High-frequency taVNS modulates olfaction-related brain activity in patients with subjective cognitive decline

Subjective cognitive decline (SCD) is considered a high-risk factor for Alzheimer's disease and serves as a critical window of the prevention and treatment. Transcutaneous auricular vagus nerve stimulation (taVNS) has shown therapeutic effects on cognitive impairment, but there is a lack of research on its application in SCD.

This study aimed to explore the immediate modulatory effects of taVNS at different frequencies on the brain function in patients with SCD.

Seventy SCD and 49 healthy control (HC) were enrolled. Resting-state functional MRI data were collected at baseline and during taVNS with three stimulation conditions: 1 Hz-taVNS, 20 Hz-taVNS, and sham taVNS (staVNS), respectively. Regional homogeneity (ReHo) analysis was used to identify spontaneous neural activity changes in SCD; the abnormal brain regions were then used as seed for subsequent functional connectivity (FC) analysis. In addition, ReHo and FC analyses were performed to assess the immediate modulatory effects of taVNS in SCD.

Compared with HC, SCD showed abnormal ReHo and FC mainly involving olfaction-related brain regions, and the reduced value was positively associated with Shape Trail Test-part B. During taVNS, we found that 20 Hz-taVNS significantly increased ReHo in the bilateral olfactory cortex compared with baseline, and decreased FC between the left medial orbitofrontal cortex and the right precentral and postcentral gyri. No significant ReHo or FC changes were observed during 1 Hz-taVNS and staVNS.

These findings suggest that SCD exhibits reduced spontaneous activity and disrupted FC in the olfaction-related brain regions, which may reflect early functional alterations before objective impairment; 20 Hz-taVNS can modulate these cerebral functional abnormalities and may hold potential as a noninvasive neuromodulation strategy in SCD.