NCS-FO: Closed-loop neuromodulation for chronic pain

NCS-FO：慢性疼痛的闭环神经调节

• 批准号: 1835000
• 负责人: Zhe Chen
• 金额: $ 87.72万
• 依托单位: New York University Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1835000&HistoricalAwards=false
• 关键词: NCS; FO; Closed; loop; neuromodulation

Proposal Title: NSF-FO: Closed-loop neuromodulation for chronic painPain is a complex and multi-dimensional experience that nevertheless occurs commonly in people's daily lives. Chronic pain affects 1.5 billion people worldwide and has contributed to major healthcare costs. The treatment of chronic pain remains insufficient, highlighted by the current opioid epidemic. In the past few decades, neuroscience research has provided accumulating knowledge of pain processing in the central nervous system. However, effective analgesic options with limited side effects remain elusive, in large part because the neural mechanism for how chronic pain is perceived and modulated in the brain is poorly understood. This proposal tries to challenge the status quo using chronic pain-treated rodent models. The use of rodent models would allow researchers to examine the brain activity at specific localized neural circuits at a cellular resolution, and to further provide a guideline for neuromodulation-based pain treatment. The project has great translational potential to advance personalized pain medicine and provide therapy for the chronic pain associated with a wide range of neuropsychiatric disorders. This project will also promote education and diversity in training undergraduate/graduate students or postdoctoral fellows, and will be committed to data sharing and outreach activity in order to maximize the benefit to society. This research project will integrate behavior and electrophysiology studies to investigate the causal impact of neuromodulation on neocortical circuits in chronic pain conditions. The ultimate objective of this proposal is to develop a noninvasive brain machine interface system for detecting and relieving chronic pain in a rodent model. On the one hand, this project will investigate examine basic neuroscience questions regarding the neural variability underlying complex sensory and affective processes. On the other hand, this project will investigate a minimally invasive neuromodulation strategy for treating chronic pain. In Aim 1, in vivo extracellular neural activity (including the ensemble spike activity and local field potentials) will be recorded from the primary somatosensory cortex and anterior cingulate cortex of freely behaving chronic pain-treated rats. This will allow researchers to characterize nociceptive response variability under different chronic pain conditions. In Aim 2, a closed-loop rodent neuromodulation interface will be developed for chronic pain control, which combines the detection of pain signals (?detection arm?) and neuromodualtion (?treatment arm?). This aim will optimize neural signal processing using multi-region local field potentials and further leverage advances in neuromodulation techniques to employ epicranial current stimulation on the targeted brain region (such as the primary motor cortex). In Aim 3, the current stimulation parameters (e.g., intensity and duration) will be optimized using online neurofeedback to improve the efficacy of neuromodulation in light of reinforcement learning. In summary, the brain-machine interface system will tease apart the mechanism of cortical pain circuits, and characterize the nociceptive response variability under different (inflammatory vs. neuropathic) chronic pain conditions. Together, these results will reveal novel insights into circuit mechanisms of chronic pain.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

提案标题：NSF-FO：慢性疼痛的闭环神经调节疼痛是一种复杂且多维的体验，但在人们的日常生活中却很常见。慢性疼痛影响着全球 15 亿人，并造成巨大的医疗费用。当前阿片类药物的流行凸显了慢性疼痛的治疗仍然不足。在过去的几十年里，神经科学研究积累了中枢神经系统疼痛处理的知识。然而，副作用有限的有效镇痛选择仍然难以捉摸，很大程度上是因为人们对大脑如何感知和调节慢性疼痛的神经机制知之甚少。该提案试图利用慢性疼痛治疗的啮齿动物模型来挑战现状。啮齿动物模型的使用将使研究人员能够以细胞分辨率检查特定局部神经回路的大脑活动，并进一步为基于神经调节的疼痛治疗提供指导。该项目具有巨大的转化潜力，可以推进个性化疼痛医学，并为与多种神经精神疾病相关的慢性疼痛提供治疗。该项目还将促进本科生/研究生或博士后培训的教育和多样性，并将致力于数据共享和外展活动，以最大限度地造福社会。该研究项目将整合行为和电生理学研究，以研究神经调节对慢性疼痛条件下新皮质回路的因果影响。该提案的最终目标是开发一种非侵入性脑机接口系统，用于检测和缓解啮齿动物模型中的慢性疼痛。一方面，该项目将研究有关复杂感觉和情感过程背后的神经变异性的基本神经科学问题。另一方面，该项目将研究治疗慢性疼痛的微创神经调节策略。在目标 1 中，将从自由行为的慢性疼痛治疗大鼠的初级体感皮层和前扣带皮层记录体内细胞外神经活动（包括整体尖峰活动和局部场电位）。这将使研究人员能够表征不同慢性疼痛条件下伤害性反应的变异性。在目标 2 中，将开发用于慢性疼痛控制的闭环啮齿动物神经调节接口，该接口结合了疼痛信号的检测（“检测臂”）和神经调节（“治疗臂”）。这一目标将利用多区域局部场电位优化神经信号处理，并进一步利用神经调节技术的进步，对目标大脑区域（例如初级运动皮层）采用颅内电流刺激。在目标 3 中，将使用在线神经反馈来优化当前的刺激参数（例如强度和持续时间），以根据强化学习提高神经调节的功效。总之，脑机接口系统将梳理皮质疼痛回路的机制，并表征不同（炎症性与神经性）慢性疼痛条件下伤害性反应的变异性。总之，这些结果将揭示对慢性疼痛回路机制的新颖见解。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Efficient Position Decoding Methods Based on Fluorescence Calcium Imaging in the Mouse Hippocampus.

• DOI: 10.1162/neco_a_01281
• 发表时间: 2020-06
• 期刊: Neural computation
• 影响因子: 2.9
• 作者: Tu M;Zhao R;Adler A;Gan WB;Chen ZS
• 通讯作者: Chen ZS

Predictive coding models for pain perception.

• DOI: 10.1007/s10827-021-00780-x
• 发表时间: 2021-05
• 期刊: Journal of computational neuroscience
• 影响因子: 1.2
• 作者: Song Y;Yao M;Kemprecos H;Byrne A;Xiao Z;Zhang Q;Singh A;Wang J;Chen ZS
• 通讯作者: Chen ZS

Granger causality analysis of rat cortical functional connectivity in pain.

• DOI: 10.1088/1741-2552/ab6cba
• 发表时间: 2020-02-07
• 期刊: Journal of neural engineering
• 影响因子: 4
• 作者: Guo X;Zhang Q;Singh A;Wang J;Chen ZS
• 通讯作者: Chen ZS

A prototype closed-loop brain-machine interface for the study and treatment of pain.

• DOI: 10.1038/s41551-021-00736-7
• 发表时间: 2023-04
• 期刊: Nature biomedical engineering
• 影响因子: 28.1

Pain, from perception to action: A computational perspective.

• DOI: 10.1016/j.isci.2022.105707
• 发表时间: 2023-01-20
• 期刊: iScience
• 影响因子: 5.8
• 作者: Chen ZS;Wang J
• 通讯作者: Wang J