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.