This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2020 / Cataloged from student-submitted PDF of thesis. / Includes bibliographical references (pages 208-242). / Contemporary technological approaches to address limb loss and neuromuscular dysfunction consist of synthetic, mechanical devices which lack an intimate bidirectional interface with nervous tissues. On the therapeutic front, the current amputation paradigm disrupts neuromuscular architecture, discards sensory organs and provides no anatomical or prosthetic replacement. This precludes the generation of afferent sensory feedback, which is critical for sensory integration, motor planning, peripheral and central neurological health, and myoelectric prosthesis control. Utilizing a paradigm of coevolution, I simultaneously engineer neuromuscular anatomy and bioelectronics to enable seamless, bidirectional neuroprosthetic interfacing. In this dissertation, I describe the design and preclinical validation of the regenerative agonist-antagonist myoneural interface (AMI) and myodermal interface (MI), which are reconstructive surgical models to restore musculotendinous and cutaneous sensory feedback, respectively. Then, through case-control studies, the functional outcomes of human subjects who have undergone below-knee and above-knee amputations incorporating native AMIs are compared to standard amputation controls. The effect of AMI amputation on sensorimotor neuroplasticity is investigated through anatomical and functional neuroimaging. These preclinical and clinical evaluations demonstrate the a) production of graded efferent and afferent signals, b) the maintenance of peripheral limb volume and central sensorimotor substrates, c) improvements in phantom sensation, phantom pain, and neuroprosthetic controllability, and d) decreased dependence on compensatory visuomotor circuitry. To address challenges with functional electrical stimulation (FES) of neuromusculature, employed for prosthetic feedback and control, I develop a closed-loop functional optogenetic stimulation system (FOS) for peripheral neuromuscular control. This system demonstrates greater accuracy, biomimetic orderly recruitment of fibers, and minimized fatigue during cyclic movements as compared to FES. Spanning from animal models to human implementation, this dissertation presents 1) a model to design new surgical techniques for afferent/efferent signaling, 2) characterize the physiology following clinical translation, and 3) recursively apply the lessons to the design of neural interfaces back at the bench. In summary, the results of this work steer a shift of the clinical amputation paradigm towards one that performs strategic rewiring of neuromuscular constructs to enable improved neurological health and neural interfacing. / Shriya Srinivasan. / Ph. D. in Medical Engineering and Medical Physics / Ph. D. in Medical Engineering and Medical Physics Harvard-MIT Program in Health Sciences and Technology
| Identifer | oai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/150455 |
| Date | January 2020 |
| Creators | Srinivasan, Shriya, author. |
| Contributors | Harvard--MIT Program in Health Sciences and Technology,, Harvard University--MIT Division of Health Sciences and Technology |
| Publisher | Massachusetts Institute of Technology |
| Source Sets | M.I.T. Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Academic theses., Academic theses., Thesis |
| Format | 243 pages, application/pdf |
| Rights | MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided., http://dspace.mit.edu/handle/1721.1/7582 |
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