CRCNS: Optimization of closed-loop control of gamma oscillations

在整个大脑中，专门的系统执行不同但互补的功能，有时 独立的，但经常合作的。然而，我们不了解它们的活动是如何动态的 这种协调和失调与许多精神健康状况有关。神经元 可以在不同频率的局域场势(LFP)中检测到的振荡是一种很有前途的方法 这一协调的目标。特别是伽马振荡(40-100赫兹)自那以后就被挑出来了 它们增强刺激反应，促进大脑区域之间的相互作用，并表达 普遍存在于皮质和皮质下区域。事实上，伽马振荡发生在基准面 杏仁核(BL)，情绪行为的重要调节器。BL伽马振荡是 在觅食任务期间的高度警觉期间得到加强，在情绪上突出 体验，以及在呈现与社会相关的刺激时。参与的各种情况 它使它成为总体上影响情绪行为的干预措施的一个有希望的目标。然而，技术上 挑战比比皆是，因为伽马表现为短暂的间歇性振荡爆发，层叠在 其他频段的许多正在进行的活动。这就排除了专门操纵伽马的可能性 使用传统的药理学、光遗传学或化学遗传学方法，因为这些方法具有实质性的 对正在进行的非伽马活动的影响，并且无论伽马爆发是否 出席或缺席。为了克服这一点，开发了一种闭环算法来监控LFP在 实时伽马振荡并提供精确定时的光遗传刺激，能够 在逐周期的基础上增强或抑制伽马强度。虽然这在状态上有所改善 现状，还需要进一步完善。该提案的目标1试图澄清伽马调制是如何 该技术通过对产生伽马的BL中的局部电路进行生物物理详细建模来操作， 光遗传刺激的效果，以及闭环算法。AIM 2设计更好的信号 用于实时检测和参数化伽马的处理例程。目标3开发了一种方法来 创建定制的生物物理模型，再现个体观察到的伽马属性 受试者，当与目标1和目标2的结果相结合时，应允许对 个体受试者的伽马振荡。 相关性(请参阅说明)： 伽马振荡发生在杏仁核的基底外侧，这是一个与情绪调节有关的大脑区域。 通过开发更好的方法来操纵这些振荡，我们希望更好地理解它们 发挥作用，提高我们控制情绪状态和行为的能力。

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.