Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial

Background: Repetitive transcranial magnetic stimulation (rTMS) offers a promising approach for the treatment of insomnia; however, the precise targets and underlying neural mechanisms remain unclear. This randomized, wait-controlled trial aimed to evaluate the clinical efficacy of neuronavigated rT...

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Main Authors: Liang Gong, Xi Yang, Yuan He, Haoyu Li, Wen Zhou, Duan Liu, Bei Zhang, Chunhua Xi
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225000853
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author Liang Gong
Xi Yang
Yuan He
Haoyu Li
Wen Zhou
Duan Liu
Bei Zhang
Chunhua Xi
author_facet Liang Gong
Xi Yang
Yuan He
Haoyu Li
Wen Zhou
Duan Liu
Bei Zhang
Chunhua Xi
author_sort Liang Gong
collection DOAJ
description Background: Repetitive transcranial magnetic stimulation (rTMS) offers a promising approach for the treatment of insomnia; however, the precise targets and underlying neural mechanisms remain unclear. This randomized, wait-controlled trial aimed to evaluate the clinical efficacy of neuronavigated rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) in chronic insomnia disorder (CID) and to identify potential neural mechanisms associated with therapeutic outcomes. Methods: Fifty patients with CID were randomized to receive 20 sessions of 1 Hz rTMS targeting the right DLPFC or to a waitlist control group. Stimulation coordinates were selected (MNI: 40,39,11) based on our previous neuroimaging meta-analysis, and were precisely localized using MRI-guided neuronavigation. Clinical assessments and resting-state fMRI were conducted before and after the intervention, respectively. Target-based functional connectivity (FC) analysis was used to map rTMS-associated network changes, while causal mediation analysis was used to examine the relationships between neural changes and clinical improvements. Results: Compared to waitlist controls, the rTMS group showed greater improvements in insomnia and mood symptoms (all p < 0.001), with higher response rates (54.55 % vs. 9.09 %) and remission rates (68.18 % vs. 13.64 %). FC analysis showed significant group × time effects on the bilateral DLPFC, middle cingulate cortex, and right anterior cerebellar vermis. Mediation analysis indicated that FC changes in the right DLPFC mediated 24 % of the improvement in insomnia severity (Insomnia Severity Index, p = 0.048). Conclusion: These preliminary findings suggest that precision neuronavigated rTMS targeting the right DLPFC may alleviate insomnia symptoms, with the observed clinical improvements potentially related to the reorganization of the DLPFC network. While these results are encouraging, further research based on placebo-controlled study designs is required to confirm these effects and better understand the underlying mechanisms. This study provides preliminary evidence supporting the integration of precision targeting with neuroimaging to explore the mechanisms underlying the effects of rTMS in insomnia treatment.
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spelling doaj-art-4edc3dec9abc4f668fb975b1e12ed4b52025-08-20T03:45:45ZengElsevierNeuroImage: Clinical2213-15822025-01-014710381510.1016/j.nicl.2025.103815Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trialLiang Gong0Xi Yang1Yuan He2Haoyu Li3Wen Zhou4Duan Liu5Bei Zhang6Chunhua Xi7Department of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, China; Chengdu Medical College, Chengdu, Sichuan 610500, China; Corresponding authors at: Department of Neurology, Chengdu Second People’s Hospital, No 10, Qingyunnan Road, Chengdu, Sichuan 610017, China (L. Gong). Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Huaihe Road 390, Heifei, Anhui 230061, China (C. Xi).Chengdu Medical College, Chengdu, Sichuan 610500, China; Department of Applied Psychology, Chengdu Medical College, Chengdu, Sichuan 610500, ChinaNorth Sichuan Medical College, Nanchong, Sichuan 637199, China; Department of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, ChinaChengdu Medical College, Chengdu, Sichuan 610500, China; Department of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, China; Chengdu Medical College, Chengdu, Sichuan 610500, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, China; Chengdu Medical College, Chengdu, Sichuan 610500, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, Sichuan 610017, China; Chengdu Medical College, Chengdu, Sichuan 610500, ChinaDepartment of Neurology, The Third Affiliated Hospital of Anhui Medical University, Heifei, Anhui 230061, China; Corresponding authors at: Department of Neurology, Chengdu Second People’s Hospital, No 10, Qingyunnan Road, Chengdu, Sichuan 610017, China (L. Gong). Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Huaihe Road 390, Heifei, Anhui 230061, China (C. Xi).Background: Repetitive transcranial magnetic stimulation (rTMS) offers a promising approach for the treatment of insomnia; however, the precise targets and underlying neural mechanisms remain unclear. This randomized, wait-controlled trial aimed to evaluate the clinical efficacy of neuronavigated rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) in chronic insomnia disorder (CID) and to identify potential neural mechanisms associated with therapeutic outcomes. Methods: Fifty patients with CID were randomized to receive 20 sessions of 1 Hz rTMS targeting the right DLPFC or to a waitlist control group. Stimulation coordinates were selected (MNI: 40,39,11) based on our previous neuroimaging meta-analysis, and were precisely localized using MRI-guided neuronavigation. Clinical assessments and resting-state fMRI were conducted before and after the intervention, respectively. Target-based functional connectivity (FC) analysis was used to map rTMS-associated network changes, while causal mediation analysis was used to examine the relationships between neural changes and clinical improvements. Results: Compared to waitlist controls, the rTMS group showed greater improvements in insomnia and mood symptoms (all p < 0.001), with higher response rates (54.55 % vs. 9.09 %) and remission rates (68.18 % vs. 13.64 %). FC analysis showed significant group × time effects on the bilateral DLPFC, middle cingulate cortex, and right anterior cerebellar vermis. Mediation analysis indicated that FC changes in the right DLPFC mediated 24 % of the improvement in insomnia severity (Insomnia Severity Index, p = 0.048). Conclusion: These preliminary findings suggest that precision neuronavigated rTMS targeting the right DLPFC may alleviate insomnia symptoms, with the observed clinical improvements potentially related to the reorganization of the DLPFC network. While these results are encouraging, further research based on placebo-controlled study designs is required to confirm these effects and better understand the underlying mechanisms. This study provides preliminary evidence supporting the integration of precision targeting with neuroimaging to explore the mechanisms underlying the effects of rTMS in insomnia treatment.http://www.sciencedirect.com/science/article/pii/S2213158225000853Chronic insomnia disorderNeuronavigationrTMSDLPFCFunctional connectivity
spellingShingle Liang Gong
Xi Yang
Yuan He
Haoyu Li
Wen Zhou
Duan Liu
Bei Zhang
Chunhua Xi
Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
NeuroImage: Clinical
Chronic insomnia disorder
Neuronavigation
rTMS
DLPFC
Functional connectivity
title Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
title_full Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
title_fullStr Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
title_full_unstemmed Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
title_short Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial
title_sort precision targeting of right dorsolateral prefrontal cortex with neuronavigated rtms alleviates chronic insomnia via functional connectivity reorganization a randomized neuroimaging trial
topic Chronic insomnia disorder
Neuronavigation
rTMS
DLPFC
Functional connectivity
url http://www.sciencedirect.com/science/article/pii/S2213158225000853
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