Investigating Network Plasticity Effects of Repetitive Brain Stimulation Following Invasive and Noninvasive Methods in Humans

研究人类侵入性和非侵入性方法重复大脑刺激的网络可塑性效应

• 批准号: 10415845
• 负责人: Nicholas Thomas Trapp
• 金额: $ 18.68万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415845
• 关键词: Affect; Anterior; Antidepressive Agents; Area; Beds; Brain; Brain Diseases; Brain region; Clinical; Clinical Trials Design; Data; Disease remission; Electric Stimulation; Electroencephalography; Electrophysiology (science); Emotional; Environment; Epilepsy; Evoked Potentials; Future; Generations; Goals; Gold; Human; Implanted Electrodes; Individual; Insula of Reil; Intractable Epilepsy; Iowa; Lateral; Light; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Measures; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Modality; Monitor; Moods; Operative Surgical Procedures; Outcome; Parietal Lobe; Patient Care; Patients; Pattern; Pharmaceutical Preparations; Physiologic pulse; Physiology; Prefrontal Cortex; Protocols documentation; Psychotherapy; Refractory; Reproducibility; Research; Resolution; Rest; Scalp structure; Seizures; Site; Stimulus; Structure; Surface; Techniques; Testing; Therapeutic; Therapeutic Uses; Training; Transcranial magnetic stimulation; Treatment Efficacy; Treatment Protocols; Universities; Work; antidepressant effect; base; career; cingulate cortex; depressed patient; design; disability; experience; human subject; improved; indexing; neurophysiology; neuropsychiatric disorder; neuroregulation; new technology; novel; novel strategies; persistent symptom; repetitive transcranial magnetic stimulation; response; spatiotemporal; standard measure; targeted biomarker; tool; treatment response

Project Summary The goal of this Mentored Patient-Oriented Research Career Development Award (K23) application is to support the additional training, mentorship and experience needed to develop a new methodology for analyzing the effects of repetitive brain stimulation using intracranial electroencephalography (iEEG) in humans. One form of repetitive brain stimulation is transcranial magnetic stimulation (TMS). TMS has revolutionized the field of therapeutics for neuropsychiatric disorders – it is a novel, noninvasive treatment option used most commonly for medication-refractory major depressive disorder. Despite this, remission rates from its use are suboptimal and ideal stimulation parameters are unknown. Suboptimal outcomes are due in large part to our poor understanding of TMS neurophysiology and antidepressant effects. TMS is thought to work by altering brain excitability within a network of targeted brain structures; for depression, this target is an emotional network including the dorsolateral prefrontal cortex. The ability of the brain to change excitability in response to repeated stimuli is referred to as plasticity. Noninvasive methods of measuring plasticity, such as scalp EEG and magnetic resonance imaging (MRI), are often imprecise and unreliable. This project proposes a novel method to invasively characterize brain plasticity induced by intracranial stimulation (Aim 1) or TMS (Aim 2) with exquisite spatiotemporal resolution. The method involves using iEEG single-pulse evoked potentials to probe and quantify excitability change (a correlate of plasticity) after repetitive stimulation in epilepsy patients. Network connectivity profiles will be analyzed with both iEEG and resting state MRI (Aim 3) to provide a unique bridge between invasive and noninvasive physiology measures. This project tests the hypothesis that repetitive brain stimulation (delivered via TMS and intracranial stimulation) will alter brain excitability in a parameter-dependent manner, and these effects will be most pronounced within the nodes of the stimulated brain network. A better understanding of how repetitive stimulation propagates through brain networks and alters brain excitability will revitalize the to-date fruitless search for reproducible biomarkers of target engagement and treatment response with these new technologies. Novel aspects of this study include the use of TMS in human subjects with iEEG, and the unique combination of both invasive and noninvasive connectivity measures (iEEG and MRI) to deeply characterize network effects of stimulation. Future directions will be 1) using this method to evaluate and refine novel brain stimulation protocols to optimize plasticity and therapeutic efficacy, and 2) applying learned principles about network effects of repetitive stimulation to inform clinical trial design and therapeutic use in other brain disorders, such as depression. The University of Iowa and this mentor team provide a rich research environment and world-class facilities for implementing this proposal. These K23 activities align with my long-term career goal of optimizing therapeutic brain stimulation to improve patient care.

项目摘要 这个受过指导的注重患者研究职业发展奖（K23）的目标是 支持开发一种新方法所需的额外培训，精神训练和经验 使用颅内脑电图（IEEG）在重复性大脑刺激中的影响 人类。重复性大脑刺激的一种形式是扭转磁刺激（TMS）。 TMS有 彻底改变了神经精神疾病的理论领域 - 这是一种新颖的无创治疗 选项最常用于药物难治性重度抑郁症。尽管如此，缓解率 从其使用中是次优的，理想的刺激参数尚不清楚。 次优的结果在很大程度上是由于我们对TMS神经生理学和 抗抑郁作用。人们认为TM可以通过改变目标大脑网络中令人兴奋的大脑来起作用 结构；对于抑郁症，该目标是一个情感网络，包括背侧前额叶皮层。 大脑因反复刺激而改变令人兴奋的能力被称为可塑性。无创 测量可塑性的方法，例如头皮脑电图和磁共振成像（MRI），通常是 不精确和不可靠。该项目提出了一种新颖的方法，可以使大脑可塑性表征 由颅内刺激（AIM 1）或TMS（AIM 2）诱导，具有独家空间临时分辨率。这 方法涉及使用IEEG单脉冲诱发的电位来探测和量化令人兴奋的变化（a 癫痫患者重复刺激后的可塑性相关。网络连接配置文件将是 与IEEG和静止状态MRI（AIM 3）进行分析，以提供侵入性和 非侵入性生理学措施。该项目检验了重复大脑刺激的假设 （通过TMS和颅内模拟传递）将改变与参数有关的大脑 方式，这些影响将在刺激的大脑网络的节点中最为明显。 更好地理解重复刺激如何通过大脑网络传播并改变大脑 令人兴奋的将振兴待命的毫无结果寻找目标参与的可再现生物标志物和 这些新技术的治疗反应。这项研究的新颖方面包括在人类中使用TMS 具有IEEG的主题，以及侵入性和无创连通性措施的独特组合（IEEG 和MRI）以深刻地表征刺激的网络效应。未来的指示将为1）使用此方法 评估和完善新的大脑刺激方案以优化可塑性和治疗效率，2） 应用有关重复刺激网络影响的学习原则，以告知临床试验设计和 在其他脑部疾病（例如抑郁症）中的治疗用途。爱荷华大学和这个心理团队 提供丰富的研究环境和世界一流的设施来实施该建议。这些K23 活动符合我优化治疗性大脑刺激以改善患者护理的长期职业目标。