On the judicious use of metrics for cerebral autoregulation.
On the judicious use of metrics for cerebral autoregulation.
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关于明智地使用大脑自动调节指标。
DOI：
10.1007/s00421-013-2718-4
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发表时间：
2013
影响因子：
3
通讯作者：
Taylor,JAndrew
中科院分区：
文献类型：
--
作者：
Tan,CanOzan;Taylor,JAndrew
我们怀着极大的兴趣阅读了曾和安斯利(2013)的综述，并赞赏他们强调当前范式的局限性，以探索大脑自动调节。显然，许多现有的方法…基于可能会引起误导性解读的简单化假设。的确，尽管轻松捕捉大量相互作用变量上的零星数据的能力导致了许多独特的见解，但这些同样的见解往往会受到我们应用知情分析的能力的限制。事实上，如果违反了支撑分析方法的假设，相同的数据可能会导致不同的结论。作者强调了不同指标之间的不一致性，并强调只有“少数指标”显示出彼此之间的统计关联。尽管缺乏一致性可能表明假设有缺陷，但也可能表明一些指标不适合研究正在调查的现象。指标之间缺乏趋同可能证明“缺乏共同的功能基础”，因此研究人员可能会问“应该使用哪个指标或指标组合”。然而，拟议指标的结构效度可能提供了答案。自动调节的特点是对动脉压变化的缓冲能力，表现为血压和脑血流波动之间缺乏线性相关性(即，低交叉谱相关性或低相关性)。事实上，大多数衡量标准都是基于这样的表现：当自动调节完好无损时，压力-流量波动表现出低一致性(或相关性)，而当自动调节受损时，则显示出密切的线性关系。但是，问题是，如果压力-流量关系表现出低线性关系(例如，相干性)，它不能通过线性分析可靠地量化。自动监管本身的性质限制了线性估计的效用。因此，虽然所有的线性指标都可以显示大脑自动调节的“存在”或“不存在”，但当自动调节完好无损时，没有一个能可靠地量化压力-流量关系。因此，寻找能够对…进行多变量量化的分析创新线阵…大脑循环的特性也会受到完全相同的限制。例如，用三元Windkesel模型来描述自动调节的近似只是一个多元线性回归，因此很容易受到这一限制；尽管它可能在总体水平上提供很好的拟合，但它对个体内部关系的效用仍不清楚。正如作者所说，“生理推断只有在我们的方法论方法中固有的假设下才是有效的。”我们最近的两项研究特别代表了这个问题。我们最近的两项研究表明，在低于0.06赫兹(即，慢于15 S)的频率下，阻断α-肾上腺素能和毒碱能受体可以增加压力和血流之间的一致性和增益关系。在这两项研究中，由于下半身负压的使用，压力和流量是高度一致的，因此，作者认为在多大程度上仍不清楚。
We read the review by Tzeng and Ainslie (2013) with great interest and appreciate their emphasis on limitations in current paradigms to explore cerebral autoregulation. Clearly,‘‘many extant methods… are based on simplistic assumptions that can give rise to misleading interpretations.’’Indeed, though the ability to easily capture beat-bybeat data on a myriad of interacting variables has led to numerous unique insights, these same insights can often be limited by our ability to apply well-informed analyses. In fact, the same data may lead to different conclusions if the assumptions that underlie the analytic methods are violated. The authors highlight the inconsistency between different metrics, and underscore that only ‘‘few [metrics] exhibit statistical associations with each other.’’Though lack of agreement may indicate flawed assumptions, it might also indicate that some metrics are unfit to study the phenomenon under investigation. The lack of convergence between metrics may evidence ‘‘a lack of a common functional basis’’, and hence the researcher might ask ‘‘which metric, or combination of metrics, one should use.’’However, the construct validity of the proposed metrics may provide the answer. The hallmark of autoregulation is the ability to buffer against arterial pressure changes and is manifested as a lack of linear dependence between pressure and cerebral blood flow fluctuations (ie, low cross-spectral coherence or poor correlation). Most metrics are, in fact predicated on this manifestation: pressure-flow fluctuations exhibit low coherence (or correlation) when autoregulation is intact, and a close linear relation indicates when autoregulation is impaired. But, the issue is that if the pressure-flow relation displays a low linear relation (eg, coherence), it cannot be quantified reliably via linear analyses. Autoregulation by its very nature limits the utility of linear estimates. Therefore, while all linear metrics may indicate the ‘presence’or ‘absence’of cerebral autoregulation, none can reliably quantitate the pressure-flow relation when autoregulation is intact. Therefore, the search for ‘‘analytical innovations that enable multivariate quantification of… linear… properties of the cerebral circulation’’will suffer from the exact same limitations. For example, approximation of a three-element Windkessel model to characterize autoregulation is simply a multiple linear regression, and thus, is vulnerable to this very limitation; although it may provide excellent fits at the population level, its utility for intra-individual relationships remains unclear. As the authors state,‘‘physiological inferences are only as valid as the assumptions inherent in our methodological approaches.’’Our two recent studies, wherein we showed that alpha-adrenergic and muscarinic receptor blockade increases the coherence and gain relation between pressure and flow at frequencies less than 0.06 Hz (ie, slower than 15 s) were cited as particularly representative of this issue. Pressure and flow were highly coherent in both studies due to the use of oscillatory lower body negative pressure, thus, the authors suggest that it remains unclear to what extent