Matching Items (28)
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 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
Description
Head movement is known to have the benefit of improving the accuracy of sound localization for humans and animals. Marmoset is a small bodied New World monkey species and it has become an emerging model for studying the auditory functions. This thesis aims to detect the horizontal and vertical rotation of head movement in marmoset monkeys.
Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection.
The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per second. In comparison, the natural alert signal - door opening and closing - evoked the faster head turns than other stimulus conditions. These results suggest that behaviorally relevant stimulus such as alert signals evoke faster head-turn responses in marmoset monkeys.
Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection.
The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per second. In comparison, the natural alert signal - door opening and closing - evoked the faster head turns than other stimulus conditions. These results suggest that behaviorally relevant stimulus such as alert signals evoke faster head-turn responses in marmoset monkeys.
ContributorsSimhadri, Sravanthi (Author) / Zhou, Yi (Thesis advisor) / Turaga, Pavan (Thesis advisor) / Berisha, Visar (Committee member) / Arizona State University (Publisher)
Created2014
Description
This study consisted of several related projects on dynamic spatial hearing by both human and robot listeners. The first experiment investigated the maximum number of sound sources that human listeners could localize at the same time. Speech stimuli were presented simultaneously from different loudspeakers at multiple time intervals. The maximum of perceived sound sources was close to four. The second experiment asked whether the amplitude modulation of multiple static sound sources could lead to the perception of auditory motion. On the horizontal and vertical planes, four independent noise sound sources with 60° spacing were amplitude modulated with consecutively larger phase delay. At lower modulation rates, motion could be perceived by human listeners in both cases. The third experiment asked whether several sources at static positions could serve as "acoustic landmarks" to improve the localization of other sources. Four continuous speech sound sources were placed on the horizontal plane with 90° spacing and served as the landmarks. The task was to localize a noise that was played for only three seconds when the listener was passively rotated in a chair in the middle of the loudspeaker array. The human listeners were better able to localize the sound sources with landmarks than without. The other experiments were with the aid of an acoustic manikin in an attempt to fuse binaural recording and motion data to localize sounds sources. A dummy head with recording devices was mounted on top of a rotating chair and motion data was collected. The fourth experiment showed that an Extended Kalman Filter could be used to localize sound sources in a recursive manner. The fifth experiment demonstrated the use of a fitting method for separating multiple sounds sources.
ContributorsZhong, Xuan (Author) / Yost, William (Thesis advisor) / Zhou, Yi (Committee member) / Dorman, Michael (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2015
Description
Alzheimer's disease (AD) is the most common form of dementia leading to cognitive dysfunction and memory loss as well as emotional and behavioral disorders. It is the 6th leading cause of death in United States, and the only one among top 10 death causes that cannot be prevented, cured or slowed. An estimated 5.4 million Americans live with AD, and this number is expected to triple by year 2050 as the baby boomers age. The cost of care for AD in the US is about $200 billion each year. Unfortunately, in addition to the lack of an effective treatment or AD, there is also a lack of an effective diagnosis, particularly an early diagnosis which would enable treatment to begin before significant neuronal damage has occurred.
Increasing evidence implicates soluble oligomeric forms of beta-amyloid and tau in the onset and progression of AD. While many studies have focused on beta-amyloid, soluble oligomeric tau species may also play an important role in AD pathogenesis. Antibodies that selectively identify and target specific oligomeric tau variants would be valuable tools for both diagnostic and therapeutic applications and also to study the etiology of AD and other neurodegenerative diseases.
Recombinant human tau (rhTau) in monomeric, dimeric, trimeric and fibrillar forms were synthesized and purified to perform LDH assay on human neuroblastoma cells, so that trimeric but not monomeric or dimeric rhTau was identified as extracellularly neurotoxic to neuronal cells. A novel biopanning protocol was designed based on phage display technique and atomic force microscopy (AFM), and used to isolate single chain antibody variable domain fragments (scFvs) that selectively recognize the toxic tau oligomers. These scFvs selectively bind tau variants in brain tissue of human AD patients and AD-related tau transgenic rodent models and have potential value as early diagnostic biomarkers for AD and as potential therapeutics to selectively target toxic tau aggregates.
Increasing evidence implicates soluble oligomeric forms of beta-amyloid and tau in the onset and progression of AD. While many studies have focused on beta-amyloid, soluble oligomeric tau species may also play an important role in AD pathogenesis. Antibodies that selectively identify and target specific oligomeric tau variants would be valuable tools for both diagnostic and therapeutic applications and also to study the etiology of AD and other neurodegenerative diseases.
Recombinant human tau (rhTau) in monomeric, dimeric, trimeric and fibrillar forms were synthesized and purified to perform LDH assay on human neuroblastoma cells, so that trimeric but not monomeric or dimeric rhTau was identified as extracellularly neurotoxic to neuronal cells. A novel biopanning protocol was designed based on phage display technique and atomic force microscopy (AFM), and used to isolate single chain antibody variable domain fragments (scFvs) that selectively recognize the toxic tau oligomers. These scFvs selectively bind tau variants in brain tissue of human AD patients and AD-related tau transgenic rodent models and have potential value as early diagnostic biomarkers for AD and as potential therapeutics to selectively target toxic tau aggregates.
ContributorsTian, Huilai (Author) / Sierks, Michael R (Thesis advisor) / Dai, Lenore (Committee member) / Tillery, Stephen H (Committee member) / Nielsen, David R (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2014
Description
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
Sound localization can be difficult in a reverberant environment. Fortunately listeners can utilize various perceptual compensatory mechanisms to increase the reliability of sound localization when provided with ambiguous physical evidence. For example, the directional information of echoes can be perceptually suppressed by the direct sound to achieve a single, fused auditory event in a process called the precedence effect (Litovsky et al., 1999). Visual cues also influence sound localization through a phenomenon known as the ventriloquist effect. It is classically demonstrated by a puppeteer who speaks without visible lip movements while moving the mouth of a puppet synchronously with his/her speech (Gelder and Bertelson, 2003). If the ventriloquist is successful, sound will be “captured” by vision and be perceived to be originating at the location of the puppet. This thesis investigates the influence of vision on the spatial localization of audio-visual stimuli. Participants seated in a sound-attenuated room indicated their perceived locations of either ISI or level-difference stimuli in free field conditions. Two types of stereophonic phantom sound sources, created by modulating the inter-stimulus time interval (ISI) or level difference between two loudspeakers, were used as auditory stimuli. The results showed that the light cues influenced auditory spatial perception to a greater extent for the ISI stimuli than the level difference stimuli. A binaural signal analysis further revealed that the greater visual bias for the ISI phantom sound sources was correlated with the increasingly ambiguous binaural cues of the ISI signals. This finding suggests that when sound localization cues are unreliable, perceptual decisions become increasingly biased towards vision for finding a sound source. These results support the cue saliency theory underlying cross-modal bias and extend this theory to include stereophonic phantom sound sources.
ContributorsMontagne, Christopher (Author) / Zhou, Yi (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Yost, William A. (Committee member) / Arizona State University (Publisher)
Created2015
Description
Music training is associated with measurable physiologic changes in the auditory pathway. Benefits of music training have also been demonstrated in the areas of working memory, auditory attention, and speech perception in noise. The purpose of this study was to determine whether long-term auditory experience secondary to music training enhances the ability to detect, learn, and recall new words.
Participants consisted of 20 young adult musicians and 20 age-matched non-musicians. In addition to completing word recognition and non-word detection tasks, each participant learned 10 nonsense words in a rapid word-learning task. All tasks were completed in quiet and in multi-talker babble. Next-day retention of the learned words was examined in isolation and in context. Cortical auditory evoked responses to vowel stimuli were recorded to obtain latencies and amplitudes for the N1, P2, and P3a components. Performance was compared across groups and listening conditions. Correlations between the behavioral tasks and the cortical auditory evoked responses were also examined.
No differences were found between groups (musicians vs. non-musicians) on any of the behavioral tasks. Nor did the groups differ in cortical auditory evoked response latencies or amplitudes, with the exception of P2 latencies, which were significantly longer in musicians than in non-musicians. Performance was significantly poorer in babble than in quiet on word recognition and non-word detection, but not on word learning, learned-word retention, or learned-word detection. CAEP latencies collapsed across group were significantly longer and amplitudes were significantly smaller in babble than in quiet. P2 latencies in quiet were positively correlated with word recognition in quiet, while P3a latencies in babble were positively correlated with word recognition and learned-word detection in babble. No other significant correlations were observed between CAEPs and performance on behavioral tasks.
These results indicated that, for young normal-hearing adults, auditory experience resulting from long-term music training did not provide an advantage for learning new information in either favorable (quiet) or unfavorable (babble) listening conditions. Results of the present study suggest that the relationship between music training and the strength of cortical auditory evoked responses may be more complex or too weak to be observed in this population.
Participants consisted of 20 young adult musicians and 20 age-matched non-musicians. In addition to completing word recognition and non-word detection tasks, each participant learned 10 nonsense words in a rapid word-learning task. All tasks were completed in quiet and in multi-talker babble. Next-day retention of the learned words was examined in isolation and in context. Cortical auditory evoked responses to vowel stimuli were recorded to obtain latencies and amplitudes for the N1, P2, and P3a components. Performance was compared across groups and listening conditions. Correlations between the behavioral tasks and the cortical auditory evoked responses were also examined.
No differences were found between groups (musicians vs. non-musicians) on any of the behavioral tasks. Nor did the groups differ in cortical auditory evoked response latencies or amplitudes, with the exception of P2 latencies, which were significantly longer in musicians than in non-musicians. Performance was significantly poorer in babble than in quiet on word recognition and non-word detection, but not on word learning, learned-word retention, or learned-word detection. CAEP latencies collapsed across group were significantly longer and amplitudes were significantly smaller in babble than in quiet. P2 latencies in quiet were positively correlated with word recognition in quiet, while P3a latencies in babble were positively correlated with word recognition and learned-word detection in babble. No other significant correlations were observed between CAEPs and performance on behavioral tasks.
These results indicated that, for young normal-hearing adults, auditory experience resulting from long-term music training did not provide an advantage for learning new information in either favorable (quiet) or unfavorable (babble) listening conditions. Results of the present study suggest that the relationship between music training and the strength of cortical auditory evoked responses may be more complex or too weak to be observed in this population.
ContributorsStewart, Elizabeth (Author) / Pittman, Andrea (Thesis advisor) / Cone, Barbara (Committee member) / Zhou, Yi (Committee member) / Arizona State University (Publisher)
Created2017
Description
Auditory scene analysis (ASA) is the process through which listeners parse and organize their acoustic environment into relevant auditory objects. ASA functions by exploiting natural regularities in the structure of auditory information. The current study investigates spectral envelope and its contribution to the perception of changes in pitch and loudness. Experiment 1 constructs a perceptual continuum of twelve f0- and intensity-matched vowel phonemes (i.e. a pure timbre manipulation) and reveals spectral envelope as a primary organizational dimension. The extremes of this dimension are i (as in “bee”) and Ʌ (“bun”). Experiment 2 measures the strength of the relationship between produced f0 and the previously observed phonetic-pitch continuum at three different levels of phonemic constraint. Scat performances and, to a lesser extent, recorded interviews were found to exhibit changes in accordance with the natural regularity; specifically, f0 changes were correlated with the phoneme pitch-height continuum. The more constrained case of lyrical singing did not exhibit the natural regularity. Experiment 3 investigates participant ratings of pitch and loudness as stimuli vary in f0, intensity, and the phonetic-pitch continuum. Psychophysical functions derived from the results reveal that moving from i to Ʌ is equivalent to a .38 semitone decrease in f0 and a .75 dB decrease in intensity. Experiment 4 examines the potentially functional aspect of the pitch, loudness, and spectral envelope relationship. Detection thresholds of stimuli in which all three dimensions change congruently (f0 increase, intensity increase, Ʌ to i) or incongruently (no f0 change, intensity increase, i to Ʌ) are compared using an objective version of the method of limits. Congruent changes did not provide a detection benefit over incongruent changes; however, when the contribution of phoneme change was removed, congruent changes did offer a slight detection benefit, as in previous research. While this relationship does not offer a detection benefit at threshold, there is a natural regularity for humans to produce phonemes at higher f0s according to their relative position on the pitch height continuum. Likewise, humans have a bias to detect pitch and loudness changes in phoneme sweeps in accordance with the natural regularity.
ContributorsPatten, K. Jakob (Author) / Mcbeath, Michael K (Thesis advisor) / Amazeen, Eric L (Committee member) / Glenberg, Arthur W (Committee member) / Zhou, Yi (Committee member) / Arizona State University (Publisher)
Created2017
Description
Head turning is a common sound localization strategy in primates. A novel system that can track head movement and acoustic signals received at the entrance to the ear canal was tested to obtain binaural sound localization information during fast head movement of marmoset monkey. Analysis of binaural information was conducted with a focus on inter-aural level difference (ILD) and inter-aural time difference (ITD) at various head positions over time. The results showed that during fast head turns, the ITDs showed significant and clear changes in trajectory in response to low frequency stimuli. However, significant phase ambiguity occurred at frequencies greater than 2 kHz. Analysis of ITD and ILD information with animal vocalization as the stimulus was also tested. The results indicated that ILDs may provide more information in understanding the dynamics of head movement in response to animal vocalizations in the environment. The primary significance of this experimentation is the successful implementation of a system capable of simultaneously recording head movement and acoustic signals at the ear canals. The collected data provides insight into the usefulness of ITD and ILD as binaural cues during head movement.
ContributorsLabban, Kyle John (Author) / Zhou, Yi (Thesis director) / Buneo, Christopher (Committee member) / Dorman, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Volumetric cell imaging using 3D optical Computed Tomography (cell CT) is advantageous for identification and characterization of cancer cells. Many diseases arise from genomic changes, some of which are manifest at the cellular level in cytostructural and protein expression (functional) features which can be resolved, captured and quantified in 3D far more sensitively and specifically than in traditional 2D microscopy. Live single cells were rotated about an axis perpendicular to the optical axis to facilitate data acquisition for functional live cell CT imaging. The goal of this thesis research was to optimize and characterize the microvortex rotation chip. Initial efforts concentrated on optimizing the microfabrication process in terms of time (6-8 hours v/s 12-16 hours), yield (100% v/s 40-60%) and ease of repeatability. This was done using a tilted exposure lithography technique, as opposed to the backside diffuser photolithography (BDPL) method used previously (Myers 2012) (Chang and Yoon 2004). The fabrication parameters for the earlier BDPL technique were also optimized so as to improve its reliability. A new, PDMS to PDMS demolding process (soft lithography) was implemented, greatly improving flexibility in terms of demolding and improving the yield to 100%, up from 20-40%. A new pump and flow sensor assembly was specified, tested, procured and set up, allowing for both pressure-control and flow-control (feedback-control) modes; all the while retaining the best features of a previous, purpose-built pump assembly. Pilot experiments were performed to obtain the flow rate regime required for cell rotation. These experiments also allowed for the determination of optimal trapezoidal neck widths (opening to the main flow channel) to be used for cell rotation characterization. The optimal optical trap forces were experimentally estimated in order to minimize the required optical power incident on the cell. Finally, the relationships between (main channel) flow rates and cell rotation rates were quantified for different trapezoidal chamber dimensions, and at predetermined constant values of laser trapping strengths, allowing for parametric characterization of the system.
ContributorsShetty, Rishabh M (Author) / Meldrum, Deirdre R (Thesis advisor) / Johnson, Roger H (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2013