Impulsivity is a common and multifaceted personality trait that is characterized by the presence of heightened reward sensitivity, novelty seeking, lack of premeditation, and behavioural and emotional inhibition deficits (Leshem, 2016a). These behaviours are often associated with substance abuse, gambling disorders, obesity, abnormal time perception, and other psychological and neurological conditions (Bari & Robbins, 2013; Berlin & Rolls, 2004). Reward processing deficits have also been well documented, with many researchers finding an association between impulsivity and the inclination towards smaller, immediate, rewards over larger, delayed rewards (Petry, 2001). Additionally, a larger reward positivity amplitude – an event-related potential component associated with rewards and expectancy – was found for the immediate rewards, relative to delayed rewards in high impulsivity individuals (Cherniawsky & Holroyd, 2013; B. Schmidt, Holroyd, Debener, & Hewig, 2017). The purpose of this thesis was to replicate and extend previous findings, by having participants complete two tasks: delayed gratification and time estimation. In the time estimation task, participants estimated the length of one second. The first task, a replication, assesses subject’s preference for immediate rewards; moreover, the second task extended previous research and functioned as an additional way of assessing reward processing and examined participant’s ability to estimate time. Abnormal time perception in impulsive individuals is thought to contribute to atypical delay gratification behaviour (Wittmann & Paulus, 2008). Electroencephalography (EEG) was recorded from participants during both tasks. Based on previous research on impulsivity (Cherniawsky & Holroyd, 2013; Coull, Cheng, & Meck, 2011; Holroyd & Krigolson, 2007; B. Schmidt et al., 2017), I predicted that impulsivity would affect performance on the time estimation task (which is novel in its use with impulsivity and EEG), and response times and reward positivity amplitudes on both tasks. Counter to my hypothesis, I found that response times and task performance were not affected by impulsivity levels. I also observed that the reward positivity was mediated by impulsivity in the delayed gratification task, but not in the time estimation tasks, suggesting that the tasks activate different neural pathways for reward processing. My results indicate that impulsivity can influence the amplitude of the reward positivity, but that different neural pathways are associated with distinct tasks. Further investigation into quantifiable measures of impulsivity and their effect on various reward processing tasks needs to be conducted. / Graduate / 2020-04-22

A primary symptom of depression is anhedonia, or the loss of interest or pleasure. Anhedonic individuals can have deficits in anticipatory pleasure (‘wanting’ things) or consummatory pleasure (‘liking’ things). Depressed individuals generally have deficits in anticipatory but not consummatory pleasure. A possible buffer against anticipatory anhedonia is action orientation, or the ability to upregulate positive affect in pursuit of goals when stressed. To examine the relationship between stress, action/state orientation, and anhedonia, highly anhedonic individuals who were either action- or state-oriented underwent a demanding mood induction, and completed the Effort-Expenditure for Reward Task, a measure of motivation for reward. Evidence did not support action orientation as a buffer; however, individuals who showed fluctuation in self-reported motivation were less motivated to work for reward. Evidence emerged suggesting that fluctuation in motivation over time may predict less willingness to work. Future research can examine the relationship between variability in motivation and depression.

Substance use disorders (SUDs) are a growing concern in today’s society. Substantial research has advanced our understanding of how cognitive control, reward processing, and emotional difficulties may contribute to the development and maintenance of SUDs; however, the impact of affective instability in SUDs has received limited attention. I sought to examine how different dimensions of affective instability interact to increase substance misuse, and to investigate the impact of affective instability and substance use on neural mechanisms of reward and emotion processing. Specifically, I was interested in two event-related potential (ERP) components, the reward positivity and the late positive potential (LPP), which respectively reflect the neural mechanisms of reward and emotion processing. Toward this end, I recorded the ongoing electroencephalogram (EEG) from undergraduate students as they navigated two T-maze tasks in search of rewards. Further, one of the tasks included neutral, pleasant, and unpleasant pictures from the International Affective Picture System (IAPS). Participants also completed several questionnaires pertaining to substance use and personality. A principal components analysis (PCA) revealed a factor related to affective instability, which I named reactivity. This factor significantly predicted increased substance use. Interestingly, individuals reporting higher levels of affective reactivity also displayed a larger reward positivity following stimuli with emotional content. The current study identified a group of high-risk substance users characterized by greater levels of affective reactivity and increased reward processing. It is my hope that these results further elucidate the complexities of SUDs and help to create efficacious, individually-tailored treatment programs for those struggling with SUDs. / Graduate

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are highly co-occurring and both are associated with dysfunction in neural networks that mediate reward processing and motivated behavior. Furthermore, despite their high comorbidity rate, limited research into their shared neural mechanisms or potential prospective risk factors exists. This study attempted to elucidate common neural pathways for these disorders, and adds to the small but growing literature on possible prospective predictors of these disorders. We employed a task-based functional magnetic resonance imaging (fMRI) study to examine regions-of-interest (ventral striatum [VS], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], dorsolateral prefrontal cortex [dlPFC]) and connectivity (VS-OFC, VS-vmPFC, vmPFC-dlPFC) analyses to examine neural reward processing as potential predictors of future substance and mood symptoms, and to explore differences among groups of participants with and without BSDs and SUDs. Results from this study provided evidence that blunted activation in the VS and dlPFC and greater negative connectivity between the vmPFC and dlPFC, key reward and control circuits, is implicated in prospective substance use. However, we did not find evidence to support our hypothesis that reward-related neural responses predict BSD symptoms or could differentiate individuals with co-occurring BSDs and SUDs from healthy volunteers. The study highlights the importance of larger, longitudinal studies to more fully probe neurodevelopmental trajectories in mood, substance, and related disorders. We also conducted an extensive review of the neural reward literature in BSDs and SUDs to understand possible pre-existent mechanisms. Results of the review provided support for an equifinality/multifinality perspective in that similar neural reward processing dysfunctions can lead to both BSDs and SUDs and different neural reward processing abnormalities can lead to a single outcome (e.g., SUDs). Taken together, results from the dissertation address an important gap in the literature on BSD-SUD comorbidity, suggest possible shared mechanisms that predispose to both disorders, and provide a backdrop for future work in this area to inform more theoretically-targeted interventions and prevention. / Psychology

Non-suicidal self-injury (NSSI), defined as the deliberate damaging or destruction of body tissue without intent to die, are common behaviors amongst youth. Although prior work has shown heightened response to negative outcomes and dampened response to positive outcomes across multiple methods, including behavioral and physiological measures, little is known about the neural processes involved in NSSI. This study examined associations between NSSI engagement and responsivity to rewards and losses in youth with and without a lifetime engagement in NSSI. We employed a task-based functional magnetic resonance imaging (fMRI) study to examine differences between regions of interest (ROIs; ventral and dorsal striatum [VS, DS], anterior cingulate cortex [ACC], orbitofrontal cortex [OFC], ventrolateral and ventromedial prefrontal cortex [vlPFC; vmPFC], and insula) and whole-brain connectivity (utilizing bilateral DS, mPFC, and insula seed ROIs) in youth with and without NSSI. We used two reward tasks, in order to examine differences between groups across domains of reward (i.e., monetary and social). Additionally, we examined the specificity of the associations by controlling for dimensional levels of related psychopathology (i.e., aggression and depression). Results from the current study found that NSSI was associated with decreased activation following monetary gains in all ROIs. Further, these differences remained significant when controlling for comorbid psychopathology, including symptoms of aggression and depression. Finally, exploratory connectivity analyses found that NSSI was associated with differential connectivity between regions including the DS, vmPFC, insula, parietal operculum cortex, supramarginal gyrus, cerebellum, and central opercular cortex. Weakened connectivity between these regions could suggest deficits in inhibitory control of emotions in individuals with NSSI, as well as dysfunction in pain processing in individuals with NSSI, whereby these individuals experience pain as more salient or rewarding than individuals without NSSI. Although results did not support our hypotheses, findings suggest disrupted reward processes in youth with NSSI, contributing to our understanding of the role that reward processes may play in NSSI, in the engagement and reinforcement of these behaviors. We also conducted an extensive systematic review of the studies indexing neural structure and function in NSSI, summarizing the literature on the neurobiological correlates of several psychological processes implicated in NSSI engagement, including emotion processes, pain processes, executive processes, social processes, and reward processes. Results of the review highlighted the neural regions most consistently associated with NSSI, including the amygdala, insula, frontal, prefrontal, and orbitofrontal cortices, and the anterior cingulate, dorsal striatum, and ventral striatum. Additionally, data showed that NSSI is associated with greater emotional responses in negative situations, poorer down-regulation of negative emotions, and poorer inhibitory control over impulsive behaviors. Overall, findings suggest that NSSI is associated with maladaptive coping, and that this down-regulation of negative emotion resulting from NSSI may be experienced as rewarding and may serve to reinforce engagement in these behaviors. Finally, this review highlighted the importance of standardizing the methods of indexing neural structure and function in NSSI, specifically in terms of how NSSI is categorized, which comorbid disorders are examined, and how neuroimaging data are collected and analyzed, so that research in this area is comparable and reproducible. / Psychology

Cannabis is widely consumed by humans for pharmacological effects that are mediated by THC, though there is little evidence that THC is a primary reinforcer in non-human animal models. We hypothesized that THC may have potent reinforcement enhancing effects, comparable to other drugs (e.g., nicotine and caffeine) which are also widely consumed by humans, but difficult to establish as primary reinforcers in non-humans. In three experiments with male and female rats saccharin (SACC) or a visual stimulus (VS) served as reinforcers for operant behavior. We explored several pharmacological parameters of THC on responding for SACC or VS, including THC dose, intervals between THC injections and testing, and intervals between test sessions. THC acts as a reinforcement enhancer for both SACC and a VS across a range of doses and intervals. Daily THC injections systematically reduced behavior, possibly due to accumulation of THC bioavailability.

Much work has been done in the neuroscience of reward processing, such as; mapping brain areas, key neurotransmitters, and connectivity patterns related to different aspects of reward-related behavior. There are a lot of suggested behavioral and neural sex differences in reward processing, primarily based on animal studies of reward behavior. This review aimed to systematically review publications on human neurofunctional sex differences in reward processing, and provide a more stable footing for future research in the field. Two searches through Web of Science and Scopus for publications that combined neuroimaging with behavioral tasks for examining functional sex differences in neural reward processing. The searches produced nine studies (n=9) that were included after the screening process. There are significant differences between males and females in reward processing, specifically in the striatum, orbitofrontal cortex, prefrontal cortex, nucleus accumbens, and insula. However, the full extent of these differences, and the underlying causes, are still not clear. There is a lack of control for important confounding factors in the present field of sex differences in reward processing. Future research in this field has to consider all of the underlying factors that cause men and women to differ, such as the impact of gonadal hormone fluctuations and societal pressures. If these factors were taken into account, data of higher validity and generalizability could have been produced.

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

Master of Science / Department of Psychology / Kimberly Kirkpatrick / Several studies have examined timing and impulsive choice behavior in spontaneously hypertensive rats (SHR) as a possible pre-clinical model for Attention Deficit Hyperactivity Disorder (ADHD). However, the strain has not been specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. This study investigated whether SHR would exhibit timing deficits, poor reward processing and impulsive behavior in comparison to the Wistar Kyoto (WKY) control strain in a discrete-trial choice task. In addition, as a first approach to find another potential animal model of ADHD, we evaluated a strain that has shown high levels of impulsivity, the Lewis (LEW) rats and compared them with the Wistar (WIS) rats. In the first phase of the experiment, rats could chose a lever associated with a Smaller-sooner (SS) reward of 1 pellet delivered after 10 s and a Larger-later (LL) reward of 2 pellets delivered after 30 s. Subsequently, the rats were exposed to different phases, where the reward on the LL choice was increased to 3 and 4 pellets and where the delay to the SS choice was increased to 15 and 20 s. The SHR and WKY strains did not differ in their timing or choice behavior. In comparison to WIS, LEW showed timing deficits in both manipulations and deficits in choice behavior in the delay manipulation, indicating deficits in time processing. Individual differences among the rat within a strain accounted a significant proportion of the total variance and contributed more variance than the strain of the rat. These results indicate that the SHR and LEW strains are not sufficiently homogeneous with respect to impulsive choice behavior to be considered as viable models for impulse control disorders such as ADHD.

Background. Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). Methods. fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. Results. AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. Conclusion. Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.