Effects of brain stimulation on neuronal dynamics and behavior

 描述（由申请人提供）：神经电振荡反映了神经元集合中的同步兴奋性波动，普遍存在于清醒（和睡眠）的大脑中，并且被认为是适应性大脑功能的基本工具。尽管最近在理解神经元振荡的生理基础和功能意义方面取得了进展，但重置和夹带过程的细胞生理学，使大脑能够利用振荡作为感知和认知的构建模块，尚不清楚。最近的研究结果表明，它是可能的操纵神经元振荡使用弱经颅电刺激（TES）与直流和交流电（tDCS和tACS分别）。这就提出了因果操纵的可能性，可以帮助确认 特定振荡动力学在感知和行为的特定方面的作用，以及治疗神经精神疾病的可能性，其中大脑动力学的破坏是认知缺陷的基础。我们建议研究的影响，tDCS和tACS的电场测量和建模，电生理和行为测量在清醒的猕猴的组合。我们的具体目标是：1）优化模型，以tDCS和tACS靶向特定的大脑区域。广泛传播。使用长期植入的48通道立体定向EEG（s-EEG）阵列的“宏观尺度”颅内记录将确定颅内电场如何受到刺激参数的影响，例如，强度、频率（tACS）和刺激电极nu 成员（最多8个）和位置。2)定义tDCS和tACS在主动感觉处理中的生理和行为效应。我们将使用宏观尺度网络分析（AIM 1）的有限（24通道）版本，沿着微尺度测量，在猴子中进行听觉辨别并对目标进行手动响应。微尺度的措施包括层流场电位（FP），电流源密度（CSD）和多单位活动（MUA）的配置文件采样与多电极阵列在选定的新皮层区域的层。CSD和MUA分析用于定义突触活动（由电流汇和电流源索引）的概况和跨皮层的伴随神经元放电的包络，从而将刺激效应与参与振荡动力学的特定细胞群、电路和生理过程联系起来。在感觉处理、目标检测和运动响应期间测量网络和细胞回路活动模式将提供稳健和灵敏的手段来衡量电刺激对这些关键过程的脑动力学的影响。成功将支持和告知更广泛的努力，以开发更详细的神经元集合特性的具体图片，这些神经元集合创建大脑节律并组织它们执行基本的认知操作。改善对脑刺激效应的机械理解可能会导致改善脑刺激方案，治疗精神分裂症、自闭症和ADHD等疾病，其中低频和高频的感觉夹带明显受损或受损。

 DESCRIPTION (provided by applicant): Neuroelectric oscillations reflect synchronous excitability fluctuations in ensembles of neurons, ubiquitous in the waking (and sleeping) brain, and are believed to be fundamental instruments in adaptive brain function. Despite recent progress in understanding the physiological underpinnings and functional significance of neuronal oscillations, the cellular physiology of the reset and entrainment processes, that allow the brain to harness oscillations as building blocks of perception and cognition, are unclear. Recent findings suggest that it is possible to manipulate neuronal oscillations using weak transcranial electrical stimulation (TES) both with direct and alternating currents (tDCS and tACS respectively). This raises possibilities for causal manipulations that can help to confirm the role of specific oscillatory dynamics in specific aspects of perception and behavior, as well as the possibility of treating neuropsychiatric disorders in which disruptions of brain dynamics underlie cognitive deficits. We propose to examine effects of tDCS and tACS with a combination of electric field measurements and modelling, electrophysiological and behavioral measurements in awake-behaving macaque monkeys. Our Specific Aims are: 1) Optimize models to target specific brain regions with tDCS and tACS. Widespread. "macro-scale" intracranial recordings with chronically-implanted, 48 channel stereotactic EEG (s-EEG) arrays will determine how intracranial electric fields are affected by stimulation parameters, e.g., intensity, frequency (tACS) and variations in stimulating electrode nu mber (up to 8) and positions. 2) Define physiological and behavioral effects of tDCS and tACS in active sensory processing. We will use a limited (24 channel) version of the macro-scale network analysis (AIM 1), along with micro-scale measures in monkeys performing auditory discriminations and making manual responses to targets. Micro-scale measures include laminar field potential (FP), current source density (CSD) and multiunit activity (MUA) profiles sampled with multielectrode arrays across the layers of selected neocortical areas. CSD and MUA analyses are used to define the profiles of synaptic activity (indexed by current sinks and sources) and envelope of concomitant neuronal firing across the cortical layers, thus linking stimulation effects to specific cell populations, circuits and physiological processes engaged in oscillatory dynamics. Measuring network and cell-circuit activity patterns during sensory processing, target detection and motor responding will provide robust and sensitive means to gauge electrical stimulation effects on brain dynamics underlying these key processes. Success will support and inform a broader effort to develop a more detailed concrete picture of the properties of neuronal ensembles that create brain rhythms and organize them to perform fundamental cognitive operations. Improved mechanistic understanding of brain stimulation effects may lead to improved brain stimulation protocols, treatments disorders such as schizophrenia, autism and ADHD, in which sensory entrainment at both low and high frequencies is demonstrably or putatively impaired.