Computational modeling of excitatory/inhibitory balance impairments in schizophrenia.
Computational modeling of excitatory/inhibitory balance impairments in schizophrenia.
复制标题
精神分裂症中兴奋性/抑制平衡障碍的计算模型。
DOI：
10.1016/j.schres.2020.03.027
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发表时间：
2022-11
影响因子：
4.5
通讯作者：
Javitt DC
中科院分区：
文献类型：
--
作者：
Qian N;Lipkin RM;Kaszowska A;Silipo G;Dias EC;Butler PD;Javitt DC
在精神分裂症（SZ）中，神经元能功能的缺陷是公认的，反映在感觉系统的“输入”功能障碍中。相比之下，很少有人知道的贡献GABA能系统的损伤兴奋/抑制平衡。我们通过测量精神分裂症受试者和匹配对照者的方向检测、方向辨别力和方向-倾斜-后效曲线的对比度阈值来研究这个问题。这些措施取决于潜在的方向调谐曲线，这反过来又取决于兴奋性和抑制性的相互作用的幅度和宽度。通过模拟一个完善的V1方向选择性模型及其与感知的联系，我们证明了减少皮层兴奋和抑制都是必要的，以解释我们的心理物理数据。GABA能反馈的减少可能代表SZ中对受损的多巴胺能输入的代偿反应，或单独的病理生理事件。我们还发现了广泛接受的证据，但很少测试，方向辨别力和调谐宽度之间的反比关系。
Deficits in glutamatergic function are well established in schizophrenia (SZ) as reflected in “input” dysfunction across sensory systems. By contrast, less is known about contributions of the GABAergic system to impairments in excitatory/inhibitory balance. We investigated this issue by measuring contrast thresholds for orientation detection, orientation discriminability, and orientation-tilt-aftereffect curves in schizophrenia subjects and matched controls. These measures depend on the amplitude and width of underlying orientation tuning curves, which, in turn, depend on excitatory and inhibitory interactions. By simulating a well-established V1 orientation selectivity model and its link to perception, we demonstrate that reduced cortical excitation and inhibition are both necessary to explain our psychophysical data. Reductions in GABAergic feedback may represent a compensatory response to impaired glutamatergic input in SZ, or a separate pathophysiological event. We also found evidence for the widely accepted, but rarely tested, inverse relationship between orientation discriminability and tuning width.
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