Freedman R, Adler L E, Myles-Worsley M, Nagamoto H T, Miller C, Kisley M, McRae K, Cawthra E, Waldo M
Department of Psychiatry, Denver Veterans Administration Medical Center, Colo, USA.
Arch Gen Psychiatry. 1996 Dec;53(12):1114-21. doi: 10.1001/archpsyc.1996.01830120052009.
Altered sensory response is a prominent feature of schizophrenia. Inhibitory gatting mechanisms, shown by diminished P50 evoked responses to repeated auditory stimuli, seem to be deficient in schizophrenic persons. These inhibitory mechanisms usually are studied by averaging the electroencephalographic responses to many presentations of pairs of stimuli. Although averaging increases signal-to-noise ratio, it may obscure trial-to-trial differences. We compared differences between schizophrenic and normal persons in single trials and averages of P50 response.
Recordings from 10 schizophrenic patients and 10 normal subjects were analyzed using conventional averaging and single-trial measurements. A computer simulation of both methods examined their ability to extract evoked responses from background activity. Related single-neuron activity in the hippocampus in an animal model also was studied, because neuronal action potentials can be reliably identified in single trials.
Averaged evoked potentials showed significant suppression of the P50 response to the second stimulus of the pair in normal patients, but not in schizophrenic patients. Single-trial analysis did not detect a response above background activity. Computer simulations gave similar results, suggesting that failure to detect suppression in single trials comes from inadequate differentiation of signal from noise. Recordings in animals confirmed almost complete suppression of the response of hippocampal pyramidal neurons to the second stimulus.
The normal inhibition of response to repeated auditory stimuli seems to be compromised in schizophrenia. This loss of inhibitory gating could reflect a physiological deficit of hippocampal interneurons that is consonant with other evidence for interneuron pathologic defects in schizophrenia.
感觉反应改变是精神分裂症的一个显著特征。抑制性门控机制表现为对重复听觉刺激的P50诱发电位反应减弱，在精神分裂症患者中似乎存在缺陷。这些抑制性机制通常通过对成对刺激的多次呈现的脑电图反应进行平均来研究。虽然平均提高了信噪比，但可能会掩盖逐次试验之间的差异。我们比较了精神分裂症患者和正常人在单次试验和P50反应平均值方面的差异。
使用传统的平均法和单次试验测量法对10名精神分裂症患者和10名正常受试者的记录进行分析。对这两种方法的计算机模拟检验了它们从背景活动中提取诱发电位的能力。还研究了动物模型中海马体中的相关单神经元活动，因为在单次试验中可以可靠地识别神经元动作电位。
平均诱发电位显示，正常患者对成对刺激中的第二个刺激的P50反应有显著抑制，而精神分裂症患者则没有。单次试验分析未检测到高于背景活动的反应。计算机模拟给出了类似的结果，表明在单次试验中未能检测到抑制是由于信号与噪声的区分不足。动物记录证实海马锥体细胞对第二个刺激的反应几乎完全被抑制。
精神分裂症患者对重复听觉刺激的正常抑制似乎受到损害。这种抑制性门控的丧失可能反映了海马中间神经元的生理缺陷，这与精神分裂症中间神经元病理缺陷的其他证据一致。
