Functional Imaging of the Nicotinic Basis for Attention Deficits in Schizophrenia

精神分裂症注意力缺陷的烟碱基础的功能成像

• 批准号: 8712995
• 负责人: Jason Smucny
• 金额: $ 2.97万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8712995
• 关键词: Achievement; Anterior; Area; Attention; Auditory; Behavior; Behavioral; Brain; Brain region; Characteristics; Clinical Research; Cognitive deficits; Colorado; Communities; Cues; Diagnosis; Employee Strikes; Environment; Experimental Designs; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hippocampus (Brain); Human; Hyperactive behavior; Impaired cognition; Journals; Knowledge; Laboratories; Life; Mental Health; National Research Service Awards; Neurobehavioral Manifestations; Neurobiology; Neurons; Neuropharmacology; Nicotine; Nicotinic Agonists; Nicotinic Receptors; Noise; Occupations; Parietal Lobe; Patients; Performance; Pharmaceutical Preparations; Phenotype; Physiological; Placebos; Prefrontal Cortex; Quality of life; Reaction Time; Recruitment Activity; Relative (related person); Reporting; Research; Research Personnel; Resources; Rest; Schizophrenia; Sensory; Social Work; Stimulus; Symptoms; System; TNFRSF5 gene; Task Performances; Testing; Ticks; Training; Universities; Work; base; cholinergic; data acquisition; distraction; improved; meetings; neuroimaging; pre-doctoral; psychosocial; public health relevance; receptor expression; relating to nervous system; response; selective attention; sensory stimulus; social; sound; symposium; therapeutic development; transmission process

DESCRIPTION (provided by applicant): The purpose of this study is to better understand the neural correlates of selective attention deficits in schizophrenia and determine how these mechanisms can be pharmacologically modulated by nicotine. Patients commonly report being overwhelmed by sensory stimuli in the environment, causing difficulties at work and social situations and thereby lowering quality of life. Neurobiologically, this phenotype is partially due to reduced efficacy of nicotinic receptor systems that modulate inhibitory circuitry, and may be demonstrated in fMRI studies showing cortical hyperactivity in response to noise. Sensitivity to noise may have deleterious effects on attention-related neuronal response when the noise is task-irrelevant, although this has not been conclusively demonstrated. The proposed study will include two specific aims. In the first aim, the effects of distracting environmental noise on auditory attention task-related neuronal activity and behavior will be studied in schizophrenia patients and healthy controls using fMRI. It is hypothesized that a distraction condition (noise or silence) by diagnosis (patient or control) interaction will be observed, driven by a relative decrease in activity associated with attention networks in patients during noise (relative to silence), but the reverse effect (a relative increase) in activity in controls. The second aim will determine if response abnormalities during (a) passive listening and (b) the auditory attention task with noise distraction can be improved by a nicotinic agonist (nicotine). In the first task, subjects will listen to environmental noise or cued silence. It is expected that relative to placeb, nicotine will normalize (i.e. reduce) response to noise in the hippocampus in patients. In the second task, subjects will perform the same auditory attention task as in the first aim; it is hypothesized that relative to placebo, noise-induced change in neuronal response and performance will be similarly normalized by nicotine. The current study will be the first to examine the neuronal effects of cholinergic modulation on selective attention in schizophrenia, and has methodological and pharmacologic implications for therapeutic development. Through completion of this research, in combination with additional activities including coursework, participation in an active clinical research group, and the University of Colorado research community, the NRSA will enable Mr. Smucny to achieve the following goals of his predoctoral training: 1) To acquire expertise in the neurobiology of schizophrenia 2) to expand his knowledge of fMRI experimental design, data acquisition, and statistical analyses, and 3) to become proficient in presenting his work in journals and at conferences. Achievement of these goals is an important step towards Mr. Smucny's long-term goal of becoming a productive independent researcher in the mental health field, with a focus on using neuroimaging to better understand the neurobiology and neuropharmacology of schizophrenia.

描述（由申请人提供）：本研究的目的是更好地了解精神分裂症选择性注意力缺陷的神经相关性，并确定尼古丁如何对这些机制进行药理学调节。患者通常报告被环境中的感官刺激淹没，导致工作和社交场合困难，从而降低生活质量。从神经生物学角度来看，这种表型部分是由于 调节抑制电路的烟碱受体系统的功效降低，并且可能在显示皮质对噪音反应过度活跃的功能磁共振成像研究中得到证实。当噪音与任务无关时，对噪音的敏感性可能会对注意力相关的神经元反应产生有害影响，尽管这一点尚未得到最终证明。拟议的研究将包括两个具体目标。第一个目标是使用功能磁共振成像技术在精神分裂症患者和健康对照中研究分散注意力的环境噪音对听觉注意任务相关神经元活动和行为的影响。假设分心条件（噪音或 将观察到诊断（患者或对照）交互作用，这是由噪音期间（相对于沉默）患者注意力网络相关活动相对减少驱动的，但对照中活动的相反效果（相对增加）。第二个目标将 确定烟碱激动剂（尼古丁）是否可以改善（a）被动聆听和（b）噪音分散的听觉注意力任务期间的反应异常。在第一个任务中，受试者将聆听环境噪音或暗示的沉默。预计相对于安慰剂，尼古丁将使患者海马体对噪音的反应正常化（即减少）。在第二个任务中，受试者将执行与第一个目标相同的听觉注意任务；据推测，相对于安慰剂，噪音引起的神经元反应和表现的变化同样会被尼古丁标准化。目前的研究将是第一个检查胆碱能调节对精神分裂症选择性注意力的神经元影响的研究，并对治疗开发具有方法学和药理学意义。通过完成这项研究，结合课程作业、参与活跃的临床研究小组和科罗拉多大学研究社区等其他活动，NRSA 将使 Smucny 先生能够实现其博士前培训的以下目标：1) 获得精神分裂症神经生物学的专业知识 2) 扩展他在功能磁共振成像实验设计、数据采集和统计分析方面的知识，以及 3) 精通 在期刊和会议上展示他的工作。这些目标的实现是 Smucny 先生实现成为心理健康领域富有成效的独立研究员的长期目标的重要一步，重点是利用神经影像学更好地了解精神分裂症的神经生物学和神经药理学。