Characteristics of locus coeruleus functional connectivity network in patients with comorbid migraine and insomnia

Sep 28, 2024The journal of headache and pain

Brainstem arousal system connections in people with both migraine and insomnia

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Abstract

Patients with comorbid migraine and insomnia exhibited altered in the compared to healthy controls.

No significant differences in demographic characteristics or behavioral performance were found between patients with migraine and insomnia and those with migraine alone.
Altered connectivity was noted in several brain regions, including the dorsomedial and dorsolateral prefrontal cortices, thalamus, and parahippocampal gyrus.
Lower connectivity between the locus coeruleus and dorsolateral prefrontal cortex was associated with greater insomnia severity.
Higher connectivity between the locus coeruleus and dorsomedial prefrontal cortex was linked to longer migraine attack duration in patients with comorbid conditions.
These findings suggest that disruptions in the locus coeruleus connectivity may play a role in the relationship between migraine and insomnia.

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BACKGROUND: Migraine and insomnia are prevalent conditions that often co-occur, each exacerbating the other and substantially impacting the quality of life. The (LC), a brainstem region responsible for norepinephrine synthesis, participates in pain modulation, sleep/wake cycles, and emotional regulation, rendering it a potential nexus in the comorbidity of migraine and insomnia. Disruptions in the LC-noradrenergic system have been hypothesized to contribute to the comorbidities of migraine and insomnia, although neuroimaging evidence in humans remains scarce. In this study, we aimed to investigate the intrinsic (FC) network of the LC in patients with comorbid migraine and subjective chronic insomnia and patients with migraine with no insomnia (MnI) using resting-state functional magnetic resonance imaging (rs-fMRI) and seed-based FC analyses.

METHODS: In this cross-sectional study, 30 patients with comorbid migraine and chronic insomnia (MI), 30 patients with MnI, and 30 healthy controls (HCs) were enrolled. Participants underwent neuropsychological testing and rs-fMRI. The LC-FC network was constructed using seed-based voxel-wise FC analysis. To identify group differences in LC-FC networks, voxel-wise covariance analysis was conducted with sex and age as covariates. Subsequently, a partial correlation analysis was conducted to probe the clinical relevance of aberrant LC-FC in patients with MI and MnI.

RESULTS: Except for the insomnia score, no other significant difference was detected in demographic characteristics and behavioral performance between the MI and MnI groups. Compared with HCs, patients with MI exhibited altered LC-FC in several brain regions, including the dorsomedial prefrontal cortex (DMPFC), anterior cerebellum, dorsolateral prefrontal cortex (DLPFC), thalamus, and parahippocampal gyrus (PHG). Lower FC between the LC and DLPFC was associated with greater insomnia severity, whereas higher FC between the LC and DMPFC was linked to longer migraine attack duration in the MI group.

CONCLUSION: Our findings reveal the presence of aberrant LC-FC networks in patients with MI, providing neuroimaging evidence of the interplay between these conditions. The identified LC-FC alterations may serve as potential targets for therapeutic interventions and highlight the importance of considering the LC-noradrenergic system in the management of MI.

Key numbers

Participants with comorbid migraine and insomnia

Number of patients in the MI group

Participants with migraine only

Number of patients in the MnI group

Healthy controls

Number of healthy participants in the study

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Characteristics of locus coeruleus functional connectivity network in patients with comorbid migraine and insomnia

Abstract

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