Effects of brain stimulation on neuronal dynamics and behavior

 描述(申请人提供)：神经电振荡反映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，被认为是适应性大脑功能的基本工具。尽管最近在了解神经元振荡的生理基础和功能意义方面取得了进展，但允许大脑利用振荡作为感知和认知的基石的重置和夹带过程的细胞生理学尚不清楚。最近的发现表明，使用弱的经颅电刺激(TES)和直流电和交流电(分别为TDC和TAC)来操纵神经元振荡是可能的。这增加了因果操纵的可能性，有助于确认 具体的振荡动力学在感知和行为的特定方面的作用，以及治疗神经精神障碍的可能性，在神经精神障碍中，大脑动力学的破坏是认知缺陷的基础。我们建议结合电场测量和建模、电生理和行为测量来检验tdcs和tacs对清醒行为猕猴的影响。我们的具体目标是：1)使用tdcs和tacs优化模型以针对特定的大脑区域。很普遍。采用长期植入的48导联立体定向脑电(S-EEG)阵列的“宏观”颅内记录将确定刺激参数，如强度、频率(TAC)和刺激电极NU的变化对颅内电场的影响 Mber(最多8个)和位置。2)明确tdcs和tacs在主动感觉加工中的生理和行为效应。我们将使用有限(24个通道)版本的宏观网络分析(AIM 1)，以及对猴子进行听觉辨别和对目标进行手动反应的微观尺度测量。微尺度测量包括层流场电位(FP)、电流源密度(CSD)和多单位活度(MUA)分布，这些分布是通过多电极阵列在选定的新皮质区域的各层上采样的。CSD和MUA分析被用来定义突触活动的轮廓(由电流汇和源来索引)和皮层上伴随的神经元放电的包络，从而将刺激效应与参与振荡动力学的特定细胞群体、电路和生理过程联系起来。测量感觉加工、目标检测和运动反应过程中的网络和细胞电路活动模式将提供稳健和灵敏的手段，以衡量电刺激对这些关键过程背后的大脑动力学的影响。成功将支持并促进更广泛的努力，以开发更详细的具体图景，了解创造大脑节奏并组织它们执行基本认知操作的神经元集合的特性。改善对脑刺激效应的机械理解可能会导致改进脑刺激方案，治疗精神分裂症、自闭症和ADHD等精神障碍，在这些疾病中，低频和高频的感觉夹带都明显或推定地受损。

 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.