A Longitudinal Multimodal Neuroimaging Study to Examine Relationships Between Resting State Glutamate and Task Related BOLD Response in Schizophrenia
A Longitudinal Multimodal Neuroimaging Study to Examine Relationships Between Resting State Glutamate and Task Related BOLD Response in Schizophrenia
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DOI：
10.3389/fpsyt.2018.00632
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发表时间：
2018-11-29
影响因子：
4.7
通讯作者：
Lahti, Adrienne C.
中科院分区：
文献类型：
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作者：
Cadena, Elyse J.;White, David M.;Lahti, Adrienne C.
先前的研究已经观察到精神分裂症患者的脑功能和神经代谢物水平均有损伤。在这项研究中，我们通过质子磁共振波谱（1H-MRS）和功能磁共振成像（fMRI）相结合，研究了停药期精神分裂症患者脑活动和神经化学之间的关系，以及这种关系是否在抗精神病药物治疗后发生改变。我们对22名精神分裂症（SZ）患者（最初停药和利培酮治疗6周后）进行Stroop颜色命名任务时在双侧背前扣带皮层（ACC）和功能磁共振成像（fMRI）中获得的单体素MRS进行研究，并对20名匹配的健康对照（HC）进行两次研究，间隔6周。我们观察到，与HC相比，服药的SZ患者ACC谷氨酸+谷氨酰胺(Glx)/肌酸（Cr）水平显著降低，但与停药基线相比没有显著降低。在停药期SZ中，ACC Glx/Cr水平与突出网络（SN）和后置默认模式网络（DMN）区域的血氧水平依赖（BOLD）反应的关系与HC相反。6周后，两组间Glx与BOLD反应的关系仍然相反；然而，对于两组，从基线到第6周，关系的方向发生了变化。这些结果提示了一种机制，即皮层谷氨酸和BOLD反应之间关系的改变破坏了服务于认知过程的主要神经网络的调节，可能影响认知。虽然这些关系似乎随着患者的治疗而正常化，但对结果的解释却因Glx水平的显着组差异以及Glx与HC中BOLD反应之间随时间变化的关系而混淆，这可能是由对任务或扫描仪环境的习惯等因素驱动的。
Previous studies have observed impairments in both brain function and neurometabolite levels in schizophrenia. In this study, we investigated the relationship between brain activity and neurochemistry in off-medication patients with schizophrenia and if this relationship is altered following antipsychotic medication by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI). We used single voxel MRS acquired in the bilateral dorsal anterior cingulate cortex (ACC) and fMRI during performance of a Stroop color-naming task in 22 patients with schizophrenia (SZ), initially off-medication and after a 6-week course of risperidone, and 20 matched healthy controls (HC) twice, 6 weeks apart. We observed a significant decrease in ACC glutamate + glutamine (Glx)/Creatine (Cr) levels in medicated SZ patients compared to HC but not compared to their off-medication baseline. In off-medication SZ, the relationship between ACC Glx/Cr levels and the blood oxygen level-dependent (BOLD) response in regions of the salience network (SN) and posterior default mode network (DMN) was opposite than of HC. After 6 weeks, the relationship between Glx and the BOLD response was still opposite between the groups; however for both groups the direction of the relationship changed from baseline to week 6. These results suggest a mechanism whereby alterations in the relationship between cortical glutamate and BOLD response is disrupting the modulation of major neural networks subserving cognitive processes, potentially affecting cognition. While these relationships appear to normalize with treatment in patients, the interpretations of the results are confounded by significant group differences in Glx levels, as well as the variability of the relationship between Glx and BOLD response in HC over time, which may be driven by factors including habituation to task or scanner environment.