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-γ PAC) is associated with motor symptoms of Parkinson's disease. However, the causal relationship between β-low-γ PAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of the β-low-γ PAC in the resting state by neurofeedback training (NFT) to control the β-low-γ PAC, such that the motor performance changes in accordance with the changes in β-low-γ PAC in the resting state. 
Methods
We developed an NFT to control the strength of the β-low-γ PAC 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 days, 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 the β-low-γ PAC. 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 (***) and UMIN-CTR (***).
Results
The β-low-γ PAC 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 in β-low-γ PAC during rest and RTs.
Conclusion
The proposed MEG NFT was demonstrated to change the β-low-γ PAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.