BACKGROUND Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses. METHODS Forty-five healthy subjects and 62 patients with a schizophrenia spectrum disorder completed a battery of tests of executive function and underwent diffusion-weighted imaging. Probabilistic tractography was used to quantify anatomical connectivity between six cortical regions, including PFC, and the thalamus. Thalamocortical anatomical connectivity was compared between healthy subjects and patients with schizophrenia using region-of-interest and voxelwise approaches, and the association between PFC-thalamic anatomical connectivity and severity of executive function impairment was examined in patients. RESULTS Anatomical connectivity between the thalamus and PFC was reduced in schizophrenia. Voxelwise analysis localized the reduction to areas of the mediodorsal thalamus connected to lateral PFC. Reduced PFC-thalamic connectivity in schizophrenia correlated with impaired working memory but not cognitive flexibility and inhibition. In contrast to reduced PFC-thalamic connectivity, thalamic connectivity with somatosensory and occipital cortices was increased in schizophrenia. CONCLUSIONS The results are consistent with models implicating disrupted PFC-thalamic connectivity in the pathophysiology of schizophrenia and mechanisms of cognitive impairment. PFC-thalamic anatomical connectivity may be an important target for procognitive interventions. Further work is needed to determine the implications of increased thalamic connectivity with sensory cortex.

中文翻译：

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精神分裂症患者的前额叶-丘脑解剖连接和执行认知功能

背景执行认知功能，包括工作记忆、认知灵活性和抑制，在精神分裂症中受损。执行功能依赖于前额叶皮层 (PFC) 和丘脑，尤其是内侧核之间的协调信息处理。这增加了 PFC 和内侧丘脑之间的解剖连接可能 1) 在精神分裂症中减少和 2) 与执行功能缺陷相关的可能性。目前的调查检验了这些假设。方法 45 名健康受试者和 62 名精神分裂症谱系障碍患者完成了一系列执行功能测试并接受了弥散加权成像。概率纤维束成像用于量化六个皮质区域（包括 PFC）和丘脑之间的解剖连接。使用感兴趣区域和体素方法比较健康受试者和精神分裂症患者之间的丘脑皮质解剖连接，并在患者中检查 PFC-丘脑解剖连接与执行功能障碍严重程度之间的关联。结果 精神分裂症患者丘脑和 PFC 之间的解剖连接降低。体素分析将减少定位到与外侧 PFC 相连的内侧丘脑区域。精神分裂症患者 PFC-丘脑连接减少与工作记忆受损有关，但与认知灵活性和抑制无关。与 PFC-丘脑连接减少相反，精神分裂症患者丘脑与躯体感觉和枕叶皮质的连接增加。结论 结果与暗示精神分裂症病理生理学和认知障碍机制中 PFC-丘脑连接中断的模型一致。PFC-丘脑解剖连接可能是认知干预的重要目标。需要进一步的工作来确定增加丘脑与感觉皮层连接的影响。