Nestor P G, Han S D, Niznikiewicz M, Salisbury D, Spencer K, Shenton M E, McCarley R W
Department of Psychiatry, Harvard Medical School, Brockton VAMC-116A, 940 Belmont Street, Brockton, MA 02401, USA.
Biol Psychol. 2001 Jul-Aug;57(1-3):23-46. doi: 10.1016/s0301-0511(01)00088-6.
We view schizophrenia as producing a failure of attentional modulation that leads to a breakdown in the selective enhancement or inhibition of semantic/lexical representations whose biological substrata are widely distributed across left (dominant) temporal and frontal lobes. Supporting behavioral evidence includes word recall studies that have pointed to a disturbance in connectivity (associative strength) but not network size (number of associates) in patients with schizophrenia. Paralleling these findings are recent neural network simulation studies of the abnormal connectivity effect in schizophrenia through 'lesioning' network connection weights while holding constant network size. Supporting evidence at the level of biology are in vitro studies examining N-methyl-D-aspartate (NMDA) receptor antagonists on recurrent inhibition; simulations in neural populations with realistically modeled biophysical properties show NMDA antagonists produce a schizophrenia-like disturbance in pattern association. We propose a similar failure of NMDA-mediated recurrent inhibition as a candidate biological substrate for attention and semantic anomalies of schizophrenia.
我们认为精神分裂症会导致注意力调节功能失效，进而致使对语义/词汇表征的选择性增强或抑制出现障碍，而这些表征的生物学基础广泛分布于左侧（优势）颞叶和额叶。支持这一观点的行为学证据包括单词回忆研究，该研究表明精神分裂症患者存在连接性（联想强度）障碍，但网络规模（联想数量）并无异常。与这些发现相似的是，近期通过“损伤”神经网络连接权重同时保持网络规模不变，对精神分裂症异常连接效应进行的神经网络模拟研究。生物学层面的支持证据来自体外研究，该研究检测了N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对反复抑制的作用；对具有真实生物物理特性的神经群体进行的模拟显示，NMDA拮抗剂会在模式关联中产生类似精神分裂症的障碍。我们提出，NMDA介导的反复抑制功能出现类似故障，是精神分裂症注意力和语义异常的一种潜在生物学基础。
