Dynamic multimodal connectivity analysis of brain networks in focal epilepsy

局灶性癫痫脑网络的动态多模态连接分析

• 批准号: 10678514
• 负责人: Derek J Doss
• 金额: $ 3.28万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678514
• 关键词: Academic Medical Centers; Activities of Daily Living; Acute; Address; Adult; Affect; Anatomy; Area; Arousal; Awareness; Brain; Brain Diseases; Brain region; Chronic; Cognitive; Cognitive deficits; Conscious; Data; Disease; Distant; Electroencephalography; Electrophysiology (science); Engineering; Environment; Epilepsy; Fellowship; Focal Seizure; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Image; Impairment; Knowledge; Lead; Link; Mediating; Memory; Mentors; Modality; Nature; Neocortex; Neurocognitive; Neurocognitive Deficit; Operative Surgical Procedures; Partial Epilepsies; Pathology; Patients; Persons; Population; Quality of life; Recurrence; Regional Anatomy; Research Training; Rest; Scalp structure; Seizures; Structure; Temporal Lobe; Temporal Lobe Epilepsy; Unconscious State; Work; atmospheric sciences; comparison control; executive function; functional magnetic resonance imaging/electroencephalography; improved; multimodality; neocortical; nervous system disorder; network dysfunction; neurocognitive test; neuroregulation; new therapeutic target; postoperative recovery; processing speed; scientific atmosphere; sustained attention; vigilance

PROJECT SUMMARY/ABSTRACT Epilepsy is a debilitating neurological disorder that affects 1% of the population worldwide and temporal lobe epilepsy (TLE) is the most common form. Seizure onset in TLE is typically localized to the mesial temporal lobe, however, patients can suffer from distant effects such as loss of consciousness during seizures (ictally) and neurocognitive deficits between seizures (interictally), both of which impair one’s activities of daily living, ability to work, and quality of life. Prior work investigating these global effects have resulted in the Network Inhibition Hypothesis, which states that focal seizure activity observed with stereotactic electroencephalography (SEEG) spreads to subcortical structures responsible for neocortical activation, resulting in ictal loss of consciousness in focal impaired awareness seizures (FIAS). Studies with functional MRI (fMRI) have provided evidence that the same anatomical areas have abnormal functional connectivity (FC). It thought that recurrent FIAS lead to chronic interictal decreases in subcortical to neocortical FC, but this knowledge gap but this knowledge gap has not been addressed. We aim to relate FC of ictal and interictal states using SEEG (Aim 1). I specifically hypothesize during FIAS ictal FC will decrease in the same anatomical regions as those implicated in interictal FC abnormalities. In addition to recurrent seizures, patients can also have devastating interictal neurocognitive deficits. These widespread neurocognitive deficits suggest that there is a common factor, which is thought to be the subcortical arousal structures. It has been shown that fMRI FC abnormalities of subcortical to neocortical structures are associated with neurocognitive deficits, seizure frequency, and can recover after surgery. While general subcortical to neocortical abnormalities have been outlined, there is a gap in understanding of specific brain networks associated with neurocognitive deficits. This could be due in part to not adequately controlling for arousal state. The high vigilance or “sustained attention” state, is a state of cognitive engagement mediated by subcortical arousal structures which fluctuates at rest. It is associated with subcortical to neocortical FC changes, associated with extratemporal neurocognitive deficits, the state active during neurocognitive testing, and thought to be a confounder for resting-state fMRI by some. We aim to link specific subcortical to neocortical network abnormalities with neurocognitive deficits by controlling for the high vigilance state with fMRI-EEG (Aim 2). I specifically hypothesize that during high vigilance states, patients will have significantly decreased FC within subcortical to neocortical networks compared to controls, that the decrease will be associated with extratemporal neurocognitive deficits, and that the network will recover after successful surgery. This proposed fellowship will provide research training in a collaborative research atmosphere with expert mentors. 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. Studying multiple modalities to characterize epileptic networks may lead to improved neuromodulation targets for TLE.

项目概要/摘要 癫痫是一种使人衰弱的神经系统疾病，影响全世界 1% 的人口和颞叶 癫痫（TLE）是最常见的形式。 TLE 的癫痫发作通常局限于内侧颞叶， 然而，患者可能会遭受远程影响，例如癫痫发作期间失去知觉（发作期间）和 癫痫发作之间的神经认知缺陷（发作间期），两者都会损害一个人的日常生活活动、能力 工作和生活质量。先前调查这些全球影响的工作导致了网络抑制 假设，该假设指出通过立体定向脑电图 (SEEG) 观察到局灶性癫痫活动 扩散到负责新皮质激活的皮质下结构，导致发作性意识丧失 局灶性意识障碍癫痫发作（FIAS）。功能性磁共振成像 (fMRI) 研究提供的证据表明 相同的解剖区域具有异常的功能连接（FC）。人们认为反复发生的 FIAS 会导致慢性 发作间期皮质下至新皮质 FC 减少，但这种知识差距尚未得到解决 已解决。我们的目标是使用 SEEG 将发作期和发作间期状态的 FC 联系起来（目标 1）。我具体假设在 FIAS 发作期 FC 会在与发作间期 FC 异常相关的相同解剖区域中减少。在 除了反复发作之外，患者还可能出现严重的发作间期神经认知缺陷。这些 广泛的神经认知缺陷表明存在一个共同因素，这被认为是皮质下 唤醒结构。研究表明，功能磁共振成像 (fMRI) 皮质下到新皮质结构的 FC 异常与 与神经认知缺陷、癫痫发作频率相关，并且可以在手术后恢复。虽然一般 皮质下到新皮质异常已经概述，但对特定大脑的理解存在差距 与神经认知缺陷相关的网络。这可能部分是由于没有充分控制 觉醒状态。高度警惕或“持续关注”状态是一种由以下因素介导的认知参与状态 皮质下唤醒结构在休息时波动。它与皮质下到新皮质 FC 的变化有关， 与颞外神经认知缺陷、神经认知测试期间的活跃状态以及思维相关 一些人认为静息态功能磁共振成像是一个混杂因素。我们的目标是将特定的皮质下网络连接到新皮质网络 通过 fMRI-EEG 控制高度警惕状态来控制神经认知缺陷的异常（目标 2）。我 特别假设在高度警惕状态下，患者的 FC 会显着降低 与对照组相比，皮层下到新皮层网络的减少与颞外神经网络有关 神经认知缺陷，并且网络将在手术成功后恢复。这项拟议的研究金将 在专家导师的协作研究氛围中提供研究培训。研究培训将 在世界学术医疗中心和 4 级癫痫中心相结合的环境中进行 一流的影像学院和工程学院都在一个校区。研究多种方式来表征癫痫 网络可能会改善 TLE 的神经调节目标。