Hoang Kimberly B, Cassar Isaac R, Grill Warren M, Turner Dennis A
Department of Neurosurgery, Duke University, Durham, NC, United States.
Department of Biomedical Engineering, Duke University, Durham, NC, United States.
Front Neurosci. 2017 Oct 10;11:564. doi: 10.3389/fnins.2017.00564. eCollection 2017.
The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.
本综述的目的是描述如何基于相关生物标志物来提供和调整反馈或适应性刺激。尽管在多种神经系统疾病中已证明治疗性脑刺激具有疗效，但其潜在的具体治疗机制仍不清楚。脑刺激似乎对与特定疾病实体相关的特定神经网络产生广泛影响。在清醒患者中，这些神经网络的激活或抑制可通过症状缓解（如震颤、强直、癫痫发作）或生理标准来评估，这些标准可能预示着预期的症状性治疗。通过与症状性疾病改善相关的特定生物标志物对网络激活进行二次验证可能有多种原因。例如，这些生物标志物可辅助术中最佳定位，可能提高疗效或效率（如降低功率需求），并提供刺激参数的长期适应性自动调整。可用于便携式或植入式设备的可能生物标志物范围广泛，从持续的生理性脑活动、诱发的局部场电位（LFP）和间歇性病理活动，到可穿戴设备、生化、血流、光学或磁共振成像（MRI）变化、温度变化或光遗传学信号。然而，首先，潜在的生物标志物必须直接与症状或疾病治疗以及网络激活相关联。尽管针对各种刺激适应症正在考虑众多生物标志物，但这些方法的可行性尚未完全确定。特别是，关于使用自适应系统是否能比持续刺激提高疗效、促进刺激干预的调整以及增进我们对异常网络功能在疾病机制中作用的理解，存在关键问题。
