Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O₂) and room air (1 min episodes of 20.9% O₂). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.