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

Abstract

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. Approach. 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 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 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 (NCT03837548) and UMIN-CTR (UMIN000032937). Main 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. Significance. 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.