A multistudy analysis reveals that evoked pain intensity representation is distributed across brain systems

Abstract

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.

Computational and neural mechanisms of statistical pain learning

“…Pain can constrain cognitive functions, such as working memory and attention [22][23][24] . Furthermore, the cortical representation of pain is distributed 25 and a primary brain region for pain has not been found 26 .…”

When knowledge hurts: humans are willing to receive pain for obtaining non-instrumental information

“…the perception of pain and of uncertainty) is also plausible when considering their neural basis. Pain intensity has been found to be represented by multiple cortical and subcortical systems [28, [46][47][48][49][50]. A mesolimbic system comprising the ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAc) has been suggested to be involved in creating the pain experience [30,51], the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) are thought to be involved in regulating the level of pain experienced [52] and the informational value of pain states [53].…”

Direct and Indirect Nociceptive Input from the Trigeminal Dorsal Horn to Pain-Modulating Neurons in the Rostral Ventromedial Medulla

“…The direct pathway could engage RVM circuits to permit the immediate nocifensive response. These pathways could also cooperate to determine information about pain, such as intensity, that is encoded by activation of multiple brain regions (Petre et al, 2022), highlighting the interrelationships within pain-modulating networks and of these modulatory networks with pain-transmission pathways. Our data also revealed that the effects of recruiting the direct and indirect pathway were consistent between the sexes.…”