The parietal operculum preferentially encodes heat pain and not salience

Abstract

Substantial controversy exists as to which part of brain activity is genuinely attributable to pain-related percepts and which activity is due to general aspects of sensory stimulation, such as its salience, or the accompanying arousal. The challenge posed by this question rests largely in the fact that pain per se exhibits highly intense but unspecific characteristics. These therefore should be matched by potential control conditions. Here, we used a unique combination of functional magnetic resonance imaging (fMRI) and behavioral and autonomic measures to address this longstanding debate in pain research. Subjects rated perceived intensity in a sequence alternating between heat and sound stimuli. Neuronal activity was monitored using fMRI. Either modality was presented in 6 different intensities, 3 of which lay above the pain threshold (for heat) or the unpleasantness threshold (for sound). We performed our analysis on 26 volunteers in which psychophysiological responses (as per skin conductance responses [SCRs]) did not differ between the 2 stimulus modalities. Having thus ascertained a comparable amount of stimulation-related but unspecific activation, we analyzed stimulus-response functions (SRFs) after painful stimulation and contrasted them with those of the matched acoustic control condition. Furthermore, analysis of fMRI data was performed on the brain surface to circumvent blurring issues stemming from the close proximity of several regions of interest located in heavily folded cortical areas. We focused our analyses on insular and peri-insular regions that are strongly involved in processing of painful stimuli. We employed an axiomatic approach to determine areas showing higher activation in painful compared to nonpainful heat and, at the same time, showing a steeper SRF for painful heat compared to unpleasant sound. Intriguingly, an area in the posterior parietal operculum emerged, whose response showed a pain preference after satisfying all axiomatic constraints. This result has important implications for the interpretation of functional imaging findings in pain research, because it clearly demonstrates that there are areas where activity following painful stimulation is not due to general attributes or results of sensory stimulation, such as salience or arousal. Conversely, several areas did not conform to the formulated axioms to rule out general factors as explanations.

Increased Salience Network Connectivity Following Manual Therapy is Associated with Reduced Pain in Chronic Low Back Pain Patients

“…Additionally, as SLN has been linked with autonomic processing 20 . SLN connectivity to the thalamus was increased following MANIP (see Figure 3) and the thalamic cluster spanned important nuclei for pain modulation -ventral lateral posterior (VLp), ventral posterior lateral (VPL), and medial dorsal (MD), as evident by overlay with the canonical Morel thalamus atlas in MNI space.…”

A review on the ongoing quest for a pain signature in the human brain

“…In their study, a brain area would be considered to be preferentially responding to pain if it meets the following four criteria: (1) the effect of painful stimulation should be larger than that of nonpainful heat; (2) the effect of painful stimulation should be larger than that of saliencematched unpleasant sound; (3) the relationship of ratings and fMRI response should be stronger for painful heat than for nonpainful heat; and (4) the positive relationship of pain ratings and fMRI responses should be stronger for painful heat than for salience-matched unpleasant sound. They found that an area in the posterior parietal operculum satisfied all four criteria and thus showed a preference for pain processing [87]. This study made an important progress in identifying brain regions having a preferential role in pain processing by matching saliency between painful and non-painful stimuli.…”

“…In one study, Horing et al used skin conductance responses (SCRs) as a measure of stimulus saliency, and compared the fMRI responses to painful heat with saliency-unmatched non-painful heat and with saliency-matched unpleasant sound [87]. In their study, a brain area would be considered to be preferentially responding to pain if it meets the following four criteria: (1) the effect of painful stimulation should be larger than that of nonpainful heat; (2) the effect of painful stimulation should be larger than that of saliencematched unpleasant sound; (3) the relationship of ratings and fMRI response should be stronger for painful heat than for nonpainful heat; and (4) the positive relationship of pain ratings and fMRI responses should be stronger for painful heat than for salience-matched unpleasant sound.…”

Reactivation of single-episode pain patterns in the hippocampus and decision making

“…In contrast, the gradual learning of stimulus-value associations over multiple experiences is known to involve systems including the dopaminergic midbrain, striatum, insula, and amygdala (Schultz et al, 1997;LeDoux, 2000;Seymour and al., 2004;Schiller et al, 2008). In the case of learning from aversive stimuli such as heat, a network of regions including the insula and secondary somatosensory cortex respond to pain Apkarian et al, 2005;Tracey and Mantyh, 2007;Roy et al, 2014;Horing et al, 2019), suggesting a potential substrate for memory for the value of pain.…”