Multimodal imaging of memory in epilepsy from whole brain networks to local neuronal responses: Implications for surgical decision-making

前额叶切除术(ATL)是一种非常成功的消除癫痫发作的治疗方法。 颞叶癫痫(TLE)。然而，ATL诱导的记忆力下降是频繁的，通常是严重的，具有 对生活质量和功能结果的有害影响。立体定向激光杏仁核海马区切除术 (SLAH)已经作为一种可以将内存风险降至最低的微创替代方案而引入 拒绝。然而，目前尚不清楚哪些患者将从SLAH中受益最大，以及SLAH是否 与ATL相比，降低了情节记忆下降的关键方面的风险。在上一次拨款期间 在融资期间，我们展示了结合结构性(SMRI)、弥散- 加权(DMRI)和功能(FMRI)成像，以更好地表征基础神经网络 术前语言和记忆障碍及(重新)组织和TLE。我们建议同样的 多模式成像(MMI)方法可用于量化术后记忆衰退的风险。在这款R01中， 我们扩展了我们的MMI方法，将sMRI/dMRI/fMRI与颅内记录(IEEG)相结合，使我们能够 深入研究TLE中情节记忆网络的空间和时间动态。我们采用多式联运 联想学习任务具有现实世界的含义(例如，将一张脸与一个名字配对)，这是以前没有的 在外科的背景下学习。此外，我们还借鉴了海马区的认知神经科学模型 这可能解释了为什么许多患者在记忆上难以做出细微的区分(即，受损 图案分离)，即使简单的项目记忆看起来完好无损。我们建议我们的MMI方法将 对TLE中的情节记忆网络进行了更完整的刻画，揭示了TLE的结构和 个体患者的功能重组，并在以下情况下启用个性化的风险评估方法 正在考虑手术方案。最后，我们将跟踪ATL和SLAH术后认知和成像的变化，并确定 促进重组和改善认知结果的患者特定因素。这样做的目的是 更新完全符合2020年NINDS癫痫研究基准(第四部分)，其中 强调迫切需要进行研究，以限制或预防癫痫发作及其不良后果 在整个生命周期内接受治疗。我们的更新直接满足了这一要求，努力改进外科手术 决策，这将对病人护理产生直接和持久的影响。癫痫是一种常见的疾病 每年给医疗保健系统造成约155亿美元损失的神经系统疾病， 影响生活质量、就业和健康状况。目前的项目对公共卫生有很大的影响 因为它致力于通过使用先进的、非侵入性的 识别记忆衰退的个体预测因素的技术，有助于指导手术决定和 可能会减少与切除或消融大脑能言区相关的发病率。

Anterior temporal lobectomy (ATL) is a highly sucessful treatment for eliminating seizures in patients with temporal lobe epilepsy (TLE). However, ATL-induced memory decline is frequent and often severe, having a deleterious impact on quality of life and functional outcomes. Stereotactic laser amygdalohippocampectomy (SLAH) has been introduced as a minimally-invasive alternative that could minimize risk of memory decline. However, it is unclear which patients would benefit the most from SLAH and whether SLAH decreases risk for critical aspects of episodic memory decline compared to ATL. During the previous grant funding period, we demonstrated the clinical value of combining information from structural (sMRI), diffusion- weighted (dMRI), and functional (fMRI) imaging to better characterize the neural networks that underlie preoperative language and memory impairment and (re)organization and in TLE. We propose that the same multimodal imaging (MMI) approach can be used to quantify risk for postoperative memory decline. In this R01, we extend our MMI approach, combining sMRI/dMRI/fMRI with intracranial recordings (iEEG), enabling us to delve deep into the spatial and temporal dynamics of episodic memory networks in TLE. We employ multimodal associative learning tasks with real-world implications (i.e., pairing a face with a name) that have not before been studied in the surgical context. In addition, we draw from cognitive neurosicence models of hippocampal functioning that may inform why many patients struggle to make fine-grain distinctions in memory (i.e., impaired pattern separation), even when simple item memory appears intact. We propose that our MMI approach will yield a more complete characterization of episodic memory networks in TLE, reveal patterns of structural and functional reorganization in individual patients, and enable a personalized approach to risk assessment when considering surgical options. Finally, we will track cognitive and imaging changes post-ATL and SLAH and identify patient-specific factors that promote reorganization and improved cognitive outcomes. The goals of this renewal are perfectly aligned with the 2020 NINDS Benchmarks for Epilepsy Research (Part IV), which stress the critical need for reseach to limit or prevent adverse consequences of seizures and their treatments across the lifespan. Our renewal directly addresses this request, striving to improve surgical decision-making, which will have an immediate and sustained impact on patient care. Epilepsy is a common neurological disease that costs the healthcare system approximately $15.5 billion annually and can negatively impact quality of life, employment, and health status. The current project has strong implications for public health because it strives to improve health outcomes in patients with epilepsy by using advanced, noninvasive technology to identify individual predictors of memory decline that can help to guide surgical decisions and possibly reduce morbidity associated with removal or ablation of eloquent brain regions.