Stephan K E, Magnotta V A, White T, Arndt S, Flaum M, O'Leary D S, Andreasen N C
Computational Systems Neuroscience Group, C. & O. Vogt Brain Research Institute, Heinrich-Heine-University, Düsseldorf, Germany.
Psychol Med. 2001 Aug;31(6):1065-78. doi: 10.1017/s0033291701004330.
According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task.
fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses.
The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum.
Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.
根据当前理论，精神分裂症是由大脑中负责基本认知操作的神经回路连接性改变所致。因此，抗精神病药物治疗中那些尚未被充分理解的机制或许可以通过此类网络内功能相互作用的改变来解释。“认知失调”模型推测，这些回路中的一个关键结构是小脑。为研究奥氮平对小脑功能连接性（CFC）的影响，在一项针对简单手指敲击任务的功能磁共振成像（fMRI）研究中采用了种子体素相关分析（SVCA）。
在无药物和奥氮平治疗两种条件下，对6名精神分裂症患者进行fMRI扫描，并在相应时间点对6名健康受试者组成的匹配对照组进行扫描。对小脑前部在解剖学和功能上标准化的种子体素进行SVCA。然后通过三种不同的随机分析对SVCA结果进行处理。
分析显示，奥氮平引起了CFC的广泛变化，包括前额叶皮质和丘脑背内侧核的显著变化。两组内相减后发现运动结构有显著变化，因此这可能表明是重复效应而非药物效应。奥氮平使患者右侧小脑的CFC模式“正常化”，但左侧小脑未出现这种情况。
即使对于简单的运动任务，奥氮平也会影响小脑与许多非运动脑区之间的功能相互作用，包括“认知失调”回路的组成部分。总体而言，我们的研究结果表明，奥氮平对前额叶皮质和丘脑神经活动的差异效应比对运动结构的效应更强。
