The Depue & Collins model is intended to explain a normal human personality trait: extraversion. In contrast, attention-deficit/hyperactivity disorder (ADHD) is generally considered to be a type of psychopathology not found in so-called normals; however, the clinical and neurobiological research done on ADHD seems to amplify and support Depue & Collins's model.

Depue & Collins [D&C] propose a well-conceived and nicely detailed theory of the involvement of dopaminergic connections in extraversion. Since these systems are hypothesized to be associated with reward sensitivity, other neural systems that are involved with reward sensitivity should be considered as well. In this commentary it is argued that there is now enough evidence for the involvement of the left and right frontal regions of the brain in approach and withdrawal behavior that it should also be considered in theories of personality such as D&C's. Integration of predominantly subcortical and cortical theories of personality/brain function may produce a more comprehensive picture of temperament and personality.

Depue & Collins's (D&C's) work relies on extrapolation from data obtained through studies in experimental animals, and needs support from studies of the role of dopamine (DA) neurotransmission in human behaviour. Here we review evidence from two sources: (1) studies of patients with Parkinson's disease and (2) positron emission tomography (PET) studies of DA neurotransmission, which we believe lend support to Depue & Collins's theory, and which can potentially form the basis for a true neurochemistry of personality.

Structure entails arrangements and interrelations of parts that organize the whole (i.e., personality). It involves stability of traits over time. Extraversion varies along a continuum towards introversion. Multiple behavioral and biological variables in several systems vary and are regulated homeostatically within the normal range. If there is a fixed point for an individual, what inhibits variation in the biological parameter?

The evolutionary theory of sex implies a theoretically principled account of the causal mechanisms underlying personality systems in which males pursue a relatively high-risk strategy compared to females and are thus higher on traits linked to sensation seeking and social dominance. Females are expected to be lower on these traits but higher on traits related to nurturance and attraction to long-term relationships. The data confirm this pattern of sex differences. It is thus likely that these traits have been a focus of natural selection rather than the traits of gregarious/aloof and arrogant/unassuming hypothesized by Depue & Collins.

Data from further human experiments touch four open questions in the target article. (1) Extinction of reward acquisition postulated by Depue & Collins's model could not be confirmed if correlating craving for, liking of, and satisfaction from smoking. (2) Intraindividual correspondence between responsivity to dopamine agonists and antagonists could likewise not be confirmed. (3) Nicotine craving and drug-induced hormone responses were not substantially correlated. (4) Low serotonin can be the cause and not just the moderator of dopaminergic sensitivity, and personality correlates of low dopamine/low MAO (aggressive impulsive traits) can hardly be related to the positive emotion associated with dopaminergic activity.

Sensitivity to incentive motivation has a formative influence on extraversion. Mesoamygdaloid dopamine (DA) activity may, at one level, act as a micro-gate permitting an incentive to influence behavioral organization – “Go/No-Go” in this scheme. Data on function elsewhere in the mesocorticolimbic DA system are taken to support this particular function. At another level of analysis, the data in Depue & Collins's review, along with those on the rest of the ventral tegmental area (VTA) system, may fit better with a “switching” function in information processing. This link is supported by correlations between measures of extraversion, learned inattention, and overall DA activity. The point is extended to the novelty-seeking feature of the extraverted personality.

A major dopaminergic role for extraversion is compromised by the fact that affiliation and impulsivity tend to be reduced by psychostimulants. Also, the large clinical literature on the treatment of ADHD with drugs that promote dopamine activity provides little or no support for a major role for dopamine in human extraversion. Dopamine facilitation of agency may be more evident for inanimate rather than animate rewards.

Depue & Collins associate dopaminergically mediated incentive motivational processes with extraversion. In this commentary I consider dopaminergic indices from neuroimaging investigations which correlate more closely with impulsive sensation seeking personality traits than with extraversion. Measures of relevant behavioural processes also appear to correlate with personality measures other than extraversion.

Depue & Collins's general idea of a functional relationship between DA activity and extraversion is an important step toward an integrative biological model of personality. However, focusing primarily on incentive motivation and variations in VTA DA activity as basic behavioral and biological components underlying extraversion appears too limited. Existing data suggest that responsivity to changes in DA activity is higher in introverts than in extraverts. This may reflect a general, extraversion- related characteristic of the entire dopaminergic network in the brain.

This commentary examines the implications of the Depue & Collins model for the etiology and treatment of depression, specifically, whether it can account for findings concerning neurobiological, behavioral, and phenomenological facets of depression. Drawing upon the construct of self-regulation, I explore the fit of the model to current knowledge about depression, conceptualized as a dysfunction within a hypothetical brain/behavior system for maximizing positive outcomes.

Sex differences in motivation and emotional reactions to casual sex suggest that the links to extraversion, constraint, impulsivity-sensation seeking, and sexual behavior differ for men and women. Because both testosterone and dominance, and dominance and number of sex partners appear to correlate in men but not in women, it is plausible that testosterone is involved in the creation and maintenance of these sex differences in linkage among the behavioral subsystems involved in sexuality and extraversion.

Depue & Collins propose that extraversion should be separated from the impulsivity-constraint dimension of personality, and that the VTA dopamine system is the primary engine of extraversion. Although their focus is on personality traits, it may be useful to consider the evidence on psychological state changes, related both to affective arousal and to drug effects. This evidence shows that there are inherent relations between extraversion and impulsivity-constraint, and that there are influences of dopamine on impulsivity-constraint that are not consistent with the Depue & Collins model. Increased positive affect leads to increased extraversion, and this is associated with more impulsivity and less constraint. The evidence on drug effects shows that greater dopaminergic control is associated with more constraint, and with anxiety and vigilance rather than positive affect.

Upon consideration of the unconditioned and particularly the conditioned stimuli that have been proposed to participate in the generation of incentive motivational states and, by extension, of extraversion, the nature of the contribution of NAS DA becomes less clear. Different kinds of conditioned stimuli can also exert strong control over the expression of behavioral sensitization. How might such stimuli affect the ability of experience-dependent processes to introduce stable individual differences in the development and expression of extraversion trait levels?

Is a generalized positive incentive motivation a construct appropriate to the human level of behavior or would sensation or novelty seeking be a more appropriate one? Is positive incentive motivation, or susceptibility to signals of reward, a mechanism related only to extraversion traits including sociability, activation, social potency, and positive affect? Research shows that susceptibility to reward is related to impulsive sensation seeking and aggression as well as sociability and an aroused type of positive affect. Comparative and indirect human correlates suggest an involvement of dopaminergic reactivity in sensation seeking and sociability.

The commentaries on our target article address three main areas: (1) the relative importance of extraversion and other related traits to DA functioning, (2) how the long-term stability of extraversion can be conceptualized within a highly plastic central nervous system, and (3) the nature of DA functioning in the MOC network and in extraversion. We have organized our Response, therefore, into three major sections.

This commentary on Müller's target article is designed to help bridge the gap between method and theory in neurobiological approaches to language. We focus on pathonormal inference as reflective of broader conceptual issues concerning universality and modularity. Our commentary directs attention to how current methodological and analytic procedures are less than optimal and minimize possibilities for reaching theoretical consensus. We make suggestions about alternative analytic strategies that provide a direction for future scientific progress.

The natural communication system of chimpanzees has some unique characteristics rooted in two possible ways of producing call variants in primates. The chimpanzee call repertoire contains variants available to all group members. The transfer presupposes voluntary control and learnability. Chimpanzee vocalization (or its homologue in the common ancestor of chimpanzee and man) seems to represent a real precursor of human language.

The two commentaries appear supportive of the target article. Ujhelyi's commentary can be complemented with recent evidence supporting continuity of language and cognitive evolution in hominids. Gow & Rodkin's caveats regarding “pathonormal inference” and the single-case methodology are discussed from a developmental neurobiological perspective. Early structural brain lesion and developmental disorders can serve as pathological models of normal neurofunctional variability resulting from neurodevelopmental imprecision. A final point concerns the advantages of integrating multiple structural and functional imaging modalities in neuropsychological studies.