Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex

Abstract

Purpose Acute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex. Methods Eleven healthy, right-handed participants completed two testing sessions: (1) AIH (comprising 3 min in hypoxia [fraction of inspired oxygen ~ 10%] and 2 min in normoxia repeated over five cycles) and (2) normoxia (NOR) (equivalent duration to AIH). Single- and paired-pulse transcranial magnetic stimulations were delivered to the primary motor cortex, before and 0, 25, and 50 min after AIH and normoxia. Results The mean nadir in arterial oxygen saturation was lower (p < 0.001) during the cycles of AIH (82.5 ± 4.9%) than NOR (97.8 ± 0.6%). There was no significant difference in corticospinal excitability, intracortical facilitation, or intracortical inhibition between AIH and normoxia conditions at any time point (all p > 0.05). There was no association between arterial oxygen saturation and changes in corticospinal excitability after AIH (r = 0.05, p = 0.87). Conclusion Overall, AIH did not modify either corticospinal excitability or excitability of intracortical facilitatory and inhibitory circuits within the primary motor cortex. Future research should explore whether a more severe or individualised AIH dose would induce consistent, measurable changes in corticospinal excitability.

Intermittent hypoxia-induced enhancements in corticospinal excitability predict gains in motor learning and metabolic efficiency

“…We generated recruitment curves by plotting the peak-to-peak MEP amplitudes against the normalized stimulus intensities based on the participant’s resting motor threshold (RMT) ( Fig. 1 ) 11 . To assess changes in CSE, we quantified TMS indices such as changes in the maximum MEP amplitude (MEP max ), the area under the recruitment curve, the peak slope of the recruitment curve, and RMT.…”

“…Recruitment curves were generated by plotting the peak-to-peak amplitudes of the TA MEPs against their corresponding stimulus intensities. To compare changes in CSE across participants and testing sessions pre- to post-AIH, we normalized the recruitment curves to the RMT during each respective testing session 11 . Thus, the recruitment curve sampling involved a pseudo-randomized sequence of stimulations ranging from 90% to 140% of the RMT 56 , 57 , with 6 pulses applied per intensity (Signal; CED, USA) 58 .…”

“…Previous studies in able-bodied individuals have shown that AIH may facilitate corticospinal excitability (CSE) to the upper limb 9 , 10 . However, contrasting evidence indicates that prolonged hypoxic exposures do not alter CSE 11 , and even milder exposures result in inconsistencies in both the time course and stimulus intensity required for such augmentation 9 , 10 . These discrepancies underscore a critical gap in our understanding of AIH-induced plasticity, including uncertainties regarding how AIH may differentially affect lower limb motor areas that support locomotor control.…”

Control of Breathing

“…201,202 While improvements in respiratory and nonrespiratory motor function have been observed following therapeutic AIH in people with chronic spinal cord injury, the underlying mechanisms are poorly understood. 203,204 Poikilocapnic AIH does not appear to enhance corticospinal neurotransmission in respiratory nor limb muscles, [205][206][207] although this remains controversial. 208 Recent work shows that in healthy humans, AIH paired with concurrent hypercapnia (i.e., acute intermittent hypercapnic-hypoxia) enhances the amplitude diaphragmatic motor-evoked potentials induced by transcranial magnetic stimulation, without change in the amplitude of diaphragm potentials evoked by peripheral nerve stimulation.…”