Enhancing cognitive abilities through transcutaneous auricular vagus nerve stimulation: Findings from prefrontal functional connectivity analysis and virtual brain simulation.

Recent studies have indicated the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as an intervention for cognitive decline. In this study, we systematically analyzed the effects of taVNS on cognitive enhancement from the perspective of brain networks, by combining functional near-infrared spectroscopy (fNIRS) signal analysis with virtual brain simulations. Behavioral experiments with older adults demonstrated that participants with low baseline performance experienced significant improvements in working memory performance following taVNS, while those with high baseline performance tended to decline. This pattern was closely associated with functional connectivity (FC) in the prefrontal cortex (PFC) concurrently measured during the behavioral tasks, i.e., task performance correlated with FC in the PFC, particularly in the medial PFC (mPFC). Moreover, the changes in performance due to taVNS, which varied based on baseline performance, exhibited a notable alignment with the FC changes in the mPFC. These findings were further explored through virtual brain simulations. The simulation results demonstrated that the brain's functional state could vary depending on the network coupling parameter-capable of reflecting loss of structural brain connectivity associated with aging-and that the modulation effects induced by taVNS may also differ based on those functional states. Current results indicate that the efficacy of taVNS interventions for cognitive enhancement may vary according to the pre-intervention structural and functional states of individual brains. Therefore, the development of personalized optimization strategies for taVNS intervention is crucial, and digital brain research holds significant promise in advancing this field.