Most of the extant humor research has focused on humor comprehension with only a few studies investigating humor appreciation as a separate construct. The purpose of this investigation was to determine the relation between humor and underlying cognitive processes. Literature on brain injured individuals has indicated that working memory, verbal and visual-spatial reasoning, cognitive flexibility, and concept formation are related to performance on comprehension tests of humor. In this study, cognitive processes underlying both verbal and nonverbal humor were investigated in a sample of healthy young adults. There is evidence that semantic and phonological humor are associated with different neural networks; therefore, both semantic and phonological humor were explored. Studies investigating physiological arousal and humor have indicated that arousal is necessary for the experience of humor. This suggests that the appreciation of humor may require the integration of cognitive and affective information, a process mediated by the ventromedial prefrontal cortex (VMPFC). Thus, a second goal of this study was to investigate the relationship between humor comprehension and appreciation and the VMPFC, by including experimental tasks that previously have been linked to VMPFC functioning. Participants included 94 undergraduate psychology students between the ages of 18 and 39 years. Participants watched film clips and listened to jokes. After the presentation of each joke and each film clip, they completed a humor comprehension/appreciation inventory developed for this study. They also completed measures assessing a range of cognitive abilities hypothesized to underlie humor perception. Hierarchical regression analyses revealed that verbal reasoning was predictive of semantic humor comprehension, indicating that verbal reasoning is a core cognitive ability for the comprehension of jokes in which the humor depends on factors other than simple word play. Cognitive measures were not predictive of phonological humor comprehension or nonverbal humor comprehension. Hierarchical regression analyses revealed that the indicators of VMPFC functioning did not correlate with either humor comprehension or humor appreciation and did not moderate the relation between humor comprehension and humor appreciation. Future research is necessary to elucidate the relationships between cognitive abilities and humor perception and to further explore the contribution of the VMPFC to humor appreciation.

Major depressive disorder (MDD) is a debilitating disorder affecting hundreds of millions of people worldwide. The etiology of the disease is unknown, and how antidepressant medications reverse depression is unclear. However, imaging and postmortem studies of MDD patients show abnormalities in several limbic areas of the brain, including the prefrontal cortex. The involvement of the ventromedial prefrontal cortex (vmPFC) in depression has been particularly intriguing, for this region demonstrates reduced metabolic activity in remission, and this reduction is unique to treatment responders. In addition, deep brain stimulation targeting the subgenual cingulate cortex in the vmPFC has been shown to be effective in treating 'treatment-resistant' patients. Furthermore, neuroanatomical studies have shown that this region projects to many downstream limbic areas implicated to play roles in MDD. I therefore hypothesized that 1) the vmPFC may be an important target of antidepressant drugs, and that 2) this region may play a role in the generation of depression-associated behaviors. To test the first hypothesis, I administered desipramine (DMI), a tricyclic antidepressant, to rats. I found that the rat vmPFC was significantly activated by DMI, whereas the dorsomedial PFC (dmPFC) was not. I also found that the drug increases neuronal activity in the nucleus accumbens, but this activation was dependent on the integrity of the vmPFC. To test the second hypothesis, I induced neuronal lesions in the rat dmPFC or vmPFC and subjected the animals to behavioral tests. I found that while lesions in both areas led to increased REM sleep, only vmPFC-lesioned animals had reduced REM latency, increased sleep fragmentation and increased forced swim test immobility. Together, these results demonstrate that the vmPFC may be an important region for both antidepressant action and the generation of depression-like behaviors.

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.

Fear generalization, the generalization of fear to innocuous stimuli, is a characteristic component of pathological anxiety. For example, after returning from war, a person might begin to experience fear in response to the sound of fireworks, a stimulus typically regarded as safe. When excessive, “overgeneralization” serves as a core feature of fear and anxiety-related disorders, such as PTSD. The present collection of studies sought to investigate the neural correlates and temporal dynamics of fear generalization in humans. The first study sought to investigate the causal role of the ventromedial prefrontal cortex (vmPFC) and hippocampus in the generalization of fear. Contrary to hypotheses, individuals with focal damage to the vmPFC (N=8) or hippocampus (N=12) did not demonstrate significantly increased fear generalization relative to individuals with brain damage outside of these regions (N=16) or normal comparison participants (N=20). Potential explanations for this finding are explored. The second study sought to investigate the time course of fear generalization in humans. Participants (N = 107) completed a fear generalization task over the course of two sessions. Results indicate that fear generalization significantly increased as the duration of time between training and testing increased. This suggests that a stimulus may elicit a generalized fear response at one arbitrarily selected time point, but not another. This study establishes a novel paradigm that can be used in future work to investigate changes in the neural correlates of fear generalization over time. Fear generalization is found across an array of anxiety disorders, making it a compelling area of study. The present work highlights the dynamic nature of fear generalization in humans. Further, the present study leads to a number of questions for future research.

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The ventromedial prefrontal cortex (vmPFC) has been suggested to be of great importance for moral decision-making. It has been suggested that during moral decision-making, lesions to the vmPFC increases what researchers term “utilitarian” decision-making. This systematic review summarizes four peer-reviewed studies that were filtered and selected from the databases Web of Science, Scopus and Medline EBSCO. The studies selected compared participants with vmPFC lesions to controls during moral decision-making. One study tested moral evaluation through moral transgressions and distractions. Two studies tested moral responses during personal, impersonal and non-moral dilemmas. One study tested whether direct involvement in a dilemma alters the utilitarian response. The overall results all point towards the vmPFC being directly involved in moral decision-making and that higher rates of utilitarian decision-making were shown in patients with vmPFC lesions compared to controls.

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.

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.

Conversation is a highly interactive and coordinated effort between interactants. For example, interactants often mimic the behaviors and speech of one another and coordinate the timing of behaviors, or interactional synchrony. Despite being affected in certain neurological and psychiatric disorders, the neural mechanisms underlying these processes are not understood. The goal of this study is to understand the role of the ventromedial prefrontal cortex (vmPFC), an area of the brain involved in social and emotional behavior, for interpersonal coordination, including mimicry and interactional synchrony. To test the role of the vmPFC for mimicry, normal comparison (NC), brain damaged comparison (BDC), and participants with vmPFC damage interacted in two sessions with a research assistant (RA) who was performing a target behavior (1st session: nodding, 2nd session: face touching). The amount of time the participants spent nodding or touching their face in each session was recorded. NC and BDC participants tended to mimic the partner and nodded slightly more in the session in which the RA was nodding, and touched their face slightly more in the session in which the RA was touching their face. In contrast, vmPFC patients showed no difference in their behaviors in either session, suggesting that they were not influenced by the partner's behaviors and did not mimic them. In a second experiment, all of the above participant groups had a naturalistic conversation with an unfamiliar interactional partner. The conversational data were analyzed for numerous aspects of interpersonal coordination, including convergence of number of words, words per turn and backchannels, reciprocity of self-disclosures, the use of questions, interactional synchrony, and a time series analysis of response latency and speech rate. The vmPFC participants performed consistently worse than NC participants on convergence of words and words per turn, self-disclosures and asking questions. All brain-damaged participants were impaired on aspects of interactional synchrony, and no conclusive results were found for the time series analysis of response latency and speech rate. This study provides support for the hypothesis that the vmPFC is important for interpersonal coordination as the vmPFC group differed significantly from the NC group on the majority of the analyses. The final goal of this study was to understand the effects of traumatic brain injury (TBI) on interpersonal coordination. TBI patients participated in all of the experiments described above and preliminary results showed that they also seemed to be impaired on the mimicry task, and they performed slightly worse than NC participants on many of the interpersonal coordination analyses of the conversational data. This suggests that TBI also does seem to affect certain aspects of interpersonal coordination.