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）是消除颞叶癫痫（TLE）患者癫痫发作的一种非常成功的治疗方法。然而，ATL诱导的认知功能下降是频繁的，往往是严重的，对生活质量和功能结果的有害影响。最近，立体定向激光杏仁核切除术（SLAH）已被引入作为一种微创的替代方案，可以最大限度地减少认知能力下降的风险。然而，目前尚不清楚哪些患者会从SLAH中受益以及哪些认知领域。在最初的拨款资助期间，我们证明了结合结构，弥散和功能成像信息的临床价值，以更好地表征TLE术前语言（重组）和损伤的神经网络。我们建议，相同的多模态成像（MMI）方法可用于量化术后认知功能下降的风险。在这个竞争性的更新应用中，我们以几个关键方式扩展了我们的研究。首先，我们讨论了MMI如何用于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MMI如何用于量化ATL与SLAH后认知功能下降的风险。在初步分析中，我们还将评估是否术后重组发生在一个子集的患者，可能进一步影响认知结果。这些目标将通过以下方法实现。首先，神经激活将在额叶，颞叶和顶叶区域使用任务相关的和静息状态的功能磁共振成像（fMRI）进行检查，以探测TLE患者的语言，记忆和执行功能的大脑网络。其次，关键的白色物质纤维束的完整性将使用先进的扩散技术，限制光谱成像（RSI）进行量化。第三，将从结构MRI（sMRI）量化海马体积。第四，来自fMRI、RSI和sMRI的信息将被结合起来，以预测个体在语言、记忆和执行功能方面的认知变化风险。此次更新的目标与2014年NINDS癫痫研究基准（第四部分，限制或预防癫痫发作及其在整个生命周期中的治疗的不良后果）完全一致，鼓励减轻手术干预对癫痫认知共病的影响。我们的更新直接解决了这一要求，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，并可能对生活质量，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技术来识别认知下降的个体预测因子，从而改善癫痫患者的健康状况，这些预测因子可以帮助指导手术决策，并可能降低与切除功能皮层相关的发病率。

 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.