Etiology of Working Memory Deficit in Schizophrenia

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，可能决定功能结果。工作记忆(WM)缺陷被认为是深圳地区神经认知缺陷的重要组成部分之一。WM是一种容量有限的、活跃的短期记忆系统，它引导和控制行为。大多数SZ患者及其健康的一级亲属中约有一半患有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，不可能开发出可能改善WM缺陷和改善适应功能的有针对性的干预措施。本研究旨在从认知神经科学的角度研究深圳地区工作记忆缺陷的构成因素，以确定工作记忆缺陷的核心因素、它们的神经关联以及工作记忆缺陷对社会功能的影响。认知和神经解剖学数据表明，选择性注意和情感调节了WM的编码和维持，但SZ患者无法有效地整合注意力和情感来指导目标导向行为。在研究1中，我们将通过一系列认知实验来考察知觉、注意和情感因素在编码中的作用，以明确最佳和不利的编码条件。编码影响所有形式的记忆，因此具有深远的影响。除了编码受损外，SZ的异常维持也有很好的证据。在研究2中，将考察注意控制和情感对维持的影响，以确定SZ的脆弱性所在。在研究3中，前额叶和顶叶皮质在正常和异常WM中的作用将通过与事件相关的fMRI实验来研究。我们将观察正确和错误表现的神经关联，以阐明大脑中记忆和遗忘之间的区别。综上所述，目前的建议旨在确定深圳特区受试者及其未受影响的同胞的腰围缺陷的主要组成部分。识别和阐明SZ的核心神经认知缺陷将有助于理解SZ的皮质功能和认知缺陷之间复杂的相互作用。此外，明确WM中与注意力、情感和大脑激活模式相关的异常机制可能会导致有针对性的策略，可能会改善SZ的WM缺陷和改善适应功能。

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.