L'adaptation comportementale est primordiale pour faire face à l'environnement flexible dans lequel les individus évoluent chaque Jour, notamment par l'élaboration de comportements d'exploration ou de vérification. Le cortex préfrontal a depuis longtemps été considéré comme le siège du contrôle exécutif nécessaire à la genèse de ces comportements. Deux régions semblent essentielles: le cortex préfrontal latéral (LPFC) et le cortex midcingulaire (MCC). Bien que diverses théories attribuent à ces régions les fonctions d'évaluation des performances et de contrôle cognitif respectivement, leurs rôles dans les comportements de recherche d'information restent imprécis, et cela malgré l'apport potentiel aussi bien dans un contexte normal que pathologique (i.e. troubles obsessionnels compulsifs). Pour mieux comprendre la spécificité de ces régions dans les comportements d’exploration, les travaux que nous avons menés au cours de cette thèse emploient différentes approches comportementales et électrophysiologiques chez les primates humains et non humains. Ils ont permis de (1) raffiner la compréhension de l'implication des régions frontales dans le contrôle cognitif et l'effort attentionnel, (2) développer des tâches comportementales induisant des vérifications, basées sur le Jugement des performances ou l'évaluation de l'environnement, et (3) souligner la spécificité des comportements de vérification. En particulier, nos enregistrements intracérébraux chez le singe en comportement montrent l'importance du MCC pour signaler le besoin d'explorer sur la base de l'évaluation des performances, tandis que le LPFC contribue à la mise en oeuvre de la conduite comportementale à adopter / Behavioural adaptation is an essential element of our quest to survive and flourish in a volatile environment, in particular by the use of exploration and verification behaviours. The prefrontal cortex has long been considered a critical source of these behaviours given it role in executive control. Two regions appear to be particularly critical – the lateral prefrontal cortex (LPFC), and the midcingulate cortex (MCC). Although numerous theories associate these regions with the functions of performance evaluation and cognitive control, the role of these regions in the search for information remains lacking, despite the importance of these behaviours and their apparent role in pathologies such as obsessive compulsive disorders. This thesis seeks to understand the specific roles of these regions in exploratory behaviours, employing a range of behavioural and electrophysiological techniques in both human and non human primates. The work here helps to refine our understanding of the role of frontal cortical regions in cognitive control and attentional effort. Moreover, we have developed a number of behavioural tasks that induce verification behavior based on subjects’ evaluation of their own performance or on an evaluation of the environment. Our work reveals the specificity of verification behaviour as well as specific roles for the MCC and LPFC in this search for information. Our intra cerebral recordings in monkeys working on such tasks underline the importance of the MCC for signalling the need to explore the environment on the basis of performance evaluation, whilst we have also shown the role of LPFC in the implementation of the necessary behavioural adaptations

The overall goal of this dissertation is to elucidate the cellular and circuit mechanisms underlying flexible behavior in the prefrontal cortex. We are often faced with situations in which the appropriate behavior in one context is inappropriate in others. If these situations are familiar, we can perform the appropriate behavior without relearning how the context relates to the behavior — an important hallmark of intelligence. Neuroimaging and lesion studies have shown that this dynamic, flexible process of remapping context to behavior (task switching) is dependent on prefrontal cortex, but the precise contributions and interactions of prefrontal subdivisions are still unknown. This dissertation investigates two prefrontal areas that are thought to be involved in distinct, but complementary executive roles in task switching — the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC). Using electrophysiological recordings from macaque monkeys, I show that synchronous network oscillations in the dlPFC provide a mechanism to flexibly coordinate context representations (rules) between groups of neurons during task switching. Then, I show that, wheras the ACC neurons can represent rules at the cellular level, they do not play a significant role in switching between contexts — rather they seem to be more related to errors and motivational drive. Finally, I develop a set of web-enabled interactive visualization tools designed to provide a multi-dimensional integrated view of electrophysiological datasets. Taken together, these results contribute to our understanding of task switching by investigating new mechanisms for coordination of neurons in prefrontal cortex, clarifying the roles of prefrontal subdivisions during task switching, and providing visualization tools that enhance exploration and understanding of large, complex and multi-scale electrophysiological data.

O córtex pré-frontal medial ventral (CPFMv) é uma estrutura límbica que está envolvida em respostas autonômicas associadas a reações aversivas. O CPFMv é dividido em córtex pré- límbico (PL), córtex infralímbico (IL) e córtex dorsopeduncular (DP). A estimulação elétrica ou química destas regiões causa respostas defensivas e alterações autonômicas tais como respostas cardiovasculares, dependendo da sub-região estimulada. O estresse de restrição (ER) causa alterações hormonais e respostas autonômicas, tais como aumento de pressão arterial (PA) e frequência cardíaca (FC). A ativação de neurônios presentes no CPFMv durante essa situação aversiva, assim como os resultados da inibição farmacológica das sinapses presentes no PL e IL sugerem o envolvimento destas estruturas na modulação das respostas cardiovasculares causadas pelo ER. Entretanto, os possíveis neurotransmissores presentes no vCPFM, envolvidos nesta modulação, ainda não foram elucidados. O sistema opioidérgico central modula o sistema cardiovascular inclusive durante situações aversivas, sendo que tanto receptores quanto peptídeos opióides estão presentes no CPFMv. Considerando o exposto acima, a hipótese a ser testada no presente trabalho foi que a neurotransmissão opioidérgica do PL e IL está envolvida na modulação das respostas cardiovasculares de aumento da PA e FC desencadeadas pelo ER. Assim, a administração de naloxona (antagonista não-seletivo de receptores opióides) no PL ou IL reduziu a resposta pressora e taquicardíaca induzida pelo ER, sendo o perfil da curva dose-inibição em forma de U-invertido. A administração de CTAP (antagonista dos receptores opióides µ) ou nor-BNI (antagonista dos receptores opióides ?) no PL também reduziu a resposta pressora e taquicardíaca induzida pelo ER, de forma semelhante à naloxona, sugerindo o envolvimento desses receptores na modulação das respostas cardiovasculares desencadeadas pelo ER, enquanto que no IL, apenas a administração de nor-BNI reduziu a resposta cardiovascular induzida pelo ER. O tratamento com naltrindole (antagonista ?-seletivo) em ambas as estruturas não alterou a resposta pressora e taquicardíaca gerada pelo ER. A administração de UPF-101 (antagonista ORL-1) no PL potencializou a resposta taquicardíaca, sem alterar a resposta pressora enquanto a administração no IL não gerou efeito. Em resumo, os resultados indicam que o sistema opioidérgico, presente no PL e IL, desempenha papel facilitatório sobre as respostas cardiovasculares induzidas pelo ER, enquanto o sistema nociceptina/orfanina FQ apresentaria papel inibitório. / The ventral medial prefrontal cortex (vMPFC) is a limbic structure involved in the mediation of autonomic responses associated to aversive situations. The vMPFC is divided into prelimbic cortex (PL), infralimbic cortex (IL) and dorsal peduncular cortex (DP). The electrical or chemical stimulation of these regions cause defensive responses and autonomic changes, such as cardiovascular responses, depending on the subregion stimulated. The restraint stress (RS) evokes hormonal and autonomic responses, as well as arterial pressure and heart rate increases. Neuronal activation in the vMPFM was reported during this aversive situation, and the pharmacological inhibition of synapses in the PL and IL has suggested the involvement of these structures in the modulation of cardiovascular responses caused by RS. However, the possible neurotransmitters present in vCPFM that are involved in this modulation have not yet been identified. Opioid peptides and their receptors are present in the CPFMv. Furthermore, the central opioid system is known to modulate the cardiovascular system, even during aversive situations. Therefore, the hypothesis of this study was that PL and IL opioid neurotransmission is involved in the modulation of cardiovascular responses caused by RS. Naloxone (opioid nonselective antagonist) administration in PL or IL reduced the pressure and tachycardiac response evoked by RS, with the dose-inhibition curve having an U-inverset shape. Similar to naloxone, the selective µ-opioid antagonist CTAP and the selective ?-opioid antagonist nor-BNI when administered into the PL also reduced the pressor and tachycardiac response induced by RS, thus suggesting an involvement of these receptors in the modulation of cardiovascular responses evoked by RS, while in the IL, only administration of nor- BNI reduced the cardiovascular response induced by RS. In both structures, the treatment with the selective ?-opioid antagonist naltrindole did not affect the pressor and tachycardic response caused by RS. The pretreatment of the PL with the selective ORL-1 antagonist UPF-101 increased the tachycardic response, without affecting the RSevoked pressor, while the administration of UPF-101 into the IL did not affect the RS-evoked cardiovascular response. In summary, the opioid system in PL and IL appear to play a facilitatory role on the cardiovascular responses induced by RS, while the system nociceptin / orphanin FQ would have an inhibitory role on these responses.

Damage to the ventromedial prefrontal cortex (vmPFC) can lead to disturbances in personality, emotional dysregulation, impairments in social conduct, and difficulties in decision-making. Many researchers have likened the conduct of individuals with vmPFC lesions to that of criminal psychopaths, labeling the effects of vmPFC damage “pseudopsychopathy” or “acquired sociopathy.” However, although psychopathy—a condition marked by a distinct mosaic of antisocial personality traits and behaviors—has been studied and characterized as a psychological and behavioral disorder by many researchers, the overlap between acquired sociopathy and psychopathy remains ambiguous. This study assessed the severity of psychopathic personality traits in neurological patients with acquired damage to the vmPFC using both informant-report and self-report measures. On both informant-report and self-report measures, individuals with vmPFC damage showed no significant elevations across a wide range of psychopathic traits relative to demographically-matched neurologically healthy comparison participants and patients with damage outside of the vmPFC. The results showed only one trait, Fearlessness, that was significantly higher in patients with vmPFC lesions relative to the neurologically-healthy comparison group.

Decision makers flexibly deploy decision-making strategies based on the specific features of the problems they face (Ford, Schmitt, Schechtman, Hults, & Doherty, 1989; Payne, Bettman, & Johnson, 1993). However, research on the neuroscience of decision making has focused on a "policy capture" approach that utilizes static decision problems to study the relationships between input (the problem presented), output (the choices made), and the brain. Since the decision problems are prepackaged, this approach does not provide information about the neural bases of predecisional processes critical for flexible decision making, such as selecting an appropriate decision-making strategy and dynamically acquiring and integrating the information needed to progress toward choice. The aim of the current project is to use the lesion method to explore the neural bases of predecisional processes. The fronto-limbic information acquisition network (FLIAN) is proposed as a neural framework critical for predecisional processes in flexible decision making. According to the FLIAN model, the ventromedial prefrontal cortex (vmPFC) represents the decision problem as currently perceived (i.e., the decision space), which is the basis for selecting a decision strategy via interactions with limbic structures. The vmPFC implements the strategy through the coordination of attribute-based information acquisition induced by the amygdala and relational, option-based acquisition induced by the hippocampus. In Chapter 1, the literature pertinent to FLIAN structures is reviewed, including the neuroanatomical and functional backgrounds of those structures, their roles in decision making, and their potential roles in predecisional processes. Chapter 2 provides a review of the behavioral literature on predecisional processes and outlines the FLIAN model in detail. Chapters 3 and 4 present studies that test, and provide partial support for, the FLIAN model using the lesion method and information board tasks. As predicted, the hippocampus is shown to be critical for relational, option-based information acquisition. The vmPFC is shown to be critical for determining how attributes are weighted in the decision space representation and for organizing predecisional behavior. The amygdala was not found to play its role in attribute-based acquisition, but previous studies do support this function and further research is warranted on the role of the amygdala, as well as the hippocampus and vmPFC, in predecisional processes. Future research should also explore the consequences of abnormal predecisional functioning for social behavior, memory, and emotion processing.

Philosophical and scientific investigations into the nature of belief and knowledge are ancient, extending back to the beginnings of rational thought. It is not until the last few decades that we have been able to peer into and examine the organ of belief, the brain. Neuroanatomical perspectives have begun to address the long-standing questions of epistemology by identifying specific neural regions that are critical for the storage and evaluations of beliefs. Here, a novel neuroanatomical model of belief and doubt is presented, where post-rolandic association cortices are critical for the storage of beliefs and the prefrontal cortex is necessary for the doubt and evaluation process. It is proposed that the singular function of the prefrontal cortex is "false tagging" (the neuroanatomical essence of doubt) to mental representations in post-rolandic cortices. Individuals that have dysfunction to the prefrontal cortex, such as patients with explicit damage to the prefrontal cortex, from tumor resections or cerebral vascular events, should show a "doubt deficit", accompanied by a general increased belief to information. Evidence is presented indicating that deficiencies in the "false tagging" function may explain a wide assortment of abnormalities in neurological and psychiatric patients. Several experiments in various populations (neurological, developmental, and psychiatric) were conducted to examine the role of specific brain regions in the believing and doubting process. First, two studies gave participants explicitly-labeled false beliefs and measured the ability of the participants to falsify these beliefs. It was predicted that participants with dysfunction to the prefrontal cortex would be poor at falsifying novel beliefs. Results confirmed the predictions. Second, participants were given pairs of statements that represented opposite opinions on some issue and responded by agreeing or disagreeing with each statement. Participants with dysfunction to the prefrontal cortex, who, theoretically, have a "doubt deficit," should show compartmentalized minds, where cognitions are easily believed but rarely doubted against other extant mental information. Results suggested that participants with prefrontal cortex dysfunction were more likely to agree to opposing statements. Third, individuals with dysfunction to the prefrontal cortex should lack a dissonant state that can change attitudes, when two cognitions are in conflict. Using a free-choice paradigm, it was found that participants with prefrontal dysfunction showed either extreme attitude change after choice or no attitude change after choice, which is consistent with a "no dissonance" state. Finally, individuals with compartmentalized minds tend evince an authoritarian personality. A psychometric scale and a behavioral measure of authoritarianism were examined in the participants. Results indicated that participants with prefrontal cortex dysfunction showed increased authoritarianism on the psychometric scale, but decreased authoritarian behavior, reflecting a dissociation between knowledge and behavior. In conclusion, the results support the theoretical assertions that the prefrontal cortex is critical for "false tagging" or doubting cognitive representations. Data from neurological, developmental, and psychiatric populations are broadly consistent with the theory and offer strong external validity.

This thesis provides an overview of the literature both in the field of academic anxiety and emotion regulation. The two research fields have proceeded independently in the literature at least until recently and the thesis highlights their integration. The thesis aims to answer: what happens in the brain during cognitive reappraisal and how can we use cognitive reappraisal as a strategy for dealing with academic anxiety. Brain-imaging studies show that cognitive reappraisal (an emotion regulation strategy) involves many different higher-order cognitive processes, such as emotion processing, manipulation of appraisals in working memory, inhibiting the old and selecting new appraisals. Different regions of the prefrontal cortex are believed to support these functions, moreover, the prefrontal cortex modulates amygdala activity and decreases negative emotions. Previous research in the lab and in the classroom suggests that cognitive reappraisal might be a strategy for dealing with academic anxiety. The arousal reappraisal intervention encourages students to reinterpret their increased arousal as beneficial to their performance. Only a small number of studies have tested the intervention in academic contexts, however the results are promising, e.g. students improved exam performance. The goal is to teach students that it is possible to perform well regardless of one’s anxiety. The findings presented in this thesis provide an initial glimpse into the fruitful integration of these two research fields.

The current set of experiments was designed to test the hypothesis that there is a sex difference in impulsivity and in brain areas associated with impulse control in prepubertal and adult rats, such that females have greater inhibitory control than do males. Preliminary studies established that neonatal testosterone exposure is able to masculinize and increase impulsive behavior in prepubertal female rats. In the current study, male and female prepubertal rats exposed to treatments that resulted in either neonatal androgen or estrogen receptor activation made more impulsive choices than did control females and their performance mirrored that of control males. Assessment of impulsivity in adult rats indicated that impulsive choice behavior was similar in males and females whereas impulsive action behavior was greater in males than in females. Analysis of protein levels of markers of dopaminergic and noradrenergic reuptake in the orbital frontal cortex (OFC) and dorsal striatum (dSTR), two brain areas important for impulse control, revealed no differences between male and female prepubertal or adult rats, whereas analysis of protein levels of markers of myelination in the OFC and dSTR revealed similar levels between the sexes in prepubertal rats but increased myelin levels in the OFC but not dSTR of adult female rats as compared to males. Furthermore, analysis of the projections from the OFC to dSTR discovered that the strength of these projections was significantly greater in adult females as compared to males. However, inactivation of the OFC during an impulsive action task in adult rats failed to have an effect on impulsive action responding. Collectively, these results demonstrate for the first time that there is a sex difference in impulsive choice control in prepubertal rats that is organized neonatally by actions of both androgens and estrogens, this sex difference subsides in adulthood, but a sex difference in impulsive action control is present in adulthood. Furthermore, the novel discovery that adult female rats have increased levels of myelination within the OFC and increased strength of projections from the OFC to dSTR as compared to males establishes a molecular sex difference that could underlie the enhanced impulse control in females. / acase@tulane.edu

The evolutionary forces that led to the unprecedented expansion of the human brain and the extreme cognitive prowess possessed by humans have always attracted a great deal of attention from the scientific community. Presented here is a novel theoretical perspective, where the driving force on human brain evolution was the need for enhanced ability to infer social values of conspecifics in the face of degradation and loss of chemosensory signalling mechanisms necessary for social communication present in most mammals. The lack of chemosensory communication of biologically relevant information between humans in the face of the need to make adaptive and accurate social evaluations, led to an exaption of mammalian chemosensory brain regions for the more complex task of inferring social values from behavioural cues that are variable, ambiguous, or otherwise difficult to detect and interpret. This change in social processing from perceptual evaluation to inferential computation placed a premium on cognitive capacity, thus selecting for larger more powerful brains. These selective processes would have left an indelible mark on the human brain, where the human homologues of regions involved in mammalian conspecific chemical communication, in particular the target regions of this study the amygdala and ventromedial prefrontal cortex (VMPC), should be involved in the processing of biologically relevant information and social inference. Several experiments were conducted to examine the role of these brain regions in social inferential processing using the lesion deficit method. First, given that conspecific chemical communication is particularly relevant for biologically imperative evaluation for the purposes of reproduction, VMPC and amygdala damage may result in abnormal mate-related decisions. Second, normal social attributions exhibit the correspondence bias, however damage to the target regions may result in an abnormal lack correspondence bias. Third, the current hypothesis is contrasted with another leading hypothesis, the Social Brain Hypothesis whose proponents predict a relationship between group-size and social cognition. Finally, if the target brain regions are truly integral in inferring social information, then damage to these regions will interfere with the ability to utilize transitive inference in social situations, and potentially in using transitive inference in general. Damage to the target areas produces limited effects on mate-related decisions and preferences. However, the current hypothesis may suggest that the target brain regions are only involved when the problem is inferential in nature rather than simpler perception of social information. In support of this notion, damage to the target regions results in a lack of the correspondence bias when making economic decisions. This alteration in social attributions actually leads to more `rational' decision-making in this context. In contrast to the predictions of the Social Brain Hypothesis, damage to the target regions produces no observed reduction in social group size, nor is there any observed relationship between perspective-taking ability and group size. Finally, damage to the VMPC produces deficits in using transitive inference in a non-social context perhaps hinting at the underlying computations of this region in inferring social information. In conclusion, it appears that the notion that the human brain regions that have been exapted from their duties in chemosensation and communication in mammalian brains has at least some validity. Moreover, these brain regions have been shifted by evolution to a more computationally complex process of social inference possibly providing the push toward larger and more powerful human brains.

Decision-making in the context of leadership, has received scant attention in the management literature, which has traditionally centered on general mental ability and personality as predictors of effectiveness. This research effort bridges the neuroscientific and management literatures to offer an alternative, neuropsychological profile of effective leadership by proposing prefrontal brain processes (executive function) as a key component and predictor of complex decision-making and leadership effectiveness. While the management literature has largely viewed decision-making as a cognitive ability, neuroscience informs us that this complex function emerges from the integration of affective and cognitive signals in the prefrontal cortex. In an attempt to identify the neural predictors of effective leadership decision-making, 105 corporate leaders were assessed on a robust array of neuropsychological indices of prefrontal brain function. These were in turn correlated with their leadership and decision-making abilities after controlling for general mental ability and personality, utilizing structural equation modeling. Executive function incrementally predicts complex decision-making and transformational leadership effectiveness, above and beyond general mental ability. Complex decision-making does not appear to be central to leadership effectiveness, while extraversion emerges as the strongest predictor of transformational leadership followed by executive function. Executive function, extraversion and general mental ability do not predict transactional leadership. These results would need replication in a larger dataset to establish their validity, especially in the case of executive function. While the heritability of leadership ability has emerged as fairly significant, this opens the field to unearthing the biological variables and predictors of leadership ability. Neuroscience thus has the potential to offer biomarkers and metrics of leadership that can further not only our foundational knowledge of organizational behavior, but can also find useful applications in recruitment, training and development practice, though this cross-disciplinary initiative is in its infancy. Based on the preliminary results from this study, executive function (which has so far remained in the domain of neurology) has the potential to inform and measure leadership effectiveness.