Multimodal imaging of cognitive networks in epilepsy: Implications for surgery

 描述(由申请人提供)：前颞叶切除术(ATL)是一种非常成功的治疗方法，可以消除颞叶癫痫(TLE)患者的癫痫发作。然而，ATL引起的认知功能下降是频繁的，通常是严重的，对生活质量和功能结果有有害的影响。最近，立体定向激光杏仁核海马区切除术(SLAH)作为一种可以将认知能力下降的风险降至最低的微创替代方案被引入。然而，目前还不清楚哪些患者将从SLAH中受益，以及哪些认知领域会受益。在最初的拨款资助期间，我们展示了结合结构、扩散和功能成像信息的临床价值，以更好地表征TLE术前语言(Re)组织和损害的神经网络。我们建议，同样的多模式成像(MMI)方法也可以用于量化术后认知功能下降的风险。在这个竞争性的续订申请中，我们在几个关键方面扩展了我们的研究。首先，我们讨论了如何使用MMI来预测三个重要认知领域的术后结果：语言、记忆和执行功能。其次，我们评估了如何使用MMI来量化ATL和SLAH后认知功能下降的风险。在初步分析中，我们还将评估术后重组是否发生在可能进一步影响认知结果的患者子集中。这些目标将使用以下方法来实现。首先，将使用任务相关和静息状态功能磁共振(FMRI)检查额叶、颞叶和顶叶区域的神经激活情况，以探索支撑TLE患者语言、记忆和执行功能的大脑网络。其次，关键白质纤维束的完整性将使用一种先进的扩散技术-限制光谱成像(RSI)进行量化。第三，海马体体积将通过结构磁共振成像(SMRI)进行量化。第四，来自功能磁共振成像、RSI和sMRI的信息将被结合起来，以预测在语言、记忆和执行功能的测量上，手术导致认知变化的个体风险。这次更新的目标与2014年NINDS癫痫研究基准(第四部分，限制或预防癫痫发作及其终身治疗的不良后果)完全一致，该基准鼓励减轻手术干预对癫痫认知合并症的影响。我们的续签直接满足了这一要求，努力改善手术决策，这将对患者护理产生直接和持续的影响。癫痫是一种常见的神经系统疾病，每年花费医疗保健系统约155亿美元，并会对生活质量、就业和健康状况产生负面影响。目前的项目对公众健康具有重大影响，因为它致力于通过使用先进的非侵入性技术来识别认知能力下降的个体预测因素，从而努力改善癫痫患者的健康结果，这些预测因素可以帮助指导手术决定，并可能减少与切除口才皮质相关的发病率。

 DESCRIPTION (provided by applicant): Anterior temporal lobectomy (ATL) is a highly sucessful treatment for eliminating seizures in patients with temporal lobe epilepsy (TLE). However, ATL-induced cognitive decline is frequent and often severe, having a deleterious impact on quality of life and functional outcomes. Recently, stereotactic laser amygdalohippocampectomy (SLAH) has been introduced as a minimally-invasive alternative that could minimize risk of cognitive decline. However, it is unclear which patients would benefit from SLAH and in which cognitive domains. During the initial grant funding period, we demonstrated the clinical value of combining information from structural, diffusion and functional imaging to better characterize the neural networks that underlie preoperative language (re)organization and impairment in TLE. We propose that the same multimodal imaging (MMI) approach can be used to quantify risk for postoperative cognitive decline. In this competing renewal application we expand our research in several key ways. First, we address how MMI can be used to predict postoperative outcomes in three important cognitive domains: language, memory, and executive functioning. Second, we evaluate how MMI can be used to quantify risk for cognitive decline following ATL versus SLAH. In a preliminary analysis, we will also evaluate whether postoperative reorganization occurs in a subset of patients that may further influence cognitive outcomes. These goals will be accomplished using the following methods. First, neural activations will be examined in frontal, temporal, and parietal regions using task-related and resting state functional MRI (fMRI) to probe the brain networks that underlie language, memory, and executive functioning in patients with TLE. Second, the integrity of critical white matter fibe tracts will be quantified using an advanced diffusion technique, restriction spectrum imaging (RSI). Third, hippocampal volumes will be quantified from structural MRI (sMRI). Fourth, information from fMRI, RSI, and sMRI will be combined to predict individual risk for surgically-induced cognitive changes on measures of language, memory, and executive functioning. The goals of this renewal are perfectly aligned with the 2014 NINDS Benchmarks for Epilepsy Research (Part IV, Limit or prevent adverse consequences of seizures and their treatment across the lifespan), which encourage mitigating the effects of surgical interventions on cognitive co-morbidities in epilepsy. 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 cognitive decline that can help to guide surgical decisions an possibly reduce morbidity associated with removal of eloquent cortex.