Hoffman R E, McGlashan T H
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Am J Psychiatry. 1997 Dec;154(12):1683-9. doi: 10.1176/ajp.154.12.1683.
After peaking during childhood, synaptic density in the human frontal cortex declines by 30%-40% during adolescence because of progressive elimination of synaptic connections. The characteristic age at onset of schizophrenia--late adolescence and early adulthood--suggests that the disorder could arise from irregularities involving this neurodevelopmental process.
A computer simulation of a speech perception neural network was developed. Connections within the working memory component of the network were eliminated on the basis of a "Darwinian rule" in order to model loss of synapses. As a comparison, neuronal cell death, also postulated as being linked to both neurodevelopment and schizophrenia, was simulated. The authors determined whether these alterations at low levels could enhance perceptual capacity and at high levels produce spontaneous speech percepts that simulate hallucinated speech or "voices."
Eliminating up to 65% of working memory connections improved perceptual ability; beyond that point, network performance declined and speech hallucinations emerged. Simulating excitotoxic neuronal loss at low levels also improved network performance, but in excess it did not produce hallucinations.
The model demonstrates perceptual advantages of selective synaptic elimination as well as selective neuronal loss, suggesting a functional explanation for these aspects of neurodevelopment. The model predicts that psychosis arises from a pathological extension of one of these neurodevelopmental trends, namely, synaptic elimination.
人类额叶皮质的突触密度在童年期达到峰值后，在青春期会因突触连接的逐渐消除而下降30%-40%。精神分裂症的特征性发病年龄——青春期晚期和成年早期——表明该疾病可能源于涉及这一神经发育过程的异常情况。
开发了一个语音感知神经网络的计算机模拟模型。根据“达尔文规则”消除网络工作记忆组件内的连接，以模拟突触丧失。作为对照，还模拟了同样被认为与神经发育和精神分裂症相关的神经元细胞死亡。作者们确定了这些低水平的改变是否能提高感知能力，以及在高水平时是否会产生模拟幻觉性言语或“幻听”的自发性言语感知。
消除高达65%的工作记忆连接可提高感知能力；超过这一比例，网络性能下降，言语幻觉出现。低水平模拟兴奋性毒性神经元丧失也可改善网络性能，但过量时不会产生幻觉。
该模型展示了选择性突触消除以及选择性神经元丧失的感知优势，为神经发育的这些方面提供了一种功能性解释。该模型预测，精神病源于这些神经发育趋势之一的病理性扩展，即突触消除。
