Identification of human genomic signatures of episodic memory

项目总结 我们的提议寻求将当代神经科学中的两个强大工具结合起来：清醒时的大脑记录， 行为个体和人脑组织的大规模基因表达。我们希望了解更多 通过研究与大脑相关的基因表达谱了解癫痫等疾病的认知功能 振荡信息。这一建议的关键创新之处在于从 同一患者在不同阶段对癫痫进行评估和治疗。在我们的第一个目标中，我们将在 我们最近的发现通过生成一个新的大分子来检验基因/振荡相关性 通过将我们的分析扩展到包括情节记忆过程中的项目提取，来研究大脑振荡的数据集。在……里面 我们的第二个目标是，我们将通过收集脑电振荡数据作为对象来构建一个全新的数据集 进行情景记忆任务，然后收集相同患者的颞叶组织样本。 这是因为患者首先用颅内电极进行癫痫标测，然后再进行 切除颞叶。这提供了捕获振荡和基因表达数据的可能性 所有受试者的组织都是一样的。在我们的第三个目标中，我们将生成外科癫痫的基因表达数据 并将这些特征与来自身体组织样本的数据集进行比较。这些比较将 作为控制来帮助解释我们的关联结果，并作为对其文献的重大贡献 这是你的权利。尽管这一雄心勃勃的计划需要拥有基因表达专业知识的实验室之间的紧密结合 分析和信号处理，并且需要用于处理在手术室中获得的组织的管道 以及特定的手术技术来制作良好的标本，我们拥有的方法学基础 我们展示的既定和初步数据表明，我们的计划有很高的成功机会。基因 我们认为与助记法高度相关的记忆加工将是进一步研究动物的有力候选者 实验和潜在的治疗靶向。我们相信这一调查是一种新的方式来解决 癫痫和潜在的其他疾病，如轻度认知障碍，认知能力下降的问题。

PROJECT SUMMARY Our proposal seeks to unite two powerful tools in contemporary neuroscience: brain recordings from awake, behaving individuals and large-scale gene expression from human brain tissue. We hope to understand more about cognitive function in epilepsy and other disorders by studying gene expression profiles linked with brain oscillation information. The key innovation of this proposal is the collection of these two types of data from the same patients at different stages of their evaluation and treatment for epilepsy. In our first aim, we will build upon our recent findings examining gene/oscillation correlations through the generation of a proposed new large dataset of brain oscillations and by extending our analysis to include item retrieval during episodic memory. In our second aim, we will build an entirely new dataset by collecting intracranial EEG oscillatory data as subjects perform an episodic memory task and then also collect temporal lobe tissue specimens from the same patients. This is because the patients first undergo seizure mapping with intracranial electrodes, and then undergo resection of the temporal lobe. This offers the possibility of capturing oscillatory and gene expression data from the same tissue across subjects. In our third aim, we will generate gene expression data from surgical epilepsy patients and compare these profiles to datasets derived from cadaveric tissue samples. These comparisons will serve as a control to help interpret our correlation results and as a substantial contribution to the literature in its own right. Although this ambitious plan requires close integration between labs with expertise in gene expression analysis and signal processing, and requires a pipeline for processing tissue obtained in the operating room as well as specific surgical techniques to produce good specimens, the methodological groundwork we have established and preliminary data we show demonstrate that our plans have a high chance of success. The genes we identify as being highly correlated with mnemonic processing will be strong candidates for further animal experimentation and potential therapeutic targeting. We believe this line of investigation is a novel way to address the problem of cognitive decline in epilepsy and potentially other disorders such as mild cognitive impairment.