Yang Genevieve J, Murray John D, Wang Xiao-Jing, Glahn David C, Pearlson Godfrey D, Repovs Grega, Krystal John H, Anticevic Alan
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511; Interdepartmental Neuroscience Program, Department of Neurobiology, Yale University, New Haven, CT 06520; Abraham Ribicoff Research Facilities, Department of Psychiatry, Connecticut Mental Health Center, New Haven, CT 06519;
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511; Center for Neural Science, New York University (NYU), New York, NY 06510;
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E219-28. doi: 10.1073/pnas.1508436113. Epub 2015 Dec 23.
Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
精神分裂症可能涉及皮质微回路中兴奋/抑制（E/I）比率升高。目前尚不清楚这种调节紊乱如何映射到神经影像学结果上。为了解决这个问题，我们在大规模功能连接的神经模型中实施了E/I扰动，该模型预测E/I升高后会出现超连接。为了验证预测结果，我们对161名精神分裂症患者和164名健康受试者进行了静息态功能磁共振成像检查。正如预测的那样，患者表现出功能连接升高，且与症状水平相关，在联合皮质（如额顶控制网络）中最为明显。双相情感障碍患者（n = 73）未出现这种模式。为了解释在精神分裂症中观察到的模式，我们将联合与感觉递归神经元动力学中神经生物学上合理的层次差异整合到我们的模型中。这种计算机模拟架构揭示了联合网络对E/I失衡的优先易损性，我们通过实验进行了验证。报告的结果表明，广泛的微回路E/I失衡是精神分裂症中出现不均匀性连接障碍的一种简约机制。
