Psychiatry, University of California San Francisco , San Francisco, CA , USA ; Mental Health Service, San Francisco VA Medical Center , San Francisco, CA , USA.
Front Psychiatry. 2013 Sep 10;4:92. doi: 10.3389/fpsyt.2013.00092. eCollection 2013.
The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) performance in youth at clinical high-risk (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls (HC). We hypothesized that the DMN would show load-dependent suppression during WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate pattern.
fMRI data were collected from CHR (n = 32), ESZ (n = 22), and HC (n = 54) participants, ages 12-30. DMN regions were defined via seed-based connectivity analysis of resting-state fMRI data from an independent HC sample. Load-dependent deactivations of these DMN regions in response to WM probes were interrogated.
Healthy controls showed linear load-dependent increases in DMN deactivation. Significant Group-by-Load interactions were observed in DMN regions including medial prefrontal and lateral posterior parietal cortices. Group-by-Load effects in posterior DMN nodes resulted from less suppression at higher WM loads in ESZ relative to HC, with CHR differing from neither group. In medial prefrontal cortex, suppression of activity at higher WM loads was significantly diminished in both CHR and ESZ groups, relative to HC. In addition, investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that ESZ activated right DLPFC significantly more than HC, with CHR differing from neither group.
While HC showed WM load-dependent modulation of DMN suppression, CHR individuals had deficient higher-load DMN suppression that was similar to, but less pronounced than, the distributed suppression deficits evident in ESZ patients. These results suggest that DMN dysregulation associated with schizophrenia predates psychosis onset.
默认模式网络（DMN）是一组在休息时通常被激活并在外来认知时被抑制的大脑区域。精神分裂症与 DMN 抑制不足有关，但 DMN 功能障碍在精神病发作前的程度尚不清楚。本研究在精神病临床高风险（CHR）、早期精神分裂症（ESZ）患者和健康对照（HC）中检查了工作记忆（WM）表现期间的 DMN 抑制。我们假设在 HC 中，DMN 在 WM 检索过程中会表现出依赖于负荷的抑制，而在 ESZ 中则不会，CHR 参与者表现出中间模式。
从 12-30 岁的 CHR（n=32）、ESZ（n=22）和 HC（n=54）参与者中收集 fMRI 数据。通过对独立 HC 样本的静息状态 fMRI 数据进行基于种子的连通性分析来定义 DMN 区域。研究了这些 DMN 区域对 WM 探针的依赖于负荷的去激活。
健康对照者显示 DMN 去激活的线性依赖于负荷的增加。在包括内侧前额叶和外侧顶后皮质的 DMN 区域观察到显著的组-负荷交互作用。ESZ 相对于 HC ，在较高 WM 负荷下，后 DMN 节点的组-负荷效应是由于抑制较少，而 CHR 与两组均不同。在内侧前额叶皮质中，在较高 WM 负荷下，活动的抑制明显降低，在 CHR 和 ESZ 组均低于 HC。此外，对背外侧前额叶皮质（DLPFC）激活的研究表明，ESZ 比 HC 显著更多地激活右侧 DLPFC，而 CHR 与两组均不同。
虽然 HC 显示 WM 负荷依赖于 DMN 抑制的调节，但 CHR 个体存在缺陷的高负荷 DMN 抑制，与 ESZ 患者明显的分布式抑制缺陷相似，但程度较轻。这些结果表明，与精神分裂症相关的 DMN 失调在精神病发作前就已经存在。
