Browsing by Author "Powley, Terry L."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation
    (Elsevier, 2020-04-15) Ward, Matthew P.; Gupta, Anita; Wo, John M.; Rajwa, Bartek; Furness, John B.; Powley, Terry L.; Nowak, Thomas V.; Medicine, School of Medicine
    Background: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism. New method: Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP). Results: Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05). Comparison with existing method(s): We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response. Conclusions: Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.
  • Thumbnail Image
    Item
    Fractal Microelectrodes for More Energy-Efficient Cervical Vagus Nerve Stimulation
    (Wiley, 2023) Lim, Jongcheon; Eiber, Calvin D.; Sun, Anina; Maples, Amanda; Powley, Terry L.; Ward, Matthew P.; Lee, Hyowon; Medicine, School of Medicine
    Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off-target effects. Microelectrodes may enable highly selective VNS that can mitigate off-target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non-Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm-scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (N = 3). A thin-film device with fractal and circle microelectrodes is fabricated to compare their neural stimulation performance on the same radial coordinate of the nerve. The results show that fractal microelectrodes can activate C-fibers with up to 52% less energy (p = 0.012) compared to circle microelectrodes. To the best of the knowledge, this work is the first to demonstrate a geometric advantage of fractal microelectrodes for VNS in vivo.
  • Thumbnail Image
    Item
    Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers
    (Springer Nature, 2021) Havton, Leif A.; Biscola, Natalia P.; Stern, Esther; Mihaylov, Plamen V.; Kubal, Chandrashekhar A.; Wo, John M.; Gupta, Anita; Baronowsky, Elizabeth; Ward, Matthew P.; Jaffey, Deborah M.; Powley, Terry L.; Surgery, School of Medicine
    The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.