CAREER:Coordination of neural activity during memory formation in humans

如今，记忆障碍影响着数百万美国人。尽管经过几十年的努力，我们几乎没有能力预防、改善或治疗这种记忆障碍。在美国国家科学基金会的支持下，Ueli Rutishauser博士和他的同事正在研究人类是如何形成、储存和检索记忆的。这项由职业生涯奖支持的研究是观察海马体中脑细胞的电活动，海马体是形成新记忆的关键区域。这项研究是在接受手术治疗癫痫的人类患者中进行的。为了定位癫痫发作，这些患者在大脑的不同部位植入了小电线，这使得研究人员能够在细胞水平上研究人类神经系统。利用这项技术，我们将研究人类脑细胞在形成新记忆时是如何变化的。具体来说，我们将测试新记忆的形成是否依赖于一种被称为“θ振荡”的大脑节奏，以及这种节奏的中断是否会导致记忆力下降。关键的是，θ波振荡可以通过电刺激来改变，这为提高记忆力提供了一种潜在的技术。通过教育、教学和指导，该职业奖将使新的研究人员和组织能够利用颅内电生理学提供的对人类神经系统进行基础研究的极其宝贵的机会。本次职业生涯奖的研究目标是在单个神经元和回路的水平上研究人类陈述性记忆的神经机制。我们和植入了微丝电极的病人一起工作他们自愿参与这项研究。目的是了解神经元网络的活动是如何协调的，从而使它们的集体行动产生可塑性和长期记忆。我们通过结合人类单神经元记录、行为测试、电刺激和计算模型来验证海马体θ波振荡介导这一过程的假设。这种方法将使我们能够评估振荡对人类记忆形成的作用和必要性，从而证明特定振荡在人类认知中的作用。我们研究i)我们确定的两种不同功能类型的海马神经元（视觉和记忆选择性）的活动如何被θ波节律调节；Ii)空间注意转移对θ波振荡的调节如何影响单个神经元；以及iii) θ波振荡与记忆强度之间是否存在因果关系。这项研究可以首次提供可塑性、振荡和人类记忆的细胞机制之间的联系。教育目标是让学生密切参与研究的各个方面，并将研究成果纳入课堂、研讨会和K-12外展计划。最终的方法、工具和数据集将被公开发布。

Memory disorders affect millions of Americans today. Despite decades of work, we have little ability to prevent, improve or treat such memory disorders. With the support of the National Science Foundation, Dr. Ueli Rutishauser and colleagues are investigating how humans form, store, and retrieve memories. The research supported by this CAREER award is to observe the electrical activity of brain cells in the hippocampus, an area essential for the formation of new memories. This research is performed with human patients who are undergoing surgery to treat epilepsy. To localize seizures, these patients are implanted with small wires in different parts of their brain, which allows researchers to investigate the human nervous system at the cellular level. Using this technique, we will investigate how human brain cells change when new memories are formed. Specifically, we will test whether the formation of new memories is dependent on a brain rhythm called the "theta oscillation", and if disruptions of this rhythm lead to poor memory. Critically, theta oscillations can be changed by electrical stimulation, which offers a potential technique to improve memory. Through education, teaching, and mentoring, this CAREER award will enable new researchers and organizations to take advantage of the extremely valuable opportunities for basic research on the human nervous system presented by intracranial electrophysiology. The research objective of this CAREER award is to investigate the neural mechanisms of human declarative memory at the level of individual neurons and circuits. We work with patients implanted with micro-wire electrodes who volunteer to participate in this research. The objective is to understand how the activity of networks of neurons is coordinated such that their collective action results in plasticity and long-term memories. We test the hypothesis that hippocampal theta oscillations mediate this process by combining human single-neuron recordings, behavioral testing, electrical stimulation, and computational modelling. This approach will allow us to assess the role and necessity of oscillations for the formation of human memories and thereby demonstrate the role of a specific oscillation in human cognition. We study i) how the activity of two distinct functional types of hippocampal neurons that we identified (visual and memory selective) are modulated by the theta rhythm; ii) how modulation of theta oscillations by shifts in spatial attention impacts individual neurons; and iii) whether there is a causal link between theta oscillations and memory strength. This study could provide, for the first time, a link between the cellular mechanisms of plasticity, oscillations, and human memory. The educational objective is to closely involve students in all aspects of the research, and to incorporate research results into classes, workshops and a K-12 outreach program. The resulting methods, tools, and datasets will be publicly released.