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Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n= 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterized post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and ΔFosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.

Anxiety has become one of the common problems in society in recent years. As an emerging interactive medium, games can create a first-hand experience for players. Therefore, it is possible to guide the player through behavioral experiments implemented with the game. But in order to reduce the direct damage to the player and make the problem more obvious, metaphorical game is one of the good choices.   In order to design and make such a metaphorical game, I firstly need to collect anxiety triggers and game design related theories into an initial design framework. These theories mainly include metaphorical game, experiential game model and reflection game design. After two iterations of game design core development, I'll be doing demos and interviews with several players. After that, I will summarize these data into several themes. These themes will extend the original design framework, which will also serve as an outcome of this paper. The two most prominent points in the expansion are beat chart and reward.

This paper focuses on how to design a childrens game to help them realize that they can have a positive influence on the environment. We present a detailed description and analysis of our work process from brainstorming to the discussions after playtesting our prototype. Playing while learning has been the motivation of our work which is divided into three specific topics: How to involve the users in the design process, what type of social aspects exist in our game, and the importance of a feedback and reward system in the game. We look upon earlier research and examples within these three areas. We designed our game from a user centered perspective to make the users influence and encourage a discussion and awareness about environmental questions in a way that isnʼt negative. While designing our game we wanted to shed a positive light upon a serious issue and bring the environment into the topics of play and fun. In our research we discoverd that focusing on small subjects and tasks the children started to discuss the complex theme of the environment. We focus on the interaction with the children and using their influence to make decisions in our design process. Involving them helped us to see that there is not only one way of learning. In this game, the users learned from engagement and discussion, which ended up being the most important part of the game play.

<p>Evidence suggests that a change in the firing rate of dopamine (DA) cells is a major neurobiological correlate of learning. The Temporal Difference (TD) learning algorithm provides a popular account of the DA signal as conveying the error between expected and actual rewards. Other accounts have attempted to code the DA firing pattern as conveying surprise or salience. The DA mediated cells have also been implicated in several neuropsychological disorders such as obsessive compulsive disorder and schizophrenia. Compelling neuropsychological explanations of the DA signal also frame it as conveying salience. A model-based reinforcement learning algorithm using a salience signal analogous to dopamine neurons was built and used to model existing animal behavioral data.</p> <p>Different reinforcement learning models were then compared under conditions of altered DA firing patterns. Several differing predictions of the TD model and the salience model were compared against animal behavioral data in an obsessive compulsive disorder (OCD) model using a dopamine agonist. The results show that the salience model predictions more accurately model actual animal behavior.</p> <p>The role of context in the salience model is different than the standard TD-learning algorithm. Several predictions of the salience model for how people should respond to context shifts of differing salience were tested against known behavioral correlates of endogenous dopamine levels. As predicted, individuals with behavioral traits correlated with higher endogenous dopamine levels are far more sensitive to low salience context shifts than those with correlates to lower endogenous dopamine levels. This is a unique prediction of the salience model for the DA signal which allows for better integration of reinforcement learning models and neuropsychological frameworks for discussing the role of dopamine in learning, memory and behavior.</p> / Doctor of Science (PhD)

Bipolar disorder (BD) and unipolar depression (UD) are two severe mood disorders, with BD often misdiagnosed as UD. Given their severity and high rates of misdiagnosis, it is of paramount importance to understand the psychological and neurobiological mechanisms underlying these disorders to enhance our ability to diagnose, treat, and prevent them effectively. Many neuroimaging studies have shown that mood disorders are associated with abnormal reward-related responses, particularly in the ventral striatum (VS). Yet, the link between mood disorders and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of mood disorders. To provide insights into the neurobiological underpinnings of reward processing dysfunction in mood disorders, two studies were conducted. Study 1 (Chapter 2) is a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder (MDD), and 803 healthy controls (HC). It aims to address inconsistencies in the literature by synthesizing the literature quantitatively. The findings of Study 1 indicate that MDD is associated with opposing abnormalities in the reward circuit: hypo-responses in the VS and hyper-responses in the orbitofrontal cortex (OFC). These findings provide a foundation for Study 2 (Chapter 3) and help to reconceptualize our understanding of reward processing abnormalities in UD by suggesting a role for dysregulated corticostriatal connectivity. Study 2 is the first fMRI study to employ region-of-interest (VS and OFC), whole-brain, activation, connectivity, and network analyses to examine the similarities and differences in reward-related brain activation patterns between 46 children with remitted bipolar I disorder, 48 children with remitted MDD, and 46 HC. The results of Study 2 revealed differential connectivity in corticostriatal circuitry during reward processing among BD, UD, and HC in pre-adolescence. Specifically, BD exhibited increases in OFC-VS connectivity during anticipation of larger reward, whereas UD and HC showed no changes in OFC-VS connectivity across anticipation conditions ranging from large loss to large reward. Furthermore, BD and UD generally showed more abnormal whole-brain responses to reward anticipation in accordance with the valence of the stimuli than HC. These findings suggest that pre-adolescents with BD and UD exhibit reward processing dysfunction during reward anticipation relative to HC even outside of acute periods of illness. Taken together, the dissertation provides novel insight into the nature of reward processing abnormalities in mood disorders in pre-adolescence. As early onset BD or UD often is associated with long treatment delays and a persistently pernicious illness course, this dissertation may aid efforts to ensure early accurate diagnosis, which may improve our ability to intervene with appropriate treatments and result in a more benign prognosis and course of illness over the lifespan. / Psychology

Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40-70% of survivors experience neurocognitive impairment. Psychostimulants such as methylphenidate are becoming popular medications for treating these deficits in childhood cancer survivors. However, little is known about the outcome of prescribing stimulants to this population. In the research reported here, a novel preclinical mouse model of ALL treatment was developed and used to investigate the effects of early exposure to methotrexate (MTX) and cytarabine (Ara-C) on learning and memory, and the outcome of treating these deficits using a number of different stimulants. Mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or two combinations of MTX and Ara-C. At PND 35, significant impairments on learning and memory as measured by autoshaping and novel object recognition were found. Mild deficits were observed in a novel conditional discrimination task, which suggests that extensive training may ameliorate learning impairments. MTX and Ara-C treated mice also exhibited sensitivity to the rewarding and stimulatory properties of amphetamine and methylphenidate, suggesting that typical psychostimulants may become more potent following early chemotherapeutic treatment. In contrast, no increase in drug reward following early exposure to MTX and Ara-C was found for an alternative treatment with possible neuroprotective effects, atomoxetine. These findings were further supported by converging evidence that chemotherapy-treated mice displayed increased novelty-seeking. In addition, a greater percentage of MTX and Ara-C treated mice acquired cocaine self-administration, and maintained a higher number of infusions per session. Overall, these findings highlight the usefulness of preclinical models to examine the developmental effects of early exposure to chemotherapeutic agents on future learning, possible models of cognitive remediation, and the consequences of treating impairments using typical psychostimulant medications. / Psychology