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; 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，可以决定功能结果。工作记忆（WM）缺陷已被确定为SZ中神经认知缺陷的最重要组成部分之一。 WM是一种有限的活跃，主动的短期内存系统，可以指导和控制行为。大多数SZ患者及其健康的一级亲属中的大约一半患有WM缺陷，这些缺陷与社会和适应性差的功能不佳有关，但WM赤字的起源和后果尚不清楚。因此，不可能开发有针对性的干预措施，以减轻WM缺陷并改善适应性功能。本提案寻求支持，从认知神经科学方法中调查SZ中WM缺陷的组成部分，以确定这些因素是WM赤字，其神经相关性以及WM赤字对社会功能的影响。认知和神经解剖学数据表明，选择性关注和影响WM中的调制编码和维护，但SZ患者无法有效地整合注意力并影响到指导目标指导的行为。在研究1中，将检查感知，注意因素和情感因素在编码中的作用，以通过一系列认知实验来指定最佳和有害编码条件。编码会影响所有形式的记忆，因此具有深远的后果。除编码受损外，还有很好的证据证明了SZ中的异常维持。在研究2中，将检查注意力控制和影响对维护的影响，以确定SZ的脆弱性在哪里。在研究3中，将通过与均匀的fMRI实验一起研究前额叶和顶叶皮质在正常和异常WM中的作用。将观察到正确和不正确性能的神经相关性，以阐明大脑中的记忆和忘记之间的差异。总而言之，当前的提案旨在确定SZ受试者中WM缺陷的关键组成部分及其未受影响的兄弟姐妹。 SZ的核心神经认知缺陷的识别和阐明将有助于理解SZ中皮质功能和认知缺陷之间的复杂相互作用。此外，指定WM内的异常机制与注意力，情感和大脑激活模式有关，可能会导致有针对性的策略，这些策略可能会改善WM缺陷并改善SZ中的适应性功能。