Transcutaneous vagus nerve stimulation, which involves the application of electrical currents to the cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve, may be a potential treatment for improving cognitive dysfunction. taVNS may improve cognitive performance in healthy adults, and fewer studies have been performed on the effects of tcVNS on cognition in healthy subjects. We conducted a randomized, single-blind, crossover-controlled trial to investigate the effects of tcVNS stimulation on cognitive function and neural activity in the brains of healthy adults. This study provides support for further tcVNS studies for the treatment of cognitive impairment. Twenty-one participants were randomly divided into two groups, A and B. Group A received tcVNS first and then sham-tcVNS, while group B received the intervention in the reverse order, receiving sham stimulation first and then true stimulation. All subjects were required to perform cognitive function tests before and after receiving intervention, and functional magnetic resonance imaging (fMRI) was performed concurrently during the intervention. We hypothesized that tcVNS would have an effect on the cognitive performance of the subjects and alter the neural activity of the brain. The present study showed that tcVNS had beneficial effects on cognitive performance, mainly improving memory and language skills and attention. tcVNS intervention produced significant spontaneous neural activity in the calcarine gyrus, fusiform gyrus, lingual gyrus, and parahippocampal gyrus of the brain. Future tcVNS/fMRI trials will need to explore the effects of changes in stimulus parameters on the neural activity response of the brain.
IntroductionCognitive impairment is the main clinical feature after traumatic brain injury (TBI) and is usually characterized by attention deficits, memory loss, and decreased executive function. Vagus nerve stimulation (VNS) has been reported to show potential improvement in the cognition level after traumatic brain injury in clinical and preclinical studies. However, this topic has not yet been systematically reviewed in published literature. In this study, we present a systematic review and meta-analysis of the effects of VNS on cognitive function in animal models of TBI and their underlying mechanisms.MethodsWe performed a literature search on PubMed, PsycINFO, Web of Science, Embase, Scopus, and Cochrane Library from inception to December 2021 to identify studies describing the effects of VNS on animal models of TBI.ResultsOverall, nine studies were identified in animal models (36 mice, 268 rats, and 27 rabbits). An analysis of these studies showed that VNS can improve the performance of TBI animals in behavioral tests (beam walk test: SMD: 4.95; 95% confidence interval [CI]: 3.66, 6.23; p < 0.00001) and locomotor placing tests (SMD: –2.39; 95% CI: –4.07, –0.71; p = 0.005), whereas it reduced brain edema (SMD: –1.58; 95% CI: –2.85, –0.31; p = 0. 01) and decrease TNF-α (SMD: –3.49; 95% CI: –5.78, –1.2; p = 0.003) and IL-1β (SMD: –2.84; 95% CI: –3.96, –1.71; p < 0.00001) expression level in the brain tissue. However, the checklist for SYRCLE showed a moderate risk of bias (quality score between 30% and 60%), mainly because of the lack of sample size calculation, random assignment, and blinded assessment.ConclusionThe present review showed that VNS can effectively promote cognitive impairment and neuropathology in animal models of TBI. We hope that the results of this systematic review can be applied to improve the methodological quality of animal experiments on TBI, which will provide more important and conclusive evidence on the clinical value of VNS. To further confirm these results, there is a need for high-quality TBI animal studies with sufficient sample size and a more comprehensive outcome evaluation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290797, identifier: CRD42021290797.
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