Master of Science / Department of Psychological Sciences / Kimberly Kirkpatrick / Obesity is associated with impaired decision making across a range of choice behaviors including impulsive choice behavior and incentive value. Given that people make approximately 200 food choices each day (Wansink & Sobal, 2007), it is essential to better understand this relationship between obesity and impaired decision making. As such, the current study sought to understand how long-term exposure to diets high in processed fat and sugar affected impulsive choice behavior, devaluation, and food preferences. The results suggested that diet affects impulsive choice behavior. Rats exposed to diets high in processed fat or sugar were more sensitive to changes in delay, a marker of impulsivity. Results from the bisection task indicated that the diet-induced impulsivity could be a result of poor time discrimination. In addition, there were differences in incentive value. All rats successfully devalued rewards, but the high-fat and high-sugar group showed lower overall levels of responding. Further, diet-induced impulsivity could lead to overconsumption of high-fat and high-sugar foods due to differences in food preference. After 9 months on the diets, rats fed a chow and high-sugar diet displayed a sugar preference, while the rats fed a high-fat diet displayed a fat preference. Together, the results suggest that the alterations in impulsive choice and incentive valuation induced by diet could make individuals vulnerable to overeating, and thus obesity, as well as other disorders that are characterized by impulsive choice and deficits in incentive valuation.

Impulsive choice refers to the inability to delay gratification and is associated with increased drug abuse vulnerability. Understanding the underlying neural mechanisms linking impulsive choice and drug abuse can contribute to improved treatment options for individuals with substance use disorders. Evidence suggests a major role for nucleus accumbens core (NAcc) in impulsive choice and the reinforcing effects of drugs of abuse. The neurotransmitters glutamate (Glu) and dopamine (DA) are implicated in the neural adaptations observed in drug addiction; however, the role of intra-NAcc Glu and DA in impulsive choice is unclear. Rats were trained in a delay discounting task, in which animals chose between a small, immediate reinforcer and large, delayed reinforcer. Consistently choosing the small, immediate reinforcer was considered to reflect increased impulsivity. Following delay discounting, in vitro receptor autoradiography was performed to quantify the number of N-methyl-D-aspartate (NMDA) receptors and dopamine transporters (DAT) in NAcc and nucleus accumbens shell (NAcSh). In a separate experiment, rats were trained in delay discounting and were implanted with guide cannulae into NAcc. Following surgery, rats received microinfusions of either a) the Glu-selective ligands MK-801 (noncompetitive NMDA receptor channel blocker; 0, 0.3, and 1.0 μg), AP-5 (competitive NMDA receptor antagonist; 0, 0.3, and 1.0 μg), ifenprodil (NMDA NR2B subunit antagonist; 0, 0.3, and 1.0 μg), and CNQX (AMPA receptor antagonist; 0, 0.2, and 0.5 μg) or b) the DA-selective ligands SKF 38393 (D1-like receptor agonist; 0, 0.03, and 0.1 μg), SCH 23390 (D1-like receptor antagonist; 0, 0.3, and 1.0 μg), quinpirole (D2-like receptor agonist; 0, 0.3, and 1.0 μg), and eticlopride (D2-like receptor antagonist; 0, 0.3, and 1.0 μg). In NAcc and NAcSh, NMDA receptor and DAT expression did not differ between high and low impulsive rats. Furthermore, intra-NAcc administration of NDMA and DA receptor ligands did not significantly alter impulsive choice. These results suggest that Glu and DA systems within NAcc do not directly mediate impulsive decision making. Future work is needed to determine the precise role of NAcc in mediating impulsive choice.

Rationale: Impulse control deficits are thought to underlie criminal offending. Impulsive choice is a facet of impulse control that refers to a preference for immediate over delayed rewards. This facet of impulse control has been measured empirically using the Iowa Gambling Task (IGT), which provides a metric of overall disadvantageous decision-making, as well as metrics of specific maladaptive decision-making strategies. Purpose: To investigate impulsive choice as a measure of impairment in offenders as reflected by performance on the IGT, and to examine maladaptive decision-making strategies that may mimic real-life decisions to engage in illegal behaviour. Methods: 100 Canadian federal offenders (34% female, mean age = 39.14 ± 9.74) and 89 controls (39% female, mean age = 37.04 ± 10.79) completed the IGT. The IGT involves repeatedly choosing cards from four decks. Two decks are “good” and result in a net gain on the task, and two decks are “bad” and result in a net loss. Decks offer a fixed reward, but vary in loss magnitude and frequency. IGT data were analyzed for net score (number of good choices minus number of bad choices), learning across the task, and deck switching patterns. Other assessments included data on offenders’ current sentence and risk for reoffence level. Results: Offenders performed significantly poorer than controls in terms of net score. Controls learned the advantageous strategy across the task but offenders did not. Offenders also made greater use of a “win-stay/lose-shift” strategy. Low-risk offenders performed significantly better than medium- or high-risk offenders on the IGT. Conclusion: These results suggest that, compared with controls, offenders tend to make riskier choices and use maladaptive decision-making strategies that provide a larger immediate reward but are disadvantageous in the long term. The IGT, as part of a comprehensive assessment of risk, may provide valuable information for preventing criminal offending and recidivism. / Thesis / Master of Science (MSc) / Criminal offending is thought to be related to impulse control problems. Research has linked offending to poor performance on a decision-making task known as the Iowa Gambling Task (IGT). On the IGT, participants repeatedly choose cards from four decks that provide wins and losses of points. Two decks are “good” and result in an overall gain on the task, and two decks are “bad” and result in an overall loss. In this study, 100 Canadian federal offenders and 89 non-incarcerated control participants completed the IGT. Offenders performed worse than the control group overall, and control participants but not offenders learned the best strategy (i.e., choosing from good decks) over the course of the task. Additionally, offenders with a “Low” criminal risk rating did better than those at “Medium” or “High” risk levels. These results suggest that the IGT may provide important information about the cause and prevention of criminal offending.

Preference for smaller-sooner over larger-later rewards characterizes one type of impulsivity—impulsive choice. Impulsive choice is related to a number of maladaptive behaviors including substance abuse, pathological gambling, and poor health behaviors. As such, interventions designed to reduce impulsive choice may have therapeutic benefits. The purpose of this dissertation was to explore two methods to change nonhuman impulsive choice. In doing so, we hope to provide a baseline that future research can use to assess variables that are less amenable to human research (e.g., drug self-administration following reductions in impulsive choice). In Chapter 2, we failed to reduce nonhuman impulsive choice using working-memory training, a finding both inconsistent and consistent with the extant human literature. Chapters 3-5 sought to better understand a training regimen that generates large between-group differences in nonhuman impulsive choice—delay- and immediacy-exposure training. The results from Chapters 3 and 4 suggest that prolonged exposure to delayed food rewards produces large and long-lasting reductions in impulsive choice. Chapter 5 showed that the delay-exposure training effect can be obtained in fewer sessions than has previously been employed. A better understanding of the effects of delay-exposure training on nonhuman impulsive choice may have implications for the design and implementation of a human analog.

Impulsivity takes many forms, one of which is termed impulsive choice. Impulsive choice entails preference for an outcome due to its immediacy relative to more optimal outcomes that take longer to come to fruition. For example, one may wish to have another serving of a decadent dessert after dinner—but doing so may undermine a longer-term goal of improved health and nutrition. If having the extra serving becomes a habit, the consequences of that choice compound and may lead to, for example, obesity. A high degree of impulsive choice such as this is indeed related to issues such as obesity, drug addictions (e.g., alcohol, opiates), and more; it may also cause these conditions. Because impulsive choice may lead to the development of poor health conditions, being able to reduce impulsive choice may reduce the occurrence of these conditions and/or help treat them. To date, a variety of studies have been conducted to examine ways to reduce impulsive choice, but it was unclear what methods may be most useful for clinical use in humans. Thus, the first portion of the enclosed research was a literature review in which successful methods for reducing impulsive choice were identified. A particular intervention called Episodic Future Thinking (EFT), which entails vivid imagination of one’s future, was one of the most promising found. However, it was unclear if its positive effects on impulsive choice were due to EFT itself or a placebo-like effect, which can arise from being able to guess the purpose of the intervention. The remaining portions of this dissertation focused on determining whether people are able to identify the purpose of EFT, and subsequently, if this awareness accounts for the positive effects of EFT on impulsive choice. Across three experiments, we demonstrated that naïve individuals are able to figure out the purpose of EFT (Experiments 1a and 1b), but that being aware of its purpose is unrelated to its positive effects (Experiment 3). These findings give hope that this intervention could be clinically useful, but it did appear that its benefits did not generalize well to novel settings (Experiment 2). Overall, the results of the research showed that EFT produces genuine changes in impulsive choice, but that further research will need to be conducted to understand why it works, and ultimately, how its generalizability can be increased.

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.

Indiana University-Purdue University Indianapolis (IUPUI) / Impulsivity, or the tendency to act prematurely without foresight, has been linked to a diverse range of pathological conditions. Foresight refers to the ability to envision future rewards and events (i.e. prospectively sample) and has been associated with decreased impulsivity. One form of impulsivity is measured by the ability to delay gratification and is often studied in the framework of Delay Discounting (DD). DD provides the means to study impulsivity in a number of pathological conditions. However, whether impulsivity precedes the development of pathological states or results from the pathological state itself is not fully understood. This necessitates an understanding of neurobiological mechanisms contributing to decision making in both non-impulsive as well as impulsive populations of individuals. Animal models allow invasive techniques to be used to dissect the neurocircuitry involved in decision making. Given that the decision-making process is an ongoing process rather than an isolated event, optogenetics provide the temporal and spatial specificity necessary for evaluating brain region specific contributions to decision making in DD. In the present study, optogenetics were used to assess the contribution of the medial Prefrontal Cortex (mPFC), a brain region involved in ‘goal-directed’ behavior, in the planning of future choices (i.e. prospective plans) and subsequent measures of impulsivity in an adjusting amount DD procedure. Optogenetic inhibition of mPFC was conducted in Wistar rats during different epochs of a DD task in order to assess how mPFC affects planning behavior in a population of rat not considered to be highly impulsive. Although no direct effects on planning behavior (e.g. consistency) were observed, inhibiting mPFC after a trial has been initiated and directly before a choice was made (Epoch 2) was observed to increase measures of impulsivity in comparison to days where no optogenetic manipulation occurred in a delay-specific manner. This suggests that mPFC differentially contributes to decision making at different delays. A pattern of associations between choice latency, impulsivity, and consistency began to emerge for inactivation occurring in Epoch 2, suggesting that mPFC contributes to some aspect of planning choices during this epoch. Moreover, these results indicate that mPFC is involved in decision making in Wistar Rats. Understanding the direct role that mPFC plays in promoting choices of delayed rewards provides a neurobiological target for treatment aimed at reducing impulsivity in the clinical population.

<p> <i>Impulsivity</i>, or the tendency to act prematurely without foresight, has been linked to a diverse range of pathological conditions. Foresight refers to the ability to envision future rewards and events (i.e. prospectively sample) and has been associated with decreased impulsivity. One form of impulsivity is measured by the ability to delay gratification and is often studied in the framework of Delay Discounting (DD). DD provides the means to study impulsivity in a number of pathological conditions. However, whether impulsivity precedes the development of pathological states or results from the pathological state itself is not fully understood. This necessitates an understanding of neurobiological mechanisms contributing to decision making in both non-impulsive as well as impulsive populations of individuals. </p> <p> Animal models allow invasive techniques to be used to dissect the neurocircuitry involved in decision making. Given that the decision-making process is an ongoing process rather than an isolated event, optogenetics provide the temporal and spatial specificity necessary for evaluating brain region specific contributions to decision making in DD. In the present study, optogenetics were used to assess the contribution of the medial Prefrontal Cortex (mPFC), a brain region involved in ‘goal-directed’ behavior, in the planning of future choices (i.e. prospective plans) and subsequent measures of impulsivity in an adjusting amount DD procedure. Optogenetic inhibition of mPFC was conducted in Wistar rats during different epochs of a DD task in order to assess how mPFC affects planning behavior in a population of rat not considered to be highly impulsive. Although no direct effects on planning behavior (e.g. consistency) were observed, inhibiting mPFC after a trial has been initiated and directly before a choice was made (Epoch 2) was observed to increase measures of impulsivity in comparison to days where no optogenetic manipulation occurred in a delay-specific manner. This suggests that mPFC differentially contributes to decision making at different delays. A pattern of associations between choice latency, impulsivity, and consistency began to emerge for inactivation occurring in Epoch 2, suggesting that mPFC contributes to some aspect of planning choices during this epoch. Moreover, these results indicate that mPFC is involved in decision making in Wistar Rats. Understanding the direct role that mPFC plays in promoting choices of delayed rewards provides a neurobiological target for treatment aimed at reducing impulsivity in the clinical population.</p>

Fluctuating ovarian hormones have been shown to affect decision-making processes in women. While emerging evidence suggests effects of endogenous ovarian hormones such as estradiol and progesterone on value-based decision-making in women, the impact of exogenous synthetic hormones, as in most oral contraceptives, is not clear. In a between-subjects design, we assessed measures of value-based decision-making in three groups of women aged 18 to 29 years, during (1) active oral contraceptive intake (N = 22), (2) the early follicular phase of the natural menstrual cycle (N = 20), and (3) the periovulatory phase of the natural menstrual cycle (N = 20). Estradiol, progesterone, testosterone, and sex-hormone binding globulin levels were assessed in all groups via blood samples. We used a test battery which measured different facets of value-based decision-making: delay discounting, risk-aversion, risk-seeking, and loss aversion. While hormonal levels did show the expected patterns for the three groups, there were no differences in value-based decision-making parameters. Consequently, Bayes factors showed conclusive evidence in support of the null hypothesis. We conclude that women on oral contraceptives show no differences in value-based decision-making compared to the early follicular and periovulatory natural menstrual cycle phases.

Dopamine agonist therapy and deep brain stimulation (DBS) are both linked to increased impulsivity in Parkinson’s disease (PD), but the underlying mechanisms remain unclear. We trained intact and PD-like rats on a rat gambling task (rGT) measuring impulsive choice and premature responding. Animals were then retested with/without treatment, pramipexole (PPX) or DBS, administered chronically prior to rGT testing. Early PD-like rats did not exhibit major differences in rGT performance or treatment response. Our work suggests that DBS and PPX are not intrinsically linked with increases in impulsivity. Neither DBS nor PPX disrupted gambling-like behaviour in our paradigm, while differential effects on premature and perseverant responding in the task were observed with treatment. Based on our findings, the previously reported ability of PPX to increase impulsive choice might not be mediated by the dopamine D3 receptor. Interestingly, our work suggests that the effects of STN-DBS on impulse control might be amplitude-dependent.