Boosting Motor Cortex Plasticity through Respiratory Phase-Triggered Paired Associative Stimulation

Paired Associative Stimulation (PAS) has shown promise in promoting motor cortex plasticity by using transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation. However, the effectiveness of PAS is often limited by its short-lived potentiation effects. Recent research indicates that respiratory rhythms can influence cortical excitability, suggesting a potential method to enhance PAS efficacy. This study investigated the impact of synchronizing PAS with respiratory phase transitions - specifically, the transition from inspiration to expiration (I-E) and expiration to inspiration (E-I) - on motor cortical plasticity. We conducted experiments with 18 healthy volunteers (13 females, 5 males) aged 21-45 years, assessing motor-evoked potentials (MEPs) elicited by TMS applied to the left motor cortex. Participants underwent PAS sessions where paired stimuli were delivered either at I-E or E-I transitions, or at random intervals. MEPs were recorded at baseline, immediately post-PAS, and at 10, 20, and 30 minutes post-stimulation. Results showed that PAS triggered at the I-E transition significantly increased MEP amplitudes, with significant differences in MEP amplitudes at 20 minutes post-PAS between the I-E and the other conditions. This highlights the benefit of timing PAS with the I-E transition for enhanced motor cortical plasticity. These findings underscore the potential of integrating respiratory rhythms into neuromodulation techniques to improve therapeutic outcomes. Synchronizing PAS with natural respiratory phases may enhance motor recovery strategies and offers a refined approach for therapeutic interventions. This approach could be particularly relevant for stroke rehabilitation, where enhancing motor cortical plasticity is crucial for recovery. Significance StatementThis study demonstrates that syncing brain stimulation with breathing patterns can enhance motor learning. By coordinating Paired Associative Stimulation (PAS)--a technique that stimulates sensory and motor inputs--with specific phases of the breathing cycle, we observed stronger responses in the motor cortex. This approach not only improves our understanding of brain adaptability but also offers a new way to fine-tune therapeutic techniques. For stroke patients, where regaining motor function is critical, integrating natural body rhythms into treatment could lead to more effective and personalized rehabilitation strategies.