CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing, PR China.
Sino-Danish Center for Education and Research, Aarhus, Denmark.
Cereb Cortex. 2017 Jul 1;27(7):3832-3841. doi: 10.1093/cercor/bhx050.
Working memory (WM) impairment is regarded as a core aspect of schizophrenia. However, the neural mechanisms behind this cognitive deficit remain unclear. The connectivity of a frontoparietal network is known to be important for subserving WM. Using functional magnetic resonance imaging, the current study investigated whether WM-dependent modulation of effective connectivity in this network is affected in a group of first-episode schizophrenia (FES) patients compared with similarly performing healthy participants during a verbal n-back task. Dynamic causal modeling (DCM) of the coupling between regions (left inferior frontal gyrus (IFG), left inferior parietal lobe (IPL), and primary visual area) identified in a psychophysiological interaction (PPI) analysis was performed to characterize effective connectivity during the n-back task. The PPI analysis revealed that the connectivity between the left IFG and left IPL was modulated by WM and that this modulation was reduced in FES patients. The subsequent DCM analysis confirmed this modulation by WM and found evidence that FES patients had reduced forward connectivity from IPL to IFG. These findings provide evidence for impaired WM modulation of frontoparietal effective connectivity in the early phase of schizophrenia, even with intact WM performance, suggesting a failure of context-sensitive coupling in the schizophrenic brain.
工作记忆（WM）损伤被认为是精神分裂症的核心表现之一。然而，这种认知缺陷的神经机制仍不清楚。已知额顶网络的连通性对于支持 WM 很重要。本研究使用功能磁共振成像技术，在言语 n-back 任务中，比较了一组首发精神分裂症（FES）患者和表现相似的健康参与者，研究了 WM 是否会影响该网络中有效连通性的调节。通过心理生理交互（PPI）分析确定的区域（左侧额下回（IFG）、左侧顶下小叶（IPL）和初级视觉区）之间的耦合的动态因果建模（DCM）用于表征 n-back 任务期间的有效连通性。PPI 分析表明，WM 调节了左侧 IFG 和左侧 IPL 之间的连通性，而在 FES 患者中这种调节减弱。随后的 DCM 分析证实了 WM 的这种调节，并发现 FES 患者的 IPL 到 IFG 的前向连通性降低。这些发现为精神分裂症早期额顶叶有效连通性的 WM 调节受损提供了证据，即使 WM 表现正常，也表明精神分裂症大脑中上下文敏感耦合失败。
