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Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the

Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control

Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI.
ContributorsHillen, Brian (Author) / Jung, Ranu (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jit (Committee member) / Jindrich, Devin (Committee member) / Yamaguchi, Gary (Committee member) / Arizona State University (Publisher)
Created2012
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Description

The distinctions between the neural resources supporting speech and music comprehension have long been studied using contexts like aphasia and amusia, and neuroimaging in control subjects. While many models have emerged to describe the different networks uniquely recruited in response to speech and music stimuli, there are still many questions,

The distinctions between the neural resources supporting speech and music comprehension have long been studied using contexts like aphasia and amusia, and neuroimaging in control subjects. While many models have emerged to describe the different networks uniquely recruited in response to speech and music stimuli, there are still many questions, especially regarding left-hemispheric strokes that disrupt typical speech-processing brain networks, and how musical training might affect the brain networks recruited for speech after a stroke. Thus, our study aims to explore some questions related to the above topics. We collected task-based functional MRI data from 12 subjects who previously experienced a left-hemispheric stroke. Subjects listened to blocks of spoken sentences and novel piano melodies during scanning to examine the differences in brain activations in response to speech and music. We hypothesized that speech stimuli would activate right frontal regions, and music stimuli would activate the right superior temporal regions more than speech (both findings not seen in previous studies of control subjects), as a result of functional changes in the brain, following the left-hemispheric stroke and particularly the loss of functionality in the left temporal lobe. We also hypothesized that the music stimuli would cause a stronger activation in right temporal cortex for participants who have had musical training than those who have not. Our results indicate that speech stimuli compared to rest activated the anterior superior temporal gyrus bilaterally and activated the right inferior frontal lobe. Music stimuli compared to rest did not activate the brain bilaterally, but rather only activated the right middle temporal gyrus. When the group analysis was performed with music experience as a covariate, we found that musical training did not affect activations to music stimuli specifically, but there was greater right hemisphere activation in several regions in response to speech stimuli as a function of more years of musical training. The results of the study agree with our hypotheses regarding the functional changes in the brain, but they conflict with our hypothesis about musical expertise. Overall, the study has generated interesting starting points for further explorations of how musical neural resources may be recruited for speech processing after damage to typical language networks.

ContributorsKarthigeyan, Vishnu R (Author) / Rogalsky, Corianne (Thesis director) / Daliri, Ayoub (Committee member) / Harrington Bioengineering Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
The International Dyslexia Association defines dyslexia as a learning disorder that is characterized by poor spelling, decoding, and word recognition abilities. There is still no known cause of dyslexia, although it is a very common disability that affects 1 in 10 people. Previous fMRI and MRI research in dyslexia has

The International Dyslexia Association defines dyslexia as a learning disorder that is characterized by poor spelling, decoding, and word recognition abilities. There is still no known cause of dyslexia, although it is a very common disability that affects 1 in 10 people. Previous fMRI and MRI research in dyslexia has explored the neural correlations of hemispheric lateralization and phonemic awareness in dyslexia. The present study investigated the underlying neurobiology of five adults with dyslexia compared to age- and sex-matched control subjects using structural and functional magnetic resonance imaging. All subjects completed a large battery of behavioral tasks as part of a larger study and underwent functional and structural MRI acquisition. This data was collected and preprocessed at the University of Washington. Analyses focused on examining the neural correlates of hemispheric lateralization, letter reversal mistakes, reduced processing speed, and phonemic awareness. There were no significant findings of hemispheric differences between subjects with dyslexia and controls. The subject making the largest amount of letter reversal errors had deactivation in their cerebellum during the fMRI language task. Cerebellar white matter volume and surface area of the premotor cortex was the largest in the individual with the slowest reaction time to tapping. Phonemic decoding efficiency had a high correlation with neural activation in the primary motor cortex during the fMRI motor task (r=0.6). Findings from the present study suggest that brain regions utilized during motor control, such as the cerebellum, premotor cortex, and primary motor cortex, may have a larger role in dyslexia then previously considered. Future studies are needed to further distinguish the role of the cerebellum and other motor regions in relation to motor control and language processing deficits related to dyslexia.
ContributorsHoulihan, Chloe Carissa Prince (Author) / Rogalsky, Corianne (Thesis director) / Peter, Beate (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Language acquisition is a phenomenon we all experience, and though it is well studied many questions remain regarding the neural bases of language. Whether a hearing speaker or Deaf signer, spoken and signed language acquisition (with eventual proficiency) develop similarly and share common neural networks. While signed language and spoken

Language acquisition is a phenomenon we all experience, and though it is well studied many questions remain regarding the neural bases of language. Whether a hearing speaker or Deaf signer, spoken and signed language acquisition (with eventual proficiency) develop similarly and share common neural networks. While signed language and spoken language engage completely different sensory modalities (visual-manual versus the more common auditory-oromotor) both languages share grammatical structures and contain syntactic intricacies innate to all languages. Thus, studies of multi-modal bilingualism (e.g. a native English speaker learning American Sign Language) can lead to a better understanding of the neurobiology of second language acquisition, and of language more broadly. For example, can the well-developed visual-spatial processing networks in English speakers support grammatical processing in sign language, as it relies heavily on location and movement? The present study furthers the understanding of the neural correlates of second language acquisition by studying late L2 normal hearing learners of American Sign Language (ASL). Twenty English speaking ASU students enrolled in advanced American Sign Language coursework participated in our functional Magnetic Resonance Imaging (fMRI) study. The aim was to identify the brain networks engaged in syntactic processing of ASL sentences in late L2 ASL learners. While many studies have addressed the neurobiology of acquiring a second spoken language, no previous study to our knowledge has examined the brain networks supporting syntactic processing in bimodal bilinguals. We examined the brain networks engaged while perceiving ASL sentences compared to ASL word lists, as well as written English sentences and word lists. We hypothesized that our findings in late bimodal bilinguals would largely coincide with the unimodal bilingual literature, but with a few notable differences including additional attention networks being engaged by ASL processing. Our results suggest that there is a high degree of overlap in sentence processing networks for ASL and English. There also are important differences in regards to the recruitment of speech comprehension, visual-spatial and domain-general brain networks. Our findings suggest that well-known sentence comprehension and syntactic processing regions for spoken languages are flexible and modality-independent.
ContributorsMickelsen, Soren Brooks (Co-author) / Johnson, Lisa (Co-author) / Rogalsky, Corianne (Thesis director) / Azuma, Tamiko (Committee member) / Howard, Pamela (Committee member) / Department of Speech and Hearing Science (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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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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Objective: Previous studies have observed that adults with dyslexia display a reduced N1 gating when exposed to repetitive stimuli. Robust gating is associated with the ability to recognize familiar stimuli and identify the stimuli that will need novel memory representations formed. This study investigates if the mismatch negativity component in

Objective: Previous studies have observed that adults with dyslexia display a reduced N1 gating when exposed to repetitive stimuli. Robust gating is associated with the ability to recognize familiar stimuli and identify the stimuli that will need novel memory representations formed. This study investigates if the mismatch negativity component in electroencephalographic-produced Event-Related Potentials (ERPs) is affected as well by diminished memory forming in adults with dyslexia. Additionally, signal/ noise processing for auditory-based memory recollection and thus word learning is explored. Methods: Nineteen adults with dyslexia and 18 adult controls participated in a classic auditory oddball electroencephalographic experiment here referred to as DIFF, to indicate that the tones differed in frequency, while incorporating a decision-making task that signified participant tonal discrimination. Mismatch Negativity (MMN) amplitudes (AMPs) and latencies were collected from ERPs. Behavioral data consisting of reaction time (RT) and accuracy (ACC) of tone choice were documented. Results: Group differences for accuracy and reaction time in the DIFF task were highly significant. The dyslexic group produced longer reaction times and with less accuracy than the control group. The Mismatch Negativity amplitude and latency collected did not differ significantly between groups, however, correlations to other variables obtained from similar studies consisting of the same participant group were observed. Linear regression models indicated predictions for accuracy and reaction time results based upon WID scores (Word Identification Test) and SWE scores (Sight Word Efficiency) respectfully. Conclusions: Neural processing speed and the ability to form permanent memory representations of auditory sound bites for retrieval is dampened in dyslexic populations. Significance: To better illuminate and understand the neural mechanisms of dyslexia, specifically auditory processing, with the goal of improving outcomes in individuals with dyslexia through more efficient therapy treatment options.
ContributorsAbrams, Gabrielle Renee (Author) / Peter, Beate (Thesis advisor) / Rogalsky, Corianne (Committee member) / Rao, Aparna (Committee member) / Arizona State University (Publisher)
Created2022
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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
Non-invasive visualization of the trigeminal nerve through advanced MR sequences and methods like tractography is important for studying anatomical and microstructural changes due to pathology like trigeminal neuralgia (TN), facial dystonia, multiple sclerosis, and for surgical pre-planning. The use of specific anatomical markers from CT, MPRAGE and cranial nerve imaging

Non-invasive visualization of the trigeminal nerve through advanced MR sequences and methods like tractography is important for studying anatomical and microstructural changes due to pathology like trigeminal neuralgia (TN), facial dystonia, multiple sclerosis, and for surgical pre-planning. The use of specific anatomical markers from CT, MPRAGE and cranial nerve imaging (CRANI) sequences, enabled successful tractography of patient-specific trajectory of the frontal, nasociliary, infraorbital, and mandibular nerve branches extending beyond the cisternal brain stem region and leading to the face. Performance of MPRAGE sequence together with the advanced T2-weighted CRANI sequence with and without a gadolinium contrast agent, was studied to characterize identification efficiency in smaller nerve structures in the extremities. A large FOV nerve visualization exam inclusive of the anatomy of all trigeminal nerve distal branches can be obtained within an acquisition time of 20 minutes using pre-contrast CRANI and MPRAGE. Post-processing with MPR and MIP images improved nerve visualization.Transcranial electrical stimulation techniques (TES) have been used for the treatment of multiple neurodegenerative diseases. These techniques involve placing electrodes on the scalp with multiple peripheral branches of the trigeminal nerve crossing directly under that may be stimulated. This was studied through hybrid computational realistic axon models. These models also facilitated studying the effects of electrode drift during experiments on the recruitment of peripheral nerves. An optimal point of lowest threshold was found while displacing the nerve horizontally i.e., the activation thresholds of both myelinated and unmyelinated axons increased when the electrodes were displaced medially and decreased to a certain extend when the electrodes were displaced laterally, after which further lateral displacement led to increase of thresholds. Inclusion of unmyelinated axons in the modeling provided the capability of finding maximum stimulation amplitude below which side effects like pain sensation may be avoided. In the case of F3 – F4 electrode montage the maximum amplitude was 2.39 mA and in case of RS – LS montage the maximum amplitude was 2.44 mA. Such modeling studies may be useful for personalization of TES devices for finding optimal positioning of electrodes with respect to target and stimulation amplitude range that minimizes side effects.
ContributorsSahu, Sulagna (Author) / Sadleir, Rosalind (Thesis advisor) / Tillery, Stephen H (Committee member) / Crook, Sharon (Committee member) / Beeman, Scott (Committee member) / Abbas, James (Committee member) / Arizona State University (Publisher)
Created2023
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Safety and efficacy of neuromodulation are influenced by abiotic factors like failure of implants, biotic factors like tissue damage, and molecular and cellular mechanisms of neuromodulation. Accelerated lifetime test (ALT) predict lifetime of implants by accelerating failure modes in controlled bench-top conditions. Current ALT models do not capture failure modes

Safety and efficacy of neuromodulation are influenced by abiotic factors like failure of implants, biotic factors like tissue damage, and molecular and cellular mechanisms of neuromodulation. Accelerated lifetime test (ALT) predict lifetime of implants by accelerating failure modes in controlled bench-top conditions. Current ALT models do not capture failure modes involving biological mechanisms. First part of this dissertation is focused on developing ALTs for predicting failure of chronically implanted tungsten stimulation electrodes. Three factors used in ALT are temperature, H2O2 concentration, and amount of charge delivered through electrode to develop a predictive model of lifetime for stimulation electrodes. Second part of this dissertation is focused on developing a novel method for evaluating tissue response to implants and electrical stimulation. Current methods to evaluate tissue damage in the brain require invasive and terminal procedures that have poor clinical translation. I report a novel non-invasive method that sampled peripheral blood monocytes (PBMCs) and used enzyme-linked immunoassay (ELISA) to assess level of glial fibrillary acidic protein (GFAP) expression and fluorescence-activated cell sorting (FACS) to quantify number of GFAP expressing PBMCs. Using this method, I was able to detect and quantify GFAP expression in PBMCs. However, there was no statistically significant difference in GFAP expression between stimulatory and non-stimulatory implants. Final part of this dissertation assessed molecular and cellular mechanisms of non-invasive ultrasound neuromodulation approach. Unlike electrical stimulation, cellular mechanisms of ultrasound-based neuromodulation are not fully known. Final part of this dissertation assessed role of mechanosensitive ion channels and neuronal nitric oxide production in cell cultures under ultrasound excitation. I used fluorescent imaging to quantify expression of nitric oxide in neuronal cell cultures in response to ultrasound stimulation. Results from these experiments indicate that neuronal nitric oxide production increased in response to ultrasound stimulation compared to control and decreased when mechanosensitive ion channels were suppressed. Two novel methods developed in this dissertation enable assessment of lifetime and safety of neuromodulation techniques that use electrical stimulation through implants. The final part of this dissertation concludes that non-invasive ultrasound neuromodulation may be mediated through neuronal nitric oxide even in absence of activation of mechanosensitive ion channels.
ContributorsVoziyanov, Vladislav (Author) / Muthuswamy, Jitendran (Thesis advisor) / Smith, Barbara (Committee member) / Greger, Bradley (Committee member) / Abbas, James (Committee member) / Okandan, Murat (Committee member) / Arizona State University (Publisher)
Created2022