Abstract

Abstract Introduction Insomnia is associated with increased arousal. Brain regions involved in chronic insomnia are diffuse and the potential interactive role of physiological arousal in the association between insomnia symptoms and neural regions is unknown. This study examined whether physiological arousal (heart rate variability, HRV) moderated the association between sleep and gray matter (GM) volume of frontal [dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC)] and temporal [right/left (R/L) hippocampus] regions in adults with comorbid chronic widespread pain and insomnia (CWPI). Methods Forty-seven adults with CWPI (Mage=46.00, SD=13.88, 89% women) completed two weeks of diaries measuring sleep onset latency (SOL), wake time after sleep onset (WASO) and total sleep time (TST). Resting HRV was assessed via Holter monitoring (5 minutes). Root mean squared standard deviation of successive normal-to-normal heartbeats (RMSDNN) was computed. T1-weighted magnetic resonance images were obtained, segmented and co-registered to MNI space. GM volumes (DLPFC, ACC, R/L hippocampus) were estimated (FSL). Multiple regressions examined whether SOL, WASO or TST were independently associated with or interacted with RMSDNN in their associations with GM volumes, controlling for age. Results SOL interacted with RMSDNN in its association with ACC (B=-4.60, SE=2.06, p=.03, R-squared=.06). Longer SOL was associated with lower ACC volume at highest RMSDNN (lowest arousal; B=-103.54, SE=42.82, p=.02), not average/lowest RMSDNN (highest arousal, ps>.05). TST interacted with RMSDNN in its association with R hippocampus (B=-.22, SE=.10, p=.04, R-squared=.07). Shorter TST was associated with lower R hippocampal volume at lowest RMSDNN (highest arousal; B=7.39, SE=2.29, p=.002) and average RMSDNN (B=4.18, SE=1.50, p=.008), not highest RMSDNN (lowest arousal; p=.64). There was a trending association between WASO and R hippocampus volume (B=-13.67, SE=7.28, p=.07). Conclusion In patients with CWPI and highest physiological arousal, achieving longer TST may be important in terms of associations with right hippocampus volume. Improving (reducing) SOL may only impact ACC volume in those with lower physiological arousal. Trends of association between longer WASO and reduced right hippocampus volume warrant follow-up in larger samples. Findings highlight the interactive role of physiological arousal (HRV) in the neural mechanisms associated with sleep in CWPI. Support (if any) National Institute of Nursing Research (NR017168; Clinical trial: NCT02001077; PI: McCrae).

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