Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, 81675, Germany.
TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, Technische Universität München, Munich, 81675, Germany.
Brain. 2020 Dec 5;143(11):3495-3505. doi: 10.1093/brain/awaa296.
Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.
背侧纹状体中多巴胺功能异常，以及不同皮质网络和丘脑核之间的固有功能连接（iFC）异常，是精神分裂症中最一致的大规模脑成像发现之一。基于纹状体多巴胺对皮质-丘脑连接的拓扑调制的理论模型表明，这两种改变之间存在病理生理学联系。皮质-基底神经节-丘脑回路。我们假设异常的纹状体多巴胺与异常的皮质-丘脑 iFC 具有拓扑相关性，即异常的关联纹状体多巴胺与突显网络和丘脑之间的异常 iFC 相关，而异常的感觉运动纹状体多巴胺与听觉-感觉运动网络和丘脑之间的异常 iFC 相关。19 名精神分裂症患者在精神病症状缓解期间和 19 名年龄和性别匹配的对照组接受了同时氟代二羟苯丙氨酸 PET（18F-DOPA-PET）和静息状态功能磁共振成像（rs-fMRI）。基于 18F-DOPA-PET 的流入常数 kicer 用于测量纹状体多巴胺合成能力；皮质网络和感兴趣的丘脑区域的 rs-fMRI 时间序列之间的相关系数用于测量 iFC。在突显网络为中心的系统中，患者的关联纹状体多巴胺合成能力降低，与突显网络-中脑-丘脑 iFC 降低呈正相关。这种相关性在患者和健康对照组中均存在。在听觉-感觉运动网络为中心的系统中，患者的感觉运动纹状体多巴胺合成能力降低，与听觉-感觉运动网络-腹外侧丘脑 iFC 增加呈正相关。这种相关性仅存在于患者中。结果表明，纹状体多巴胺合成能力降低与精神分裂症中的皮质-丘脑内在去连接具有拓扑相关性。数据表明，在精神分裂症中，多巴胺调节的皮质-基底神经节-丘脑回路中，异常的纹状体多巴胺和皮质-丘脑去连接在病理生理学上是相关的。
