Magnetoencephalographic neurofeedback training decreases β-low-γ phase-amplitude coupling of the motor cortex of healthy adults: a double-blinded randomized crossover feasibility study

Objective.The coupling between the beta (13-30 Hz) phase and low gamma (50-100 Hz) amplitude in the motor cortex is thought to regulate motor performance. Abnormal phase-amplitude coupling (PAC) of beta-low gamma (β-low-γPAC) is associated with motor symptoms of Parkinson's disease. However, the causal relationship betweenβ-low-γPAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of theβ-low-γPAC in the resting state by neurofeedback training (NFT) to control theβ-low-γPAC, such that the motor performance changes in accordance with the changes inβ-low-γPAC in the resting state.Approach.We developed an NFT to control the strength of theβ-low-γPAC in the motor cortex, which was evaluated by magnetoencephalography (MEG) using a current source estimation technique. Twenty subjects were enrolled in a double-blind randomized crossover trial to test the feasibility of the MEG NFT. In the NFT for 2 d, the subjects were instructed to reduce the size of a black circle whose radius was proportional (down-training) or inversely proportional (up-training) to the strength of theβ-low-γPAC. The reaction times (RTs) to press a button according to some cues were evaluated before and after training. This study was registered at ClinicalTrials.gov (NCT03837548) and UMIN-CTR (UMIN000032937).Main results.Theβ-low-γPAC during the resting state was significantly decreased after down-training, although not significantly after up-training. RTs tended to decrease after both trainings, however the differences were not statistically significant. There was no significant correlation between the changes inβ-low-γPAC during rest and RTs.Significance.The proposed MEG NFT was demonstrated to change theβ-low-γPAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.