TIME-DEPENDENT EFFECT OF ACUTE HYPOXIA ON 1 CORTICOSPINAL EXCITABILITY IN HEALTHY HUMANS 2 3 Running title : Hypoxia and cortex excitability

23 24 Contradictory results regarding the effect of hypoxia on cortex excitability have been 25 reported in healthy subjects, possibly depending on hypoxia exposure duration. We evaluated 26 the effects of 1 and 3 hours hypoxia on motor corticospinal excitability, intracortical 27 inhibition and cortical voluntary activation (VA) using transcranial magnetic stimulation 28 (TMS). TMS to the quadriceps cortex area and femoral nerve electrical stimulations were 29 performed in 14 healthy subjects. Motor-evoked potentials (MEPs at 50-100% maximal 30 voluntary contraction -MVC), recruitment curves (MEPs at 30-100% maximal stimulator 31 power output at 50% MVC), cortical silent periods (CSP) and VA were measured in normoxia 32 and after 1 (n=12) or 3 (n=10) hours of hypoxia (FiO2=0.12). One-hour hypoxia did not 33 modify any parameters of corticospinal excitability but reduced slightly VA probably due to 34 the repetition of contractions 1-h apart (96±4% vs. 94±4%; P=0.03). Conversely, 3-h hypoxia 35 significantly increased i) MEPs of the quadriceps muscles at all force levels (+26±14%, 36 +24±12% and +27±17% at 50, 75 and 100% MVC, respectively; P=0.01) and stimulator 37 power outputs (e.g. +21±14% at 70% maximal power), and ii) CSP at all force levels 38 (+20±18%, +18±19% and +14±22% at 50, 75 and 100% MVC, respectively; P=0.02) and 39 stimulator power outputs (e.g. +9±8% at 70% maximal power), but did not modify VA 40 (98±1% vs. 97±3%; P=0.42). These data demonstrate a time-dependent hypoxia-induced 41 increase in motor corticospinal excitability and intra-cortical inhibition, without changes in 42 VA. The impact of these cortical changes on physical or psychomotor performances needs to 43 be elucidated to better understand the cerebral effects of hypoxemia. 44 45