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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
Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal

Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal women, such as FemhrtTM (Simon et al., 2003). Thus, EE is prescribed clinically to women at ages ranging from puberty through reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young, female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection. For these studies, the low and medium doses correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to the range of doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. For each study, cognition was evaluated with a battery of maze tasks tapping several domains of spatial learning and memory. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; this was seen for both cyclic and tonic regimens. Cyclic and tonic delivery of low EE, a dose that corresponds to doses used in the clinic today, resulted in transient and null impairments, respectively, on cognition.
ContributorsMennenga, Sarah E (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Baxter, Leslie C. (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can

Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus

Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Recognition memory was investigated for naturalistic dynamic scenes. Although visual recognition for static objects and scenes has been investigated previously and found to be extremely robust in terms of fidelity and retention, visual recognition for dynamic scenes has received much less attention. In four experiments, participants view a number of

Recognition memory was investigated for naturalistic dynamic scenes. Although visual recognition for static objects and scenes has been investigated previously and found to be extremely robust in terms of fidelity and retention, visual recognition for dynamic scenes has received much less attention. In four experiments, participants view a number of clips from novel films and are then tasked to complete a recognition test containing frames from the previously viewed films and difficult foil frames. Recognition performance is good when foils are taken from other parts of the same film (Experiment 1), but degrades greatly when foils are taken from unseen gaps from within the viewed footage (Experiments 3 and 4). Removing all non-target frames had a serious effect on recognition performance (Experiment 2). Across all experiments, presenting the films as a random series of clips seemed to have no effect on recognition performance. Patterns of accuracy and response latency in Experiments 3 and 4 appear to be a result of a serial-search process. It is concluded that visual representations of dynamic scenes may be stored as units of events, and participant's old
ew judgments of individual frames were better characterized by a cued-recall paradigm than traditional recognition judgments.
ContributorsFerguson, Ryan (Author) / Homa, Donald (Thesis advisor) / Goldinger, Stephen (Committee member) / Glenberg, Arthur (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The present series of studies examined whether a novel implementation of an

intermittent restraint (IR) chronic stress paradigm could be used to investigate hippocampal-dependent spatial ability in both sexes. In experiments 1 and 2, Sprague- Dawley male rats were used to identify the optimal IR parameters to assess spatial ability. For

The present series of studies examined whether a novel implementation of an

intermittent restraint (IR) chronic stress paradigm could be used to investigate hippocampal-dependent spatial ability in both sexes. In experiments 1 and 2, Sprague- Dawley male rats were used to identify the optimal IR parameters to assess spatial ability. For IR, rats were restrained for 2 or 6hrs/day (IR2, IR6, respectively) for five days and then given two days off, a process that was repeated for three weeks and compared to rats restrained for 6hrs/d for each day (DR6) and non-stressed controls (CON). Spatial memory was tested on the radial arm water maze (RAWM), object placement (OP), novel object recognition (NOR) and Y-maze. The results for the first two experiments revealed that IR6, but not IR2, was effective in impairing spatial memory in male rats and that task order impacted performance. In experiment 3, an extended IR paradigm for six weeks was implemented before spatial memory testing commenced in male and female rats (IR- M, IR-F). Unexpectedly, an extended IR paradigm failed to impair spatial memory in either males or females, suggesting that when extended, the IR paradigm may have become predictable. In experiment 4, an unpredictable IR (UIR) paradigm was implemented, in which restraint duration (30 or 60-min) combined with orbital shaking, time of day, and the days off from UIR were varied. UIR impaired spatial memory in males, but not females. Together with other reports, these findings support the interpretation that chronic stress negatively impairs hippocampal-dependent function in males, but not females, and that females appear to be resilient to spatial memory deficits in the face of chronic stress.
ContributorsPeay, Dylan (Author) / Conrad, Cheryl D. (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Wynne, Clive (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Although it has recently been demonstrated that source monitoring (SM) processes may mediate the relationship between working memory (WM) and false memories, little research has investigated whether the quality of monitoring processes can account for this reduction. In the current study, participants performed multiple false memory, WM, and SM tasks.

Although it has recently been demonstrated that source monitoring (SM) processes may mediate the relationship between working memory (WM) and false memories, little research has investigated whether the quality of monitoring processes can account for this reduction. In the current study, participants performed multiple false memory, WM, and SM tasks. Consistent with previous research, SM abilities mediated the relationship between WM and false memories (regardless of whether or not participants were warned of the illusions at encoding). High SM individuals were better able to recall contextual information from study to correctly reject lures, whereas low SM individuals were more likely to rely on the quality of retrieved details to reject lures. These results suggest that individuals low and high in SM abilities rely on qualitatively different monitoring processes to reduce errors, and that individual differences in diagnostic monitoring strategies may account for previous relationships found between WM and false memories.
ContributorsCoulson, Allison Rose (Author) / Brewer, Gene (Thesis director) / Ellis, Derek (Committee member) / Department of Psychology (Contributor) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Temporal discounting refers to our tendency to discount the value of future rewards. At the extreme, temporal discounting can give rise to detrimental myopic decision-making. Most studies examining the neural basis of temporal discounting in people have been performed using functional Magnetic Resonance Imaging (fMRI). However, fMRI has relatively poor

Temporal discounting refers to our tendency to discount the value of future rewards. At the extreme, temporal discounting can give rise to detrimental myopic decision-making. Most studies examining the neural basis of temporal discounting in people have been performed using functional Magnetic Resonance Imaging (fMRI). However, fMRI has relatively poor temporal resolution compared with the speed at which people make choices, so understanding choice dynamics using fMRI is difficult. We address the issue utilizing electroencephalography (EEG) to study cortical processes related to temporal discounting. The fMRI literature has found that a network of fronto-parietal brain regions plays an important role during the decision-making process. We aim to explore activity in these regions during the decision process and determine how cortical activity relates to choice parameters. Based on prior fMRI studies, we hypothesized that dorsomedial prefrontal cortex (dmPFC) may act as a regulator of dorsal lateral prefrontal cortex (dlPFC) and there will be an increase in dlPFC activity for more difficult decisions. We also hypothesized that neural activity may be directly related to the temporal discount rate we estimate behaviorally. We utilized regression analysis to determine the relationship. The results found supported our hypotheses. This study may open the door to a better understanding of the dynamic of brain regions while performing a temporal discounting task.
Created2017-05
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Description
By providing vignettes with manipulated scientific evidence, this research examined if including more or less scientific detail affected decision-making in regards to the death penalty. Participants were randomly assigned one of the two manipulations (less science and more science) after reading a short scenario introducing the mock capital trial and

By providing vignettes with manipulated scientific evidence, this research examined if including more or less scientific detail affected decision-making in regards to the death penalty. Participants were randomly assigned one of the two manipulations (less science and more science) after reading a short scenario introducing the mock capital trial and their role as jury members. Survey respondents were told that a jury had previously found the defendant guilty and they would now deliberate the appropriate punishment. Before being exposed to the manipulation, respondents answered questions pertaining to their prior belief in the death penalty, as well as their level of support of procedural justice and science. These questions provided a baseline to compare to their sentencing decision. Participants were then asked what sentence they would impose \u2014 life in prison or death \u2014 and how the fMRI evidence presented by an expert witness for the defense affected their decision. Both quantitative and qualitative measures were used to identify how the level of scientific detail affected their decision. Our intended predictor variable (level of scientific detail) did not affect juror decision-making. In fact, the qualitative results revealed a variety of interpretations of the scientific evidence used both in favor of death and in favor of life. When looking at what did predict juror decision-making, gender, prior belief in the death penalty, and political ideology all were significant predictors. As in previous literature, the fMRI evidence in our study had mixed results with regards to implementation of the death penalty. This held true in both of our manipulations, showing that despite the level of detail in evidence intended for mitigation, jurors with preconceived notions may still disregard the evidence, and some jurors may even view it is aggravating and thus increase the likelihood of a death sentence for a defendant with such brain abnormalities.
ContributorsBerry, Megan Cheyenne (Author) / Fradella, Hank (Thesis director) / Pardini, Dustin (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
Working memory is the cognitive system responsible for storing and maintaining information in short-term memory and retrieving cues from long-term memory. Working memory capacity (WMC) is needed for goal maintenance and to ignore task-irrelevant stimuli (Engle & Kane, 2003). Emotions are one type of task-irrelevant stimuli that could distract an

Working memory is the cognitive system responsible for storing and maintaining information in short-term memory and retrieving cues from long-term memory. Working memory capacity (WMC) is needed for goal maintenance and to ignore task-irrelevant stimuli (Engle & Kane, 2003). Emotions are one type of task-irrelevant stimuli that could distract an individual from a task (Smallwood, Fitzgerald, Miles, & Phillips, 2009). There are studies that show there is a relation between emotions and working memory capacity. The direction of this relationship, though, is unclear (Kensinger, 2009). In this study, emotions served as a distractor and task performance was examined for differences in the effect of emotion depending on participants' working memory capacity. The participants watched a mood induction video, then were told to complete a complex-span working memory task. The mood induction was successful- participants watching the negative emotional video were in a less positive mood after watching the video than the participants that watched a neutral video. However, the results of the complex-span working memory task showed no significant difference in the results between participants in the negative versus neutral mood. These results may provide support to an alternative hypothesis: cognitive tasks can diminish the effects of emotions (Dillen, Heslenfeld, & Koole, 2009).
ContributorsAhmed, Sania (Author) / Brewer, Gene (Thesis director) / Wingert, Kimberly (Committee member) / Blais, Chris (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05