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Description
Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive

Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive decline, and other symptoms that reduce quality of life. To ameliorate these negative consequences, estrogen-containing hormone therapy is prescribed. Findings from clinical and pre-clinical research studies suggest that menopausal hormone therapies can benefit memory and associated neural substrates. However, findings are variable, with some studies reporting null or even detrimental cognitive and neurobiological effects of these therapies. Thus, at present, treatment options for optimal cognitive and brain health outcomes in menopausal women are limited. As such, elucidating factors that influence the cognitive and neurobiological effects of menopausal hormone therapy represents an important need relevant to every aging woman. To this end, work in this dissertation has supported the hypothesis that multiple factors, including post-treatment circulating estrogen levels, experimental handling, type of estrogen treatment, and estrogen receptor activity, can impact the realization of cognitive benefits with Premarin hormone therapy. We found that the dose-dependent working memory benefits of subcutaneous Premarin administration were potentially regulated by the ratios of circulating estrogens present following treatment (Chapter 2). When we administered Premarin orally, it impaired memory (Chapter 3). Follow-up studies revealed that this impairment was likely due to the handling associated with treatment administration and the task difficulty of the memory measurement used (Chapters 3 and 4). Further, we demonstrated that the unique cognitive impacts of estrogens that become increased in circulation following Premarin treatments, such as estrone (Chapter 5), and their interactions with the estrogen receptors (Chapter 6), may influence the realization of hormone therapy-induced cognitive benefits. Future directions include assessing the mnemonic effects of: 1) individual biologically relevant estrogens and 2) clinically-used bioidentical hormone therapy combinations of estrogens. Taken together, information gathered from these studies can inform the development of novel hormone therapies in which these parameters are optimized.
ContributorsEngler-Chiurazzi, Elizabeth (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Hoffman, Steven (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Most people are experts in some area of information; however, they may not be knowledgeable about other closely related areas. How knowledge is generalized to hierarchically related categories was explored. Past work has found little to no generalization to categories closely related to learned categories. These results do not fit

Most people are experts in some area of information; however, they may not be knowledgeable about other closely related areas. How knowledge is generalized to hierarchically related categories was explored. Past work has found little to no generalization to categories closely related to learned categories. These results do not fit well with other work focusing on attention during and after category learning. The current work attempted to merge these two areas of by creating a category structure with the best chance to detect generalization. Participants learned order level bird categories and family level wading bird categories. Then participants completed multiple measures to test generalization to old wading bird categories, new wading bird categories, owl and raptor categories, and lizard categories. As expected, the generalization measures converged on a single overall pattern of generalization. No generalization was found, except for already learned categories. This pattern fits well with past work on generalization within a hierarchy, but do not fit well with theories of dimensional attention. Reasons why these findings do not match are discussed, as well as directions for future research.
ContributorsLancaster, Matthew E (Author) / Homa, Donald (Thesis advisor) / Glenberg, Arthur (Committee member) / Chi, Michelene (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Incidental learning of sequential information occurs in visual, auditory and tactile domains. It occurs throughout our lifetime and even in nonhuman species. It is likely to be one of the most important foundations for the development of normal learning. To date, there is no agreement as to how incidental learning

Incidental learning of sequential information occurs in visual, auditory and tactile domains. It occurs throughout our lifetime and even in nonhuman species. It is likely to be one of the most important foundations for the development of normal learning. To date, there is no agreement as to how incidental learning occurs. The goal of the present set of experiments is to determine if visual sequential information is learned in terms of abstract rules or stimulus-specific details. Two experiments test the extent to which interaction with the stimuli can influence the information that is encoded by the learner. The results of both experiments support the claim that stimulus and domain specific details directly shape what is learned, through a process of tuning the neuromuscular systems involved in the interaction between the learner and the materials.
ContributorsMarsh, Elizabeth R (Author) / Glenberg, Arthur M. (Thesis advisor) / Amazeen, Eric (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2013
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Description
After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle deplete ovaries. Two independent studies, in rodents that had undergone ovarian follicular depletion, found that higher serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that androstenedione impairs memory. The

After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle deplete ovaries. Two independent studies, in rodents that had undergone ovarian follicular depletion, found that higher serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that androstenedione impairs memory. The current study directly tested this hypothesis, examining the cognitive effects of androstenedione administration in a rodent model. Middle-aged ovariectomized rats received vehicle or one of two doses of androstenedione (4 or 8 mg/kg daily). Rats were tested on a spatial working and reference memory maze battery including the water radial arm maze, Morris maze, and delay-match-to-sample task. Results showed that androstenedione at the highest dose impaired reference memory and working memory, including ability to maintain performance as memory demand was elevated. The latter was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. Glutamic acid decarboxylase (GAD) levels were measured in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system mediates androstenedione's cognitive impairments. Results showed that higher entorhinal cortex GAD levels were correlated with poorer Morris maze performance, regardless of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle deplete ovary, is detrimental to spatial learning, reference memory, and working memory, and that spatial reference memory performance might be related to the GABAergic system.
ContributorsCamp, Bryan Walter (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Olive, Michael F (Committee member) / Conrad, Cheryl D. (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Globally, addiction to stimulants such as methamphetamine (METH) remains a significant public health problem. Despite decades of research, no approved anti-relapse medications for METH or any illicit stimulant exist, and current treatment approaches suffer from high relapse rates. Recently, synthetic cathinones have also emerged as popular abused stimulants, leading to

Globally, addiction to stimulants such as methamphetamine (METH) remains a significant public health problem. Despite decades of research, no approved anti-relapse medications for METH or any illicit stimulant exist, and current treatment approaches suffer from high relapse rates. Recently, synthetic cathinones have also emerged as popular abused stimulants, leading to numerous incidences of toxicity and death. However, contrary to traditional illicit stimulants, very little is known about their addiction potential. Given the high relapse rates and lack of approved medications for METH addiction, chapters 2 and 3 of this dissertation assessed three different glutamate receptor ligands as potential anti-relapse medications following METH intravenous self-administration (IVSA) in rats. In chapters 4 through 7, using both IVSA and intracranial self-stimulation (ICSS) procedures, experiments assessed abuse liability of the popular synthetic cathinones 3,4-Methylenedioxypyrovalerone (MDPV) , methylone, α-pyrrolidinovalerophenone (α-PVP) and 4-methylethylcathinone (4-MEC). Results from these seminal studies suggest that these drugs possess similar abuse potential to traditional illicit stimulants such as METH, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA). Finally, studies outlined in chapter 8 assessed the potential neurotoxic or adverse cognitive effects of METH and MDPV following IVSA procedures for the purpose of identifying potential novel pharmacotherapeutic targets. However, results of these final studies did not reveal neurotoxic or adverse cognitive effects when using similar IVSA procedural parameters that were sufficient for establishing addiction potential, suggesting that these parameters do not allow for sufficient drug intake to produce similar neurotoxicity or cognitive deficits reported in humans. Thus, these models may be inadequate for fully modeling the adverse neural and psychological consequences of stimulant addiction. Together, these studies support the notion for continued research into the abuse liability and toxicity of METH and synthetic cathinones and suggest that refinements to traditional IVSA models are needed for both more effective assessment of potential cognitive and neural deficits induced by these drugs and screening of potentially clinically efficacious pharmacotherapeutics.
ContributorsWatterson, Lucas (Author) / Olive, Michael F (Thesis advisor) / Czyzyk, Traci (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light.

Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used.
ContributorsCole, Natalie (Author) / Neisewander, Janet L (Thesis advisor) / Sanabria, Federico (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Olive, Michael F (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Theories of interval timing have largely focused on accounting for the aggregate properties of behavior engendered by periodic reinforcement, such as sigmoidal psychophysical functions and their scalar property. Many theories of timing also stipulate that timing and motivation are inseparable processes. Such a claim is challenged by fluctuations in and

Theories of interval timing have largely focused on accounting for the aggregate properties of behavior engendered by periodic reinforcement, such as sigmoidal psychophysical functions and their scalar property. Many theories of timing also stipulate that timing and motivation are inseparable processes. Such a claim is challenged by fluctuations in and out of states of schedule control, making it unclear whether motivation directly affects states related to timing. The present paper seeks to advance our understanding of timing performance by analyzing and comparing the distribution of latencies and inter-response times (IRTs) of rats in two fixed-interval (FI) schedules of food reinforcement (FI 30-s and FI 90-s), and in two levels of food deprivation. Computational modeling revealed that each component was well described by mixture probability distributions embodying two-state Markov chains. Analysis of these models revealed that only a subset of latencies are sensitive to the periodicity of reinforcement, and pre-feeding only reduces the size of this subset. The distribution of IRTs suggests that behavior in FI schedules is organized in bouts that lengthen and ramp up in frequency with proximity to reinforcement. Pre-feeding slowed down the lengthening of bouts and increased the time between bouts. When concatenated, these models adequately reproduced sigmoidal FI response functions. These findings suggest that behavior in FI fluctuates in and out of schedule control; an account of such fluctuation suggests that timing and motivation are dissociable components of FI performance. These mixture-distribution models also provide novel insights on the motivational, associative, and timing processes expressed in FI performance, which need to be accounted for by causal theories of interval timing.
ContributorsDaniels, Carter W (Author) / Sanabria, Federico (Thesis advisor) / Brewer, Gene (Committee member) / Wynne, Clive (Committee member) / Arizona State University (Publisher)
Created2015
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Description
The human body is a complex system comprised of many parts that can coordinate in a variety of ways to produce controlled action. This creates a challenge for researchers and clinicians in the treatment of variability in motor control. The current study aims at testing the utility of a

The human body is a complex system comprised of many parts that can coordinate in a variety of ways to produce controlled action. This creates a challenge for researchers and clinicians in the treatment of variability in motor control. The current study aims at testing the utility of a nonlinear analysis measure – the Largest Lyapunov exponent (1) – in a whole body movement. Experiment 1 examined this measure, in comparison to traditional linear measure (standard deviation), by having participants perform a sit-to-stand (STS) task on platforms that were either stable or unstable. Results supported the notion that the Lyapunov measure characterized controlled/stable movement across the body more accurately than the traditional standard deviation (SD) measure. Experiment 2 tested this analysis further by presenting participants with an auditory perturbation during performance of the same STS task. Results showed that both the Lyapunov and SD measures failed to detect the perturbation. However, the auditory perturbation may not have been an appropriate perturbation. Limitations of Experiment 2 are discussed, as well as directions for future study.
ContributorsGibbons, Cameron T (Author) / Amazeen, Polemnia G (Thesis advisor) / Amazeen, Eric (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2016
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Description
Self-control has been shown to predict both health risk and health protective outcomes. Although top-down or “good” self-control is typically examined as a unidimensional construct, research on “poor” self-control suggests that multiple dimensions may be necessary to capture aspects of self-control. The current study sought to create a new brief

Self-control has been shown to predict both health risk and health protective outcomes. Although top-down or “good” self-control is typically examined as a unidimensional construct, research on “poor” self-control suggests that multiple dimensions may be necessary to capture aspects of self-control. The current study sought to create a new brief survey measure of top-down self-control that differentiates between self-control capacity, internal motivation, and external motivation. Items were adapted from the Brief Self-Control Scale (BSCS; Tangney, Baumeister, & Boone, 2004) and were administered through two online surveys to 347 undergraduate students enrolled in introductory psychology courses at Arizona State University. The Self-Control Motivation and Capacity Survey (SCMCS) showed strong evidence of validity and reliability. Exploratory and confirmatory factor analyses supported a 3-factor structure of the scale consistent with the underlying theoretical model. The final 15-item measure demonstrated excellent model fit, chi-square = 89.722 p=.077, CFI = .989, RMSEA = .032, SRMR = .045. Despite several limitations including the cross-sectional nature of most analyses, self-control capacity, internal motivation, and external motivation uniquely related to various self-reported behavioral outcomes, and accounted for additional variance beyond that accounted for by the BSCS. Future studies are needed to establish the stability of multiple dimensions of self-control, and to develop state-like and domain-specific measures of self-control. While more research in this area is needed, the current study demonstrates the importance of studying multiple aspects of top-down self-control, and may ultimately facilitate the tailoring of interventions to the needs of individuals based on unique profiles of self-control capacity and motivation.
ContributorsPapova, Anna (Author) / Corbin, William R. (Thesis advisor) / Karoly, Paul (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2016
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Description
In this study, the oppositional processes theory was proposed to suggest that reliance on semantic and episodic memory systems hinder originality during idea generation for divergent thinking tasks that are generally used to assess creative potential. In order to investigate the proposed oppositional processes theory, three experiments that manipulated the

In this study, the oppositional processes theory was proposed to suggest that reliance on semantic and episodic memory systems hinder originality during idea generation for divergent thinking tasks that are generally used to assess creative potential. In order to investigate the proposed oppositional processes theory, three experiments that manipulated the memory accessibility in participants during the alternative uses tasks were conducted. Experiment 1 directly instructed participants to either generate usages based on memory or not from memory; Experiment 2 provided participants with object cues that were either very common or very rare in daily life (i.e., bottle vs. canteen); Experiment 3 replicated the same manipulation from Experiment 2 with much longer generation time (10 minutes in Experiment 2 vs. 30 minutes in Experiment 3). The oppositional processes theory predicted that participants who had less access to direct and unaltered usages (i.e., told to not use memory, were given rare cues, or were outputting items later in the generation period) during the task would be more creative. Results generally supported the predictions in Experiments 1 and 2 where participants from conditions which limited their access to memory generated more novel usages that were considered more creative by independent coders. Such effects were less prominent in Experiment 3 with extended generation time but the trends remained the same.
ContributorsXu, Dongchen (Author) / Brewer, Gene (Thesis advisor) / Glenberg, Arthur (Committee member) / Homa, Donald (Committee member) / Goldinger, Stephen (Committee member) / Arizona State University (Publisher)
Created2017