Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia
Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia
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DOI：
10.1002/hbm.24365
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发表时间：
2018-09
影响因子：
4.8
通讯作者：
Stefanie Köhler;G. Wagner;K. Bär
中科院分区：
文献类型：
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作者：
Stefanie Köhler;G. Wagner;K. Bär
有证据表明，精神分裂症患者的认知控制功能以及由前额叶皮层（PFC）和背前扣带皮层（dACC）支撑的潜在大脑网络功能失调。产生儿茶酚胺的中脑和脑干核与PFC和dACC紧密相连，在认知控制过程中发挥着重要作用。潜在的神经递质系统功能障碍被认为在精神分裂症各种症状的发生中起着核心作用。我们试图探讨精神分裂症患者认知控制过程中多巴胺能中脑核，即腹侧被盖区（VTA）和黑质以及去肾上腺素能蓝斑（LC）的异常激活模式。使用事件相关功能磁共振成像（fMRI）对28名服药患者和27名健康对照者进行手动版Stroop任务调查。主要发现是在两种Stroop任务条件下，与对照组相比，患者VTA的BOLD激活减少，这与阴性症状的程度显著相关。我们进一步在患者和健康对照中检测到类似的LC激活。然而，在对照组中，LC激活与Stroop干扰时间显著相关，而在患者中未观察到这一点。精神分裂症患者VTA激活减少的发现进一步支持了精神分裂症中DA系统功能障碍的假设。此外，尽管LC激活程度相当，但与Stroop干扰时间的不显著相关性可能表明精神分裂症患者LC功能改变，因此需要进一步研究。
Evidence suggests that cognitive control functions as well as the underlying brain network, anchored by the prefrontal cortex (PFC) and the dorsal anterior cingulate cortex (dACC), are dysfunctional in schizophrenia. Catecholamine producing midbrain and brainstem nuclei are densely connected with the PFC and dACC and exert profound contributions to cognitive control processes. Dysfunctions within the underlying neurotransmitter systems are considered to play a central role in the occurrence of various symptoms of schizophrenia. We sought to investigate the putatively abnormal activation pattern of the dopaminergic midbrain nuclei, that is, ventral tegmental area (VTA) and substantia nigra as well as that of the noradrenergic locus coeruleus (LC) in patients with schizophrenia during cognitive control. A total of 28 medicated patients and 27 healthy controls were investigated with the manual version of the Stroop task using event‐related fMRI. The main finding was a reduced BOLD activation in the VTA during both Stroop task conditions in patients in comparison to controls, which correlated significantly with the degree of negative symptoms. We further detected a comparable LC activation in in patients and healthy controls. However, in controls LC activation was significantly correlated with the Stroop interference time, which was not observed in patients. The finding of reduced VTA activation in schizophrenia patients lends further support to the assumed dysfunction of the DA system in schizophrenia. In addition, despite comparable LC activation, the nonsignificant correlation with the Stroop interference time might indicate altered LC functioning in schizophrenia and, thus, needs further investigations.