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.

项目总结/摘要 癫痫是一种使人衰弱的神经系统疾病，影响全球1%的人口， 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，患者可能会遭受远期影响，如癫痫发作期间的意识丧失（发作性）， 癫痫发作之间的神经认知缺陷（发作间期），这两者都会损害一个人的日常生活活动， 工作和生活质量。先前研究这些全局效应的工作已经导致了网络抑制 假设，即立体定向脑电图（SEEG）观察到的局灶性癫痫发作活动 扩散到负责新皮层激活的皮层下结构，导致癫痫发作性意识丧失， 局灶性意识障碍发作（FIAS）。功能性磁共振成像（fMRI）的研究提供了证据， 相同的解剖区域具有异常的功能连接（FC）。认为反复发作的FIAS导致慢性 发作间期皮质下到新皮质FC减少，但这种知识差距，但这种知识差距还没有 处理。我们的目标是使用SEEG（目标1）将发作和发作间期状态的FC联系起来。我特别假设 FIAS发作FC将在与发作间期FC异常相关的相同解剖区域中降低。在 除了反复发作外，患者还可能具有毁灭性的发作间期神经认知缺陷。这些 广泛的神经认知缺陷表明，有一个共同的因素，这被认为是皮层下 唤醒结构已经表明，皮层下到新皮层结构的fMRI FC异常是 与神经认知缺陷、癫痫发作频率相关，手术后可恢复。而一般 虽然已经概述了皮层下到新皮层的异常，但在对特定大脑的理解方面存在差距， 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 唤醒状态高度警惕或“持续注意”状态是一种认知参与的状态， 在休息时波动的皮层下唤醒结构。它与皮层下到新皮层的FC变化有关， 与颞外神经认知缺陷相关，神经认知测试期间活跃的状态，以及思维 是静息态功能磁共振成像的干扰因素。我们的目标是连接特定的皮层下到新皮层网络 通过用fMRI-EEG控制高警觉状态来控制具有神经认知缺陷的异常（目的2）。我 特别假设在高警惕状态下，患者的FC会显著降低， 与对照组相比，皮层下到新皮层网络的减少将与颞外 神经认知缺陷，并且该网络将在成功手术后恢复。拟议的研究金将 在与专家导师合作的研究氛围中提供研究培训。研究培训将是 在一个学术医疗中心与世界4级癫痫中心相结合的环境中进行 成像学院和工程学院都在一个校园里。研究多种模式来表征癫痫 网络可能导致改善TLE的神经调节靶点。