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In animals, high-frequency spinal cord stimulation (HF-SCS) applied on the ventral epidural surface at the T 2 level results in negative airway pressure generation consistent with inspiratory muscle activation. In the present study, in anesthetized dogs, we found that ventral HF-SCS (500 Hz) applied at all thoracic levels resulted in negative airway pressure generation. In the region of the lower thoracic spinal cord, negative airway pressure generation was most pronounced at the T 9 level. At this level, airway pressure generation was monitored: 1) during ventral HF-SCS over a wide range of stimulus amplitudes (0.5-15 mA) and frequencies (50-1,000 Hz) and 2) following spinal sections at C 8 (to assess potential diaphragm activation) and subsequently at T 6 (to assess potential intercostal muscle activation). The application of low stimulus currents between 1 and 2 mA and high stimulus frequencies (&gt;300 Hz) resulted in the development of large negative airway pressure generation. Stimulation with 1 mA, 500 Hz resulted in a highest negative airway pressure generation of 47 ± 2 cmH 2 O. Increasing stimulus current was associated with progressive reductions in the magnitude of negative airway pressure generation. HF-SCS (500 Hz) with 15 mA resulted in a negative airway pressure generation of 7 ± 3 cmH 2 O. C 8 section markedly reduced negative airway pressure generation, and subsequent T 6 section resulted in positive airway pressure generation after HF-SCS. Our results indicate the existence of pathways with connections to both the phrenic and inspiratory intercostal motoneuron pools in the ventral part of the lower thoracic spinal cord. We speculate that the circuits mediating the previously described excitatory intercostal-to-phrenic reflex mediate the observed responses. NEW &amp; NOTEWORTHY This study suggests that, in contrast to dorsal high-frequency spinal cord stimulation at the T 9 spinal level, which results in positive pressure generation, ventral high-frequency spinal cord stimulation at the same spinal level results in large negative airway pressure generation with low stimulus currents. This method, therefore, may provide an alternative method to restore ventilation in ventilator-dependent spinal cord-injured patients.

Inspiratory muscle activation via ventral lower thoracic high-frequency spinal cord stimulation