CRCNS: Optimization of closed-loop control of gamma oscillations

CRCNS：伽马振荡闭环控制的优化

• 批准号: 10207403
• 负责人: Satish S Nair
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-26 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207403
• 关键词: Accounting; Address; Affect; Algorithms; Amygdaloid structure; Anatomy; Behavior; Behavioral; Biophysics; Brain; Brain region; Cell Nucleus; Cells; Collaborations; Communication; Custom; Detection; Emotional; Frequencies; Genetic; Goals; Implant; Individual; Individual Differences; Instruction; Interneurons; Intervention; Machine Learning; Mental Health; Methods; Modeling; Monitor; Neurons; Performance; Pharmacology; Phase; Physiological; Property; Response to stimulus physiology; Rodent Model; Route; Scheme; Stimulus; Structure; System; Techniques; Testing; Time; Twin Multiple Birth; biophysical model; cognitive function; design; emotion regulation; emotional behavior; experience; experimental study; improved; in vivo; individual variation; insight; neurophysiology; novel; optogenetics; predictive modeling; response; signal processing; social; vigilance

Throughout the brain, specialized systems carry out different but complementary functions, sometimes independently but often in cooperation. However, we do not understand how their activity is dynamically coordinated, and dysregulation of this is associated with many mental health conditions. Neuronal oscillations, which are detectable in local field potentials (LFPs) at various frequencies, are a promising target for this coordination. Gamma oscillations (40-100 Hz) in particular have been singled out since they enhance stimulus responses, facilitate interactions between brain regions, and are expressed ubiquitously across cortical and subcortical regions. Indeed, gamma oscillations occur in the basolateral nucleus of the amygdala (BL), an important regulator of emotional behaviors. BL gamma oscillations are enhanced during periods of heightened vigilance during a foraging task, following emotionally salient experiences, and upon presentation of socially-relevant stimuli. The variety of circumstances that engage it make it a promising target for interventions affecting emotional behaviors in general. However, technical challenges abound because gamma manifests as brief intermittent oscillatory bursts, layered atop numerous ongoing activities in other frequency bands. This precludes manipulating gamma exclusively with traditional pharmacological, optogenetic, or chemogenetic approaches, since these have substantial effects on ongoing non-gamma activities, and are delivered irrespective of whether gamma bursts are present or absent. To overcome this, a closed-loop algorithm was developed that monitors the LFP in real-time for gamma oscillations and delivers precisely timed optogenetic stimulation capable of enhancing or suppressing gamma strength on a cycle-by-cycle basis. While this improves upon the status quo,, further refinement is needed. Aim 1 of this proposal seeks to clarify how the gamma modulation technique operates via biophysically detailed modeling of the local circuits in the BL that generate gamma, the effects of optogenetic stimulation, and the closed-loop algorithm. Aim 2 designs better signal processing routines for detecting and parameterizing gamma in real-time. Aim 3 develops an approach to create customized biophysical models that reproduce the properties of gamma observed in individual subjects, which when combined with the results of Aims 1 and 2 should allow for optimized control over gamma oscillations in individual subjects. RELEVANCE (See instructions): Gamma oscillations occur in the basolateral amygdala, a brain region implicated in emotional regulation. By developing improved methods to manipulate these oscillations, we hope to better understand their function and improve our ability to control emotional states and behaviors.

在整个大脑中，专业系统具有不同但互补的功能，有时 独立但经常合作。但是，我们不明白他们的活动是如何动态的 协调，失调与许多心理健康状况有关。神经元 在各种频率下在本地田间电势（LFP）中可检测到的振荡是一个有前途的 该协调的目标。自从伽马振荡（40-100 Hz）以来就已经被挑出 它们增强了刺激反应，促进大脑区域之间的相互作用，并表示 跨皮质和皮层下区域普遍存在。实际上，γ振荡发生在基底外侧 杏仁核（BL）的核，情绪行为的重要调节剂。 BLγ振荡是 在觅食任务期间的警惕期间增强 经验，并在呈现与社会相关的刺激后。参与的各种情况 它使其成为影响一般情绪行为的干预措施的有希望的目标。但是，技术 挑战比比皆是，因为伽玛表现为短暂的间歇性振荡爆发，在层次上放置 其他频带中的许多持续活动。这排除了完全操纵伽马 采用传统的药理，光学遗传学或化学遗传学方法，因为它们具有实质性 对正在进行的非伽马活动的影响，无论伽玛爆发是否是 现在或不存在。为了克服这一点，开发了一种闭环算法来监视LFP 实时用于γ振荡和提供精确定时的光遗传刺激 根据周期的基础增强或抑制伽马强度。而这改善了状态 需要进一步的完善。本提案的目标1旨在阐明伽马调制如何 技术通过生成伽玛的局部电路的生物物理详细建模， 光遗传刺激和闭环算法的影响。 AIM 2设计更好的信号 处理和参数化伽玛的处理程序实时。 AIM 3开发了一种方法 创建定制的生物物理模型，以重现单个观察到的伽马的性质 受试者与目标1和2的结果结合在一起，应允许对 各个受试者的伽马振荡。 相关性（请参阅说明）： γ振荡发生在基底外侧杏仁核中，这是一个涉及情绪调节的大脑区域。 通过开发改进的操纵这些振荡的方法，我们希望更好地了解他们 运作并提高我们控制情绪状态和行为的能力。