INTRODUCTION: Neuromodulation of cortical brain regions associated with the gut-brain axis may have the potential to modulate gastric function. Previous studies have shown phase-amplitude coupling between the electroencephalogram (EEG) alpha band frequency of the insula (Ins) and gastric slow wave (GSW) activity. This study investigated the first evidence of alpha band EEG-neurofeedback (EEG-NF) training to explore its effects on GSW activity and heart rate variability (HRV). METHODS: A randomized crossover design was employed with 20 healthy participants attending two separate sessions [active-training: uptraining left posterior Insula (LPIns) and active-control: uptraining primary visual cortex (PVC Brodmann area 17)] following the baseline recording period. A 5-min water loading test (5WLT) was conducted following the EEG-NF sessions. Finally, a post EEG-NF/5WL period was also recorded. Participants were blinded to the training program, and the sessions were randomized and conducted at least 48 h apart. Electrocardiogram (ECG), EEG, and electrogastrogram (EGG) data were recorded throughout theexperiment. In addition, the duration of successful NF training was also extracted. Correlation analysis was performed to assess the relationships between outcome variables. RESULTS: Pearson correlation coefficient analysis revealed a significant relationship between the duration of successful NF training and HRV metrics (RMSSD: r = 0.59
p = 0.005, SI: r = -0.59
p = 0.006) in the LPIns training group and EGG-gastric rhythm index (r = -0.40
p = 0.028) in the PVC training group. Moreover, the duration of successful LPIns NF correlated with EEG activity of the infraslow band over the left anterior Ins (r = 0.45
p = 0.043), slow band over the right posterior Ins (r = -0.5
p = 0.022), and beta band over the left (r = 0.44
p = 0.04) and right anterior Ins (r = 0.45
p = 0.04). Significant correlations were also observed between LPIns NF duration and connectivity in the beta and gamma bands between cortical regions of interest. CONCLUSION: The alpha band EEG-NF training of LPIns demonstrated significant association with HRV, and EEG (activity and functional connectivity)measures and did not show a negative correlation with Gastric Alimetry Rhythm Index (GA-RI) following the 5WLT as in the PVC training group. These findings underscore the importance of considering the duration of successful NF as an important variable when evaluating NF training efficacy in future studies.