Hoffman R E, McGlashan T H
Department of Psychiatry, Yale University School of Medicine, Yale-New Haven Psychiatric Hospital, New Haven, CT 06519, USA.
Pharmacopsychiatry. 2006 Feb;39 Suppl 1:S54-64. doi: 10.1055/s-2006-931496.
A number of studies suggest that schizophrenia may arise from overzealous pruning of synapses that are an extension of normal developmental pruning during adolescence. Moreover, there has been a long history of studies suggesting that this disorder arises from alterations in the dopaminergic neuromodulatory systems. In order to further assess and compare these two hypotheses, a computer simulation of some aspects of speech perception was developed utilizing a recurrent, backpropagation model of working memory previously reported by Elman . This system was found to produce spontaneous percepts simulating hallucinated speech when the working memory component either was excessively pruned or when neuronal responses were modulated to simulatea hyperdopaminergic system. These hallucinogenic systems also demonstrated disruptions in processing input information when "phonetic information" was degraded. The perceptual performance of these systems were compared to that of actual hallucinating patients and normal controls while tracking (repeating while simultaneously listening to) speech that was phonetically degraded. We found that the neural network simulation producing the best match to speech tracking performance of human hallucinators was an overpruned system with compensatory hypodopaminergic adjustments. These data suggest that the primary pathophysiology of schizophrenia arises from curtailed connectivity in working memory systems and that dopaminergic alterations reflect secondary compensatory adjustments.
多项研究表明,精神分裂症可能源于对突触的过度修剪,而这种修剪是青春期正常发育性修剪的延伸。此外,长期以来有一系列研究表明,这种疾病源于多巴胺能神经调节系统的改变。为了进一步评估和比较这两种假说,利用埃尔曼先前报道的工作记忆循环反向传播模型,开发了一个言语感知某些方面的计算机模拟。当工作记忆组件被过度修剪或神经元反应被调节以模拟高多巴胺能系统时,发现该系统会产生模拟幻听言语的自发感知。当“语音信息”退化时,这些致幻系统在处理输入信息时也表现出紊乱。在跟踪(边听边重复)语音退化的语音时,将这些系统的感知性能与实际出现幻觉的患者和正常对照进行比较。我们发现,与人类幻觉者的语音跟踪性能最匹配的神经网络模拟是一个过度修剪且伴有代偿性多巴胺能不足调整的系统。这些数据表明,精神分裂症的主要病理生理学源于工作记忆系统中连接性的减少,而多巴胺能改变反映了继发性代偿性调整。