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Description
The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH) causes great harm to both the individual user and to society; yet, no studies have examined the effects of MS on METH SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core were also investigated. Long-Evans pups and dams were separated on postnatal days (PND) 2-14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-hr daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.
ContributorsLewis, Candace (Author) / Olive, Micheal F (Thesis advisor) / Conrad, Cheryl (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
This thesis aimed to develop a consistent protocol used to effectively image the apolipoprotein E (ApoE) ε4 allele, which is a known genetic risk factor for Alzheimer’s Disease (AD). The research team used methods to extract DNA from saliva samples, amplify the DNA using polymerase chain reaction (PCR), and image the results using gel electrophoresis and a transilluminator. Extensive literature review was used to optimize these techniques. Future studies will use these methods of characterizing the ApoE ε4 allele as preliminary work towards the goal of integrating this protocol into ongoing research in aging within the Motor Rehabilitation and Learning (MRL) Lab on Arizona State University’s campus.
ContributorsWorman, Drew (Author) / Schaefer, Sydney (Thesis director) / Lewis, Candace (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Adults with autism spectrum disorder (ASD) commonly have co-morbid psychiatric symptoms which can decrease quality of life. Although many adults with ASD are achieving greater independence, including attending college, psychiatric symptoms are generally not well controlled in this group. Mindfulness Based Stress Reduction (MBSR) is a program that has successfully been used to reduce the stress, depression, and anxiety symptoms in many clinical and non-clinical groups and may also be effective for college-aged students with ASD. The present investigation assessed the demand, practicality, implementation, adaptation, and acceptability of an MBSR course for college students with ASD. A total of 22 participants completed the questionnaire containing 53 questions and were between the ages of 18 to 64. We found that the MBSR therapy is in high demand for individuals with ASD, and that the participants would be willingly complete the intervention techniques. Participants generally stated that a therapy course like MBSR may help reduce their symptoms, and that they were eager to enroll. Participants were willing to attend all 8 classes during the summer, with a preference for afternoons. Also, modifications including yoga and background music would be accepted by each participant as well as any additional modifications made to the course to meet the needs of the individuals with ASD. Next steps include enrolling and randomizing students into the MBSR course or control group, as well as collect pre- and post-intervention data. We hypothesize MBSR will reduce the psychiatric symptoms and stress levels of individuals in college with ASD, demonstrating its effectiveness in this vulnerable population.
ContributorsJones, Rachel Michelle (Author) / Braden, Blair (Thesis director) / Baxter, Leslie (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Speech and Hearing Science (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
The Development of the Strengthening Skills Program for Autistic Adults: Feasibility & Acceptability
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 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
Description
Diffusion weighted imaging utilizes magnetic resonance imaging to capture white matter tracts in the brain. Many studies have utilized this technique to measure white matter structures looking for evidence of anatomical and physiological differences in Autism Spectrum Disorder (ASD). Parkinsonian-like symptoms have been documented and self-reported in aging autistic individuals, opening up questions about a possible link between ASD and an increased risk of Parkinson’s Disease. Utilizing MRtrix3, an image processing proof-of-concept pipeline was developed for the Autism and Brain Aging (ABA) lab to generate and visualize the brain’s structural connectivity network in these populations of interest. The pipeline provides the opportunity for white matter tractography analysis in the lab’s Aging in Autism study.
ContributorsFeldman, Leslie (Author) / Ofori, Edward (Thesis advisor) / Braden, Blair (Committee member) / Rogalsky, Corianne (Committee member) / Arizona State University (Publisher)
Created2023
Description
ABSTRACTAutism spectrum disorder (ASD) is a neurodevelopmental condition associated with social communication challenges and restrictive and repetitive behaviors [2]. Despite known lifelong challenges, understanding of cognitive and brain aging with ASD is lacking. Middle-aged adults with ASD have a higher chance of developing Alzheimer’s disease (Alz) and other dementias compared to neurotypical (NT) adults [12].
Apolipoprotein E (APOE) is a lipid transport protein involved in neuronal repair and cholesterol transport and is the strongest genetic risk factor for Alz [22]. Others demonstrated that individuals with ASD are more likely to carry the APOE ε4-allele [21]. This study aimed to determine if the APOE ε4-allele negatively impacts verbal learning and memory in ASD compared to NT adults.
Participants were intellectually able 76 middle-age and older adults (MA+) between the ages of 40-71, including 35 with ASD [mean age=53.06 (±8.91)] and 41 NT adults [mean age=53.90 (±8.44)]. APOE allelic distribution was determined from salivary samples via polymerase chain reaction amplification and genotyped on a tapestation. The Auditory Verbal Learning Test (AVLT) variables were short-term memory, long-term memory, and total learning.
There was a main effect of APOE ε4 for short-term memory and verbal learning, with ε4 carriers performing worse across diagnosis groups. For verbal learning, sex was a significant predictor. So, exploratory analyses separating diagnosis groups by sex were conducted. Only males with ASD were found to be carrying APOE ε4 associated with reduced verbal learning (p=0.02). Finally, the APOE ε4-allele did not significantly affect the participants’ long-term memory.
These findings suggest that the APOE ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults, and that autistic men may be particularly vulnerable to the effects of APOE ε4 on verbal learning. This study is the first to incorporate ASD in APOE’s association with cognition and investigate how sex differences impact memory function. Future research is needed to replicate these findings using a larger sample size to further understand how the ε4-allele affects memory function trajectories in MA+ ASD as they grow older.
ContributorsAl-Hassan, Lamees (Author) / Braden, Blair (Thesis advisor) / Lewis, Candace (Committee member) / Rogalsky, Corianne (Committee member) / Arizona State University (Publisher)
Created2023
Description
The emotional enhancement of memory (EEM) has consistently suggested that memory performance is enhanced for positively and negatively valenced stimuli. Heightened arousal and activation of the noradrenergic system facilitates encoding and the formation of memory traces. However, this EEM can become maladaptive when coupled with the heightened noradrenergic activity associated with posttraumatic stress disorder (PTSD). This heightened noradrenergic response can result in chronic intrusive memories of past traumatic events. This study aims to explore overall recall, retrieval dynamics, output editing, and intrusions as a function of emotional content and prior history with traumatic experiences. Undergraduate students (N=249) from Arizona State University completed a battery surveys measuring PTSD symptomatology and other related constructs including anxiety, depression, and trauma. Participants then completed a memory task, an externalized free recall task for multiple study-blocks utilizing word list stimuli. During recall, participants were instructed to report every word that came to mind regardless of whether it was present or not in the most recent study-block, then make a judgment about recent-list membership. Main effects of valence were found for recall accuracy, intrusion generation, and successful editing. This suggests that the emotional enhancement of memory does in fact play a role in intrusion generation and the ability to edit out false recollections. Only depression levels resulted in a significant interaction effect with valence, specifically when measuring intrusion generation. This suggests that trauma level does not play a significant role in emotional intrusion memory.
ContributorsDziendziel, Hailey K (Author) / Brewer, Gene A (Thesis advisor) / Azuma, Tamiko (Committee member) / Lewis, Candace (Committee member) / Arizona State University (Publisher)
Created2023
Description
The corpus callosum is a core white matter structure that sits at the center of the brain, playing a role in both interhemispheric communication and the inhibition of hemispheric activity to promote lateralization. Structural connectivity is thought to underlie functional connectivity (FC), but cases of structural brain abnormalities allow for a better understanding of this relationship. Agenesis of the corpus callosum (AgCC) is a condition in which an individual is born without a corpus callosum. These individuals provide a unique opportunity to investigate ways in which the brain adapts its functional organization to the lack of interhemispheric structural connectivity, thereby providing unique insights into brain network organization within and between the two cerebral hemispheres. The present study uses resting-state functional magnetic resonance imaging (fMRI) to compare the network connectivity of an individual with AgCC without any significant comorbidities to a control group of neurotypical adults (n=30). Potential differences of FC within the default mode network and frontoparietal network, as well as FC between these networks and bilateral language networks were examined. The AgCC individual displayed significantly higher FC within the frontoparietal network (t(29)=1.84, p<0.05) and significantly lower FC between the default mode network and the right ventral language stream (t(29)=-1.81, p<0.05) compared to the control group. Further analyses suggest that the right hemisphere’s frontoparietal network is driving the significant difference between the case study and control group in the frontoparietal network. The stronger FC of the frontoparietal network may represent a compensatory strategy used to support lower overall levels of default mode network and dual stream language network connectivity. Overall, the findings suggest that decreased interhemispheric structural connectivity may lead to increased compensation via attention networks such as the frontoparietal network, and decreased right hemisphere language network involvement.
ContributorsDungca, Lalaine Rose (Author) / Rogalsky, Corianne (Thesis advisor) / Schaefer, Sydney (Committee member) / Braden, Blair (Committee member) / Arizona State University (Publisher)
Created2023
Description
Little is known about how cognitive and brain aging patterns differ in older adults with autism spectrum disorder (ASD). However, recent evidence suggests that individuals with ASD may be at greater risk of pathological aging conditions than their neurotypical (NT) counterparts. A growing body of research indicates that older adults with ASD may experience accelerated cognitive decline and neurodegeneration as they age, although studies are limited by their cross-sectional design in a population with strong age-cohort effects. Studying aging in ASD and identifying biomarkers to predict atypical aging is important because the population of older individuals with ASD is growing. Understanding the unique challenges faced as autistic adults age is necessary to develop treatments to improve quality of life and preserve independence. In this study, a longitudinal design was used to characterize cognitive and brain aging trajectories in ASD as a function of autistic trait severity. Principal components analysis (PCA) was used to derive a cognitive metric that best explains performance variability on tasks measuring memory ability and executive function. The slope of the integrated persistent feature (SIP) was used to quantify functional connectivity; the SIP is a novel, threshold-free graph theory metric which summarizes the speed of information diffusion in the brain. Longitudinal mixed models were using to predict cognitive and brain aging trajectories (measured via the SIP) as a function of autistic trait severity, sex, and their interaction. The sensitivity of the SIP was also compared with traditional graph theory metrics. It was hypothesized that older adults with ASD would experience accelerated cognitive and brain aging and furthermore, age-related changes in brain network topology would predict age-related changes in cognitive performance.
For both cognitive and brain aging, autistic traits and sex interacted to predict trajectories, such that older men with high autistic traits were most at risk for poorer outcomes. In men with autism, variability in SIP scores across time points trended toward predicting cognitive aging trajectories. Findings also suggested that autistic traits are more sensitive to differences in brain aging than diagnostic group and that the SIP is more sensitive to brain aging trajectories than other graph theory metrics. However, further research is required to determine how physiological biomarkers such as the SIP are associated with cognitive outcomes.
ContributorsSullivan, Georgia (Author) / Braden, Blair (Thesis advisor) / Kodibagkar, Vikram (Thesis advisor) / Schaefer, Sydney (Committee member) / Wang, Yalin (Committee member) / Arizona State University (Publisher)
Created2022
Description
Older adults often experience communication difficulties, including poorer comprehension of auditory speech when it contains complex sentence structures or occurs in noisy environments. Previous work has linked cognitive abilities and the engagement of domain-general cognitive resources, such as the cingulo-opercular and frontoparietal brain networks, in response to challenging speech. However, the degree to which these networks can support comprehension remains unclear. Furthermore, how hearing loss may be related to the cognitive resources recruited during challenging speech comprehension is unknown. This dissertation investigated how hearing, cognitive performance, and functional brain networks contribute to challenging auditory speech comprehension in older adults. Experiment 1 characterized how age and hearing loss modulate resting-state functional connectivity between Heschl’s gyrus and several sensory and cognitive brain networks. The results indicate that older adults exhibit decreased functional connectivity between Heschl’s gyrus and sensory and attention networks compared to younger adults. Within older adults, greater hearing loss was associated with increased functional connectivity between right Heschl’s gyrus and the cingulo-opercular and language networks. Experiments 2 and 3 investigated how hearing, working memory, attentional control, and fMRI measures predict comprehension of complex sentence structures and speech in noisy environments. Experiment 2 utilized resting-state functional magnetic resonance imaging (fMRI) and behavioral measures of working memory and attentional control. Experiment 3 used activation-based fMRI to examine the brain regions recruited in response to sentences with both complex structures and in noisy background environments as a function of hearing and cognitive abilities. The results suggest that working memory abilities and the functionality of the frontoparietal and language networks support the comprehension of speech in multi-speaker environments. Conversely, attentional control and the cingulo-opercular network were shown to support comprehension of complex sentence structures. Hearing loss was shown to decrease activation within right Heschl’s gyrus in response to all sentence conditions and increase activation within frontoparietal and cingulo-opercular regions. Hearing loss also was associated with poorer sentence comprehension in energetic, but not informational, masking. Together, these three experiments identify the unique contributions of cognition and brain networks that support challenging auditory speech comprehension in older adults, further probing how hearing loss affects these relationships.
ContributorsFitzhugh, Megan (Author) / (Reddy) Rogalsky, Corianne (Thesis advisor) / Baxter, Leslie C (Thesis advisor) / Azuma, Tamiko (Committee member) / Braden, Blair (Committee member) / Arizona State University (Publisher)
Created2019