According to a “presence/absence hypothesis,” the hippocampus is not necessary for the formation of learned associations between currently present stimuli and responses (as in classical conditioning), but is necessary whenever a stimulus, if it is to activate a particular response, must first activate a memory-representation of something not present in the here-and-now. The distinction between responses made to present stimuli as opposed to (memories of) absent stimuli was first stressed by Romanes (1889), but we find evidence in the target article that supports the relevance of this distinction to our understanding of hippocampal functioning.

Aggleton & Brown rightly point out the shortcomings of the medial temporal lobe hypothesis as an approach to anterograde amnesia. Their broader perspective is a necessary corrective, and one hopes it will be taken very seriously. Although they correctly note the dangers of conflating recognition and recall, they themselves make a similar mistake in discussing familiarity; we suggest an alternative approach. We also discuss implications of their view for an analysis of retrograde amnesia. The notion that there are two routes by which the hippocampus can reactivate neuronal ensembles in the neocortex could help us understand some currently puzzling facts about the dynamics of memory consolidation.

Three comments are made. The proposal that recollection and familiarity-based recognition take different thalamic routes does not fit recent experimental evidence, suggesting that mediodorsal thalamus acts in an integrative role with respect to prefrontal cortex. Second, the role of frontal cortex in episodic memory has been understated. Third, the role of the hippocampal axis is likely to be the computation and storage of ideothetic information.

Aggleton & Brown suggest that whereas familiarity is computed in perirhinal cortex, the hippocampus contributes to recollection. This account raises issues about the definition of amnesia, clarifies confusion about dual-process models of recognition, and sits comfortably with accounts of hippocampal function from outside the amnesia literature. The model can – and should – be tested. Some preliminary data suggest that it may need changes.

What exactly is going on via fornical connections? Aggleton & Brown's target article correctly stresses their importance, but a detailed understanding of their role in memory appears to require fresh research approaches.

Recent studies of the contribution made by the hippocampus to spatial behavior suggest that it plays a role in integrating and double integrating distance and direction information using cues generated by self-movement. This and other evidence that the hippocampus plays a central role in spatial behavior seems inconsistent with proposals that it is primarily involved in episodic memory.

Aggleton & Brown propose that familiarity-based recognition depends on a perirhinal-medial dorsal thalamic system. However, connections between these structures are sparse or absent. In contrast, the perirhinal cortex is connected to midline/intralaminar nuclei. In a human, a lesion in this thalamic domain, sparing the medial dorsal nucleus, impaired familiarity-based recognition while sparing recollective-based recognition. It is thus more likely that the intralaminar/midline nuclei are involved in recognition.

Aggleton & Brown argue that a hippocampal-anterior thalamic system supports the “recollection” of contextual information about previous events, and that a separate perirhinal-medial dorsal thalamic system supports detection of stimulus “familiarity.” Although there is a growing body of human literature that is in agreement with these claims, when recollection and familiarity have been examined in amnesics using the process dissociation or the remember/know procedures, the results do not seem to provide consistent support. We reexamine these studies and describe the results of an additional experiment using a receiver operating characteristic (ROC) technique. The results of the reanalysis and the ROC experiment are consistent with Aggleton & Brown's proposal. Patients with damage to both regions exhibit severe deficits in recollection and smaller, but consistent, deficits in familiarity.

The proposal that the hippocampus is important for the encoding of episodic information, but not familiarity-based recognition, is incompatible with the available data. An alternative way to think about functional specialization within the medial temporal lobe memory system is suggested, based on neuroanatomy.

The goal of our target article was to review a number of emerging facts about the effects of limbic damage on memory in humans and animals, and about divisions within recognition memory in humans. We then argued that this information can be synthesized to produce a new view of the substrates of episodic memory. The key pathway in this system is from the hippocampus to the anterior thalamic nuclei. There seems to be a general agreement that the importance of this pathway has previously been underestimated and that it warrants further study. At the same time, a number of key questions remain. These concern the relationship of this system to another temporal-lobe/diencephalic system that contributes to recognition, and the relationship of these systems to prefrontal cortex activity.

Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation.

Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system.

Individual differences in the functioning of this network arise from functional variation in the ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, “experience-expectant,” and “experience-dependent.” Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive context and incentive motivation and behavior.

Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.

We propose that a control system will address the causal dynamics of the neural network that Depue & Collins regard as underlying extraversion. We briefly describe a control system approach and articulate the notion of integration. The integration of goals and regards is achieved by subcortical assessment of reward in the nucleus accumbens and VTA (ventral tegmental area) transmission of this information largely by dopaminergic systems and representation of reward in the MOC (medial orbital cortex). Thus reward information is collected, integrated, and evaluated in the MOC. Such control decisions rely on constraining processes, a functional property of the MOC mediated largely by serotonergic neurons.

The target article approaches individual differences in terms of phenotypic differences developing through the interaction between a specific genetic make up and environmental variables. This interaction is proposed to be cooperative and oriented toward a progressive stabilisation of the trait. However, experimental data from animal studies indicate that environmental pressure promotes dramatic changes in phenotypic expression in mature organisms. Indeed, environmental constraint not only promotes the phenotypic expression of facilitated VTA-NAS DA transmission in genotype-resistant individuals; it also inhibits its expression in genetically prone individuals. This is in line with negative genotype-environment correlation revealed by behavior genetics.

I focus on a number of issues arising from Depue & Collins's target article that require further consideration: (1) data that fail to confirm extraversion effects in positive incentive experiments; (2) the role of personality factors, other than extraversion, in dopamine agonism on positive mood states; (3) the role of extraversion in nonspecific arousal, indicating that extraversion may not be an homogeneous trait; and (4) the problem of identifying neurobiologically important traits from existing structural models of personality. I applaud the heuristic value of the model presented and suggest ways in which aspects of the model may be used to identify the personality traits associated with positive incentive motivation.

Studies of human performance indicate that extraverts show enhanced motivation in relation to reward signals, but not in relation to safety signals under defensive conditions. When it occurs under defensive conditions, enhanced motivation may be related to neuroticism. While extraverts show some attentional skills consistent with frontal dopaminergic facilitation, other frontal capacities may be related to conscientiousness. These findings suggest that dopaminergic influences on response and attentional processes may contribute to additional personality dimensions such as neuroticism and conscientiousness.

We make two suggestions with regard to Depue & Collins's (D&C's) target article. First, regarding the functioning of MOC13, we provide data indicating that, contrary to D&C's apparent position, this structure is not necessary for instrumental conditioning. Second, we suggest that D&C's approach would be advanced by reference to formal computational theory, in particular the work of Grossberg. We suggest that an integration of Grossberg's and D&C's models can provide a more complete account of extraversion.

The neurobiological mechanisms associated with affiliation, that Depue & Collins argue are a central component of extraversion are not specified in their model. In addition, only the involvement of the prefrontal cortex in extraversion is discussed, although recent evidence suggests that activity associated with additional cortical regions may be related to this trait. Finally, the assumption that neurobiological mechanisms underlie or play a causal, and therefore, more fundamental role than psychological constructs in the trait is challenged.

As well as data indicating relationships (emphasised in the target article) (1) between dopaminergic transmission in the nucleus accumbens and positive incentive motivation, and (2) between dopaminergic transmission and extraversion, other data (not accounted for by the hypotheses developed in the target article) indicate relationships (3) between accumbens dopaminergic transmission and cognitive, especially perceptual, processes that are disrupted in schizophrenia, and (4) between dopaminergic transmission and psychoticism. The tension between relationships 1 + 2 and 3 + 4 is discussed and a tentative resolution proposed.

Depue & Collins's model of incentive-motivational modulation of goal-directed behavior subserved by a medial orbital prefrontal cortical (MOC) network is appealing, but it leaves several questions unanswered: How are the stimuli that elicit an incentive motivational state selected? How does the incentive motivational state created by the MOC network modulate behavior? What is the function of the dopaminergic input to the striatum? This commentary suggests possible answers, based on the open-interconnected model of basal-ganglia-thalamocortical circuits, in which the limbic circuit selects goals and, via its connections with the motor and the associative circuits, directs behavior according to those goals, elaborating on the role of dopamine.

Interpreting VTA dopamine activity as a facilitator of affective engagement fits Depue & Collins's agency dimension of extraverted personality and also Watson's and Tellegen's (1985) engagement dimension of state mood. Serotonin, by turning down the gain on dopaminergic affective engagement, would permit already prepotent responses or habits to prevail against the behavior-switching incentive-simulation-driven temptations of the moment facilitated by fickle VTA DA. Intelligent switching between openly responsive affective engagement and constraint by long-term plans, goals, or values presumably involves environment-sensitive balancing of these neuromodulators, such as socially dominant primates may show.