Pleasure is part of hedonic well-being, with roots back to Epicurus 2000 years ago. With the new evolving neuroscientific methods of the late 20th and beginning of the 21st century, we are now able to study the biological components of pleasure. This thesis aims to review empirical studies on the neural correlates of pleasure, which can have important implications for well-being, and treatment of addiction and affective disorders. Recent studies have suggested that pleasure can be separated into coding and causing. Discoveries show that causing of pleasure is created in so called hedonic hot spots, areas of the brain that intensely creates pleasure in the shell of nucleus accumbens and in the ventral pallidum. Areas that codes pleasure on the other hand is represented into more cortical areas of the brain, including orbitofrontal cortex, anterior cingulate cortex and anterior insular cortex. There has been a growing understanding about how pleasure is represented in the brain, and a discussion on interpretations and limitations are provided followed by future research suggestions in the final section.

This essay is about the somatosensory system, which is divided into different kinds of touch. Described briefly are the proprioceptive touch, which is transported to the brain via A-alfa fibers and transmits information about e. g. limb position and movement. The cutaneous touch is the main focus and it is divided into discriminative touch and affective touch. The first corresponds to stimuli such as vibration and pressure and is transported via A-beta axons. The second, affective touch, corresponds to e.g. painful and pleasant stimuli which are transported to the brain via A-delta and C-fibers. The aim of the essay is to give an overview of the sense of touch, by doing a literature search, including a discussion of relevant neuronal correlates focusing particularly on affective touch. Moreover, the physiological aspects of touch will be presented. The sources that are used are review and original articles taken from databases such as ScienceDirect, and some articles send by the author. Some books have also been used to find more general knowledge. The conclusion for the essay is that touch is important for humans to function in everyday life. Additional, a specific receptor called C- tactile (CT) is identified to correspond to gentle touch and is suggested to have a vital role for humans in maintaining and forming social bounds. Moreover, discriminative touch is associated with activation in the primary and secondary somatosensory cortex, whereas affective touch seems to be associated with activity in the orbitofrontal cortex, cingulate cortex and the insula cortex, as well as the prefrontal cortex, which is suggested to be activated during interpersonal touch. Further, the sense touch needs to be more researched in order to understand its functions and benefits deeper.

Social isolation is commonly reported in individuals with isolated cleft lip and palate (ICLP), and is often cited as due to secondary factors of living with a facial malformation. However, the data are mixed, and the literature is biased to self-report studies. This study aimed to go beyond self-report data, and various components of social functioning were examined in a group of males with and without ICLP. The main aim of the study was to assess and compare social motivation in ICLP, and to relate social adjustment to brain structure. It was predicted that males with ICLP would be more likely to be socially isolated; however, self-concept was predicted to be similar to the comparison group (NC). Additionally, males with ICLP were predicted to have reduced social motivation (i.e., social abulia). Finally, volumes of the medial orbitofrontal cortex (mOFC) and the cerebellum were predicted to be related to social outcomes. The sample's age range was 13 - 25 years old, and 20 males with ICLP were compared to a group of 20 NC males. MRI scans were obtained from all the participants. As expected, males with ICLP were more likely to be socially isolated. Against predictions, they also had lower self-concept relative to the NC group. However, self-concept was not related to the extent of facial abnormality in the ICLP group. In line with predictions, the study did provide evidence for social abulia as a mechanism for social isolation, as males with ICLP had a more positive attitude after being socially excluded relative to excluded NC males. Unexpectedly however, the groups responded the same to social pressure, as all participants were more likely to take riskier turns in a driving simulator experiment when someone behind them was honking. Finally, social adjustment was significantly correlated with the volume of the mOFC, and posterior cerebellum white matter. Both correlations suggested that individuals with larger volumes were more likely to be better socially adjusted. In conclusion, the study provided evidence for a potentially different mechanism of social isolation in ICLP, and showed that brain morphology may at least partly underlie social dysfunction as well.

Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC.

Behaviour is guided by accumulated experience, valuation and comparison. While many aspects associated with these functions are mediated by the frontal lobes, the precise contribution from particular regions remains debated. This thesis will deal with how an organism comes to select an option and will specifically focus on the role of the orbitofrontal cortex (OFC) in two mechanisms in this process: learning of outcome specificities and selecting between multiple options based on their expected values. Despite evidence emphasizing anatomical and connective heterogeneity within this structure, the OFC is often regarded as a uniform region. This thesis aims to resolve some of this uncertainty by assuming that the medial and lateral regions of the OFC contribute differentially to learning and decision-making. Two distinct methodologies were used in these investigations. First, the contribution of the medial OFC to social and emotional processing was examined. The findings from this study disprove previously held beliefs that the medial regions of the OFC guide social and emotional behaviours, but indicted a role for this region in value-guided decision-making. The second study examined functional differences between the lateral and medial OFC by making circumscribed lesions to either region in macaque monkeys. The animals performed a number of 3-armed bandit tasks which were designed to investigate different aspects of value assignment and comparison. The results show that while lateral OFC was required for "credit assignment" – the correct assignment of values to visual cues – medial OFC was critical for comparison of the cues' values during decision-making. In unchanging probabilistic environments, mOFC lesions induced decision-making impairments when value comparison was difficult without affecting credit assignment and associative learning. By contrast, lateral OFC lesions caused the opposite pattern of impairment. The final study used human-neuroimaging techniques to investigate the differential representation of outcome-specific contingency learning and found not only that the expectation of a unique outcome facilitated learning and memory recall but that this was supported by a neural network which included the lateral regions of the OFC and the anterior cingulate cortex. Activity in the mOFC did not correlate with outcome-specific contingency learning but instead reflected both the value associated with the receipt and expectation of a reward. Taken together, the results from this thesis suggest that specific parts of the OFC make markedly different contributions to these very different cognitive functions.

The ability to take effective decisions is fundamental for successful environmental adaptation and survival. In this thesis, I investigated situations in which decisions appear irrational, at least from certain standpoints. I conducted a behavioural decision-making experiment in two groups of macaques: controls and a group with ventromedial prefrontal cortex/medial orbitofrontal cortex (vmPFC/ mOFC) lesions. Some choices lead to compound outcomes composed of different constituent parts. Control macaques' decisions suggested their estimates of the value of the compound were biased away from the sum of the values of the constituents and towards their mean. Lesions of vmPFC/mOFC diminished the size of the effect so that macaques in some ways appeared to make more rational decisions. Based on the results of this experiment I devised a similar Functional Magnetic Resonance Imaging (fMRI) paradigm with the control animals. This demonstrated strong vmPFC/mOFC activity when similar decisions were made and suggested a value comparison process. In addition, I investigated the role of dopamine in learning using Fast-Scan Cyclic Voltammetry (FSCV), while rats performed a simple decision-making task. Theories about the role of dopamine in learning have focused on the possibility that it codes scalar reward value prediction errors. Less consideration has been given to the possibility that dopamine might reflect prediction errors about reward identities regardless of value. I measured dopamine in the nucleus accumbens when unexpected changes in reward value or identity occurred while rats executed a two-choice two-reward instrumental task. Dopamine levels in the nucleus accumbens reflected reward value prediction errors. In addition, however, they also reflected some information about reward identity under some circumstances. Further investigation suggested that this might be due to differences in the nutritional value of different reward types that did not have clear measurable impacts of behaviour in the tasks that I used.

Cocaine use disorder is a significant health problem, negatively impacting individuals afflicted. While preclinical self-administration research has provided invaluable insight into the neurobehavioral mechanisms that underlie cocaine abuse, cocaine use outside of the laboratory occurs within an environment where other goods are also available ubiquitously. Although there is an ever-increasing literature investigating drug vs. non-drug choice in rodent models and how alternative goods can compete with the subjective value of cocaine, the neurobiological mechanisms that are associated with cocaine preference remains largely unknown. Additionally, current drug vs. non-drug choice studies use procedures that confound preference with intake, such that preference measures are directly reflective of individual experience with drug and non-drug reinforcers earned through the choices that are made; simply, preference and intake are the same. Moreover, differences in cocaine experience can result in differential neural adaptations, thus making it difficult to determine if the neurobiological mechanisms underlying choice are related to preference or drug intake. Herein a novel choice procedure, which controls for reinforcer intake (controlled reinforcer ratio; CRR), was used to explore how certain reinforcer dimensions (i.e., magnitude and frequency) influence cocaine preference. In addition, neuronal activity, measured via c-fos expression, in the orbitofrontal cortex and nucleus accumbens, areas associated with decision-making and valuation, for cocaine and food were independently targeted and labeled using fluorescent in situ hybridization and fluorescent immunohistochemistry. First, unlike prototypical choice procedures where preference and intake are confounded, the CRR choice procedure was able to dissociate the two. Under the CRR choice procedure, it was revealed that both magnitude and frequency, independent dimensions of reinforcement, greatly influence preference for cocaine. Furthermore, the CRR choice procedure was sensitive to manipulations known to influence cocaine preference while keeping reinforcer intake constant. When neuronal activity was examined after CRR training, the number of cocaine activated cells, relative to food activated cells, did not correlate with individual preferences for cocaine despite overall reinforcer intake being held constant. Instead, results suggest neuronal activity for cocaine was related to overall cocaine intake. Overall, these results give impetus for utilizing the CRR choice procedure to better investigate how drug and non-drug reinforcers are afforded differential subjective value and compete for preference. Moreover, use of a CRR choice procedure may lead to identification of specific neurobehavioral mechanisms and lead toward future development of more effective pharmacological and behavioral treatments to ameliorate substance use disorders.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

Previous research has indicated that the perirhinal cortex (PRh) and posterior parietal cortex (PPC) functionally interact to mediate crossmodal object representations in rats; however, it remains to be seen whether other cortical regions contribute to this cognitive function. The prefrontal cortex (PFC) has been widely implicated in crossmodal tasks and might underlie either a unified multimodal or amodal representation or comparison mechanism that allows for integration of object information across sensory modalities. The hippocampus (HPC) is also a strong candidate, with extensive polymodal inputs, and has been implicated in some aspects of object recognition. A series of lesion based experiments assessed the roles of HPC, PFC and PFC sub regions [medial prefrontal (mPFC) and orbitofrontal cortex (OFC)], revealing functional dissociations between these brain regions using two versions of crossmodal object recognition: 1. spontaneous crossmodal matching (CMM), which requires rats to compare between a stored tactile object representation and visually-presented objects to discriminate the novel and familiar stimuli; and 2. crossmodal object association (CMA), in which simultaneous pre-exposure to the tactile and visual elements of an object enhances CMM performance across long retention delays. Notably, while inclusive PFC lesions impaired both CMM and CMA tasks, selective OFC lesions disrupted only CMM, whereas selective mPFC damage did not impair performance on either task. Furthermore, there was no impact of HPC lesions on either CMM or CMA tasks. Thus, the PFC and the OFC play a selective role in crossmodal object recognition but the exact contributions and interactions of the regions will require further research to elucidate. / PDF Document / Natural Sciences and Engineering Research Council of Canada (NSERC)