Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate-in the spatial memory task, during memory recall-that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process.

中文翻译：

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θ相耦合受损是精神分裂症的额颞不连通性的基础。

额颞不通是精神分裂症的关键病理。这种不连通的具体性质尚不清楚，但动物模型暗示海马体​​与内侧前额叶皮层（mPFC）之间的θ功能失调。我们通过检查18名有精神分裂症诊断的参与者（包括药物治疗和非药物治疗）的神经动力学来检验该假设。和26位年龄，性别和智商相匹配的对照组。所有参与者都完成了两项引起海马-前额叶theta耦合的任务：空间记忆任务（在脑磁图检查期间）和记忆整合任务。另外，一组33名精神分裂症和29名对照受试者的重叠组接受了PET，以测量表达α5亚基的GABAAR的可用性（集中在海马生长抑素中间神经元上）。我们在空间记忆任务中演示 在记忆回忆中-精神分裂症患者左内侧颞叶（mTL）的theta功率增加受到损害，mPFC和mTL之间的theta相耦合也是如此。重要的是，后者不能用theta功率变化，头部运动，抗精神病药，大麻使用或IQ来解释，在其他频带中找不到。此外，mPFC-mTL theta偶联与对照组的表现密切相关，但与精神分裂症患者无关，精神分裂症患者在空间记忆任务中轻度受损，在记忆整合任务中的机率并不比偶然好。最后，在更广泛的精神分裂症PET样本中，精神分裂症磁脑图参与者中显示相耦合减少的mTL区域与α5-GABAAR可用性降低的区域基本重叠。