Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam
Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam
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DOI：
10.1002/hbm.24889
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发表时间：
2019-12-06
影响因子：
4.8
通讯作者：
Muthukunnaraswanny, Suresh D.
中科院分区：
文献类型：
--
作者：
Forsyth, Anna;McMillan, Rebecca;Muthukunnaraswanny, Suresh D.
大脑功能连接的药理学调节可能是多种神经和精神疾病治疗效果的基础。功能磁共振成像（fMRI）提供了一种评估这种调节的无创方法，然而，血氧水平依赖性信号的间接性质限制了神经与生理贡献的区分。在这里，我们采用两种方法来评估 fMRI 功能连接在开发药物生物标志物中的有效性，在氯胺酮和咪达唑仑的安慰剂对照、三向交叉设计中使用同步脑电图 (EEG)/fMRI。首先，我们比较了七种不同的预处理管道，以确定它们对常见静息状态网络连接的影响。与采用生理噪声模型或来自脑脊液或白质的平均信号的管道相比，独立成分分析 (ICA) 去噪导致氯胺酮后连接性降低更明显，而咪达唑仑后连接性增加更弱。这表明管道决策应反映药物独特的噪声结构，如果这是未知的，那么在选择广泛的 ICA 去噪管道时接受可能的信号损失可能会增加对剩余结果的信心。然后，我们将功能磁共振成像的时间相关结构与脑电图的两个连接指标得出的时间相关结构进行比较，后者提供了神经活动的直接测量。虽然基于功率包络的电生理学估计比基于相位一致性的电生理学估计更接近 BOLD 信号连接，但未发现电生理学和血流动力学相关结构的变化之间存在显着关系，这意味着在对药理调节的功能连接进行跨模式比较时应谨慎行事。
The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood-oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo-controlled, three-way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting-state networks. Independent components analysis (ICA)-denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity.