Development of a Closed-loop for Measuring and Stimulating Peripheral Nervous System

Sammanfattning: Bioelectronic medicine is an emerging discipline being a intersection of neu- roscience, immunology and electrical engineering. Chronic inflammation is linked to disorders such as diabetes, rheumatoid arthritis, asthma, atheroscle- rosis, obesity and inflammatory bowel disease. Chronic inflammatory diseases have been recognized as the most significant cause of death in the world today, with more than 50% of all deaths being attributable to inflammation-related diseases. To find specific parameters for the stimulation of the vagus nerve would be a major advancement in the field, since it will help restore the vagal tone optimally. A systematic review has been made to understand and explore the tissue damage, stimulation sites, FDA approved parameters and the safety and efficacy in vagus nerve stimulation (VNS). A control closed- loop system was developed based on the needs of the field and a human clinical trial protocol was proposed.    The control close-loop system is able to receive feedback from a continuous real-time measurement of the pressure of the peripheral blood flow and send a VNS based on a heart rate (HR) settled threshold. The stimulation is delivered with previously settled parameters such as, pulse width, output current, duty cycle and frequency and helps observe if the nerve has been correctly targeted or not. From the results, it becomes clear that the connection of the devices has been correctly accomplished and that the HR reduction is being measured by the control close-loop which would stimulate again when the HR threshold is surpassed. Based on the concept of this control close-loop a human protocol has been proposed to test if the hypothesis that patients have their best inflammatory response with different output current rather than all having one best performing one and that non-healthy patients will lower their HR baseline after VNS treatment showing the increase of vagus nerve activity. This report adds value on the creation of a new control close-loop device between the MouseOx and Intan devices. Controlling the stimulation parameters in VNS can be a powerful technique that will increase patient specificity and will help non respondents to different drug treatments to have a more effective alternative. The HR is a simple biomarker to detect VNS bioactivity but lots of further research on non-invasive devices and software limitations are still needed to be overcome to have clear guidance in the field. The proposal of a new human clinical trial that might give a clear and feasible solution to either find an efficient stimulation setting or the assurance of the real need for an interactive control close-loop system that would tailor the stimulation parameters for each specific patient is presented.