Winterer Georg, Musso Francesco, Beckmann Christian, Mattay Venkata, Egan Michael F, Jones Douglas W, Callicott Joseph H, Coppola Richard, Weinberger Daniel R
Genes, Cognition and Psychosis Program, NIH, NIMH, 10 Center Dr., MSC 1379, Bethesda, MD 20892, USA.
Am J Psychiatry. 2006 Nov;163(11):1960-8. doi: 10.1176/ajp.2006.163.11.1960.
Prefrontal dysfunction is considered a fundamental characteristic of schizophrenia. Recent electrophysiological evidence points to a major instability of signal processing in prefrontal cortical microcircuits because of reduced phase-synchronization (i.e., an increased stimulus-related variability [noise] of single-trial responses in the spatial and time domain). The authors used functional magnetic resonance imaging (fMRI) during a visual two-choice reaction task in order to measure, with higher topographic accuracy, signal stability in patients with schizophrenia and its relationship to more traditional measures of activation.
Twelve clinically stable inpatients with schizophrenia and 16 matched comparison subjects were evaluated. Event-related blood-oxygen-level-dependent responses were subjected to an analysis of residual noise variance and to independent data dimension independent component analysis in the medial prefrontal cortex.
In patients with schizophrenia, the authors found increased residual noise variance of the blood-oxygen-level-dependent response that predicted the level of prefrontal activation in these subjects. In the left hemisphere, residual noise variance strongly correlated with psychotic symptoms. Independent component analysis revealed a "fractionized" and unfocussed pattern of activation in patients.
These findings suggest that unstable cortical signal processing underlies classic abnormal cortical activation patterns as well as psychosis in schizophrenia.
前额叶功能障碍被认为是精神分裂症的一个基本特征。最近的电生理学证据表明，由于相位同步性降低（即单次试验反应在空间和时间域中与刺激相关的变异性[噪声]增加），前额叶皮质微回路中的信号处理存在重大不稳定性。作者在视觉二选一反应任务期间使用功能磁共振成像（fMRI），以便更精确地测量精神分裂症患者的信号稳定性及其与更传统的激活测量指标之间的关系。
对12名临床症状稳定的精神分裂症住院患者和16名匹配的对照受试者进行评估。对事件相关的血氧水平依赖反应进行内侧前额叶皮质的残余噪声方差分析和独立数据维度独立成分分析。
在精神分裂症患者中，作者发现血氧水平依赖反应的残余噪声方差增加，这可预测这些受试者的前额叶激活水平。在左半球，残余噪声方差与精神病症状密切相关。独立成分分析显示患者存在“分散化”且不集中的激活模式。
这些发现表明，不稳定的皮质信号处理是精神分裂症中典型的异常皮质激活模式以及精神病的基础。
