1 NORTHWESTERN UNIVERSITY the Refinement of Control

1 NORTHWESTERN UNIVERSITY the Refinement of Control

1 NORTHWESTERN UNIVERSITY The Refinement of Control Strategies for Cortically-Controlled Functional Electrical Stimulation A DISSERTATION SUBMITTED TO THE GRADUATE SCHOOL IN PARTIAL FULFILLMENT OF THE REQUIREMENTS For the degree DOCTOR OF PHILOSOPHY Field of Biomedical Engineering By Stephanie Naufel Naufel EVANSTON, ILLINOIS September 2017 2 Abstract Paralysis resulting from spinal cord injury (SCI) is devastating, dramatically reducing the independence of affected individuals. Currently, functional electrical stimulation (FES), controlled by a patient’s residual movements, is used clinically to restore a limited range of voluntary movement. However, if FES could be controlled using signals recorded from the brain, it might allow patients with high-level SCI to regain even more natural and sophisticated movements. Cortically-controlled FES has been successfully used in animal experiments and in preliminary human clinical trials, but it needs refinement before it can be fully translated to the clinic. Here I present three distinct studies, each of which addresses the improvement of a system control strategy. Taken together, my three studies offer insights that will improve the future implementation of cortically-controlled FES. In my first study, I evaluated the ability to use peripheral nerve stimulation to selectively activate muscles for FES. I demonstrated that the Flat Interface Nerve Electrode (FINE) can selectively stimulate a subset of wrist and hand muscles, and that this stimulation is stable over a period of 4 months. In future implementations of FES, nerve stimulation can therefore be used to selectively stimulate a subset of muscles without the need to implant these muscles individually. This method may be especially useful for muscles which are difficult to individually implant and stimulate intramuscularly without current spillover. Cortically-controlled FES also relies on the ability to accurately predict muscle signals (EMG) from neural activity in motor cortex (M1) using a mathematical algorithm, or neural “decoder”. In my second and third studies, I address the question of how accurate a decoder needs to be, both for making accurate EMG predictions across behaviors, and for facilitating intuitive user control. No decoder can be expected to be perfect, but I also evaluate the brain’s ability to adapt to imperfect decoders, which may ultimately enable the successful restoration of movement. I first examine the accuracy of a single decoder for predicting actual wrist EMG across three highly varied dynamical conditions: isometric forces, unloaded movements, and movements against an elastic load. To allow a decoder to perform well across these tasks, it needs to be trained on data from all three, and furthermore, needs to be nonlinear. Second, I evaluate the ability of monkeys to learn two different kinds of altered decoders: one that preserved the natural coactivation 3 patterns of muscles, and one that didn’t. The monkeys are better able to learn to use the former decoder, and never accomplish all task goals in the latter case. Taken together, my results suggest that neural decoders should include robust multi-task training, and should account for nonlinearities in the motor system. They also suggest that imperfect EMG decoders can be learned, as long as they take into account the natural activation patterns of muscles. Overall, the results presented in this dissertation offer insights and tools that will improve the future implementation of cortically-controlled FES. 4 Acknowledgements In my time at Northwestern, I have worked in many different teams, and have been inspired by the excellent scientists and clinicians that I’ve met and worked with over the past six years. I would first like to thank my committee members, Dr. Nicho Hatsopoulos, Dr. Eric Perreault, and Dr. Sandro Mussa-Ivaldi for their valuable feedback on my projects, as well as for their encouragement. I enjoyed consulting with them on my specific projects as well as on general scientific ideas. I would also like to thank Dr. Sara Solla, though she was not an official committee member, for serving as a mentor figure and role model for me. She approached every topic with enthusiasm, and was an expert at clearly and comprehensively explaining complicated topics – a skill that should be bottled and sold. I also thank my doctoral advisor, Dr. Lee Miller, for the resources and scientific advice he provided to me over the years. He was always ready and available to discuss new results and experimental plans, and was a role model of responsibility. I would also like to thank my colleagues in the Miller lab for their helpful feedback on my projects, their collaboration, and for their general camaraderie. I especially thank Drs. Christian Ethier and Nicholas Sachs, who were patient mentors to me in my early years of graduate school. I also give my earnest thanks to Matt Perich, who was my main cheerleader for many years during this graduate adventure, for which I will forever be grateful. I would like to thank our veterinary staff, especially Dr. Charlette Cain, Dr. Tracy Gluckman, and Dr. Rebecca Erickson, along with Carey Nichols, Danielle Stephens, Katie Mahoney, and Kourtney Wallace. These individuals all showed an earnest care for our animal subjects, and were quick and capable responders during emergencies. They were also patient with us when procedures ran long, which we sincerely appreciated. I would furthermore like to thank the plastic surgery residents who volunteered their time to help us with these long and complicated surgical procedures, which at times lasted up to 11 hours: Dr. Jennie Cheesborough, Dr. Michael Gart, Dr. Chad Purnell, Dr. Steve Lanier, and Dr. Elbert Vaca. 5 My research also included collaborations with a number of labs. I would first like to acknowledge Dr. Konrad Kording and Joshua Glaser. They both provided me with useful comments for how to write compelling scientific papers, and Josh’s perseverance in trying so many different analyses was wonderful to behold, and greatly benefitted our joint project. For their help and support for my rat experiments, I would like to thank Dr. Matt Tresch and Dr. Ben Rellinger. Matt very graciously let me use his lab setup for these experiments, and Ben patiently taught me how to conduct rat surgeries in general, as well as the specifics of implanting EMG wires in rat hindlimb muscles. I would like to thank Dr. Mitra Hartmann, who was very kind to allow me to collaborate with her team on a somatosensory project. I really appreciated the opportunity to be involved in sensory research again, and I was inspired by Mitra’s enduring and contagious excitement for science. I would like to thank my colleagues at Case Western Reserve University, with whom we collaborated on the nerve stimulation experiments described in Chapter 2: Drs. Dustin Tyler, Natalie Brill, and Katherine Polasek. I found their nerve cuffs very exciting, and I was thankful to be a part of this project with them. I also thank Dr. Kate Murray and Rebecca Moore for assisting with the chronic nerve stimulation experiments we performed. I would also like to acknowledge Drs. Steve Helms Tillery, Veronica Santos, and Jason Robert for being my mentors during my formative years as a researcher, and for their continued friendship and encouragement throughout my doctoral studies. I particularly thank Steve and Jason for believing in my idea to have graduate students in ethics to do a semester-long rotation in research labs. Not only did they procure the funding to make these ideas a reality, they also facilitated my ability to help oversee the pilot implementation of the program, even while I was at Northwestern. 6 I also thank my husband Jon, who has been a friend and confidant since Day 0, when we both arrived in Chicago for recruitment weekend, wondering if Northwestern was in our future. I also thank my supportive family members for their encouragement. I additionally extend my thanks to my friends, some of whom have navigated through graduate school with me, for their encouragement and exemplary resilience to life’s obstacles. I feel lucky to be surrounded by such admirable people. Finally, I would like to explicitly acknowledge my research subjects – Fish, Jaco, Jango, Kevin, Nacho, and Spike – for their cooperation and their contribution to science. Successful experiments required a trusting and tacit agreement between trainer and subject, and it was meaningful to me to build and maintain a relationship with each of these animals. Even after nearly a decade of primate research, the excitement of seeing a task “click” with a monkey has never faded for me. I took my responsibility to be an ethical researcher seriously, and sincerely hope the sacrifice of these animals has served to benefit a greater good. 7 Preface In 1818, Mary Shelley published her famed novel Frankenstein, detailing the story of a scientist who creates a fearsome living being out of cadaver parts and a “spark” (Shelley 1818). While fantastical, some of her ideas were not completely foreign for the time. A few decades prior, Luigi Galvani had successfully elicited muscle contractions from dissected frog legs using electric current (Galvani 1791). His experiments were purportedly the inspiration behind Shelley’s story, but even more importantly, they set the stage for a future of electrical stimulation to medically treat the human body. Today, as we rapidly approach the bicentennial of Frankenstein’s publication, and are more than 200 years past Galvani’s frog studies, several medical devices exist in the market that electrically stimulate the body, either to provide and restore functionality, or to treat illness. These devices include cochlear implants, which electrically stimulate the auditory nerve to provide a mode of hearing to the profoundly deaf (Wilson and Dorman 2017), and deep brain stimulation, which can treat the symptoms of Parkinson’s disease, dystonia and even obsessive-compulsive disorder (Perlmutter and Mink 2006).

View Full Text

Details

  • File Type
    pdf
  • Upload Time
    -
  • Content Languages
    English
  • Upload User
    Anonymous/Not logged-in
  • File Pages
    140 Page
  • File Size
    -

Download

Channel Download Status
Express Download Enable

Copyright

We respect the copyrights and intellectual property rights of all users. All uploaded documents are either original works of the uploader or authorized works of the rightful owners.

  • Not to be reproduced or distributed without explicit permission.
  • Not used for commercial purposes outside of approved use cases.
  • Not used to infringe on the rights of the original creators.
  • If you believe any content infringes your copyright, please contact us immediately.

Support

For help with questions, suggestions, or problems, please contact us