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The recent spotlight on concussion has illuminated deficits in the current standard of care with regard to addressing acute and persistent cognitive signs and symptoms of mild brain injury. This stems, in part, from the diffuse nature of the injury, which tends not to produce focal cognitive or behavioral deficits

The recent spotlight on concussion has illuminated deficits in the current standard of care with regard to addressing acute and persistent cognitive signs and symptoms of mild brain injury. This stems, in part, from the diffuse nature of the injury, which tends not to produce focal cognitive or behavioral deficits that are easily identified or tracked. Indeed it has been shown that patients with enduring symptoms have difficulty describing their problems; therefore, there is an urgent need for a sensitive measure of brain activity that corresponds with higher order cognitive processing. The development of a neurophysiological metric that maps to clinical resolution would inform decisions about diagnosis and prognosis, including the need for clinical intervention to address cognitive deficits. The literature suggests the need for assessment of concussion under cognitively demanding tasks. Here, a joint behavioral- high-density electroencephalography (EEG) paradigm was employed. This allows for the examination of cortical activity patterns during speech comprehension at various levels of degradation in a sentence verification task, imposing the need for higher-order cognitive processes. Eight participants with concussion listened to true-false sentences produced with either moderately to highly intelligible noise-vocoders. Behavioral data were simultaneously collected. The analysis of cortical activation patterns included 1) the examination of event-related potentials, including latency and source localization, and 2) measures of frequency spectra and associated power. Individual performance patterns were assessed during acute injury and a return visit several months following injury. Results demonstrate a combination of task-related electrophysiology measures correspond to changes in task performance during the course of recovery. Further, a discriminant function analysis suggests EEG measures are more sensitive than behavioral measures in distinguishing between individuals with concussion and healthy controls at both injury and recovery, suggesting the robustness of neurophysiological measures during a cognitively demanding task to both injury and persisting pathophysiology.
ContributorsUtianski, Rene (Author) / Liss, Julie M (Thesis advisor) / Berisha, Visar (Committee member) / Caviness, John N (Committee member) / Dorman, Michael (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Exome sequencing was used to identify novel variants linked to amyotrophic lateral sclerosis (ALS), in a family without mutations in genes previously linked to ALS. A F115C mutation in the gene MATR3 was identified, and further examination of other ALS kindreds identified an additional three mutations in MATR3; S85C, P154S

Exome sequencing was used to identify novel variants linked to amyotrophic lateral sclerosis (ALS), in a family without mutations in genes previously linked to ALS. A F115C mutation in the gene MATR3 was identified, and further examination of other ALS kindreds identified an additional three mutations in MATR3; S85C, P154S and T622A. Matrin 3 is an RNA/DNA binding protein as well as part of the nuclear matrix. Matrin 3 interacts with TDP-43, a protein that is both mutated in some forms of ALS, and found in pathological inclusions in most ALS patients. Matrin 3 pathology, including mislocalization and rare cytoplasmic inclusions, was identified in spinal cord tissue from a patient carrying a mutation in Matrin 3, as well as sporadic ALS patients. In an effort to determine the mechanism of Matrin 3 linked ALS, the protein interactome of wild-type and ALS-linked MATR3 mutations was examined. Immunoprecipitation followed by mass spectrometry experiments were performed using NSC-34 cells expressing human wild-type or mutant Matrin 3. Gene ontology analysis identified a novel role for Matrin 3 in mRNA transport centered on proteins in the TRanscription and EXport (TREX) complex, known to function in mRNA biogenesis and nuclear export. ALS-linked mutations in Matrin 3 led to its re-distribution within the nucleus, decreased co-localization with endogenous Matrin 3 and increased co-localization with specific TREX components. Expression of disease-causing Matrin 3 mutations led to nuclear mRNA export defects of both global mRNA and more specifically the mRNA of TDP-43 and FUS. Our findings identify ALS-causing mutations in the gene MATR3, as well as a potential pathogenic mechanism attributable to MATR3 mutations and further link cellular transport defects to ALS.
ContributorsBoehringer, Ashley (Author) / Bowser, Robert (Thesis advisor) / Liss, Julie (Committee member) / Jensen, Kendall (Committee member) / Ladha, Shafeeq (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The activation of the primary motor cortex (M1) is common in speech perception tasks that involve difficult listening conditions. Although the challenge of recognizing and discriminating non-native speech sounds appears to be an instantiation of listening under difficult circumstances, it is still unknown if M1 recruitment is facilitatory of second

The activation of the primary motor cortex (M1) is common in speech perception tasks that involve difficult listening conditions. Although the challenge of recognizing and discriminating non-native speech sounds appears to be an instantiation of listening under difficult circumstances, it is still unknown if M1 recruitment is facilitatory of second language speech perception. The purpose of this study was to investigate the role of M1 associated with speech motor centers in processing acoustic inputs in the native (L1) and second language (L2), using repetitive Transcranial Magnetic Stimulation (rTMS) to selectively alter neural activity in M1. Thirty-six healthy English/Spanish bilingual subjects participated in the experiment. The performance on a listening word-to-picture matching task was measured before and after real- and sham-rTMS to the orbicularis oris (lip muscle) associated M1. Vowel Space Area (VSA) obtained from recordings of participants reading a passage in L2 before and after real-rTMS, was calculated to determine its utility as an rTMS aftereffect measure. There was high variability in the aftereffect of the rTMS protocol to the lip muscle among the participants. Approximately 50% of participants showed an inhibitory effect of rTMS, evidenced by smaller motor evoked potentials (MEPs) area, whereas the other 50% had a facilitatory effect, with larger MEPs. This suggests that rTMS has a complex influence on M1 excitability, and relying on grand-average results can obscure important individual differences in rTMS physiological and functional outcomes. Evidence of motor support to word recognition in the L2 was found. Participants showing an inhibitory aftereffect of rTMS on M1 produced slower and less accurate responses in the L2 task, whereas those showing a facilitatory aftereffect of rTMS on M1 produced more accurate responses in L2. In contrast, no effect of rTMS was found on the L1, where accuracy and speed were very similar after sham- and real-rTMS. The L2 VSA measure was indicative of the aftereffect of rTMS to M1 associated with speech production, supporting its utility as an rTMS aftereffect measure. This result revealed an interesting and novel relation between cerebral motor cortex activation and speech measures.
ContributorsBarragan, Beatriz (Author) / Liss, Julie (Thesis advisor) / Berisha, Visar (Committee member) / Rogalsky, Corianne (Committee member) / Restrepo, Adelaida (Committee member) / Arizona State University (Publisher)
Created2018
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Description
A previous study demonstrated that learning to lift an object is context-based and that in the presence of both the memory and visual cues, the acquired sensorimotor memory to manipulate an object in one context interferes with the performance of the same task in presence of visual information about a

A previous study demonstrated that learning to lift an object is context-based and that in the presence of both the memory and visual cues, the acquired sensorimotor memory to manipulate an object in one context interferes with the performance of the same task in presence of visual information about a different context (Fu et al, 2012).
The purpose of this study is to know whether the primary motor cortex (M1) plays a role in the sensorimotor memory. It was hypothesized that temporary disruption of the M1 following the learning to minimize a tilt using a ‘L’ shaped object would negatively affect the retention of sensorimotor memory and thus reduce interference between the memory acquired in one context and the visual cues to perform the same task in a different context.
Significant findings were shown in blocks 1, 2, and 4. In block 3, subjects displayed insignificant amount of learning. However, it cannot be concluded that there is full interference in block 3. Therefore, looked into 3 effects in statistical analysis: the main effects of the blocks, the main effects of the trials, and the effects of the blocks and trials combined. From the block effects, there is a p-value of 0.001, and from the trial effects, the p-value is less than 0.001. Both of these effects indicate that there is learning occurring. However, when looking at the blocks * trials effects, we see a p-value of 0.002 < 0.05 indicating significant interaction between sensorimotor memories. Based on the results that were found, there is a presence of interference in all the blocks but not enough to justify the use of TMS in order to reduce interference because there is a partial reduction of interference from the control experiment. It is evident that the time delay might be the issue between context switches. By reducing the time delay between block 2 and 3 from 10 minutes to 5 minutes, I will hope to see significant learning to occur from the first trial to the second trial.
ContributorsHasan, Salman Bashir (Author) / Santello, Marco (Thesis director) / Kleim, Jeffrey (Committee member) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Studies in Second Language Acquisition and Neurolinguistics have argued that adult learners when dealing with certain phonological features of L2, such as segmental and suprasegmental ones, face problems of articulatory placement (Esling, 2006; Abercrombie, 1967) and somatosensory stimulation (Guenther, Ghosh, & Tourville, 2006; Waldron, 2010). These studies have argued that

Studies in Second Language Acquisition and Neurolinguistics have argued that adult learners when dealing with certain phonological features of L2, such as segmental and suprasegmental ones, face problems of articulatory placement (Esling, 2006; Abercrombie, 1967) and somatosensory stimulation (Guenther, Ghosh, & Tourville, 2006; Waldron, 2010). These studies have argued that adult phonological acquisition is a complex matter that needs to be informed by a specialized sensorimotor theory of speech acquisition. They further suggested that traditional pronunciation pedagogy needs to be enhanced by an approach to learning offering learners fundamental and practical sensorimotor tools to advance the quality of L2 speech acquisition.



This foundational study designs a sensorimotor approach to pronunciation pedagogy and tests its effect on the L2 speech of five adult (late) learners of American English. Throughout an eight week classroom experiment, participants from different first language backgrounds received instruction on Articulatory Settings (Honickman, 1964) and the sensorimotor mechanism of speech acquisition (Waldron 2010; Guenther et al., 2006). In addition, they attended five adapted lessons of the Feldenkrais technique (Feldenkrais, 1972) designed to develop sensorimotor awareness of the vocal apparatus and improve the quality of L2 speech movement. I hypothesize that such sensorimotor learning triggers overall positive changes in the way L2 learners deal with speech articulators for L2 and that over time they develop better pronunciation.

After approximately eight hours of intervention, analysis of results shows participants’ improvement in speech rate, degree of accentedness, and speaking confidence, but mixed changes in word intelligibility and vowel space area. Albeit not statistically significant (p >.05), these results suggest that such a sensorimotor approach to L2 phonological acquisition warrants further consideration and investigation for use in the L2 classroom.
ContributorsLima, J. Alberto S., Jr (Author) / Pruitt, Kathryn (Thesis advisor) / Gelderen, Elly van (Thesis advisor) / Liss, Julie (Committee member) / James, Mark (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Audiovisual (AV) integration is a fundamental component of face-to-face communication. Visual cues generally aid auditory comprehension of communicative intent through our innate ability to “fuse” auditory and visual information. However, our ability for multisensory integration can be affected by damage to the brain. Previous neuroimaging studies have indicated the superior

Audiovisual (AV) integration is a fundamental component of face-to-face communication. Visual cues generally aid auditory comprehension of communicative intent through our innate ability to “fuse” auditory and visual information. However, our ability for multisensory integration can be affected by damage to the brain. Previous neuroimaging studies have indicated the superior temporal sulcus (STS) as the center for AV integration, while others suggest inferior frontal and motor regions. However, few studies have analyzed the effect of stroke or other brain damage on multisensory integration in humans. The present study examines the effect of lesion location on auditory and AV speech perception through behavioral and structural imaging methodologies in 41 left-hemisphere participants with chronic focal cerebral damage. Participants completed two behavioral tasks of speech perception: an auditory speech perception task and a classic McGurk paradigm measuring congruent (auditory and visual stimuli match) and incongruent (auditory and visual stimuli do not match, creating a “fused” percept of a novel stimulus) AV speech perception. Overall, participants performed well above chance on both tasks. Voxel-based lesion symptom mapping (VLSM) across all 41 participants identified several regions as critical for speech perception depending on trial type. Heschl’s gyrus and the supramarginal gyrus were identified as critical for auditory speech perception, the basal ganglia was critical for speech perception in AV congruent trials, and the middle temporal gyrus/STS were critical in AV incongruent trials. VLSM analyses of the AV incongruent trials were used to further clarify the origin of “errors”, i.e. lack of fusion. Auditory capture (auditory stimulus) responses were attributed to visual processing deficits caused by lesions in the posterior temporal lobe, whereas visual capture (visual stimulus) responses were attributed to lesions in the anterior temporal cortex, including the temporal pole, which is widely considered to be an amodal semantic hub. The implication of anterior temporal regions in AV integration is novel and warrants further study. The behavioral and VLSM results are discussed in relation to previous neuroimaging and case-study evidence; broadly, our findings coincide with previous work indicating that multisensory superior temporal cortex, not frontal motor circuits, are critical for AV integration.
ContributorsCai, Julia (Author) / Rogalsky, Corianne (Thesis advisor) / Azuma, Tamiko (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2017
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This dissertation explores applications of machine learning methods in service of the design of screening tests, which are ubiquitous in applications from social work, to criminology, to healthcare. In the first part, a novel Bayesian decision theory framework is presented for designing tree-based adaptive tests. On an application to youth

This dissertation explores applications of machine learning methods in service of the design of screening tests, which are ubiquitous in applications from social work, to criminology, to healthcare. In the first part, a novel Bayesian decision theory framework is presented for designing tree-based adaptive tests. On an application to youth delinquency in Honduras, the method produces a 15-item instrument that is almost as accurate as a full-length 150+ item test. The framework includes specific considerations for the context in which the test will be administered, and provides uncertainty quantification around the trade-offs of shortening lengthy tests. In the second part, classification complexity is explored via theoretical and empirical results from statistical learning theory, information theory, and empirical data complexity measures. A simulation study that explicitly controls two key aspects of classification complexity is performed to relate the theoretical and empirical approaches. Throughout, a unified language and notation that formalizes classification complexity is developed; this same notation is used in subsequent chapters to discuss classification complexity in the context of a speech-based screening test. In the final part, the relative merits of task and feature engineering when designing a speech-based cognitive screening test are explored. Through an extensive classification analysis on a clinical speech dataset from patients with normal cognition and Alzheimer’s disease, the speech elicitation task is shown to have a large impact on test accuracy; carefully performed task and feature engineering are required for best results. A new framework for objectively quantifying speech elicitation tasks is introduced, and two methods are proposed for automatically extracting insights into the aspects of the speech elicitation task that are driving classification performance. The dissertation closes with recommendations for how to evaluate the obtained insights and use them to guide future design of speech-based screening tests.
ContributorsKrantsevich, Chelsea (Author) / Hahn, P. Richard (Thesis advisor) / Berisha, Visar (Committee member) / Lopes, Hedibert (Committee member) / Renaut, Rosemary (Committee member) / Zheng, Yi (Committee member) / Arizona State University (Publisher)
Created2023
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Parkinson’s Disease is one of the most complicated and abundantneurodegenerative diseases in the world. Previous analysis of Parkinson’s disease has identified both speech and gait deficits throughout progression of the disease. There has been minimal research looking into the correlation between both the speech and gait deficits in those diagnosed with Parkinson’s. There

Parkinson’s Disease is one of the most complicated and abundantneurodegenerative diseases in the world. Previous analysis of Parkinson’s disease has identified both speech and gait deficits throughout progression of the disease. There has been minimal research looking into the correlation between both the speech and gait deficits in those diagnosed with Parkinson’s. There is high indication that there is a correlation between the two given the similar pathology and origins of both deficits. This exploratory study aims to establish correlation between both the gait and speech deficits in those diagnosed with Parkinson’s disease. Using previously identified motor and speech measurements and tasks, I conducted a correlational study of individuals with Parkinson’s disease at baseline. There were correlations between multiple speech and gait variability outcomes. The expected correlations ranged from average harmonics-to-noise ratio values against anticipatory postural adjustments-lateral peak distance to average shimmer values against anticipatory postural adjustments-lateral peak distance. There were also unexpected outcomes that ranged from F2 variability against the average number of steps in a turn to intensity variability against step duration variability. I also analyzed the speech changes over 1 year as a secondary outcome of the study. Finally, I found that averages and variabilities increased over 1 year regarding speech primary outcomes. This study serves as a basis for further treatment that may be able to simultaneously treat both speech and gait deficits in those diagnosed with Parkinson’s. The exploratory study also indicates multiple targets for further investigation to better understand cohesive and compensatory mechanisms.
ContributorsBelnavis, Alexander Salvador (Author) / Peterson, Daniel (Thesis advisor) / Daliri, Ayoub (Committee member) / Berisha, Visar (Committee member) / Arizona State University (Publisher)
Created2022
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The brain uses the somatosensory system to interact with the environment and control movements. Additionally, many movement disorders are associated with deficits in the somatosensory sensory system. Thus, understanding the somatosensory system is essential for developing treatments for movement disorders. Previous studies have extensively examined the role of the somatosensory

The brain uses the somatosensory system to interact with the environment and control movements. Additionally, many movement disorders are associated with deficits in the somatosensory sensory system. Thus, understanding the somatosensory system is essential for developing treatments for movement disorders. Previous studies have extensively examined the role of the somatosensory system in controlling the lower and upper extremities; however, little is known about the contributions of the orofacial somatosensory system. The overall goal of this study was to determine factors that influence the sensitivity of the orofacial somatosensory system. To measure the somatosensory system's sensitivity, transcutaneous electrical current stimulation was applied to the skin overlaying the trigeminal nerve on the lower portion of the face. After applying stimulation, participants' sensitivity was determined through the detection of the electrical stimuli (i.e., perceptual threshold). The data analysis focused on the impact of (1) stimulation parameters, (2) electrode placement, and (3) motor tasks on the perceptual threshold. The results showed that, as expected, stimulation parameters (such as stimulation frequency and duration) influenced perceptual thresholds. However, electrode placement (left vs. right side of the face) and motor tasks (lip contraction vs. rest) did not influence perceptual thresholds. Overall, these findings have important implications for designing and developing therapeutic neuromodulation techniques based on trigeminal nerve stimulation.
ContributorsKhoury, Maya Elie (Author) / Daliri, Ayoub (Thesis advisor) / Patten, Jake (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2022
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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