Age-related differences in functional connectivity associated with pain modulation.

Growing evidence suggests that aging is associated with impaired endogenous pain modulation, and that this likely underlies the increased transition from acute to chronic pain in older individuals. Resting-state functional connectivity (rsFC) offers a valuable tool to examine the neural mechanisms behind these age-related changes in pain modulation. RsFC studies generally observe decreased within-network connectivity due to aging, but its relevance for pain modulation remains unknown. We compared rsFC within a set of brain regions involved in pain modulation between young and older adults and explored the relationship with the efficacy of distraction from pain. This revealed several age-related increases and decreases in connectivity strength. Importantly, we found a significant association between lower pain relief and decreased strength of three connections in older adults, namely between the periaqueductal gray and right insula, between the anterior cingulate cortex (ACC) and right insula, and between the ACC and left amygdala. These findings suggest that the functional integrity of the pain control system is critical for effective pain modulation, and that its function is compromised by aging.

Baseline heart rate variability predicts placebo hypoalgesia in men, but not women.

Introduction: Placebo hypoalgesic effects vary greatly across individuals, making them challenging to control for in clinical trials and difficult to use in treatment. We investigated the potential of resting vagally-mediated heart rate variability (vmHRV) to help predict the magnitude of placebo responsiveness. Methods: In two independent studies (total N = 77), we administered a placebo paradigm after measuring baseline HRV. In Study I, we delivered heat pain to the forearm, on skin patches treated with "real" and "control" cream (identical inactive creams). In Study II, electrical pulses to the forearm were modulated by sham transcutaneous electrical nerve stimulation. We combined data from both studies to evaluate the relationship between vagally-mediated HRV (vmHRV) parameters and the placebo response size, while also assessing sex differences in this relationship. Results and Discussion: This revealed a positive association between vmHRV and the degree of pain relief, and this effect was driven by men. These results not only reveal new insights into the (sex-specific) mechanisms of placebo hypoalgesia, but also suggest that measuring vmHRV may be helpful in predicting placebo responsiveness. Given that placebo hypoalgesic effects contribute substantially to treatment outcomes, such a non-invasive and easily obtained predictor would be valuable in the context of personalized medicine.

Better Executive Functions Are Associated With More Efficient Cognitive Pain Modulation in Older Adults: An fMRI Study.

Growing evidence suggests that aging is associated with less efficient endogenous pain modulation as demonstrated by reduced conditioned pain modulation, and that these changes may be mediated by differences in frontal functioning. Yet, little is known about potential age-related changes in cognitive pain modulation, such as distraction from pain. In a first session, 30 healthy young (19-35 years) and 30 healthy older (59-82 years) adults completed a battery of neuropsychological tests. In a second session, we acquired functional brain images while participants completed a working memory task with two levels of cognitive load (high vs. low) and concurrently received individually adjusted heat stimuli (warm vs. painful). In both age groups, completing the high load task was associated with a significant reduction in the perceived intensity and unpleasantness of painful stimuli and a reduction in activation of brain regions involved in pain processing. Group comparisons revealed that young adults showed a stronger de-activation of brain regions involved in pain processing during the high load vs. the low load task, such as the right insula, right mid cingulate cortex and left supramarginal gyrus, compared to older adults. Older adults, on the other hand, showed an increased activation in the anterior cingulate cortex during the high load vs. low load task, when compared to young adults. Covariate analyses indicated that executive functions significantly predicted neural pain modulation in older adults: Better executive functions were associated with a more pronounced de-activation of the insula, thalamus and primary somatosensory cortex and increased activation of prefrontal regions during the high vs. low load task. These findings suggest that cognitive pain modulation is altered in older age and that the preservation of executive functions may have beneficial effects on the efficacy of distraction from pain.

When Less Is More: Investigating Factors Influencing the Distraction Effect of Virtual Reality From Pain.

Virtual reality (VR) is a powerful method of redirecting attention away from pain. Yet, little is known about which factors modulate the size of this distraction effect. The aim of this study was to investigate the role of cognitive load and inter-individual differences in the cognitive and affective domain on heat pain thresholds during a VR game. Ninety healthy participants (mean age ± SD: 23.46 ± 3.28; 50% identified as male and 50% as female) played a low and high load version of a VR game while heat pain thresholds and heart rate were recorded. The effects of cognitive load were assessed by computing the difference in pain thresholds between the high and low load condition for each participant. In addition, we computed the difference in heart rate variability (HRV) measures between both conditions to explore whether these would be correlated with the difference in heat pain thresholds. Prior to the VR session, participants completed questionnaires about their emotional distress, pain-related cognitions, and different executive functioning tasks. Contrary to our expectations, not all participants benefitted from a higher load in terms of distraction from pain. Logistic regression analysis revealed that participants who reported more emotional distress were more likely to exhibit higher pain thresholds in the low relative to the high load condition. Accordingly, these participants tended to show marginally higher HRV in the low compared to the high load condition. Our study demonstrates that the potential benefits of an increased cognitive load in VR on pain sensitivity depends on individual differences in affective state.

Memory suppression and its deficiency in psychological disorders: A focused meta-analysis.

It is still debated whether suppressing the retrieval of unwanted memories causes forgetting and whether this constitutes a beneficial mechanism. To shed light on these 2 questions, we scrutinize the evidence for such suppression-induced forgetting (SIF) and examine whether it is deficient in psychological disorders characterized by intrusive thoughts. Specifically, we performed a focused meta-analysis of studies that have used the think/no-think procedure to test SIF in individuals either affected by psychological disorders or exhibiting high scores on related traits. Overall, across 96 effects from 25 studies, we found that avoiding retrieval leads to significant forgetting in healthy individuals, with a small to moderate effect size (0.28, 95% CI [0.14, 0.43]). Importantly, this effect was indeed larger than for more anxious (-0.21, 95% CI [-0.41, -0.02]) or depressed individuals (0.05, 95% CI [-0.19, 0.29])-though estimates for the healthy may be inflated by publication bias. In contrast, individuals with a stronger repressive coping style showed greater SIF (0.42, 95% CI [0.32, 0.52]). Furthermore, moderator analyses revealed that SIF varied with the exact suppression mechanism that participants were instructed to engage. For healthy individuals, the effect sizes were considerably larger when instructions induced specific mechanisms of direct retrieval suppression or thought substitution than when they were unspecific. These results suggest that intact suppression-induced forgetting is a hallmark of psychological well-being, and that inducing more specific suppression mechanisms fosters voluntary forgetting. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Distraction from pain: The role of selective attention and pain catastrophizing.

BACKGROUND: Previous research has demonstrated the efficacy of cognitive engagement in reducing concurrent pain. However, little is known about the role of individual differences in inhibitory control abilities and negative pain-related cognitions in modulating the magnitude of this type of distraction from pain. METHODS: In a pain distraction paradigm, 41 participants completed a working memory task with both a demanding high load condition (2-back) and an easy low load condition (0-back), while receiving warm or painful thermal stimuli to their left forearm. To control for individual differences in sensitivity to pain and perceived task difficulty, nociceptive stimulus intensity and task speed were individually calibrated. Additionally, participants completed a set of cognitive inhibition tasks (flanker, go/nogo, Stroop) and questionnaires about negative pain-related cognitions (fear of pain, pain catastrophizing) prior to the distraction paradigm. RESULTS: As expected, engaging in the high load condition significantly reduced perceived intensity and unpleasantness of nociceptive stimuli, compared to the low load condition. The size of the distraction effect correlated significantly with better cognitive inhibition and selective attention abilities, as measured by the flanker task. A moderation analysis revealed a significant interaction between pain catastrophizing and performance in the flanker task in predicting the distraction effect size: Participants who performed well on the flanker task showed more pain reduction, but only when they were average to high pain catastrophizers. CONCLUSIONS: Selective attention abilities and pain catastrophizing seem to be important factors in explaining individual differences in the size of the analgesic response to a distractive task. SIGNIFICANCE: Understanding which factors influence the effectiveness of cognitive engagement in distracting from pain could help to optimize its therapeutic application in patient care. This study shows that a complex interplay of cognitive inhibition abilities, specifically selective attention, and negative pain-related cognitions, such as pain catastrophizing, modulate the magnitude of the distraction effect.

In context: emotional intent and temporal immediacy of contextual descriptions modulate affective ERP components to facial expressions.

In this study, we explored how contextual information about threat dynamics affected the electrophysiological correlates of face perception. Forty-six healthy native Swedish speakers read verbal descriptions signaling an immediate vs delayed intent to escalate or deescalate an interpersonal conflict. Each verbal description was followed by a face with an angry or neutral expression, for which participants rated valence and arousal. Affective ratings confirmed that the emotional intent expressed in the descriptions modulated emotional reactivity to the facial stimuli in the expected direction. The electrophysiological data showed that compared to neutral faces, angry faces resulted in enhanced early and late event-related potentials (VPP, P300 and LPP). Additionally, emotional intent and temporal immediacy modulated the VPP and P300 similarly across angry and neutral faces, suggesting that they influence early face perception independently of facial affect. By contrast, the LPP amplitude to faces revealed an interaction between facial expression and emotional intent. Deescalating descriptions eliminated the LPP differences between angry and neutral faces. Together, our results suggest that information about a person's intentions modulates the processing of facial expressions.