1.Convergent modulation of default mode network effective connectivity by modified Suanzaoren Decoction and estazolam in patients with chronic insomnia disorder
Ke WANG ; Yiding HAN ; Haohao YAN ; Xingyan GUO ; Wuhong LIN ; Ping YAO ; Min LIU ; Min CHEN ; Longbiao CUI ; Wenbin GUO ; Dongsheng LYU
Sichuan Mental Health 2026;39(4):356-366
BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder (CID). Default mode network (DMN) dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However, it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity (EC) of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam, so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder, third edition (ICSD-3) were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference, patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group (n=52) or the estazolam group (n=30). Ultimately, 66 patients completed follow-up assessments (modified Suanzaoren Decoction group, n=41; estazolam group, n=25). All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex (mPFC), bilateral inferior parietal lobule (IPL), and precuneus (PCUN) were selected as seed regions. Granger causality analysis (GCA) was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline, significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus (t=5.24, Z=4.84, voxel-level P<0.001, cluster-level P<0.05, GRF-corrected), with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions (P>0.05). Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically, EC from the left IPL to the supplementary motor area (SMA) decreased after treatment (modified Suanzaoren Decoction group: t=-6.28, Z=5.208; estazolam group: t=-5.58, Z=4.425). Conversely, EC from the SMA to the left IPL increased (modified Suanzaoren Decoction group: t=5.89, Z=4.968; estazolam group: t=6.15, Z=4.720). Furthermore, both groups demonstrated reduced EC from the PCUN to the left IPL (modified Suanzaoren Decoction group: t=-5.85, Z=4.94; estazolam group: t=-5.75, Z=4.515), and elevated EC from the left IPL to the PCUN (modified Suanzaoren Decoction group: t=5.29, Z=4.579; estazolam group: t=4.55, Z=3.826) (voxel-level P<0.001, cluster-level P<0.05, GRF-corrected). No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group (P>0.05). ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome, both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. [Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region (number, 2019MS08099); ClinicalTrials.gov number, NCT06452953]

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