This study tested the mechanism of the ventromedial prefrontal cortex (vmPFC) in representing schemata, be it excitatory or inhibitory. Participants were administered a behavioural task distinguishing their ability to activate a relevant schema from their ability to inhibit an irrelevant schema. Healthy participants were highly accurate throughout the task, indicating proficiency in both abilities. However, older adults demonstrated a need for greater cognitive resources to inhibit a previously relevant schema. Non-confabulating patients with vmPFC lesions acted similarly to control participants, while patients with vmPFC lesions with either current or prior demonstration of confabulation performed abnormally. Specifically, their inability to inhibit irrelevant schemata was more severe than their inability to activate a relevant one. The results suggest that the nature of vmPFC damage leading to confabulation may also be responsible for erroneous schema representations. A sub-region of the vmPFC is proposed to underlie the representation of schemata through semantic lateral inhibition.

This study tested the mechanism of the ventromedial prefrontal cortex (vmPFC) in representing schemata, be it excitatory or inhibitory. Participants were administered a behavioural task distinguishing their ability to activate a relevant schema from their ability to inhibit an irrelevant schema. Healthy participants were highly accurate throughout the task, indicating proficiency in both abilities. However, older adults demonstrated a need for greater cognitive resources to inhibit a previously relevant schema. Non-confabulating patients with vmPFC lesions acted similarly to control participants, while patients with vmPFC lesions with either current or prior demonstration of confabulation performed abnormally. Specifically, their inability to inhibit irrelevant schemata was more severe than their inability to activate a relevant one. The results suggest that the nature of vmPFC damage leading to confabulation may also be responsible for erroneous schema representations. A sub-region of the vmPFC is proposed to underlie the representation of schemata through semantic lateral inhibition.

Processing information related to the self and inferring the mental state of another person is known to involve the ventromedial prefrontal cortex (VMPFC) in both younger and older adults (Stone et al., 2008; Kelley et al., 2002; Hynes et al., 2006; Ruby et al., 2009). According to the dorsolateral prefrontal (DLPF) theory of cognitive ageing, processing of the self should not be affected by healthy adult ageing as functions related to the VMPFC remain relatively preserved compared to functions related to the DLPF cortex (MacPherson et al., 2002). Similarly, no age difference should emerge in those tasks thought to tap functions of the VMPFC. The aim of this PhD is to investigate the effect of healthy adult ageing on the ability to process information related to the self and others. A series of experiments was designed to compare the performance of younger and older adults on tasks that investigate processing and retrieval of self-related information (e.g. behaviour prediction, personality judgement, mental state inferences, self-referential). The tasks differ in the extent to which they rely on cognitive effort. The results show that ageing does not affect self-related judgements. A further series of experiments designed to investigate affective and cognitive Theory of Mind (ToM) show that the affective performance, thought to rely on VMPFC activity, is not affected by age. In contrast, the performance of older participants differs from that of younger adults on cognitive ToM task, thought to involve DLPFC brain areas. A final experiment investigated the ability to make self versus other related judgments in a confabulating patient. The results show that the ability to reflect on the self but not on others was intact. In summary, the findings demonstrate that processing self-information and making ToM inferences remains intact in older individuals and is not overtly impaired by confabulation.

According to Joshua Greene’s dual-process theory, our moral judgments are processed in one of two systems in the brain referred to as the emotional (quick, unconscious) and rational (slow, conscious) system. The reason for why people tend to answer differently in the footbridge dilemma compared to the trolley dilemma is because the emotional system is dominating over the rational system. Research has demonstrated that patients with ventromedial prefrontal cortex damage make more utilitarian judgments in moral dilemmas in relation to harmful situations. According to the dual-process theory, this is because the emotional system has been impaired which results in that the only working system is the rational system. The aim of this thesis is to investigate how the dual-process theory tries to explain why our moral judgments tend to differ in some moral dilemmas. This thesis will also look at how the dual-process theory tries to explain why patients with ventromedial prefrontal cortex damage make utilitarian judgments in relation to harmful situations. This thesis will sustain that the dual-process theory have gained strong empirical support, especially from the research that has been made on patients with ventromedial prefrontal cortex damage. This thesis will also argue that some modifications needs to be made on the dual-process theory in order to make it stronger.

HINTERGRUND: Gefühle zu kontrollieren ist wichtig für ein erfolgreiches Agieren im täglichen Leben. Eine der häufigsten psychischen Störungen sind Angststörungen, bei denen fehlende Kontrolle der Emotionen vorliegt. Drei unterschiedliche Studientypen haben sich mit der Regulation negativer Emotionen auseinandergesetzt. Mittels Furchtextinktion, Placebobehandlung und willentlicher Emotionsregulation ist es möglich negative Emotionen zu reduzieren. ZIEL: Das Ziel war es, die Ergebnisse publizierter hirnbildgebender Studien zu vergleichen um ein mögliches übergreifendes Regulationszentrum über negative Emotionen zu identifizieren. MATERIAL UND METHODEN: Mit Hilfe der activation likelihood estimation (ALE) wurde eine koordinatenbasierte Metaanalyse der Ergebnisse bildgebender Studien gesunder Probanden der Jahre 2000 bis 2010 durchgeführt um Gehirnaktivierungen und- deaktivierungen bei Reduktion negativer Emotionen zu identifzieren. ERGEBNISSE: Es zeigten sich Gehirnaktivierungen im ventromedialen präfrontralem Kortex (VMPFC) in allen drei domänspezifischen ALE-Metaanalysen, begleitet von einer Amygdaladeaktivierung. In den Placebo- und Emotionsregulationsstudien wurden zudem Gehirnaktivierungen im anterioren Gyrus cinguli und der anterioren Inselrinde beobachtet. FAZIT: Der VMPFC scheint als Regulationszentrum über negative Emotionen eine entscheidende Rolle während der Emotionskontrolle einzunehmen und die Amygdala als Teil des limbischen Systems zu deaktivieren. Zudem scheinen zusätzliche Gehirnregionen bei anspruchsvolleren Formen der Emotionsregulation eine Rolle zu spielen.

Einige psychische Störungen, darunter Angst- und Suchterkrankungen, zeichnen sich durch eine abnorme Beteiligung basaler assoziativer Lernprozesse aus. Pawlow’sche Rückfallphänomene den langfristigen Erfolg extinktionsbasierter Therapien. Damit kommt der Untersuchung pharmakologischer Interventionen zur Unterstützung des Extinktionslernens bzw. -abrufs eine zentrale Bedeutung zu. Die vorliegende Dissertation umfasst vier Studien und bedient sich translationaler Pawlow’scher Lernmodelle, um (i) behaviorale und neuronale Mechanismen appetitiver Pawlow’scher Rückfallphänomene beim Menschen zu untersuchen (Studien I und II) sowie (ii) den Effekt des partiellen NMDA Rezeptor Agonisten D-Cycloserin (DCS) zur Unterstützung des Extinktionslernens appetitiver und aversiver Stimuli zu testen (Studien III und IV). Studie I demonstriert, dass appetitive Pawlow’sche Rückfalleffekte im Labor untersucht werden können und lieferte Evidenz für differenzielle Einflüsse der Amygdala und des vmPFC beim Wiederauftreten der konditionierten Reaktion. Studie II belegt die Sensitivität verschiedener, teilweise neuer okularer Reaktionsmaße für die appetitive Konditionierungsforschung. Studie III zeigte, dass DCS mit einer attenuierten BOLD-Antwort in der Amygdala und einer gesteigerten funktionellen Amygdala-vmPFC Konnektivität während des appetitiven Extinktionsabrufs assoziiert war. Studie IV ergab, dass Probanden der DCS- Gruppe attenuierte Arousal Ratings wie auch neuronale Aktivierungen in der Amygdala und dem posterioren Hippocampus im Vergleich zur Placebo-Gruppe aufwiesen. Die vorliegende Arbeit erweitert unser Verständnis appetitiver Pawlow’scher Rückfallphänomene und weist dem vmPFC eine bedeutsame Rolle beim Extinktionsabruf zu. Weiterhin unterstützt sie die Hypothese, dass DCS das Extinktionslernen unterstützt und damit Rückfallphänomene reduziert. / Pavlovian learning mechanisms play an important role in the development, maintenance, and relapse of psychiatric conditions like drug addiction and anxiety disorders. Pavlovian relapse phenomena challenge the long-term success of extinction-based exposure treatments. As such, investigating pharmacological adjuncts that could help to improve extinction learning or long- term retention are of great clinical importance. This dissertation comprises four studies applying translational human laboratory models of Pavlovian learning (i) to characterize the behavioral and neural mechanisms of appetitive Pavlovian relapse (Studies I and II), and (ii) to investigate D-cycloserine (DCS), a partial NMDA receptor agonist, as a pharmacological adjunct to augment Pavlovian extinction learning of appetitive and aversive stimuli (Studies III and IV). In Study I, we showed that appetitive Pavlovian relapse can be successfully modeled in the laboratory and provided evidence for opposing roles of amygdala and vmPFC in mediating the return of conditioned responding. Study II showed the usefulness of different and partly novel ocular response measures for appetitive conditioning research. Finally, we found DCS to attenuate amygdala reactivity during appetitive extinction recall and enhance amygdala-vmPFC coupling (Study III). Corroborating these results, Study IV showed DCS to reduce return of fear on behavioral arousal ratings and in brain areas associated with defense reactions like amygdala and posterior hippocampus. Overall, the present work extends evidence on experimentally induced return of fear to the appetitive research domain and suggests an overarching regulatory role of the vmPFC during extinction recall. Finally, it supports the hypothesis that DCS can augment extinction learning, thereby reducing the risk of relapse phenomena.

Humans are a social species. Automatic affective responses generated by neural systems wired into our brains create a moral intuition or “gut-feeling” of wrong and right that guides our moral judgments. Humans are also an intelligent, problem solving and planning species with neural structures that enable cognitive control and the ability to reason about the costs and benefits of decisions, and moral judgments, not the least. Previous research suggests that moral intuition and moral reasoning operates on different neural networks - a dual process of moral cognition, that sometimes gives rise to an inner conflict in moral judgments. Early lesion studies found correlations between damage to the ventromedial prefrontal cortex (VMPFC) and changes in moral behaviour. This has been further established through brain imaging studies and the suggestion is that VMPFC mediates affective signals from the amygdala in moral decision making and is highly involved in generating the gut-feeling of right and wrong. However, some moral issues are complex and demand higher level processing than intuition, and the dorsolateral prefrontal cortex (DLPFC) seems to be responsible for the rational, cost-benefit reasoning during moral judgments. Further, recent research suggests that during moral judgments, the brain employ neural systems that generates the representation of value, perspective and cognitive control as well as the representation of the mental and emotional states of others. The present thesis aims to investigate prominent and up to date research on the neural correlates of necessary components in moral cognition, and to examine the function of moral intuition versus reason in relation to current complex moral issues. Moral intuition is supposedly an adaption to favour “us” before “them”, not to be concerned with large scale cooperation, which may explain why we treat many moral issues with ignorance. Understanding how the moral brain works involve understanding what sort of tasks the neural mechanisms in moral cognition evolved to handle, which may explain why some modern issues are so difficult to solve.

Attention biases to trauma-related information contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD); this phenomenon has been observed through various behavioral studies, although findings from studies using a precise, direct bias task, the dot probe, have been mixed. PTSD neuroimaging studies have indicated atypical function in specific brain regions involved with attention bias; when viewing emotionally-salient cues or engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions implicated in cognitive control and attention allocation, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC) and amygdala. However, remarkably few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and include emotionally-salient information. In the current study of attention biases in highly traumatized African-American adults, a version of the dot probe task that includes stimuli that are both salient (threatening facial expressions) and relevant (photographs of African-American faces) was administered to 19 participants with and without PTSD during functional magnetic resonance imaging (fMRI). I hypothesized that: 1) individuals with PTSD would show a significantly greater attention bias to threatening faces than traumatized controls; 2) PTSD symptoms would be associated with a significantly greater attentional bias toward threat expressed in African-American, but not Caucasian, faces; 3) PTSD symptoms would be significantly associated with abnormal activity in the mPFC, dlPFC, and amygdala during presentation of threatening faces. Behavioral data did not provide evidence of attentional biases associated with PTSD. However, increased activation in the dlPFC and regions of the mPFC in response to threat cues was found in individuals with PTSD, relative to traumatized controls without PTSD; this may reflect hyper-engaged cognitive control, attention, and conflict monitoring resources in these individuals. Additionally, viewing threat in same-race, both not other-race, faces was associated with increased activation in the mPFC. These findings have important theoretical and treatment implications, suggesting that PTSD, particularly in those individuals who have experienced chronic or multiple types of trauma, may be characterized less by top-down “deficits” or failures, but by imbalanced neurobiological and cognitive systems that become over-engaged in order to “control” the emotional disruption caused by trauma-related triggers.

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Attention biases to trauma-related information contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD); this phenomenon has been observed through various behavioral studies, although findings from studies using a precise, direct bias task, the dot probe, have been mixed. PTSD neuroimaging studies have indicated atypical function in specific brain regions involved with attention bias; when viewing emotionally-salient cues or engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions implicated in cognitive control and attention allocation, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC) and amygdala. However, remarkably few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and include emotionally-salient information. In the current study of attention biases in highly traumatized African-American adults, a version of the dot probe task that includes stimuli that are both salient (threatening facial expressions) and relevant (photographs of African-American faces) was administered to 19 participants with and without PTSD during functional magnetic resonance imaging (fMRI). I hypothesized that: 1) individuals with PTSD would show a significantly greater attention bias to threatening faces than traumatized controls; 2) PTSD symptoms would be associated with a significantly greater attentional bias toward threat expressed in African-American, but not Caucasian, faces; 3) PTSD symptoms would be significantly associated with abnormal activity in the mPFC, dlPFC, and amygdala during presentation of threatening faces. Behavioral data did not provide evidence of attentional biases associated with PTSD. However, increased activation in the dlPFC and regions of the mPFC in response to threat cues was found in individuals with PTSD, relative to traumatized controls without PTSD; this may reflect hyper-engaged cognitive control, attention, and conflict monitoring resources in these individuals. Additionally, viewing threat in same-race, both not other-race, faces was associated with increased activation in the mPFC. These findings have important theoretical and treatment implications, suggesting that PTSD, particularly in those individuals who have experienced chronic or multiple types of trauma, may be characterized less by top-down “deficits” or failures, but by imbalanced neurobiological and cognitive systems that become over-engaged in order to “control” the emotional disruption caused by trauma-related triggers.