Ascertaining Neurocircuitry to Enhance Neuromodulation Development ASCEND

确定神经回路以增强神经调节发展 ASCEND

• 批准号: 10341194
• 负责人: Colin Hawco
• 金额: $ 55.17万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10341194
• 关键词: 3-Dimensional; Advanced Development; Adverse effects; Amygdaloid structure; Anterior; Anterograde Amnesia; Antidepressive Agents; Behavior; Biomedical Engineering; Biometry; Brain region; Clinical; Clinical Research; Clinical Trials; Cognitive; Computer Models; Corpus striatum structure; Data; Development; Devices; Disease; Electric Stimulation; Electroconvulsive Therapy; Ensure; Functional Magnetic Resonance Imaging; Funding; Goals; Head; Hippocampus (Brain); Individual Differences; Infrastructure; Insula of Reil; International; Intervention; Investigation; Knowledge; Lateral; Link; Literature; Magnetic Resonance Imaging; Magnetism; Major Depressive Disorder; Medial; Medical center; Memory; Memory impairment; Mental Health; Methods; Modality; Modeling; Morbidity - disease rate; National Institute of Mental Health; Neurocognitive; Neuropsychology; Outcome; Patients; Pattern; Penetration; Physiologic pulse; Physiological; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Property; Psychiatry; Public Health; Research; Resistance; Rest; Retrograde amnesia; Risk; Role; Safety; Sample Size; Sampling; Science; Seizures; Site; Solid; Specificity; Structure; Temporal Lobe; Therapeutic; United States Food and Drug Administration; Weight; Width; Work; addiction; antidepressant effect; barrier to care; cingulate cortex; clinical practice; clinically significant; cognitive function; computational neuroscience; depressive symptoms; design; disability; electric field; emotion regulation; experience; functional disability; imaging facilities; improved; innovation; magnetic field; magnetic seizure therapy; mortality; neural circuit; neuroimaging; neuromechanism; neurophysiology; neuroregulation; novel therapeutics; personalized medicine; public health relevance; relating to nervous system; response; side effect; symptomatic improvement; treatment effect; treatment response; treatment-resistant depression; trial comparing

PROJECT ABSTRACT Major depressive disorder (MDD) is ranked second among all diseases in global impact. Unfortunately, many patients have treatment-resistant MDD (TRD), for which the most effective antidepressant treatment option is electroconvulsive therapy (ECT). However, the neurocognitive adverse effects (e.g., anterograde and retrograde amnesia) induced by ECT mitigate the attainment of desired clinical outcomes. As such, the development of new and safe neuromodulatory antidepressant interventions is strongly warranted. One new type of neuromodulation treatment that has antidepressant properties and is under active development is magnetic seizure therapy (MST). MST is neurocognitively safer than ECT because it uses magnetic rather than electrical fields to induce seizures, which have shallower penetration and therefore avoid the undesired side- effect of delivering intense electrical stimulation to the medial temporal lobe. As yet there has been no research into the neuromechanisms underlying MST’s antidepressant and neurocognitive effects. To systematically uncover these mechanisms, we are building upon an international, NIMH funded (R01 MH112815), US Food and Drug Administration Investigational Device Exemption (IDE; #G170127) approved clinical study that will compare and contrast clinical and neurocognitive outcomes of ECT and MST. The goal of this R01 is to conduct research Ascertaining Neurocircuitry to Enhance Neuromodulation Development (ASCEND). In the proposed study, we will capitalize on that project by adding advanced magnetic resonance imaging (MRI), individualized 3-D computational head modeling of ECT and MST (E-fields in stimulated brain regions), and neurophysiological modeling of activity propagation and plasticity resulting from each treatment type. This innovative 5-year project has two aims: 1) Determine the common and distinct neural circuit correlates of antidepressant treatment response between RUL-UB-ECT and MST, and 2) Determine the common and distinct neural circuit correlates of memory side effects between RUL-UB-ECT and MST. The proposed study will draw upon an interdisciplinary team from diverse backgrounds including translational neurocognitive science, neuropsychology, computational neuroscience, psychiatry, neuroimaging, bioengineering, and biostatistics. The synthesis of physical (E-field) and physiological (neural activity and dynamics) computational modeling and MRI with the clinical and neurocognitive metrics from the current NIMH-funded clinical trial will allow us to determine neuromodulation-induced changes in neurocircuitry, and their corresponding relationships to behavior. Such knowledge will elucidate the neural mechanisms of antidepressant seizure therapy (ECT, MST) to inform new treatment methods that optimally target neurocircuitry related to symptom improvement, while ensuring neurocognitive safety. These developments will make a major contribution to improving the lives of the many patients with TRD and yield a substantial positive public health impact.

项目摘要 重度抑郁症（MDD）对全球影响在所有疾病中排名第二。不幸的是，许多 患有难治性抑郁症（TRD）的患者，最有效的抗抑郁治疗选择是 电休克治疗（ECT）。然而，神经认知不良反应（例如，顺行和 ECT 引起的逆行性遗忘症（retrograde amnesia）会影响预期临床结果的实现。因此， 开发新的、安全的神经调节抗抑郁干预措施是非常有必要的。一件新的 具有抗抑郁特性且正在积极开发的神经调节治疗类型是 磁癫痫治疗（MST）。 MST 在神经认知方面比 ECT 更安全，因为它使用的是磁性而不是 电场诱发癫痫发作，其穿透力较浅，因此避免了不良的副作用 向内侧颞叶提供强烈电刺激的效果。目前还没有研究 深入了解 MST 抗抑郁和神经认知作用的神经机制。为了系统地 为了揭示这些机制，我们正在建立一个国际性的、NIMH 资助的 (R01 MH112815)、美国食品 和药物管理局研究设备豁免（IDE；#G170127）批准的临床研究，将 比较和对比 ECT 和 MST 的临床和神经认知结果。 R01 的目标是 开展确定神经回路以增强神经调节发展（ASCEND）的研究。在 在拟议的研究中，我们将通过添加先进的磁共振成像（MRI）来利用该项目， ECT 和 MST（受刺激大脑区域的电场）的个性化 3D 计算头部建模，以及 每种治疗类型产生的活动传播和可塑性的神经生理学模型。这 这个为期 5 年的创新项目有两个目标：1）确定共同和独特的神经回路相关性 RUL-UB-ECT 和 MST 之间的抗抑郁治疗反应，以及 2) 确定共同点和 RUL-UB-ECT 和 MST 之间记忆副作用的不同神经回路相关。拟议的研究 将利用来自不同背景的跨学科团队，包括转化神经认知 科学、神经心理学、计算神经科学、精神病学、神经影像学、生物工程和 生物统计学。物理（电场）和生理（神经活动和动力学）计算的综合 使用当前 NIMH 资助的临床试验中的临床和神经认知指标进行建模和 MRI 使我们能够确定神经调节引起的神经回路变化及其相应的变化 与行为的关系。这些知识将阐明抗抑郁药物癫痫发作的神经机制 疗法（ECT、MST），以提供最佳针对与症状相关的神经回路的新治疗方法 改善，同时确保神经认知安全。这些发展将做出重大贡献 改善许多 TRD 患者的生活，并对公共健康产生重大积极影响。