Spatiotemporal alterations of thalamocortical circuitry functioning underlie pain

丘脑皮质回路功能的时空变化是疼痛的根源

• 批准号: 10659569
• 负责人: JIAN KONG
• 金额: $ 65.44万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659569
• 关键词: Acute Pain; Address; Advocate; Anxiety; Attenuated; Back; Brain; Cephalic; Chronic; Chronic low back pain; Clinical; Clinical assessments; Complex; Coupled; Development; Dimensions; Double-Blind Method; Electroencephalography; Enrollment; Exhibits; Experimental Models; Florida; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; General Hospitals; Goals; Hyperactivity; Impairment; Investigation; Limbic System; Link; Maintenance; Methodology; Modeling; Noise; Pain; Pain management; Participant; Pathology; Patients; Periodicity; Protocols documentation; Reproducibility; Rest; Role; Sampling; Severities; Site; Symptoms; Thalamic structure; Therapeutic; Therapeutic Effect; Translating; Treatment Cost; Validation; active control; chronic pain; clinical pain; design; effective intervention; experience; experimental study; functional magnetic resonance imaging/electroencephalography; functional restoration; insight; multimodal neuroimaging; neural; neuropsychiatric disorder; neuroregulation; novel; pain perception; pain symptom; pressure; recruit; response; spatiotemporal

SUMMARY Pain is a highly debilitating condition that is complex and difficult to manage. The neural basis of pain involves alterations in thalamocortical (TC) circuitry functioning, which can manifest as TC dysconnectivity and dysrhythmia (especially, impaired alpha oscillations). While likely reflecting inherently coupled (spatial and temporal) aspects of TC circuitry dysfunction, to date, TC dysconnectivity and dysrhythmia have only been examined independently, precluding fundamental understanding and effective intervention of this important pathology of pain. Capitalizing on our fully developed multimodal neuroimaging methodology (simultaneous EEG-fMRI and combined EEG-MEG-fMRI) and transcranial alternating current stimulation (tACS), the current R01 aims to address this critical gap. Aim 1 (Expt. 1) will directly link the spatial (via fMRI TC connectivity) and temporal (via EEG/MEG alpha oscillations) aspects to demonstrate coupled spatiotemporal alterations in TC circuitry functioning in experimental (tonic) and clinical (chronic low back) pain. Aims 2 & 3 will causally unify and upregulate the coupled spatiotemporal TC circuitry functioning in experimental and clinical pain, as causal manipulation of one aspect (TC dysrhythmia) via tACS of alpha oscillations (α-tACS) induces TC-circuit-wide functional restoration. Implementing a rigorously controlled experiment with a double-blind, double-controlled (active and passive control), crossover tACS design (Expt. 2), Aim 2 will establish an experimental model of this hitherto unexplored mechanism of pain. Through four weeks of α-tACS among patients with chronic low back pain (Expt. 3), Aim 3 will ascertain this unified TC circuitry pathology of pain (and reveal potential therapeutic effects of neuromodulation of alpha oscillations). Leveraging special but complementary expertise and facilities of our two labs, the three Aims pursue a broad and in-depth investigation, translating basic experimental insights into mechanistic understanding of acute and chronic pain. The project also emphasizes rigor and reproducibility through parallel recruitment of large and diverse samples (200 healthy participants and 140 patients) and multi-point cross/within-site validation and integration. Findings from this project will cast a “new look”—a unified spatiotemporal account—on TC pathology of pain and hence inspire novel pain treatments.

概括 疼痛是一种高度令人衰弱的状况，很复杂且难以管理。疼痛的神经基础涉及 丘脑皮质（TC）电路功能的改变，可以表现为TC Dysconnectionitive和 心律失常（尤其是α振荡受损）。虽然可能反映固有的耦合（空间和 迄今 独立研究，排除了对这一重要的基本理解和有效的干预 疼痛的病理。 利用我们完全开发的多模式神经影像学方法（同时进行EEG-FMRI和 EEG-MEG-FMRI）和thrancranial交流电流刺激（TACS），电流R01的目的是 解决这个关键的差距。 AIM 1（ext。1）将直接链接空间（通过fMRI TC连接）和临时链接 （通过EEG/MEG Alpha振荡）方面证明了TC电路中的时空变化 在实验（补品）和临床（慢性下背部）疼痛中功能。目标2和3将因果关系统一和 上调在实验和临床疼痛中起作用的时空TC电路，作为因果关系 通过Alpha振荡（α-TACS）的TAC对一个方面（TC异常）操纵（TC动力学）可诱导TC循环范围 功能恢复。通过双盲，双控制的严格控制实验 （主动和被动控制），跨界TACS设计（ext。2），AIM 2将建立一个实验模型 这种击球手意外的疼痛机制。在慢性低的患者中，在四个星期的α-TAC中 背痛（3），AIM 3将确定疼痛的统一TC电路病理学（并揭示了潜力 α振荡神经调节的治疗作用）。 利用我们两个实验室的特殊但完整的专业知识和设施，这三个目标追求广泛的目标 和深入研究，将基本的实验见解转化为对急性和的机械理解 慢性疼痛。该项目还通过并行招募大型和 多种样本（200名健康参与者和140名患者）和多点交叉/内部验证和 一体化。该项目的调查结果将投入“新外观”（一个统一的时空帐户） 疼痛的病理，因此激发了新颖的疼痛治​​疗。