Humans have an inherent capability of performing highly dexterous and skillful tasks with their arms, involving maintaining posture, movement and interacting with the environment. The latter requires for them to control the dynamic characteristics of the upper limb musculoskeletal system. Inertia, damping and stiffness, a measure of mechanical impedance, gives a strong representation of these characteristics. Many previous studies have shown that the arm posture is a dominant factor for determining the end point impedance in a horizontal plane (transverse plane). The objective of this thesis is to characterize end point impedance of the human arm in the three dimensional (3D) space. Moreover, it investigates and models the control of the arm impedance due to increasing levels of muscle co-contraction. The characterization is done through experimental trials where human subjects maintained arm posture, while perturbed by a robot arm. Moreover, the subjects were asked to control the level of their arm muscles' co-contraction, using visual feedback of their muscles' activation, in order to investigate the effect of the muscle co-contraction on the arm impedance. The results of this study showed a very interesting, anisotropic increase of the arm stiffness due to muscle co-contraction. This can lead to very useful conclusions about the arm biomechanics as well as many implications for human motor control and more specifically the control of arm impedance through muscle co-contraction. The study finds implications for the EMG-based control of robots that physically interact with humans.

This research is focused on two separate but related topics. The first uses an electroencephalographic (EEG) brain-computer interface (BCI) to explore the phenomenon of motor learning transfer. The second takes a closer look at the EEG-BCI itself and tests an alternate way of mapping EEG signals into machine commands. We test whether motor learning transfer is more related to use of shared neural structures between imagery and motor execution or to more generalized cognitive factors. Using an EEG-BCI, we train one group of participants to control the movements of a cursor using embodied motor imagery. A second group is trained to control the cursor using abstract motor imagery. A third control group practices moving the cursor using an arm and finger on a touch screen. We hypothesized that if motor learning transfer is related to the use of shared neural structures then the embodied motor imagery group would show more learning transfer than the abstract imaging group. If, on the other hand, motor learning transfer results from more general cognitive processes, then the abstract motor imagery group should also demonstrate motor learning transfer to the manual performance of the same task. Our findings support that motor learning transfer is due to the use of shared neural structures between imaging and motor execution of a task. The abstract group showed no motor learning transfer despite being better at EEG-BCI control than the embodied group. The fact that more participants were able to learn EEG-BCI control using abstract imagery suggests that abstract imagery may be more suitable for EEG-BCIs for some disabilities, while embodied imagery may be more suitable for others. In Part 2, EEG data collected in the above experiment was used to train an artificial neural network (ANN) to map EEG signals to machine commands. We found that our open-source ANN using spectrograms generated from SFFTs is fundamentally different and in some ways superior to Emotiv's proprietary method. Our use of novel combinations of existing technologies along with abstract and embodied imagery facilitates adaptive customization of EEG-BCI control to meet needs of individual users.

Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge in both of the aforementioned applications is the efficient delivery of siRNA molecules, plasmids or transcription factors to primary cells such as neurons. A majority of the current non-viral techniques, including chemical transfection, bulk electroporation and sonoporation fail to deliver with adequate efficiencies and the required spatial and temporal control. In this study, a novel optically transparent biochip is presented that can (a) transfect populations of primary and secondary cells in 2D culture (b) readily scale to realize high-throughput transfections using microscale electroporation and (c) transfect targeted cells in culture with spatial and temporal control. In this study, delivery of genetic payloads of different sizes and molecular characteristics, such as GFP plasmids and siRNA molecules, to precisely targeted locations in primary hippocampal and HeLa cell cultures is demonstrated. In addition to spatio-temporally controlled transfection, the biochip also allowed simultaneous assessment of a) electrical activity of neurons, b) specific proteins using fluorescent immunohistochemistry, and c) sub-cellular structures. Functional silencing of GAPDH in HeLa cells using siRNA demonstrated a 52% reduction in the GAPDH levels. In situ assessment of actin filaments post electroporation indicated a sustained disruption in actin filaments in electroporated cells for up to two hours. Assessment of neural spike activity pre- and post-electroporation indicated a varying response to electroporation. The microarray based nature of the biochip enables multiple independent experiments on the same culture, thereby decreasing culture-to-culture variability, increasing experimental throughput and allowing cell-cell interaction studies. Further development of this technology will provide a cost-effective platform for performing high-throughput genetic screens.

The ability to plan, execute, and control goal oriented reaching and grasping movements is among the most essential functions of the brain. Yet, these movements are inherently variable; a result of the noise pervading the neural signals underlying sensorimotor processing. The specific influences and interactions of these noise processes remain unclear. Thus several studies have been performed to elucidate the role and influence of sensorimotor noise on movement variability. The first study focuses on sensory integration and movement planning across the reaching workspace. An experiment was designed to examine the relative contributions of vision and proprioception to movement planning by measuring the rotation of the initial movement direction induced by a perturbation of the visual feedback prior to movement onset. The results suggest that contribution of vision was relatively consistent across the evaluated workspace depths; however, the influence of vision differed between the vertical and later axes indicate that additional factors beyond vision and proprioception influence movement planning of 3-dimensional movements. If the first study investigated the role of noise in sensorimotor integration, the second and third studies investigate relative influence of sensorimotor noise on reaching performance. Specifically, they evaluate how the characteristics of neural processing that underlie movement planning and execution manifest in movement variability during natural reaching. Subjects performed reaching movements with and without visual feedback throughout the movement and the patterns of endpoint variability were compared across movement directions. The results of these studies suggest a primary role of visual feedback noise in shaping patterns of variability and in determining the relative influence of planning and execution related noise sources. The final work considers a computational approach to characterizing how sensorimotor processes interact to shape movement variability. A model of multi-modal feedback control was developed to simulate the interaction of planning and execution noise on reaching variability. The model predictions suggest that anisotropic properties of feedback noise significantly affect the relative influence of planning and execution noise on patterns of reaching variability.

Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of grip and load force rates during the period between initial contact with the object and object lift. However, this has not been validated in tasks that do not constrain digit placement. The purposes of this thesis were (1) to validate the hypothesis that force rate profiles are indicative of the control strategy used for object manipulation and (2) to test this hypothesis by comparing manipulation tasks performed with and without digit placement constraints. The first objective comprised two studies. In the first study an additional light or heavy mass was added to the base of the object. In the second study a mass was added, altering the object's center of mass (CM) location. In each experiment digit force rates were calculated between the times of initial digit contact and object lift. Digit force rates were fit to a Gaussian bell curve and the goodness of fit was compared across predictable and unpredictable mass and CM conditions. For both experiments, a predictable object mass and CM elicited bell shaped force rate profiles, indicative of feedforward control. For the second objective, a comparison of performance between subjects who performed the grasp task with either constrained or unconstrained digit contact locations was conducted. When digit location was unconstrained and CM was predictable, force rates were well fit to a bell shaped curve. However, the goodness of fit of the force rate profiles to the bell shaped curve was weaker for the constrained than the unconstrained digit placement condition. These findings seem to indicate that brain can generate an appropriate feedforward control strategy even when digit placement is unconstrained and an infinite combination of digit placement and force solutions exists to lift the object successfully. Future work is needed that investigates the role digit positioning and tactile feedback has on anticipatory control of object manipulation.

In this thesis I introduce a new direction to computing using nonlinear chaotic dynamics. The main idea is rich dynamics of a chaotic system enables us to (1) build better computers that have a flexible instruction set, and (2) carry out computation that conventional computers are not good at it. Here I start from the theory, explaining how one can build a computing logic block using a chaotic system, and then I introduce a new theoretical analysis for chaos computing. Specifically, I demonstrate how unstable periodic orbits and a model based on them explains and predicts how and how well a chaotic system can do computation. Furthermore, since unstable periodic orbits and their stability measures in terms of eigenvalues are extractable from experimental times series, I develop a time series technique for modeling and predicting chaos computing from a given time series of a chaotic system. After building a theoretical framework for chaos computing I proceed to architecture of these chaos-computing blocks to build a sophisticated computing system out of them. I describe how one can arrange and organize these chaos-based blocks to build a computer. I propose a brand new computer architecture using chaos computing, which shifts the limits of conventional computers by introducing flexible instruction set. Our new chaos based computer has a flexible instruction set, meaning that the user can load its desired instruction set to the computer to reconfigure the computer to be an implementation for the desired instruction set. Apart from direct application of chaos theory in generic computation, the application of chaos theory to speech processing is explained and a novel application for chaos theory in speech coding and synthesizing is introduced. More specifically it is demonstrated how a chaotic system can model the natural turbulent flow of the air in the human speech production system and how chaotic orbits can be used to excite a vocal tract model. Also as another approach to build computing system based on nonlinear system, the idea of Logical Stochastic Resonance is studied and adapted to an autoregulatory gene network in the bacteriophage λ.

An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.