Defining the Neuromolecular Signature of TMS-Augmented Hypnotic Analgesia in Fibromyalgia Syndrome

定义纤维肌痛综合征 TMS 增强催眠镇痛的神经分子特征

• 批准号: 10016076
• 负责人: JAMES HART BISHOP
• 金额: $ 6.74万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10016076
• 关键词: Absence of pain sensation; Address; Anterior; Behavior Therapy; Brain; Clinical; Cognitive; Dangerousness; Data; Development; Development Plans; Doctor of Medicine; Doctor of Philosophy; Dorsal; Double-Blind Method; Educational workshop; Ensure; Fibromyalgia; Fingerprint; Functional Magnetic Resonance Imaging; Funding; Glutamates; Glutamine; Goals; Grant; Handedness; Hypnosis; Individual; Inositol; International; Intervention; Left; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manuscripts; Measurement; Measures; Mediating; Neurologist; Neurons; Neurotransmitters; Opioid; Opioid Receptor Binding; Outcome; Outcome Measure; Pain; Pain management; Participant; Pathway interactions; Patients; Perception; Periodicity; Pharmacology; Physiological; Pilot Projects; Population; Postdoctoral Fellow; Predisposition; Prefrontal Cortex; Process; Psychiatry; Psychologist; Publishing Peer Reviews; Radiology Specialty; Research; Research Personnel; Resources; Rest; Risk; Scanning; Scientist; Site; Spectrum Analysis; Stimulus; Structure; Symptoms; Techniques; Testing; Training; Transcranial magnetic stimulation; Treatment Efficacy; Universities; Validation; Writing; addiction; base; behavior measurement; body-mind; brain circuitry; brain dysfunction; career development; central pain; cingulate cortex; clinical pain; design; falls; fibromyalgia pain; fibromyalgia patients; gamma-Aminobutyric Acid; hypnotic; internal control; mu opioid receptors; neural circuit; neurochemistry; neuroinflammation; neuroregulation; novel; pain processing; pain relief; parent grant; patient population; professor; psychologic; repetitive transcranial magnetic stimulation; response; secondary outcome; skills; spectroscopic imaging; symposium; therapeutic biomarker; therapeutic target; tool; trait

Project Summary / Abstract Fibromyalgia syndrome is a troubling idiopathic pain condition that is complicated by a cyclical mind-body relationship, involving both physiological and psychological processes. One therapy with potential to mitigate fibromyalgia pain is hypnotic analgesia – a technique that can modulate perception of noxious stimuli. Susceptibility to hypnosis is a quantifiable trait described as hypnotizability, but only a subset of the population is hypnotizable. Hypnotizability has been found to be associated with higher resting state functional connectivity between the L-DLPFC and the dACC. However, the neurochemical signature that underlies altered functional connectivity between the default mode network and (L-DLPFC) is unknown, but could provide critical indications of therapeutic efficacy. Targeted neuromodulation of the L-DLPFC by transcranial magnetic stimulation (TMS) may prove a useful tool to modulate hypnotizability, expanding the clinical reach of hypnotic analgesia in fibromyalgia pain. This leads us to the hypothesis that altered functional connectivity in fibromyalgia pain is associated with L-DLPFC GABA and Glx concentrations. Transcranial Magnetic Stimulation (TMS) modulation of L-DLPFC GABA and GLx concentrations can alter susceptibility to hypnosis and therefore the efficacy of hypnosis in reducing fibromyalgia symptoms. In Aim 1, we will characterize baseline associations between behavioral measures (clinical pain / hypnotizability) and GABA, Glx, and myo-inositol concentrations in the L-DLPFC in subjects with fibromyalgia syndrome. To test this, we will measure brain neurochemistry non-invasively by performing magnetic resonance spectroscopy (MRS) in an L-DLPFC target identified through functional magnetic resonance imaging (fMRI). In Aim 2, we will collect pilot data to test the effect of L-DLPFC targeted TMS on a) GABA/Glx concentrations and connectivity and b) determine whether efficacy of hypnotic analgesia is associated with a change in L-DLPFC neurochemistry. These aims will be completed in the context of a training plan at Stanford University sponsored by David Spiegel, M.D., a professor of psychiatry and expert hypnosis practitioner, and co-sponsored by Daniel Spielman, Ph.D., a professor of radiology and leading researcher in spectroscopy imaging, and Nolan Williams, M.D., a dually trained neurologist-psychologist and leader in the field of neuromodulation including TMS. The training plan will include research, technical proficiency, and professional development for the applicant and postdoctoral fellow, James Bishop, Ph.D. The research will focus on the relationship between altered brain neurochemistry in fibromyalgia pain and TMS, with the goal of increasing hypnotizability and hypnotic analgesia. James will develop skills related to TMS, and MRS through directly training alongside his sponsors, and completing external coursework, seminars, and workshops. Career development will include training in the responsible conduct in research, publishing peer-reviewed manuscripts, attending international conferences, and grant writing, in addition to resources provided by professional development offices at Stanford University. Weekly discussions between James and his sponsors and formation of individualized development plan (IDP) will ensure that he receives the training necessary to pursue his objective as an independent academic scientist.

项目摘要 /摘要 纤维肌痛综合征是一种令人不安的特发性疼痛疾病，它因周期性的身心关系而复杂化，涉及身体和心理过程。一种有可能减轻纤维肌痛疼痛的疗法是催眠镇痛 - 这种技术可以调节对有害刺激的感知。催眠的启发性是一种可量化的性状，称为催眠性，但只有一部分人口可催眠。已经发现催眠性与L-DLPFC和DACC之间的静息状态功能连通性较高有关。但是，默认模式网络和（l-DLPFC）之间的功能连通性基础的神经化学签名尚不清楚，但可以提供有关治疗效率的关键指示。通过经颅磁刺激（TMS）对L-DLPFC的靶向神经调节可能证明是调节催眠能力的有用工具，从而扩大了纤维肌痛疼痛中催眠镇痛的临床覆盖率。这使我们提出了这样的假设，即纤维肌痛疼痛的功能连通性与L-DLPFC GABA和GLX浓度有关。 L-DLPFC GABA和GLX浓度的经颅磁刺激（TMS）调节可以改变对催眠的敏感性，因此催眠在减轻纤维肌痛症状方面的效率。 在AIM 1中，我们将表征L-DLPFC在患有纤维肌痛综合征的受试者中L-DLPFC中行为测量（临床疼痛 /催眠率）与GABA，GLX和肌醇浓度之间的基线关联。为了测试这一点，我们将通过通过功能磁共振成像（fMRI）鉴定的L-DLPFC靶标（fMRI）中的L-DLPFC靶标（MRS）进行磁共振光谱（MRS）来测量脑神经化学。在AIM 2中，我们将收集试验数据，以测试靶标TMS对a）GABA/GLX浓度和连通性和b）确定催眠镇痛的有效性是否与L-DLPFC神经化学的变化有关。 这些目标将在斯坦福大学的培训计划的背景下完成，由戴维·斯皮格尔（David Spiegel）包括TMS。包括研究，技术水平以及适用和博士后研究员的专业发展，James Bishop博士。该研究将重点介绍纤维肌痛疼痛和TMS中脑神经化学改变的关系，目的是增加催眠率和催眠镇痛。詹姆斯将通过与赞助商一起直接培训与TMS以及MRS相关的技能，并完成外部课程工作，半手和讲习班。职业发展还将包括研究负责任的研究，出版同行评审的手稿，参加国际会议和赠款写作，以及斯坦福大学专业发展办公室提供的资源。詹姆斯和他的赞助商之间的每周讨论与个性化发展计划（IDP）的成立将确保他接受必要的培训，以追求自己作为独立学术科学家的目标。