NEUROPHYSIOLOGICAL BIOMARKERS IN PRECLINICAL ASSAYS OF SUSTAINED ATTENTION

持续注意力临床前测定中的神经生理学生物标志物

基本信息

批准号：
10375904
负责人：
Gregory V Carr
金额：
$ 65.43万
依托单位：
LIEBER INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10375904
关键词：
Agonist Amphetamines Anatomy Animal Model Anterior Attention Attention deficit hyperactivity disorder Attentional deficit Behavior Behavioral Biological Biological Assay Biological Markers Brain Diseases Catecholamines Conflict (Psychology)Coupling Cues Detection Disease Dopamine Dopamine D1 Receptor Dorsal Dose Electroencephalogram Electrophysiology (science)Enhancers Functional Magnetic Resonance Imaging Human Image Impaired cognition Impairment Length Measurement Measures Mental disorders Mission Mus Neuromodulator Pathway interactions Patients Pattern Performance Pharmaceutical Preparations Pharmacology Phase Play Process Quality of life Rattus Reaction Time Ritalin Rodent Role Schizophrenia Signal Transduction Stimulus Task Performances Testing Time Translations United States National Institutes of Health Ventral Tegmental Area addiction attenuation base cingulate cortex design drug development drug discovery experimental study flexibility functional outcomes improved in vivo innovation insight neural circuit neurophysiology nonhuman primate novel therapeutics optogenetics performance tests pre-clinical psychostimulant relating to nervous system response side effect sustained attention symptom treatment tolcapone tool touchscreen translational study

项目摘要

Project Summary Sustained attention, the ability to focus on an activity or stimulus over time, is impaired in many brain disorders. Continuous performance tests (CPTs) have been designed to measure sustained attention in multiple species. Similar neural circuits are engaged in both humans and model organisms during CPT performance, supporting their use in translational studies that screen for novel therapeutics. The human dorsal anterior cingulate cortex (dACC), which plays critical roles in attentional processes, shows functional and anatomical similarity to the mouse prelimbic region (PrL). These homologous regions are involved in both conflict detection and allocation of attention to cues before orientation, important components in go/no-go tasks like CPTs. Electroencephalogram (EEG) studies show that neural activity in the dACC is correlated with task engagement and performance in the CPT. The neuromodulator dopamine is hypothesized to play a critical role in regulating attention, a notion supported by the fact that dopamine D1 receptor agonists and antagonists improve and impair CPT performance, respectively. In this application we propose to optimize a mouse touchscreen-based CPT to include measurements of the effects of stimulus degradation and session length (time on task) on accuracy, reaction times, and other task parameters. In this optimized paradigm we will identify electrophysiological correlates of task performance by analyzing spectral measures of power and coupling from the EEG and PrL local field potential. We will evaluate the optimized CPT paradigm by assessing behavioral performance and EEG/LFP correlates in response to pharmacological enhancers that are documented to improve attention. Finally, we will mechanistically test the role of dopaminergic input to the dACC/PrL from the ventral tegmental area on behavioral performance and EEG/LFP correlates in the CPT.

项目摘要在许多脑部疾病中，持续关注，随着时间的流逝，专注于活动或刺激的能力受到损害。连续性能测试（CPT）旨在测量多种物种的持续关注。在CPT性能期间，类似的神经回路也参与了人类和模型生物，支持它们在翻译研究中的使用，以筛选新的治疗疗法。人背扣带皮质（DACC）在注意过程中起着关键作用，显示出与小鼠前缘区域（PRL）。这些同源区域都参与冲突检测和分配在方向前关注提示，诸如CPT之类的GO/NO-GO任务中的重要组成部分。脑电图（EEG）研究表明，DACC中的神经活动与任务参与相关和CPT的性能。假设神经调节剂多巴胺在调节中起关键作用注意，这一事实支持了多巴胺D1受体激动剂和拮抗剂的改善，并且分别损害CPT性能。在此应用程序中，我们建议优化基于鼠标触摸屏 CPT包括测量刺激降解和会话长度（任务时间）对的影响精度，反应时间和其他任务参数。在这个优化的范式中，我们将确定通过分析功率和耦合的光谱测量，任务性能的电生理相关性来自EEG和PRL局部领域的潜力。我们将通过评估评估优化的CPT范式行为表现和脑电图/LFP与药理学增强剂的响应相关有记录以提高注意力。最后，我们将机械地测试多巴胺能输入的作用来自腹侧对行性性能的DACC/PRL和脑电图/LFP在CPT中相关。