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ORIGINAL RESEARCH article

Front. Psychiatry

Sec. Sleep Disorders

Multimodal Neuroimaging of Locus Coeruleus-Default Mode Network Connectivity for Predicting Dexmedetomidine Response in Chronic Insomnia Disorder

  • 1. The Second People's Hospital of Changzhou, Changzhou, China

  • 2. Jinshan Hospital of Fudan University, Shanghai, China

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Abstract

Objectives: To explore whether pre-treatment functional connectivity between the locus coeruleus (LC) and default mode network (DMN), nodal graph-theoretical features, and gray matter volume can identify chronic insomnia patients who respond poorly to dexmedetomidine patient-controlled sleep therapy (PCSL). Methods: Chronic insomnia patients underwent PCSL with sub-anesthetic dexmedetomidine and were classified as responders or non-responders based on changes in the Pittsburgh Sleep Quality Index. All patients and matched matched good sleeper received pre-treatment resting-state functional Magnetic Resonance Imaging (MRI) and structural MRI. Functional connectivity, graph metrics, and gray matter volumes of LC and DMN regions were extracted. Predictors were selected using univariate analysis and Least Absolute Shrinkage and Selection Operator regression (LASSO), then used in a multivariate logistic model. Model performance was assessed via Receiver Operating Characteristic (ROC), calibration, decision curve analysis, and bootstrap validation. Results: No gray matter volume differences were found between responders and non-responders except increased right hippocampal volume in non-responders versus controls. Non-responders showed widespread increased LC-DMN connectivity pre-treatment, especially between right LC and left lateral temporal cortex versus responders. Graph metrics of key nodes (temporoparietal junction, lateral temporal cortex) were significantly reduced in non-responders. Three imaging features were included in the model, achieving an AUC of 0.816 with good calibration and clinical utility. Conclusion: Pre-treatment LC-DMN functional and network topology differences may underlie variable responses to dexmedetomidine PCSL in chronic insomnia. The multimodal imaging model effectively predicts treatment sensitivity and may guide personalized interventions.

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Keywords

chronic insomnia disorder, default mode network (DMN), Dexmedetomidine (DEX), Locus coeruleus (LC), PCSL

Received

04 October 2025

Accepted

29 January 2026

Copyright

© 2026 Tao, Zhou, Tang, Wu, LI and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Zhouquan Wu; Ying LI; Hai-Feng Shi

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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