Phase-Amplitude Coupling in Response to Transcutaneous Vagus Nerve Stimulation: Focus on Regions Implicated in Mood and Memory.

OBJECTIVE

This study aimed to investigate whether transcutaneous vagus nerve stimulation (tVNS) at different frequencies affects phase-amplitude coupling among regions of the brain linked to mood and memory disorders using simultaneous magnetoencephalography (MEG) in healthy participants.

MATERIALS AND

METHODS

Phase-amplitude coupling was measured among brain areas in response to different stimulation frequencies of tVNS using concurrent MEG and tVNS in 17 healthy participants. The 4 protocols were: 24 Hz cymba concha, 1 Hz cymba concha, PFM cymba concha, and 24 Hz ear lobe. A driven autoregressive method was used to estimate the coupling among brain areas in different physiological frequency bands in response to these protocols.

RESULTS

Different tVNS stimulation protocols led to alterations in phase-amplitude coupling among multiple brain regions linked to mood and memory, notably the prefrontal cortex, hippocampus, and temporal pole. Stimulation delivered at 24 Hz was observed to decrease delta-gamma coupling within the temporal pole and cingulate cortex when contrasted with 24-Hz sham stimulation. Increased alpha-gamma coupling was observed between the hippocampus and prefrontal cortex when contrasting 24 Hz with pulse-frequency-modulated stimulation. Finally, a comparison of 24-Hz with low-frequency 1-Hz stimulation showed an increase in theta-gamma coupling within the prefrontal cortex.

SIGNIFICANCE: To our knowledge, this study represents the first attempt to quantify phase-amplitude coupling in response to tVNS and suggests that different stimulation frequencies can modulate coupling between different areas of the brain. Abnormal phase-amplitude coupling has been linked to multiple mood and memory disorders. Further investigations using different stimulation frequencies of tVNS to alter phase-amplitude coupling may lead to the development of tVNS as a therapeutic option for different medical conditions.