Dartmouth College, Hanover, New Hampshire, United States of America.
University of Colorado Boulder, Colorado, United States of America.
PLoS Biol. 2022 May 2;20(5):e3001620. doi: 10.1371/journal.pbio.3001620. eCollection 2022 May.
Information is coded in the brain at multiple anatomical scales: locally, distributed across regions and networks, and globally. For pain, the scale of representation has not been formally tested, and quantitative comparisons of pain representations across regions and networks are lacking. In this multistudy analysis of 376 participants across 11 studies, we compared multivariate predictive models to investigate the spatial scale and location of evoked heat pain intensity representation. We compared models based on (a) a single most pain-predictive region or resting-state network; (b) pain-associated cortical-subcortical systems developed from prior literature ("multisystem models"); and (c) a model spanning the full brain. We estimated model accuracy using leave-one-study-out cross-validation (CV; 7 studies) and subsequently validated in 4 independent holdout studies. All spatial scales conveyed information about pain intensity, but distributed, multisystem models predicted pain 20% more accurately than any individual region or network and were more generalizable to multimodal pain (thermal, visceral, and mechanical) and specific to pain. Full brain models showed no predictive advantage over multisystem models. These findings show that multiple cortical and subcortical systems are needed to decode pain intensity, especially heat pain, and that representation of pain experience may not be circumscribed by any elementary region or canonical network. Finally, the learner generalization methods we employ provide a blueprint for evaluating the spatial scale of information in other domains.
信息在大脑的多个解剖学尺度上进行编码:局部、分布在区域和网络之间以及全局。对于疼痛,其表示的尺度尚未经过正式测试,并且缺乏对跨区域和网络的疼痛表示进行定量比较。在这项涉及 11 项研究的 376 名参与者的多研究分析中,我们比较了多元预测模型,以研究诱发热痛强度表示的空间尺度和位置。我们比较了基于以下三种模型的结果:(a) 单个最能预测疼痛的区域或静息状态网络;(b) 基于先前文献开发的与疼痛相关的皮质-皮质下系统(“多系统模型”);以及 (c) 涵盖整个大脑的模型。我们使用留一研究外交叉验证(CV;7 项研究)来估计模型准确性,然后在 4 项独立的保留研究中进行验证。所有空间尺度都传达了关于疼痛强度的信息,但分布式、多系统模型比任何单个区域或网络更准确地预测疼痛,并且更适用于多模态疼痛(热、内脏和机械),并且更具体地针对疼痛。全脑模型在预测疼痛方面没有优于多系统模型的优势。这些发现表明,多个皮质和皮质下系统需要解码疼痛强度,尤其是热痛,并且疼痛体验的表示可能不受任何基本区域或规范网络的限制。最后,我们采用的学习器泛化方法为评估其他领域的信息空间尺度提供了蓝图。
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