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The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex

The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
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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
Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind

Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Newbern, Jason M. (Committee member) / Orchinik, Miles (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2018
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Description
With a growing number of adults with autism spectrum disorder (ASD), more and more research has been conducted on majority male cohorts with ASD from young, adolescence, and some older age. Currently, males make up the majority of individuals diagnosed with ASD, however, recent research states that the gender ga

With a growing number of adults with autism spectrum disorder (ASD), more and more research has been conducted on majority male cohorts with ASD from young, adolescence, and some older age. Currently, males make up the majority of individuals diagnosed with ASD, however, recent research states that the gender gap is closing due to more advanced screening and a better understanding of how females with ASD present their symptoms. Little research has been published on the neurocognitive differences that exist between older adults with ASD compared to neurotypical (NT) counterparts, and nothing has specifically addressed older women with ASD. This study utilized neuroimaging and neuropsychological tests to examine differences between diagnosis and sex of four distinct groups: older men with ASD, older women with ASD, older NT men, and older NT women. In each group, hippocampal size (via FreeSurfer) was analyzed for differences as well as correlations with neuropsychological tests. Participants (ASD Female, n = 12; NT Female, n = 14; ASD Male, n = 30; NT Male = 22), were similar according to age, IQ, and education. The results of the study indicated that the ASD Group as a whole performed worse on executive functioning tasks (Wisconsin Card Sorting Test, Trails Making Test) and memory-related tasks (Rey Auditory Verbal Learning Test, Weschler Memory Scale: Visual Reproduction) compared to the NT Group. Interactions of sex by diagnosis approached significance only within the WCST non-perseverative errors, with the women with ASD performing worse than NT women, but no group differences between men. Effect sizes between the female groups (ASD female vs. NT female) showed more than double that of the male groups (ASD male vs. NT male) for all WCST and AVLT measures. Participants with ASD had significantly smaller right hippocampal volumes than NT participants. In addition, all older women showed larger hippocampal volumes when corrected for total intracranial volume (TIV) compared to all older men. Overall, NT Females had significant correlations across all neuropsychological tests and their hippocampal volumes whereas no other group had significant correlations. These results suggest a tighter coupling between hippocampal size and cognition in NT Females than NT Males and both sexes with ASD. This study promotes further understanding of the neuropsychological differences between older men and women, both with and without ASD. Further research is needed on a larger sample of older women with and without ASD.
ContributorsWebb, Christen Len (Author) / Braden, B. Blair (Thesis advisor) / Azuma, Tamiko (Committee member) / Dixon, Maria (Committee member) / Arizona State University (Publisher)
Created2019
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Description
This pilot study evaluated whether Story Champs and Puente de Cuentos helped bilingual preschoolers increase their usage of emotional terms and ability to tell stories. Participants in this study included 10 Spanish-English bilingual preschoolers. Intervention was conducted in 9 sessions over 3 days using the Test of Narrative Retell to

This pilot study evaluated whether Story Champs and Puente de Cuentos helped bilingual preschoolers increase their usage of emotional terms and ability to tell stories. Participants in this study included 10 Spanish-English bilingual preschoolers. Intervention was conducted in 9 sessions over 3 days using the Test of Narrative Retell to measure results. Results did not find significant gains in either emotional term usage or ability to tell stories, but the results were promising as a pilot study.
ContributorsSato, Leslie Mariko (Author) / Restrepo, Maria (Thesis director) / Dixon, Maria (Committee member) / Department of Speech and Hearing Science (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
The study focuses on the creation of the Strengthening Skills Program (SSP) and its feasibility and acceptability among autistic adults across the lifespan. Over the course of two years, the program has been developed and delivered to autistic adults with the aim of improving quality of life. The program included

The study focuses on the creation of the Strengthening Skills Program (SSP) and its feasibility and acceptability among autistic adults across the lifespan. Over the course of two years, the program has been developed and delivered to autistic adults with the aim of improving quality of life. The program included adapted social skills training from the UCLA Program for the Education and Enrichment of Relational Skills (PEERS) for young adults, adapted mindfulness training from Mindfulness-Based Stress Reduction, and custom executive skills training. Pre- and post-intervention acceptability questionnaires were gathered from 42 participants. Participants were separated into three groups (SSP, PEERS, and Delayed Treatment Control [DTC]; n=14 per group) stratified by age, gender, and if the participant had a program partner who would attend the program alongside as support. All groups were administered over Zoom once per week and lasted for 16 weeks each. The SSP group met for three hours each week and the PEERS group met for an hour and a half. Qualitative analysis was implemented on participant feedback to identify thematic codes related to their experiences with the programs. Overall, results suggest the SSP intervention had significantly higher acceptability ratings compared to PEERS alone and could be a useful addition to the limited interventions available for autistic adults.
ContributorsHill, Ethan Reed (Author) / Braden, Blair (Thesis advisor) / Matthews, Nicole (Committee member) / Dixon, Maria (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The prevalence of Autism Spectrum Disorders (ASD) has resulted in research on treatment efficacy, lending itself to quantitative analyses. In contrast, ethnographic studies have offered the benefits of analyzing lived experiences and exploring the uniqueness of ASD individuals. Using the Linguistic Ethnography (LE) perspective, this case study investigates the connection

The prevalence of Autism Spectrum Disorders (ASD) has resulted in research on treatment efficacy, lending itself to quantitative analyses. In contrast, ethnographic studies have offered the benefits of analyzing lived experiences and exploring the uniqueness of ASD individuals. Using the Linguistic Ethnography (LE) perspective, this case study investigates the connection between multilingual practices, behavior management, and behavior-logging app usage. It looks at one cross-cultural family (Indonesian-Belgian) with two children diagnosed with autism. Multimodal data were collected for ten weeks virtually and five weeks in the family’s home in Belgium. The data collection focused on the family's multilingual and behavior management practices and specifically on mobile app usage to document the behaviors of the non-verbal son. Analytical frameworks were drawn from Multimodal Ethnography (Dicks et al., 2006) and Multimodal Discourse Analysis (Kress, 2011a). The findings indicated that linguistic and cultural diversity, both internally and externally, caused a layer of complexity in attending to a non-verbal child. The case study showed positive outcomes of multilingualism. However, it highlighted the struggle of building consistent communication between family members and health professionals, which affected the effort to find a successful treatment plan. The behavior logging app helped parents identify parts of the son’s behaviors and reflect on their behavior management strategies. However, it also underscored the real-life challenges of documentation. In this case, mobile technology may be more useful when supported by health professionals. Although the case study notes family successes, it calls attention to the extraordinary realities of cross-cultural ASD families that need more representation through ethnographic research.
ContributorsQodri, Asri Nurul (Author) / Smith, David Bryan (Thesis advisor) / SturtzSreetharan, Cindi (Committee member) / Dixon, Maria (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Autistic adults face heightened risk of psychiatric disorders, with depression occurrence estimated at quadruple the rate of the general population. Mindfulness Based Stress Reduction (MBSR), an intensive 8-week in-person intervention, reduces depressive symptoms in adults with autism spectrum disorder (ASD). However, access to these programs is restricted due to financial,

Autistic adults face heightened risk of psychiatric disorders, with depression occurrence estimated at quadruple the rate of the general population. Mindfulness Based Stress Reduction (MBSR), an intensive 8-week in-person intervention, reduces depressive symptoms in adults with autism spectrum disorder (ASD). However, access to these programs is restricted due to financial, geographic, and scheduling limitations. Additionally, lapses in practice post-intervention cause these effects to be short-lived. This study examines antidepressant effects of an 8-week app-delivered mindfulness meditation intervention using Ten Percent Happier in adults with ASD and explores whether anchoring meditation practice to a preexisting behavior will improve therapy compliance and depression-related efficacy. Ninety-seven participants were randomly assigned to either App Only (n=30), App + Habit training (n=27) or Waitlist Control (n=40). App Only and App + Habit groups were requested to meditate a minimum of 10 minutes per day, 5 days per week for 8 consecutive weeks using the mobile application. The App + Habit group received additional instruction to anchor leaving the bathroom each morning with meditation; The App Only group was only provided with education on habit formation. Participants completed the Beck Depression Inventory-II (BDI-II) at pre- and post-intervention. All groups received weekly ecological momentary assessments (EMAs) to assess frequency and length of practice. The App + Habit group was additionally assessed for cue-initiated meditation frequency. Data were analyzed using repeated measures analysis of variance (ANOVA). Pre-to-post changes on BDI-II scores indicated a group by time interaction (p=0.04) and a main effect of time (p <0.001). Post-hoc analysis revealed the App + Habit group exclusively showed significant decline in depressive symptoms (p<0.001). The App + Habit group showed greater number of days meditated, average minutes per day of meditating, and continuation of meditation practice 8-weeks after the intervention period, compared to the App Only group. Findings support app-delivered mindfulness interventions as an accessible and cost-effective alternative to traditional in-person mindfulness training for Autistic adults. However, results suggest app-based mindfulness tools may only be effective when delivered with specific habit formation instruction. Additionally, habit formation instruction led to greater adherence to meditation practice after the study period ended.
ContributorsVink, Schuyler Rae (Author) / Braden, B. Blair (Thesis advisor) / Stecher, Chad (Committee member) / Dixon, Maria (Committee member) / Rogalsky, Corriane (Committee member) / Arizona State University (Publisher)
Created2022