Multimodal analysis of interictal and ictal brain connectivity in temporal lobe epilepsy

颞叶癫痫发作间期和发作期脑连接的多模态分析

• 批准号: 10002315
• 负责人: Hernan Francisco Jose Gonzalez
• 金额: $ 3.02万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002315
• 关键词: Academic Medical Centers; Acute; Address; Adult; Affect; Arousal; Atrophic; Behavior Therapy; Brain; Brain Stem; Brain region; Cessation of life; Clinical; Cognitive; Complex; Conscious; Diagnosis; Disease; Distal; Electroencephalography; Electrophysiology (science); Engineering; Ensure; Environment; Epilepsy; Excision; Fellowship; Focal Seizure; Freedom; Frequencies; Functional Magnetic Resonance Imaging; Human; Image; Impairment; Individual; Institutes; Knowledge; Lead; Link; Location; Maps; Measures; Medical; Mentors; Neocortex; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Operative Surgical Procedures; Partial Epilepsies; Patients; Pattern; Performance; Persons; Postoperative Period; Recovery; Recurrence; Refractory; Research; Research Training; Rest; Rodent; Seizures; Severity of illness; Signal Transduction; Simple Partial Seizures; Structure; Temporal Lobe; Temporal Lobe Epilepsy; Thalamic structure; Time; Training; Work; basal forebrain; comorbidity; executive function; experience; gray matter; improved; innovation; mortality risk; multimodality; neocortical; nervous system disorder; network dysfunction; neural network; neurophysiology; neuroregulation; psychosocial; relating to nervous system; response; scientific atmosphere; targeted treatment; translational neuroscience

7. PROJECT SUMMARY/ABSTRACT Temporal lobe epilepsy (TLE) is the most common form of epilepsy, a debilitating disease that affects 50 million people in the world. In TLE, seizure onset is typically localized to an epileptogenic zone (EZ) in the mesial temporal lobe. Unfortunately, the negative effects of TLE are not limited to the EZ. Previous studies have shown widespread neocortical decreases in resting state functional connectivity (RSFC) in patients with TLE versus healthy controls and have related these RSFC decreases to neuropsychological impairments. Previous works have resulted in the “network inhibition hypothesis,” that proposes that focal seizures may influence widespread neocortex by affecting deep arousal structures that are important for cortical activation. The hypothesis of this proposed work is that recurrent seizures in patients with TLE result in altered connectivity between arousal structures and the neocortex, leading to decreased neocortical connectivity and impaired neurocognition. To explore this hypothesis, this work will use an innovative, multimodal approach to overcome the limitations of prior TLE studies to elucidate brain network dysfunction and its clinical implications. First, this study will use functional magnetic resonance imaging (fMRI) to measure RSFC between arousal center structures and the neocortex in pre-operative patients with TLE. Then, to determine if surgical treatment results in improved connectivity in patients that achieve seizure freedom after surgery, fMRI connectivity analyses will be repeated at least one year after surgery (Aim 1). Second, to understand the clinical implications of arousal center network perturbations, pre- and post-operative RSFC patterns will be related to clinical measures of disease severity and specific neurocognitive parameters. This work expects that larger RSFC perturbations will be associated with increased disease severity and worse neurocognitive performance, and that after surgery patients with seizure freedom will experience improvement in neurocognitive domains most closely related to frontoparietal function (Aim 2). Third, thus far, no direct relationship has been shown between ictal network perturbations and interictal connectivity disturbances. This work will address this knowledge gap by performing dynamic functional connectivity (DFC) analyses using intracranial EEG during and between CPS and SPS. This work expects that during CPS, but not SPS, neocortical DFC will be decreased compared to interictal connectivity (Aim 3). This proposed fellowship will provide research training in in a collaborative research atmosphere with expert mentors in translational neuroscience and engineering research. Research training will be conducted in an environment that combines an academic medical center with a level 4 epilepsy center, world class imaging institute, and engineering all on one campus, ensuring an environment uniquely suited to excellent training in all aspects of this proposed work. Studying arousal network dysfunction in TLE may lead to improved neuromodulation targets or behavioral therapies for this disorder and may improve our mechanistic understanding of Sudden Unexplained Death in Epilepsy (SUDEP).

7.项目总结/摘要 颞叶癫痫（TLE）是最常见的癫痫形式，是一种使人衰弱的疾病， 世界上的百万人。在TLE中，癫痫发作通常局限于大脑皮层中的致痫区（EZ）。 内侧颞叶不幸的是，TLE的负面影响不仅限于EZ。以前的研究 已经显示，在患有以下疾病的患者中，静息状态功能连接（RSFC）的新皮质广泛减少： TLE与健康对照组相比，并将这些RSFC降低与神经心理学损伤相关。 先前的研究提出了“网络抑制假说”，认为局灶性癫痫发作可能 通过影响对皮层激活很重要的深层唤醒结构来影响广泛的新皮层。 这项工作的假设是，TLE患者的反复发作会导致TLE患者的神经功能改变。 唤醒结构和新皮层之间的连接，导致新皮层连接减少， 神经认知受损为了探索这一假设，这项工作将使用一种创新的，多模式的方法， 克服了先前TLE研究的局限性，以阐明脑网络功能障碍及其临床意义。 首先，本研究将使用功能性磁共振成像（fMRI）来测量唤醒之间的RSFC TLE患者术前的中枢结构和新皮质。然后为了确定手术治疗 在手术后实现癫痫发作自由的患者中，fMRI连接 分析将在手术后至少一年重复进行（目标1）。二、了解临床 唤醒中心网络扰动的影响，术前和术后RSFC模式将与 疾病严重程度和特定神经认知参数的临床测量。这项工作预计， RSFC扰动将与疾病严重程度增加和神经认知表现较差相关， 手术后癫痫发作的患者将在神经认知领域得到改善 与额顶叶功能关系最密切（目标2）。第三，到目前为止，还没有显示出直接的关系。 发作网络扰动和发作间期连通性扰动之间的关系。这项工作将解决这一问题 通过使用颅内EEG进行动态功能连接（DFC）分析， 在CPS和SPS之间。这项工作预计，在CPS，但不是SPS，新皮层DFC将是 与发作间期连通性相比降低（目标3）。这项拟议的研究金将提供以下方面的研究培训： 在与转化神经科学和工程专家导师的合作研究氛围中 research.研究培训将在一个结合学术医疗中心的环境中进行 4级癫痫中心，世界一流的影像研究所和工程都在一个校园，确保 环境独特，适合在本拟议工作的各个方面进行出色的培训。研究唤醒网络 TLE中的功能障碍可能导致针对这种障碍的神经调节靶点或行为疗法的改善， 可能会提高我们对癫痫不明原因猝死（SUDEP）的机械理解。