Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: Relationship with impaired cognition, behavioral disorganization, and global function
Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: Relationship with impaired cognition, behavioral disorganization, and global function
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DOI：
10.1176/appi.ajp.2008.07060945
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发表时间：
2008-08-01
影响因子：
17.7
通讯作者：
Carter, Cameron S.
中科院分区：
文献类型：
--
作者：
Yoon, Jong H.;Minzenberg, Michael J.;Carter, Cameron S.
目的：虽然认知控制的缺陷被认为有助于精神分裂症患者的各种认知和行为异常，但这些缺陷背后的神经机制仍不清楚。在这项与事件相关的功能性磁共振成像（fMRI）研究中，作者验证了一个假设，即在认知控制任务中，精神分裂症患者背外侧前额叶皮层的激活受损与该前额叶区域和支持认知控制的分布式大脑网络之间的协调活动中断有关。方法：通过使用事件相关设计，25例首发精神分裂症患者和24名健康对照受试者，匹配的人口统计学特征，进行评估，同时执行版本的AX连续性能任务。功能性神经影像学数据采用1）单变量（感兴趣区域血氧水平依赖性[ BOLD]时间序列和全脑体素回归）分析，以确认背外侧前额叶皮质功能障碍的存在，2）多变量分析，以检查背外侧前额叶皮质功能连接。此外，背外侧前额叶皮层功能连接和以下变量之间的相关性进行了研究：临床症状，任务性能，并协调与认知control.Results相关的大脑活动：精神分裂症患者表现出特定的赤字在认知控制，与BX条件相对于任何其他条件的准确性显着降低。单变量功能磁共振成像显示背外侧前额叶皮质功能障碍，在高认知控制条件。多变量分析显示，背外侧前额叶皮层和任务相关的大脑区域之间的功能连接显着受损。背外侧前额叶皮层功能连接和认知性能，行为紊乱，和全球functioning.Conclusions之间也发现了显着的相关性：这些研究结果表明，有背外侧前额叶皮层活动和连接和任务相关的神经网络之间的关联。这种协调性大脑活动的缺陷可能导致精神分裂症患者与认知受损相关的致残性混乱症状。
Objective: Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control.Method: Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygenlevel-dependent [ BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control.Results: Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. Significant correlations were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning.Conclusions: These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia.