Dynamic multimodal connectivity analysis of brain networks in focal epilepsy

项目摘要/摘要 癫痫是一种使人衰弱的神经疾病，影响全球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，患者可能会受到遥远的影响，如癫痫发作期间失去意识(尤其是癫痫发作)和 癫痫发作之间的神经认知缺陷(发作间歇期)，两者都损害日常生活活动能力 工作，和生活质量。先前研究这些全局效应的工作导致了网络抑制 假说，即用立体定向脑电(SEEG)观察到的局灶性癫痫活动 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。 局灶性意识受损癫痫(FIA)。功能磁共振成像(FMRI)的研究提供了证据表明 相同的解剖区域有异常的功能连接(FC)。它认为反复发生的FIA会导致慢性 发作间期皮质下到新皮质的FC减少，但这一知识差距但这一知识差距尚未出现 地址。我们的目标是使用SEEG(目标1)来关联发作期和发作间期状态的FC。我特别假设在 FIAS发作期FC将在与发作间期FC异常有关的相同解剖区域减少。在……里面 除了反复发作，患者还可能有毁灭性的发作间期神经认知缺陷。这些 普遍存在的神经认知缺陷表明有一个共同的因素，被认为是皮质下 唤醒结构。已有研究表明，皮质下到新皮质结构的fMRI Fc异常 与神经认知障碍、癫痫发作频率有关，术后可恢复。虽然一般 已经概述了皮质下到新皮质的异常，对特定大脑的理解存在差距 与神经认知缺陷相关的网络。这在一定程度上可能是由于没有充分控制 唤醒状态。高警戒状态或“持续注意”状态，是一种由 静息时波动的皮质下觉醒结构。它与皮质下到新皮质的Fc变化有关， 与暂时性神经认知缺陷有关，在神经认知测试和思维过程中状态活跃 对一些人来说，静息状态功能磁共振成像是一个混乱的问题。我们的目标是将特定的皮质下网络与新皮质网络联系起来 通过fMRI-EEG控制高警戒状态来控制神经认知障碍的异常(目标2)。我 具体地说，假设在高度警惕状态下，患者的Fc在 与对照组相比，皮质下到新皮质网络的减少将与颞外相关 神经认知障碍，手术成功后网络会恢复。这项拟议的奖学金将 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 在学术医疗中心和4级癫痫中心相结合的环境中进行，世界 一流的成像学院，和工程都在一个校园里。研究多种模式来表征癫痫 网络可能会改善TLE的神经调节靶点。

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.