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Description
Our eyes never stop moving, even during attempted gaze fixation. Fixational eye movements, which include tremor, drift, and microsaccades, are necessary to prevent retinal image adaptation, but may also result in unstable vision. Fortunately, the nervous system can suppress the retinal displacements induced by fixational eye movements and consequently kee

Our eyes never stop moving, even during attempted gaze fixation. Fixational eye movements, which include tremor, drift, and microsaccades, are necessary to prevent retinal image adaptation, but may also result in unstable vision. Fortunately, the nervous system can suppress the retinal displacements induced by fixational eye movements and consequently keep our vision stable. The neural correlates of perceptual suppression during fixational eye movements are controversial. Also, the contribution of retinal versus extraretinal inputs to microsaccade-induced neuronal responses in the primary visual cortex (i.e. area V1) remain unclear. Here I show that V1 neuronal responses to microsaccades are different from those to stimulus motions simulating microsaccades. Responses to microsaccades consist of an initial excitatory component followed by an inhibitory component, which may be attributed to retinal and extraretinal signals, respectively. I also discuss the effects of the fixation target's size and luminance on microsaccade properties. Fixation targets are frequently used in psychophysical and electrophysiological research, and may have uncontrolled influences on experimental results. I found that microsaccade rates and magnitudes change linearly with fixation target size, but not with fixation target luminance. Finally, I present ion a novel variation of the Ouchi-Spillmann illusion, in which fixational eye movements may play a role.
ContributorsNajafian Jazi, Ali (Author) / Buneo, Christopher (Thesis advisor) / Martinez-Conde, Susana (Thesis advisor) / Macknik, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Intracortical microstimulation (ICMS) within somatosensory cortex can produce artificial sensations including touch, pressure, and vibration. There is significant interest in using ICMS to provide sensory feedback for a prosthetic limb. In such a system, information recorded from sensors on the prosthetic would be translated into electrical stimulation and delivered directly

Intracortical microstimulation (ICMS) within somatosensory cortex can produce artificial sensations including touch, pressure, and vibration. There is significant interest in using ICMS to provide sensory feedback for a prosthetic limb. In such a system, information recorded from sensors on the prosthetic would be translated into electrical stimulation and delivered directly to the brain, providing feedback about features of objects in contact with the prosthetic. To achieve this goal, multiple simultaneous streams of information will need to be encoded by ICMS in a manner that produces robust, reliable, and discriminable sensations. The first segment of this work focuses on the discriminability of sensations elicited by ICMS within somatosensory cortex. Stimulation on multiple single electrodes and near-simultaneous stimulation across multiple electrodes, driven by a multimodal tactile sensor, were both used in these experiments. A SynTouch BioTac sensor was moved across a flat surface in several directions, and a subset of the sensor's electrode impedance channels were used to drive multichannel ICMS in the somatosensory cortex of a non-human primate. The animal performed a behavioral task during this stimulation to indicate the discriminability of sensations evoked by the electrical stimulation. The animal's responses to ICMS were somewhat inconsistent across experimental sessions but indicated that discriminable sensations were evoked by both single and multichannel ICMS. The factors that affect the discriminability of stimulation-induced sensations are not well understood, in part because the relationship between ICMS and the neural activity it induces is poorly defined. The second component of this work was to develop computational models that describe the populations of neurons likely to be activated by ICMS. Models of several neurons were constructed, and their responses to ICMS were calculated. A three-dimensional cortical model was constructed using these cell models and used to identify the populations of neurons likely to be recruited by ICMS. Stimulation activated neurons in a sparse and discontinuous fashion; additionally, the type, number, and location of neurons likely to be activated by stimulation varied with electrode depth.
ContributorsOverstreet, Cynthia K (Author) / Helms Tillery, Stephen I (Thesis advisor) / Santos, Veronica (Committee member) / Buneo, Christopher (Committee member) / Otto, Kevin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions

Humans' ability to perform fine object and tool manipulation is a defining feature of their sensorimotor repertoire. How the central nervous system builds and maintains internal representations of such skilled hand-object interactions has attracted significant attention over the past three decades. Nevertheless, two major gaps exist: a) how digit positions and forces are coordinated during natural manipulation tasks, and b) what mechanisms underlie the formation and retention of internal representations of dexterous manipulation. This dissertation addresses these two questions through five experiments that are based on novel grip devices and experimental protocols. It was found that high-level representation of manipulation tasks can be learned in an effector-independent fashion. Specifically, when challenged by trial-to-trial variability in finger positions or using digits that were not previously engaged in learning the task, subjects could adjust finger forces to compensate for this variability, thus leading to consistent task performance. The results from a follow-up experiment conducted in a virtual reality environment indicate that haptic feedback is sufficient to implement the above coordination between digit position and forces. However, it was also found that the generalizability of a learned manipulation is limited across tasks. Specifically, when subjects learned to manipulate the same object across different contexts that require different motor output, interference was found at the time of switching contexts. Data from additional studies provide evidence for parallel learning processes, which are characterized by different rates of decay and learning. These experiments have provided important insight into the neural mechanisms underlying learning and control of object manipulation. The present findings have potential biomedical applications including brain-machine interfaces, rehabilitation of hand function, and prosthetics.
ContributorsFu, Qiushi (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Santos, Veronica (Committee member) / Artemiadis, Panagiotis (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present

Reaching movements are subject to noise in both the planning and execution phases of movement production. Although the effects of these noise sources in estimating and/or controlling endpoint position have been examined in many studies, the independent effects of limb configuration on endpoint variability have been largely ignored. The present study investigated the effects of arm configuration on the interaction between planning noise and execution noise. Subjects performed reaching movements to three targets located in a frontal plane. At the starting position, subjects matched one of two desired arm configuration 'templates' namely "adducted" and "abducted". These arm configurations were obtained by rotations along the shoulder-hand axis, thereby maintaining endpoint position. Visual feedback of the hand was varied from trial to trial, thereby increasing uncertainty in movement planning and execution. It was hypothesized that 1) pattern of endpoint variability would be dependent on arm configuration and 2) that these differences would be most apparent in conditions without visual feedback. It was found that there were differences in endpoint variability between arm configurations in both visual conditions, but these differences were much larger when visual feedback was withheld. The overall results suggest that patterns of endpoint variability are highly dependent on arm configuration, particularly in the absence of visual feedback. This suggests that in the presence of vision, movement planning in 3D space is performed using coordinates that are largely arm configuration independent (i.e. extrinsic coordinates). In contrast, in the absence of vision, movement planning in 3D space reflects a substantial contribution of intrinsic coordinates.
ContributorsLakshmi Narayanan, Kishor (Author) / Buneo, Christopher (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
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Description
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
Learning by trial-and-error requires retrospective information that whether a past action resulted in a rewarded outcome. Previous outcome in turn may provide information to guide future behavioral adjustment. But the specific contribution of this information to learning a task and the neural representations during the trial-and-error learning process is not

Learning by trial-and-error requires retrospective information that whether a past action resulted in a rewarded outcome. Previous outcome in turn may provide information to guide future behavioral adjustment. But the specific contribution of this information to learning a task and the neural representations during the trial-and-error learning process is not well understood. In this dissertation, such learning is analyzed by means of single unit neural recordings in the rats' motor agranular medial (AGm) and agranular lateral (AGl) while the rats learned to perform a directional choice task. Multichannel chronic recordings using implanted microelectrodes in the rat's brain were essential to this study. Also for fundamental scientific investigations in general and for some applications such as brain machine interface, the recorded neural waveforms need to be analyzed first to identify neural action potentials as basic computing units. Prior to analyzing and modeling the recorded neural signals, this dissertation proposes an advanced spike sorting system, the M-Sorter, to extract the action potentials from raw neural waveforms. The M-Sorter shows better or comparable performance compared with two other popular spike sorters under automatic mode. With the sorted action potentials in place, neuronal activity in the AGm and AGl areas in rats during learning of a directional choice task is examined. Systematic analyses suggest that rat's neural activity in AGm and AGl was modulated by previous trial outcomes during learning. Single unit based neural dynamics during task learning are described in detail in the dissertation. Furthermore, the differences in neural modulation between fast and slow learning rats were compared. The results show that the level of neural modulation of previous trial outcome is different in fast and slow learning rats which may in turn suggest an important role of previous trial outcome encoding in learning.
ContributorsYuan, Yu'an (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Chae, Junseok (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Animals learn to choose a proper action among alternatives according to the circumstance. Through trial-and-error, animals improve their odds by making correct association between their behavioral choices and external stimuli. While there has been an extensive literature on the theory of learning, it is still unclear how individual neurons and

Animals learn to choose a proper action among alternatives according to the circumstance. Through trial-and-error, animals improve their odds by making correct association between their behavioral choices and external stimuli. While there has been an extensive literature on the theory of learning, it is still unclear how individual neurons and a neural network adapt as learning progresses. In this dissertation, single units in the medial and lateral agranular (AGm and AGl) cortices were recorded as rats learned a directional choice task. The task required the rat to make a left/right side lever press if a light cue appeared on the left/right side of the interface panel. Behavior analysis showed that rat's movement parameters during performance of directional choices became stereotyped very quickly (2-3 days) while learning to solve the directional choice problem took weeks to occur. The entire learning process was further broken down to 3 stages, each having similar number of recording sessions (days). Single unit based firing rate analysis revealed that 1) directional rate modulation was observed in both cortices; 2) the averaged mean rate between left and right trials in the neural ensemble each day did not change significantly among the three learning stages; 3) the rate difference between left and right trials of the ensemble did not change significantly either. Besides, for either left or right trials, the trial-to-trial firing variability of single neurons did not change significantly over the three stages. To explore the spatiotemporal neural pattern of the recorded ensemble, support vector machines (SVMs) were constructed each day to decode the direction of choice in single trials. Improved classification accuracy indicated enhanced discriminability between neural patterns of left and right choices as learning progressed. When using a restricted Boltzmann machine (RBM) model to extract features from neural activity patterns, results further supported the idea that neural firing patterns adapted during the three learning stages to facilitate the neural codes of directional choices. Put together, these findings suggest a spatiotemporal neural coding scheme in a rat AGl and AGm neural ensemble that may be responsible for and contributing to learning the directional choice task.
ContributorsMao, Hongwei (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Cao, Yu (Committee member) / Santello, Marco (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
Vagus nerve stimulation (VNS) has shown benefits beyond its original therapeutic application, though there is a lack of research into these benefits in healthy and athletic populations. To address this gap in the VNS literature, the present study addresses the feasibility and possible efficacy of transcutaneous VNS (tVNS) in improving

Vagus nerve stimulation (VNS) has shown benefits beyond its original therapeutic application, though there is a lack of research into these benefits in healthy and athletic populations. To address this gap in the VNS literature, the present study addresses the feasibility and possible efficacy of transcutaneous VNS (tVNS) in improving performance and various biometrics during two athletic tasks: golf tee shots and baseball pitching. Performance, cortical dynamics, anxiety measures, muscle excitation, and heart rate characteristics were assessed before and after stimulation using electroencephalography (EEG), the State-Trait Anxiety Inventory (STAI), and electrocardiography (ECG) during the baseball and golf tasks as well as electromyography (EMG) for muscle excitation in the golf participants. Golfers exhibited increased perceived quality of each repetition (independent from outcome) and an improvement in state and trait anxiety after stimulation. Golfers in the active stimulation group also showed a greater reduction in right upper trapezius muscle excitation when compared to the sham stimulation group. Baseball pitchers exhibited an increase in perceived quality of each repetition (independent from outcome) after active stimulation but not an improvement of state and trait anxiety. No significant effects of stimulation Priming, stimulation Type, or the Priming×Type interaction were seen in heart rate, EEG, or performance in the golf or baseball tasks. The present study supports the feasibility of tVNS in sports and athletic tasks and suggests the need for future research to investigate further into the effects of tVNS on the performance, psychologic, and physiologic attributes of athletes during competition.
ContributorsLindley, Kyle (Author) / Tyler, William J (Thesis advisor) / Wyckoff, Sarah (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2019