Acute Intermittent Hypoxia and Cortical Evoked Potentials in Human Diaphragm

Abstract

Episodic carotid body activation via acute intermittent hypoxia (AIH) elicits respiratory motor plasticity (known as long‐term facilitation [LTF]) in humans and other mammals. In rodents, AIH‐induced LTF requires serotonergic neuron activation in the medullary raphe nuclei and episodic serotonin release within respiratory motor nuclei, thereby strengthening descending synaptic inputs to spinal respiratory motor neurons. Humans exhibit ventilatory LTF under certain circumstances, although the details of its underlying mechanism are less clear. Recent evidence demonstrates that AIH enhances corticospinal motor evoked potentials (MEP) in a non‐respiratory motor pool innervating the first dorsal interosseous muscle of the hand. It is not known if AIH has similar effects on the phrenic/diaphragm system in humans. Thus, we tested the hypothesis that AIH augments diaphragm MEP amplitude. Twelve healthy young adults were recruited (age = 30 ± 7 years; 5 female). On Day 1, diaphragm MEPs and compound muscle action potentials (CMAPs) were assessed using transcranial (TMS) and cervical (CMS) magnetic stimulation, respectively. The diaphragm electromyogram was recorded using surface electrodes on the chest wall. Reliability of TMS‐ and CMS‐evoked potentials were determined prior to testing. Following baseline measures, subjects were exposed to AIH (15, 1‐minute episodes of 9% O2, with 1‐minute normoxic intervals) via a facemask attached to a hypoxic generator. Cardiovascular responses (heart rate, blood pressure and oxygen saturation) were monitored throughout. Stimulus‐response curves were determined for each subject by delivering stimuli prior to and 30 minutes post AIH. On Day 2 (at least 7 days later), 6 subjects returned for a normoxic (sham) trial. Subjects were blinded to the gas composition delivered on each visit. No significant AIH effects were observed in MEP (change = −1 ± 7%, p= 0.96) or CMAP amplitude (+1 ± 5%, p= 0.97) across the stimulus‐response curve. At an intensity equivalent to 50% of baseline peak amplitude (V50), the mean changes in MEP and CMAP amplitude were +4 ± 14% (p= 0.81) and −5 ± 6% (p= 0.75), respectively. Further, no effect of normoxic sham exposures was found during the control visit (MEP = −8 ± 9%, p= 0.97; CMAP = +7 ± 31%, p= 0.79). Between‐block coefficients of variation for TMS‐ and CMS‐evoked potentials were 22.9% and 6.9%, respectively. Within‐session reproducibility of evoked responses to TMS and CMS were good to excellent (ICC > 0.8). In conclusion, AIH alone does not influence cortical evoked potentials in the diaphragm as it does in a non‐respiratory motor system. We speculate that repetitive daily AIH and/or concomitant hypercapnia during AIH may reveal plasticity in diaphragm cortical evoked potentials in humans.Support or Funding InformationThis work was supported by the UF McKnight Brain Institute, DoD (SCIRP), NIH R01 HL147554 & OT2OD023854, Brooks Rehabilitation, and the Brooks PHHP Research Collaboration.