Test-retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers
Test-retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers
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DOI：
10.1016/j.neuroimage.2012.09.037
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发表时间：
2013-01-01
期刊：
影响因子：
5.7
通讯作者：
Mehta, M. A.
中科院分区：
文献类型：
--
作者：
De Simoni, S.;Schwarz, A. J.;Mehta, M. A.
药理学MRI（phMRI）技术正越来越多地用于临床前和临床模型，以研究药理学对无任务脑功能的影响。氯胺酮是一种N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂，可诱导强烈的phMRI反应，是一种有前途的药理学模型，可用于研究多巴胺能异常在精神病学中的作用。本研究的目的是评估对氯胺酮的脑反应是否可靠，以验证氯胺酮phMRI作为脑功能障碍的机制标志物，并确定其在重复测量设计中的实用性，以检测其他药物的调节作用。因此，我们评估了在健康志愿者的氯胺酮脑反应的重测可靠性，并确定了一个最佳的建模方法与可靠性作为我们的选择criterion.PhMRI数据收集10名健康男性参与者，在休息，在两个不同的场合。在两个阶段中给予亚麻醉剂量的氯胺酮静脉输注（目标血浆水平50 ng/mL和75 ng/mL）。针对一系列时间设计矩阵，包括设计用于模拟形状方差、线性漂移和头部运动的滋扰回归量的不同组合，按体素和预定义ROI评估氯胺酮phMRI响应的重测可靠性。所有模型在预测的大脑网络中对低剂量氯胺酮表现出显著和广泛的反应，正如预期的那样，增加模型参数的数量改善了模型拟合。在评估的不同模型之间，预定义ROI的可靠性不同。使用可靠性作为选择标准，捕获受试者运动和线性漂移的模型在两个会话中表现最好。所有模型的效应解剖分布与先前人类成像研究的结果一致，其中BOLD信号在包括中线扣带回和扣带回上皮层、丘脑、丘脑、前颞叶和腹外侧前额叶结构在内的区域增加，而BOLD信号在膝下扣带皮层减少。这项研究代表了该测试的第一次调查-BOLD phMRI对急性氯胺酮激发反应的重测可靠性。尽管与最高可靠性相关的设计矩阵可能代表了更适合重复测量设计的稳健且充分表征的氯胺酮phMRI试验，但所有检测模型均有效描述了氯胺酮响应。该氯胺酮试验适用于作为神经递质功能障碍模型，适合作为药效学成像工具测试和验证调节干预，作为精神疾病中NMDA功能减退的模型，并可用于了解NMDAR拮抗剂的潜在抗抑郁和镇痛作用。(C)2012 Elsevier Inc. All rights reserved.
The pharmacological MRI (phMRI) technique is being increasingly used in both pre-clinical and clinical models to investigate pharmacological effects on task-free brain function. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, induces a strong phMRI response and represents a promising pharmacological model to investigate the role of glutamatergic abnormalities in psychiatric symptomatology. The aim of this study was to assess whether the brain response to ketamine is reliable in order to validate ketamine phMRI as a mechanistic marker of glutamatergic dysfunction and to determine its utility in repeated measures designs to detect the modulatory effect of other drugs. Thus we assessed the test-retest reliability of the brain response to ketamine in healthy volunteers and identified an optimal modelling approach with reliability as our selection criterion.PhMRI data were collected from 10 healthy male participants, at rest, on two separate occasions. Sub-anaesthetic doses of I.V. ketamine infusion (target plasma levels 50 ng/mL and 75 ng/mL) were administered in both sessions. Test-retest reliability of the ketamine phMRI response was assessed voxel-wise and on pre-defined ROIs for a range of temporal design matrices including different combinations of nuisance regressors designed to model shape variance, linear drift and head motion. Effect sizes are also reported.All models showed a significant and widespread response to low-dose ketamine in predicted cerebral networks and as expected, increasing the number of model parameters improved model fit. Reliability of the predefined ROIs differed between the different models assessed. Using reliability as the selection criterion, a model capturing subject motion and linear drift performed the best across two sessions. The anatomical distribution of effects for all models was consistent with results of previous imaging studies in humans with BOLD signal increases in regions including midline cingulate and supracingulate cortex, thalamus, insula, anterior temporal lobe and ventrolateral prefrontal structures, and BOLD signal decreases in the subgenual cingulate cortex.This study represents the first investigation of the test-retest reliability of the BOLD phMRI response to acute ketamine challenge. All models tested were effective at describing the ketamine response although the design matrix associated with the highest reliability may represent a robust and well-characterised ketamine phMRI assay more suitable for repeated-measures designs. This ketamine assay is applicable as a model of neurotransmitter dysfunction suitable as a pharmacodynamic imaging tool to test and validate modulatory interventions, as a model of NMDA hypofunction in psychiatric disorders, and may be adapted to understand potential antidepressant and analgesic effects of NMDAR antagonists. (C) 2012 Elsevier Inc. All rights reserved.