Department of Psychiatry, University of California, San Diego, La Jolla, California.
Department of Cognitive Sciences, Halicioğlu Data Science Institute, and Neurosciences Graduate Program, University of California, San Diego, La Jolla, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):562-568. doi: 10.1016/j.bpsc.2020.02.004. Epub 2020 Feb 22.
Abnormalities in cortical excitation and inhibition (E/I) balance are thought to underlie sensory and information processing deficits in schizophrenia. Deficits in early auditory information processing mediate both neurocognitive and functional impairment and appear to be normalized by acute pharmacologic challenge with the NMDA antagonist memantine (MEM).
Thirty-six subjects with a diagnosis of schizophrenia and 31 healthy control subjects underwent electroencephalographic recordings. Subjects ingested either placebo or MEM (10 or 20 mg) in a double-blind, within-subject, crossover, randomized design. The aperiodic, 1/f-like scaling property of the neural power spectra, which is thought to index relative E/I balance, was estimated using a robust linear regression algorithm.
Patients with schizophrenia had greater aperiodic components compared with healthy control subjects (p < .01, d = 0.64), which was normalized after 20 mg MEM. Analysis revealed a significant dose × diagnosis interaction (p < .0001, d = 0.82). Furthermore, the MEM effect (change in aperiodic component in MEM vs. placebo conditions) was associated with baseline attention and vigilance (r = .54, p < .05) and MEM-induced enhancements in gamma power (r = -.60, p < .01).
Findings confirmed E/I balance abnormalities in schizophrenia that were normalized with acute MEM administration and suggest that neurocognitive profiles may predict treatment response based on E/I sensitivity. These data provide proof-of-concept evidence for the utility of E/I balance indices as metrics of acute pharmacologic sensitivity for central nervous system therapeutics.
皮质兴奋和抑制（E/I）平衡异常被认为是精神分裂症患者感觉和信息处理缺陷的基础。早期听觉信息处理缺陷介导神经认知和功能障碍，并且似乎可以通过 NMDA 拮抗剂美金刚（MEM）的急性药物挑战来正常化。
36 名被诊断为精神分裂症的患者和 31 名健康对照者接受了脑电图记录。在双盲、自身对照、交叉、随机设计中，受试者口服安慰剂或 MEM（10 或 20mg）。使用稳健的线性回归算法估计神经功率谱的非周期性、1/f 样标度性质，这被认为是相对 E/I 平衡的指标。
与健康对照组相比，精神分裂症患者的非周期性成分更大（p<0.01，d=0.64），在服用 20mg MEM 后得到正常化。分析显示剂量与诊断的显著交互作用（p<0.0001，d=0.82）。此外，MEM 效应（MEM 与安慰剂条件下非周期性成分的变化）与基线注意力和警觉性相关（r=0.54，p<0.05），并且与 MEM 诱导的伽马功率增强相关（r=-0.60，p<0.01）。
这些发现证实了精神分裂症中 E/I 平衡异常，并且在急性 MEM 给药后得到正常化，并表明神经认知特征可能基于 E/I 敏感性预测治疗反应。这些数据提供了 E/I 平衡指数作为中枢神经系统治疗剂急性药物敏感性指标的概念验证证据。
