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Autism spectrum disorder (ASD) is a developmental neuropsychiatric condition with early childhood onset, thus most research has focused on characterizing brain function in young individuals. Little is understood about brain function differences in middle age and older adults with ASD, despite evidence of persistent and worsening cognitive symptoms. Functional Magnetic

Autism spectrum disorder (ASD) is a developmental neuropsychiatric condition with early childhood onset, thus most research has focused on characterizing brain function in young individuals. Little is understood about brain function differences in middle age and older adults with ASD, despite evidence of persistent and worsening cognitive symptoms. Functional Magnetic Resonance Imaging (MRI) in younger persons with ASD demonstrate that large-scale brain networks containing the prefrontal cortex are affected. A novel, threshold-selection-free graph theory metric is proposed as a more robust and sensitive method for tracking brain aging in ASD and is compared against five well-accepted graph theoretical analysis methods in older men with ASD and matched neurotypical (NT) participants. Participants were 27 men with ASD (52 +/- 8.4 years) and 21 NT men (49.7 +/- 6.5 years). Resting-state functional MRI (rs-fMRI) scans were collected for six minutes (repetition time=3s) with eyes closed. Data was preprocessed in SPM12, and Data Processing Assistant for Resting-State fMRI (DPARSF) was used to extract 116 regions-of-interest defined by the automated anatomical labeling (AAL) atlas. AAL regions were separated into six large-scale brain networks. This proposed metric is the slope of a monotonically decreasing convergence function (Integrated Persistent Feature, IPF; Slope of the IPF, SIP). Results were analyzed in SPSS using ANCOVA, with IQ as a covariate. A reduced SIP was in older men with ASD, compared to NT men, in the Default Mode Network [F(1,47)=6.48; p=0.02; 2=0.13] and Executive Network [F(1,47)=4.40; p=0.04; 2=0.09], a trend in the Fronto-Parietal Network [F(1,47)=3.36; p=0.07; 2=0.07]. There were no differences in the non-prefrontal networks (Sensory motor network, auditory network, and medial visual network). The only other graph theory metric to reach significance was network diameter in the Default Mode Network [F(1,47)=4.31; p=0.04; 2=0.09]; however, the effect size for the SIP was stronger. Modularity, Betti number, characteristic path length, and eigenvalue centrality were all non-significant. These results provide empirical evidence of decreased functional network integration in pre-frontal networks of older adults with ASD and propose a useful biomarker for tracking prognosis of aging adults with ASD to enable more informed treatment, support, and care methods for this growing population.
ContributorsCatchings, Michael Thomas (Author) / Braden, Brittany B (Thesis advisor) / Greger, Bradley (Thesis advisor) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements

Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements of the hand (grasp) but not individuated movements of the finger (finger abduction) were susceptible. It was suggested that this resulted from different neural mechanisms involved in each task; however it is possible this was the result of task familiarity. The objective of this study was to evaluate a more familiar individuated finger movement, typing, to determine if this task was susceptible to SEM. We hypothesized that typing movements will be susceptible to SEM in all fingers. These results indicate that individuated movements of the fingers are susceptible to SEM when the task involves a more familiar task, since the electromyogram (EMG) latency is faster in SCM+ trials compared to SCM- trials. However, the middle finger does not show a difference in terms of the keystroke voltage signal, suggesting the middle finger is less susceptible to SEM. Given that SEM is thought to be mediated by the brainstem, specifically the reticulospinal tract, this suggest that the brainstem may play a role in movements of the distal limb when those movements are very familiar, and the independence of each finger might also have a significant on the effect of SEM. Further research includes understanding SEM in fingers in the stroke population. The implications of this research can impact the way upper extremity rehabilitation is delivered.
ContributorsQuezada Valladares, Maria Jose (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed

Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed with difficulty. While the presence of SEM in the stroke survivor population advances scientific understanding of movement capabilities following a stroke, published studies using the SEM phenomenon only examined one joint. The ability of SEM to generate multi-jointed movements is understudied and consequently limits SEM as a potential therapy tool. In order to apply SEM as a therapy tool however, the biomechanics of the arm in multi-jointed movement planning and execution must be better understood. Thus, the objective of our study was to evaluate if SEM could elicit multi-joint reaching movements that were accurate in an unrestrained, two-dimensional workspace. Data was collected from ten subjects with no previous neck, arm, or brain injury. Each subject performed a reaching task to five Targets that were equally spaced in a semi-circle to create a two-dimensional workspace. The subject reached to each Target following a sequence of two non-startling acoustic stimuli cues: "Get Ready" and "Go". A loud acoustic stimuli was randomly substituted for the "Go" cue. We hypothesized that SEM is accessible and accurate for unrestricted multi-jointed reaching tasks in a functional workspace and is therefore independent of movement direction. Our results found that SEM is possible in all five Target directions. The probability of evoking SEM and the movement kinematics (i.e. total movement time, linear deviation, average velocity) to each Target are not statistically different. Thus, we conclude that SEM is possible in a functional workspace and is not dependent on where arm stability is maximized. Moreover, coordinated preparation and storage of a multi-jointed movement is indeed possible.
ContributorsOssanna, Meilin Ryan (Author) / Honeycutt, Claire (Thesis director) / Schaefer, Sydney (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized

A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Aim 1a, the effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three participants (22.75±4.6 y/o), performed a visuomotor rotation task and received TNS before encountering rotation of hand visual feedback. In Aim 1b, TNS at 3 kHz, which has been shown to be more tolerable at higher current intensities, was evaluated in 42 additional subjects (23.4±4.6 y/o). Results indicated that 3 kHz stimulation accelerated learning while 60 Hz stimulation slowed learning, suggesting a frequency-dependent effect on learning. In Aim 2, the effect of online TNS using 120 and 60 Hz were characterized to determine if this protocol would deliver better outcomes. Sixty-three participants (23.2±3.9 y/o) received either TNS or sham concurrently with perturbed visual feedback. Results showed no significant differences among groups. However, a cross-study comparison of results obtained with 60 Hz offline TNS showed a statistically significant improvement in learning rates with online stimulation relative to offline, suggesting a timing-dependent effect on learning. In Aim 3, TNS and ONS were compared using the best protocol from previous aims (offline 3 kHz). Additionally, concurrent stimulation of both nerves was explored to look for potential synergistic effects. Eighty-four participants (22.9±3.2 y/o) were assigned to one of four groups: TNS, ONS, TNS+ONS, and sham. Visual inspection of learning curves revealed that the ONS group demonstrated the fastest learning among groups. However, statistical analyses did not confirm this observation. In addition, the TNS+ONS group appeared to learn faster than the sham and TNS groups but slower than the ONS only group, suggesting no synergistic effects using this protocol, as initially hypothesized. The results provide new information on the potential use of TNS and ONS in neurorehabilitation and performance enhancement in the motor domain.
ContributorsArias, Diego (Author) / Buneo, Christopher (Thesis advisor) / Schaefer, Sydney (Committee member) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2023
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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

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
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Description
Stroke is a debilitating disorder and 75% of individuals with stroke (iwS) have upper extremity deficits. IwS are prescribed therapies to enhance upper-extremity mobility, but current most effective therapies have minimum requirements that the individuals with severe impairment do not meet. Thus, there is a need to enhance the therapies.

Stroke is a debilitating disorder and 75% of individuals with stroke (iwS) have upper extremity deficits. IwS are prescribed therapies to enhance upper-extremity mobility, but current most effective therapies have minimum requirements that the individuals with severe impairment do not meet. Thus, there is a need to enhance the therapies. Recent studies have shown that StartReact -the involuntary release of a planned movement, triggered by a startling stimulus (e.g., loud sound)- elicits faster and larger muscle activation in iwS compared to voluntary-initiated movement. However, StartReact has been only cursorily studied to date and there are some gaps in the StartReact knowledge. Previous studies have only evaluated StartReact on single-jointed movements in iwS, ignoring more functional tasks. IwS usually have abnormal flexor activity during extension tasks and abnormal muscle synergy especially during multi-jointed tasks; therefore, it is unknown 1) if more complex multi-jointed reach movements are susceptible to StartReact, and 2) if StartReact multi-jointed movements will be enhanced in the same way as single-jointed movements in iwS. In addition, previous studies showed that individuals with severe stroke, especially those with higher spasticity, experienced higher abnormal flexor muscle activation during StartReact trials. However, there is no study evaluating the impact of this elevated abnormal flexor activity on movement, muscle activation and muscle synergy alterations during voluntary-initiated movements after exposure to StartReact.
This dissertation evaluates StartReact and the voluntary trials before and after exposure to StartReact during a point-to-point multi-jointed reach task to three different targets covering a large workspace. The results show that multi-jointed reach tasks are susceptible to StartReact in iwS and the distance, muscle and movement onset speed, and muscle activations percentages and amplitude increase during StartReact trials. In addition, the distance, accuracy, muscle and movement onsets speeds, and muscle synergy similarity indices to the norm synergies increase during the voluntary-initiated trials after exposure to StartReact. Overall, this dissertation shows that exposure to StartReact did not impair voluntary-initiated movement and muscle synergy, but even improved them. Therefore, this study suggests that StartReact is safe for more investigations in training studies and therapy.
ContributorsRahimiTouranposhti, Marziye (Author) / Honeycutt, Claire F. (Thesis advisor) / Roh, Jinsook (Committee member) / Berman, Spring (Committee member) / Lee, Hyunglae (Committee member) / Marvi, Hamid (Committee member) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Previous work indicates that structural changes in the right hemisphere following left hemisphere stroke may be related to language abilities. However, the mechanisms behind this relationship remain unclear, particularly regarding the relative contributions of gray and white matter. The present study examined how structural and diffusion measures in the right

Previous work indicates that structural changes in the right hemisphere following left hemisphere stroke may be related to language abilities. However, the mechanisms behind this relationship remain unclear, particularly regarding the relative contributions of gray and white matter. The present study examined how structural and diffusion measures in the right hemisphere differ between chronic left hemisphere stroke survivors and matched control subjects, and the relationships between language and cognition measures and these right hemisphere measures. T1-weighted MRI, diffusion tensor images (DTI), and a battery of cognitive tests were obtained from 27 chronic left hemisphere stroke survivors and 44 neurologically intact matched control participants. Cortical and volumetric measures of gray and white matter in regions of interest were obtained from the T1 images and compared between groups, and correlated with behavioral measures. Tract-Based Spatial Statistics and tractography methods from the DTI were examined in a similar manner. The T1 MRI-based analyses revealed that the stroke survivors did not differ from the control group in any of the gray or white matter volume measurements. The cortical thickness and mean curvature analyses identified right lateral frontal and insular ROIs exhibiting thinner and greater curvature (an indication of atrophy) in the left hemisphere stroke survivors compared to controls. The DTI-based results showed that the stroke survivors had lower fractional anisotropy and fewer reconstructed fibers in the right language ventral-stream tracts. Regarding correlations between the right hemisphere measures and behavioral performance, there were no significant results within the DTI data, and only one significant result in the gray matter analyses: faster processing speed was correlated with greater cortical thickness in the right frontal cortex in chronic left hemisphere stroke survivors. Overall, the present study provides support for the idea that the right hemisphere exhibits post-stroke changes, particularly in right dorsal stream gray matter and the ventral stream’s white matter, and that these differences are not captured by T1-imaging alone; in fact, the DTI tract-specific analyses were perhaps the most revealing. Future studies are needed, perhaps incorporating functional neuroimaging, to elucidate how these right hemisphere differences in left hemisphere stroke survivors is related to language recovery.
ContributorsHsueh, Yi-Ting (Author) / Reddy, Corianne (Thesis advisor) / Braden, Brittany (Committee member) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Stroke is the leading cause of long-term disability in the U.S., with up to 60% of strokescausing speech loss. Individuals with severe stroke, who require the most frequent, intense speech therapy, often cannot adhere to treatments due to high cost and low success rates. Therefore, the ability to make functionally

Stroke is the leading cause of long-term disability in the U.S., with up to 60% of strokescausing speech loss. Individuals with severe stroke, who require the most frequent, intense speech therapy, often cannot adhere to treatments due to high cost and low success rates. Therefore, the ability to make functionally significant changes in individuals with severe post- stroke aphasia remains a key challenge for the rehabilitation community. This dissertation aimed to evaluate the efficacy of Startle Adjuvant Rehabilitation Therapy (START), a tele-enabled, low- cost treatment, to improve quality of life and speech in individuals with severe-to-moderate stroke. START is the exposure to startling acoustic stimuli during practice of motor tasks in individuals with stroke. START increases the speed and intensity of practice in severely impaired post-stroke reaching, with START eliciting muscle activity 2-3 times higher than maximum voluntary contraction. Voluntary reaching distance, onset, and final accuracy increased after a session of START, suggesting a rehabilitative effect. However, START has not been evaluated during impaired speech. The objective of this study is to determine if impaired speech can be elicited by startling acoustic stimuli, and if three days of START training can enhance clinical measures of moderate to severe post-stroke aphasia and apraxia of speech. This dissertation evaluates START in 42 individuals with post-stroke speech impairment via telehealth in a Phase 0 clinical trial. Results suggest that impaired speech can be elicited by startling acoustic stimuli and that START benefits individuals with severe-to-moderate post-stroke impairments in both linguistic and motor speech domains. This fills an important gap in aphasia care, as many speech therapies remain ineffective and financially inaccessible for patients with severe deficits. START is effective, remotely delivered, and may likely serve as an affordable adjuvant to traditional therapy for those that have poor access to quality care.
ContributorsSwann, Zoe Elisabeth (Author) / Honeycutt, Claire F (Thesis advisor) / Daliri, Ayoub (Committee member) / Rogalsky, Corianne (Committee member) / Liss, Julie (Committee member) / Schaefer, Sydney (Committee member) / Arizona State University (Publisher)
Created2022
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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

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