Feinberg I, Thode H C, Chugani H T, March J D
VA Medical Center, Martinez, CA 94553.
J Theor Biol. 1990 Jan 23;142(2):149-61. doi: 10.1016/s0022-5193(05)80218-8.
We analyzed the available ontogenetic data (birth to 30 years of age) for: amplitude of delta EEG (DA) waves during sleep; cortical metabolic rate (CMR) measured with positron emission tomography; and synaptic density (SD) in frontal cortex. Each is at the adult level at birth, increases to about twice this level by 3 years of age, and then gradually falls back to the adult level over the next two decades. Statistical analyses revealed that individual gamma distribution models fit each data set as well as did the best ad hoc polynomial. A test of whether a single gamma distribution model could describe all three data sets gave good results for DA and CMR but the fit was unsatisfactory for SD. However, because so few data were available for SD, this test was not conclusive. We proposed the following model to account for these changes. First, cortical neurons are stimulated by birth to enter a proliferative state (PS) that creates many connections. Next, as a result of interactions in the PS, neurons are triggered into a transient organizational state (OS) in which they make enduring connections. The OS has a finite duration (minutes to years), and is characterized by high rates of information-processing and metabolism. Levels of CMR, SD and DA, therefore, are proportional to the number of neurons in the OS at any time. Thus, the cortex after birth duplicates, over a vastly greater time scale, the overproduction and regression of neural elements that occurs repeatedly in embryonic development. Finally, we discussed the implications of post-natal brain changes for normal and abnormal brain function. Mental disorders that have their onset after puberty (notably schizophrenia and manic-depressive psychoses) might be caused by errors in these late maturational processes. In addition to age of onset, this neurodevelopmental hypothesis might explain several other puzzling features of these subtle disorders.
我们分析了以下各项可获得的个体发育数据（出生至30岁）：睡眠期间脑电图δ波（DA）的振幅；用正电子发射断层扫描测量的皮质代谢率（CMR）；以及额叶皮质的突触密度（SD）。每项指标在出生时就已达到成人水平，到3岁时增加至约成人水平的两倍，然后在接下来的二十年中逐渐回落至成人水平。统计分析表明，个体伽马分布模型与每个数据集的拟合效果与最佳的特殊多项式一样好。对单个伽马分布模型是否能描述所有三个数据集进行的检验，对于DA和CMR得出了良好结果，但对SD的拟合并不令人满意。然而，由于SD可用的数据很少，该检验并不具有决定性。我们提出了以下模型来解释这些变化。首先，皮质神经元在出生时受到刺激，进入增殖状态（PS），从而建立许多连接。接下来，由于PS中的相互作用，神经元被触发进入短暂的组织状态（OS），在该状态下它们建立持久连接。OS具有有限的持续时间（从几分钟到几年），其特征是高信息处理和代谢率。因此，CMR、SD和DA的水平在任何时候都与OS中的神经元数量成正比。因此，出生后的皮质在一个大得多的时间尺度上重复了胚胎发育中反复出现的神经元过度产生和消退过程。最后，我们讨论了出生后脑变化对正常和异常脑功能的影响。青春期后发病的精神障碍（尤其是精神分裂症和躁郁症）可能是由这些后期成熟过程中的错误引起的。除了发病年龄外，这种神经发育假说可能还解释了这些细微障碍的其他几个令人困惑的特征。
