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

7.项目摘要/摘要 颞叶癫痫(TLE)是最常见的癫痫形式，是一种影响50%的衰弱疾病 世界上有一百万人。在TLE中，癫痫发作通常局限于癫痫形成区(EZ)。 内侧颞叶。不幸的是，TLE的负面影响并不局限于EZ。以前的研究 已显示患者静息状态功能连接性(RSFC)广泛的新皮质减少 TLE与健康对照组比较，并将这些RSFC下降与神经心理损害联系起来。 先前的工作已经导致了“网络抑制假说”，该假说认为局灶性癫痫发作可能 通过影响对皮质激活很重要的深层觉醒结构来影响广泛的新皮质。 这项拟议工作的假设是，TLE患者反复发作会导致改变 觉醒结构和新皮质之间的连接，导致新皮质连接减少和 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方法来 克服先前TLE研究的局限性，阐明脑网络功能障碍及其临床意义。 首先，这项研究将使用功能磁共振成像(FMRI)来测量唤醒之间的RSFC TLE患者术前中枢结构和新皮质的研究然后，为了确定手术治疗是否 结果改善了术后实现癫痫缓解的患者的连接性，fMRI连接性 分析将在手术后至少一年重复(目标1)。第二，了解临床 觉醒中枢网络扰动的含义，术前和术后的RSFC模式将与 疾病严重程度的临床测量和特定的神经认知参数。这项工作预计会更大 RSFC的紊乱将与疾病严重程度的增加和神经认知能力的下降有关， 手术后，癫痫发作缓解的患者将在神经认知领域得到改善 与额顶功能关系最密切(目标2)。第三，到目前为止，还没有显示出直接的关系 发作间网络干扰和发作间连通性干扰之间的关系。这项工作将解决这个问题 使用颅内脑电进行动态功能连接(DFC)分析的知识差距 以及在CPS和SPS之间。这项工作预计，在CPS期间，而不是SPS期间，新皮质DFC将 与发作间连通性(目标3)相比降低。这项拟议的研究金将在以下方面提供研究培训 在与翻译神经科学和工程学专家导师合作的研究氛围中 研究。研究培训将在一个学术医学中心相结合的环境中进行 拥有4级癫痫中心、世界级成像研究所和工程技术人员，在一个校园内确保 唯一适合这项拟议工作各方面优秀培训的环境。研究唤醒网络 TLE的功能障碍可能导致改善神经调节靶点或对这种疾病的行为治疗 可能会提高我们对癫痫原因不明猝死(SUDEP)的机械理解。

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).