Acute taVNS modulates lateralized hypoactivity in the right cerebral hemisphere in individuals with subjective cognitive decline

Abstract

Background Subjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer’s disease and represents a critical window for early intervention. Transcutaneous auricular vagus nerve stimulation (taVNS) can modulate cognition-related brain networks. However, its effects in SCD remain unclear. Purpose This study aimed to investigate the immediate neural responses of the brain to taVNS at different frequencies in individuals with SCD. Methodology Fifty-one individuals with SCD and forty healthy controls (HCs) were enrolled. Individuals with SCD underwent acute taVNS at 1 Hz and 20 Hz, as well as sham stimulation. The amplitude of low-frequency fluctuation (ALFF) was used to assess regional brain activity and the immediate effects of different taVNS frequencies in SCD. Results Forty-nine SCD and 39 HC were included. Compared with HCs, SCD exhibited reduced ALFF values in the right inferior frontal gyrus (opercular part), right inferior temporal gyrus, right middle temporal gyrus, and right superior frontal gyrus, and these reductions were associated with subjective cognitive complaints and some standard neuropsychological measures. In SCD, 1 Hz taVNS increased ALFF values in the right fusiform, lingual, inferior occipital, middle temporal, and inferior temporal gyri, and decreased ALFF in the left superior and middle frontal gyri. Similar patterns were observed with 20 Hz taVNS, with additional modulation of the left insula. Conclusion SCD showed right-frontotemporal hypoactivity that may reflect an underlying pathophysiological mechanism. Both 1 Hz and 20 Hz taVNS can modulate the intrinsic neural activity within multiple cognitive-related brain networks SCD. Long-term intervention and comprehensive cognitive testing are required to verify persistent clinical benefits.