Cardiac cycle shapes spinal cord excitability

The heart exerts a rhythmic influence on the nervous system, modulating neural excitability throughout the cardiac cycle. Although cardiac-phase effects on cortical excitability have been extensively studied, the temporal profile and mechanisms of cardiac-cycle modulation of spinal excitability remain largely unknown. Addressing this gap is important both for a more complete understanding of heart–brain interactions and for development of neurostimulation-based rehabilitation strategies. We investigated cardiac-phase-dependent modulation of cervical spinal excitability in 20 healthy volunteers using real-time, heart-rate-adapted trans-spinal magnetic stimulation (TSMS). Single-pulse TSMS was delivered at five cardiac phases (0%, 15%, 30%, 60%, and 85% of the RR interval), spanning systole and diastole. Motor-evoked potential (MEP) amplitude served as an index of spinal excitability. Linear mixed-effects models (LMMs) were used to assess cardiac-phase effects while controlling for RR-intervals duration and respiratory phase. MEP amplitudes varied significantly across the cardiac cycle, with maximal facilitation during mid-diastole (60% of the RR interval). This temporal profile contrasts with the systolic facilitation previously reported for cortical excitability. Additionally, LMM showed that preceding RR-interval duration was significantly associated with spinal excitability, whereas respiratory phase was not. We discuss our findings in the context of two non-exclusive mechanisms: (1) physiological modulation via baroreflex-related pathways and (2) mechanical displacement of the spinal cord within the cardiac cycle. Our findings highlight the importance for future studies of heart–nervous system interactions to account for both mechanisms, as each has implications for understanding of how neurostimulation-based treatments work and for developing advanced clinical protocols.