Noncontact Midair Ultrasonic Neuromodulation of the Median and Ulnar Nerves Induces Frequency-Specific Parasympathetic and Cortical Network Responses in Healthy Adults.

INTRODUCTION

Autonomic imbalance, characterized by disrupted sympathetic and parasympathetic equilibrium in the autonomic nervous system (ANS), underlies conditions such as epilepsy, depression, anxiety, and cardiac issues, and is often treated with drugs or neuromodulation. Peripheral nerve stimulation, including vagal and median nerves, is widely used to modulate parasympathetic activity. Our recent research suggests that specific median nerve stimulation frequencies are needed to induce parasympathetic effects. This novel study explored noncontact midair ultrasonic stimulation with low and high frequencies to elicit tactile stimulation of the left median and ulnar nerves to modulate the activity of the ANS and associated cortical networks.

MATERIALS AND

METHODS

In a single-blind, randomized cross-over design, 24 healthy participants received low-frequency stimulation (LFS) at 1-second repeat gap mode, high-frequency stimulation (HFS) at 0.01-second repeat gap mode, and the placebo stimulation (PLS). The ANS response was measured by heart rate variability (HRV) from electrocardiography. Time-domain HRV parameters were analyzed, including the root mean square of successive differences (RMSSD, reflecting parasympathetic activity) and stress index (SI, reflecting sympathetic activity). Electroencephalography (EEG) was used to investigate the cortical activity within the regions of central autonomic network (CAN), salience network (SN), and default mode network (DMN).

RESULTS

Among the HFS, LFS, and PLS, only the LFS showed a significant increase in RMSSD (p = 0.0357) for HRV analysis, suggesting autonomic effects are specific to lower frequencies for midair ultrasonic stimulation. EEG analysis also revealed the significant effects of the LFS on CAN regions, including the right posterior and right anterior insula (p = 0.0034 alpha and p = 0.0005 alpha respectively), dorsal anterior cingulate cortex (dACC, p = 0.0034 theta, p = 0.00018 alpha), rostral anterior cingulate cortex (p = 0.00021 alpha), and posterior cingulate cortex and precuneus (PCC-Prec) (p = 0.0016 beta, p = 0.0013 gamma). HFS showed significant effects on cortical regions for SN, including anterior insula (p = 0.0032 slow frequency), dACC (p = 0.0043 theta, p = 0.0039 alpha, p = 0.00061 beta, and p = 0.0029 gamma), and PCC-Prec (p = 0.0061 theta). Both LFS and HFS modulated PCC-prec of DMN, but LFS significantly modulated PCC-prec at multiple EEG bands. PLS did not show any significant impact on HRV or EEG.

DISCUSSION: The present study revealed low-frequency noncontact midair ultrasonic stimulation of the left median and ulnar nerves as a novel technique for noncontact modulation of the ANS. This could offer a potential alternative to existing neuromodulation modalities to relieve autonomic imbalances and associated clinical conditions. Further research is required to refine stimulation parameters for clinical benefit.