A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.

The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.

Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.

Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.

Spike sorting is a critical step for single-unit-based analysis of neural activities extracellularly and simultaneously recorded using multi-channel electrodes. When dealing with recordings from very large numbers of neurons, existing methods, which are mostly semiautomatic in nature, become inadequate.

This dissertation aims at automating the spike sorting process. A high performance, automatic and computationally efficient spike detection and clustering system, namely, the M-Sorter2 is presented. The M-Sorter2 employs the modified multiscale correlation of wavelet coefficients (MCWC) for neural spike detection. At the center of the proposed M-Sorter2 are two automatic spike clustering methods. They share a common hierarchical agglomerative modeling (HAM) model search procedure to strategically form a sequence of mixture models, and a new model selection criterion called difference of model evidence (DoME) to automatically determine the number of clusters. The M-Sorter2 employs two methods differing by how they perform clustering to infer model parameters: one uses robust variational Bayes (RVB) and the other uses robust Expectation-Maximization (REM) for Student’s 𝑡-mixture modeling. The M-Sorter2 is thus a significantly improved approach to sorting as an automatic procedure.

M-Sorter2 was evaluated and benchmarked with popular algorithms using simulated, artificial and real data with truth that are openly available to researchers. Simulated datasets with known statistical distributions were first used to illustrate how the clustering algorithms, namely REMHAM and RVBHAM, provide robust clustering results under commonly experienced performance degrading conditions, such as random initialization of parameters, high dimensionality of data, low signal-to-noise ratio (SNR), ambiguous clusters, and asymmetry in cluster sizes. For the artificial dataset from single-channel recordings, the proposed sorter outperformed Wave_Clus, Plexon’s Offline Sorter and Klusta in most of the comparison cases. For the real dataset from multi-channel electrodes, tetrodes and polytrodes, the proposed sorter outperformed all comparison algorithms in terms of false positive and false negative rates. The software package presented in this dissertation is available for open access.

The avalanche of ongoing bioscience research has resulted in an unprecedented range of opportunities for the creation of new medical diagnostics and therapies. As the potential to develop treatments for the human body expands, the ability to control, modify, and interfere with abstract parts of an individual's self increases. While basic components of the self - such as the mind, consciousness, and personality - can presently only be altered by natural processes and diseases, current and emerging technologies that can cause changes in the self are in development. It is likely that as understanding of the brain and mind increases, scientists and engineers will be develop the ability to alter the mind and consciousness in profound new ways. Such a paradigm shift will be fraught with ethical concerns, and if those concerns are not handled in an appropriate manner, there is significant potential for harm. This potential for causing harm is not without precedent. Genome editing technology is an area of research which deals with an element of the fundamental self. In recent years, advancements in genome editing technology in the form of the CRISPR/Cas9 system have caused alarm and debate within scientific communities concerning the ethicalness of its use and application. Using lessons learned from the ways in which the CRISPR technology has been beneficially used, an ethical framework might be developed in order to guide the development of emerging neurotechnology. Early implementation of a framework such as the one herein proposed could guide research that is already being conducted. There is still time to influence the way that neurological device research is conducted, and it is duty of ethical scientists in this field to understand and correct these problems clearly and quickly so as to prevent harm. An ethical framework that is consistent with current ethical standards and understandings might be created by reviewing the history and development of CRISPR.

Central to current conceptions concerning the function of the nervous system is the consideration of how it manages to maintain precise control for repetitive tasks such as reaching, given the extensive observable mechanical degrees of freedom. Especially in the upper extremities, there are an infinite number of orientations (degrees of freedom) that can produce the same ultimate outcome. Consider, for example, a man in a seated position pointing to an object on a table with his index finger: even if we vastly simplify the mechanics involved in that action by considering three principle joints - the shoulder, elbow, and wrist - there are an infinite number of upper arm orientations that would result in the same position of the man's index finger in three-dimensional space. It has been hypothesized that the central nervous system is capable of simplifying reaching tasks by organizing the DOFs; this suggests that repetitive, simple tasks such as reaching can be planned, that the variability in repetitive tasks is minimized, and that the central nervous system is capable of increasing stability by instantaneously resisting perturbations. Previous literature indicates that variability is decreased and stability increased in trained upper extremity movement. In this study, mechanical discrepancies between violinists of varying levels of experience were identified. It was hypothesized that variability in the positional error (deviation from an expected line of motion) and velocity of the bow, as well as the produced variability in resultant elbow angles, would decrease with increasing proficiency, and that training would have no observable effect on average peak bow velocity. Data acquisition was accomplished by constructing LED triads and implementing a PhaseSpace 3D Motion Capture system. While the positional variance and peak velocity magnitude of the bow appeared unaffected by training (p >> 0.05), more advanced players demonstrated significantly higher variability in bow velocity (p << 0.001). As such, it can be concluded that repetitive training does manifest in changes in variability; however, further investigation is required to reveal the nature of these changes.

The purpose of this experiment is to study whether there is a difference in applied finger force between violinists of different skill proficiencies. It has been hypothesized that more experienced violinists will apply less force during play in their thumb and index fingers. It was found that there was significant difference in the peak forces applied by the index finger, thumb, and grip (p < 0.05) in all groups except beginner and intermediate violinists in peak thumb force. Significant differences were also found in the continuous force applied by the index finger and grip as well as the standard deviation of the continuous force applied by the thumb (p < 0.05). Additionally, there were no significant differences in the correlation between continuous applied index finger and thumb forces or latency in index and thumb force between different levels or proficiencies (p > 0.05). Due to these results, the hypothesis could not be fully accepted signifying that further testing must be performed.

Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may involve changes in cerebral blood flow. The vagus nerve plays a significant role in the regulation of heart rate and cerebral blood flow that are altered during VNS. Here, we examined the effects of acute vagal nerve stimulation on both heart rate and cerebral blood flow. Laser Speckle Contrast Analysis (LASCA) was used to analyze the cerebral blood flow of male Long\u2014Evans rats. Results showed two distinct patterns of responses whereby animals either experienced a mild or severe decrease in heart rate during VNS. Further, animals that displayed mild heart rate decreases showed an increase in cerebral blood flow that persisted beyond VNS. Animals that displayed severe decreases showed a transient decrease in cerebral blood flow followed by an increase that was greater than that observed in mild animals but progressively decreased after VNS. The results suggest two distinct patterns of changes in both heart rate and cerebral blood flow that may be related to the intensity of VNS.

Object manipulation is a common sensorimotor task that humans perform to interact with the physical world. The first aim of this dissertation was to characterize and identify the role of feedback and feedforward mechanisms for force control in object manipulation by introducing a new feature based on force trajectories to quantify the interaction between feedback- and feedforward control. This feature was applied on two grasp contexts: grasping the object at either (1) predetermined or (2) self-selected grasp locations (“constrained” and “unconstrained”, respectively), where unconstrained grasping is thought to involve feedback-driven force corrections to a greater extent than constrained grasping. This proposition was confirmed by force feature analysis. The second aim of this dissertation was to quantify whether force control mechanisms differ between dominant and non-dominant hands. The force feature analysis demonstrated that manipulation by the dominant hand relies on feedforward control more than the non-dominant hand. The third aim was to quantify coordination mechanisms underlying physical interaction by dyads in object manipulation. The results revealed that only individuals with worse solo performance benefit from interpersonal coordination through physical couplings, whereas the better individuals do not. This work showed that naturally emerging leader-follower roles, whereby the leader in dyadic manipulation exhibits significant greater force changes than the follower. Furthermore, brain activity measured through electroencephalography (EEG) could discriminate leader and follower roles as indicated power modulation in the alpha frequency band over centro-parietal areas. Lastly, this dissertation suggested that the relation between force and motion (arm impedance) could be an important means for communicating intended movement direction between biological agents.

Cochlear implants are electronic medical devices that create hearing capabilities in those with inner ear damage that results in total or partial hearing loss. The decision to get a cochlear implant can be difficult and controversial. Cochlear implants have many physical and social impacts on cochlear implant users. The aim of this study was to evaluate how patient narratives written by people with cochlear implants (or their caregivers) express issues of quality of life and personhood related to the use of this medical device. The methodology used to answer this question was a content analysis of patient narratives. The content analysis was done using grounded theory and the constant comparative method. Two sensitizing concepts, quality of life and personhood, were used and became the large umbrella themes found in the narratives. Under the major theme of quality of life, the sub-themes that emerged were improved hearing, improved communication skills, and assimilation into the hearing world. Under the major theme of personhood, the sub-themes that emerged were confidence, self-image, and technology and the body. Another major theme, importance of education, also emerged. In general, cochlear implant users and their caregivers expressed in their narratives that cochlear implants have positive effects on the quality of life of cochlear implant users. This is because almost all of the narrative writers reported improved hearing, improved communication skills, and better assimilation into the hearing world. In addition, it was found that cochlear implants do not have a significant affect on the actual personal identity of cochlear implant users, though they do make them more confident. The majority of cochlear implant users expressed that they view the cochlear implant device as an assistive tool they use as opposed to a part of themselves. Lastly, there is a need for more awareness of or access to education and therapy for cochlear implant users.

Background. Proprioception plays a large role in everyday functioning, involving both information of body position and movement (Johnson & Panayotis, 2010). Clinical assessments of proprioception are largely subjective and are not reliable measures for testing proprioception in impaired or unimpaired individuals. Recent advancements in technology and robotics have brought about new assessments that involve position matching and other paradigms. However, the results are confined to the horizontal plane and only look at a very small subset of human proprioceptive ability. Objective. The present study looks to overcome these limitations and examine differences in proprioceptive sensitivity across different directions in 3D space. Methods. Participants were recruited from Arizona State University to perform a "same-different" discrimination test using a robotic arm. Each participant was tested along two of the three directions, and within each direction, proprioception at four distances (1-4 cm) was tested. Performance was quantified using percent correct, d' analysis, and permutation testing on median and variance values. Results. Proprioceptive sensitivity was significantly greater in the up direction vs. down and back across all distances. The greatest difference in sensitivity occurred at 3 cm; permutation tests using median and variance values from percent correct and d' found statistical significance at this distance in the up vs. down and up vs. back comparisons. Conclusions. There is evidence that proprioceptive sensitivity is greater in an anti-gravity direction (up), in comparison to gravity-assisted or gravity-neutral (down and back) directions.

The human hand relies on information from surrounding environment to distinguish objects based on qualities like size, texture, weight, and compliance. The size of an object can be determined from tactile feedback, proprioception, and visual feedback. This experiment aims to determine the accuracy of size discrimination in physical and virtual objects using proprioceptive and tactile feedback. Using both senses will help determine how much proprioceptive and tactile feedback plays a part in discriminating small size variations and whether replacing a missing sensation will increase the subject's accuracy. Ultimately, determining the specific contributions of tactile and proprioceptive feedback mechanisms during object manipulation is important in order to give prosthetic hand users the ability of stereognosis among other manipulation tasks. Two different experiments using physical and virtual objects were required to discover the roles of tactile and proprioceptive feedback. Subjects were asked to compare the size of one block to a previous object. The blocks increased in size by two millimeter increments and were randomized in order to determine whether subjects could correctly identify if a box was smaller, larger, or the same size as the previous box. In the proprioceptive experiment subjects had two sub-sets of experiments each with a different non-tactile cue. The experiment demonstrated that subjects performed better with physical objects compared to virtual objects. This suggests that size discrimination is possible in the absence of tactile feedback, but tactile input is necessary for accuracy in small size discrimination.