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.

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.

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.

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.

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.

Background: In the United States, approximately 50,000 teens with Autism Spectrum Disorder (ASD) age into adulthood every year (Shattuck et al., 2012). A hallmark symptom of ASD includes pronounced difficulties in social interactions and verbal and nonverbal communication (Lai, Lombardo, & Baron-Cohen, 2014). These social cognition difficulties consist of difficulties interpreting social cues, employing appropriate adaptive behavioral responses in various social contexts, as well as the ability to interpret emotions and mental states of others, known as theory of mind (TOM; Premack & Woodruff, 1978). In neurotypical (NT) adults, women perform better on social cognition tasks and difficulties become more prevalent with age, however little is known how sex differences and aging may impact social cognition in adults with ASD (Carstensen, Fung, & Charles 2003).

Objective: This research intended to characterize the influence of sex and age on social cognition in adults with ASD using an adult sample. We hypothesized Reading the Mind in the Eyes (RME) scores would be lower in adults with ASD, with a stronger relationship between decreasing performance aging effects compared to NTs. Additionally, we hypothesized deficits would be more severe in in males with ASD compared to females with ASD.

Methods: The RME task was administered to 181 adults to quantify ToM abilities. The participants consisted of 100 adults with ASD (69 males, 32 females; age range: 18-71, mean=39.45±1.613) and matched 81 NT adults (47 males, 34 females; age range: 18-70, mean=41.51±1.883). Multiple regression analyses examined interactions between diagnosis and age, diagnosis and sex, and diagnosis by age by sex. Exploratory within group analyses assessed 1) sex differences using ANCOVA, and 2) associations with age using Pearson correlation in SPSS.

Results: We found that NT adults performed better on the RME task than adults with ASD. Worse performance on the RME task correlated with greater age for the NT, but not ASD. Additionally, no influence of sex on RME scores was identified.

Discussion: These results are consistent with other studies indicate social cognition deficits in adults with ASD compared to NT adults. Additionally, we replicated findings that suggest ToM performance declines with age in NT adults. Fewer social relationships, smaller social networks, and reduced social engagement have been associated with aging in both NTs and individuals with ASD (Pratt & Norris, 1994). However, our cross-sectional sample suggests ToM abilities may not decline with age in adults with ASD as hypothesized. Longitudinal studies are needed to corroborate these findings. Further developments in this line of research may inform novel interventions tailored toward the growing population of adults with ASD. Ultimately, our research aims to improve quality of life across the lifespan for an already vulnerable population.

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.

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.