Effects of brain stimulation on neuronal dynamics and behavior

脑刺激对神经元动力学和行为的影响

• 批准号: 9102628
• 负责人: CHARLES E SCHROEDER
• 金额: $ 24.26万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9102628
• 关键词: Address; Affect; Anterior; Area; Attention deficit hyperactivity disorder; Auditory; Autistic Disorder; Behavior; Behavioral; Brain; Brain region; Cell membrane; Cell physiology; Cells; Cognition; Cognitive; Cognitive deficits; Data; Detection; Disease; Electric Stimulation; Electrodes; Electroencephalography; Electrophysiology (science); Event; Focused Ultrasound; Frequencies; Future; Goals; Hippocampus (Brain); Implant; Intervention; Lead; Link; Macaca; Manuals; Measurement; Measures; Methods; Modality; Modeling; Monkeys; Motor; Neocortex; Neurons; Pathway Analysis; Pattern; Perception; Performance; Phase; Physiological; Physiological Processes; Physiology; Population; Positioning Attribute; Process; Property; Role; Sampling; Schizophrenia; Sensory; Sensory Process; Site; Sleep; Source; Speech; Stream; Synapses; Testing; Treatment Protocols; Variant; auditory discrimination; awake; behavior measurement; cognitive ability; cognitive function; density; electric field; follow-up; high risk; improved; indexing; instrument; multi-electrode arrays; neocortical; neuropsychiatric disorder; novel; operation; public health relevance; relating to nervous system; research study; response; sensory discrimination; sensory stimulus; success; tool

 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.

 描述（由申请人提供）：神经电振荡反映了神经元群的同步兴奋性波动，在清醒（和睡眠）大脑中普遍存在，并且被认为是适应性大脑功能的基本工具，尽管最近在理解生理基础和功能方面取得了进展。神经振荡的重要性，即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，最近的研究结果表明，可以使用直流电和交流电（分别为 tDCS 和 tACS）的弱经颅电刺激（TES）来操纵神经元振荡，这提高了因果操作的可能性，有助于确认。 特定振荡动力学在感知和行为特定方面的作用，以及治疗神经精神疾病的可能性，其中大脑动力学破坏导致认知缺陷，我们建议结合电场测量和建模来检查 tDCS 和 tACS 的影响。 ，对清醒行为的猕猴进行电生理学和行为测量。我们的具体目标是：1）优化模型以使用 tDCS 和 tACS 来定位特定的大脑区域。使用长期植入的 48 通道立体定向脑电图 (s-EEG) 阵列进行“宏观尺度”颅内记录将确定刺激参数（例如强度、频率 (tACS) 和刺激电极 nu 的变化）如何影响颅内电场 琥珀色（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 我们将使用宏观网络分析 (AIM 1) 的有限（24 通道）版本以及微观网络分析。 - 猴子进行听觉辨别并对目标做出手动反应的尺度测量 微观尺度测量包括用多电极采样的层流场电位 (FP)、电流源密度 (CSD) 和多单元活动 (MUA) 剖面。跨选定新皮质区域层的阵列用于定义突触活动的概况（由电流汇和源索引）和跨皮质层的伴随神经放电的包络，从而将刺激效果与特定细胞群联系起来，在感觉处理、目标检测和运动响应过程中测量参与振荡动力学的网络和细胞电路活动模式将提供强大而灵敏的方法来测量电刺激对这些关键过程的大脑动力学的影响。成功将支持和指导更广泛的努力，以开发更详细的神经整体属性的具体图片，这些神经整体创造大脑节律并组织它们执行基本的认知操作。改善对大脑刺激效果的机械理解可能会导致改善大脑刺激方案和治疗。精神分裂症、自闭症和多动症等疾病，其中低频和高频的感觉夹带明显或推定受损。