Major Depressive Disorder (MDD) is an affective disorder characterized by prominent and persistent features such as mood depression, Globally, approximately 322 million individuals are affected by MDD, with a prevalence rate of 4.4% (Kok and Reynolds, 2017). Globally, approximately 322 million individuals are affected by MDD, with a prevalence rate of 4.4% (Nestler et al., 2002). The current state of treatment for MDD is mainly based on pharmacotherapy, psychotherapy and physical therapy (Demyttenaere et al., 2008). Antidepressant medications are regarded as first‐line treatment strategy for MDD, however, about one third of patients with depression remains treatment resistant and does not respond to multiple pharmacological treatment regimens (van Geffen et al., 2010). Although psychotherapy is used as another common treatment modality for depression, traditional face-to-face psychotherapy is time-consuming and less prevalent. Therefore, the search for effective non-pharmacological therapies is particularly urgent. Some non-invasive neuromodulation techniques have emerged, including repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Direct Current Stimulation (tDCS), transcutaneous Electrical Cranial Stimulation (TECS), and transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be used to treat MDD through non-invasive modulation of the central nervous system (Caparelli et al., 2022, Aust et al., 2022, Tsai, 2015, Rong et al., 2016).

Noninvasive electrical stimulation of cranial nerves, in particular trigeminal nerve and vagus nerve has attracted increasing interest over the past decade (Cook et al., 2014, Adair et al., 2020). Interestingly, we found that Yin We discovered that GV20 and GV29 are located in the trigeminal innervation area, which corresponds to the stimulation site of Transcutaneous Electrical Cranial Stimulation (TECS) (Acupuncture Moxibustion Cao, 2014, Cook et al., 2016). taVNS overlaps with the stimulation sites of auricular liver (CO12) and heart (CO15), which are located in the distribution area of the auricular branch of the vagus nerve (Liu et al., 2017). Moreover, neuroimaging evidence suggests that trigeminal and vagus nerve electrical stimulation modulates several similar brain regions involved in emotional and cognitive processing (Wang et al., 1992, Cook et al., 2013, Zhao et al., 2019, Fang et al., 2016). In light of this, we combined the TEAS of GV20 and GV29 with the taVNS of C012 and C015 to create a new stimulation method called Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). TECAS could generate therapeutic potentials of the two cranial nerve stimulations in an additive or even synergistic manner. In previous studies, it was found that TECAS has antidepressant effects, with an efficacy of approximately 66.4%, and is comparable in effectiveness to escitalopram. Both escitalopram and TECAS treatment achieved antidepressant effects by modulating the default mode network (DMN) connectivity (Ma et al., 2023). However, there is a limited number of similar studies validating these findings..

Resting-state functional magnetic resonance imaging (rs-fMRI), a neuroimaging technique based on blood oxygenation dependent (BOLD) levels for detecting brain activity patterns, is one of the main methods used to study the the mechanisms of acupuncture efficacy (Pandarakalam, 2018). MDD exhibit abnormal functional connectivity in multiple resting-state brain networks, with the DMN being the most extensively studied (Groenewold et al., 2013). DMN is involved in self-awareness, monitoring internal and external environmental information, and other cognitive functions. Dysfunction of the DMN has been closely associated with typical clinical manifestations of MDD, such as depressed mood, impaired self-awareness, and rumination (Williams, 2017, Kaiser et al., 2015). However, the mechanism of the brain effect of TECAS on MDD has not been elucidated. Increased research on the mechanisms of the effects of TECAS is more conducive to improving the understanding of the overall efficacy mechanisms of TECAS. Therefore, in this study, we used rs-fMRI technique to observe the changes of ALFF and FC in MDD patients before and after TECAS treatment. We hypothesized that TECAS has an modulatory effect on DMN in MDD patients.We hope that this study will provide information and clues to elucidate the neural mechanisms of TECAS in MDD patients.