isolate an experimentally interesting stretch of DNA derived from one strain on the background genome of another strain to allow stronger inferences about the role of that stretch of DNA.
• Genetic engineering – The genome may also be experimentally-manipulated; for example, knockout mice can be engineered to lack a particular gene, or a gene may be expressed in a strain which does not normally do so (the 'transgenic'). Advanced techniques may also permit the expression or suppression of a gene to occur by injection of some regulating chemical.

Other research methods

Computational models - Using a computer to formulate real-world problems to develop solutions. Although this method is often focused in computer science, it has begun to move towards other areas of study.For example, psychology is one of these areas. Computational models allow researchers in psychology to enhance their understanding of the functions and developments in nervous systems. Examples of methods include the modelling of neurons, networks and brain systems and theoretical analysis. Computational methods have a wide variety of roles including clarifying experiments, hypothesis testing and generating new insights. These techniques play an increasing role in the advancement of biological psychology.

Limitations and advantages

Different manipulations have advantages and limitations. Neural tissue destroyed as a primary consequence of a surgery, electric shock or neurotoxin can confound the results so that the physical trauma masks changes in the fundamental neurophysiological processes of interest. For example, when using an electrolytic probe to create a purposeful lesion in a distinct region of the rat brain, surrounding tissue can be affected: so, a change in behavior exhibited by the experimental group post-surgery is to some degree a result of damage to surrounding neural tissue, rather than by a lesion of a distinct brain region. Most genetic manipulation techniques are also considered permanent. Temporary lesions can be achieved with advanced in genetic manipulations, for example, certain genes can now be switched on and off with diet. Pharmacological manipulations also allow blocking of certain neurotransmitters temporarily as the function returns to its previous state after the drug has been metabolized.

Topic areas

In general, behavioral neuroscientists study similar themes and issues as academic psychologists, though limited by the need to use nonhuman animals. As a result, the bulk of literature in behavioral neuroscience deals with mental processes and behaviors that are shared across different animal models such as:

• Sensation and perception
• Motivated behavior (hunger, thirst, sex)
• Control of movement
• Learning and memory
• Sleep and biological rhythms
• Emotion

However, with increasing technical sophistication and with the development of more precise noninvasive methods that can be applied to human subjects, behavioral neuroscientists are beginning to contribute to other classical topic areas of psychology, philosophy, and linguistics, such as:

• Language
• Reasoning and decision making
• Consciousness

Behavioral neuroscience has also had a strong history of contributing to the understanding of medical disorders, including those that fall under the purview of clinical psychology and biological psychopathology (also known as abnormal psychology). Although animal models do not exist for all mental illnesses, the field has contributed important therapeutic data on a variety of conditions, including:

• Parkinson's disease, a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech.
• Huntington's disease, a rare inherited neurological disorder whose most obvious symptoms are abnormal body movements and a lack of coordination. It also affects a number of mental abilities and some aspects of personality.
• Alzheimer's disease, a neurodegenerative disease that, in its most common form, is found in people over the age of 65 and is characterized by progressive cognitive deterioration, together with declining activities of daily living and by neuropsychiatric symptoms or behavioral changes.
• Clinical depression, a common psychiatric disorder, characterized by a persistent lowering of mood, loss of interest in usual activities and diminished ability to experience pleasure.
• Schizophrenia, a psychiatric diagnosis that describes a mental illness characterized by impairments in the perception or expression of reality, most commonly manifesting as auditory hallucinations, paranoid or bizarre delusions or disorganized speech and thinking in the context of significant social or occupational dysfunction.
• Autism, a brain development disorder that impairs social interaction and communication, and causes restricted and repetitive behavior, all starting before a child is three years old.
• Anxiety, a physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create the feelings that are typically recognized as fear, apprehension, or worry.
• Drug abuse, including alcoholism.