Etiology of Working Memory Deficit in Schizophrenia

精神分裂症工作记忆缺陷的病因学

• 批准号: 7147706
• 负责人: SOHEE PARK
• 金额: $ 27.54万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-17 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147706
• 关键词: attention; behavioral /social science research tag; brain; clinical research; disease /disorder etiology; emotions; family genetics; frontal lobe /cortex; functional magnetic resonance imaging; goal oriented behavior; human subject; memory disorders; neuropsychological tests; neuropsychology; parietal lobe /cortex; patient oriented research; perception; psychological adaptation; schizophrenia; short term memory; siblings; social behavior; social psychology; stimulus /response; visual stimulus

DESCRIPTION (provided by applicant): Neurocognitive deficits are core features of schizophrenia (SZ) that may determine functional outcome. Working memory (WM) deficit has been identified as one of the most important components of the neurocognitive deficits in SZ. WM is a limited-capacity, active short-term memory system that guides and controls behavior. A majority of SZ patients and about half of their healthy first-degree relatives have WM deficits and these deficits are linked to poor social and adaptive functioning yet the origins and consequences of WM deficit are unclear. Thus it has not been possible to develop targeted interventions that might ameliorate WM deficits and improve adaptive functioning. The present proposal seeks support to investigate components of WM deficits in SZ from a cognitive neuroscience approach, to identify the factors are central to WM deficit, their neural correlates and the effects of WM deficit on social functioning. Cognitive and neuroanatomical data suggest that selective attention and affect modulate encoding and maintenance in WM but SZ patients are unable to effectively integrate attention and affect to guide goal-directed behavior. In Study 1, the roles of perceptual, attentional and affective factors in encoding will be examined to specify both optimal and detrimental encoding conditions with a series of cognitive experiments. Encoding affects all forms of memory and thus has far-reaching consequences. In addition to impaired encoding there is good evidence for abnormal maintenance in SZ. In Study 2, the effects of attentional control and affect on maintenance will be examined to identify where vulnerabilities of SZ lie. In Study 3, the roles of prefrontal and parietal cortices in normal and abnormal WM will be investigated with even-related fMRI experiments. The neural correlates of correct and incorrect performance will be observed to elucidate the difference between remembering and forgetting in the brain. In sum, the current proposal aims to identify the key components of WM deficits in SZ subjects, and their unaffected siblings. Identification and elucidation of core neurocognitive deficits of SZ will contribute towards the understanding of the complex interplay between cortical functions and cognitive deficits in SZ. Moreover, specifying abnormal mechanisms within WM in relation to attention, affect and brain activation patterns could lead to targeted strategies that might ameliorate WM deficits and improve adaptive functioning in SZ.

描述（由申请人提供）：神经认知缺陷是精神分裂症（SZ）的核心特征，可能决定功能结局。工作记忆（WM）缺陷已被确定为SZ神经认知缺陷的最重要组成部分之一。WM是一个容量有限的、活跃的短期记忆系统，它引导和控制行为。大多数SZ患者和大约一半的健康一级亲属有WM缺陷，这些缺陷与不良的社会和适应功能有关，但WM缺陷的起源和后果尚不清楚。因此，还没有可能制定有针对性的干预措施，可能会改善WM缺陷和改善适应功能。目前的建议寻求支持调查组件的WM赤字在SZ从认知神经科学的方法，以确定的因素是中央WM赤字，其神经相关的WM赤字的社会功能的影响。认知和神经解剖学数据表明，选择性注意和影响调制编码和维护WM，但SZ患者无法有效地整合注意和影响，以指导目标导向的行为。研究一通过一系列的认知实验，考察知觉、注意和情感因素在编码中的作用，以确定最佳和有害的编码条件。编码影响所有形式的记忆，因此具有深远的影响。除了受损的编码，有很好的证据表明，在深圳异常维护。在研究2中，注意控制和情感对维持的影响将被检查，以确定SZ的弱点所在。在研究三中，前额叶和顶叶皮质的作用，正常和异常WM将被调查与even-related功能磁共振成像实验。正确和不正确的表现的神经相关性将被观察，以阐明大脑中记忆和遗忘之间的差异。总之，目前的建议旨在确定深圳受试者的WM缺陷的关键组成部分，以及他们的未受影响的兄弟姐妹。鉴定和阐明SZ的核心神经认知缺陷将有助于理解SZ中皮质功能和认知缺陷之间复杂的相互作用。此外，指定异常的机制WM中的注意，影响和大脑激活模式可能会导致有针对性的策略，可能会改善WM赤字和改善适应性功能在SZ。