Electrophysiological Investigation of Brain Stimulation Strategies to Improve Hearing Restoration via Auditory Neural Prostheses

University of Minnesota Ph.D. dissertation. December 2013. Major: Biomedical Engineering. Advisor: Hubert Lim. 1 computer file (PDF); xxvi, 173 pages.The auditory lemniscal system, the core pathway thought to be responsible for conducting high-fidelity auditory information, is yet to be well-understood, particularly at the level of the midbrain. The lack of understanding of the auditory lemniscal system resulted in limited performance of a central auditory neuroprosthesis called the auditory midbrain implant (AMI). The AMI is a linear array of 20 sites designed to stimulate the auditory lemniscal nucleus in the midbrain, the central nucleus of the inferior colliculus (ICC). In the first clinical trial, five patients were implanted with the AMI, which gave users improved lip reading abilities and environmental awareness. However, the AMI was unable to deliver sufficient temporal information, which is likely associated with suboptimal placement and stimulation strategies within the ICC. This doctoral thesis project investigated the central lemniscal system in order to improve results for future AMI patients. First, the organization of responses to auditory stimuli was investigated within the auditory lemniscal midbrain. This study found different response properties within a rostral-lateral verses caudal medial ICC region, corresponding to subregions with differential input and output projection patterns. Next, we investigated various stimulation strategies that would allow the AMI to deliver sufficient temporal information. Repeated stimulation of a single site in the ICC, which was the initial strategy of the AMI, resulted in refractory effects in the auditory cortex that could only be overcome by co-activating neurons along a lamina of the ICC. This co-activation resulted in cortical activity that was enhanced beyond the sum of individual neural activation, with the greatest enhancement occurring in supragranular cortical layers. Moreover, this enhancement was largest when stimulating the rostral-lateral rather than the caudal-medial ICC region. These ICC locations with different electrical stimulation properties matched the two subregions with different acoustic-driven response properties. Together, these studies found consistent differences in physiological properties within two subregions of the ICC, confirming the presence of dual lemniscal pathways from the midbrain to the cortex. In addition, these studies identified a potential stimulation strategy and implantation location for improving AMI performance: co-activating rostral-lateral neurons along the isofrequency laminae of the ICC

Characterizing Longitudinal Changes in the Impedance Spectra of In-Vivo Peripheral Nerve Electrodes

Characterizing the aging processes of electrodes in vivo is essential in order to elucidate the changes of the electrode⁻tissue interface and the device. However, commonly used impedance measurements at 1 kHz are insufficient for determining electrode viability, with measurements being prone to false positives. We implanted cohorts of five iridium oxide (IrOx) and six platinum (Pt) Utah arrays into the sciatic nerve of rats, and collected the electrochemical impedance spectroscopy (EIS) up to 12 weeks or until array failure. We developed a method to classify the shapes of the magnitude and phase spectra, and correlated the classifications to circuit models and electrochemical processes at the interface likely responsible. We found categories of EIS characteristic of iridium oxide tip metallization, platinum tip metallization, tip metal degradation, encapsulation degradation, and wire breakage in the lead. We also fitted the impedance spectra as features to a fine-Gaussian support vector machine (SVM) algorithm for both IrOx and Pt tipped arrays, with a prediction accuracy for categories of 95% and 99%, respectively. Together, this suggests that these simple and computationally efficient algorithms are sufficient to explain the majority of variance across a wide range of EIS data describing Utah arrays. These categories were assessed over time, providing insights into the degradation and failure mechanisms for both the electrode⁻tissue interface and wire bundle. Methods developed in this study will allow for a better understanding of how EIS can characterize the physical changes to electrodes in vivo

Closed-loop neuromuscular electrical stimulation using feedforward-feedback control and textile electrodes to regulate grasp force in quadriplegia

Abstract Background Transcutaneous neuromuscular electrical stimulation is routinely used in physical rehabilitation and more recently in brain-computer interface applications for restoring movement in paralyzed limbs. Due to variable muscle responses to repeated or sustained stimulation, grasp force levels can change significantly over time. Here we develop and assess closed-loop methods to regulate individual finger forces to facilitate functional movement. We combined this approach with custom textile-based electrodes to form a light-weight, wearable device and evaluated in paralyzed study participants. Methods A textile-based electrode sleeve was developed by the study team and Myant, Corp. (Toronto, ON, Canada) and evaluated in a study involving three able-body participants and two participants with quadriplegia. A feedforward-feedback control structure was designed and implemented to accurately maintain finger force levels in a quadriplegic study participant. Results Individual finger flexion and extension movements, along with functional grasping, were evoked during neuromuscular electrical stimulation. Closed-loop control methods allowed accurate steady state performance (< 15% error) with a settling time of 0.67 s (SD = 0.42 s) for individual finger contact force in a participant with quadriplegia. Conclusions Textile-based electrodes were identified to be a feasible alternative to conventional electrodes and facilitated individual finger movement and functional grasping. Furthermore, closed-loop methods demonstrated accurate control of individual finger flexion force. This approach may be a viable solution for enabling grasp force regulation in quadriplegia. Trial registration NCT, NCT03385005 . Registered Dec. 28, 201

The Argo: a high channel count recording system for neural recording in vivo

ObjectiveDecoding neural activity has been limited by the lack of tools available to record from large numbers of neurons across multiple cortical regions simultaneously with high temporal fidelity. To this end, we developed the Argo system to record cortical neural activity at high data rates.ApproachHere we demonstrate a massively parallel neural recording system based on platinum-iridium microwire electrode arrays bonded to a CMOS voltage amplifier array. The Argo system is the highest channel count in vivo neural recording system, supporting simultaneous recording from 65 536 channels, sampled at 32 kHz and 12-bit resolution. This system was designed for cortical recordings, compatible with both penetrating and surface microelectrodes.Main resultsWe validated this system through initial bench testing to determine specific gain and noise characteristics of bonded microwires, followed by in-vivo experiments in both rat and sheep cortex. We recorded spiking activity from 791 neurons in rats and surface local field potential activity from over 30 000 channels in sheep.SignificanceThese are the largest channel count microwire-based recordings in both rat and sheep. While currently adapted for head-fixed recording, the microwire-CMOS architecture is well suited for clinical translation. Thus, this demonstration helps pave the way for a future high data rate intracortical implant