NCS-FO: Probing the Functional Significance of Brain Oscillations through Closed-Loop Phase-Locked Stimulation

大脑中的振荡活动早已为人所知，但其功能意义仍在争论中。最近有人提出，神经振荡在控制信息如何在大脑中流动以及哪些神经元群能够交换信息方面起着重要作用，从而使大脑能够灵活地适应不同的任务需求。虽然这一观点得到了来自特定子系统的大脑活动记录的支持，但对这一观点的严格测试需要对大脑活动进行操纵，以建立同步大脑活动和神经通信之间的因果关系。虽然抑制或增强神经活动的实验技术很容易获得，但解决这一科学问题需要新的技术来操纵神经活动，并与正在进行的神经活动保持精确的定时关系。该研究项目的目标是开发一种闭环刺激系统，该系统可以实时分析正在进行的大脑振荡，并利用所得信息触发神经刺激。这就允许操纵神经活动，将其锁定在大脑另一个位置正在进行的活动上。与科学界分享这一工具有望为同步大脑活动在各种神经系统中的功能意义提供新颖的、基本的见解，这是目前可用技术无法获得的。该技术还可能应用于神经假体和脑刺激系统，用于治疗神经和精神疾病。该项目包括：1)开发一种算法，该算法可以可靠地从局部场电位中提取主导振荡分量的瞬时频率和相位，并准确预测下一个特定相角的发生。2)在软件和硬件的组合中实现算法，速度足够快，可以实时控制刺激设备。3)体内闭环刺激技术的验证及在皮质-皮质和丘脑-皮质通讯研究中的应用。这种系统的成功开发将为测试有关神经信号时间的功能意义的理论，特别是同步节奏活动，消除一个主要障碍。它将允许超越相关测量，并探索人工操纵神经信号的行为（和神经）后果，这些神经信号取决于当前正在进行的神经活动的时间。在这项技术的帮助下，在理解神经信号在神经元群之间编码和传递信息时的作用方面取得了重大进展。

Oscillatory activity in the brain has been known for a long time, but its functional significance is still being debated. It has recently been proposed that neural oscillations play an important role in controlling how information flows in the brain and which ensembles of neurons are able to exchange information, allowing the brain to flexibly adjust to varying task demands. While this view has been supported by recordings of brain activity from particular subsystems, a rigorous test of the ideas requires manipulation of brain activity to establish a causal link between synchronized brain activity and neural communication. While experimental techniques for generally suppressing or enhancing neural activity are readily available, addressing this scientific question requires new technology for manipulating neural activity with a precise timing relationship relative to ongoing neural activity. The goal of this research project is to develop a closed-loop stimulation system that can analyze ongoing brain oscillations in real time and that uses the resulting information to trigger neural stimulation. This allows manipulating neural activity time-locked to ongoing activity at another location in the brain. Sharing this tool with the scientific community is expected to provide novel, fundamental insights into the functional significance of synchronized brain activity in a variety of neural systems, which cannot be obtained with currently available technology. The technique might also find application in neural prostheses and brain stimulation systems for the treatment of neurologic and psychiatric disorders. The project involves: 1) Developing an algorithm that reliably extracts instantaneous frequency and phase of a dominant oscillatory component from a local field potential and accurately predicts the next occurrence of particular phase angles. 2) Implementing the algorithm(s) in a combination of software and hardware that is fast enough for real-time control of a stimulation device. 3) Validating the closed-loop stimulation technique in vivo and developing applications for studying cortico-cortical and thalamo-cortical communication. Successful development of such a system would remove a major obstacle for testing theories about the functional significance of the timing of neural signals, in particular synchronized rhythmic activity. It would allow going beyond correlational measures and exploring the behavioral (and neural) consequences of artificial manipulation of neural signals contingent on the timing of currently ongoing neural activity. With the help of this technology, a major advance in understanding the role of the timing of neural signals in coding and transmitting information between ensembles of neurons is expected.