Qi Meng, Huang Yiting, Mai Runru, Yan Zhaoxian, Xu Biyun, Liu Bo, Zhang Yue
Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
BMC Med. 2025 Jul 9;23(1):412. doi: 10.1186/s12916-025-04126-7.
BACKGROUND: Dysfunctional basal forebrain (BF) connectivity contributes to primary insomnia (PI). This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) modulates BF functional connectivity (FC) in patients with PI and whether baseline FC predicts taVNS treatment response. METHODS: Seventy patients with PI were randomized to real or sham taVNS for 4 weeks. Clinical assessments-including Pittsburgh Sleep Quality Index (PSQI], Insomnia Severity Index (ISI] and Zung's Self-Rating Anxiety (SAS], and Depression Scale (SDS)-and resting-state fMRI data were collected at baseline and after treatment. FC of the bilateral BF subregions (Ch_123, Ch_4) was analyzed, and pre-to-post intervention changes in FC and clinical scores were compared between groups. Baseline FC was used to predict treatment response using a support vector regression (SVR) model, validated on an independent dataset. RESULTS: Sixty-seven patients completed the study (33 real taVNS, 34 sham taVNS). Changes in clinical outcomes showed that real taVNS significantly reduce PSQI, ISI, and SAS scores compared to sham. FC analysis revealed reduced connectivity between bilateral BF and areas involved in visual (superior occipital gyrus, SOG; middle occipital gyrus, MOG; fusiform gyrus, FFG), somatosensory (supplementary motor area, SMA) cortex and medial prefrontal cortex (mPFC) after taVNS treatment. Reduced FC between bilateral BF and left MOG correlated positively with ISI improvement (r = 0.490, p = 0.008, Bonferroni correction). The SVR model effectively predicted treatment response based on BF-visual circuit connectivity (r = 0.520, p = 0.0014, 5000 permutation test) and generalized well to an independent dataset (r = 0.443, p = 0.0354, 5000 permutation test). CONCLUSIONS: Our findings suggest that taVNS may alleviate symptoms of primary insomnia through modulation of basal forebrain connectivity with visual, sensorimotor, and medial prefrontal cortical regions. Preliminary investigations indicate that baseline functional connectivity in the BF-visual circuit could represent a candidate biomarker for taVNS response, potentially informing personalized treatment strategies. TRIAL REGISTRATION: The study was registered with the China Clinical Trial Registry (Clinical Trial No. ChiCTR1900022535).
背景：基底前脑（BF）功能连接异常导致原发性失眠（PI）。本研究调查经皮耳迷走神经刺激（taVNS）是否能调节PI患者的BF功能连接（FC），以及基线FC是否能预测taVNS治疗反应。 方法：70例PI患者被随机分为接受真正的或假的taVNS治疗4周。在基线和治疗后收集临床评估数据，包括匹兹堡睡眠质量指数（PSQI）、失眠严重程度指数（ISI）、zung氏自评焦虑量表（SAS）和抑郁量表（SDS），以及静息态功能磁共振成像数据。分析双侧BF亚区（Ch_123、Ch_4）的FC，并比较两组干预前后FC和临床评分的变化。使用支持向量回归（SVR）模型，以独立数据集验证，用基线FC预测治疗反应。 结果：67例患者完成研究（33例接受真正的taVNS，34例接受假的taVNS）。临床结果变化表明，与假刺激相比，真正的taVNS显著降低了PSQI、ISI和SAS评分。FC分析显示，taVNS治疗后，双侧BF与视觉相关区域（枕上回、中枕回、梭状回）、体感相关区域（辅助运动区）及内侧前额叶皮质之间的连接性降低。双侧BF与左侧中枕回之间FC的降低与ISI的改善呈正相关（r = 0.490，p = 0.008，Bonferroni校正）。SVR模型基于BF-视觉回路连接性有效地预测了治疗反应（r = 0.520，p = 0.0014，5000次置换检验），并能很好地推广到独立数据集（r = 0.443，p = 0.0354，5000次置换检验）。 结论：我们的研究结果表明，taVNS可能通过调节基底前脑与视觉、感觉运动和内侧前额叶皮质区域的连接性来缓解原发性失眠症状。初步研究表明，BF-视觉回路中的基线功能连接可能是taVNS反应的候选生物标志物，有可能为个性化治疗策略提供依据。 试验注册：本研究在中国临床试验注册中心注册（临床试验编号：ChiCTR1900022535）。
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