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: 9262276
• 负责人: CHARLES E SCHROEDER
• 金额: $ 20.21万
• 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 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9262276
• 关键词: Address; Affect; Anterior; Area; Attention deficit hyperactivity disorder; Auditory; Autistic Disorder; Behavior; Behavioral; Brain; Brain region; Cell membrane; Cell physiology; Cells; Chronic; Cognition; Cognitive; Cognitive deficits; Data; Detection; Disease; Electric Stimulation; Electrodes; Electroencephalography; Electrophysiology (science); Event; Focused Ultrasound; Frequencies; Future; Goals; Hippocampus (Brain); Impairment; Implant; Intervention; Lead; Link; Macaca; Manuals; Measurement; Measures; Methods; Modality; Modeling; Monkeys; Motor; Neocortex; Neurons; Pathway Analysis; Pattern; Perception; Performance; Periodicity; Pharmacology; Phase; Physiological; Physiological Processes; Physiology; Population; Positioning Attribute; Process; Property; Protocols documentation; Role; Sampling; Schizophrenia; Sensory; Site; Sleep; Source; Speech; Stream; Synapses; Testing; Variant; auditory discrimination; awake; behavior measurement; cognitive ability; cognitive function; density; electric field; experimental study; follow-up; high risk; improved; indexing; instrument; multi-electrode arrays; neocortical; neuropsychiatric disorder; novel; operation; public health relevance; relating to nervous system; 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（由适用提供）：神经电振荡反映了神经元合奏中的同步令人兴奋的波动，无处不在（和睡眠）大脑，并且被认为是自适应脑功能中的基本仪器。尽管在理解神经元振荡的物理基础和功能意义方面最近取得了进展，但重置过程的细胞生理学和盛立过程的细胞生理学，使大脑可以利用振荡作为感知和认知的基础，但尚不清楚。最近的发现表明，可以使用直接电流和替代电流（TDC和TACS）（TES）（TES）（TES）（TES）来操纵神经元振荡。这增加了因果操作的潜力，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，其中脑动力学的破坏是认知缺陷的基础。我们建议通过电场测量以及在醒着的猕猴在醒目的猕猴中检查TDC和TAC的影响。我们的具体目的是：1）优化使用TDC和TAC的特定大脑区域的模型。宽度。具有慢性植入，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刺激参数的影响，例如强度，频率（TAC）和刺激性的Electronde nu nu nu nu nu nu nu nu nu nu nu nu nu nu nu nu nu MBER（最多8个）和位置。 2）定义TDC和TAC在主动感觉处理中的身体和行为效应。我们将使用有限的（24个频道）版本的宏观网络分析（AIM 1），以及在执行听觉歧视并对目标做出手动响应的猴子中的微观测量。微观尺度衡量标准包括层流势（FP），电流源密度（CSD）和多单位活动（MUA）剖面，并在选定的新皮层区域的层中用多电极阵列采样。 CSD和MUA分析用于定义突触活性的特征（由当前的水槽和源索引）和跨皮质层的神经元触发的包络，从而将刺激效应与振动性动力学参与的特定细胞种群，电路和物理过程联系起来。在感觉处理，目标检测和运动响应期间测量网络和细胞电路活性模式将提供强大而敏感的手段，以评估对这些关键过程基础的脑动力学的电刺激影响。成功将支持并为更广泛的努力提供更详细的具体图片，以了解神经元合奏的特性，这些神经元合奏的特性会产生大脑节奏并组织起来以执行基本的认知操作。对脑刺激作用的机械理解的改善可能会导致改善大脑刺激方案，治疗障碍，例如精神分裂症，自闭症和多动症，其中低频和高频的感觉入口在低频和高频上都显然受到了损害。

项目成果

Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates.

• DOI: 10.1038/srep31236
• 发表时间: 2016-08-18
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Opitz A;Falchier A;Yan CG;Yeagle EM;Linn GS;Megevand P;Thielscher A;Deborah A R;Milham MP;Mehta AD;Schroeder CE
• 通讯作者: Schroeder CE