Imaging Consortium for Drug Development, USA.
Neuroimage. 2010 Feb 1;49(3):2275-86. doi: 10.1016/j.neuroimage.2009.10.053. Epub 2009 Oct 23.
Pain and somatosensory processing involves an interaction of multiple neuronal networks. One result of these complex interactions is the presence of differential responses across brain regions that may be incompletely modeled by a straightforward application of standard general linear model (GLM) approaches based solely on the applied stimulus. We examined temporal blood oxygenation-level dependent (BOLD) signatures elicited by two stimulation paradigms (brush and heat) providing innocuous and noxious stimuli. Data were acquired from 32 healthy male subjects (2 independent cohorts). Regional time courses and model-free analyses of the first cohort revealed distinct temporal features of the BOLD responses elicited during noxious versus innocuous stimulation. Specifically, a biphasic (dual peak) BOLD signal was observed in response to heat but much less so in response to brush stimuli. This signal was characterized by a stimulus-locked response along with a second peak delayed by approximately 12.5 s. A cross-validation error analysis determined a modified design matrix comprising two explanatory variables (EVs) as a parsimonious means to model the biphasic responses within a GLM framework. One EV was directly derived from the stimulation paradigm (EV1), while the second EV (EV2) was EV1 shifted by 12.5 s. The 2EV GLM analysis enabled a more detailed characterization of the elicited BOLD responses, particularly during pain processing. This was confirmed by application of the model to a second, independent cohort[AU1]. Furthermore, the delayed component of the biphasic response was strongly associated with the noxious heat stimuli, suggesting that this may represent a sensitive fMRI link of pain processing.
疼痛和躯体感觉处理涉及多个神经网络的相互作用。这些复杂相互作用的结果之一是，大脑区域的反应存在差异，这些差异可能无法通过仅基于应用刺激的标准广义线性模型 (GLM) 方法来完全建模。我们检查了由两种刺激范式（刷子和热）引起的时间血氧水平依赖 (BOLD) 信号，这些刺激提供了无害和有害的刺激。数据来自 32 名健康男性受试者（2 个独立队列）。第一队列的区域时程和无模型分析显示，有害刺激与无害刺激引起的 BOLD 反应具有明显的时间特征。具体来说，在热刺激下观察到双峰（双峰）BOLD 信号，但在刷子刺激下则较少。该信号的特征是具有刺激锁定响应以及延迟约 12.5 秒的第二个峰值。交叉验证错误分析确定了一个包含两个解释变量 (EV) 的简化设计矩阵，作为在 GLM 框架内对双相反应进行建模的一种简约方法。一个 EV 直接来自刺激范式（EV1），而第二个 EV（EV2）是 EV1 延迟 12.5 秒。2EV GLM 分析能够更详细地描述诱发的 BOLD 反应，特别是在疼痛处理期间。通过将模型应用于第二个独立队列[AU1]来确认这一点。此外，双相反应的延迟成分与有害热刺激强烈相关，这表明这可能代表疼痛处理的敏感 fMRI 联系。
