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: 7897787
• 负责人: SOHEE PARK
• 金额: $ 26.83万
• 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 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897787
• 关键词: Address; Affect; Affective; Attention; Behavior; Behavior Control; Behavioral; Brain; Brain region; Cognitive; Cognitive deficits; Complex; Data; Development; Etiology; Event; Failure; First Degree Relative; Functional Magnetic Resonance Imaging; Future; Goals; Individual; Individual Differences; Intervention; Lead; Link; Maintenance; Memory; Memory impairment; Methods; Modeling; Neuroanatomy; Neurocognitive; Neurocognitive Deficit; Parietal Lobe; Patients; Pattern; Performance; Prefrontal Cortex; Process; Research Design; Role; Schizophrenia; Series; Short-Term Memory; Siblings; Social Functioning; Specific qualifier value; Sum; System; Therapeutic Intervention; Time; To specify; Visuospatial; Work; base; cognitive neuroscience; experience; forgetting; functional outcomes; improved; memory encoding; neuroimaging; neuropsychological; oculomotor; rehabilitation strategy; relating to nervous system; remediation; research study; response; selective attention; social

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，可能决定功能结果。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 是一种容量有限、活跃的短期记忆系统，用于指导和控制行为。大多数 SZ 患者及其大约一半的健康一级亲属都存在 WM 缺陷，这些缺陷与较差的社交和适应功能有关，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 缺陷和提高适应性功能的有针对性的干预措施。本提案寻求支持从认知神经科学方法研究深圳 WM 缺陷的组成部分，以确定 WM 缺陷的核心因素、它们的神经相关性以及 WM 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 WM 的编码和维持，但 SZ 患者无法有效整合注意力和情感来指导目标导向行为。在研究 1 中，将检查感知、注意力和情感因素在编码中的作用，通过一系列认知实验来指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。除了编码受损之外，还有充分的证据表明 SZ 维护异常。在研究 2 中，将检查注意力控制的影响和对维护的影响，以确定 SZ 的漏洞所在。在研究 3 中，将通过偶数相关的功能磁共振成像实验来研究前额叶和顶叶皮质在正常和异常 WM 中的作用。将观察正确和不正确表现的神经相关性，以阐明大脑中记忆和遗忘之间的差异。总之，当前的提案旨在确定 SZ 受试者及其未受影响的兄弟姐妹 WM 缺陷的关键组成部分。识别和阐明 SZ 的核心神经认知缺陷将有助于理解 SZ 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，从而改善 WM 缺陷并改善 SZ 的适应性功能。

项目成果

WORKING MEMORY IMPAIRMENT AS AN ENDOPHENOTYPIC MARKER OF A SCHIZOPHRENIA DIATHESIS.

• DOI: 10.1016/j.scog.2014.09.005
• 发表时间: 2014-09-01
• 期刊: Schizophrenia research. Cognition

Empathy, schizotypy, and visuospatial transformations.

• DOI: 10.1080/13546801003711350
• 发表时间: 2010-09
• 期刊: Cognitive neuropsychiatry
• 影响因子: 1.7
• 作者: Thakkar KN;Park S
• 通讯作者: Park S

Impaired contingent attentional capture predicts reduced working memory capacity in schizophrenia.

偶然注意力捕获受损预示着精神分裂症患者的工作记忆能力下降。

• DOI: 10.1371/journal.pone.0048586
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Mayer,JuttaS;Fukuda,Keisuke;Vogel,EdwardK;Park,Sohee
• 通讯作者: Park,Sohee

Altered brain activation during action imitation and observation in schizophrenia: a translational approach to investigating social dysfunction in schizophrenia.

• DOI: 10.1176/appi.ajp.2013.13040498
• 发表时间: 2014-05
• 期刊: The American journal of psychiatry
• 作者: Thakkar KN;Peterman JS;Park S
• 通讯作者: Park S

The associations between multisensory temporal processing and symptoms of schizophrenia.

• DOI: 10.1016/j.schres.2016.09.035
• 发表时间: 2017-01
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Stevenson RA;Park S;Cochran C;McIntosh LG;Noel JP;Barense MD;Ferber S;Wallace MT
• 通讯作者: Wallace MT