Lerman Imanuel, Bu Yifeng, Singh Rahul, Silverman Harold A, Bhardwaj Anuj, Mann Alex J, Widge Alik, Palin Joseph, Puleo Christopher, Lim Hubert
Department of Electrical and Computer Engineering, University of California San Diego, Atkinson Hall, 3195 Voigt Dr., La Jolla, CA, 92093, USA.
Center for Stress and Mental Health (CESAMH) VA San Diego, La Jolla, CA, 92093, USA.
Bioelectron Med. 2025 Jan 21;11(1):1. doi: 10.1186/s42234-024-00163-4.
The field of bioelectronic medicine has advanced rapidly from rudimentary electrical therapies to cutting-edge closed-loop systems that integrate real-time physiological monitoring with adaptive neuromodulation. Early innovations, such as cardiac pacemakers and deep brain stimulation, paved the way for these sophisticated technologies. This review traces the historical and technological progression of bioelectronic medicine, culminating in the emerging potential of closed-loop devices for multiple disorders of the brain and body. We emphasize both invasive techniques, such as implantable devices for brain, spinal cord and autonomic regulation, while we introduce new prospects for non-invasive neuromodulation, including focused ultrasound and newly developed autonomic neurography enabling precise detection and titration of inflammatory immune responses. The case for closed-loop non-invasive autonomic neuromodulation (incorporating autonomic neurography and splenic focused ultrasound stimulation) is presented through its applications in conditions such as sepsis and chronic inflammation, illustrating its capacity to revolutionize personalized healthcare. Today, invasive or non-invasive closed-loop systems have yet to be developed that dynamically modulate autonomic nervous system function by responding to real-time physiological and molecular signals; it represents a transformative approach to therapeutic interventions and major opportunity by which the bioelectronic field may advance. Knowledge gaps remain and likely contribute to the lack of available closed loop autonomic neuromodulation systems, namely, (1) significant exogenous and endogenous noise that must be filtered out, (2) potential drift in the signal due to temporal change in disease severity and/or therapy induced neuroplasticity, and (3) confounding effects of exogenous therapies (e.g., concurrent medications that dysregulate autonomic nervous system functions). Leveraging continuous feedback and real-time adjustments may overcome many of these barriers, and these next generation systems have the potential to stand at the forefront of precision medicine, offering new avenues for individualized and adaptive treatment.
生物电子医学领域已从基础的电疗法迅速发展到前沿的闭环系统，该系统将实时生理监测与自适应神经调节相结合。早期的创新成果，如心脏起搏器和深部脑刺激，为这些先进技术铺平了道路。本综述追溯了生物电子医学的历史和技术发展进程，最终聚焦于闭环设备在多种脑和身体疾病中展现出的新兴潜力。我们既强调侵入性技术，如用于脑、脊髓和自主神经调节的可植入设备，同时也介绍非侵入性神经调节的新前景，包括聚焦超声以及新开发的自主神经成像技术，其能够精确检测和调节炎症免疫反应。通过其在脓毒症和慢性炎症等病症中的应用，阐述了闭环非侵入性自主神经调节（结合自主神经成像和脾脏聚焦超声刺激）的情况，展示了其变革个性化医疗的能力。如今，尚未开发出能通过响应实时生理和分子信号来动态调节自主神经系统功能的侵入性或非侵入性闭环系统；这代表了一种变革性的治疗干预方法，也是生物电子领域取得进展的重大机遇。知识空白依然存在，这可能导致可用的闭环自主神经调节系统匮乏，具体而言，包括：（1）必须滤除的大量外源性和内源性噪声；（2）由于疾病严重程度的时间变化和/或治疗诱导的神经可塑性导致的信号潜在漂移；（3）外源性治疗的混杂效应（例如，同时使用的药物会使自主神经系统功能失调）。利用持续反馈和实时调整可能会克服其中许多障碍，而这些下一代系统有潜力站在精准医学的前沿，为个体化和适应性治疗提供新途径。
