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

Abstract

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.

Keywords: aging; distraction; executive functions; fMRI; gray matter volume; pain modulation; prefrontal cortex.

FIGURE 1

Experimental design and trial timeline. Each trial consisted of a cue word signaling the upcoming task, followed by the task (20 s) with thermal stimulation starting 4 s after task onset and lasting for 16 s. After each task, participants were asked to rate the intensity and unpleasantness of the thermal stimulation. The low and high load task consisted of a 0-back and 2-back working memory task, respectively. Each letter was presented for 500 ms, preceded by a fixation cross (250 ms) and followed by a blank inter-character interval. The duration of the inter-character interval was individually adjusted in a calibration phase prior to, and throughout, the experiment to account for differences in task difficulty by adjusting the task speed.

FIGURE 2

Average ratings for the four different conditions. Young (YA) and older adults (OA) rated all stimuli on (A) a 200-point intensity scale and (B) a 200-point unpleasantness scale. A rating of 100 on the intensity scale corresponds to the pain threshold (“just pain”) and a rating of 100 on the unpleasantness scale corresponds to being “neutral”. Painful stimuli were rated as significantly less intense and unpleasant when these were presented during the high load task as compared to the low load task. ***p < 0.001. Error bars represent the standard error of the mean (SEM).

FIGURE 3

Pain-related neural activation. Painful compared to warm stimuli (pain > warm) collapsed across task conditions and groups [visualized at a threshold of p(unc) = 0.005, k ≥ 10; see also Supplementary Table 5].

FIGURE 4

Neural distraction effect and mechanism. (A) Neural distraction effect (i.e., regions showing less activation during the high-load than during the low-load task) across groups (see also Table 2); (B) neural distraction effect for YA > OA; (C) neural distraction mechanism (i.e., regions showing more activation during the high-load than during the low-load task) across groups; (D) neural distraction mechanism for OA > YA. All contrasts are visualized at p(unc) = 0.005, k ≥ 10. Note that the color of the clusters in (B,D) is not indicative of the t-value.

FIGURE 5

Correlations between executive functions and the neural distraction mechanism in young adults. (A) Regions showing a negative correlation between the TMT difference score and the neural distraction mechanism [(pain > warm) _{high load} > (pain > warm) _{low load}] in young adults [visualized at p(unc) = 0.001, k ≥ 20; see also Table 3]. (B) Parameter estimates extracted from the cluster maximum in the mid cingulate gryus (position of cross hairs in A) for the neural distraction mechanism contrast. A smaller TMT difference score indicates better executive functions.

FIGURE 6

Correlations between executive functions and the neural distraction effect and mechanism in older adults. (A) A smaller flanker effect (i.e., better interference control abilities) was associated with a greater neural distraction effect [(pain > warm) _{low load} > (pain > warm) _{high load}] in the left insula and (B) the right thalamus (see also Table 4); (C) smaller difference scores in the TMT (i.e., better executive functions) were associated with a greater neural distraction mechanism [(pain > warm) _{high load} > (pain > warm) _{low load}] in the left superior frontal gyrus (see also Table 3); (D) digit span (i.e., working memory ability) correlated positively with the neural distraction mechanism in the left inferior frontal gyrus and right middle frontal gyrus. [All activation maps are visualized at p(unc) = 0.001, k ≥ 20].

FIGURE 7

Results from the gray matter volume analyses. (A) Young adults > older adults contrast for the GM images (visualized at a FWE-corrected p = 0.05, k ≥ 20; see also Supplementary Table 11). (B) Regions showing a positive correlation between the behavioral distraction effect size (on the unpleasantness scale) and GM volume in older adults [visualized at p(unc) = 0.001, k ≥ 20; see also Table 5].