Distinct brain activity in females with or without chronic low back pain and comorbid insomnia

This case-control study aimed to characterize spontaneous resting brain activity among four groups of age-matched females, including those with or without CLBP, insomnia, and concomitant conditions.

One hundred female participants (mean age: 34.3±11.4 years) were enrolled and categorized into four subgroups: (1) CLBP and insomnia (CLBP+I, n = 25); (2) CLBP alone (CLBP+, n = 25); (3) insomnia alone (Insomnia+, n = 25); and (4) controls without CLBP nor insomnia (Controls, n = 25). Insomnia was determined by the Brief Insomnia Questionnaire according to the DSM-5 criteria. All participants completed clinical questionnaires and five-minute resting-state electroencephalography (EEG) recordings with eyes closed. DISCOVER-EEG, a comprehensive EEG pipeline designed for resting-state analysis, was used to automate preprocessing and extract physiologically meaningful brain function features, including spectral analysis, functional connectivity, and graph theory. Group differences were examined using one-way analysis of variance (ANOVA) with false discovery rate (FDR) correction. To account for multiple correlation analyses, spearman correlation analyses were performed to examine the associations between various clinical variables and EEG measures that showed significant between-group differences. 

The analysis of global relative power spectra revealed higher delta (p = 0.012) and theta (p = 0.027) power and lower alpha (p = 0.017) power in CLBP+I compared to CLBP+, Insomnia+, or Controls. Additionally, CLBP+I exhibited increased amplitude-based connectivity at the theta (p 0.006) and beta (p 0.044) bands and decreased phase-based connectivity at the alpha (p 0.049) band compared to the other three groups. Graph-theory analyses found increased amplitude-based local cluster coefficient (p = 0.001) and small-world networks (p = 0.007) at the beta band in CLBP+I compared to Controls. We also identified significant associations between brain abnormalities and pain-related measures or sleep disturbance.

This is the first empirical study to characterize oscillatory brain activity and functional connectivity among four well-characterized groups of females with or without CLBP or insomnia. Our findings showed increased delta and theta but decreased alpha bands, consistent with the thalamocortical dysrhythmia model in chronic pain and the hyperarousal model in insomnia. Furthermore, the comorbid states showed increased beta band information processing, potentially reflecting a compensatory adaptation to the information overload from both pain and insomnia. 

Our neurophysiological findings offer promise in facilitating patient phenotyping, better understanding of the neural underpinning of the comorbid state, and potentially guiding personalized treatment protocols based on neurophysiological biomarkers in individuals with this condition. These distinct neurophysiological signatures also represent a crucial initial step toward developing biomarkers for diagnosing, monitoring, and treating individuals with chronic pain and comorbid insomnia.