Schlösser Ralf, Gesierich Thomas, Kaufmann Bettina, Vucurevic Goran, Hunsche Stefan, Gawehn Joachim, Stoeter Peter
Department of Psychiatry, University of Mainz, Mainz, Germany.
Neuroimage. 2003 Jul;19(3):751-63. doi: 10.1016/s1053-8119(03)00106-x.
The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.
本研究旨在探讨精神分裂症患者在执行2-back工作记忆任务时有效连接性的改变。对12名接受典型或非典型抗精神病药物治疗的右利手精神分裂症患者和6名健康对照者进行了功能磁共振成像（fMRI）研究，他们在执行“2-back”工作记忆任务。评估并比较了两组在用于记忆信息处理的皮质-皮质下-小脑网络内的有效连接性。路径模型包括由顶叶联合皮质、腹外侧前额叶皮质（VLPFC）和背外侧前额叶皮质（DLPFC）组成的皮质-皮质连接，以及由前额叶皮质、对侧小脑和丘脑组成的皮质-小脑反馈回路。采用堆叠模型方法分析组间差异。相对于正常对照组，两个患者组均显示前额叶-小脑和小脑-丘脑分支内的连接性降低，但皮质-小脑回路的丘脑-皮质分支内的连接性增强。此外，对两个治疗组的直接比较显示，接受非典型抗精神病药物治疗的患者皮质联合区域之间的半球间连接性增强。然而，接受非典型抗精神病药物治疗的患者组中，右侧前额叶和左侧顶叶-前额叶路径系数较低。研究结果表明，皮质-皮质下小脑网络病变与相关功能连接性之间的关系是复杂的，可能包括连接性增加和减少的方面，这与精神分裂症中“认知失调”的概念一致。在皮质-小脑回路的前一个分支内有效连接性中断的情况下，观察到丘脑-皮质投射内明显的连接性可能归因于丘脑输入的代偿性增加。该研究证明了结构方程模型用于研究有效连接性的组间差异和治疗相关差异的可行性，并为进一步阐明功能能力改变与相关fMRI信号变化之间的关系提供了一种有前景的方法。
