The Instant Spontaneous Neuronal Activity Modulation of Transcutaneous Auricular Vagus Nerve Stimulation on Patients With Primary Insomnia

Abstract

Keywords: primary insomnia, transcutaneous auricular vagus nerve stimulation, spontaneous neuronal activity, amplitude of low frequency fluctuations, functional connectivity Frontiers in Neuroscience | www.frontiersin.org

Brain Functional Mechanisms Determining the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Primary Insomnia

“…Sleep behaviors are regulated by cholinergic neurons of the vagus nerve (Mu and Huang, 2019); taVNS may improve sleep quality by directly regulating the activity of this nerve (Hallböök et al, 2005). Patients with insomnia often exhibit hyperactivation of the default mode network (DMN) and visual areas of the brain; taVNS was shown to inhibit activity in these brain regions, thereby alleviating sleep disorder and hypersensitivity to light (Zhao et al, 2020). Additionally, taVNS may relieve depression and anxiety symptoms that often accompany PI by regulating the activity of the amygdala and DMN (Rong et al, 2016).…”

“…Any discrepancies in diagnosis were resolved through discussion or with input from more senior neurosurgeons. The patients met the following inclusion criteria (Huls et al, 2018;Zhao et al, 2020): (1) age 18-65 years and right-handed, (2) at least one of the three typical symptoms of insomnia (i.e., difficulty in falling asleep, difficulty in maintaining a sleep state, or insufficient sleep time) lasting > 3 months and meeting the diagnostic criteria of PI, (3) Pittsburgh Sleep Quality Index (PSQI) score > 7, Self-Rating Anxiety Scale (SAS) score < 59, and Self-Rating Depression Scale (SDS) score < 62, (4) patients with no nervous system disease, metal implants in the body, claustrophobia, or any other contraindication for MRI, and (5) education level of at least junior high school (in order to be able to understand the scales). The exclusion criteria (Huls et al, 2018) were as follows: (1) patients with a history of head injury, nervous system diseases, drug abuse, and other objective environmental factors that could cause insomnia symptoms, (2) patients with tumors or other serious primary diseases of the hematopoietic or endocrine system, (3) PSQI score ≤ 7, SAS score ≥ 59, or SDS score ≥ 62, (4) patients with contraindications for vagus nerve stimulation such as arrhythmia and asthma, (5) allergic reaction in or damage to the skin of the stimulation area, and (6) participation in other clinical trials in the previous 6 months or taking anticholinergic or other drugs that could inhibit cerebral cortex or nervous system activity at the time of the examination.…”

“…A taVNS device (SDZ-IIB; Hwato, Suzhou, China) was used to stimulate the auricular cavum concha of the vagus nerve (Figure 1) with the following parameters (Rong et al, 2016;Kong et al, 2018;Zhao et al, 2020): (1) density waves adjusted to 20 Hz, with a wave width of 0.2 ms, (2) intensity adjusted based on the tolerance of the patient (7-12 mA), and (3) similar to a previous study design, the taVNS treatments consisted of 40 sessions (two sessions a day, 5 days per week for 4 weeks).…”

“…Transcutaneous auricular vagus nerve stimulation (taVNS) is known to be effective in the treatment of insomnia (Luo et al, 2017;Jiao et al, 2020;Zhao et al, 2020). Patients with PI often exhibit autonomic nervous system imbalance (Javaheri and Redline, 2017), elevated levels of neurogenic inflammatory factors (Irwin et al, 2016), and hypersensitivity to external noise or emotional stimulation (Lauriola et al, 2019).…”

“…Amplitude of low-frequency fluctuations (ALFF) or fractional (f)ALFF is an important parameter in functional magnetic resonance imaging (fMRI) that reflects the activity in a given brain region and has been used to explore the neural basis of insomnia and monitor treatment response (Zou et al, 2008;Liu et al, 2016;Zhao et al, 2020). We speculated that the variable efficacy of continuous taVNS among patients with PI is due to differences in autonomic responses and brain activity.…”