Arazi Ayelet, Toso Alessandro, Grent-'t-Jong Tineke, Uhlhaas Peter J, Donner Tobias H
Section Computational Cognitive Neuroscience, Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, 13353 Berlin, Germany.
Sci Adv. 2025 Aug 15;11(33):eads0400. doi: 10.1126/sciadv.ads0400. Epub 2025 Aug 13.
Psychotic disorders affect GABAergic inhibition and glutamatergic excitation via NMDA receptors across the cerebral cortex. The mechanisms by which these distributed synaptic alterations produce the heterogenous symptoms of psychosis remain poorly understood. Using magnetoencephalographical source imaging, we mapped psychosis-related alterations of various features of intrinsic neural population dynamics across the human cortex. The cortex-wide patterns of these features were highly reproducible and related to the anatomical hierarchy of cortical areas. We found similar changes in these patterns for individuals with a first episode of psychosis and those at clinical high risk for psychosis. Maps of psychosis-induced changes in dynamics resembled the maps of GABA-A receptor densities and of pharmacological GABA-A or NMDA manipulation effects on cortical dynamics in healthy participants. The level of pattern similarity to GABA-A manipulation effects in individual patients correlated with positive symptoms, while the pattern similarity to NMDA effects correlated with negative symptoms. Our results open up a window on the distributed mechanisms of psychotic symptoms.
精神障碍通过NMDA受体影响整个大脑皮层的GABA能抑制和谷氨酸能兴奋。这些分布性突触改变产生精神分裂症异质性症状的机制仍知之甚少。我们使用脑磁图源成像技术，绘制了人类皮层中内在神经群体动力学各种特征与精神分裂症相关的改变。这些特征在全皮层的模式具有高度可重复性，且与皮层区域的解剖层次相关。我们发现首次发作精神分裂症的个体和临床高危个体在这些模式上有类似变化。精神分裂症引起的动力学变化图谱类似于健康参与者中GABA-A受体密度图谱以及GABA-A或NMDA药物对皮层动力学影响的图谱。个体患者中与GABA-A药物作用效应的模式相似程度与阳性症状相关，而与NMDA效应的模式相似程度与阴性症状相关。我们的研究结果为精神症状的分布式机制打开了一扇窗口。
