Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee.
Vanderbilt University Institute of Imaging Science, Nashville, Tennessee.
Biol Psychiatry. 2018 Mar 15;83(6):509-517. doi: 10.1016/j.biopsych.2017.09.022. Epub 2017 Sep 28.
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.
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.
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.
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.
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）和丘脑之间的协调信息处理，特别是中背侧核。这就提出了一种可能性，即 PFC 和中背侧丘脑之间的解剖连通性可能 1）在精神分裂症中降低，2）与执行功能缺陷有关。目前的研究检验了这些假设。
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。概率追踪用于量化包括 PFC 在内的六个皮质区域与丘脑之间的解剖连通性。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-皮质解剖连通性，并在患者中检查 PFC-丘脑解剖连通性与执行功能损伤严重程度的关系。
精神分裂症患者丘脑与 PFC 之间的解剖连通性降低。体素分析将这种减少定位于与外侧 PFC 相连的中背侧丘脑区域。精神分裂症患者 PFC-丘脑连通性的降低与工作记忆受损相关，但与认知灵活性和抑制无关。与 PFC-丘脑连通性降低相反，精神分裂症患者丘脑与躯体感觉和枕叶皮质的连通性增加。
这些结果与暗示 PFC-丘脑连通性中断在精神分裂症的病理生理学和认知损伤机制中的作用的模型一致。PFC-丘脑解剖连通性可能是促进认知干预的重要靶点。需要进一步的工作来确定增加与感觉皮层的丘脑连通性的意义。
