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: 10655436
• 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/10655436
• 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; Human; Implanted Electrodes; Individual; Insula of Reil; Intractable Epilepsy; Iowa; Lateral; 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; career; cingulate cortex; depressed patient; design; disability; experience; hands-on learning; human subject; improved; indexing; magnetic resonance imaging/electroencephalography; 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.

项目概要 这项以患者为导向的研究职业发展奖（K23）申请的目标是 支持开发新方法所需的额外培训、指导和经验 使用颅内脑电图（iEEG）分析重复脑刺激的影响 人类。重复性脑刺激的一种形式是经颅磁刺激（TMS）。 TMS 有 彻底改变了神经精神疾病的治疗领域——这是一种新颖的非侵入性治疗方法 最常用于治疗难治性重度抑郁症的选项。尽管如此，缓解率 从其使用来看，效果并不理想，并且理想的刺激参数未知。 次优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。 TMS 被认为是通过改变目标大脑网络内的大脑兴奋性来发挥作用的。 结构；对于抑郁症，这个目标是一个情绪网络，包括背外侧前额叶皮层。这 大脑响应重复刺激而改变兴奋性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 不精确且不可靠。该项目提出了一种侵入性表征大脑可塑性的新方法 由颅内刺激（目标 1）或 TMS（目标 2）诱导，具有精致的时空分辨率。这 该方法涉及使用 iEEG 单脉冲诱发电位来探测和量化兴奋性变化（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 使用 iEEG 和静息态 MRI 进行分析（目标 3），以在侵入性和静息态 MRI 之间提供独特的桥梁 无创生理学措施。该项目测试了重复大脑刺激的假设 （通过 TMS 和颅内刺激传递）将改变参数依赖性的大脑兴奋性 方式，这些效应在受刺激的大脑网络的节点内最为明显。 更好地理解重复刺激如何通过大脑网络传播并改变大脑 兴奋性将重振迄今为止对目标参与的可重复生物标志物的毫无成果的搜索和 这些新技术的治疗反应。这项研究的新颖之处包括 TMS 在人体中的使用 具有 iEEG 的受试者，以及侵入性和非侵入性连接测量的独特组合（iEEG 和 MRI）来深入表征刺激的网络效应。未来的方向将是 1) 使用此方法 评估和完善新型脑刺激方案以优化可塑性和治疗效果，2) 应用有关重复刺激网络效应的学习原理为临床试验设计和 治疗其他脑部疾病，例如抑郁症。爱荷华大学和这个导师团队 为实施该提案提供丰富的研究环境和世界一流的设施。这些K23 这些活动符合我的长期职业目标，即优化大脑刺激治疗以改善患者护理。

项目成果

Neuroimaging Correlates of Post-Traumatic Stress Disorder in Traumatic Brain Injury: A Systematic Review of the Literature.

创伤性脑损伤中创伤后应激障碍的神经影像学相关性：文献的系统回顾。

• DOI: 10.1089/neu.2021.0453
• 发表时间: 2023
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: Esagoff,AaronI;Stevens,DanielA;Kosyakova,Natalia;Woodard,Kaylee;Jung,Diane;Richey,LisaN;Daneshvari,NicholasO;Luna,LiciaP;Bray,MichaelJC;Bryant,BarryR;Rodriguez,CarlaP;Krieg,Akshay;Trapp,NicholasT;Jones,MelissaB;Roper
• 通讯作者: Roper

Behavioral and Emotional Dyscontrol Following Traumatic Brain Injury: A Systematic Review of Neuroimaging and Electrophysiological Correlates.

• DOI: 10.1016/j.jaclp.2022.05.004
• 发表时间: 2022-11
• 期刊: JOURNAL OF THE ACADEMY OF CONSULTATION-LIAISON PSYCHIATRY
• 影响因子: 2.3
• 作者: Bryant, Barry R.;Richey, Lisa N.;Jahed, Sahar;Heinzerling, Amanda;Stevens, Daniel A.;Pace, Benjamin D.;Tsai, Jerry;Bray, Michael J. C.;Esagoff, Aaron I.;Adkins, Jaxon;Cohen, Ilana;Narapareddy, Bharat R.;Rodriguez, Carla P.;Jones, Melissa B.;Roper, Carrie;Goldwaser, Eric L.;Lobner, Katie;Siddiqi, Shan;Sair, Haris, I;Lauterbach, Margo;Luna, Licia P.;Peters, Matthew E.;Trapp, Nicholas T.
• 通讯作者: Trapp, Nicholas T.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

• DOI: 10.1097/yct.0000000000000840
• 发表时间: 2022-09-01
• 期刊: The journal of ECT
• 作者: Zandi PP;Morreale M;Reti IM;Maixner DF;McDonald WM;Patel PD;Achtyes E;Bhati MT;Carr BR;Conroy SK;Cristancho M;Dubin MJ;Francis A;Glazer K;Ingram W;Khurshid K;McClintock SM;Pinjari OF;Reeves K;Rodriguez NF;Sampson S;Seiner SJ;Selek S;Sheline Y;Smetana RW;Soda T;Trapp NT;Wright JH;Husain M;Weiner RD
• 通讯作者: Weiner RD

The Neuropsychiatric Approach to the Assessment of Patients in Neurology.

• DOI: 10.1055/s-0042-1745741
• 发表时间: 2022-04
• 期刊: SEMINARS IN NEUROLOGY
• 影响因子: 2.7
• 作者: Trapp, Nicholas T.;Martyna, Michael R.;Siddiqi, Shan H.;Bajestan, Sepideh N.
• 通讯作者: Bajestan, Sepideh N.