与精神分裂症工作记忆缺陷相关的前额叶-丘脑和感觉运动-丘脑回路的失衡。
Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia.
机构信息
Department of Psychiatry, the Second Xiangya Hospital, Central South University, Changsha, China.
Mental Health Institute of Central South University, Changsha, China.
出版信息
Schizophr Bull. 2022 Jan 21;48(1):251-261. doi: 10.1093/schbul/sbab086.
BACKGROUND
Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia.
METHODS
Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis.
RESULTS
During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively.
CONCLUSIONS
The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function.
背景
在前额叶-丘脑连接不足和感觉运动-丘脑连接过度的特点下，丘脑皮质回路失衡在精神分裂症（SCZ）患者的静息状态中得到了一致的证实。然而，迄今为止，尚未在任务参与期间研究这种丘脑皮质失衡，这限制了我们对其在精神分裂症认知功能障碍中的作用的理解。
方法
从 172 名 SCZ 患者和 103 名健康对照组（HC）中同时采集 n 回工作记忆（WM）任务 fMRI 和静息态 fMRI 数据。一个独立的由 49 名 SCZ 和 48 名 HC 组成的复制样本也被获得。采用 16 个丘脑亚区作为分析的种子。
结果
在任务执行和休息期间，与对照组相比，SCZ 表现出与感觉运动皮质的丘脑过度连接，但与前额叶-小脑区域的连接不足。较高的感觉运动-丘脑连接和较低的前额叶-丘脑连接均与 WM 表现较差（较低的任务准确性和更长的反应时间）以及在 n 回任务中区分目标与非目标（较低的 d'分数）困难相关。在 SCZ 和 HC 中，前额叶-丘脑的连接不足与感觉运动-丘脑的连接过度均呈负相关；这种负相关在认知需求较低时（休息>0 回>2 回）更为明显。这些发现可以很好地在第二个样本中得到验证。最后，在 SCZ 中，静息状态下的连接不足和过度模式与 2 回任务状态下的连接不足和过度模式呈正相关。
结论
在 SCZ 中，前额叶-丘脑连接不足和感觉运动-丘脑连接过度所反映的丘脑皮质失衡既存在于静息状态，也存在于任务参与状态，与工作记忆表现有关。这种丘脑皮质失衡的前额叶减少、感觉运动增强模式是 SCZ 的一种状态不变特征，影响核心认知功能。
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