Chronic Musculoskeletal Pain Moderates the Association between Sleep Quality and Dorsostriatal-Sensorimotor Resting State Functional Connectivity in Community-Dwelling Older Adults

Abstract

Aging is associated with poor sleep quality and greater chronic pain prevalence, with age-related changes in brain function as potential underlying mechanisms. Objective. The following cross-sectional study aimed to determine whether self-reported chronic musculoskeletal pain in community-dwelling older adults moderates the association between sleep quality and resting state functional brain connectivity (rsFC). Methods. Community-dwelling older individuals (mean age = 73.29 years) part of the NEPAL study who completed the Pittsburg Sleep Quality Index (PSQI) and a rsFC scan were included (n = 48) in the present investigation. To that end, we tested the effect of chronic pain-by-PSQI interaction on rsFC among atlas-based brain regions-of-interest, controlling for age and sex. Results and Discussion. A significant network connecting the bilateral putamen and left caudate with bilateral precentral gyrus, postcentral gyrus, and juxtapositional lobule cortex, survived global multiple comparisons (FDR; q < 0.05) and threshold-free network-based-statistics. Greater PSQI scores were significantly associated with greater dorsostriatal-sensorimotor rsFC in the no-pain group, suggesting that a state of somatomotor hyperarousal may be associated with poorer sleep quality in this group. However, in the pain group, greater PSQI scores were associated with less dorsostriatal-sensorimotor rsFC, possibly due to a shift of striatal functions toward regulation sensorimotor aspects of the pain experience, and/or aberrant cortico-striatal loops in the presence of chronic pain. This preliminary investigation advances knowledge about the neurobiology underlying the associations between chronic pain and sleep in community-dwelling older adults that may contribute to the development of effective therapies to decrease disability in geriatric populations.

Figure 1

Significant networks in the chronic pain-connectivity moderation analysis of the R2R rsFC when testing the PAIN_GROUP × PSQI interaction. Connections are represented by lines. The PAIN_GROUP × PSQI interaction was negative in all connections. The network formed by all eleven connections survived the TFNBS for the S-SP ROI configuration. The network formed by the blue solid and red connections survived the TFNBS for the SP-SP ROI configuration. The network formed by the red connections survived the TFNBS for the SP-A ROI configuration. The network formed by the solid red lines survived the TFNBS (marginally: left-tailed) for the S-A ROI configuration. The individual connection represented by the thicker red line was significant for all ROI configurations (p < 0.05, FDR corrected). The nodes of these networks are ROIs of the Harvard-Oxford AAL atlas. To clarify their anatomical extent, cortical ROIs are shown projected onto a semi-inflated white matter surface and subcortical ROIs are represented in the medial view of this surface. Pu = putamen. Cau = caudate. SMA = juxtapositional lobule cortex. PreCG = precentral gyrus. PostCG = postcentral gyrus.

Figure 2

Scatter plot of the rsFC values of the eleven connections that survived the TFNBS in the R2R connectivity analyses (when testing the PAIN_GROUP × PSQI interaction with the S-S ROI configuration) versus PSQI. The values of functional connectivity were adjusted by removing the demeaned residuals explained by age and sex. Thus, for each group (i.e., no-pain and chronic pain) the adjusted fitted rsFC lie in a straight line that represents the slope of the rsFC-PSQI dependency within the group. The negative PAIN_GROUP × PSQI interaction is explained by a change in slope from positive to negative when switching from the no-pain to the chronic pain group. For each connection, the Cohen's f² local effect size index is shown, that is, the proportion of variance explained by the PAIN_GROUP × PSQI interaction divided by the residual variance. All effects were medium (0.15 ≤ f² < 0.35) or large (f² ≥ 0.35) [65]. Pu = putamen. Cau = caudate. SMA = juxtapositional lobule cortex. PreCG = precentral gyrus. PostCG = postcentral gyrus. R = right. L = left.