Ingestible Electronic Devices for Non-Invasive Vagal Stimulation

项目总结/摘要 大约有2500万美国人患有2型糖尿病。此外，约3500万 > 20岁的美国人被诊断为糖尿病前期。超过三分之一的美国人肥胖， 从1960年到2010年，发病率几乎增加了两倍。最近的研究表明肠脑轴 在消化和代谢疾病中起着关键作用。此外，感官之间的直接沟通 肠道中的神经元和大脑中的神经奖励回路在检测化学线索方面起着至关重要的作用， 如激素、饱腹感信号或肠道细菌产生的小分子代谢物。中的化学物质 小肠是由专门的上皮细胞检测的，上皮细胞将化学信号转化为神经元活动 可以被中枢神经系统解读。一种可摄取的装置，取代化学线索， 直接使用电子脉冲刺激感觉神经元可以模拟肠道中的化学环境， 与健康的代谢和消化状态有关。管腔内感觉神经的时空控制 刺激肠道可以帮助我们理解消化系统中的化学信号之间的联系， 以及大脑中由肠脑轴调节的神经回路。在这里，我们提出了一种可摄取的 具有柔性电极的电子设备，可以在猪模型的肠道中起搏感觉神经活动。 将测量生理反应，并使用功能磁共振成像监测大脑活动。起初，这个项目 将在猪受试者中使用拴系电极验证该概念验证。特别是感觉神经元 将使用仿生波形来起搏肠道中的起搏，该仿生波形将模拟猪受试者的进食或禁食状态 同时用功能磁共振成像测量大脑活动。这些结果将有助于我们了解 味觉信号，感觉神经活动和大脑中的神经奖励回路之间的联系， 饱腹感未来，我们将设计一种完全自主的智能药丸，带有板载电源和电路 其选择性和非侵入性地刺激或阻断人肠道中感觉神经元的活动 科目如果成功的话，这种智能药丸可以作为一种低风险的基于设备的方法来帮助理解 并潜在地治疗肠-脑轴的消化和代谢紊乱，例如肥胖和糖尿病。

PROJECT SUMMARY / ABSTRACT There are approximately 25 million Americans that suffer from Type 2 diabetes. Furthermore, about 35 million Americans >20 years old are diagnosed with prediabetes. More than one-third of Americans are also obese, an incidence that has nearly tripled from 1960 to 2010. Recent studies have shown that the gut-brain axis places a critical role in digestive and metabolic diseases. Further, direct communication between the sensory neurons in the gut and neural reward circuits in the brain plays a crucial role in detecting chemical cues such as hormones, satiety signals, or small molecule metabolites produced by bacteria in the gut. Chemicals in the small intestine are detected by specialized epithelial cells that transduce chemical signals into neuronal activity that can be interpreted by the central nervous system. An ingestible device that supersedes chemical cues and stimulates sensory neurons directly using electronic pulses could mimic the chemical milieu in the gut that is associated with healthy metabolic and digestive states. Spatiotemporal control of intraluminal sensory nerve stimulation in the gut could with help us understand the link between chemical signaling in the digestive system and neural circuits in the brain that are modulated by the gut-brain axis. Here we propose an ingestible electronic device with flexible electrodes that can pace sensory nerve activity in the gut of a pig model. Physiological responses will be measured, and brain activity will be monitored using fMRI. Initially, this project will validate this proof-of-concept using tethered electrodes in porcine subjects. Specifically, sensory neurons in the gut will be paced using biomimetic waveforms that will simulate fed or fasted states in porcine subjects while brain activity will be measured simultaneously using fMRI. These results will help us understand the connection between gustatory signaling, sensory nerve activity, and neural reward circuits in the brain such as satiety. In the future, we will design a fully autonomous smart pill with an on-board power supply and circuitry that selectively and non-invasively stimulate or block the activity of sensory neurons in the gut of human subjects. If successfully, this smart pill could serve as a low-risk device-based approach to help understand and potentially treat digestive and metabolic disorders of the gut-brain axis such as obesity and diabetes.