Background: Although inspiratory muscle training (IMT) is an effective intervention for improving breath perception, brain mechanisms have not been studied yet. Purpose: To examine the effects of IMT on insula and default mode network (DMN) using resting-state functional MRI (RS-fMRI). Study Type: Prospective. Population: A total of 26 healthy participants were randomly assigned to two groups as IMT group (n = 14) and sham IMT groups (n = 12). Field Strength/Sequence: A 3-T, three-dimensional T2* gradient-echo echo planar imaging sequence for RS-fMRI was obtained. Assessment: The intervention group received IMT at 60% and sham group received at 15% of maximal inspiratory pressure (MIP) for 8 weeks. Pulmonary and respiratory muscle function, and breathing patterns were measured. Groups underwent RS-fMRI before and after the treatment. Statistical Tests: Statistical tests were two-tailed P < 0.05 was considered statistically significant. Student's t test was used to compare the groups. One-sample t-test for each group was used to reveal pattern of functional connectivity. A statistical threshold of P < 0.001 uncorrected value was set at voxel level. We used False discovery rate (FDR)-corrected P < 0.05 cluster level. Results: The IMT group showed more prominent alterations in insula and DMN connectivity than sham group. The MIP was significantly different after IMT. Respiratory rate (P = 0.344), inspiratory time (P = 0.222), expiratory time (P = 1.000), and inspiratory time/total breath time (P = 0.572) of respiratory patterns showed no significant change after IMT. All DMN components showed decreased, while insula showed increased activation significantly. Data Conclusion: Differences in brain activity and connectivity may reflect improved ventilatory perception with IMT with a possible role in regulating breathing pattern by processing interoceptive signals.Evidence Level: 2 Technical Efficacy: Stage 4

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